Biotransformation Of Sulfamethoxazole Research Articles

Sequential Anaerobic-Aerobic Treatment Enhances Sulfamethoxazole Removal: From Batch Cultures to Observations in a Large-Scale Wastewater Treatment Plant.

Sulfamethoxazole (SMX) passes through conventional wastewater treatment plants (WWTPs) mainly unaltered. Under anoxic conditions sulfate-reducing bacteria can transform SMX but the fate of the transformation products (TPs) and their prevalence in WWTPs remain unknown. Here, we report the anaerobic formation and aerobic degradation of SMX TPs. SMX biotransformation was observed in nitrate- and sulfate-reducing enrichment cultures. We identified 10 SMX TPs predominantly showing alterations in the heterocyclic and N4-arylamine moieties. Abiotic oxic incubation of sulfate-reducing culture filtrates led to further degradation of the major anaerobic SMX TPs. Upon reinoculation under oxic conditions, all anaerobically formed TPs, including the secondary TPs, were degraded. In samples collected at different stages of a full-scale municipal WWTP, anaerobically formed SMX TPs were detected at high concentrations in the primary clarifier and digested sludge units, where anoxic conditions were prevalent. Contrarily, their concentrations were lower in oxic zones like the biological treatment and final effluent. Our results suggest that anaerobically formed TPs were eliminated in the aerobic treatment stages, consistent with our observations in batch biotransformation experiments. More generally, our findings highlight the significance of varying redox states determining the fate of SMX and its TPs in engineered environments.

Enhanced simultaneous removal of sulfamethoxazole and zinc (II) in the biochar-immobilized bioreactor: Performance, microbial structures and gene functions

Biochar-immobilized functional bacteria Bacillus SDB4 was applied for sulfamethoxazole (SMX) and zinc (Zn2+) simultaneous removal in the bioreactor. Under the optimal operating conditions of HRT of 10 h, pH of 7.0, SMX concentration of 10 mg L−1 and Zn2+ concentration of 50 mg L−1, the removal efficiencies of SMX and Zn2+ by the immobilized reactor (IR) were 97.42% and 96.14%, respectively, 20.39% and 30.15% higher than those by free bioreactor (FR). SEM-EDS and FTIR results revealed that the functional groups and light metals on the carrier promoted the biosorption and biotransformation of SMX and Zn2+ in IR. Moreover, the improvement of SMX and Zn2+ removal might be related to the abundance enhancement of functional bacteria and genes. Bacillus SDB4 responsible for SMX and Zn2+ removal was the main strain in IR and FR. Biochar increased the relative abundance of Bacillus from 32.12% in FR to 38.73% in IR and improved the abundances of functional genes (such as carbohydrate metabolism, replication and repair and membrane transport) by 1.82%–11.04%. The correlations among the physicochemical properties, microbial communities, functional genes and SMX-Zn2+ co-contaminant removal proposed new insights into the mechanisms of biochar enhanced microbial removal of antibiotics and heavy metals in biochar-immobilized bioreactors.

Biotransformation of sulfamethoxazole by newly isolated surfactant-producing strain Proteus mirabilis sp. ZXY4: Removal efficiency, pathways, and mechanisms

In this study, the SMX degrading strain Proteus mirabilis sp. ZXY4 with surfactant manufacturing potential was isolated from sludge utilizing blood agar and CTAB agar plate. FTIR analysis indicated that the biosurfactant generated by strain ZXY4 was glycolipid. 3D-EEM demonstrated that SMX biodegradation was strongly connected to biosurfactants, the synergistic effect of biodegradation and biosurfactant made strain ZXY4 have excellent SMX degradation performance. Under the optimal conditions of inoculation dosage of 15%, temperature of 30 ℃, pH of 7 and initial SMX concentration of 5 mg L-1, strain ZXY4 could completely degrade SMX within 24 h. SMX biodegrades at low concentrations (less than5 mg L-1) followed by the zero-order kinetic model, high concentration (>5 mg L-1) is more consistent with the first-order kinetic model. LC-MS analysis revealed 14 SMX degradation intermediates, and five potential biodegradation mechanisms were postulated. The findings provide new insights into the biodegradation of SMX.

