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This study aimed to investigate the effect of vermicomposting process in removal of sulfamethoxazole (SMX) and trimethoprim (TMP) antibiotics in cattle manure. In this experimental study, vermicomposting process was performed in 6 reactors on a pilot scale. The cattle manure (3.5 kg) and Eisenia foetida worms (120 g) were added to each reactor. Sulfamethoxazole and trimethoprim antibiotics were added to reactors in four different concentrations of 10, 20, 50, and 100 mg/kg and two reactors were control free-worm with antibiotic and free antibiotic. Vermicomposting quality tests, including pH, electric conductivity (EC), total and volatile solids (VS), ash content, C/N, and potassium (K) were performed during the vermicomposting process for 8 weeks. Antibiotics concentration was analyzed using a high-performance chromatography (HPLC), and toxicity assessment of the final product was evaluated by germination index (GI) test. The results showed that there was a decrease in total solid, K and C/N and an increase in pH, EC, VS, and ash content parameters. Moreover, investigations showed a significant reduction in antibiotic concentrations at the end of the process. Antibiotics changes during the vermicomposting process showed that SMX had a faster removal rate compared to TMP and reached ≥ 99.99% at the end of the fourth week. In reactors with lower antibiotic concentrations, a faster removal rate was observed. The biodegradation of antibiotics follows first-order kinetics. GI toxicity assessment shows that this index reached 90% at the end of the process. Finally, it seems that vermicomposting is an effective method in reducing antibiotics in cattle manure. [ABSTRACT FROM AUTHOR]

Nucleocytoplasmic large DNA viruses (NCLDVs; also called giant viruses), constituting the phylum Nucleocytoviricota, can infect a wide range of eukaryotes and exchange genetic material with not only their hosts but also prokaryotes and phages. A few NCLDVs were reported to encode genes conferring resistance to beta‑lactam, trimethoprim, or pyrimethamine, suggesting that they are potential vehicles for the transmission of antibiotic resistance genes (ARGs) in the biome. However, the incidence of ARGs across the phylum Nucleocytoviricota, their evolutionary characteristics, their dissemination potential, and their association with virulence factors remain unexplored. Here, we systematically investigated ARGs of 1416 NCLDV genomes including those of almost all currently available cultured isolates and high-quality metagenome-assembled genomes from diverse habitats across the globe. We reveal that 39.5% of them carry ARGs, which is approximately 37 times higher than that for phage genomes. A total of 12 ARG types are encoded by NCLDVs. Phylogenies of the three most abundant NCLDV-encoded ARGs hint that NCLDVs acquire ARGs from not only eukaryotes but also prokaryotes and phages. Two NCLDV-encoded trimethoprim resistance genes are demonstrated to confer trimethoprim resistance in Escherichia coli. The presence of ARGs in NCLDV genomes is significantly correlated with mobile genetic elements and virulence factors. Nucleocytoplasmic large DNA viruses, or 'giant viruses', infect a wide range of eukaryotes and can exchange genetic material not only with their hosts but also with bacteria and phages. Here, the authors show that many giant viruses carry diverse antibiotic resistance genes, which are associated with mobile genetic elements and genes encoding potential virulence factors. [ABSTRACT FROM AUTHOR]

