Analysis, fate and effects of the antibiotic sulfadiazine in soil ecosystems

Trends Trends in Analytical Chemistry, Vol. 28, No. 5, 2009

Analysis, fate and effects of theantibiotic sulfadiazine in soilecosystemsKristina Schauss, Andreas Focks, Holger Heuer, Anja Kotzerke, Heike Schmitt,

Soren Thiele-Bruhn, Kornelia Smalla, Berndt-Michael Wilke,

Michael Matthies, Wulf Amelung, Jorg Klasmeier, Michael Schloter

This review summarizes current knowledge about the interplay between fate and effects of the antibiotic sulfadiazine in soil

ecosystems. In applying manure from antibiotic-treated animals to arable soils, sulfadiazine can reach the environment, but fate

and transformation processes and the consequences for soil microorganisms and soil functions have not been studied adequately.

Since antibiotics are explicitly designed to affect microorganisms, they are likely to affect ‘‘non-target’’ microbes in the soil

ecosystem. Recent papers provide new insights into the disappearance dynamics of sulfadiazine, its effects on distinct microbial

communities and the development of antibiotic resistance.

ª 2009 Elsevier Ltd. All rights reserved.

Keywords: Antibiotic resistance; Chemical analysis; Disappearance dynamics; Ecosystem; Fate; Microbial community; Microorganism; Soil;

Sulfadiazine; Transformation process

Kristina Schauss*, Michael Schloter

Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Institute for Soil

Ecology, Ingolstadter Landstr. 1, 85764 Neuherberg, Germany

Andreas Focks, Michael Matthies, Jorg Klasmeier

University of Osnabruck, Institute of Environmental Systems Research, Barbarastr. 12, 49069

Osnabruck, Germany

Holger Heuer, Kornelia Smalla

Julius Kuhn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and

Pathogen Diagnostics, Messeweg 11-12, 38104 Braunschweig, Germany

Anja Kotzerke, Berndt-Michael Wilke

Berlin University of Technology, Institute of Ecology, Franklinstr. 29, 10587 Berlin, Germany

Heike Schmitt

Utrecht University, Institute for Risk Assessment Sciences (IRAS), PO Box 80175, 3508 TD Utrecht,

The Netherlands

Soren Thiele-Bruhn

University of Trier, Department of Soil Science, Behringstr. 21, 54286 Trier, Germany

Wulf Amelung

University of Bonn, Institute of Crop Science and Resource Conservation – Soil Science and Soil

Ecology, Nussallee 13, 53115 Bonn, Germany

*Corresponding author.

Tel.: +49 (0)89 3187 3054;

Fax: +49 (0)89 3187 3376;

E-mail: kristina.schauss@

helmholtz-muenchen.de

612 0165-9936/$ - see front matter ª 2009 Elsev

1. Introduction

Since the first steps in antibiotic therapyby Paul Ehrlich at the beginning of thetwentieth century, much effort has beenmade to develop new antibiotic com-pounds to treat infectious diseases and toprotect human and animal health. In theEuropean Union, more than 3900 Mg oftherapeutic antibiotics were consumed in1999 for veterinary purposes only [1],while estimated 16 000 Mg are consumedannually in the USA for therapeutic andnon-therapeutic use [2]. In agriculture,manure is commonly used as organic fer-tilizer, so large amounts of bio-activeforms of veterinary drugs (parental com-pounds or metabolites) may reach theenvironment via this pathway. Conse-quently, hundreds of grams of antibioticsper hectare may be spread annually onagricultural soils [3]. However, knowledgeabout the fate, the behavior and adverseeffects of antibiotic compounds in theenvironment (e.g., on soil communitystructures, microbial functioning, andmicrobial resistance) is scarce [4–6].

ier Ltd. All rights reserved. doi:10.1016/j.trac.2009.02.009

mailto:kristina.schauss@�helmholtz-muenchen.de

mailto:kristina.schauss@�helmholtz-muenchen.de

Trends in Analytical Chemistry, Vol. 28, No. 5, 2009 Trends

Sulfonamides belong to one of the important groups ofveterinary drugs worldwide, mainly in pig production[7]. They are poorly adsorbed in the animal gut, so thatmost of them are excreted unchanged in urine and feces[8–11]. The fate of antibiotics in soil depends on manyinteracting factors (e.g., water solubility, soil texture,sorption capacity, pH value, moisture content, drainage,temperature, and timing of manure application) (re-viewed, e.g., in [4,5,12]). There is evidence that sulfon-amides can persist for prolonged periods of time in soils[13], so they may exert long-term effects. However, thereis considerable uncertainty about the nature of sulfon-amide residues in aged soils, which, to a great extent,resist solvent-extraction procedures and result in a so-called non-extractable residue fraction [14].

