Antibiotics versus placebo for prevention of postoperative infection after appendicectomy. (Review

Antibiotics versus placebo for prevention of postoperative

infection after appendicectomy. (Review)

Andersen BR, Kallehave FL, Andersen HK

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2005, Issue 3

http://www.thecochranelibrary.com

Antibiotics versus placebo for prevention of postoperative infection after appendicectomy. (Review)

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .49DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 1 Wound infection. . . . . . . 54Analysis 1.2. Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 2 Postoperative intra abdominal abscess. 58Analysis 1.3. Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 3 Length of stay in hospital. . . . 60Analysis 2.1. Comparison 2 Systemic antibiotics vs placebo (Pathoanatomic), Outcome 1 Wound infection. . . . 61Analysis 2.2. Comparison 2 Systemic antibiotics vs placebo (Pathoanatomic), Outcome 2 Postoperative intra abdominal

abscess. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63Analysis 3.1. Comparison 3 Topical Antibiotics vs Placebo, Outcome 1 Wound infection. . . . . . . . . . . 64Analysis 3.3. Comparison 3 Topical Antibiotics vs Placebo, Outcome 3 Lenght of stay in hospital. . . . . . . . 65Analysis 4.1. Comparison 4 Pre-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 1

Wound infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66Analysis 4.2. Comparison 4 Pre-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 2

Postoperative intra abdominal abscess. . . . . . . . . . . . . . . . . . . . . . . . . . 68Analysis 4.3. Comparison 4 Pre-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 3

Length of stay in hospital. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69Analysis 5.1. Comparison 5 Pre-operatively administered multiple agent, single dose Antibiotics vs Placebo, Outcome 1

Wound infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70Analysis 6.1. Comparison 6 Per-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 1

Wound infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71Analysis 6.2. Comparison 6 Per-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 2

Postoperative intra abdominal abscess. . . . . . . . . . . . . . . . . . . . . . . . . . 72Analysis 6.3. Comparison 6 Per-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 3

Length of stay in hospital. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Analysis 7.1. Comparison 7 Per-operatively administered multiple agent, single dose Antibiotics vs Placebo, Outcome 1

Wound infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74Analysis 8.1. Comparison 8 Operatively single agent and post-operatively single agent, single dose Antibiotics vs placebo,

Outcome 1 Wound infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75Analysis 8.2. Comparison 8 Operatively single agent and post-operatively single agent, single dose Antibiotics vs placebo,

Outcome 2 Postoperative intra abdominal abscess. . . . . . . . . . . . . . . . . . . . . . 76Analysis 9.1. Comparison 9 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo,

Outcome 1 Wound infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77Analysis 9.2. Comparison 9 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo,

Outcome 2 Postoperative intra abdominal abscess. . . . . . . . . . . . . . . . . . . . . . 79Analysis 9.3. Comparison 9 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo,

Outcome 3 Length of stay in hospital. . . . . . . . . . . . . . . . . . . . . . . . . . 80Analysis 11.1. Comparison 11 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs

placebo, Outcome 1 Wound infection. . . . . . . . . . . . . . . . . . . . . . . . . . 81Analysis 11.2. Comparison 11 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs

placebo, Outcome 2 Postoperative intra abdominal abscess. . . . . . . . . . . . . . . . . . . 82

iAntibiotics versus placebo for prevention of postoperative infection after appendicectomy. (Review)


Analysis 11.3. Comparison 11 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vsplacebo, Outcome 3 Length of stay in hospital. . . . . . . . . . . . . . . . . . . . . . . 83

Analysis 12.1. Comparison 12 Systemic antibiotics vs Placebo in children, Outcome 1 Wound infection. . . . . 84Analysis 12.2. Comparison 12 Systemic antibiotics vs Placebo in children, Outcome 2 Postoperative intra abdominal

abscess. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85Analysis 13.1. Comparison 13 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs

Placebo in children, Outcome 1 Wound infection. . . . . . . . . . . . . . . . . . . . . . 86Analysis 13.2. Comparison 13 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs

Placebo in children, Outcome 2 Postoperative intra abdominal abscess. . . . . . . . . . . . . . . 87Analysis 14.1. Comparison 14 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs

placebo, children, Outcome 1 Wound infection. . . . . . . . . . . . . . . . . . . . . . . 88Analysis 14.2. Comparison 14 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs

placebo, children, Outcome 2 Postoperative intra abdominal abscess. . . . . . . . . . . . . . . . 8989WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .91NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .91INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iiAntibiotics versus placebo for prevention of postoperative infection after appendicectomy. (Review)


[Intervention Review]

Antibiotics versus placebo for prevention of postoperativeinfection after appendicectomy.

Betina Ristorp Andersen2, Finn Lasse Kallehave3, Henning Keinke Andersen1

1Building 11 B„ Colorectal Cancer Group, Copenhagen, Denmark. 2Department of Obstetrics and Gynecology, Hillerød UniversityHospital, Hillerød, Denmark. 3Departement A, Surgical gastroenterology, Ålborg Hospital, Ålborg, Denmark

Contact address: Henning Keinke Andersen, Building 11 B„ Colorectal Cancer Group, 23 Bispebjerg Bakke, Copenhagen, DK 2400CPH NV, Denmark. [email protected].

Editorial group: Cochrane Colorectal Cancer Group.Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.Review content assessed as up-to-date: 19 April 2005.

Citation: Andersen BR, Kallehave FL, Andersen HK. Antibiotics versus placebo for prevention of postoperative infection after appen-dicectomy.. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD001439. DOI: 10.1002/14651858.CD001439.pub2.


A B S T R A C T

Background

Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. The cause of appendicitis is unclear andthe mechanism of pathogenesis continues to be debated. Despite improved asepsis and surgical techniques, postoperative complications,such as wound infection and intraabdominal abscess, still account for a significant morbidity. Several studies implicate that postoperativeinfections are reduced by administration of antimicrobial regimes.

Objectives

This review evaluated the use of antibiotics compared to placebo or no treatment in patients undergoing appendectomy. Will thesepatients benefit from antimicrobial prophylaxis? The outcomes were described according to the nature of the appendix, as either simpleappendicitis (including the non-infectious stage) and complicated appendicitis. The efficacy of different antibiotic regimens were notevaluated.

Search methods

We searched The Cochrane Central Register of Controlled Trials (Cochrane Library 2005 issue 1); Pubmed ; EMBASE; and theCochrane Colorectal Cancer Group Specialised Register (April 2005). In addition, we manually searched the reference lists of theprimary identified trials.

Selection criteria

We evaluated Randomised Controlled Trials (RCTs) and Controlled Clinical Trials (CCTs) in which any antibiotic regime werecompared to placebo in patients suspected of having appendicitis, and undergoing appendectomy. Both studies on children and adultswere reviewed. The outcome measures of the studies were: Wound infection, intra abdominal abscess, length of stay in hospital, andmortality.

Data collection and analysis

Eligibility and trial quality were assessed, recorded and cross-checked by two reviewers.

1Antibiotics versus placebo for prevention of postoperative infection after appendicectomy. (Review)


mailto:[email protected]

Main results

Forty-five studies including 9576 patients were included in this review. The overall result is that the use of antibiotics is superior toplacebo for preventing wound infection and intraabdominal abscess, with no apparant difference in the nature of the removed appendix.Studies exclusively on children and studies examining topical application reported results in favour to the above, although the resultswere not significant.

Authors’ conclusions

Antibiotic prophylaxis is effective in the prevention of postoperative complications in appendectomised patients, whether the admin-istration is given pre-, peri- or post-operatively, and could be considered for routine in emergency appendectomies.

P L A I N L A N G U A G E S U M M A R Y

Antibiotic prophylaxis could be considered for routine in emergency appendectomies.

Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. This is associated with increased risk ofpostoperative complications, wound infection being the most commonly reported. Standard prophylaxis is an anti-bacterial treatment.In order to reduce cost, toxicity and the risk of developing bacterial resistance, it is desirable to establish the shortest and most effectiveprophylaxis for postoperative complications.

This review reports that antibiotic prophylaxis is effective in the prevention of postoperative complications in people who had theappendix removed. Regardless whether the antibiotic was given before, during or after the surgery.

B A C K G R O U N D

Appendicitis is the most common cause of acute abdominal painrequiring surgical intervention, and affects all age groups. On sus-picion of acute appendicitis the standard procedure is surgery.

The number of patients undergoing appendectomy (removal ofthe appendix) in the population is significantly higher than thenumber of diagnosed acute appendicitis. Fenyö (Fenyö1995) re-ported that 15-30% of all appendectomies are unnecessary dueto a non-inflamed appendix, and Luckmann (Luckmann 1989)suggests even higher numbers. The actual incidence of acute ap-pendicitis varies, the overall lifetime risk for acute appendicitis is6-20% (Blewett 1995; Addiss 1990). Addiss reported 8.6% formales and 6.7% for females, compared to an overall life time riskfor appendectomy of 12% (males) and 23.1% (females) in US.

Removal of the appendix is most frequently reported in adolescents(10-20 years of age). The incidence in children under the age of 5,and in adults over 70 years of age, is small (Graffeo 1996; Addiss1990; Luckmann 1989).

The cause of acute appendicitis is unclear. The mechanism ofpathogenesis could involve obstruction of the appendiceal lumen,preventing the escape of intraluminal secretion (Arnbjörnsson

1983). This could result in increased intraluminal pressure, lead-ing to transmural tissue necrosis . However, the mechanisms ofpathogenesis continue to be debated.

The predominant microbial flora associated with acute appen-dicitis are E.Coli, Kleibciella, Proteus and Bacteroides (Altemeier1938; Leigh 1974; Bennion 1990; Blewett 1995). These microbesmay cause postoperative infection depending on the degree of in-flammation of appendix, surgical technique and duration of oper-ation. Postoperative complications parallel that found from perfo-rated viscus of any cause. The most common being intra abdomi-nal abscess and wound infection was reported in as high as 40% ofall appendectomy cases (Almqvist 1995). Despite improved asep-sis and surgical techniques, postoperative infections still accountsfor morbidity and increased length of stay in hospital as majorconsequences.

Several studies have implicated that postoperative infections arereduced by the administration of antimicrobial regimes. The gen-eral assumption is that it is better to treat patients with compli-cated appendicitis with antibiotics than with placebo, in contrastto patients with simple appendicitis. Yet other studies have ques-tioned the use of antibiotics at all in appendectomised patients. Inorder to reduce cost, toxicity and the risk of developing bacterial



resistance, it is desirable to establish the shortest and most effectiveprophylaxis for postoperative complications.

Bearing the above points in mind, and given that the use of an-tibiotics in clinical practice is frequently questioned, in this sys-tematic review we examined the effect of antimicrobial treatmentversus placebo treatment in appendectomised patients. To reflectthe clinical decision-making process we wanted to explore whetherpatients operated on suspicion of appendicitis could prevent post-operative infection if they received antimicrobial therapy prior tosurgery or during surgery. This implicates that appendectomy iscarried out for reasons other than acute appendicitis (negative ap-pendectomy), and is included in this study as well, due to exposureof the colonic microbial flora.

A description of the alternatives to antimicrobial prophylaxis, suchas delayed closure and surgical lavage, will not be covered in thisreview.

The clinical diagnosis of appendicitis is generally divided in twosubgroups:

Simple appendicitis include terms like ’non-inflamed’ (normal ap-pendix), ’acutely inflamed’, ’phlegmonous’, ’acute’, ’suppurative’,’mildly inflamed with or without peritonitis’. This condition alsocovers minimal appendicitis, early appendicitis, and uncompli-cated appendicitis.

Complicated appendicitis includes ’gangrenous appendicitis’,’perforated appendicitis’, ’local pus collection at operation’, ’gen-eral peritonitis’, and ’intra abdominal abscess’.

The analyses are stratified to include subgroups of patients withsimple appendicitis and complicated appendicitis.

O B J E C T I V E S

A systematic search for relevant literature from controlled clinicaltrials was performed to find evidence relating to the use of antibi-otics in patients undergoing appendectomy on the suspicion ofappendicitis.

Relevant data were extracted from these reports of clinical trialsand analysis performed which reflects the clinical decision-makingprocess. Given the fact, that patients are operated upon suspicionof appendicitis, we wished to explore whether postoperative in-fection and prolonged stay in hospital could be prevented if thepatients were given antimicrobial therapy prior to, under, or afterthe surgery.

M E T H O D S

Criteria for considering studies for this review

Types of studies

This review evaluated randomised controlled trials (RCTs) andcontrolled clinical trials (CCTs) in which treatment with any an-timicrobial regime was compared to placebo in patients with sus-pected appendicitis undergoing appendectomy. The authors didnot discriminate between trials that describe appendices in variousstages, that is if they are non inflamed or perforated.Studies in which the antimicrobial regime was compared to a con-trol group receiving no treatment were excluded from this review,unless perioperative treatment was stated and subject blinding wasfound adequate.

Types of participants

Children and adults with suspected appendicitis based on eitherclinical conditions or intra operatively diagnosed by the surgeon.No restrictions to age or gender.Appendectomised patients were ideally reported in two subgroups:Simple appendicitis and complicated appendicitis. If pathologywas not stated in a trial, the data were admitted statistically intothe subgroup ’appendicitis’, which covers all aspects of pathology.The definition of ’simple appendicitis’ includes the appendixwhich is normal at operation (non-inflamed); acutely inflamed;phlegmonous; acute; suppurative; mildly inflamed with or with-out peritonitis. This condition also covers minimal appendicitis;early appendicitis; and uncomplicated appendicitis.The definition of ’complicated appendicitis’ includes gangrenousappendicitis; perforated appendicitis; local pus collection at oper-ation; general peritonitis; and intra abdominal abscess.Trials reporting patients with periappendicular abscess not oper-ated upon are excluded from this review.

Types of interventions

Trials comparing any antimicrobial regime versus placebo adminis-tered before, during, or after appendicectomy, and reporting post-operative infection, length of stay in hospital, and mortality, wereconsidered for this review.The primary topic was to examine whether antimicrobial therapygiven to patients operated on suspicion of appendicitis could pre-vent postoperative infection.The types of intervention are specified in the table of comparisons.The term ’clinical diagnosis’ refers to the condition pre- or periop-eratively diagnosis, usually performed by the clinician. The use ofparaclinical diagnosis (bloodtest, urintest e.g.) is included in thisterm.The term ’pathoanatomical diagnosis’ refers to the more accuratepostoperative diagnosis in which the nature of the removed ap-pendix have been established either macroscopically or microscop-ically.Trials reporting patients treated topically with antimicrobial agentsdisolved in aqueous solution were considered for inclusion if the



comparison group was treated with the aqueous solution. Other-wise we excluded the study.

Types of outcome measures

Trials were considered if one or more of the following clinicaloutcomes were reported:1) Wound infection (discharge of pus from the wounds).2) Postoperative intra abdominal abscess (persistent pyrexia with-out any other focus, after operation, palpable mass in the abdomenor discharge of pus from the rectum).3) Length of stay in hospital4) MortalityIn this review we analysed patients with a normal appendix andpatients with perforated appendix. This approach considered thepathoanatomical distinction of appendicitis, using the terms forsubgroup analysis as described above.

Search methods for identification of studies

The following bibliographic databases were searched in order toidentify relevant primary studies:Cochrane Central Register of Controlled Trials (CENTRAL),Cochrane Library 2005 issue 1PubMed, from 1966 to April 2005EMBASE, from 1980 to April 2005Cochrane Colorectal Cancer Group Specialised Register, April2005The following strategy was used to search the Pubmed database,combined with the Cochrane Collaboration highly sensitive searchstrategy for identifying randomised controlled trials and controlledclinical trials:#1 appendic*#2 appendec*#3 appendek*#4 #1 or #2 or #3#5 apendic*#6 apendec*#7 apendek*#8 #5 or #6 or #7#9 appendix*#10 apendix*#11 #9 or #10#12 #4 or #8 or #11From the studies identified with the search term appendix* wehave excluded Boon*, Spong*, Neuro* and Psyc*.The Cochrane Central Register of Controlled Trials (CENTRAL)and CCCG specialised register were searched using the abovesearch strategy, but without the Cochrane Collaboration highlysensitive search strategy for identifying randomised controlled tri-als and controlled clinical trials.

The search strategies were then combined with free text words(truncation as indicated):#1 antibiot*#2 antimic*#3 metronida*#4 #1 or #2 or #3All identified trials from the search were evaluated for inclusion.Identified and included studies were further examined for addi-tional studies from the respective reference list. .The EMBASE database was searched using the following strategy.Search string from #22 to #33 describes the filter used for iden-tification of randomised controlled trials and controlled clinicaltrials:#35 #29 or #34#34 #21 and #33#33 random*#32 #29 or #31#31 #21 and #28#30 case*#29 #21 and #27#28 random* or clin*#27 #22 or #24 or #26#26 #23 not #25#25 ’case-control-study’ / all subheadings#24 ’randomization-’ / all subheadings#23 explode ’controlled-study’ / all subheadings#22 explode ’clinical-trial’ / all subheadings#21 #19 not #20#20 boon* or spong*#19 #17 not #18#18 neuro* or psyc*#17 #8 and #16#16 #11 or #15#15 #12 or #13 or #14#14 metronida*#13 antimic*#12 antibiot*#11 #9 or #10#10 explode ’antibiotics-and-their-derivatives’ / all subheadings# 9 explode ’antibiotic-agent’ / all subheadings# 8 #1 or #7# 7 #5 or #6# 6 #2 or #3 or #4# 5 ’appendectomy-’ / all subheadings# 4 ’appendix-perforation’ / all subheadings# 3 ’acute-appendicitis’ / all subheadings# 2 ’appendicitis-’ / all subheadings# 1 append* or apend*The final number was manually searched for trials fulfilling theinclusion criteria.This update revealed 11 new eligible studies, of which five wereconsidered for inclusion (Harahsheh 2002; McGreal 2002; Taylor



2000; Taylor 2004; Simpson 2002). The remaining six trials de-scribed interventions outside the scope of this review. None of thefive studies fulfilled the inclusion criteria for various reasons. Onestudy was an abstract (Simpson 2002) and is awaiting assessment,and the four studies were excluded as described in the table ofcharacteristics of excluded studies

Data collection and analysis

Appropriate criteria for assessing the quality of the included stud-ies are methods (either qualitative or quantitative) that combinesearches, outcomes, and meta-analysis.Location and selecting studies:All identified trials were reviewed independently by two authors(HKA and BRA) in order to evaluate, whether the trial shouldbe included or should be excluded. A data extraction form wasprepared prior to the search for literature. Disagreements weresolved in an consensus meeting eventually with help from a thirdauthor.Excluded studies were detailed in the table of excluded studies.Critical appraisal of studies:The methodological quality of each trial was assessed by the sametwo authors. Details of the randomisation method, blinding, andthe number of patients lost during the study were recorded. Whennecessary information was missing from a published trial, the pri-mary author were contacted for clarification.Collecting data:Data was independently extracted using a standard data extractionform. Recorded data was cross-checked. The data was entered intoMetaview in RevMan 4.2.6 for analysis. The following parame-ters were extracted: wound infections; intra abdominal abscesses;number of days in hospital; and mortality.

