Sulfadiazine

Large amounts of manure have been applied to arable soils as fertilizer worldwide. Manure is often contaminated with veterinary antibiotics which enter the soil together with antibiotic resistant bacteria. However, little information is available regarding the main responders of bacterial communities in soil affected by repeated inputs of antibiotics via manure. In this study, a microcosm experiment was performed with two concentrations of the antibiotic sulfadiazine (SDZ) which were applied together with manure at three different time points over a period of 133 days. Samples were taken 3 and 60 days after each manure application. The effects of SDZ on soil bacterial communities were explored by barcoded pyrosequencing of 16S rRNA gene fragments amplified from total community DNA. Samples with high concentration of SDZ were analyzed on day 193 only. Repeated inputs of SDZ, especially at a high concentration, caused pronounced changes in bacterial community compositions. By comparison with the initial soil, we could observe an increase of the disturbance and a decrease of the stability of soil bacterial communities as a result of SDZ manure application compared to the manure treatment without SDZ. The number of taxa significantly affected by the presence of SDZ increased with the times of manure application and was highest during the treatment with high SDZ-concentration. Numerous taxa, known to harbor also human pathogens, such as Devosia, Shinella, Stenotrophomonas, Clostridium, Peptostreptococcus, Leifsonia, Gemmatimonas, were enriched in the soil when SDZ was present while the abundance of bacteria which typically contribute to high soil quality belonging to the genera Pseudomonas and Lysobacter, Hydrogenophaga, and Adhaeribacter decreased in response to the repeated application of manure and SDZ.

This study is aimed to assess the biodegradation of sulfadiazine (SDZ) and characterization of heavy metal resistance in three pure bacterial cultures and also their chemotactic response towards 2-aminopyrimidine. The bacterial cultures were isolated from pig manure, activated sludge and sediment samples, by enrichment technique on SDZ (6 mg L-1). Based on the 16S rRNA gene sequence analysis, the microorganisms were identified within the genera of Paracoccus, Methylobacterium and Kribbella, which were further designated as SDZ-PM2-BSH30, SDZ-W2-SJ40 and SDZ-3S-SCL47. The three identified pure bacterial strains degraded up to 50.0, 55.2 and 60.0% of SDZ (5 mg L-1), respectively within 290 h. On the basis of quadrupole time-of-flight mass spectrometry and high performance liquid chromatography, 2-aminopyrimidine and 4-hydroxy-2-aminopyrimidine were identified as the main intermediates of SDZ biodegradation. These bacteria were also able to degrade the metabolite, 2-aminopyrimidine, of the SDZ. Furthermore, SDZ-PM2-BSH30, SDZ-W2-SJ40 and SDZ-3S-SCL47 also showed resistance to various heavy metals like copper, cadmium, chromium, cobalt, lead, nickel and zinc. Additionally, all three bacteria exhibited positive chemotaxis towards 2-aminopyrimidine based on the drop plate method and capillary assay. The results of this study advanced our understanding about the microbial degradation of SDZ, which would be useful towards the future SDZ removal in the environment.

Infection control is necessary for improved burn wound regeneration. In this study contact burn wounds were induced on the dorsum of the rats and were infected with Pseudomonas aeruginosa (107cfu/ml of saline) and left overnight (12-14 hours) to establish the infection. After 12 hours, the wounds were treated with PEGylated fibrin hydrogel containing 50 mgs of silver sulfadiazine (SSD) loaded chitosan microsphere (SSD-CSM-FPEG). On day 9, SSD-CSM-FPEG treated burn wounds further received adipose derived stem cell (5×104 ASCs cells/ml) embedded in PEGylated fibrin hydrogel. Wounds were assessed for the healing outcomes such as neovascularization, granulation tissue formation, wound closure and collagen maturation. Analysis of bacterial load in the burn wound biopsies, demonstrated that SSD-CSM-FPEG significantly reduced bacterial infection, while overt infection was still observed in the untreated groups on day 14. Sequential treatment of infected wounds with SSD-CSM-FPEG followed by ASC-FPEGs (SSD-CSM-ASC-FPEG) significantly reduced bacterial colonization (9 log reduction) and pro-inflammatory cytokine (TNF-α) expression. A significant increase in neovascularization markers; NG2 and vWF was also observed. Histological analysis indicated the wounds treated with SSD-CSM-ASC-FPEG increased amount of dermal collagen matrix deposition, a thicker granulation tissue on day 21 and more mature collagen on day 28. This work demonstrates that the sequential treatment of infected burn wounds with SSD-CSM-FPEG followed by ASC-FPEG reduces bacterial infection as well as promotes neo-vascularization with improved matrix remodeling.

BackgroundPotentiated sulphonamides, combining trimethoprim (TMP) with a sulphonamide such as sulfadiazine (SDZ) or sulfamethoxazole (SMX), are widely used in canine medicine. The standard 1:5 dose ratio was initially designed to achieve a plasma concentration ratio of approximately 1:19 in humans, considered optimal for antibacterial synergy. However, species differences in pharmacokinetics may influence whether this ratio is achieved and maintained in dogs. Updated pharmacokinetic data based on modern analytical techniques and unbound (active) drug concentrations are lacking. This study aimed to characterise and compare the pharmacokinetics and plasma protein binding of TMP/SDZ and TMP/SMX in dogs.MethodsBeagle dogs were administered TMP/SDZ or TMP/SMX intravenously and orally in a crossover design. In addition, TMP was administered orally alone once. Plasma concentrations of TMP, SDZ and SMX were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Population pharmacokinetic analysis was performed using nonlinear mixed-effects modelling. Protein binding was determined by ultrafiltration, and free fractions were estimated using linear mixed-effects models.ResultsOral bioavailability was high for all compounds (93-97%). TMP exhibited substantially higher clearance (0.44 L/h/kg) and a shorter elimination half-life (4.2 h) than SDZ (0.05 L/h/kg; 7.6 h) and SMX (0.026 L/h/kg; 12.6 h). TMP also showed a markedly larger apparent volume of distribution (2.67 L/kg) compared to the sulphonamides (approximately 0.5 L/kg). Protein binding differed between compounds, with population mean free fractions of 0.50 for SDZ, 0.33 for SMX, and 0.43 for TMP. Following both intravenous and oral administration, the free sulphonamide-to-TMP concentration ratios were only close to the proposed 1:19 ratio during the first hours after dosing. Thereafter, the ratios progressively increased due to the more rapid elimination of TMP.ConclusionsTMP/SDZ and TMP/SMX display distinct pharmacokinetic profiles in dogs, particularly with respect to clearance, half-life and protein binding. The commonly used 1:5 dose ratio does not maintain a stable 1:19 free concentration ratio over a 12 h dosing interval. These findings provide clinically relevant pharmacokinetic data to support rational and species-specific use of potentiated sulphonamides in dogs.