The present study investigated the degradation of trimethoprim using Eosin Y-sensitized ZnFe2O4-g-C3N4 photocatalyst under natural sunlight using a parabolic trough reactor. The photocatalyst performance was optimized for three independent variables: pollutant dosage (10–25 mg/l), catalyst dose (0.4–1.2 g/l), and solution pH (4–10). The central composite design (CCD) was used to generate the design matrix and the response surface for degradation and total organic carbon (TOC) removal as the responses. Multiple regression techniques for each response generated two quadratic polynomial models. The coefficient of determination (R2) for trimethoprim degradation and TOC removal was 0.99 and 0.96, respectively, and these models could explain the variability in response surface. The analysis of variance (ANOVA) revealed that the initial pollutant dose and catalyst dose were most significant (p < 0.05) in contributing to both degradation and TOC removal. The optimum parameters obtained by desirability function for pollutant concentration, pH, and catalyst concentration were 10 mg/l, 7.19, and 0.72 g/l. This yielded an optimum degradation and TOC removal of 89.52% and 49.12%, respectively. Validation studies using optimized conditions for single-factor experiments had negligible variation from the predicted values, with actual degradation and TOC removal being 87.02% and 46.33%, respectively. Considering the good predictability and validity of the models, Response Surface Methodology is a potential mathematical tool for modeling the photodegradation of different antibiotics in aquatic environments. [ABSTRACT FROM AUTHOR]

Mathematical manipulation technique has proven to be a very powerful tool for efficient processing and handling of highly overlapped spectra. This work introduced two green and sustainable approaches for the successful recovery of the ternary mixture, Tylosin tartarate (TYL), Sulfadimdine (SLD), and Trimethoprim (TRI). The approaches were constructed using three different methods, derivative ratio spectrum zero-crossing method (DRSZ), double divisor ratio spectra derivative method (DDRD), and factorized derivative ratio method coupled with spectrum subtraction (FDRM-SS). The two approaches succeeded in recovering the three drugs (Linearity range achieved were 0.5–5 µg/mL for TYL, 0.3–1.3 µg/mL for SLD, and 0.3–5 µg/mL for TRI), giving convenient standard deviations and satisfactory recovery percentages. The recommended methods have been verified in accordance with (ICH) guidelines. When the results were statistically compared to the official methods, no significant difference was found. Both AGREE—Analytical GREEnness Metric Approach and Software, and White Analytical Chemistry (WAC) RGB model gave scores of 0.93 and 97.2%, respectively, which proved that the approaches were eco-friendly and abiding by the sustainability principles. [ABSTRACT FROM AUTHOR]

Pharmaceutical pollutants are among the most important issues in human life. The reason for investigating and controlling environmental pollution is the entry of these pollutants into the food cycle and drug resistance, which causes many environmental risks. In this study, the rate of photocatalytic degradation of TMP, a model organic pollutant, was investigated using NiFe2O4@MoO3 nanocomposites. The characteristics of the nanocomposites were identified using XRD, FESEM, EDX, and VSM techniques. This study aimed to explore the effects of different factors on the photocatalytic removal of the trimethoprim antibiotic (TMP) using a central composite design (CCD) and response surface method (RSM). Significant variables were identified, including initial pH (3–9), catalyst dose (5–100 mg/L), pollutant concentration (20–100 mg/L), and contact time (0–120 min), and 30 experiments were conducted to optimize the process. Statistical analysis based on analysis of variance (ANOVA) showed that the following factors influenced the response. In addition, the results showed that the efficiency of the photocatalytic process increased with an increase in catalyst and residence time, and the efficiency of the photocatalytic process increased with an increase in pH up to 6.3. RSM results revealed the best experimental conditions for TMP degradation under UV light. They showed that the initial pollutant concentration and pH had a greater impact on the degradation process than did the catalyst dose and retention time. This suggests that optimizing operational factors can significantly improve the performance of photocatalytic processes for removing antibiotics such as trimethoprim. [ABSTRACT FROM AUTHOR]