The effectiveness of sulfonamides towards a broadspectrum of bacteria rests upon the inhibition of multi-plication of most Gram-positive and many Gram-nega-tive bacteria by competitive inhibition of p-aminobenzoicacid in the folic-acid-metabolism cycle [15], so not onlymight animal pathogens be affected but also soil bacteriathat relate to soil quality and turnover processes. Theinteraction with and effects on soil fauna are in manycases associated with uptake of sulfonamides by theorganisms [16], which is again linked to the availabilityof sulfonamides in the environment.

This review gives an overview on papers concerninganalyses, fate and effects of sulfonamide sulfadiazine(SDZ) in soil ecosystems with emphasis on recentlypublished results directly linking the development ofsulfonamide concentrations in soil over time with im-pacts on soil microbiology.

2. Chemical fate of sulfonamides in soils

Sulfonamides are characterized by two dissociationconstants (pKa). The lower one indicates protonation ofthe amino group, whereas the other signifies deproto-nation of the SO2NH moiety [17]. In the environment,sulfonamides are present in neutral (uncharged) andanionic (deprotonated) forms, with the latter being moreabundant at higher pH values. For example, sulfadiazine(pKa2 = 6.5) is more than 50% deprotonated underneutral conditions but its speciation is very sensitive tothe pH value in the environmentally-relevant range. Asshown by a number of studies, the sorption of sulfona-mides to soil clearly depends on the environmental pHvalue [13,14,18,19], implying that transport andtransformation are also thereby affected.

Ultimate bio-degradation or transformation intometabolites may form a sink for sulfonamides in soils.For sulfadiazine, two main metabolites (i.e. 4-hydroxy-SDZ and N-acetyl-SDZ) have been identified as beingformed during the passage through the animal [11]. Ofparticular interest with respect to biological effects is the

hydroxyl-metabolite due to its potential to exert biolog-ical effects via the active moiety of the molecule [20]. Inmanure-amended soil containing 14C-labeled SDZ and itsmain metabolites, the only significant transformationprocess assessed was de-acetylation of biologically-inac-tive N-acetyl-SDZ to the parent compound SDZ [21].Ultimate biodegradation could be excluded as a signifi-cant sink [22,23]. In all these studies, the amount of14C-CO2 remained below 2% of the radioactivity applied.

In recent years, several studies addressed the questionof sulfonamide dynamics in manure and manure-amended soil [24–26]. The extraction of sulfonamidesemerged as a critical step in analyses of environmentalsamples that often resulted in unsatisfactory yield. Shakeextraction using various solvents of different polarity(recovery 30–55%) proved to be inferior compared tomore vigorous methods (e.g., accelerated solventextraction [27] or microwave extraction [28]), whichreached extraction yields P 70%. Also, the temperatureof extraction turned out to be an important factor forgood recoveries of sulfonamides. The best results wereachieved with accelerated solvent extraction at 200�C(acetonitrile/water, 15/85) and microwave extraction at150�C (acetonitrile/water, 25/75) with SDZ recoveries of93% after 90 min for accelerated solvent extraction [27]and 70% and 80% after 8 days for accelerated solventextraction and microwave extraction, respectively [28].

A common finding of all studies was that recovery ofsulfonamides from field soils and spiked soils decreasedsignificantly with increasing contact time, regardless ofwhich extraction method was applied. This phenome-non, known as aging or sequestration, is often ascribedto slow, but reversible, sorption processes forming aresidual fraction [29]. This is consistent with the findingof increasing apparent sorption coefficients in standardbatch experiments [14]. Laboratory experiments with14C-labeled SDZ revealed an additional effect of applyingmanure on the extractability of the compound from soils[26]. Recovery after three days of incubation was sig-nificantly lower in batches applying test slurry comparedto purely spiked soil samples, indicating that SDZ is morerapidly transferred into the non-extractable residuefraction under the influence of manure. However, thenature of the non-extractable residue fraction and theunderlying processes are still unclear, so aging is alsodiscussed with respect to the bioavailability issue [30].Bialk and Pedersen [31] showed that sulfonamides areable to form covalent bonds with humic substances.Such a bound-residue fraction would be an ultimate sinkfor the compounds, whereas slow sorption leaves themavailable in the long term due to possible remobilizationby slow desorption.