Biotransformation of sulfamethoxazole (SMX) by aerobic granular sludge: Removal performance, degradation mechanism and microbial response

Aerobic granular sludge (AGS) is a promising biotechnology for the treatment of antibiotic−rich wastewater. However, little is known about the antibiotics degradation mechanism and microbial response in a sulfamethoxazole (SMX)-loaded AGS system. Herein, the results of a continuous 240 days test suggested that 0.5–5 mg/L of SMX could be thoroughly removed by AGS via adsorption and degradation. The degradation pathway of SMX involved the hydrolysis of the sulfonamide bond and cleavage of NS or CS bonds, subsequently leading to the production of small molecular substances (e.g. benzene and 5-methyl-isoxazole). In terms of the AGS system, it exhibited a strong resistance to 0.5 mg/L of SMX, while 1 and 5 mg/L of SMX significantly inhibited the microbial growth, declined the nitrification efficiency, weakened the sludge settleability, and triggered the excessive growth of filamentous bacteria. Besides, the secretion of extracellular polymer substances was suppressed by 57.3% when increasing the SMX concentration from 0.5 to 5 mg/L, which was not conducive to the system stability. The long−term presence of SMX enhanced the proliferation of antibiotics resistance genes (sul1and sul2) and exerted a strong selection pressure on the microbial community, especially with Thiothrix being the dominating genus. Overall, this study elucidated that AGS qualified promising application prospects in the removal of SMX present in wastewater, but SMX at high concentrations posed great adverse impacts on the performance of the AGS system, which causes concern when treating SMX rich wastewaters.

Biotransformation of sulfamethoxazole by a novel strain, Nitratireductor sp. GZWM139: Characterized performance, metabolic mechanism and application potential

A novel strain, Nitratireductor sp. GZWM139 capable of efficient removal of SMX was isolated from mariculture sewage, and Nitratireductor was reported to conduct the removal of antibiotics for the first time. Strain GZWM139 exhibited desirable adaptations to environmental factors with SMX removal efficiencies more than 90 % at temperatures of 28–38 °C, pH values of 4.5–8.5, salinities of 20–30 ‰, SMX levels of 1–5 mg/L and shaking speeds of 20–260 rpm. SMX removal was a cooperated process implemented by intracellular enzymes and extracellular enzymes, and was achieved through four proposed biotransformation pathways with the occurrences of demethylation, hydroxylation, nitration, formylation, oxidation, bond cleavage and ring opening. Strain GZWM139 responded to the SMX removal process by altering properties of cell membrane and motivating activities of xenobiotic-metabolizing enzymes and antioxidant system. Genomic analysis proved the existence of functional genes relevant to the SMX removal in strain GZWM139 and provided echoing genetic insights for revealing the SMX removal mechanism. Strain GZWM139 performed efficient detoxification of SMX and accomplished simultaneous removal of SMX and nitrogen in both mariculture sewage and domestic sewage. The findings are significant to the effective elimination of SMX pollution and comprehensive cognitions on metabolic mechanisms of SMX removal.