R E S U L T S

Description of studies

See: Characteristics of included studies; Characteristics of excludedstudies.Forty-five studies, including 9576 patients, were included in themeta-analyses of this review. Twelve studies had more than onearm; seven studies had two arms and five studies had three arms.Age-range of the included patients was three months to 94 yearsof age. Sixteen studies reported the male/female ratio. The mor-phologic descriptions of the pathoanatomical distinction of ap-pendicitis were very weakly described. Twenty-one of the studiesdid not divide the appendix into pathological subgroups. Twenty-one of the studies reported a division into simple or complicated

appendicitis. No attempt was made to elucidate age- or genderrelated correlations.In summary, including the arms of all identified studies we exam-ined 63 trials; 46 trials examined single drug therapy and 17 trialsexamined a combination of two or more drugs. The antibioticsused in the studies were divided into nine major antibiotic groups.The most common antibiotics used were Cephalosporin and im-idazole derivatives.All forty-five studies reported wound infection. Twelve studiesreported intra abdominal abscess and ten studies reported lengthof stay in hospital. Only two studies reported mortality.Thirty-two of the identified studies were excluded for various rea-sons, and one study is awaiting assesment (Simpson 2002). Al-location concealment being the major factor, followed by insuf-ficient information on treatment strategies. Sixteen of those werepotentially eligible for the meta-analysis, but any doubt on sub-ject blinding led to their exclusion. In eleven of the studies thepatients in the placebo group received no treatment. In nine stud-ies, the antibiotics in the treatment group was administrated in away, that made it possible for the patient as well as the clinicianto know whether the patient was in the treatment group or in thecontrol group. These studies were excluded because of inadequateblinding (Amgwerd 1981, Bates 1974, Bröte 1976, Evans 1973,Feltis 1967, Gómez-Alonso 1984, Kling 1985, McLean 1983,Okubadejo 1976). Two trials (Crosfill 1969, Gilmore 1975) wereexcluded because it was unclear which patients received systemicantibiotics. Yet another three studies described interventions thatcould make it difficult to establish the effect of antibiotics alone(Harahsheh 2002; Taylor 2000; Taylor 2004). One trial (Birkigt1989) was excluded due to discord in the table of the results.Another trial (Herrera-Garcia 1985) did not distinguish betweenwound infection and intra abdominal abscess in the result section.Yet another study was excluded due to irrigation with physiologi-cal serum in the control group (Badia 1994).Five studies did not fulfil the inclusion criteria for any meta-anal-yses. Two of the trials did not have results on appendicitis exclu-sively (Dixon 1984, Pollock 1972) and one (Rambo 1972) onlyreported one case of appendicitis. One trial was an abstract whichdid not obtain all the necessary details and it was impossible toget the full study. One trial were based on prior published trials(Leigh 1978). A detailed description is available in the referencelist under “excluded studies”.

Risk of bias in included studies

The methodological quality of each trial were assessed by thesame two authors (HKA and BRA). Details of the randomisa-tion method, blinding, and the number of patients lost during thestudy were recorded.Missing information from reports of trials was sought by contact-ing the authors.



As a common denominator studies were excluded if the placebogroup was not stated. However, if subject blinding was adequatelydescribed, studies reporting “control” or “no treatment” were con-sidered for peri-operatively treatment only .The randomisation method of included studies was adequatelydefined in 17 of the 45 studies, either by computerised randomnumbers or sealed envelopes. In twenty-three studies the randomi-sation method was not stated. The last five studies were indexedas quasi-randomised (CCT), by using birth date as concealmentmethod. These studies were all categorised as having inadequaterandomisation. Thirty of the studies were double or triple blinded.Ten of the studies had at least blinding of the patient, but unclearblinding of surgeon and outcome assessor. In five of the studiesthe blinding was found unclear.Six studies displayed odd numbers in the comparison groups. Theywere individually evaluated for drop-outs or other reasons to clarifythe imbalance and were finally included.Wound infection was defined in 34 of the studies. The definitiondiffered, but the major description was discharge of pus from thewounds. Three out of eleven studies defined intra abdominal ab-scess.We did not observe any time related variations regarding themethodological quality of the studies. Older studies such as Stoller1965 were found to be adequately randomised and fully compa-rable to newer studies.

Effects of interventions

Study validation in meta-analysis

In the current updated systematic review we have identified a totalof 78 RCT’s and CCT’s for inclusion, of which 32 studies wereexcluded for various reasons. One trial is awaiting assessment.In the first published version of this systematic review, we identified70 RCT’s and CCT’s, of which 27 were excluded. In the firstupdated version (2003) we identified additional three studies, onewas included and two were excluded. In this updated version weidentified additional five studies, four excluded and one awaitingassessment.Forty-five controlled trials (9576 patients), of which five trials weredealing with topical use of antibiotics, were included in the meta-analysis of this review. Outcome measures were sought divided ineither simple or complicated appendicitis according to the defini-tion in “types of participants”. If no attempt was made to sub-di-vide the patients, results were presented as “appendicitis”. Resultsare pooled data from all studies and focus on appendectomiedpatients without specification of the clinical severity of disease orpato-anatomic characterisation of the removed appendix. Anal-yses of pato-anatomic clinical relevant entities (normal removedappendix, simple appendicitis (phlegmonuos) or complicated ap-pendicitis (gangrenous or perforated) confirmed the overall result:An effect of antibiotics when compared to placebo. A subgroup

analysis of different treatment strategies (see table 1) confirmedthis overall result.The clinical heterogeneity

amongst the trials was reflected in parameters such as study popu-lation; diagnosis; strategy of treatment; type of antibiotics; the out-come analysis and length of follow up. The majority of includedstudies did not distinguish between adults and children. Six trialsexclusively on children (a total of 776 patients, aged 3 months- 15 years of age) were reported. Included studies were differentin strategy and use of antibiotics but all compared to placebo orcontrol treatment (subject blinded).The statistical heterogeneity depends on the clinical and method-ological differences within the trials. We used a validated qual-ity scale (Jadad 1996) in order to identify systematic differencesamong the included trials. This scale produces scores from 0-5points. Trials with less than 3 point considered “poor quality stud-ies”. Each of the included trials was quality assessed independentlyby two of the three authors and the scores were compared.Visual inspection of trials sorted by either size or quality score didnot affect the outcome. Therefore, it was decided not to excludelow score studies.To assess publication bias we used the regression test for asymme-try in the funnel plot a specified cut-off number of five trials inthe meta-analysis was chosen. In total we performed visual inspec-tion for asymmetry in a total of nine different outcomes, withoutdetecting any discrepancies. This finding further supports the no-tion, that small trials show the same results as greater trials.Sub-group analysis after randomisation may introduce bias due tosignificantly different population sizes. In addition, we observedthat some of the included studies were unequally randomised as 3:2 or 2:1 and even 2:1:1 in multiple arm studies. Observed imbal-ance in the comparisons groups were evaluated to ensure an effectof the study design or any drop-outs on the overall results. Rea-sons for odd numbers in comparisons group were either multiplearm studies (Donovan 1979 A, Foster 1981 A, Viitanen 1984 A),unequally numbers of post-operative drop-outs or other reasons(Azabache 1987 A, Gledhill 1983, Keiser 1983, Stoller 1965).In summary, we found that none of the included 45 studies re-vealed any significant discrepancy from the overall result. Con-clusively, the statistical and clinical heterogeneity of the trials in-cluded in this review still make comparison of the individual trialspossible with respect to the overall question - antibiotics versusplacebo (no treatment).Outcomes:The major outcome “wound infection” was described in all in-cluded trials. However it must be emphasised, that the definitionof wound infection is subject to a broad variety and in 9 of the45 included trials no description was stated. In addition, clinicaltest for wound infection was also subject to broad variety in thestudies describing this parameter.The outcome “intra abdominal abscess” was described in 16 of the45 included trials.



The outcome “length of hospital stay” was described in nine ofthe 45 included trials. Despite a marked heterogeneity amongthe trials, we decided to present the meta-analysis. The overalltendency in the included trials was no intention of describing thelength of follow-up.The outcome “mortality” was described in two trials with a totalof three deaths. One patient died from lung emboli after threemonths, another from cardiac infarction and a third from peri-tonitis due to a perforated appendix. Therefore, no direct com-parison was made possible, and no meta-analysis was made.Study groups and results:Thirty-four of the included trials include patients with all clinicalaspects of appendicitis. The meta-analysis of this review are pre-sented according to the clinical distinguishable diagnosis:normal removed appendix, simple appendicitis (phlegmonuos) orcomplicated appendicitis (gangrenous or perforated).The overall result is that the use of antibiotics is superior to placebofor the outcomes “wound infection” and “intra abdominal ab-scess”.None of the 45 trials described “exclusion of children”, rathera variety in age for included patients. seven trials exclusively onchildren (776 patients, aged 3 months - 15 years) were reported,and the resulting meta-analysis showed non-significant effects.Four trials examined topical application of antibiotics comparedto placebo ( 679 patients). The meta-analysis did not show a sig-nificant effect.Treatment strategies and subgroup results are presented in ’com-parisons and data’. The drugs are administered either systemic ortopical, without distinguishing between antibiotic regimens. Timeof administration was divided in either pre- or peri-operatively, asthe term post-operatively from a clinical point of view is irrelevantand not reported in the studies. However, the later may be relevantwith one of the two former.Number of drugs used is characterised as either ’single agent’ or’multiple agents’. Frequency of administration is divided in either’single dose’ or ’repetitive dose’.The results are presented summarically as Peto/odds ratio (95%CI), fixed-effect model (log scale ranging from 0.01 to 10.00shown in the meta-analysis graphs). Values less than 1.0 favourtreatment with antibiotics. In addition the numerical values arenotified as incidences/included patients for each Group (antibi-otics versus placebo). The overall result shows a significant ad-vantage for the use of antibiotics compared to administration ofplacebo.

D I S C U S S I O N

Recent studies have produced significant evidence to support theuse of antibiotic therapy in patients undergoing appendectomy.We therefore tested the hypothesis:

“Does antibiotic treatment reduce post-operative infection ratesin appendectomised patients”?

Antibiotic prophylaxis is one of many measures that should betaken into account in order to reduce postoperative morbidity(primarily wound infection). Many have reviewed the value of an-timicrobial prophylaxis in clean-contaminated, contaminated andin clean operations, but even though benefits are well established,no general recommendations on antibiotic prophylaxis have beensettled. This systematic review focus on appendectomised patients,randomly assigned either antibiotic therapy or placebo (control)treatment. Recommended duration of antibiotic administrationis not possible from the presented meta-analysis, as we did notcompare single dose versus multiple dose. In addition, the efficacyof the therapeutic use of different antibiotic regimens efficacy wasnot the scope of this review.

From a clinical point of view, the main concern on administrationof antibiotics is how to reduce post surgical complications andthe intention to shorten the length of the hospital stay. We didnot address the use of antibiotics in the treatment of appendicitiswithout surgery.

The results confirm an overall effect of antibiotics, regardless ad-ministered as either prophylactics (single dose administration)in case of “normal removed appendix” or “simple appendici-tis”(phlegmonous), or as repetitive treatment in case of “compli-cated appendicitis” (gangrenous or perforated).

Wound infection (superficial) or intra abdominal abscess (deepinfection) are the most common post surgical complications andreflect the severity of disease and/or quality of surgical procedure.Long-term complications such as intestinal obstruction and in-fertility are not addressed in the included controlled studies withshort follow up period, but need analysis from large epidemiolog-ical trials.

The outcome “length of hospital stay” is closely associated withthe nature of post surgical infections and indirectly to the efficacyof antibiotics. A limited number of placebo controlled studiesreviewed the length of hospital stay (Bates 1980, Bauer 1989,Busuttil 1981 A, Gurry 1976, Keiser 1983, Paakkonen 1982,Raahave 1970, Winslow 1983). From a historical point of view,we have to emphasise radical changes in “hospital stay policy”,presently favouring early hospital discharge.

In summary, the presented meta-analysis on this parameter is basedon studies from the past three decades and therefore difficult tointerpret.

Mortality is a rare complication to appendectomy and only re-ported in two trials. Since the main outcome is short term investi-gation on the effect of antibiotic versus placebo on wound infec-tion and intra abdominal abscess, this could explain the low num-ber of reported deaths due to exclusion from study. Only one trialreported short term mortality as a reason for exclusion of patients



from the study. An overview on actual mortality rate should besought in epidemiological studies rather than randomised studies.

Seven trials exclusively on children (age: 3 months -15 year) wereidentified. Both nature of disease and treatment were compara-ble to the ones for adults. Interestingly, subgroup analysis of thispopulation showed a non-significant reduction in infection rate,which can be explained by a limited number of patients withoutheterogeneity between single study results. Another factor is thereported pathogenesis of appendicitis in children, which showshigher incidence of complicated appendicitis. However, althoughnot divided in specific sub-populations, the majority of studiesinclude children in their analysis. It is only reasonable to assumethat the overall antibiotic efficacy also is representative for chil-dren. Several non-randomised studies have revealed differences inthe pathology of the diagnosed appendicitis which could explainthe non-significant reduction in the infection rate.

The meta-analysis on topical use of antibiotics shows clinical het-erogeneity, primarily explained in a reported diversity of experi-mental set-up. Eklund 1987 exclude all patients with perforatedappendicitis and Gurry 1976 only include those patients. Eklund1987 exclude patients treated with additional antibiotics beforerandomisation and Stoller 1965 exclude those patients after ran-domisation. Gurry 1976 and Foster 1981 A do not describe theirprocedure. In addition, the trials use four types of antibiotics anddifferent ways of administration. Eklund 1987 and Gurry 1976use a solution, Foster 1981 A uses powder and Stoller 1965 usesan aerosol. Regarding statistical heterogeneity, the trials expresssome methodological differences as well. Three of the trials arerandomised-controlled trials and one of the trials is a controlledclinical trial. Foster 1981 A uses single blinding (patients), Eklund1987 double blinding, and Gurry 1976 and Stoller 1965 triple-blinding.

Therefore, non-significant results could be explained by clinicaland methodological differences. Historically, topical use of antibi-otics is now generally replaced with a higher hygienic standard.

Wound infection is significantly reduced in pooled data as wellas subgroup analysis, without any indication of statistical hetero-geneity, confirmed by quality assessment of single studies, wherehigh quality studies were compared to low quality studies withoutdiscrepancies in the effect parameter. Only deviance from this pat-tern is the non-significant result from topical use of antibiotics.

The meta-analysis of intra abdominal abscess show identical pat-terns, but only the analyse of the pooled data is statistical signifi-cant. Interestingly, the subgroup analysis show non-significant ef-fect of antibiotics, which can be explained by the limited numberof patients / events rather than heterogeneity or study quality.

We analysed the efficacy of antibiotics, administered either pro-phylactic or post-surgically, notified as “short term versus longterm treatment”. Both strategies reduces wound infection signif-icantly and intra abdominal abscess non-significantly (again due

to a low number of events). Although significant results we arenot in a position of comparing these strategies, which needs to beadressed in a review comparing the different regimens.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

It seems reasonable to conclude that antibiotic prophylaxis is ef-fective in the prevention of post-operative complications in ap-pendectomied patients, whether the administration is given pre-, per- or post-operatively, and should be considered for routineuse in emergency appendicectomy. The overall strategy (type ofantibiotics and/or preferred time of administration) needs to beevaluated in another systematic review.

Our results indicate that single doses have the same impact as mul-tiple doses. In order to reduce cost, toxicity and the risk of devel-oping bacterial resistance, it is desirable to establish the shortest,effective prophylaxis for post-operative complications, and fromthe meta-analysis it seem that single doses have the same impactas multiple doses.

The general assumption is that it is better to treat patients withcomplicated appendicitis with antibiotics than with placebo, incontrast to patients with simple appendicitis. Yet other studieshave questioned the use of antibiotics at all in appendectomisedpatients.

Implications for research

Despite the presented meta-analysis indicate similar results on sin-gle dose efficacy and multiple dose efficacy, we did not comparethese outcome parameters. In addition, the time for administra-tion did not seem to have any significant impact at all, but weren’tcompared either. Conclusively these parameters should thereforebe reviewed. Other strategies such as irrigation and delayed clo-sure could alternatively have positive effects on reduction of post-operative complications, but need further examination in anothersystematic review.

This review confirms the effect of antibiotics in reducing woundinfection and abscess formation in all pato-anatomic subgroupand after removal of a normal appendix. Recommendations to theuse of antibiotics in all cases of appendectomies patients is stillcontroversy regarding the general accepted recommendations pre-scribing only use of antibiotics in case of complicated appendici-tis. On the other hand the literature stated superior effects follow-ing preoperatively administration incompatible to per operativelyverifying (by visualisation) of the disease severity as condition forinitialisation of antibiotic treatment.



A C K N O W L E D G E M E N T S

We are specially grateful for a careful reading, valuable commentsand suggestions from the peer reviewers, Dr. Roland Andersson,Department of surgery, Rykov Hospital, Jönköping Sweden, andProfessor Mario Lise, University Hospital, Padova, Italy, and thekey editor of the manuscript, Professor Ole Kronborg, OdenseUniversity Hospital, Denmark.

And for the incoming suggestions for improvenment from variouscolleagues.

R E F E R E N C E S

References to studies included in this review

Ahmed 1987 {published data only}∗ Ahmed ME, Ibrahim SZ, Arabi YE, Hassan MA.Metronidazole prophylaxis in acute mural appendicitis:failure of a single intra-operative infusion to reduce woundinfection. J Hosp Infect 1987;10:260–4.

Azabache 1987 A {published data only}∗ Azabache PW, Gonzales GV, Santa MariaRB. Antibioticoprofilaxis según tipo de heridapostapendicectomía [Antibioticoprofilaxis según tipo deherida postapendicectomía]. Rev Gastroenterol (Peru) 1987;7:112–5.

Azabache 1987 B {published data only}

As Azabache 1987 A.

Bates 1980 {published data only}∗ Bates T, Touquet VLR, Tutton MK, Mahmoud SE,Reuther WA. Prophylactic metronidazole in appendectomy:a controlled trial. Br J Surg 1980;67:547–50.

Bauer 1989 {published data only}∗ Bauer T, Vennits B, Holm B, Hahn-Pedersen J, LysenD, Galatius H, et al.Antibiotic prophylaxis in acutenonperforated appendicitis. Ann Surg 1989;209(3):307–11.

Bergmark 1985 {published data only}∗ Bergmark C, Lahnborg G. Prophylactic trimethoprim-sulpha plus metronidazole in appendectomy - a controlledstudy. Opmear 1985;30(3):93–5.

Browder 1989 A {published data only}∗ Browder W, Smith JW, Vivoda LM, Nichols RL.Nonperforative appendicitis: a continuing surgicaldilemma. J Infect Dis 1989;159(6):1088–94.

Browder 1989 B {published data only}

As Browder 1989 A.

Busuttil 1981 A {published data only}∗ Busuttil RW, Davidson RK, Fine M, Tompkins RK.Effect of prophylactic antibiotics in acute nonperforatedappendicitis: a prospective, randomized, double-blindclinical study. Ann Surg 1981;194(4):502–9.

Busuttil 1981 B {published data only}

As Busuttil 1981 A.

Chiam 1983 A {published data only}∗ Chiam HL, Chee CP, Cheah KC, Somasundaram K,Puthucheary SD. The prevention of postappendicectomysepsis by metronidazole and cotrimoxazole: a controlleddouble blind trial. Aust Nz J Surg 1983;53(5):421–5.