To elucidate the sequestration behavior of SDZ and itsmain metabolites further, Forster et al. [21] used asequential extraction (CaCl2 solution followed by meth-anol extraction and microwave extraction at 150�C with

http://www.elsevier.com/locate/trac 613


acetonitrile/water, 25/75) to analyze manure-amendedsoil samples over 218 days of incubation. After a fewdays, the amount extracted in the first two fractionsdecreased to <50% of the radioactivity applied, whereasan increase of SDZ and its hydroxyl metabolite in themicrowave fraction was observed. These findings indi-cate that sulfonamides are sequestered in soil, forming aresidual fraction that can be extracted only by morevigorous extraction methods (higher temperatures).However, this residual fraction is obviously not cova-lently bound, so it can be remobilized to present a pos-sible long-term risk in soil.

Several data sets on the fate of SDZ after application tosoil with manure are available [21,22,32]. Althoughthese data sets differ with respect to the experimentalconditions, the extraction methods applied and thenumber of measurements, the dynamics of SDZ appearedvery similar in all cases. The time course of SDZ is mainlydominated by two phases:� an initial phase, in which fast sequestration of SDZ

into the residual fraction is observed; and,� a second phase, where the concentration in the CaCl2

and methanol extract decreases only very slowly, pos-sibly due to increasing remobilization from the resid-ual fraction.This leads to concentrations of several lg/kg, still

detectable 200 days after applying manure [21,22]. Thehypothesis of reversible sequestration into a residualfraction is corroborated by model simulations with amechanistic fate model that can deliver a plausible,consistent explanation of the dynamics observed [33]. Asa consequence of this disappearance dynamics of SDZ,long-lasting, low-level concentrations that are found inthe CaCl2 fraction may cause adverse effects on soilmicroorganisms.

3. Effects on the microbial community structureand activity

There have been only a few studies investigating theeffects of sulfonamides on the microbial structure of soil.Some sulfonamides had been reported to affect generaland potential microbial activities and the bacterialcommunity structure [34], and shifts from bacteria tofungi had been observed [35]. However, effects dependon the energy source added, so the effect of sulfonamidesis likely to be linked to adding a substrate to promotemicrobial growth. This is mainly relevant for manure asthe main carrier of antibiotics to soil. Hammesfahr andco-workers [32] investigated the effect of 10 mg/kg and100 mg/kg sulfadiazine (added to manure) on themicrobial community structure and bacterial diversity insoil. The results revealed clear reduction of microbialbiomass, decreased ratio of bacteria to fungi, and alter-ation of the bacterial population in the SDZ-treated

614 http://www.elsevier.com/locate/trac

samples. Increases in fungal biomasses in soil were alsofound in microcosm experiments with sulfamethoxazoleat concentrations of 20 mg/kg and 500 mg/kg [36].Further, changes in the microbial community structuretowards higher pollution-induced community tolerancewere also observed for sulfachloropyridazine [37,38] andsulfamethoxazole [36] (detected through increased tol-erance of leucine incorporation and/or multiple sub-strate utilization for adding antibiotics).

Sulfonamides have also been reported to affect theactivity of soil microorganisms [39]. For example, per-sistent inhibitory effects on the growth rate of soilmicroorganisms were observed for sulfamethoxazole[36]. Soil respiration is another frequently investigatedparameter for microbial activity, which provides infor-mation about the broad status of microbial activity insoil. Kotzerke and co-workers [40] studied the impact ofsulfadiazine on substrate-induced respiration in two dif-ferent arable soils, focusing on the dynamics of microbialcommunities in response to the antibiotic at two con-centrations (10 mg/kg and 100 mg/kg) together withapplying manure. In the loamy sand soil in the first daysafter SDZ application, they observed reduced CO2 pro-duction, with a decelerated response to adding glucosebeing more pronounced in the higher SDZ treatment.After 32 days, the soil microbes had recovered in thelower SDZ treatment but not in the higher SDZ treat-ment. By contrast, in the silty loam, lower, delayed CO2

production was found only at the higher sulfadiazineconcentration in the first days and recovered after32 days. Overall, the antibiotic effects of SDZ dependedon time, dose and soil, which was in agreement withother studies.

4. Effects on nitrogen turnover and functionalmicrobial communities

Soil microbial populations are of fundamental impor-tance for ecosystem functioning due to their perfor-mance of nutrient-cycling processes [41]. One of themost important nutrient cycles in terrestrial environ-ments is the nitrogen cycle with nitrification (oxidationof ammonia to nitrate via nitrite) and denitrification(reduction of nitrate to molecular nitrogen via nitrite,nitric oxide and nitrous oxide) being essential transfor-mation processes, which are both mainly driven byprokaryotes. The occurrence of antibiotic compoundstherefore might compromise microbiological nitrogen-turnover processes in soils, but knowledge of ecotoxicityand effects on soil microbial functioning is poor [4–6].