Background: To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center experience switching from ciprofloxacin to fosfomycin trometamol (FMT) alone and to an augmented prophylaxis combining fosfomycin and trimethoprim/sulfamethoxazole (TMP/SMX). Methods: Between 01/2019 and 12/2020 we compared three different regimes. The primary endpoint was the clinical diagnosis of an infection within 4 weeks after biopsy. We enrolled 822 men, 398 (48%) of whom received ciprofloxacin (group-C), 136 (16.5%) received FMT (group-F) and 288 (35%) received the combination of TMP/SMX and FMT (group-BF). Results: Baseline characteristics were similar between groups. In total 37/398 (5%) postinterventional infections were detected, of which 13/398 (3%) vs 18/136 (13.2%) vs 6/288 (2.1%) were detected in group-C, group-F and group-BF respectively. The relative risk of infectious complication was 1.3 (CI 0.7–2.6) for group-C vs. group-BF and 2.8 (CI 1.4–5.7) for group-F vs. group-BF respectively. Conclusion: The replacement of ciprofloxacin by fosfomycin alone resulted in a significant increase of postinterventional infections, while the combination of FMT and TMP/SMX had a comparable infection rate to FQ without apparent adverse events. Therefore, this combined regimen of FMT and TMP/SMX is recommended. [ABSTRACT FROM AUTHOR]

Objective: This article is focused on synthesis and characterisation of 1,1-(((5-(3,4,5triethoxybenzyl)pyrimidine-2,4-diyl))bis(azanediyl))bis(substituted phenyl methylene))bis(naphthalen-2-ol) moieties and evaluated for antibacterial and antioxidant activities as well as molecular docking and molecular dynamic simulation investigations. Methods: In this article we conducted one-pot three component reactions through Betti type reaction. Agar diffusion method was used to evaluate anti-bacterial properties. The DPPH method was used to determine antioxidant activity results. Results: A series of 1,1-(((5-(3,4,5triethoxybenzyl)-pyrimidine-2,4-diyl))bis(azanediyl))bis(substituted phenyl methylene))bis(naphthalen-2-ol) were synthesized via Betti type reaction and evaluated for their antibacterial and antioxidant activities. Further, all the synthesized compounds were characterized by FT-IR, 1H, and 13C NMR, and mass spectral analysis. Discussion: Molecular docking was carried out to study possible potential binding interaction of synthesized Betti base derivatives with 1NC6 PDB as receptor. The molecular dynamic (MD) was performed to investigate stability of binding interaction of drug-target (protein–ligand) complex. All the synthesized compounds were investigated for their antibacterial and antioxidant activity. Conclusions: Betti base derivatives were synthesized and studied on the basis of computer aided drug design including docking and molecular dynamic (MD) simulations and pharmacologically assessed for antioxidant and antibacterial activity. Molecular docking investigation revealed that compounds showed better binding energies in the range –4.1 to –7.3 kcal/mol suggests that the binding occurs efficiently in the receptor–ligand complex. These Betti base derivatives were synthesized via Betti base protocol at 70oC through one-pot three component reaction with acceptable yields, as cost efficient, high yield, easy workup and environmental friendliness. Afterwards, obtained molecules have characterized by FT-IR, NMR, and Mass spectra which confirms the chemical structure of the synthesized compounds. [ABSTRACT FROM AUTHOR]

There is no specific treatment for proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a disease that is very rare in the pediatric population. We report the case of a 15-year-old boy who presented with mildly reduced kidney function and nephrotic syndrome. Kidney biopsy revealed PGNMID with monoclonal deposits of IgG3 with kappa light chain restriction. Flow cytometry showed a significant CD38 plasma cell population in the peripheral blood in the absence of other signs of hematological malignancy. The patient was treated with a 6-month course of daratumumab, a monoclonal antibody targeting CD38. There was a significant reduction in proteinuria and normalization of kidney function. Based on positive experience with adults, daratumumab should also be studied in children with PGNMID. [ABSTRACT FROM AUTHOR]

High-performance thin-layer chromatography (HPTLC) is a cost-effective method for the separation of small molecules, such as active pharmaceutically ingredients. The method can be used without sophisticated equipment. For example, the detection and quantification of colored compounds on an HPTLC plate can be performed with a CCD camera. For noncolored compounds, a new dipping solution for the generation of chemiluminescence on an HPTLC plates is presented. In combination with a charge-coupled diode (CCD) camera, this can be used as a universal detection system. The efficiency of this new staining reagent is demonstrated by the detection of trimethoprim and sulfamethoxazole from a fixed-dose combination in a ratio of 1:5. [ABSTRACT FROM AUTHOR]