Mechanisms underlying enhanced bioremediation of sulfamethoxazole and zinc(II) by Bacillus sp. SDB4 immobilized on biochar

Microbial remediation is an eco-friendly and promising approach for the decontamination of wastewater containing sulfamethoxazole (SMX) and Zn2+. However, free bacteria are sensitive to environmental variation, limiting the application. In this study, biochar-immobilized Bacillus paramycoides SDB4 (ISDB4) was used to overcome the disadvantages. The results showed that the removal by ISDB4 was significantly increased under different pH conditions and initial combined contaminant concentrations. Notably, at pH 7, SMX (20 mg L−1) and Zn2+ (100 mg L−1) were completely removed by ISDB4, and their levels were 29.28% and 92.34% higher than that of SDB4, respectively. Besides, ISDB4 showed excellent reusability with 43.24% of SMX and 50.34% of Zn2+ removal efficiencies after five continuous cycles. Such improvements might be related to enhanced biotransformation of SMX from 45.81% with SDB4 to 89.98% with ISDB4. Compared with SDB4, the contributions of ion exchange and complexation of ISDB4 with Zn2+ increased by 9.53% and 6.72%, respectively. In case of ISDB4, SEM-EDS and FTIR showed that biochar provided sufficient space for the attachment and proliferation of SDB4, and the removal of combined contaminants was enhanced by SDB4 due to the presence of functional groups and light metals on biochar. This study provides a green and effective strategy for the bioremediation of antibiotic and heavy metal co-contaminated aquaculture wastewater.

Biotransformation of sulfamethoxazole by microalgae: Removal efficiency, pathways, and mechanisms

Recently, the biotransformation of sulfamethoxazole (SMX) by microalgae has attracted increasing interest. In particular, cytochrome P450 (CYP450) has been suggested to be the main enzymatic contributor to this biodegradation. However, the molecular evidence of CYP450 enzymes being involved in SMX biodegradation remains relatively unclear, hindering its applicability. Herein, the biodegradation of SMX by Chlorella sorokiniana (C. sorokiniana) was investigated, and comprehensively elucidated the reaction mechanism underlying CYP450-mediated SMX metabolism. C. sorokiniana was able to efficiently remove over 80% of SMX mainly through biodegradation, in which CYP450 enzymes responded substantially to metabolize SMX in cells. Additionally, screening of transformation products (TPs) revealed that N4-hydroxylation-SMX (TP270) was the main TP in the SMX biodegradation pathway of microalgae. Molecular dynamics (MD) simulation suggested that the aniline of SMX was the most prone to undergo metabolism, while density functional theory (DFT) indicated that SMX was metabolized by CYP450 enzymes through H-abstraction-OH-rebound reaction. Collectively, this work reveals key details of the hydroxylamine group of SMX, elucidates the SMX biodegradation pathway involving CYP450 in microalgae in detail, and accelerates the development of using microalgae-mediated CYP450 to eliminate antibiotics.

Sulfamethoxazole removal from mariculture wastewater in moving bed biofilm reactor and insight into the changes of antibiotic and resistance genes

Antibiotics are widely dosed in mariculture sector, resulting in substantial antibiotics residues. Hence, mariculture wastewater is urgent to be treated before discharging. In this study, the anoxic/oxic moving bed biofilm reactor (A/O-MBBR) was used to treat the wastewater containing sulfamethoxazole (SMX) from mariculture, SMX removal mechanism and the variation of antibiotic-resistant genes (ARGs) were investigated. The results showed that 22%–33% of SMX was removed by the bioreactor, where a small amount of SMX was adsorbed and stored by the extracellular polymers and most of SMX (>80%) was biodegraded in the anoxic tank. Occurrence of nitrate in anoxic condition was conducive to SMX degradation. Pseudomonas, Desulfuromusa, and Methanolobus species, as well as microbial catalase contributed to the SMX biotransformation. Quantitative PCR analysis of ARGs (sul1, sul2 and int1) and mRNA (sul1, sul2) showed that SMX enriched SMX-related ARGs and enhanced the expression of corresponding genes. Most of ARGs finally were discharged with effluent. Hence, the effluent from biologically based processes treating mariculture wastewater still contained antibiotics residue and resistance genes, which should be further controlled by suitable techniques.