The effect of a single application of pig manure spikedwith two different concentrations of sulfadiazine (10 mg/kg and 100 mg/kg) was investigated in two arable soilson abundance and diversity of distinct functionalgroups of soil bacteria involved in nitrification and


denitrification [42,43]. Ammonia-oxidizing bacteria(AOB) and archaea (AOA) can perform the first step innitrification but belong to two phylogenetically differentgroups of microorganisms [44,45]. By contrast, denitri-fying bacteria belong to a wide variety of taxonomicgroups and have been determined via functional genesnirK and nirS that both encode the enzyme nitritereductase. Sulfadiazine concentrations in CaCl2 extractswere measured over time as an approximation for thebio-available fraction of the antibiotic.

In terms of denitrifying bacteria, the numerically moreimportant nitrite reducers harboring the nirS gene in-creased in abundance when bio-available SDZ had de-clined, whereas the nitrite reducers harboring the nirKgene mainly decreased in abundance compared to thecontrol treatment. Possibly, nirS nitrite reducers recoverfaster after sulfadiazine stress than their counterpart.

Concerning the effect on nitrification, in both soils,SDZ notably inhibited the growth of AOB, whereas AOAwere affected to a lesser extent. However, clear differ-ences were also found between the soils, probably based,amongst other reasons, on the different ratios ofAOA:AOB (73:1 in the silt loam and 7:1 in the loamysand, respectively). In the silt loam soil, growth of AOAwas even observed in the higher SDZ treatment, result-ing in increased maximum ratios of AOA:AOB of morethan 100:1. By contrast, changes in AOA abundancewere hardly pronounced in the loamy sand soil.

Based on the observed nitrification dynamics in themicrocosm experiment, a new model approach allowedthe simulation of nitrification processes in SDZ-amendedsoils [42]. The model simulations relied on calculatedcontributions of the functional biomasses to ammoniaoxidation that were determined by the abundances ofAOA and AOB, the maximum ammonia-oxidation rateconstants per cell (separately for AOA and AOB) and theavailability of ammonium. The dynamics of nitrification

Figure 1. Simulated values of the in situ nitrification rates in the siltloam soil amended with manure (solid), manure with 10 mg SDZ/kg (dashed), and manure with 100 mg SDZ/kg (dotted). For detailsof the nitrification model, refer to [30].

after applying pure manure and SDZ-containing manurewere described well by the model, so that the effect ofSDZ on the simulated in situ nitrification rates could becalculated. Sulfadiazine in both concentrations de-creased the nitrification rates (e.g., at day 30 by 40%and 50% in lower and higher treatments, respectively)(Fig. 1).

From the nitrifier abundances in both SDZ treatmentsin the silt loam soil, EC50 constants could be estimatedfor AOA and AOB, respectively. AOA seemed to beconsiderably more resistant to SDZ stress with an esti-mated inhibition constant of 30 mg SDZ/kg that fittedboth sulfadiazine treatments. For AOB, an EC50 value of0.01 mg/kg was estimated in the lower SDZ treatment,whereas, in the higher SDZ treatment, AOB grew despitecontinually higher SDZ concentrations, so that an inhi-bition constant of 8 mg/kg was estimated here. Thiselevated inhibition constant for AOB very probably re-sulted from selection of a more resistant AOB sub-pop-ulation under the pressure of >20 mg SDZ/kg for at least32 days, so, in both SDZ treatments, AOA maintainedammonia oxidation at a certain level and even grew overtime at the higher SDZ concentration.

5. Effects on the dynamics of bacterial resistancegenes

Bacterial resistance to sulfonamides is mainly mediatedby genes sul1, sul2 and sul3 coding for dihydropteroatesynthases, which are insensitive to sulfonamides[46,47]. The genes occur in a wide range of bacterialspecies, because they are often located on transposableelements of self-transferable or mobilizable broad host-range plasmids [48]. When soils are treated with man-ure, residues of antibiotics, nutrients and bacteria car-rying antibiotic-resistance genes are introduced into thesoil. The accumulation of sul genes in manured soil de-pends on the input of resistant bacteria from the man-ure, the horizontal transfer of sul genes on mobilegenetic elements to soil-adapted bacteria, and the inputand the selective pressure of sulfonamides in soil. Piggerymanure is a reservoir of bacteria carrying antibioticresistance genes [49,50]. Genes sul1 and sul2 especiallywere found in high amounts [22,51]. In a recent study,significant amounts of sul genes were detected inmanure from pigs, which had never been treated withantibiotics [52]. Storage of manure is not sufficient toreduce sulfonamide-resistance genes, because nearly allthe excreted SDZ persisted in manure at inhibitory con-centrations [22].