Chiam 1983 B {published data only}

As Chiam 1983 A.

Chiam 1983 C {published data only}

As Chiam 1983 A.

Corbett 1979 {published data only}∗ Corbett R, Prout WG, Hewitt GW, Tuke W,Okubadejo OA. The value of metronidazole prophylaxis inappendectomy patients. Proc R Soc Med Int Congress and

Symposium Series 1979;18:111–13.

Creve 1980 A {published data only}∗ Creve U, Hubens A. Single-dose parenteral antibioticprophylaxis in gastrointestinal surgery. Acta Chir Belg 1980;79:27–33.

Creve 1980 B {published data only}

As Creve 1980 A.

Donovan 1979 A {published data only}∗ Donovan IA, Ellis D, Gatehouse D, Little G, GrimleyR, Armistead S, Keighley MR, Strachan CJ. One-doseantibiotic prophylaxis against wound infection afterappendicectomy: a randomized trial of clindamycin,cefazolin sodium and a placebo. Br J Surg 1979;66:193–6.

Donovan 1979 B {published data only}

As Donovan 1979 A.

Eklund 1987 {published data only}∗ Eklund AE, Tunevall G. Prevention of postoperativewound infection after appendectomy by local application oftinidazole: a double-blind study. World J Surg 1987;11(2):263–6.

El-Sefi 1986 A {published data only}∗ el-Sefi TA, el-Awadi HM, Shehata MI, Al-HindiMA. The place of antibiotics in the prevention of post-appendicectomy sepsis: a prospective study of 400 cases. Int

Surg 1986;71(1):18–21.

El-Sefi 1986 B {published data only}

As el Sefi 1986 A.



El-Sefi 1986 C {published data only}

As el Sefi 1986 A.

Foster 1978 {published data only}∗ Foster PD, O’Toole RD. Primary appendectomy. Theeffect of prophylatic cephaloridine on postoperative woundinfection. JAMA 1978;239(14):1411–2.

Foster 1981 A {published data only}∗ Foster GE, Bourke JB, Bolwell J, Doran J, BalfourTW, Holliday A, Hardcastle JD, Marshall DJ. Clinicaland economic consequences of wound sepsis afterappendicectomy and their modification by metronidazoleor povidone iodine. Lancet 1981;1(8223):769–71.

Foster 1981 B {published data only}

As Foster 1981 A.

Giacomantonio 1982 {published data only}∗ Giacomantonio M, Bortolussi R, Gillis DA. Shouldprophylactic antibiotics be given perioperatively in acuteappendicitis without perforation?. Can J Surg 1982;25(5):555.

Gledhill 1983 {published data only}∗ Gledhill T, Odurny A, Weaver PC. A controlled studyof single dosage cefamandole in the prophylaxis of woundinfections in appendectomy. Surg Gynaecol Obstetr 1983;156(3):295–7.

Go 1986 {published data only}∗ Go PM, Luyendijk R, Munting JD. [Metronidazoleprophylaxis in appendectomy]. [Dutch][Metronidazolprofylaxe bij appendectomie.]. Ned Tijdschr

Geneeskd 1986;130(17):775–8.

Gottrup 1979 {published data only}

Gottrup F. Prophylactic metronidazole in prevention ofinfection after appendicectomy: report of a double-blindtrial. Acta Chir Scand 1980;146(2):133–6.∗ Gottrup F, Sorensen I. [Infection after appendectomy.Effect of preventive metronidazole therapy].[Danish] [Infektion efter appendektomi. Effekten afmetronidazolprofylakse.]. Ugeskr Læger 1979;141(34):2293–6.

Greenall 1979 {published data only}∗ Greenall MJ, Bakran A, Pickford IR, Bradley JA, HalsallA, Macfie J, Odell M, Cooke EM, Lincoln C, McMahonMJ. A double-blind trial of a single intravenous dose ofmetronidazole as prophylaxis against wound infectionfollowing appendicectomy. Br J Surg 1979;66(6):428–9.

Griffiths 1976 {published data only}∗ Griffiths DA, Simpson RA, Shorey BA, SpellerDC, Williams NB. Single-dose peroperative antibioticprophylaxis in gastrointestinal surgery. Lancet 1976;2(7981):325–8.

Gurry 1976 {published data only}∗ Gurry JF, King DW, Rutter KP, Brooke BN. A controlledtrial if intraperitoneal noxytiolin in perforated appendicitis.Br J Surg 1976;63(5):400–1.

Harnoss 1986 {published data only}∗ Harnoss BM, Raetzel G, Görtz G, Häring R, HilgemannK, Hopfenmüller W. A prospective randomized study of

antibiotic prophylaxis with metronidazole in appendicitis.Krankenhausartz 1986;59(8):589–93.

Hutchinson 1983 {published data only}∗ Hutchinson GH, Patel BG, Doig CM. A double-blindcontrolled trial of metronidazole suppositories in childrenundergoing appendicectomy. Current Medical Research &

Opinion (England) 1983;8(6):441–5.

Keiser 1983 {published data only}∗ Keiser TA, MacKenzie RL, Feld R, Leers N. Prophylacticmetronidazole in appendectomy: a double-blind controlledtrial. Surgery 1983;93(1 pt 2):201–3.

Kekomäki 1983 {published data only}∗ Kekomäki M, Louhimo I. [Metronidazolein appendectomy] [Finnish] [Metronidatsoli jaappendisektomia]. Suomen Löökörilehti 1983;38:353–57.

Kizilcan 1992 A {published data only}∗ Kizilcan F, Tanyel FC, Buyukpamukcu N, Hicsonmez A.The necessity of prophylactic antibiotics in uncomplicatedappendicitis during childhood. J Pediatric Surg 1992;27(5):586–8.

Kizilcan 1992 B {published data only}

As Kizilcan 1992 A.

Kizilcan 1992 C {published data only}

As Kizilcan 1992 A.

Kortelainen 1982 {published data only}∗ Kortelainen P, Huttunen R, Kairaluoma MI, MokkaREM, Laitinen S, Larmi TKI. Single-dose intrarectalmetronidazole prophylaxis against wound infection afterappendectomy. Am J Surg 1982;143:244–45.

Leigh 1976 {published data only}∗ Leigh DA, Pease R, Henderson H, Simmons K, RussR. Prophylactic lincomycin in the prevention of woundinfection following appendicectomy: a double blind study.Br J Surg 1976;63(12):973–7.

Morris 1980 A {published data only}∗ Morris WT, Innes DB, Richardson RA, Lee AJ, Ellis-Pegler RB. The prevention of post-appendicectomy sepsisby metronidazole and cefazolin: a controlled double blindtrial. Aust NZJ Surg 1980;50(4):429–33.

Morris 1980 B {published data only}

As Morris 1980 A.

Morris 1980 C {published data only}

As Morris 1980 A.

Paakkonen 1982 {published data only}∗ Paakkonen M, Mononen P, Kostiainen S. The value of asingle intravenous dose of metronidazole as prophylaxisagainst wound infection after appendicectomy. Ann Chir

Gynaecol 1982;71(2):137–9.

Raahave 1970 {published data only}∗ Raahave D, Poulsen PE. Perforated appendicitis andantibiotics. A survey and a controlled clinical trial. Acta

Chir Scand 1970;136(8):715–23.

Richards 1981 {published data only}∗ Richards DG, Clark RG, Rowlands BJ, Moore PJ, Eyre-Brook I, Kay PH. Antibiotic prophylaxis against wound



infection in emergency abdominal surgery. J Royal Coll Surg

Edinb 1981;26(4):232–37.

Rodgers 1979 {published data only}∗ Rodgers J, Ross D, McNaught W, Gillespie G. Intrarectalmetronidazole in the prevention of anaerobic infectionsafter emergency appendicectomy: a controlled clinical trial.Br J Surg 1979;66(6):425–7.

Rowlands 1982 {published data only}∗ Rowlands BJ, Clark RG, Richards DG. Single-doseintraoperative antibiotic prophylaxis in emergencyabdominal surgery. Arch Surg 1982;117(2):195–9.

Saario 1981 {published data only}∗ Saario I, Wuokko E, Saario L, Silvola H. Metronidazoleprophylaxis against wound infection in patients undergoingappendicectomy. Ann Chir Gynaecol 1981;70(2):71–4.

Salo 1981 {published data only}∗ Salo J, Silvennoinen E, Hulkko A, Ervasti E, HolopainenO. Tinidazole in the prophylaxis of post-appendicectomyinfections. Ann Chir Gynaecol 1981;70(4):187–90.

Sole 1982 {published data only}∗ Sole GM, Studley JGN, Powis SJA. Post-appendicectomywound sepsis the prophylactic value of Metronidazole andCefoxitin. Br J Clin Pract 1982;36(3):90–2.

Stoller 1965 {published data only}∗ Stoller JL. Topical antibiotic therapy in acute appendicitis.Br J Clin Practice 1965;19(12):687–8.

Söderquist 1995 A {published data only}∗ Söderquist-Elinder C, Hirsch K, Bergdahl S, RutqvistJ, Frenckner B. Prophylactic antibiotics in uncomplicatedappendicitis during childhood - a prospective randomisedstudy. Eur J Pediatr Surg 1995;5:282–285.

Söderquist 1995 B {published data only}

Söderquist-Elinder C, Hirsch K, Bergdahl S, Rutqvist J,Frenckner B. Prophylactic antibiotics in uncomplicatedappendicitis during childhood - a prospective randomisedstudy. Eur J Pediatr Surg 1995;5:282–285.

Tanner 1980 {published data only}∗ Tanner WA, Ali AE, Collins PG, Fahy AM, Lane BE,McCormack T. Single dose intra-rectal metronidazole asprophylaxis against wound infection following emergencyappendicectomy. Br J Surg 1980;67(11):809–10.

Viitanen 1984 A {published data only}∗ Viitanen J, Tunturi T, Auvinen O, Pessi T. Tinidazoleprophylaxis in appendicectomies. A controlled study ofsingle-dose versus 3-day therapy. Scand J Gastroenterol

1984;19(1):111–5.

Viitanen 1984 B {published data only}

As Viitanen 1984 A.

Wayand 1982 {published data only}∗ Wayand W, Trost A. Perioperative antibiotic prophylaxiswith cefamandol before appendectomy: a prospectiverandomized double blind study. Fortschr Med 1982;100(5):190–4.

Willis 1976 {published data only}∗ Willis AT, Ferguson IR, Jones PH, Phillips KD, Tearle PV,Berry RB, Fiddian RV, Graham DF, Harland DH, InnesDB, Mee WM, Rothwell-Jackson RL, Sutch I, Kilbey C,Edwards D. Metronidazole in prevention and treatmentof bacteroides infections after appendicectomy. Br Med J

1976;1(6005):318–21.

Winslow 1983 {published data only}∗ Winslow RE, Dean RE, Harley JW. Acute nonperforatingappendicitis. Efficacy of brief antibiotic prophylaxis. Arch

Surg 1983;118(5):651–5.

References to studies excluded from this review

Amgwerd 1981 {published data only}∗ Amgwerd R, Biegger P. Acute nonperforating appendicitis.Efficacy of brief antibiotic prophylaxis [Prospektive Studiezur Verhutung von Wundinfekten nach Appendektomie beiAppendicitis acuta]. Schweiz Med Wochenschr 1981;111

(35):1269–73.

Andersen 1972 {published data only}∗ Andersen B, Bendtsen A, Holbraad L, Schantz A. Woundinfections after appendicectomy. I. A controlled trial on theprophylactic efficacy of topical ampicillin in non-perforatedappendicitis. II. A controlled trial on the prophylacticefficacy of delayed primary suture and topical ampicillinin perforated appendicitis. Acta Chir Scand 1972;38(5):531–6.

Badia 1994 {published data only}∗ Badia JM, Martinez-Rodenas F, Oms LM, ValverdeJ, Franch G, Rosales A, Serrano R, Sitges-Serra A.[Randomized prospective study on antibiotic prophylaxiscompared with lavage of the surgical wound in unperforatedappendicitis] [Spanish] [Estudio prospectivo aleatorizado dela profilaxis antibiotica comparada con el lavado de la heridaquirurgica en apendicitis no perforada]. Med Clin (Barc)

1994;103(6):201–4.

Bates 1974 {published data only}∗ Bates T, Down RH, Houghton MC, Lloyd GJ. Topicalampicillin in the prevention of wound infection afterappendicectomy. Br J Surg 1974;61(6):489–92.

Birkigt 1989 {published data only}∗ Birkigt HG, Beyer H, Schmidt U. [Preventiveuse of single dose antibiotics in acute appendicitis.Results of a prospective randomized clinical study].[German] [Single–dose–Antibiotikaprophylaxe bei akuterAppendizitis. Ergebnisse einer prospektiven randomisiertenklinischen Studie.]. Zentralbl Chir 1989;114(20):1348–54.

Birkigt 1991 {published data only}∗ Birkigt HG, Beyer H. [General or individually calculatedpreventive antibiotic administration. Summary of theMagdeburg appendicitis study]. [German] [Generelle oderindividuell kalkulierte Antibiotikaprophylaxe. Rusumee derMagdeburger Appendizitisstudie]. Zentralbl Chir 1991;116

(13):795–800.



Bröte 1976 {published data only}∗ Brote L, Gillquist J, Hojer H. Prophylactic cephalothinin gastrointestinal surgery. Acta Chir Scand 1976;142(3):238–45.

Calman 1971 {published data only}∗ Calman KC, Kennedy F, Meudell CM, Sleigh JD.Prophylaxis of wound infection. Brit Med J 1971;4:232.

Crosfill 1969 {published data only}∗ Crosfill M, Hall R, London D. The use of chlorhexidineantisepsis in contaminated surgical wounds. Br J Surg 1969;56(12):906–8.

Dixon 1984 {published data only}∗ Dixon JM, Armstrong CP, Duffy SW, Chetty U, DaviesGC. A randomized prospective trial comparing thevalue of intravenous and preincisional cefamandole inreducing postoperative sepsis after operations upon thegastrointestinal tract.. Surg Gynaecol Obstet 1984;158(4):303–7.

Evans 1973 {published data only}∗ Evans C, Pollock AV. The reduction of surgical woundinfections by prophylactic parenteral cephaloridine. Acontrolled clinical trial. Br J Surg 1973;60(6):434–7.

Everson 1977 {published data only}∗ Everson NW, Fossard DP, Nash JR, Macdonald RC.Wound infection following appendicectomy: the effect ofextraperitoneal wound drainage and systemic antibioticprophylaxis. Br J Surg 1977;64(4):236–8.

Feltis 1967 {published data only}∗ Feltis JM jr, Hamit HF. Use of prophylactic antimicrobialdrugs to prevent postoperative wound infections. Am J Surg

1967;114(6):867–70.

Gilmore 1973 {published data only}∗ Gilmore OJ, Martin TD, Fletcher BN. Prevention ofwound infection after appendicectomy. Lancet 1973;1(7797):220–2.

Gilmore 1975 {published data only}∗ Gilmore OJ, Sanderson PJ. Prophylactic interparietalpovidone-iodine in abdominal surgery. Br J Surg 1975;62

(10):792–9.

Gómez-Alonso 1984 {published data only}∗ Gomez-Alonso A, Lozano F, Perez A, Almazan A, Abdel-lah A, Cuadrado F. Systemic prophylaxis with gentamicin-metronidazole in appendicectomy and colorectal surgery: aprospective controlled clinical study. Int Surg 1984;69(1):17–20.

Harahsheh 2002 {published data only}∗ Harahsheh B, Hiyasat B, Abulail A, Al-Basheer M.Management of wound infection after appendectomy: areparenteral antibiotics useful?. East Mediterr Health J 2002;8(4-5):638–44. [MEDLINE: 15603047]

Herrera-Garcia 1985 {published data only}∗ Herrera-Garcia A, Dibildox M, Albarran Trevino C.[Efficacy of a single intravenous dose of antimicrobials inprevention against post-appendectomy wound infection: ablind comparative study of metronidazole, clindamycin and

a placebo] [Spanish]. Rev Gastroenterol Mex. 1985;50(1):41–5.

Kling 1985 {published data only}∗ Kling PA, Holmlund D, Burman LG. Prevention ofpost-operative infection in appendicectomy by single doseintravenous metronidazole. Acta Chir Scand 1985;151(1):73–6.

Leigh 1978 {published data only}∗ Leigh DA. Indications for antibiotic prophylaxis andtreatment in patients undergoing appendicectomy. J

Antimicrob Chemoth 1978;4(suppl CS):15–23.

Marti 1978 {published data only}∗ Marti MC, Moser G. [Prevention of parietal septiccomplications by irrigation of the surgical wound]. [French][Prevention des complications septiques parietales parirrigation de la plaie operatoire]. Helv Chir Acta 1979;45

(6):739–42.

McGreal 2002 {published data only}

McGreal GT, Joy A, Manning B, Kelly JL, O’Donell JA,Kirwan WW, Redmond HP. Antiseptic wick: does it reducethe incidence of wound infection following appendectomy?.World J Surg 2002;26(5):631–4. [MEDLINE: 12098059]

McLean 1983 {published data only}∗ McLean MD, Buick RG, Boston VE. The influenceof metronidazole prophylaxis and the method of closureon wound infection in non-perforating appendicitis inchildhood. Z Kinderchir 1983;38:283–5.

Okubadejo 1976 {published data only}∗ Okubadejo DA, Peet TND, Turner DTL. Clindamycinprophylaxis in appendectomy wound infections.Chemotherapy 1976;1:287–93.

Pietila 1982 {published data only}∗ Pietila J, Jauhiainen K, Davidsson L. [Metronidazoleprophylaxis in excision of the appendix]. [Finnish][Metronidatsoliprofylaksi umpilisakkeen poistonyhteydessa.]. Duodecim 1982;98(4):267–71.

Pollock 1972 {published data only}∗ Pollock AV, Tindal DS. The effect of a single-doseparenteral antibiotic in the prevention of wound infection.A controlled trial. Br J Surg 1972;59(2):98–9.

Rambo 1972 {published data only}∗ Rambo WM. Irrigation of the peritoneal cavity withcephalothin. Am J Surg 1972;123(2):192–5.

Tanphiphat 1978 {published data only}∗ Tanphiphat C, Sangsubhan C, Vongvaravipatr V, La-Ongthong B, Chodchoy V, Treesaranuvatana S, IttipongP. Wound infection in emergency appendicectomy: aprospective trial with tropical ampicillin and antisepticsolution irrigation. Br J Surg 1978;65(2):89–91.

Taylor 2000 {published data only}∗ Taylor E, Dev V, Shah D, Festekjian J, Gaw F. Complicatedappendicitis: is there a minimum intravenous antibioticrequirements? A prospective randomized trial.. Am Surg

2000;66:887–90. [MEDLINE: 10993623]



Taylor 2004 {published data only}∗ Taylor E, Berjis A, Bosch T, Hoehne F, Ozaeta M. Theefficacy of postoperative oral antibiotics in appendicitis: arandomized prospective double-blinded study.. Am Surg

2004;70(10):858–62. [MEDLINE: 15529837]

Walsh 1981 {published data only}∗ Walsh JA, Watts JMCK, McDonald PJ, Findlay-Jones J.The effect of topical povidone-iodine on the incidence ofinfection in surgical wounds. Br J Surg 1981;68:185–89.