A comparative study on the mineralization of antibiotic trimethoprim (TMP) in neutral medium was investigated by applying irradiation with five types of ultraviolet lamps. Among these lamps, the whole envelope of one lamp contained ordinary quartz, which could only transmit ultraviolet-C (UVC) light. For the other four lamps, approximately one tenth, a quarter, a half, and full of envelopes were comprised of high-purity synthetic quartz, which can transmit both vacuum ultraviolet (VUV) and UVC light. TMP decay was well fitted to pseudo-first-order reaction kinetics and occurred more quickly as the VUV intensity increased. Poor mineralization was achieved in the absence of VUV light, whereas the mineralization efficiency was also enhanced with increasing VUV intensity. The presence of hydroxyl radicals (•OH), superoxide radicals (O2•−) and singlet oxygen (1O2) during VUV photolysis of water was confirmed by electron paramagnetic resonance (EPR) analysis. Appropriate radical quenching experiments and fluorescent molecular probe detection provided the evidence that •OH played a significant role in TMP mineralization. Higher VUV intensity favored the generation of H2O2 and •OH. The evolution of NH4+ and NO3− as well as carboxylic acids (formic, acetic, oxalic, and oxamic acids) released in the treated solution were quantified. Ten aromatic intermediates were also identified by UPLC-QTOF-MS. Thereby, a plausible reaction sequence for TMP mineralization in VUV/UVC photolysis was finally proposed. [ABSTRACT FROM AUTHOR]

The combination of trimethoprim and sulfamethoxazole as a fixed-dose combination in the ratio 1:5 is known as cotrimoxazole. It is used as antibiotic to treat a variety of bacterial infections. Cotrimoxazole is part of the World Health Organization's list of essential medicines. Cotrimoxazole is an example of a drug that was partially unavailable in Germany during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the Ukraine war. The dependency on foreign sources of medicines is well known in Europe and resulted in the Pharmaceutical Strategy for Europe 2020, a strategy concept "will support the competitiveness and innovative capacity of the EU's pharmaceutical industry". High-performance thin-layer chromatography (HPTLC) is a cost-effective method for quantifying pharmaceutically active compounds. Diode-array detection (DAD) in conjunction with HPTLC can simultaneously detect ultraviolet‒visible (UV‒VIS) and fluorescence spectra directly from the plate. Visualization as a contour plot helps to identify the optimal wavelengths for compound quantification and reduce uncertainty in the determination. The quantification of trimethoprim and sulfamethoxazole is presented in a case study that highlights the key aspects for HPTLC quantification of pharmaceutical fixed-dose combinations with minimal uncertainty. HPTLC‒DAD allows quantification of trimethoprim and sulfamethoxazole with a required relative standard deviation of less than 2.5%. [ABSTRACT FROM AUTHOR]

Temporal control of protein levels in cells and living animals can be used to improve our understanding of protein function. In addition, control of engineered proteins could be used in therapeutic applications. PRoteolysis-TArgeting Chimeras (PROTACs) have emerged as a small-molecule-driven strategy to achieve rapid, post-translational regulation of protein abundance via recruitment of an E3 ligase to the target protein of interest. Here, we develop several PROTAC molecules by covalently linking the antibiotic trimethoprim (TMP) to pomalidomide, a ligand for the E3 ligase, Cereblon. These molecules induce degradation of proteins of interest (POIs) genetically fused to a small protein domain, E. coli dihydrofolate reductase (eDHFR), the molecular target of TMP. We show that various eDHFR-tagged proteins can be robustly degraded to 95% of maximum expression with PROTAC molecule 7c. Moreover, TMP-based PROTACs minimally affect the expression of immunomodulatory imide drug (IMiD)-sensitive neosubstrates using proteomic and biochemical assays. Finally, we show multiplexed regulation with another known degron-PROTAC pair, as well as reversible protein regulation in a rodent model of metastatic cancer, demonstrating the formidable strength of this system. Altogether, TMP PROTACs are a robust approach for selective and reversible degradation of eDHFR-tagged proteins in vitro and in vivo. The ability to control proteins in cells and animals is important for experimental research and may have therapeutic applications. Here, the authors developed a new set of heterobifunctional small molecules based on the antibiotic trimethoprim that can degrade proteins that are genetically tagged with E. coli dihydrofolate reductase (eDHFR). [ABSTRACT FROM AUTHOR]