Heuer and co-workers [22,53] investigated the effectsof SDZ and manure on the abundance, the diversity andthe transfer potential of sulfonamide-resistance genes ina silt loam, which was never fertilized with manure, anda loamy sand from a periodically manured field.



Manuring increased the relative number of sul genes inboth soils. Significantly higher amounts of sul1 and sul2were detected in soil up to two months after manuring.The effect was more pronounced with manure contain-ing SDZ.

Sulfonamide-resistant bacteria from manure may notbe well adapted to soil conditions so their environmentalspread is restricted. Horizontal gene transfer, which isenhanced by manure, can overcome this barrier [50,54].Manuring significantly increased the abundance ofantibiotic-resistant bacteria with low GC-type plasmidsin soil [22]. When the manure contained SDZ, the effectwas detectable for at least two months, which suggestedthat SDZ helped plasmid-carrying bacteria to persist.There was evidence that the plasmids transferred to awide range of bacterial species where sul2 becamechromosomally located, while the replicon itself wastypically not stably inherited, except in Acinetobacter spp.This plasmid host might be especially important, becauseantibiotic-resistant Acinetobacter baumannii, which areopportunistic pathogens, are emerging as a threatworldwide [55].

Risk assessment of the intensive veterinary use ofantibiotics has often ignored important mechanisms(e.g., cross-species spread of resistance by plasmidtransfer [56]). It is necessary to consider that humansare continually exposed to bacteria in their environment,which is highly interconnected with other habitats byexchanges of bacterial populations and genetic material[57,58], so veterinary antibiotics and spread manure arelikely to contribute to the problem of antimicrobialresistance in human therapy of infectious diseases.

Based on experiments, a mathematical model wasdeveloped relating the fate of SDZ and its metabolites to

Figure 2. Dynamics of bacterial sulfonamide-resistance genes sul1(diamonds, simulations with solid lines) and sul2 (stars, dashedlines) in soil amended with manure from sulfadiazine-treated pigs.Gene target numbers were adjusted to target numbers of bacterial16S rRNA genes in the same sample. The dotted line results fromthe simulation of sul1 genes without SDZ effect. For parameter esti-mations, refer to [14].


selection of antibiotic-resistance genes in stored manureand manured soils [22]. The model explicitly consideredthe costs of a resistance gene in the absence of selectivepressure, the positive selection of a resistance gene underantibiotic pressure, and the horizontal gene transfer ofresistance genes. Model parameters and confidenceintervals were estimated from the respective data. Usingthe model, the time course of experimentally quantifiedsul1 and sul2 resistance genes in soil could be simulatedwith reasonable accuracy (Fig. 2). With an integratedmodel approach, it was possible to determine the SDZconcentration at which the sul2 genes were selected overa time period of about 65 days down to a concentrationof 0.15 mg/kg.

6. Effects on organisms other than bacteria

Only a very few investigations have addressed effects onsoil organisms other than bacteria. Generally, one mightexpect indirect effects mediated through changes in soilbacteria rather than direct effects on higher soil organ-isms, as the latter do not synthesize folates and therebylack the enzymatic target of sulfonamides (dihydrofolatereductase). For example, sulfachloropyridazine did notaffect earthworm mortality in terrestrial multi-speciessystems [59] at concentrations up to 100 mg/kg. Plantsmight form an exception, as it has been shown that thedihydropteroate synthetase enzyme of plants is highlyhomologous to that of bacteria [60]. Indeed, aquaticplants [61–63] and green algae [64,65] have beenshown to be affected by sulfonamides. However, effects insoil-plant systems were limited to concentrations around100 mg/kg of sulfadimethoxime [66] and sulfachloro-pyridazine [59] (with hormesis-like effects at lowerconcentrations), possibly due to different bio-availabilityin soil. Finally, though sulfachloropyridazine has beentested in multi-species test systems, including a range ofdifferent taxa [59], no investigation to date has specifi-cally addressed indirect effects of changes in bacterial orfungal populations on the soil food chain.