Willis 1979 {published data only}∗ Willis AT. Metronidazole in the prevention and treatmentof anaerobic sepsis. Scandinavian Journal of Infectious

Diseases - Supplement 1979;19:98–104.

References to studies awaiting assessment

Simpson 2002 {published data only}∗ Simpson ET, Corbett H. Antibiotic use in appendicitis[abstract]. ANZ Journal of Surgery 2002;72 Suppl:A72.

Additional references

Addiss 1990

Addiss DG, Shaffer N, Fowler BS, Tauxe RV. Theepidemiology of appendicitis and appendectomy in theUnited States. Am J Epiderm 1990;132(5):910–925.

Almqvist 1995

Almqvist P, Leandoer L, Törnqvist A. Timing of AntibioticTreatment in Non-perforated Gangrenous Appendicitis.Eur J Surg 1995;161:431–433.

Altemeier 1938

Altemeier WA. The bacterial flora of acute perforatedappendicitis with peritonitis. Ann Surg 1938;107:517–528.

Arnbjörnsson 1983

Arnbjörnsson E, Bengmark S. Obstruction of the appendixlumen in relation to pathogenesis of acute appendicitis.Acta Chir Scand 1983;149:789–791.

Bennion 1990

Bennion RS, Thompson JE, Baron EJ, Finegold SM.Gangrenous and perforated appendicitis with peritonitis:treatment and bacteriology. Clin Ther 1990;12(suppl. c):31–44.

Blewett 1995

Blewett JC, Krummel TM. Perforated appendicitis: Pastand future controversies. Seminars in Pediatric Surgery 1995;4(4):234–38.

Fenyö 1995

Fenyö G. [Appendectomy in Sweden] [Swedish][Appendektomi i Sverige]. Nord Med 1995;110:11–113.

Graffeo 1996

Graffeo CS, Counselmann FL. Appendicitis. Emergency

Medicine Clinics of North America 1996;14(4):653–.

Jadad 1996

Jadad AR, Moore RA, Carroll D, Jenkinson C, ReynoldsDJ, Cavaghan DJ, McQuay HJ. Assessing the quality ofreports of randomized clinical trials: Is blinding necessary?.Controlled Clinical Trials 1996;17(1):1–12.

Leigh 1974

Leigh DA, Simmons K, Norman E. Bacterial flora of theappendix fossa in appendicitis and postoperative woundinfections. J Clin Pathol 1974;27(12):997–1000.

Luckmann 1989

Luckmann R. Incidence and case fatality rates for acuteappendicitis in California. Am J Epidem 1989;129(5):905–918.

∗ Indicates the major publication for the study



C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Ahmed 1987

Methods Randomised controlled trial. Randomisation method not stated.Double-blinded. Unclear blinding of outcome assessor.

Participants 190 patients enrolled in the study.Age-range: Treatment group: 10-45, Placebo group: 10-40Mean: Treatment group: 19,2 +/- 6,7 (s.d.), Placebo group: 21,3 +/- 8,7 (s.d.)Patients with normal, gangrenous or perforated appendix and antibiotics prior to surgery were excludedbefore randomisation

Interventions Treatment group: Metronidazole 500 mg=100 ml i.v inter-operatively.Placebo group: Saline 100 ml i.v peroperatively

Outcomes Wound infection (Purulent discharge from the incision).

Notes No drain treatment.

Risk of bias

Item Authors’ judgement Description

Allocation concealment? Unclear B - Unclear

Azabache 1987 A

Methods Randomised controlled trial. Randomisation method stated as simple. Patient and surgeon blinded. Un-clear blinding of outcome assesor

Participants 258 eligible patients. 92 excluded before randomisation. 166, 88 males and 78 females enrolled in thestudy.Age-range: 6-71Mean: 2312 patients excluded after randomisation.The study has 2 subgroups (see Azabache 1987 B).In Azabache 1987 A 110 patients enrolled in study.

Interventions Treatment group: Gentamycin 4 mg/kg and Clindamycin 15 mg/kg one hour inter-operatively hereafterGentamycin eighthourly and Clindamycin sixhourly for 24 hours if appendix was suppurativ and 72hours if appendix was gangrenous/perforated.Placebo group: Not stated. Regime as above.

Outcomes Wound infection (Pus in the cellular space under or above the rectusmuscle 3 weeks postoperatively)




Azabache 1987 A (Continued)

Risk of bias



Azabache 1987 B

Methods Randomised controlled trial. Randomisation method stated

Participants 258 eligible patients. 92 excluded before randomisation. 166, 88 males and 78 females enrolled in thestudy.Age-range: 6-71Mean: 2312 patients excluded after randomisation.The study has 2 subgroups (see Azabache 1987 A).In Azabache 1987 B 110 patients enrolled in study.

Interventions Treatment group:Penicilin G 400.000 UI/kg and Chloramphnicol 50 mg/kg one hour intra operatively. Hereafter penicillinG each four hour and chloramphenicol each six hour for 24 hours, if appendix was suppurative and 22hours if appendix was gangrenous/perforated.Placebo: Not stated. Regimen as above.

Outcomes Wound infection (Pus in the cellular space under or above the rectusmuscle 3 weeks postoperatively)


Risk of bias



Bates 1980

Methods Controlled clinical trial. Random allocation by the admittiong house surgeon. No blinding of the patient.Adequate blinding of surgeon and unclear blinding of outcome assesor

Participants 200 eligible patients. 30 excluded after randomisation. 170, 90 males and 80 females enrolled in study.Age-range: 0-90

Interventions Treatment group: 1 g metronidazole supp 1 hour preoperatively and 1 g supp or orally 8 hourly postop-eratively for 7 days. children below 12 received half dose.Placebo group: No treatment



Bates 1980 (Continued)

Outcomes Woundinfection (A frank discharge of pus)Lenght of stay in hospital

Notes No drain treatment

Risk of bias


Allocation concealment? No C - Inadequate

Bauer 1989

Methods Randomised controlled trial. Randomisation method not stated.Patient blinded. Unclear blinding of surgeon and out-come assessor

Participants 2387 eligible patients. 652 excluded after randomisation. 1735 enrolled in study.Age-range: 3 months - 90 years. Mean 23Patients with allergy to Cefoxitin or Cefalosoprins, moribund, in coma, impaired renal function, shock,antibiotics within 3 days, lactating and pregnant women, younger than 3 months of age were excludedbefore randomisation

Interventions Treatment group: Cefoxitin 2 g (children <12: 40 mg/kg) i.v inter-operatively.Placebo group: No treatment.

Outcomes Wound infection (Discharge of pus from the wounds occurring spontaneously or after incision).Postoperative intraabdominal absces (Persistent pyrexia without any other focus, after operation, palpablemass in the abdomen or discharge of pus per rectum).Length of stay in hospitalNo postoperative deaths. One died from aorta aneurism, 1 from livercancer and 2 from thrombosis a.mesenterica

Notes No drain treatment.Antibiotics administered 3-5 min before surgery.

Risk of bias





Bergmark 1985

Methods Randomised controlled trial. Randomisation method not stated.Double-blinded. Unclear blinding of out-come assessor.

Participants 183 eligible patients. 50 patients excluded after randomisation. 133 patients, 59 males and 74 femalesenrolled in the study.Age-range: Treatment group: 16-72, Placebo group: 17-69Mean: Treatment group 39, Placebo group 36

Interventions Treatment group: Trimethoprim 240 mg and Sulfametizole 1200 mg and Metronidazole 1,5 g (15 ml) i.v preoperatively.Placebo group: Saline 0,9% 15 ml i.v preoperatively.

Outcomes Wound infection (Pus precent in the wounds or if microbiological culture was positive from a woundopening spontaneously or opened by a surgeon when an infefection was inspected)


Risk of bias



Browder 1989 A

Methods RCT, Computer-generated double-blind trial

Participants 175 eligible122 enrolled

Interventions Ceftizoxime, Cefamandole versus placebo given IV pre-op and 6-12 hours after surgeryThree arm study

Outcomes Wound infection (not defined)

Notes Only Pt’s with non-perforative appendicitis were enrolled

Risk of bias


Allocation concealment? Yes A - Adequate



Browder 1989 B

Methods As above

Participants As above

Interventions As above

Outcomes As above

Notes As above

Risk of bias


Allocation concealment? Unclear D - Not used

Busuttil 1981 A

Methods Randomised controlled trial. Randomisation from a masterlist outside the experimential protocol section.Triple-blinded.

Participants 189 eligible patients. 52 patients excluded after randomisation. 136 patients enrolled in study.Age-range: 4-75, mean 23.The study has 3 subgroups (see Busuttil 1981 B).In Busuttil 1981 A 90 patients enrolled in the study.Patients with perforated appendix, allergy to cephalosporins or penicillins, antibiotic therapy within 72hours before surgery, pregnacy, inability to 30- days follow-up, serious underlying illnes expected to requireantibiotic therapy, were excluded before randomisation

Interventions Treatment group: Cefamandole 2 g (children 100-150 mg/kg/day) and Carbenicillin 3 g (children 400-500 mg/kg/day) i.v preoperatively, 4 hours postoperatively and every 6 hour thereafter for 24 hours.Placebo treatment: Equivalent volumes of dilution i.v preoperatively, 4 hours postoperatively and every 6hour thereafter for 24 hours

Outcomes Wound infection (Collection of pus drained spontaneously or by incision).Length of stay in hospital


Risk of bias





Busuttil 1981 B

Methods Randomised controlled trial. Randomisation from a masterlist outsite the experimental protocol section.Triple-blinded.

Participants 189 eligible patients. 52 patients excluded after randomisation. 136 patients enrolled in the study.Age-range: 4-75, mean 23The study has 3 subgroups (see Busuttil 1981 A).In Busuttil 1981 B 91 patients enrolled in the study.Patients with perforated appendix, allergy to cephalosporins or penicillins, antibiotic therapy within 72hours before surgery, pregnacy, inability to 30- days follow-up, serious underlying illnes expected to requireantibiotic therapy, were excluded before randomisation

Interventions Treatment group: Cefamandole 2 g i.v preoperatively, 4 hours postoperatively and every 6 hours thereafterfor 24 hours. Children 100-150 mg/kg/day.Placebo treatment: Equivalent volume of dilution i.v preoperatively, 4 hours postoperatively and every 6hours thereafter for 24 hours

Outcomes Wound infection (Collection of pus drained spontaneously or by incision).Length of stay in hospital


Risk of bias



Chiam 1983 A

Methods Randomised controlled trial. Randomisation by random numbers. Double-blinded. Unclear blinding ofoutcome assessor

Participants 400 eligible patients. 117 excluded after randomisation. 283 enrolled in the study.All patients above 12 years of age.Patients already receiving antibiotics or steroids, diabetic and preoperative diagnosis of perforated appendixwere excluded before randomisation.The study has 4 subgroups (see Chiam 1983 B & C).In Chiam 1983 A 147 patients enrolled in study.

Interventions Treatment group: Metronidazole 1 g supp preoperatively and eight-hourly for 3 days and Cotrimoxazole2 ml i.m preoperatively and twice daily for 3 days.Placebo group: Not specified, but administred as supp and i.m as regime above

Outcomes Wound infection (Pus in the main wound).

Notes Patients with the operative diagnosis of perforated appendix were included in the study.No comments on drain treatment.



Chiam 1983 A (Continued)

Risk of bias



Chiam 1983 B


Participants 400 eligible patients. 117 excluded after randomisation. 283 enrolled in study.All patients above 12 years of age.Patients already receiving antibiotics or steroids, diabetic and preoperative diagnosis of perforated ap-pendix, were excluded before randomisation.The study has 4 subgroups (see Chiam 1983 A & C).In Chiam 1983 B 150 patients enrolled in the study.

Interventions Treatment group: Metronidazole 1 g supp preoperatively and eight-hourly for 3 days.Placebo group: Not specified, regime above.


Notes Patients with the operative diagnosis of perforated appendix were included in the study.No comments on drain treatment.

Risk of bias



Chiam 1983 C


Participants 400 eligible patients. 117 excluded after randomisation. 283 enrolled in the study.All patients above 12 years of age.Patients already receiving antibiotics or steroids, diabetic and preoperative diagnosis of perforated ap-pendix, were excluded before randomisation.The study has 4 subgroups (see Chiam 1983 A & B).In Chiam 1983 C 134 patients enrolled in the study.

Interventions Treatment group: Cotrimoxazole 2 ml i.m preoperatively and twice daily for 3 daysPlacebo group: Not specified, regime as above.



Chiam 1983 C (Continued)


Notes Patients with the operative diagnosis of perforated appendix were included in study.No comments on drain treatment.

Risk of bias



Corbett 1979

Methods Randomised controlled trial. Randomisation method not stated.Patient blinded. Unclear blinding of surgeon and outcome assessor

Participants 105 patients enrolled in the study.Age-range 5-70.

Interventions Treatment group: Metronidazole 1 g supp preoperatively and eight-hourly for 3 days. (children <14: ½dosis)Placebo group: supp regime as above.

Outcomes Wound infection (Definite cellulitis and pyrexia, copious seropurulent discharge)

Notes Some patients received drain.

Risk of bias



Creve 1980 A

Methods Randomised cotrolled trial. Randomisation by sealed envelopes. Blinding of patients and surgeon. Unclearblinding of outcome assesor

Participants 13 patients enrolled in the study.Age-range: 18-76

Interventions Treatment group: Gentamycin 80 mg i.v. inter-operatively.Placebo group: No treatment

Outcomes Wound infection (presense of pus which either spontaneously discharged or required evacuation)



Creve 1980 A (Continued)

Notes No comments on drain treatment.The results are a part of a study including other kind of gastrointestinal sugery

Risk of bias



Creve 1980 B

Methods Randomised cotrolled trial. Randomisation by sealed envelopes. Blinding of patients and surgeon. Unclearblinding of outcome assesor

Participants 4 patients enrolled in the study.Age-range: 18-76

Interventions Treatment group: Gentamycin 80 mg and Clindamycin 600 mg i.v inter-operatively.Placebo group: No treatment

Outcomes Wound infection (presense of pus which either spontaneously discharged or required evacuation)

Notes No comments on drain treatment.The results are a part of a study including other kind of gastrointestinal sugery

Risk of bias



Donovan 1979 A

Methods Randomised controlled trial. Randomisation based on a table of random numbers.Patient blinded. Unclear blinding of surgeon and outcome-assesor

Participants 250 eligible patients.12 patients were excluded after randomisation. 238 patients were enrolled in thestudy. All patients above 12 years of age.The study has 3 subgroups (see Donovan B).In Donovan 1979 A 153 patients enrolled in the study.Patients who received antibiotics within the previous 7 days before operation or had allergy to penicillin,were excluded before randomisation

Interventions Treatment group: Clindamycin 600 mg i.m preoperatively to the anaesthetized patient.Placebo treatment: Saline 3 ml i.m preoperatively to the anaesthetized patient



Donovan 1979 A (Continued)

Outcomes Wound infection (Discharge of pus from the wound either spontaneously or after incision).One patient died 3 months postoperative from pulmonary embolism

Notes Draining of the wound depending on surgeon. 14 patients in the treatment group were drained, 8contracted wound infection. 12 patients in the placebo group were drained, 6 contracted wound infection.Some patients received additional antibiotics starting more than 48 hours postoperatively.Some patients received additional antibiotics starting within 48 hours postoperatively. They were excludedunless they developed a wound infection

Risk of bias



Donovan 1979 B

Methods Randomised controlled trial. Randomisation based on a table of random numbers.Patient blinded. Unclear blinding of surgeon and outcome assessor

Participants 250 eligible patients.12 patients were excluded after randomisation. 238 patients were enrolled in thestudy. All patients above 12 years of age.The study has 3 subgroups (see Donovan A).In Donovan 1979 B 157 patients enrolled in the study.Patients who received antibiotics within the previous 7 days before operation or had allergy to penicillin,were excluded before randomisation

Interventions Treatment group: Cefazoline 1 g i.m preoperatively to the anaesthetized patient.Placebo treatment: Saline 3 ml i.m preoperatively to the anaesthetized patient

Outcomes Wound infection (Discharge of pus from the wound either spontaneously or after incision).One patient died 3 months postoperative from pulmonary embolism

Notes Draining of the wound depending on surgeon. 15 patients in the treatment group were drained, 13contracted wound infection. 12 patients in the placebo group were drained, 6 contracted wound infection.Some patients received additional antibiotics starting more than 48 hours postoperatively.Some patients received additional antibiotics starting within 48 hours postoperatively. They were excludedunless they developed a wound infection

Risk of bias





Eklund 1987

Methods Randomised controlled trial. Randomisation by a list of random numbers.Double-blinded. Unclear blinding of outcome assessor.

Participants 510 eligible patients, 214 males and 296 females enrolled in the study.All patients more than 12 years of age.Patients with perforated appendix, treated with antibiotics for other disease and patients undergoingadditional procedure were excluded before randomisation

Interventions Treatment group: Tinidazole 2 mg/ ml 200 ml topical peroperatively.Placebo group: Saline 200 ml topical peroperatively.

Outcomes Woundinfection (Wound discharge visible pus either spontaneously or after debridement)

Notes No comments on drain treatment.180 patients had normal appendix.

Risk of bias



El-Sefi 1986 A


Participants 480 eligible patients. 80 patients excluded after randomisation. 400 enrolled in the study.Patients with perforated appendix were excluded after randomisation.The study has 4 subgroups (see El-Sefi 1986 B & C).In El-Sefi 1986 A 200 patients enrolled in the study.

Interventions Treatment group: Metronidazole 500 mg IV preoperatively and eight-hourly for the next 3 days. (Whenthe patient tolerated oral medication converted to 250 orally) and Cefazolin 500 mg i.v preoperativelyand eight-hourly for the next 3 days. (When the patient tolerated oral medication converted to 250 orally).Placebo group: Not specified, same regime as above

Outcomes Wound infection (Presence of pus or a purulent exudate of the wound)

Notes No comments on drain treatment.Wrote to author to specify subgrouping on drop-outs.

Risk of bias




El-Sefi 1986 A (Continued)


El-Sefi 1986 B


Participants 480 eligible patients. 80 patients excluded after randomisation. 400 enrolled in study.Patients with perforated appendix were excluded after randomisation.The study has 4 subgroups (see El-Sefi 1986 A & C).In El-Sefi 1986 B 200 patients enrolled in the study.

Interventions Treatment group: Metronidazole 500 mg i.v preoperatively and eight-hourly for the next 3 days. (Whenthe patient tolerated oral medication converted to 250 orally) and Tobramycin 80 mg i.v preoperativelyand eight-hourly for the next 3 days. (When the patient tolerated oral medication converted to 80 mg i.m).Placebo group: Not specified same regime as above.


Notes No comments on drain treatmentWrote to author to specify subgrouping on drop-outs.

Risk of bias



El-Sefi 1986 C


Participants 480 eligible patients. 80 patients excluded after randomisation. 400 enrolled in the study.Patients with perforated appendix were excluded after randomisation.The study has 4 subgroups (see El-Sefi 1986 A & B).In El-Sefi 1986 C 200 patients enrolled in the study.

Interventions Treatment group: Metronidazole 500 mg i.v preoperatively and eight-hourly for the next 3 days. (Whenthe patient tolerated oral medication converted to 250 orally)Placebo group: Not specified same regime as above.