A screen-printed electrode (SPE) modified with the flower-like nanostructures of zinc oxide doped with terbium for forming FL-NS Tb3+/ZnO/SPE-modified electrode (electrochemical sensor) was provided for effective and rapid detection of sulfamethoxazole (SMX) and trimethoprim (TMP). Therefore, structure, composition, as well as the impact of process variables of the modified electrode, electrochemical response features of SMX and TMP, sensitivity of both simultaneous detections, and scan rate were examined in this research. According to the examinations, synergy of Tb and ZnO resulted in the promotion of the electrochemical reaction of SMX and TMP. Moreover, the difference in their oxidation peak potential was < 220 mV. In addition, the modified electrode linearly ranged from 0.001 to 900.0 μM, with the detection limit of 0.14 nM and 0.23 nM (S/N = 5) for SMX and TMP, respectively. Finally, it was found that this new FL-NS Tb3+/ZnO/SPE-modified electrode enjoys a broader smaller detection limits, linear range, and very good stability and reproducibility. [ABSTRACT FROM AUTHOR]

The effectiveness and safety of trimethoprim/sulfamethoxazole (TMP/SMX) desensitization therapy is insufficiently evaluated in hematological diseases. From 2002 to 2019, we retrospectively analyzed 112 patients with hematological diseases who underwent desensitization therapy after TMP/SMX prophylaxis withdrawal due to adverse events. They orally started TMP/SMX at 0.4 mg/2 mg, which was then increased daily to 80 mg/400 mg for 5 or 9 days. Eighty-eight patients (79%) had complete desensitization, and the major reason for failure was rash seen in 21 cases (19%). The cause of desensitization and reasons for failure matched in 22 cases (92%). Pneumocystis pneumonia was not observed throughout the study. In the failure group, the number of eosinophils and alanine aminotransferase (ALT) levels were significantly increased after desensitization. In particular in the failure group, the slight increase in eosinophils was seen through the beginning to halfway during desensitization (36/μL (0–900/μL) and 48/μL (0–2560/μL), respectively, p = 0.025). These data show that TMP/SMX desensitization therapy is effective and safe in hematological diseases. The recurrence of adverse events could help predict desensitization success. [ABSTRACT FROM AUTHOR]

This letter to the editor responds to a study comparing different antibiotic prophylaxis regimens for transrectal prostate biopsy. The study found that a combination of two antibiotics, FMT and TMP/SMX, provided protection against post-intervention infections comparable to that of Ciprofloxacin. However, the letter raises concerns about the potential adverse effects of antibiotics, particularly renal toxicity, and suggests incorporating renal toxicity assessment into future studies. The letter also mentions that the risk of infection can be reduced by using transperineal prostate puncture biopsy instead of transrectal biopsy. The authors express gratitude for the study and declare no competing interests. [Extracted from the article]