7. Summary and outlook

This review summarizes current knowledge about thechemical fate and the effect of sulfadiazine in soils,focusing on methods and experiments to investigate theinterplay between both. The environmental fate of SDZ isaffected by surrounding pH conditions and is charac-terized by rapid sequestration that is enhanced in thepresence of manure. Differentiation between an availablefraction, a reversibly sequestered residual fraction andbound residues requires exhaustive extraction of thesamples. Accelerated solvent extraction and microwaveextraction proved to be superior to solvent-shake


extraction, and extraction yields clearly increased withincreasing temperature. Although sequestration leads toa fast decrease of SDZ concentrations in easily availablefractions (CaCl2 extract and solvent-shake extracts), atleast parts of the non-extractable fractions can beremobilized, as shown by the higher extraction yieldswhen more vigorous methods are applied. It is suggestedthat slow reversible sorption into a residual fraction al-lows low, but effective SDZ concentrations in the soilsolution to be maintained over a long time period.

Data published so far indicate pronounced effects ofsulfadiazine applied together with manure on soil fertilityand transformation rates of nutrients, due to reducedactivity patterns of microbial communities. Such tem-porary effects could be linked to the CaCl2-extractablefraction of sulfadiazine and/or the development ofmicrobial communities with increased resistance againstthe antibiotic over time. Resistance development mightbe explained by an exchange of antibiotic-resistancegenes between microbes via mobile genetic elements or ashift in the community towards microbes that are lessaffected by sulfadiazine. A newly developed, integratedfate-effect model could contribute to clarifying the dis-appearance dynamics of sulfadiazine, to interpretingsignificant effects on nitrifying microbes, and to quanti-fying the concentration until the selection of resistancegenes takes place.

Most data relate to a single application of manurecontaminated with sulfonamides, but repeated manur-ing of the same fields, even in the same vegetation per-iod, is common agricultural practice, so further studiesare needed to clarify the consequences of repeatedapplications of sulfonamide-containing manure onantibiotic behavior and effects in soils.

Another poorly investigated aspect is the effect ofchanging weather conditions on fate and effects ofantibiotics. Most experiments were performed at con-stant soil moisture contents and constant temperatures.However, natural processes (e.g., freezing and thawingor drying and re-wetting) could affect sequestration,disintegration and release of antibiotic substances due tophysico-chemical alterations to the soil matrix, so thebio-availability of antibiotics might also differ from thatin constant climatic conditions and therefore entail dif-ferent effects on microorganisms.

Finally, data on fate and effects of one specific antibi-otic compound collected in one or two exemplary soiltypes can certainly not be generalized for other antibioticcompounds in other soil types, implying that fate andeffect of different substances must be studied intensively.

AcknowledgementThe authors are grateful for the funding of the researchgroup FOR 566 ‘‘Veterinary medicines in soils: Basic

research for risk analysis’’ by the German researchfoundation, DFG.

References[1] FEDESA, Press release, European Federation of Animal Health,

Brussels, Belgium, 2001.

[2] Union of Concerned Scientists (UCS), Press release, Hogging it!:

Estimates of antimicrobial abuse in livestock, UCS, Washington,

DC, USA, 2001.

[3] G. Hamscher, S. Sczesny, H. Hoper, H. Nau, Anal. Chem. 74

(2002) 1509.

[4] K. Kumar, S.C. Gupta, Y. Chander, A.K. Singh, in: D.L. Sparks

(Editor), Advances in Agronomy, Vol. 87, Academic Press,

Amsterdam, The Netherlands, 2005, p. 1.

[5] S. Thiele-Bruhn, J. Plant Nutr. Soil Sci. 166 (2003) 145.

[6] A.B.A. Boxall, D.W. Kolpin, B. Halling-Sørensen, J. Tolls, Environ.

Sci. Technol. 37 (2003) 286A.

[7] M. Burkhardt, C. Stamm, C. Waul, H. Singer, S. Muller, J. Environ.

Qual. 34 (2005) 1363.

[8] G.K. Elmund, S.M. Morrison, D.W. Grant, M.P. Nevins, Bull.

Environ. Contam. Toxicol. 6 (1971) 129.

[9] R.E. Alcock, A. Sweetman, K.C. Jones, Chemosphere 38 (1999)

2247.

[10] B. Halling-Sørensen, Arch. Environ. Contam. Toxicol. 40 (2001)

451.

[11] M. Lamshoft, P. Sukul, S. Zuhlke, M. Spiteller, Anal. Bioanal.

Chem. 388 (2007) 1733.

[12] A.K. Sarmah, M.T. Meyer, A.B.A. Boxall, Chemosphere 65 (2006)

725.