El-Sefi 1986 C (Continued)

Notes No comments on drain treatmentWrote to author to specify subgrouping on drop-outs.

Risk of bias



Foster 1978

Methods Randomised controlled trial. Randomisation based on a computer list kept by the hospital pharmacist.Triple-blinded

Participants 165 eligible patients. 26 excluded after randomisation. 139, 74 males and 65 females enrolled in thestudy. Patients with perforated appendix and different infections such as pelvic inflammatory disease, wereexcluded after randomisation.Patients with allergy to penicillin og cephalosporins, antibiotic administration 48 hours before surgery,expectation of need for antibiotic treatment in the immediate postoperative periode and impaired renalor hepatic function were excluded before randomisation

Interventions Treatment group: Cephaloridine 50 mg/kg i.m. The first dose given with preanaesthetic medication andpostoperatively x4 daily for 2 days.Placebo group: Not stated: Regime like the treatment group.

Outcomes Wound infection (Not defined).

Notes No comments on drain treatment

Risk of bias



Foster 1981 A

Methods Randomised controlled trial. Randomisation methode not stated.Doubleblinding. Unclear blinding of outcome assesor.

Participants 496 patients enrolled in the study.The study has 3 subgroups (see Foster 1981 B).In Foster 1981 A 377 patients enrolled in the study.

Interventions Treatment group: Metronidasole 1 g supp 40 min preoperatively.Placebo group: Identical supp 40 min preoperatively.



Foster 1981 A (Continued)


Notes Some patients got drain treatment.

Risk of bias



Foster 1981 B

Methods Randomised controlled trial. Randomisation methode not stated.Blinding of patient. No blinding of surgeon and unclear blinding of outcome assesor

Participants 496 patients enrolled in the study.The study has 3 subgroups (see Foster 1981 A).In Foster 1981 B 236 patients enrolled in the study.

Interventions Treatment group: Povidone iodine dry powder per-operatively.Placebo group: Nothing


Notes Some patients got drain treatment.

Risk of bias



Giacomantonio 1982

Methods Randomised controlled trial. Randomisation by random numbers in the pharmacy.Triple-blinded.

Participants 42 enrolled in the study.Age-range: Pediatric.Only patients with acute appendicitis without perforation.Patients allergic to penicillin og cephalosporin were excluded before randomisation

Interventions Treatment group: Cefamandole 25 mg/kg i.v / i.m preoperatively and immediately postoperatively and 6hours later.Placebo group: Not specified, same regime as above.



Giacomantonio 1982 (Continued)

Outcomes Wound infection (Presence of pus in the wound or wound pain, tendernes or erythema or sufficientmagnitude to interfere with the patient´ s well-being or to prolong hospital stay)

Notes No comments on drain treatment.

Risk of bias



Gledhill 1983

Methods Clinical controlled trial. Allocation according to the month of their day of birth.Blinding unclear.

Participants 102 enrolled in the study.mean: Treatment group: 24,9, placebo group: 26,2Patients with weight less than 25 kg, pregnant women or steroid treatment were excluded before random-sation

Interventions Treatment group: Cefamandole 2 g i.v inter-operatively.Placebo group: Nothing.


Notes Alle patients received drain treatment.

Risk of bias



Go 1986

Methods Randomised controlled trial. Randomisation method not stated.Doubleblinded. unclear blinding of outcome assesor.

Participants 159 patients enrolled in the study.Age-range: 12-79, Mean: 29,6

Interventions Treatment group: Metronidazole 1 g in 100 ml saline IV inter-operatively.Placebo group: Saline 100 ml inter-operatively.




Go 1986 (Continued)


Risk of bias



Gottrup 1979

Methods Randomised controlled trial. Randomisation by random numbers.Double-blinded

Participants 426 eligible patients. 20 patients were excluded after randomisation. 406 patients enrolled in the study.Age-range 5->50.Patients with allergy to metronidazol, pregnant women, patients with blood dyscrasia, active disease ofthe central nervous system or alcoholism were excluded before randomisation

Interventions Treatment group: Metronidazole 500 mg = 100 ml i.v preoperatively.Placebo group: 100 ml saline i.v preoperatively.

Outcomes Wound infection (Superficial accumulation of pus requiring surgical drainage).Postoperative intraabdominal abscess (Pyrexia, postoperatively for more than 72 hours, and for wich allother causes could be excluded; Abdominal tenderness or distension; Discharge of pus per rectum)


Risk of bias



Greenall 1979

Methods Randomised controlled trial. Randomisation method not stated.Double-blinded. Unclear blinding of outcome-assessor.

Participants 116 eligible patients. 16 excluded before the code was broken. 111 patients, 51 males and 49 femalesenrolled in the study.Age-range 5-73.Mean 22 +/- 15 (s.d.) in treatment group, +/- 14 (s.d.) in placebo group

Interventions Treatment group: Metronidazole 500 mg in 100 ml saline i.v preoperatively.Placebo group: Saline 100 ml i.v preoperatively.

Outcomes Wound infection (Discharge of pus form the wound).



Greenall 1979 (Continued)

Notes Draining of the wound depending on surgeon. 5 patients in the treatment group were drained, nonecontracted wound infection. 9 patients in the placebo group were drained, 3 contracted wound infection

Risk of bias



Griffiths 1976

Methods Randomised controlled trial. Randomisation method not stated.Triple-blinded.

Participants 28 enrolled in the study.Patients with antibiotic treatment prior to surgery, pregnant women, or impaired renal function wereexcluded before randomisation.Patients with perforated appendix were excluded after randomisation

Interventions Treatment group: Tobramycin 1,5 mg and Lincomycin 600 mg in 500 ml saline i.v peroperatively.Placebo group: No treatment

Outcomes Wound infection (Severe: Purulent discharge, cultures positive for potential pathogens; Mild: Erythema,scanty pus, cultures positive; Colonised: Not clinical infected, cultures positive)

Notes Treatment beginning at the time of skin incision .

Risk of bias



Gurry 1976

Methods Clinical controlled trial. Randomisation method not stated. Tripleblinded

Participants 29 patients enrolled in study. All patients had perforated appendix

Interventions Active group: Noxytioline 2,5 g in 100 ml saline instilled in the peritoneal cavity and the wound imme-diately before closure.Placebo group: 100 ml saline instilled into the peritoneal cavity and the wound immediately before closure

Outcomes Woundinfection (Not defined).Length of stay in hospital



Gurry 1976 (Continued)

Notes No drainage in either group.Postoperative antibiotics were used in two control patients and in one patient in the treatment group.(Persisting peritonitis, chest infection, septicaemia)

Risk of bias



Harnoss 1986

Methods RCT double blind

Participants 175 eligible Pts145 enrolledNo children under the age of 14 years of age

Interventions One shot 500 mg Metronidazole peri-operative, IVversus placebo (not stated)

Outcomes Wound infection in simple appendicitis

Notes No perforated appendicitis are included.An overview of other studies are described in table 4

Risk of bias



Hutchinson 1983

Methods Randomised controlled trial. Randomisation by numbered envelopes.Double-blinding. Unclear blinding af outcome assessor.

Participants 145 eligible patients. 12 excluded after randomisation. 133 patients, 91 males and 42 females enrolled inthe study.Age-range: 16 months - 15 years of age. Mean 6,7

Interventions Treatment group: Metronidazole (0-3 years 125 mg, 3-6 years 250 mg, 7-15 years 500 mg) supp. preop-eratively and eight-hourly for the next 72 hours.Placebo group: Supp. preoperatively and eight-hourly for the next 72 hours

Outcomes Wound infection (Discharge of pus from the wounds).Postoperative intraabdominal abscess (Not defined).



Hutchinson 1983 (Continued)


Risk of bias



Keiser 1983

Methods Randomised controlled trail. Randomisation by random numbers.Double-blinded. Unclear blinding of outecome assessor.

Participants 98 eligibel patients, 26 excluded after randomisation. 98 enrolled in the study.Age-range: 15-60. Mean: 27,5Patients with active neurologic diseasis, blodd dyscrasia, hypothyroidism, hypoadrenalism, were pregnant,and patients who refused to enter the stydy were excluded

Interventions Treatment group: Metronidazole 1 g IV preoperatively and 500 mg eight-hourly 5 times.Placebo treatment: Not specified. Regime as above.

Outcomes Wound infection (Wound erythema, definitely infected or purulent discharge).Length of stay in hospital


Risk of bias



Kekomäki 1983

Methods Randomised clinical controlled trial on children

Participants 115 eligible91 enrolled24 excluded due to various reasons

Interventions metronidazole versus placebo rectal suppositorium prior to surgery and 4 days follow up


Notes

Risk of bias



Kekomäki 1983 (Continued)



Kizilcan 1992 A


Participants 100, 66 males and 34 females enrolled in the study.Age-range: 0-15.Patients presenting parameters suggesting complicated appendicitis were not included.The study has 4 subgroups (see Kizilcan 1992 B & C).In Kizilcan 1992 A 50 patients enrolled in study study. 5 patients excluded after randomisation

Interventions Treatment group: Ornidazole 20 mg/kg/day divided in 2 doses initiated preoperatively.Placebo group: Not specified in same regime as above

Outcomes Wound infection (Not defined).Postoperative intraabdominal abscess (Not defined).

Notes No drain treatment.Wrote to author to specify subgrouping on drop-outs.

Risk of bias



Kizilcan 1992 B


Participants 100, 66 males and 34 females enrolled in the study.Age-range: 0-15.Patients presenting parameters suggesting complicated appendicitis were not included.The study has 4 subgroups (see Kizilcan 1992 A & C).In Kizilcan 1992 B 50 patients enrolled in the study. 5 patients excluded after randomisation

Interventions Treatment group: Penicillin 200.000 U/kg/day divided in 8 doses and Tobramycine 4 mg/kg/day dividedi 3 doses initiated preoperatively.Placebo group: Not specified in same regime as above




Kizilcan 1992 B (Continued)


Risk of bias



Kizilcan 1992 C


Participants 100, 66 males and 34 females enrolled in the study.Age-range: 0-15.Patients presenting parameters suggesting complicated appendicitis were not included.The study has 4 subgroups (see Kizilcan 1992 A & B).In Kizilcan 1992 A 50 patients enrolled in the study. 6 patients excluded after randomisation

Interventions Treatment group: Piperacillin Na 200 mg/kg/day divided in 3 doses initiated preoperatively.Placebo group: Not specified in same regime as above



Risk of bias



Kortelainen 1982

Methods Clinical controlled trial. Allocation based on the last digit of the patients birth year

Participants 315 eligible patients, 278 enrolled. Age range 15-83 years, 159 males and 119 females

Interventions Treatment group: Metronidazole suppository (1 g) 30-60 min preoperatively.Control group: No antimicrobial therapy

Outcomes Wound infection, defined as the presence of pus or a purulent exudate at the wound



Kortelainen 1982 (Continued)

Notes Appendicitis defined as either normal, inflamed or gangrenous

Risk of bias



Leigh 1976

Methods Clinical controlled trial. Randomisation method not stated. Double-blinded

Participants 200 patients, 103 males and 97 females enrolled in study. Age-range 0->40. Patients with macroscopicperforation of the appendix, pre-existing peritonitis or abscess formation were excluded

Interventions Treatment group: Lincomycin 600 mg = 2 ml i.m following closure of the wound.Control group: Saline 2 ml i.m following closure of the wound

Outcomes Wound infection (Discharge of purulent fluid from the operation wound with associated inflammationof the skin edges).Postoperative intraabdominal abscess (Not defined).

Notes 6 patients in the treatment group and 2 patients in the placebo group had microscopic perforation of theappendix.Draining of the wound depending on the surgeon. 8 patients in the treatment group were drained, nonecontracted wound infection. 6 patients in the placebo group were drained, 5 contracted wound infection.11 patients in each group recieved additional antibiotics (Wound infection, urinary tract infection, post-operative chest infection)

Risk of bias



Morris 1980 A

Methods Randomised controlled trial. Randomisation by a list of random numbers.Double-blinded. Unclear blinding of outcome-assessor.

Participants 340 eligble patients. 69 excluded after randomisation. 271 patients enrolled in the study.The study has 4 subgroups (see Morris 1980 B & C).In Morris 1980 A 133 patients enrolled in study.All patients above 14 years.Patients with diabetes or who received antibacterial or steroid treatment or had severe peritonitis requiringantibacterial therapy or had allergy to cephalosporin, were excluded before randomisation



Morris 1980 A (Continued)

Interventions Treatment group: Metronidazole 1 g suppositorium preoperatively and eight-hourly to a total of fourdoses.Placebo group: Supp. preoperatively and eight-hourly to a total of four doses

Outcomes Wound infection (Presence of pus in the wounds).


Risk of bias



Morris 1980 B


Participants 340 eligible patients. 69 excluded after randomisation. 271 patients enrolled in the study.The study has 4 subgroups (see Morris 1980 A & C).In Morris 1980 B 137 patients enrolled in the study.All patients above 14 years.Patients with diabetes or who received antibacterial or steroid treatment or had severe peritonitis requiringantibacterial therapy or had allergy to cephalosporin, were excluded before randomisation

Interventions Treatment group: Cefazolin 500 mg IV / IM preoperatively and eight-hourly to a total of four doses.Placebo group: An injection i.v /i.m preoperatively and eight-hourly to a total of four doses



Risk of bias





Morris 1980 C


Participants 340 eligble patients. 69 excluded after randomisation. 271 patients enrolled in the study.The study has 4 subgroups (see Morris 1980 A & B).In Morris 1980 C 133 patients enrolled in the study.All patients above 14 years.Patients with diabetes or who recieved antibacterial or steroid treatment or had severe peritonitis requiringantibacterial therapy or had allergy to cephalosporin, were excluded before randomisation

Interventions Treatment group: Metronidazole 1 g suppositorium and Cefazolin 500 mg i.v / i.m preoperatively andeight-hourly to a total of four doses.Placebo group: Supp. and injection i.v / i.m preoperatively and eight-hourly to a total of four doses



Risk of bias



Paakkonen 1982

Methods Randomised controlled trial. Randomisation by the anaesthetist.Double-blinded. Unclear blinding of outcome-assessor.

Participants 158 eligible patients. 27 patients excluded after randomisation. 131, 68 males and 63 females enrolled inthe study.Age-range: Treatment group 15-85, placebo group 15-80.Mean: Treatment group 39,7, placebo group 35,5

Interventions Treatment group: Metronidazole 500 mg IV preoperatively.Placebo group: Saline 100 ml i.v preoperatively.

Outcomes Wound infection (Accumulation of pus with spontanously or surgical drainage).Postoperative intraabdominal abscess (Not defined).Length of stay in hospital

Notes No drain treatment.Patients with perforated appendix all received antibiotics. That subgroup is excluded from this review

Risk of bias




Paakkonen 1982 (Continued)


Raahave 1970


Participants 30 eligible patients. 2 patients excluded after randomisation. 28 enrolled in the studyAge-range: 3-70.All patients had perforated appendix.

Interventions Treatment group: Kanamycin 250-1000 mg depending on S-crea. first dosis topical, hereafter im.Placebo group: Saline, regime as above.

Outcomes Wound infection (Not defined).Postoperative intra abdominal absces (Not defined).Length of stay in hospitalNo mortalities.


Risk of bias



Richards 1981

Methods Randomised controlled trial. Both surgeon and outcome assessor are blinded

Participants 143 eligible129 enrolledof which 55 had appendectomy

Interventions Gentamycin and glindamycin versu placebo

Outcomes post-operative infection

Notes

Risk of bias





Rodgers 1979


Participants 102 eligible patients. 12 patients were excluded after randomisation. 90 patients enrolled in the study

Interventions Treatment group: Metronidazole 1 g suppositorium preoperatively and herafter 8 hourly the next 2 days.Placebo group: Witepsol supp preoperatively and hereafter 8 hourly the next 2 days

Outcomes Wound infection (Pus or purulent exudate at the wound).Postoperative intra abdominal abscess (Not defined).

Notes Draining of the wound depending on purulent peritoneal exudate, gangrenous/perforated appendix. 8patients in the treatment group were drained, none contracted wound infection. 4 patients in the placebogroup were drained, 3 contracted wound infection

Risk of bias



Rowlands 1982

Methods Randomised controlled trial. Randomisation method not stated.Triple-blinded.

Participants 71 patients enrolled in the study.Patients who were pregnant, clinical jaundiced, had chronic liver or renal disease, astma, eczema, impairedeight nerve function, had already recieved antibiotics or hypersensitivity were excluded before randomi-sation

Interventions Treatment group: Clindamycin 600 mg IV and Gentamycin 120 mg peroperatively. (=150 ml)Placebo group: Glucose 150 ml i.v peroperatively

Outcomes Wound infection (Discharge of purulent material from the wound or stitch sites or a nonpurulent dischargefrom wich a positive bacteriological culture was obtained)

Notes Drain treatment depending on surgeon.

Risk of bias





Saario 1981

Methods Clinical controlled trial. Allocation based on the last digit of the patients birth year

Participants 203 eligible patients. 23 patients excluded after randomisation. 180 patients, 111 males and 69 femalesenrolled in the study.All patients above 6 years of age.Mean: Treatment group: 28,7 +/- 16,3 (s.d), Placebo group: 28,3 +/- 14,7 (s.d).Patients with perforated appendix, receiving antibiotics 7 days before surgery, pregnant women, or activeneurologic disease, were excluded before allocation

Interventions Treatment group: Metronidazole 500 mg IV (children half dose) inter-operatively after the surgeon hadseen the state of the appendix.Placebo group: Nothing

Outcomes Wound infection (Discharge of pus from the wound either spontaneously or after incision).Postoperative intra abdominal abscess (Not defined).Length of stay in hospital


Risk of bias



Salo 1981


Participants 223 eligible patients. 2 patients excluded after randomisation. 221 enrolled in the study.Mean: Treatment group: 32,6, Placebo group: 32,7

Interventions Treatment group: Tinidazole 500 mg in 100 ml saline i.v preoperatively.Placebo group: Saline 100 ml properatively.

Outcomes Wound infection (Presence of pus in the operation wound requiring surgical incision)

Notes No comment on drain treatment.

Risk of bias





Sole 1982

Methods Randomised controlled trial by use of sealed envelope.

Participants 231 eligible pts 113 enrolledwithdrawals not stated

Interventions 500 mg Metronidazole one shot peri-operatively. IV versus control

Outcomes Wound infection (Presence of pus in the operation wound requiring

Notes No children under the age of 12 years

Risk of bias



Stoller 1965

Methods Randomised controlled trial. Randomisation by random cards. Triple-blinded

Participants 84 enrolled in the study.Patients who were given systemic antibiotic immediate postoperatively were excluded after randomisation

Interventions Treatment group: Polybactrim spray, topical after closure of peritoneum.Placebo group: Not specified, regime as above.