Performance of partial nitrification process in a zeolite biological aerated filter with the addition of sulfamethoxazole

Due to the rapid development of medical industries, wastewater treatment plants have become sinks for residual antibiotics. However, the contribution of novel partial nitrification processes to the bioremediation of antibiotics remains unclear. In this study, the removal rate of a partial nitrification process on the biotransformation of sulfamethoxazole (SMZ) was evaluated. A biological aerated filter made from zeolite successfully achieved stable partial nitrification. A nitrite accumulation percentage (NAP) greater than 85% was obtained when the influent ammonium concentration was increased to 300 mg/L with a nitrogen loading rate of 1.24 kg/(m3 d). Batch tests were performed on support collected from different heights of the up-flow reactor at the end of the pilot monitoring experiment. The maximum ammonium oxidation rate of 5.63 mg/(g VSS·L) in one hour was recorded at a height of 0.32–0.48 m in the reactor, indicating nitrifying bacteria activity link between the free ammonia (FA) and biomass concentration was found. After the addition of SMZ (2.5 mg/L), the NAP declined to approximately 70%, and the abundance of Nitrosomonas (the main ammonia oxidizing bacteria (AOB) genus in the zeolite biological aerated filter (ZBAF)) decreased 7.24–6.10%. Lower abundance and activity of AOB oxidized ineffectively the primary amine of SMZ, which led to lower than 19% of the SMZ removal efficiency.

New biotransformation pathways from sulfamethoxazole and ciprofloxacin removal in sewage treatment along the spatial profile of an anaerobic fixed bed bioreactor

In this work, the biotransformation products (BTPs) from the removal of the antibiotics sulfamethoxazole (SMX) and ciprofloxacin (CIP) were assessed for the first time in an anaerobic packed bed biofilm reactor (APBBR) treating municipal sewage. Anaerobic batch assays at high concentrations of the antibiotics (5 mg·L−1) were performed to identify the BTPs generated during the SMX and CIP biodegradation. From the mass transitions of the identified BTPs, they were analyzed along the spatial profile of the APBBR fed with sewage (400 ngSMX·L−1 and 300 ngCIP·L−1). Three BTPs were identified: m/z 256 and m/z 270 from SMX, and m/z 316 from CIP. The molecular structures of the BTPs revealed that SMX biotransformation occurs in the isoxazole ring and a dehydroxylation in the CIP molecule. This study showed new biotransformation pathways of SMX and CIP during anaerobic digestion, contributing to the understanding of the fate of these pharmaceutical compounds in the environment.

Biotransformation of Sulfamethoxazole (Smx) by Aerobic Granular Sludge: Removal Performance, Degradation Mechanism and Microbial Response

Biotransformation of Sulfamethoxazole (Smx) by Aerobic Granular Sludge: Removal Performance, Degradation Mechanism and Microbial Response

Simultaneous high-efficiency removal of sulfamethoxazole and zinc (II) from livestock and poultry breeding wastewater by a novel dual-functional bacterium, Bacillus sp. SDB4.

The complex mixtures of antibiotics and heavy metals are commonly existed in livestock and poultry breeding wastewater. Effective and simultaneous removal of these toxic compounds by microorganisms, especially single strains, remains a considerable challenge. In this study, a novel functional strain SDB4, isolated from duck manure and identified as Bacillus sp., has been shown to possess high removal capabilities for both sulfamethoxazole (SMX) and Zn2+. The maximum removal efficiency achieved 73.97% for SMX and 84.06% for Zn2+ within 48 h in the single pollution system. It has great potential for eliminating SMX along with Zn2+, 78.45% of SMX and 52.91% of Zn2+ were removed in the 20 mg·L-1 SMX and 100 mg·L-1 Zn2+ binary system. Furthermore, the SMX-biotransformation capability of SDB4 was enhanced at low concentrations of Zn2+ (below 100 mg·L-1). The SMX biotransformation and Zn2+ adsorption data fitted well with the pseudo-first-order kinetic model, indicating that the two pollutants were in accordance with the same removal rule. N4-acetyl-SMX was identified as the main stable transformation product during SMX removal. FTIR analyses revealed that OH, NH2, C=O, C-N/N-H, and C-O-C played major roles in the adsorption of Zn2+. Our study of the dually functioning strain SDB4 provides a potential application for the simultaneous biological removal of antibiotics and heavy metals.