[13] T.L. ter Laak, W.A. Gebbink, J. Tolls, Environ. Toxicol. Chem. 25

(2006) 904.

[14] M. Kahle, C. Stamm, Chemosphere 68 (2007) 1224.

[15] G.M. Brown, J. Biol. Chem. 237 (1962) 536.

[16] C. Zarfl, M. Matthies, J. Klasmeier, Chemosphere 70 (2008) 753.

[17] F. Ingerslev, B. Halling-Sørensen, Environ. Toxicol. Chem. 19

(2000) 2467.

[18] S.T. Kurwadkar, C.D. Adams, M.T. Meyer, D.W. Kolpin, J. Agric.

Food Chem. 55 (2007) 1370.

[19] J. Gao, J.A. Pedersen, Environ. Sci. Technol. 39 (2005) 9509.

[20] E. Schoondermarkvandeven, T. Vree, W. Melchers, W. Camps, J.

Galama, Antimicrob. Agents Chemother. 39 (1995) 763.

[21] M. Forster, V. Laabs, M. Lamshoft, J. Groneweg, S. Zuhlke, M.

Spiteller, M. Krauss, M. Kaupenjohann, W. Amelung, Environ.

Sci. Technol. (2009) (DOI:10.1021/es8026538).

[22] H. Heuer, A. Focks, M. Lamshoft, K. Smalla, M. Matthies, M.

Spiteller, Soil Biol. Biochem. 40 (2008) 1892.

[23] B. Schmidt, J. Ebert, M. Lamshoft, B. Thiede, R. Schumacher-

Buffel, R. Ji, P.F.X. Corvini, A. Schaffer, J. Environ. Sci. Health.,

Part B 43 (2008) 8.

[24] G. Hamscher, H.T. Pawelzick, H. Hoper, H. Nau, Environ. Toxicol.

Chem. 24 (2005) 861.

[25] J. Heise, S. Holtge, S. Schrader, R. Kreuzig, Chemosphere 65

(2006) 2352.

[26] R. Kreuzig, S. Holtge, Environ. Toxicol. Chem. 24 (2005)

771.

[27] K. Stoob, H.P. Singer, S. Stettler, N. Hartmann, S.R. Mueller, C.H.

Stamm, J. Chromatogr., A 1128 (2006) 1.

[28] M. Forster, V. Laabs, M. Lamshoft, T. Putz, W. Amelung, Anal.

Bioanal. Chem. 391 (2008) 1029.

[29] J.J. Pignatello, Environ. Toxicol. Chem. 9 (1990) 1117.

[30] M. Alexander, Environ. Sci. Technol. 34 (2000) 4259.

[31] H.M. Bialk, J.A. Pedersen, Environ. Sci. Technol. 42 (2008) 106.

[32] U. Hammesfahr, H. Heuer, B. Manzke, K. Smalla, S. Thiele-Bruhn,

Soil Biol. Biochem. 40 (2008) 1583.


http://dx.doi.org/


[33] C. Zarfl, Chemical fate of sulfadiazine in soils: Mechanisms and

modelling approaches, Shaker verlag, Aachen, 2008. ISBN 978-

3-8322-7491-7.

[34] Y. Zielezny, J. Groeneweg, H. Vereecken, W. Tappe, Soil Biol.

Biochem. 38 (2006) 2372.

[35] S. Thiele-Bruhn, I.-C. Beck, Chemosphere 59 (2005) 457.

[36] L.A. Demoling, E. Baath, G. Greve, M. Wouterse, H. Schmitt, Soil

Biol. Biochem. (2009), doi:10.1016/j.soilbio.2009.02.001.

[37] H. Schmitt, P. van Beelen, J. Tolls, C.L. van Leeuwen, Environ. Sci.

Technol. 38 (2004) 1148.

[38] H. Schmitt, H. Haapakangas, P. van Beelen, Soil Biol. Biochem. 37

(2005) 1882.

[39] M.Y. Haller, S.R. Muller, C.S. McArdell, A.C. Alder, M.J.F. Suter, J.

Chromatogr., A 952 (2002) 111.

[40] A. Kotzerke, S. Sharma, K. Schauss, H. Heuer, S. Thiele-Bruhn, K.

Smalla, B.M. Wilke, M. Schloter, Environ. Pollut. 153 (2008) 315.

[41] K. Westergaard, A.K. Muller, S. Christensen, J. Bloem, S.J.

Sørensen, Soil Biol. Biochem. 33 (2001) 2061.

[42] K. Schauss, A. Focks, S. Leininger, A. Kotzerke, H. Heuer, S.