Outcomes Woundinfection (An inflammatory erythema in clear excess of normal healing process or if serum or pusdischarged from the wound)


Risk of bias



Söderquist 1995 A

Methods Randomised controlled trialRandomisation method not stated

Participants 857 eligible patients. 313 patients excluded after randomisation.544 patients enrolled in study. Alle children.Patients with perforated appendicitis were excluded. Patients allergic to antibiotics or recieving antibioticwithin 72 hours before surgery were excluded. 193 patients received treatment compared to 176 in the



Söderquist 1995 A (Continued)

control group

Interventions Treatment group: metronidazole 20 mg/ kg IV 1 hour preoperatively.Placebo group: No treatment

Outcomes Wound infection (subcutaneus abscess with suppuration confirmed by spontaneus wound rupture de-briemnt or incision)Intrabadominal absces (absces within the intraabdominal cagvity diagnosed at operation or by rectalexamination, x-ray or ultrasound)

Notes No comment on drain treatment

Risk of bias



Söderquist 1995 B

Methods Randomised controlled trialRandomisation method not

Participants 857 eligible patients. 313 patients excluded after randomisation.544 patients enrolled in study. Alle children.Patients with perforated appendicitis were excluded. Patients allergic to antibiotics or recieving antibioticwithin 72 hours before surgery were excluded. 175 patients received treatment compared to 176 in thecontrol group

Interventions Treatment group: Metronidazole 20 mg/kg + cefuroxime 50 mg/kg iv 1 hour preoperatively.Placebogroup: no treatment

Outcomes Wound infection (subcutaneus abscess with suppuration confirmed by spontaneus wound rupture de-briemnt or incision)Intrabadominal absces (absces within the intraabdominal cagvity diagnosed at operation or by rectalexamination, x-ray or ultrasound)

Notes No comment on drain treatment

Risk of bias





Tanner 1980

Methods Randomised controlled trial. Randomisation method not stated.Patient blinded. Unclear blinding of surgeon and outcome-assessor

Participants 111 eligible patients. 7 patients excluded. 104, 51 males and 53 females enrolled in the study.Age-range 8-71Mean: Treatment group: 26 +/- 14 (s.d.), placebo group: 25 +/- 15 (s.d)

Interventions Treatment group: Metronidazole 1 g suppositorium preoperatively.Placebo group: Glycerine supp preoperatively.

Outcomes Wound infection (Presence of pus or a purulent exudate at the wound)

Notes Drain treatment to all patients with perforated appendix.

Risk of bias



Viitanen 1984 A

Methods Clinical controlled trial. Allocation by birthday.Patient blinded. Unclear blinding of surgeon and outcome assessor

Participants 588 eligible patients. 123 excluded after randomisation. 465 enrolled in the study.Age-range: 15-94 Mean: 33,4315 enrolled in this part of the study.The study has 3 subgroups (see Viitanen 1984 B).In Viitanen 1984 A 315 patients enrolled in study.

Interventions Treatment group: Tinidazole 500 mg in 100 saline i.v preoperatively.Placebo group: No treatment.

Outcomes Wound infection (Pus from the wounds).Two patients died, 1 of peritonitis induced by perforation of the appendix, 1 died of cardiac infarction

Notes Treatment initiated on anaesthetized patient.No drain treatment.

Risk of bias





Viitanen 1984 B

Methods Clinical controlled trial. Allocation by birthday.Patient blinded. Unclear blinding of surgeon and outcome assessor

Participants 588 eligible patients. 123 excluded after randomisation. 465 enrolled in the study.Age-range: 15-94 Mean: 33,4315 enrolled in this part of the study.The study has 3 subgroups (see Viitanen 1984 A).In Viitanen 1984 B 327 patients enrolled in study.

Interventions Treatment group: Tinidazole 500 mg in 100 saline IV preoperativly and 500 mg three time daily for threedays.Placebo group: No treatment.

Outcomes Wound infection (Pus from the wounds).Two patients died, 1 of peritonitis induced by perforation of the appendix, 1 died of cardiac infarction

Notes Treatment initiated on anaesthetized patient.No drain treatment.

Risk of bias



Wayand 1982

Methods Randomised controlled trial. Randomisation by a list of random numbers.Blinding unclear.

Participants 220 eligible patients. 25 excluded after randomisation. 195, 85 males and 110 females enrolled in thestudy.Mean-age: 23Patients who received antibiotics within the previous 3 days before operation, had allergy to antibiotics,were pregnant, and breast-feeding women, patients with kreatinin >3 mg%, and patients who deniedconsent, were excluded before randomisation

Interventions Treatment group: Cefamandol 2 g IV preoperatively and eight-hourly altogether 5 doses.Placebo group: Not specified 2 g iv preoperatively and eight-hourly altogether 5 doses


Notes No comments on drain treatment

Risk of bias




Wayand 1982 (Continued)


Willis 1976

Methods Randomised controlled trial, method not stated

Participants 105 eligible pt95 enrolled10 pts excluded due to prior antibiotic record or failure in randomisation procedure

Interventions Metronidazole versus placebo as suppository for seven days

Outcomes wound infection(discharge from the wound)

Notes All suppositories contain Witepsol 35 and 75

Risk of bias



Winslow 1983

Methods Randomised controlled trial. Randomisation by the last number in the patients birthday.Triple-blinded.

Participants 147 eligible patients. 44 excluded after randomisation. 103 enrolled in the study.Age-range 4-67. Mean 22.Patients receiving antibiotics 72 hours prior of surgery, had allergy to cephalosporins or penicillin, hadimpaired renal function and serious underlying disease, were excluded before randomisation

Interventions Treatment group: Cefoxitin 1 g (children 20-40 mg/kg/dose) IV peroperatively and 6 and 12 hourspostoperatively.Placebo group: Saline regime as above.

Outcomes Wound infection (Not defined).Postoperative intra abdominal abscess (Not defined)Length of stay in hospital


Risk of bias




Winslow 1983 (Continued)


Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Amgwerd 1981 Adequate randomisation, but control group received no treatment, and treatment group received pre-operativeand post-operative IM treatment which means inadequate blinding and the results of infection may be biased

Andersen 1972 All patients received post-operative antibiotic.

Badia 1994 The treatment group (antibiotics) is compared to a ’control group’ receiving a solution with physiologicalserum

Bates 1974 Randomisation by sealed envelopes. Control group received no treatment, and treatment group received peri-operative topical treatment which means inadequate blinding and the results of infection may be biased

Birkigt 1989 Randomised clinical trial. There are discord in the table of results. The number of patients differ within thesame groups

Birkigt 1991 Unknown allocation consealment and odd distribution numbers in the treatment group versus control group

Bröte 1976 Randomisation not stated. Control group received no treatment, and treatment group received postoperativeIV treatment which means inadequate blinding and the results of infection may be biased

Calman 1971 Abstract. It has been impossible for the reviewers to get a full study

Crosfill 1969 Randomised controlled trial. Systemic antibiotics were given as supplement to topical treatment to the mostseriously ill. The author does not describe which patients that get systemic antibiotics

Dixon 1984 The trial group is patients in elective and emergency operations. No reports on appendicitis exclusively

Evans 1973 Randomisation by toss of a coin. Control group received no treatment, and treatment group received post-operative IM treatment which means inadequate blinding and the results of infection may be biased

Everson 1977 Insufficient subject blinding. Patients receiving post-operative injection three times compared to controlgroup (no treatment)

Feltis 1967 Randomisation method not stated. Control group received no treatment, and treatment group received pre-operative, peri-operative and post-operative IV treatment, which means unclear blinding, and the results ofinfection may be biased

Gilmore 1973 Inadequate allocation consealment



(Continued)

Gilmore 1975 Randomisation by af table of random numbers. Unclear which patients received systemic antibiotic treatmentwithin the topical treatment and placebogroup

Gómez-Alonso 1984 Adequate randomisation, but control group received no treatment, and treatment group received pre-opera-tively and post-operative IM treatment which means inadequate blinding and the results of infection may bebiased

Harahsheh 2002 Randomised single blin trial, in which all pts received daily antiseptic dressings with povidone-iodine (10%in alcohol)

Herrera-Garcia 1985 Adequate randomisation, but no differentiation between wound infection and intra-abdominal abscess in theresult section

Kling 1985 Adequate randomisation, but control group received no treatment, and treatment group received preoperativeIV treatment 1-3 hours prior to operation, which means unclear blinding and the results of infection may bebiased

Leigh 1978 A study based on prior publised trials, of which we have included one, excluded one (not randomised), andyet another not possible to identify

Marti 1978 Initially three arm study comparing two different antibiotics, which later becomes a two-arm study. Noindication of wound infection - only abscesses are described

McGreal 2002 All pts received antibiotic prophylaxis. Clinical question focuses on two different ways of wound closure

McLean 1983 Adequate randomisation. Control group received no treatment, and treatment group received post-operativeIV and orally administrated treatment, which means inadequate blinding and the results of infection may bebiased

Okubadejo 1976 Randomisation by Fisher´ s tabels. Control group received no treatment, and treatment group received post-operative treatment which means inadequate blinding and the results of infection may be biased

Pietila 1982 No statement of placebo/control and any indication of withdrawal of patients

Pollock 1972 The treatment group is composed of abdominal surgery, potentially contaminated operations. No reports onappendicitis exklusively

Rambo 1972 Randomisation adequate. The trial include miscellaneous emergency surgery, of which only one appendec-tomy was reported

Tanphiphat 1978 Unclear what treatment is given to who post-operatively. In addition, wound lavage is offered all enrolled pt,so it is difficult to establish a clear effect of antibiotic treatment

Taylor 2000 Both comparisons groups received antibiotic treatment

Taylor 2004 Both comparisons groups received antibiotic treatment. The protocol seem identical to the Taylor 2000reference



(Continued)

Walsh 1981 Unclear what treatment is given to who post-operative. From table 1, there is a clear distinction betweenantibiotics and control group. From table 3 it is difficult to establish a clear effect of antibiotic treatment.Therefore we decided to exclude the study

Willis 1979 A summary of metronidazole in the prevention and treatment of anaerobic sepsis, in which appendicitis is apart. Seems identical to prior publication in 1976 (which is included)



D A T A A N D A N A L Y S E S

Comparison 1. Systemic Antibiotics vs Placebo (Clinical)

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Wound infection 47 8812 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.33 [0.29, 0.38]1.1 Appendicitis 21 2343 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.31 [0.24, 0.42]1.2 Simple appendicitis 26 5317 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.37 [0.30, 0.46]1.3 Complicated appendicitis 24 1152 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.28 [0.21, 0.38]

2 Postoperative intra abdominalabscess

16 4468 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.43 [0.25, 0.73]

2.1 Appendicitis 8 1033 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.35 [0.13, 0.91]2.2 Simple appendicitis 8 2968 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.46 [0.23, 0.94]2.3 Complicated appendicitis 4 467 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.54 [0.12, 2.43]

3 Length of stay in hospital 8 1200 Mean Difference (IV, Fixed, 95% CI) -1.69 [-1.78, -1.61]

Comparison 2. Systemic antibiotics vs placebo (Pathoanatomic)


studies

No. of


1 Wound infection 21 1704 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.32 [0.22, 0.47]1.1 Normal appendix 21 1555 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.28 [0.18, 0.44]1.2 Perforated appendicitis 6 149 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.47 [0.22, 1.00]



2.1 Normal appendix 3 673 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.45 [0.10, 1.98]2.2 Perforated appendicitis 1 68 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.12 [0.02, 0.86]

Comparison 3. Topical Antibiotics vs Placebo


studies

No. of




0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable

2.1 Appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable2.2 Simple appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable2.3 Complicated appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable



3 Lenght of stay in hospital 1 29 Mean Difference (IV, Fixed, 95% CI) Not estimable

Comparison 4. Pre-operatively administered single agent, single dose Antibiotics vs Placebo


studies

No. of





2.1 Appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable2.2 Simple appendicitis 2 382 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.34 [0.05, 2.45]2.3 Complicated appendicitis 1 64 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable

3 Length of stay in hospital 1 121 Mean Difference (IV, Fixed, 95% CI) 0.40 [-0.01, 0.81]

Comparison 5. Pre-operatively administered multiple agent, single dose Antibiotics vs Placebo


studies

No. of


1 Wound infection 2 215 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.14 [0.05, 0.39]1.1 Appendicitis 1 133 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.12 [0.02, 0.61]1.2 Simple appendicitis 1 82 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.16 [0.04, 0.59]1.3 Complicated appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable




3 Length of stay in hospital 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable

Comparison 6. Per-operatively administered single agent, single dose Antibiotics vs Placebo


studies

No. of









Comparison 7. Per-operatively administered multiple agent, single dose Antibiotics vs Placebo


studies

No. of







Comparison 8. Operatively single agent and post-operatively single agent, single dose Antibiotics vs placebo


studies

No. of


1 Wound infection 3 256 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.16 [0.07, 0.36]1.1 Appendicitis 3 256 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.16 [0.07, 0.36]1.2 Simple appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable1.3 Complicated appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable



2.1 Appendicitis 2 161 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.12 [0.02, 0.89]2.2 Simple appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable2.3 Complicated appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable




Comparison 9. Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo


studies

No. of





2.1 Appendicitis 2 269 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.13 [0.01, 2.08]2.2 Simple appendicitis 1 179 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.15 [0.00, 7.38]2.3 Complicated appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable


Comparison 10. Operatively multiple agent and post operatively multiple agent, single dose Antibiotic vs Placebo


studies

No. of


1 Wound infection 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable1.1 Appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable1.2 Simple appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable1.3 Complicated appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable

2 Postoperative intra abdominalabsces




Comparison 11. Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs

placebo


studies

No. of





2.1 Appendicitis 1 133 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.98 [0.06, 15.92]2.2 Simple appendicitis 2 355 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.15 [0.01, 2.38]



2.3 Complicated appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable3 Length of stay in hospital 1 90 Mean Difference (IV, Fixed, 95% CI) Not estimable

Comparison 12. Systemic antibiotics vs Placebo in children


studies

No. of







Comparison 13. Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo

in children


studies

No. of









Comparison 14. Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs

placebo, children


studies

No. of


1 Wound infection 1 50 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable1.1 Appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable1.2 Simple appendicitis 1 50 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable1.3 Complicated appendicitis 0 0 Peto Odds Ratio (Peto, Fixed, 95% CI) Not estimable





Analysis 1.1. Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 1 Wound infection.

Review: Antibiotics versus placebo for prevention of postoperative infection after appendicectomy.

Comparison: 1 Systemic Antibiotics vs Placebo (Clinical)

Outcome: 1 Wound infection

Study or subgroup Treatment ControlPeto

Odds RatioPeto

Odds Ratio

n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI

1 Appendicitis

Bergmark 1985 0/68 6/65 0.12 [ 0.02, 0.61 ]

Browder 1989 A 3/39 8/39 0.35 [ 0.10, 1.25 ]

Browder 1989 B 0/44 8/39 0.10 [ 0.02, 0.42 ]

Chiam 1983 A 4/100 17/100 0.25 [ 0.10, 0.62 ]

Chiam 1983 B 10/100 17/100 0.55 [ 0.25, 1.24 ]

Chiam 1983 C 7/100 17/100 0.39 [ 0.17, 0.91 ]

Corbett 1979 4/52 9/53 0.43 [ 0.13, 1.36 ]

Creve 1980 A 1/6 3/7 0.32 [ 0.03, 3.11 ]

Creve 1980 B 0/2 0/2 0.0 [ 0.0, 0.0 ]

Foster 1978 1/70 8/69 0.19 [ 0.05, 0.73 ]

Giacomantonio 1982 0/21 1/21 0.14 [ 0.00, 6.82 ]

0.1 0.2 0.5 1 2 5 10

Favours Treatment Favours Control

(Continued . . . )



(. . . Continued)


Odds RatioPeto

Odds Ratio


Go 1986 2/75 6/84 0.39 [ 0.10, 1.63 ]

Greenall 1979 1/49 12/51 0.15 [ 0.05, 0.49 ]

Griffiths 1976 0/14 4/14 0.11 [ 0.01, 0.84 ]

Keiser 1983 3/30 4/40 1.00 [ 0.21, 4.79 ]

Leigh 1976 6/100 17/100 0.34 [ 0.14, 0.81 ]

Paakkonen 1982 2/58 5/63 0.44 [ 0.10, 2.02 ]

Rodgers 1979 2/42 7/48 0.34 [ 0.09, 1.34 ]

Wayand 1982 7/92 8/88 0.82 [ 0.29, 2.37 ]

Willis 1976 0/49 9/46 0.10 [ 0.03, 0.41 ]

Winslow 1983 0/51 5/52 0.13 [ 0.02, 0.76 ]

Subtotal (95% CI) 1162 1181 0.31 [ 0.24, 0.42 ]

Total events: 53 (Treatment), 171 (Control)

Heterogeneity: Chi2 = 18.87, df = 19 (P = 0.47); I2 =0.0%

Test for overall effect: Z = 8.19 (P < 0.00001)

2 Simple appendicitis

Ahmed 1987 14/96 13/94 1.06 [ 0.47, 2.40 ]

Azabache 1987 A 0/31 11/51 0.16 [ 0.04, 0.59 ]

Bates 1980 11/70 16/71 0.65 [ 0.28, 1.49 ]

Bauer 1989 12/736 52/818 0.30 [ 0.18, 0.50 ]

Busuttil 1981 A 0/43 5/42 0.12 [ 0.02, 0.72 ]

Busuttil 1981 B 1/42 5/42 0.24 [ 0.05, 1.26 ]

Donovan 1979 A 6/63 17/63 0.31 [ 0.13, 0.77 ]

Donovan 1979 B 10/60 17/63 0.55 [ 0.24, 1.29 ]

El-Sefi 1986 A 2/87 12/93 0.23 [ 0.08, 0.68 ]

El-Sefi 1986 B 2/82 12/93 0.24 [ 0.08, 0.72 ]

El-Sefi 1986 C 8/86 12/93 0.70 [ 0.28, 1.76 ]

Foster 1981 A 19/206 14/90 0.53 [ 0.24, 1.16 ]

Gledhill 1983 0/21 3/40 0.21 [ 0.02, 2.33 ]

Gottrup 1979 0/114 4/114 0.13 [ 0.02, 0.95 ]

Harnoss 1986 1/38 2/43 0.57 [ 0.06, 5.68 ]

Morris 1980 A 2/61 15/61 0.17 [ 0.06, 0.48 ]

Morris 1980 B 8/57 15/61 0.51 [ 0.21, 1.27 ]

Morris 1980 C 6/59 15/61 0.37 [ 0.15, 0.95 ]

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)


Odds RatioPeto

Odds Ratio


Rowlands 1982 1/20 7/23 0.19 [ 0.04, 0.89 ]

Saario 1981 1/68 10/75 0.19 [ 0.06, 0.65 ]

Salo 1981 1/82 5/72 0.22 [ 0.04, 1.12 ]

Soderquist 1995 A 3/138 3/126 0.91 [ 0.18, 4.59 ]

Soderquist 1995 B 2/108 3/126 0.78 [ 0.13, 4.58 ]

Tanner 1980 0/44 6/42 0.11 [ 0.02, 0.59 ]

Viitanen 1984 A 3/91 6/125 0.69 [ 0.18, 2.65 ]

Viitanen 1984 B 0/107 6/125 0.15 [ 0.03, 0.76 ]

Subtotal (95% CI) 2610 2707 0.37 [ 0.30, 0.46 ]


Heterogeneity: Chi2 = 29.18, df = 25 (P = 0.26); I2 =14%


3 Complicated appendicitis

Azabache 1987 A 1/15 6/13 0.13 [ 0.02, 0.71 ]

Bates 1980 6/17 5/12 0.77 [ 0.17, 3.44 ]

Bauer 1989 9/109 22/72 0.21 [ 0.10, 0.46 ]

Busuttil 1981 A 0/2 1/3 0.19 [ 0.00, 10.32 ]

Busuttil 1981 B 0/4 1/3 0.10 [ 0.00, 5.09 ]

Donovan 1979 A 8/18 7/9 0.27 [ 0.06, 1.32 ]

Donovan 1979 B 20/25 7/9 1.14 [ 0.18, 7.30 ]

El-Sefi 1986 A 2/13 4/7 0.15 [ 0.02, 1.07 ]

El-Sefi 1986 B 1/18 4/7 0.05 [ 0.01, 0.38 ]

El-Sefi 1986 C 5/14 4/7 0.43 [ 0.07, 2.60 ]

Foster 1981 A 24/54 19/27 0.36 [ 0.14, 0.90 ]

Gledhill 1983 10/21 9/20 1.11 [ 0.33, 3.73 ]

Gottrup 1979 0/31 8/33 0.11 [ 0.03, 0.49 ]

Harnoss 1986 0/32 2/32 0.13 [ 0.01, 2.14 ]

Morris 1980 A 0/6 5/5 0.03 [ 0.00, 0.25 ]

Morris 1980 B 6/10 5/5 0.15 [ 0.01, 1.55 ]

Morris 1980 C 8/11 5/5 0.19 [ 0.01, 2.57 ]

Rowlands 1982 1/4 5/8 0.25 [ 0.03, 2.52 ]

Saario 1981 2/19 7/18 0.22 [ 0.05, 0.98 ]

Soderquist 1995 A 1/55 7/50 0.18 [ 0.04, 0.76 ]

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)


Odds RatioPeto

Odds Ratio


Soderquist 1995 B 1/67 7/50 0.14 [ 0.03, 0.61 ]

Tanner 1980 1/10 5/8 0.11 [ 0.02, 0.73 ]

Viitanen 1984 A 7/47 15/52 0.45 [ 0.17, 1.16 ]

Viitanen 1984 B 8/43 15/52 0.58 [ 0.23, 1.47 ]

Subtotal (95% CI) 645 507 0.28 [ 0.21, 0.38 ]




Total (95% CI) 4417 4395 0.33 [ 0.29, 0.38 ]




Test for subgroup differences: Chi2 = 2.36, df = 2 (P = 0.31), I2 =15%

0.1 0.2 0.5 1 2 5 10




Analysis 1.2. Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 2 Postoperative intra

abdominal abscess.