Redox mediator, microaeration, and nitrate addition as engineering approaches to enhance the biotransformation of antibiotics in anaerobic reactors

The present work assessed some engineering approaches, such as the addition of the redox mediator anthraquinone-2,6-disulfonate (AQDS) (50 and 100 μM), microaeration (1 mL air min−1), and nitrate (100−400 mg L−1), for enhancing the biotransformation of the antibiotics sulfamethoxazole (SMX) and trimethoprim (TMP) (200 μg L−1 each) in anaerobic reactors operated at a short hydraulic retention time (7.4 h). Initially, very low removal efficiencies (REs) of SMX and TMP were obtained under anaerobic conditions (∼6%). After adding AQDS, the anaerobic biotransformation of these antibiotics significantly improved, with an increase of approximately 70% in the REs with 100 μM of AQDS. Microaeration also enhanced the biotransformation of SMX and TMP, especially when associated with AQDS, which provided REs above 70%, particularly for TMP (∼91% with 1 mL air min−1 and 50 μM of AQDS). Concerning nitrate, the higher the added concentration, the higher the REs of the antibiotics (∼86% with 400 mg L−1). Therefore, all the assessed approaches were demonstrated to be very effective in improving the limited biotransformation of SMX and TMP in anaerobic reactors, ensuring REs comparable to those found in higher-cost wastewater treatment technologies, such as conventional activated sludge, membrane bioreactors, and hybrid processes.

Removal and biotransformation pathway of antibiotic sulfamethoxazole from municipal wastewater treatment by anaerobic membrane bioreactor

A lab-scale mesophilic anaerobic membrane bioreactor (AnMBR) was used to treat synthetic municipal wastewater with variable concentrations of antibiotic Sulfamethoxazole (SMX) and bulk organics in this study. The removal and biotransformation pathway of SMX in the AnMBR were systematically investigated during a 170 d of operation under hydraulic retention time of 1 d. Average SMX removal was 97.1% under feed SMX of 10–1000 μg/L, decreasing to 91.6 and 88.0% under feed SMX of 10,000 and 100,000 μg/L due to the inhibition effects of high SMX loading rate on anaerobic microorganisms. SMX biotransformation followed pseudo-first order reaction kinetics based on SMX removal independent of feed SMX of 10–1000 μg/L during continuous operation and also in a batch test under initial SMX of 100,000 μg/L. According to the identified 7 transformation products (TPs) by gas chromatography-mass spectrometry, the biotransformation pathway of SMX from municipal wastewater treatment via AnMBR was first proposed to consist of 2 primary routes: 1) Butylbenzenesulfonamide without antibiotic toxicity dominated under feed SMX of 10–100 μg/L; 2) Sulfanilamide with much lower antibiotic toxicity than SMX dominated under feed SMX of 1000–100000 μg/L, further transforming to secondary TPs (4-Aminothiophenol, Aniline, Acetylsulfanilamide) and tertiary TPs (4-Acetylaminothiophenol, Acetylaniline).

Bioaugmentation of activated sludge with Achromobacter denitrificans PR1 for enhancing the biotransformation of sulfamethoxazole and its human conjugates in real wastewater: Kinetic tests and modelling