Thiele-Bruhn, S. Sharma, B.-M. Wilke, M. Matthies, K. Smalla, J.C.

Munch, W. Amelung, M. Kaupenjohann, M. Schloter, C. Schleper,

Environ. Microbiol. 11 (2009) 446.

[43] K. Schauss, S. Sharma, A. Kotzerke, H. Heuer, S. Thiele-Bruhn, K.

Smalla, B.-M. Wilke, M. Schloter, unpublished data.

[44] S. Leininger, T. Urich, M. Schloter, L. Schwark, J. Qi, G.W. Nicol,

J.I. Prosser, S.C. Schuster, C. Schleper, Nature (London) 442

(2006) 806.

[45] E. Bock, M. Wagner, in: M. Dworkin (Editor), The Prokaryotes,

Vol. 2, Springer, New York, USA, 2006, p. 457.

[46] V. Perreten, P. Boerlin, Antimicrob. Agents Chemother. 47

(2003) 1169.

[47] O. Skold, Drug Resist. Updates 3 (2000) 155.

[48] H. Heuer, R. Szczepanowski, S. Schneiker, A. Puhler, E.M. Top, A.

Schluter, Microbiology (Reading, U. K.) 150 (2004) 3591.


[49] H. Heuer, E. Krogerrecklenfort, E.M.H. Wellington, S. Egan, J.D.

van Elsas, L. van Overbeek, J.M. Collard, G. Guillaume, A.D.

Karagouni, T.L. Nikolakopoulou, K. Smalla, FEMS Microbiol. Ecol.

42 (2002) 289.

[50] K. Smalla, H. Heuer, A. Gotz, D. Niemeyer, E. Krogerrecklenfort, E.

Tietze, Appl. Environ. Microbiol. 66 (2000) 4854.

[51] C.T.T. Binh, H. Heuer, M. Kaupenjohann, K. Smalla, FEMS

Microbiol. Ecol. 66 (2008) 25.

[52] H. Heuer, C. Kopmann, C.T.T. Binh, E.M. Top, K. Smalla, Environ.

Microbiol. (2008) (DOI:10.1111/j.1462-2920.2008.01819.x).

[53] H. Heuer, K. Smalla, Environ. Microbiol. 9 (2007) 657.

[54] A. Gotz, K. Smalla, Appl. Environ. Microbiol. 63 (1997) 1980.

[55] L. Dijkshoorn, A. Nemec, H. Seifert, Nat. Rev. Microbiol. 5 (2007)

939.

[56] J.C. Bailar, K. Travers, Clin. Infect. Dis. 34 (2002) S135.

[57] T.F. O�Brien, Clin. Infect. Dis. 34 (2002) S78.

[58] A.O. Summers, Clin. Infect. Dis. 34 (2002) S85.

[59] S. Boleas, C. Alonso, J. Pro, M.M. Babin, C. Fernandez, G.

Carbonell, J.V. Tarazona, Environ. Toxicol. Chem. 24 (2005) 811.

[60] G.J.C. Basset, E.P. Quinlivan, J.F. Gregory, A.D. Hanson, Crop Sci.

45 (2005) 449.

[61] R.A. Brain, D.J. Johnson, S.M. Richards, H. Sanderson, P.K. Sibley,

K.R. Solomon, Environ. Toxicol. Chem. 23 (2004) 371.

[62] R.A. Brain, A.J. Ramirez, B.A. Fulton, C.K. Chambliss, B.W.

Brooks, Environ. Sci. Technol. 42 (2008) 8965.

[63] J. Pro, J.A. Ortiz, S. Boleas, C. Fernandes, G. Carbonell, J.V.

Tarazona, Bull. Environ. Contam. Toxicol. 70 (2003) 290.

[64] B. Ferrari, R. Mons, B. Vollat, B. Fraysse, N. Paxeus, R. Lo Giudice,

A. Pollio, J. Garric, Environ. Toxicol. Chem. 23 (2004) 1344.

[65] H.-C. Holten, Lutzhøft, B. Halling-Sørensen, S.E. Jørgensen, Arch.

Environ. Contam. Toxicol. 36 (1999) 1.

[66] L. Migliore, C. Civitareale, S. Cozzolino, P. Casoria, G. Brambilla, L.

Gaudio, Chemosphere 37 (1998) 2957.

http://dx.doi.org/

http://dx.doi.org/

Analysis, fate and effects of the antibiotic sulfadiazine in soil ecosystems

Documents

Transcript of Analysis, fate and effects of the antibiotic sulfadiazine in soil ecosystems