Outcome: 2 Postoperative intra abdominal abscess


Odds RatioPeto

Odds Ratio


1 Appendicitis

Browder 1989 A 0/39 2/39 0.13 [ 0.01, 2.15 ]

Browder 1989 B 0/44 2/39 0.12 [ 0.01, 1.90 ]

Leigh 1976 2/100 1/100 1.96 [ 0.20, 19.07 ]

Morris 1980 A 1/67 1/66 0.98 [ 0.06, 15.92 ]

Morris 1980 B 0/67 1/66 0.13 [ 0.00, 6.72 ]

Morris 1980 C 0/70 1/66 0.13 [ 0.00, 6.43 ]

Rodgers 1979 1/42 3/48 0.41 [ 0.06, 3.00 ]

Saario 1981 0/87 2/93 0.14 [ 0.01, 2.30 ]

Subtotal (95% CI) 516 517 0.35 [ 0.13, 0.91 ]



Test for overall effect: Z = 2.16 (P = 0.031)


Bauer 1989 8/736 12/818 0.74 [ 0.31, 1.79 ]

El-Sefi 1986 A 0/87 1/93 0.14 [ 0.00, 7.29 ]

El-Sefi 1986 B 0/82 1/93 0.15 [ 0.00, 7.74 ]

El-Sefi 1986 C 0/86 1/93 0.15 [ 0.00, 7.38 ]

Gottrup 1979 0/114 2/114 0.13 [ 0.01, 2.16 ]

Salo 1981 1/82 1/72 0.88 [ 0.05, 14.23 ]

Soderquist 1995 A 0/138 2/126 0.12 [ 0.01, 1.97 ]

Soderquist 1995 B 0/108 2/126 0.15 [ 0.01, 2.51 ]

Subtotal (95% CI) 1433 1535 0.46 [ 0.23, 0.94 ]





Bauer 1989 1/109 2/72 0.32 [ 0.03, 3.29 ]

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)


Odds RatioPeto

Odds Ratio


Gottrup 1979 0/31 0/33 0.0 [ 0.0, 0.0 ]

Soderquist 1995 A 0/55 1/50 0.12 [ 0.00, 6.20 ]

Soderquist 1995 B 2/67 1/50 1.48 [ 0.15, 14.86 ]

Subtotal (95% CI) 262 205 0.54 [ 0.12, 2.43 ]




Total (95% CI) 2211 2257 0.43 [ 0.25, 0.73 ]




Test for subgroup differences: Chi2 = 0.31, df = 2 (P = 0.86), I2 =0.0%

0.1 0.2 0.5 1 2 5 10




Analysis 1.3. Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 3 Length of stay in hospital.



Outcome: 3 Length of stay in hospital

Study or subgroup Treatment ControlMean

DifferenceMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Bates 1980 87 4.8 (2.3) 83 5.8 (3) -1.00 [ -1.81, -0.19 ]

Busuttil 1981 A 45 3.2 (0) 45 3.8 (0) 0.0 [ 0.0, 0.0 ]

Busuttil 1981 B 44 2.9 (0) 45 3.8 (0) 0.0 [ 0.0, 0.0 ]

Foster 1981 A 260 5.13 (0.17) 117 6.95 (0.47) -1.82 [ -1.91, -1.73 ]

Keiser 1983 30 5.2 (0) 40 4.85 (0) 0.0 [ 0.0, 0.0 ]

Paakkonen 1982 58 4.3 (1.2) 63 3.9 (1.1) 0.40 [ -0.01, 0.81 ]

Saario 1981 87 4.4 (1.4) 93 5.2 (2.2) -0.80 [ -1.34, -0.26 ]

Winslow 1983 51 2.5 (0) 52 2.5 (0) 0.0 [ 0.0, 0.0 ]

Total (95% CI) 662 538 -1.69 [ -1.78, -1.61 ]

Heterogeneity: Chi2 = 121.08, df = 3 (P<0.00001); I2 =98%


Test for subgroup differences: Not applicable

-10 -5 0 5 10



Analysis 2.1. Comparison 2 Systemic antibiotics vs placebo (Pathoanatomic), Outcome 1 Wound infection.


Comparison: 2 Systemic antibiotics vs placebo (Pathoanatomic)



Odds RatioPeto

Odds Ratio


1 Normal appendix

Bates 1980 4/24 2/21 1.83 [ 0.33, 10.05 ]

Bauer 1989 3/266 15/292 0.28 [ 0.11, 0.71 ]

Busuttil 1981 A 0/7 0/6 0.0 [ 0.0, 0.0 ]

Busuttil 1981 B 0/5 0/6 0.0 [ 0.0, 0.0 ]

Donovan 1979 A 1/24 4/20 0.22 [ 0.03, 1.37 ]

Donovan 1979 B 1/18 4/20 0.29 [ 0.05, 1.87 ]

Eklund 1987 3/95 2/85 1.35 [ 0.23, 7.94 ]

El-Sefi 1986 A 0/5 1/6 0.16 [ 0.00, 8.19 ]

El-Sefi 1986 B 0/8 1/6 0.10 [ 0.00, 5.09 ]

El-Sefi 1986 C 0/4 1/6 0.19 [ 0.00, 10.32 ]

Foster 1981 A 1/46 3/22 0.13 [ 0.02, 1.11 ]

Gottrup 1979 0/36 1/35 0.13 [ 0.00, 6.63 ]

Morris 1980 A 1/14 7/17 0.18 [ 0.04, 0.88 ]

Morris 1980 B 0/17 7/17 0.09 [ 0.02, 0.45 ]

Morris 1980 C 1/17 7/17 0.15 [ 0.03, 0.71 ]

Salo 1981 0/28 3/16 0.06 [ 0.01, 0.62 ]

Soderquist 1995 A 1/53 2/52 0.50 [ 0.05, 4.88 ]

Soderquist 1995 B 2/45 2/52 1.16 [ 0.16, 8.55 ]

Tanner 1980 0/9 1/9 0.14 [ 0.00, 6.82 ]

Viitanen 1984 A 1/27 3/38 0.49 [ 0.06, 3.75 ]

Viitanen 1984 B 0/26 3/38 0.18 [ 0.02, 1.83 ]

Subtotal (95% CI) 774 781 0.28 [ 0.18, 0.44 ]




2 Perforated appendicitis

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)


Odds RatioPeto

Odds Ratio


Gottrup 1979 0/35 11/33 0.09 [ 0.02, 0.32 ]

Morris 1980 A 1/3 3/3 0.08 [ 0.00, 1.82 ]

Morris 1980 C 3/3 3/3 0.0 [ 0.0, 0.0 ]

Tanner 1980 0/2 1/2 0.14 [ 0.00, 6.82 ]

Viitanen 1984 A 6/14 6/19 1.60 [ 0.39, 6.59 ]

Viitanen 1984 B 6/13 6/19 1.83 [ 0.44, 7.67 ]

Subtotal (95% CI) 70 79 0.47 [ 0.22, 1.00 ]




Total (95% CI) 844 860 0.32 [ 0.22, 0.47 ]





0.1 0.2 0.5 1 2 5 10




Analysis 2.2. Comparison 2 Systemic antibiotics vs placebo (Pathoanatomic), Outcome 2 Postoperative

intra abdominal abscess.


Comparison: 2 Systemic antibiotics vs placebo (Pathoanatomic)



Odds RatioPeto

Odds Ratio


1 Normal appendix

Bauer 1989 2/266 3/292 0.73 [ 0.13, 4.27 ]

Gottrup 1979 0/36 2/35 0.13 [ 0.01, 2.08 ]

Salo 1981 0/28 0/16 0.0 [ 0.0, 0.0 ]

Subtotal (95% CI) 330 343 0.45 [ 0.10, 1.98 ]




2 Perforated appendicitis

Gottrup 1979 0/35 4/33 0.12 [ 0.02, 0.86 ]

Subtotal (95% CI) 35 33 0.12 [ 0.02, 0.86 ]


Heterogeneity: not applicable


Total (95% CI) 365 376 0.28 [ 0.08, 0.91 ]





0.1 0.2 0.5 1 2 5 10




Analysis 3.1. Comparison 3 Topical Antibiotics vs Placebo, Outcome 1 Wound infection.


Comparison: 3 Topical Antibiotics vs Placebo



Odds Ratio WeightPeto

Odds Ratio


1 Appendicitis

Gurry 1976 9/15 7/14 10.3 % 1.48 [ 0.35, 6.23 ]

Stoller 1965 6/47 10/37 18.0 % 0.40 [ 0.13, 1.19 ]

Subtotal (95% CI) 62 51 28.3 % 0.65 [ 0.27, 1.54 ]





Eklund 1987 1/107 2/107 4.1 % 0.51 [ 0.05, 4.96 ]

Foster 1981 B 20/95 14/90 38.8 % 1.44 [ 0.69, 3.02 ]

Subtotal (95% CI) 202 197 43.0 % 1.30 [ 0.64, 2.64 ]





Eklund 1987 1/51 9/65 12.7 % 0.22 [ 0.06, 0.82 ]

Foster 1981 B 15/24 19/27 16.0 % 0.71 [ 0.22, 2.24 ]

Subtotal (95% CI) 75 92 28.7 % 0.43 [ 0.18, 1.01 ]




Total (95% CI) 339 340 100.0 % 0.77 [ 0.49, 1.23 ]





0.1 0.2 0.5 1 2 5 10




Analysis 3.3. Comparison 3 Topical Antibiotics vs Placebo, Outcome 3 Lenght of stay in hospital.


Comparison: 3 Topical Antibiotics vs Placebo

Outcome: 3 Lenght of stay in hospital


DifferenceMean

Difference


Gurry 1976 15 14 (0) 14 12 (0) 0.0 [ 0.0, 0.0 ]

Total (95% CI) 15 14 0.0 [ 0.0, 0.0 ]




-10 -5 0 5 10




Analysis 4.1. Comparison 4 Pre-operatively administered single agent, single dose Antibiotics vs Placebo,

Outcome 1 Wound infection.


Comparison: 4 Pre-operatively administered single agent, single dose Antibiotics vs Placebo




Odds Ratio


1 Appendicitis

Paakkonen 1982 2/58 5/63 3.5 % 0.44 [ 0.10, 2.02 ]

Sole 1982 4/58 12/55 7.4 % 0.30 [ 0.10, 0.85 ]

Subtotal (95% CI) 116 118 10.9 % 0.34 [ 0.14, 0.80 ]





Donovan 1979 A 6/63 17/63 10.1 % 0.31 [ 0.13, 0.77 ]

Donovan 1979 B 10/60 17/63 11.3 % 0.55 [ 0.24, 1.29 ]

Foster 1981 A 19/206 14/90 13.3 % 0.53 [ 0.24, 1.16 ]

Gottrup 1979 0/114 4/114 2.1 % 0.13 [ 0.02, 0.95 ]

Harnoss 1986 1/38 2/43 1.6 % 0.57 [ 0.06, 5.68 ]

Kortelainen 1982 0/97 8/107 4.1 % 0.14 [ 0.03, 0.57 ]

Salo 1981 1/82 5/72 3.1 % 0.22 [ 0.04, 1.12 ]

Tanner 1980 0/44 6/42 3.0 % 0.11 [ 0.02, 0.59 ]

Viitanen 1984 A 3/91 6/125 4.5 % 0.69 [ 0.18, 2.65 ]

Subtotal (95% CI) 795 719 53.1 % 0.37 [ 0.25, 0.54 ]





Donovan 1979 A 8/18 7/9 3.3 % 0.27 [ 0.06, 1.32 ]

Donovan 1979 B 20/25 7/9 2.4 % 1.14 [ 0.18, 7.30 ]

Foster 1981 A 24/54 19/27 9.7 % 0.36 [ 0.14, 0.90 ]

Gottrup 1979 0/31 8/33 3.8 % 0.11 [ 0.03, 0.49 ]

Harnoss 1986 0/32 2/32 1.0 % 0.13 [ 0.01, 2.14 ]

Kortelainen 1982 1/26 9/30 4.4 % 0.17 [ 0.04, 0.68 ]

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)



Odds Ratio


Tanner 1980 1/10 5/8 2.2 % 0.11 [ 0.02, 0.73 ]

Viitanen 1984 A 7/47 15/52 9.2 % 0.45 [ 0.17, 1.16 ]

Subtotal (95% CI) 243 200 36.0 % 0.29 [ 0.18, 0.47 ]




Total (95% CI) 1154 1037 100.0 % 0.34 [ 0.25, 0.45 ]





0.1 0.2 0.5 1 2 5 10





Outcome 2 Postoperative intra abdominal abscess.





Odds RatioPeto

Odds Ratio


1 Appendicitis

Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]



Test for overall effect: not applicable


Gottrup 1979 0/114 2/114 0.13 [ 0.01, 2.16 ]

Salo 1981 1/82 1/72 0.88 [ 0.05, 14.23 ]

Subtotal (95% CI) 196 186 0.34 [ 0.05, 2.45 ]





Gottrup 1979 0/31 0/33 0.0 [ 0.0, 0.0 ]

Subtotal (95% CI) 31 33 0.0 [ 0.0, 0.0 ]




Total (95% CI) 227 219 0.34 [ 0.05, 2.45 ]





0.1 0.2 0.5 1 2 5 10





Outcome 3 Length of stay in hospital.





Difference WeightMean

Difference


Paakkonen 1982 58 4.3 (1.2) 63 3.9 (1.1) 100.0 % 0.40 [ -0.01, 0.81 ]

Total (95% CI) 58 63 100.0 % 0.40 [ -0.01, 0.81 ]




-10 -5 0 5 10




Analysis 5.1. Comparison 5 Pre-operatively administered multiple agent, single dose Antibiotics vs Placebo,



Comparison: 5 Pre-operatively administered multiple agent, single dose Antibiotics vs Placebo




Odds Ratio


1 Appendicitis

Bergmark 1985 0/68 6/65 38.9 % 0.12 [ 0.02, 0.61 ]

Subtotal (95% CI) 68 65 38.9 % 0.12 [ 0.02, 0.61 ]





Azabache 1987 A 0/31 11/51 61.1 % 0.16 [ 0.04, 0.59 ]

Subtotal (95% CI) 31 51 61.1 % 0.16 [ 0.04, 0.59 ]





Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]




Total (95% CI) 99 116 100.0 % 0.14 [ 0.05, 0.39 ]





0.1 0.2 0.5 1 2 5 10




Analysis 6.1. Comparison 6 Per-operatively administered single agent, single dose Antibiotics vs Placebo,



Comparison: 6 Per-operatively administered single agent, single dose Antibiotics vs Placebo




Odds Ratio


1 Appendicitis

Creve 1980 A 1/6 3/7 1.2 % 0.32 [ 0.03, 3.11 ]

Go 1986 2/75 6/84 3.0 % 0.39 [ 0.10, 1.63 ]

Greenall 1979 1/49 12/51 4.5 % 0.15 [ 0.05, 0.49 ]

Gurry 1976 9/15 7/14 2.9 % 1.48 [ 0.35, 6.23 ]

Leigh 1976 6/100 17/100 8.1 % 0.34 [ 0.14, 0.81 ]

Stoller 1965 6/47 10/37 5.1 % 0.40 [ 0.13, 1.19 ]

Subtotal (95% CI) 292 293 24.8 % 0.37 [ 0.22, 0.60 ]





Ahmed 1987 14/96 13/94 9.2 % 1.06 [ 0.47, 2.40 ]

Bauer 1989 12/736 52/818 24.1 % 0.30 [ 0.18, 0.50 ]

Eklund 1987 1/107 2/107 1.2 % 0.51 [ 0.05, 4.96 ]

Foster 1981 B 20/95 14/90 11.0 % 1.44 [ 0.69, 3.02 ]

Gledhill 1983 0/21 3/40 1.0 % 0.21 [ 0.02, 2.33 ]

Saario 1981 1/68 10/75 4.0 % 0.19 [ 0.06, 0.65 ]

Subtotal (95% CI) 1123 1224 50.5 % 0.52 [ 0.37, 0.73 ]





Bauer 1989 9/109 22/72 9.8 % 0.21 [ 0.10, 0.46 ]

Eklund 1987 1/51 9/65 3.6 % 0.22 [ 0.06, 0.82 ]

Foster 1981 B 15/24 19/27 4.5 % 0.71 [ 0.22, 2.24 ]

Gledhill 1983 10/21 9/20 4.1 % 1.11 [ 0.33, 3.73 ]

Saario 1981 2/19 7/18 2.8 % 0.22 [ 0.05, 0.98 ]

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)



Odds Ratio


Subtotal (95% CI) 224 202 24.7 % 0.35 [ 0.21, 0.58 ]




Total (95% CI) 1639 1719 100.0 % 0.43 [ 0.34, 0.55 ]





0.1 0.2 0.5 1 2 5 10



Outcome 2 Postoperative intra abdominal abscess.