Achromobacter denitrificans PR1 has previously shown potential to degrade the antibiotic sulfamethoxazole, whereby sulfamethoxazole biotransformation was stimulated in the presence of biogenic substrates. This study examined the biotransformation kinetics of sulfamethoxazole and its two main conjugates, N4-acetyl-SMX and SMX-N1-Glucuronide, by activated sludge and activated sludge bioaugmented with A. denitrificans PR1. SMX biotransformation under both anoxic and aerobic conditions was tested, with and without the addition of acetate as growth substrate, to understand the range of applicable conditions for bioaugmentation purposes. Biological process models, such as the pseudo-first order kinetic and cometabolic models, were also applied and, following the estimation of kinetic parameters, could well describe data measured in bioaugmented and non-bioaugmented AS batch experiments under various test conditions. Experimental and modelling results suggest that (i) retransformation of the two conjugates to SMX in AS occurred under both aerobic and anoxic conditions, and (ii) biotransformation kinetics of SMX can vary significantly depending on redox conditions, e.g., SMX was biotransformed by AS only under aerobic conditions. Notably, SMX biotransformation was significantly enhanced when PR1 was bioaugmented in AS. Addition of acetate as biogenic substrate is not necessary, as PR1 was capable of enhancing the SMX biotransformation by using the carbon sources present in wastewater. Overall, bioaugmentation by means of A. denitrificans PR1 could be a viable strategy for enhancing SMX removal in AS wastewater treatment plants (WWTPs).

Sulfamethoxazole degradation in anaerobic sulfate-reducing bacteria sludge system

Sulfamethoxazole (SMX) is one of the most commonly used antibiotics. SMX degradation in sulfate-reducing bacteria (SRB) sludge systems has not been reported so far. This research investigated the SMX degradation using SRB sludge in a sulfate-reducing up-flow sludge bed reactor. Moreover, the mechanisms and kinetics of SMX removal were also investigated using SRB sludge via a series of batch experiments. The results showed that SMX removal was characterized by a rapid sorption onto SRB sludge, and desorption from SRB sludge to aqueous phase until achieving equilibrium, and then followed by slow biodegradation. Biodegradation was the dominant route for SMX removal. The sorption process conformed well to a pseudo-second-order kinetic model, meaning that the sorption occurred primarily via a chemical sorption process. The removal of SMX followed the pseudo-zero-order kinetic model with a specific removal rate of 13.2 ± 0.1 μg/L/d at initial SMX concentration 100 μg/L in batch tests. Based on the analysis of metabolites, most of the SMX biotransformation products' structures altered in the isoxazole ring, which were significantly different from that produced by aerobic and anaerobic sludge systems. Thus, SRB sludge system could play an important role in SMX biodegradation, especially in Sulfate-reduction Autotrophic denitrification and Nitrification Integrated (SANI) process for sewage treatment.

Generation of synthetic influent data to perform (micro)pollutant wastewater treatment modelling studies

The use of process models to simulate the fate of micropollutants in wastewater treatment plants is constantly growing. However, due to the high workload and cost of measuring campaigns, many simulation studies lack sufficiently long time series representing realistic wastewater influent dynamics. In this paper, the feasibility of the Benchmark Simulation Model No. 2 (BSM2) influent generator is tested to create realistic dynamic influent (micro)pollutant disturbance scenarios. The presented set of models is adjusted to describe the occurrence of three pharmaceutical compounds and one of each of its metabolites with samples taken every 2–4h: the anti-inflammatory drug ibuprofen (IBU), the antibiotic sulfamethoxazole (SMX) and the psychoactive carbamazepine (CMZ). Information about type of excretion and total consumption rates forms the basis for creating the data-defined profiles used to generate the dynamic time series. In addition, the traditional influent characteristics such as flow rate, ammonium, particulate chemical oxygen demand and temperature are also modelled using the same framework with high frequency data. The calibration is performed semi-automatically with two different methods depending on data availability. The ‘traditional’ variables are calibrated with the Bootstrap method while the pharmaceutical loads are estimated with a least squares approach. The simulation results demonstrate that the BSM2 influent generator can describe the dynamics of both traditional variables and pharmaceuticals. Lastly, the study is complemented with: 1) the generation of longer time series for IBU following the same catchment principles; 2) the study of the impact of in-sewer SMX biotransformation when estimating the average daily load; and, 3) a critical discussion of the results, and the future opportunities of the presented approach balancing model structure/calibration procedure complexity versus predictive capabilities.

Exogenous cofactors for the improvement of bioremoval and biotransformation of sulfamethoxazole by Alcaligenes faecalis

Sulfamethoxazole (SMX), an extensively prescribed or administered antibiotic pharmaceutical product, is usually detected in aquatic environments, because of its incomplete metabolism and elimination. This study investigated the effects of exogenous cofactors on the bioremoval and biotransformation of SMX by Alcaligenes faecalis. High concentration (100mg·L−1) of exogenous vitamin C (VC), vitamin B6 (VB6) and oxidized glutathione (GSSG) enhanced SMX bioremoval, while the additions of vitamin B2 (VB2) and vitamin B12 (VB12) did not significantly alter the SMX removal efficiency. Globally, cellular growth of A. faecalis and SMX removal both initially increased and then gradually decreased, indicating that SMX bioremoval is likely dependent on the primary biomass activity of A. faecalis. The decreases in the SMX removal efficiency indicated that some metabolites of SMX might be transformed into parent compound at the last stage of incubation. Two transformation products of SMX, N-hydroxy sulfamethoxazole (HO-SMX) and N4-acetyl sulfamethoxazole (Ac-SMX), were identified by a high-performance liquid chromatograph coupled with mass spectrometer. High concentrations of VC, nicotinamide adenine dinucleotide hydrogen (NADH, 7.1mg·L−1), and nicotinamide adenine dinucleotide (NAD+, 6.6mg·L−1), and low concentrations of reduced glutathione (GSH, 0.1 and 10mg·L−1) and VB2 (1mg·L−1) remarkably increased the formation of HO-SMX, while VB12 showed opposite effects on HO-SMX formation. In addition, low concentrations of GSH and NADH enhanced Ac-SMX formation by the addition of A. faecalis, whereas cofactors (VC, VB2, VB12, NAD+, and GSSG) had no obvious impact on the formation of Ac-SMX compared with the controls. The levels of Ac-SMX were stable when biomass of A. faecalis gradually decreased, indicating the direct effect of biomass on the formation of Ac-SMX by A. faecalis. In sum, these results help us understand the roles played by exogenous cofactors in eliminating SMX by A. faecalis and provide potential strategies for improving SMX biodegradation.

Effect of severe protein-calorie malnutrition on the penetration kinetics of trimethoprim and sulfamethoxazole to the deep tissues of Wistar rats.

This study shows the effect that severe malnourishment has on the kinetics of antibiotic penetration in tissues. A total of 104 male Wistar rats, 21 days old, were randomly divided into eight groups. Five groups of experimental rats were severely malnourished (SM) and three further groups were considered well-nourished control groups (WN). A single dose of trimethoprim-sulfamethoxazole (TMP-SMX) was administered intraperitoneally. Blood samples were taken by heart puncture and five organs were extracted 0-24 h after the administration of the drug. HPLC was used to assess the amount of trimethoprim and sulfamethoxazole in fluids. The elimination half-life for trimethoprim from plasma was longer in SM rats with a median of 3.15 h; in WN rats, it was 0.390 h. Clearance was slower in SM rats: 646.72 mL microg(-1) h(-1) vs 3036.38 mL microg(-1) h(-1) in WN rats (P < 0.05). Tissue penetration was much higher for trimethoprim, with penetration indexes of 0.80-5.66 in WN rats, compared with 0.35-2.14 in SM rats. In the case of sulfamethoxazole, penetration indexes were 0.029-1.13 for WN and 0.075-0.657 for SM rats. Similarly, the penetration ratio to muscle and heart tissue was lower in SM rats. However, penetration to kidney, lung, liver and spleen was greater in SM rats. It is evident that severe SM decreases the capacity of trimethoprim more importantly than sulfamethoxazole biotransformation.