Odds Ratio


1 Appendicitis

Leigh 1976 2/100 1/100 10.8 % 1.96 [ 0.20, 19.07 ]

Saario 1981 0/87 2/93 7.2 % 0.14 [ 0.01, 2.30 ]

Subtotal (95% CI) 187 193 18.0 % 0.69 [ 0.12, 3.99 ]





Bauer 1989 8/736 12/818 71.6 % 0.74 [ 0.31, 1.79 ]

Subtotal (95% CI) 736 818 71.6 % 0.74 [ 0.31, 1.79 ]

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)



Odds Ratio






Bauer 1989 1/109 2/72 10.3 % 0.32 [ 0.03, 3.29 ]

Subtotal (95% CI) 109 72 10.3 % 0.32 [ 0.03, 3.29 ]




Total (95% CI) 1032 1083 100.0 % 0.67 [ 0.32, 1.42 ]





0.1 0.2 0.5 1 2 5 10



Outcome 3 Length of stay in hospital.





DifferenceMean

Difference


Gurry 1976 15 14 (0) 14 12 (0) 0.0 [ 0.0, 0.0 ]

Saario 1981 87 4.4 (1.4) 93 5.2 (2.2) -0.80 [ -1.34, -0.26 ]

Total (95% CI) 102 107 -0.80 [ -1.34, -0.26 ]




-10 -5 0 5 10




Analysis 7.1. Comparison 7 Per-operatively administered multiple agent, single dose Antibiotics vs Placebo,



Comparison: 7 Per-operatively administered multiple agent, single dose Antibiotics vs Placebo



Odds RatioPeto

Odds Ratio


1 Appendicitis

Creve 1980 B 0/2 0/2 0.0 [ 0.0, 0.0 ]

Griffiths 1976 0/14 4/14 0.11 [ 0.01, 0.84 ]

Richards 1981 7/67 20/62 0.27 [ 0.12, 0.63 ]

Subtotal (95% CI) 83 78 0.24 [ 0.11, 0.52 ]





Rowlands 1982 1/20 7/23 0.19 [ 0.04, 0.89 ]

Subtotal (95% CI) 20 23 0.19 [ 0.04, 0.89 ]





Rowlands 1982 1/4 5/8 0.25 [ 0.03, 2.52 ]

Subtotal (95% CI) 4 8 0.25 [ 0.03, 2.52 ]




Total (95% CI) 107 109 0.23 [ 0.12, 0.45 ]





0.1 0.2 0.5 1 2 5 10




Analysis 8.1. Comparison 8 Operatively single agent and post-operatively single agent, single dose

Antibiotics vs placebo, Outcome 1 Wound infection.


Comparison: 8 Operatively single agent and post-operatively single agent, single dose Antibiotics vs placebo




Odds Ratio


1 Appendicitis

Browder 1989 A 3/39 8/39 38.2 % 0.35 [ 0.10, 1.25 ]

Browder 1989 B 0/44 8/39 29.1 % 0.10 [ 0.02, 0.42 ]

Willis 1976 0/49 9/46 32.8 % 0.10 [ 0.03, 0.41 ]

Subtotal (95% CI) 132 124 100.0 % 0.16 [ 0.07, 0.36 ]





Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]





Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]




Total (95% CI) 132 124 100.0 % 0.16 [ 0.07, 0.36 ]





0.1 0.2 0.5 1 2 5 10




Analysis 8.2. Comparison 8 Operatively single agent and post-operatively single agent, single dose

Antibiotics vs placebo, Outcome 2 Postoperative intra abdominal abscess.


Comparison: 8 Operatively single agent and post-operatively single agent, single dose Antibiotics vs placebo




Odds Ratio


1 Appendicitis

Browder 1989 A 0/39 2/39 50.1 % 0.13 [ 0.01, 2.15 ]

Browder 1989 B 0/44 2/39 49.9 % 0.12 [ 0.01, 1.90 ]

Subtotal (95% CI) 83 78 100.0 % 0.12 [ 0.02, 0.89 ]





Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]





Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]




Total (95% CI) 83 78 100.0 % 0.12 [ 0.02, 0.89 ]





0.1 0.2 0.5 1 2 5 10




Analysis 9.1. Comparison 9 Operatively single agent and post-operatively single agent, multiple dose

Antibiotic vs Placebo, Outcome 1 Wound infection.


Comparison: 9 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo




Odds Ratio


1 Appendicitis

Chiam 1983 B 10/100 17/100 11.1 % 0.55 [ 0.25, 1.24 ]

Chiam 1983 C 7/100 17/100 10.0 % 0.39 [ 0.17, 0.91 ]

Corbett 1979 4/52 9/53 5.4 % 0.43 [ 0.13, 1.36 ]

Foster 1978 1/70 8/69 4.0 % 0.19 [ 0.05, 0.73 ]

Giacomantonio 1982 0/21 1/21 0.5 % 0.14 [ 0.00, 6.82 ]

Keiser 1983 3/30 4/40 3.0 % 1.00 [ 0.21, 4.79 ]

Wayand 1982 7/92 8/88 6.5 % 0.82 [ 0.29, 2.37 ]

Winslow 1983 0/51 5/52 2.3 % 0.13 [ 0.02, 0.76 ]

Subtotal (95% CI) 516 523 42.7 % 0.45 [ 0.30, 0.68 ]





Bates 1980 11/70 16/71 10.4 % 0.65 [ 0.28, 1.49 ]

Busuttil 1981 B 0/43 5/42 2.2 % 0.12 [ 0.02, 0.72 ]

El-Sefi 1986 C 8/86 12/93 8.4 % 0.70 [ 0.28, 1.76 ]

Morris 1980 B 8/57 15/61 8.8 % 0.51 [ 0.21, 1.27 ]

Morris 1980 C 6/59 15/61 8.2 % 0.37 [ 0.15, 0.95 ]

Viitanen 1984 B 0/107 6/125 2.7 % 0.15 [ 0.03, 0.76 ]

Subtotal (95% CI) 422 453 40.8 % 0.46 [ 0.30, 0.70 ]





Bates 1980 6/17 5/12 3.2 % 0.77 [ 0.17, 3.44 ]

Busuttil 1981 B 0/4 1/3 0.5 % 0.10 [ 0.00, 5.09 ]

El-Sefi 1986 C 5/14 4/7 2.3 % 0.43 [ 0.07, 2.60 ]

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)



Odds Ratio


Morris 1980 B 6/10 5/5 1.3 % 0.15 [ 0.01, 1.55 ]

Morris 1980 C 8/11 5/5 1.1 % 0.19 [ 0.01, 2.57 ]

Viitanen 1984 B 8/43 15/52 8.2 % 0.58 [ 0.23, 1.47 ]

Subtotal (95% CI) 99 84 16.6 % 0.47 [ 0.24, 0.90 ]




Total (95% CI) 1037 1060 100.0 % 0.46 [ 0.35, 0.60 ]





0.1 0.2 0.5 1 2 5 10





Antibiotic vs Placebo, Outcome 2 Postoperative intra abdominal abscess.






Odds Ratio


1 Appendicitis

Morris 1980 B 0/67 1/66 33.4 % 0.13 [ 0.00, 6.72 ]

Morris 1980 C 0/70 1/66 33.3 % 0.13 [ 0.00, 6.43 ]

Subtotal (95% CI) 137 132 66.7 % 0.13 [ 0.01, 2.08 ]





El-Sefi 1986 C 0/86 1/93 33.3 % 0.15 [ 0.00, 7.38 ]

Subtotal (95% CI) 86 93 33.3 % 0.15 [ 0.00, 7.38 ]





Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]




Total (95% CI) 223 225 100.0 % 0.14 [ 0.01, 1.30 ]





0.1 0.2 0.5 1 2 5 10





Antibiotic vs Placebo, Outcome 3 Length of stay in hospital.





DifferenceMean

Difference


Bates 1980 87 4.8 (2.3) 83 5.8 (3) -1.00 [ -1.81, -0.19 ]

Busuttil 1981 B 46 2.9 (0) 45 3.8 (0) 0.0 [ 0.0, 0.0 ]

Keiser 1983 30 5.2 (0) 40 4.85 (0) 0.0 [ 0.0, 0.0 ]

Winslow 1983 51 2.5 (0) 52 2.5 (0) 0.0 [ 0.0, 0.0 ]

Total (95% CI) 214 220 -1.00 [ -1.81, -0.19 ]




-10 -5 0 5 10




Analysis 11.1. Comparison 11 Operatively multiple agent and post-operatively multiple agent, multiple

dose Antibiotics vs placebo, Outcome 1 Wound infection.


Comparison: 11 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo




Odds Ratio


1 Appendicitis

Chiam 1983 A 4/100 17/100 23.3 % 0.25 [ 0.10, 0.62 ]

Subtotal (95% CI) 100 100 23.3 % 0.25 [ 0.10, 0.62 ]





Busuttil 1981 A 0/43 5/42 5.9 % 0.12 [ 0.02, 0.72 ]

El-Sefi 1986 A 2/87 12/93 16.0 % 0.23 [ 0.08, 0.68 ]

El-Sefi 1986 B 2/82 12/93 15.9 % 0.24 [ 0.08, 0.72 ]

Morris 1980 A 2/61 15/61 18.2 % 0.17 [ 0.06, 0.48 ]

Subtotal (95% CI) 273 289 56.0 % 0.20 [ 0.11, 0.35 ]





Azabache 1987 A 1/15 6/13 6.7 % 0.13 [ 0.02, 0.71 ]

Busuttil 1981 A 0/2 1/3 1.2 % 0.19 [ 0.00, 10.32 ]

El-Sefi 1986 A 2/13 4/7 5.0 % 0.15 [ 0.02, 1.07 ]

El-Sefi 1986 B 1/18 4/7 4.1 % 0.05 [ 0.01, 0.38 ]

Morris 1980 A 0/6 5/5 3.7 % 0.03 [ 0.00, 0.25 ]

Subtotal (95% CI) 54 35 20.7 % 0.08 [ 0.03, 0.22 ]




Total (95% CI) 427 424 100.0 % 0.18 [ 0.11, 0.27 ]





0.1 0.2 0.5 1 2 5 10





dose Antibiotics vs placebo, Outcome 2 Postoperative intra abdominal abscess.






Odds Ratio


1 Appendicitis

Morris 1980 A 1/67 1/66 49.9 % 0.98 [ 0.06, 15.92 ]

Subtotal (95% CI) 67 66 49.9 % 0.98 [ 0.06, 15.92 ]





El-Sefi 1986 A 0/87 1/93 25.1 % 0.14 [ 0.00, 7.29 ]

El-Sefi 1986 B 0/82 1/93 25.0 % 0.15 [ 0.00, 7.74 ]

Subtotal (95% CI) 169 186 50.1 % 0.15 [ 0.01, 2.38 ]





Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]




Total (95% CI) 236 252 100.0 % 0.38 [ 0.05, 2.72 ]





0.1 0.2 0.5 1 2 5 10





dose Antibiotics vs placebo, Outcome 3 Length of stay in hospital.





DifferenceMean

Difference


Busuttil 1981 A 45 3.2 (0) 45 3.8 (0) 0.0 [ 0.0, 0.0 ]

Total (95% CI) 45 45 0.0 [ 0.0, 0.0 ]




-10 -5 0 5 10




Analysis 12.1. Comparison 12 Systemic antibiotics vs Placebo in children, Outcome 1 Wound infection.


Comparison: 12 Systemic antibiotics vs Placebo in children



Odds RatioPeto

Odds Ratio


1 Appendicitis

Hutchinson 1983 11/67 11/66 0.98 [ 0.39, 2.44 ]

Subtotal (95% CI) 67 66 0.98 [ 0.39, 2.44 ]





Kekomaki 1983 2/26 2/30 1.16 [ 0.15, 8.78 ]

Kizilcan 1992 A 0/25 0/25 0.0 [ 0.0, 0.0 ]

Kizilcan 1992 B 0/25 0/25 0.0 [ 0.0, 0.0 ]

Kizilcan 1992 C 0/25 0/25 0.0 [ 0.0, 0.0 ]

Soderquist 1995 A 3/138 3/126 0.91 [ 0.18, 4.59 ]

Soderquist 1995 B 2/108 3/126 0.78 [ 0.13, 4.58 ]

Subtotal (95% CI) 347 357 0.92 [ 0.33, 2.57 ]





Kekomaki 1983 3/12 1/14 3.74 [ 0.46, 30.40 ]

Soderquist 1995 A 1/55 7/50 0.18 [ 0.04, 0.76 ]

Soderquist 1995 B 1/67 7/55 0.16 [ 0.04, 0.68 ]

Subtotal (95% CI) 134 119 0.31 [ 0.12, 0.77 ]




Total (95% CI) 548 542 0.64 [ 0.37, 1.10 ]





0.1 0.2 0.5 1 2 5 10




Analysis 12.2. Comparison 12 Systemic antibiotics vs Placebo in children, Outcome 2 Postoperative intra

abdominal abscess.


Comparison: 12 Systemic antibiotics vs Placebo in children



Odds RatioPeto

Odds Ratio


1 Appendicitis

Hutchinson 1983 1/67 5/66 0.25 [ 0.05, 1.26 ]

Subtotal (95% CI) 67 66 0.25 [ 0.05, 1.26 ]





Kizilcan 1992 A 0/25 0/25 0.0 [ 0.0, 0.0 ]

Kizilcan 1992 B 0/25 0/25 0.0 [ 0.0, 0.0 ]

Kizilcan 1992 C 0/25 0/25 0.0 [ 0.0, 0.0 ]

Soderquist 1995 A 0/138 2/126 0.12 [ 0.01, 1.97 ]

Soderquist 1995 B 0/108 2/126 0.15 [ 0.01, 2.51 ]

Subtotal (95% CI) 321 327 0.14 [ 0.02, 0.98 ]





Soderquist 1995 A 0/55 1/50 0.12 [ 0.00, 6.20 ]

Soderquist 1995 B 2/67 1/50 1.48 [ 0.15, 14.86 ]

Subtotal (95% CI) 122 100 0.78 [ 0.11, 5.70 ]




Total (95% CI) 510 493 0.29 [ 0.10, 0.83 ]





0.1 0.2 0.5 1 2 5 10





Antibiotic vs Placebo in children, Outcome 1 Wound infection.


Comparison: 13 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo in children



Odds RatioPeto

Odds Ratio


1 Appendicitis

Hutchinson 1983 11/67 11/66 0.98 [ 0.39, 2.44 ]

Subtotal (95% CI) 67 66 0.98 [ 0.39, 2.44 ]





Kizilcan 1992 A 0/25 0/25 0.0 [ 0.0, 0.0 ]

Kizilcan 1992 C 0/25 0/25 0.0 [ 0.0, 0.0 ]

Soderquist 1995 A 3/138 3/126 0.91 [ 0.18, 4.59 ]

Soderquist 1995 B 2/108 3/126 0.78 [ 0.13, 4.58 ]

Subtotal (95% CI) 296 302 0.85 [ 0.26, 2.80 ]





Soderquist 1995 A 1/55 7/50 0.18 [ 0.04, 0.76 ]

Soderquist 1995 B 1/67 7/50 0.14 [ 0.03, 0.61 ]

Subtotal (95% CI) 122 100 0.16 [ 0.06, 0.44 ]




Total (95% CI) 485 468 0.52 [ 0.29, 0.93 ]





0.1 0.2 0.5 1 2 5 10





Antibiotic vs Placebo in children, Outcome 2 Postoperative intra abdominal abscess.


Comparison: 13 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo in children



Odds RatioPeto

Odds Ratio


1 Appendicitis

Hutchinson 1983 1/67 5/66 0.25 [ 0.05, 1.26 ]

Subtotal (95% CI) 67 66 0.25 [ 0.05, 1.26 ]





Ahmed 1987 0/1 0/1 0.0 [ 0.0, 0.0 ]

Kizilcan 1992 A 0/25 0/25 0.0 [ 0.0, 0.0 ]

Kizilcan 1992 C 0/25 0/25 0.0 [ 0.0, 0.0 ]

Soderquist 1995 A 0/138 2/126 0.12 [ 0.01, 1.97 ]

Soderquist 1995 B 0/108 2/126 0.15 [ 0.01, 2.51 ]

Subtotal (95% CI) 297 303 0.14 [ 0.02, 0.98 ]





Soderquist 1995 A 0/55 1/50 0.12 [ 0.00, 6.20 ]

Soderquist 1995 B 2/67 1/50 1.48 [ 0.15, 14.86 ]

Subtotal (95% CI) 122 100 0.78 [ 0.11, 5.70 ]




Total (95% CI) 486 469 0.29 [ 0.10, 0.83 ]





0.1 0.2 0.5 1 2 5 10





dose Antibiotics vs placebo, children, Outcome 1 Wound infection.


Comparison: 14 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo, children



Odds RatioPeto

Odds Ratio


1 Appendicitis

Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]





Kizilcan 1992 B 0/25 0/25 0.0 [ 0.0, 0.0 ]

Subtotal (95% CI) 25 25 0.0 [ 0.0, 0.0 ]





Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]




Total (95% CI) 25 25 0.0 [ 0.0, 0.0 ]




Test for subgroup differences: Chi2 = 0.0, df = -1 (P = 0.0), I2 =0.0%

0.1 0.2 0.5 1 2 5 10





dose Antibiotics vs placebo, children, Outcome 2 Postoperative intra abdominal abscess.


Comparison: 14 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo, children



Odds RatioPeto

Odds Ratio


1 Appendicitis

Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]





Kizilcan 1992 B 0/25 0/25 0.0 [ 0.0, 0.0 ]

Subtotal (95% CI) 25 25 0.0 [ 0.0, 0.0 ]





Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]




Total (95% CI) 25 25 0.0 [ 0.0, 0.0 ]




Test for subgroup differences: Chi2 = 0.0, df = -1 (P = 0.0), I2 =0.0%

0.1 0.2 0.5 1 2 5 10


W H A T ’ S N E W

Last assessed as up-to-date: 19 April 2005.



Date Event Description

5 September 2008 Amended Converted to new review format.

H I S T O R Y

Protocol first published: Issue 1, 1999

Review first published: Issue 2, 2001

Date Event Description

20 April 2005 New citation required and conclusions have changed Substantive amendment

C O N T R I B U T I O N S O F A U T H O R S

All three members were involved in the study design.

Two reviewers (BRA and HKA) were responsible for data extraction.

BRA and HKA performed all searches, determined inclusion, analysed the data.

All three reviewers wrote the report and performed the interpretation of the results and comments on early and final drafts of thereport.

HKA performed the searches for the update of the review, April 2005.

D E C L A R A T I O N S O F I N T E R E S T

None known

S O U R C E S O F S U P P O R T

Internal sources

• Copenhagen Hospital Corporation H:S, Denmark.



External sources

• Danish Pharmacy Foundation of 1991, Denmark.• Danish Institute for Health Technology Assessment, Denmark.

N O T E S

In figure 12.2, a study (Soderquist A+B 1995) has been included for the outcome post-operative abdominal abcess. This study is not anew one, but was previously only presented in the figure 13.2.

I N D E X T E R M S

Medical Subject Headings (MeSH)

∗Antibiotic Prophylaxis; Abdominal Abscess [∗prevention & control]; Appendectomy [∗adverse effects]; Appendicitis [surgery]; Con-trolled Clinical Trials as Topic; Length of Stay; Postoperative Complications [∗prevention & control]; Randomized Controlled Trialsas Topic; Surgical Wound Infection [prevention & control]

MeSH check words

Adult; Child; Humans



Antibiotics versus placebo for prevention of postoperative infection after appendicectomy. (Review

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