Covalent organic framework (COF) materials are one of porous sorbents with the capability to improve bioavailability and solubility of drugs, while also controlling the drug release for profound long-term implications in drug delivery systems. Here, using a facile self-assembly method, COF with high ability to modify the customary formulation of antibiotic drugs including trimethoprim (TMP) is synthesized. The resulting nanoporous COF characterized by different techniques such as field-emission scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, BET/BJH, and zeta potential, can be prescribed as an antibiotic against most of bacteria. Antibacterial properties of the TMP encapsulated by COF (TMP@COF) is investigated, leading to significantly lower minimum inhibitory concentrations (1.25 and 2.5 μg/mL) compared to pure TMP (10 μg/mL), which can propose it as a highly efficient nanocarrier against both gram-negative and gram-positive bacteria. The release kinetics of TMP@COF is also studied using zero-order, first-order, Higuchi, and Korsmeyer-Peppas models. Our results indicate that the diffusion kinetics of the COF nanodrug carrier is consistent with the Higuchi model, thus evidencing the possibility of stable TMP diffusion from the porous material. [ABSTRACT FROM AUTHOR]

Introduction: Primary care provides an opportunity to prevent community acquired, medicine or drug-induced acute kidney injury. One of the barriers to proactive prevention of medicine-induced kidney injury in primary care is the lack of a list of nephrotoxic medicines that are most problematic in primary care, particularly one that provides a comparison of risks across medicines.Objective: The aim of this study was to consolidate evidence on the risks associated with medicines and acute kidney injury, with a focus on medicines used in primary care.Method: We searched the MEDLINE and EMBASE databases to identify published studies of all medicines associated with acute kidney injury identified from spontaneous report data. For each medicine positively associated with acute kidney injury, as identified from spontaneous reports, we implemented a sequence symmetry analysis (SSA) and a case-control design to determine the association between the medicine and hospital admission with a primary diagnosis of acute kidney injury (representing community-acquired acute kidney injury). Administrative claims data held by the Australian Government Department of Veterans' Affairs for the study period 2005-2019 were used.Results: We identified 89 medicines suspected of causing acute kidney injury based on spontaneous report data and a reporting odds ratio above 2, from Japan, France and the US. Spironolactone had risk estimates of 3 or more based on spontaneous reports, SSA and case-control methods, while furosemide and trimethoprim with sulfamethoxazole had risk estimates of 1.5 or more. Positive association with SSA and spontaneous reports, but not case control, showed zoledronic acid had risk estimates above 2, while candesartan telmisartan, simvastatin, naproxen and ibuprofen all had risk estimates in SSA between 1.5 and 2. Positive associations with case-control and spontaneous reports, but not SSA, were found for amphotericin B, omeprazole, metformin, amlodipine, ramipril, olmesartan, ciprofloxacin, valaciclovir, mycophenolate and diclofenac. All with the exception of metformin and omeprazole had risk estimates above 2.Conclusion: This research highlights a number of medicines that may contribute to acute injury; however, we had an insufficient sample to confirm associations of some medicines. Spironolactone, furosemide, and trimethoprim with sulfamethoxazole are medicines that, in particular, need to be used carefully and monitored closely in patients in the community at risk of acute kidney injury. [ABSTRACT FROM AUTHOR]

Iron ore and manganese ore were used as substrate of constructed wetlands (CWs) to enhance nitrogen (N) removal. However, the N purification performance in CWs filled with iron or manganese ore under antibiotics stress needs further study. In this study, three groups of CWs filled with river sand, limonite (a kind of iron ore), and manganese ore sand were constructed, which were named as C-CWs, Fe-CWs, and Mn-CWs, respectively. The effect and mechanism of the composite antibiotics sulfamethoxazole (SMX) and trimethoprim (TMP) on N removal in CWs were investigated. While the addition of SMX and TMP inhibited about 40% nitrification and promoted about 25% denitrification in all CWs, Fe-CWs and Mn-CWs always had better N removal performance than C-CWs. Changes in microbial community structure in CWs indicated that the better N removal performance in Fe-CWs and Mn-CWs was attributed to the presence of more abundant and diverse N-associated bacteria, especially Fe- and Mn-driven autotrophic denitrifying bacteria. What's more, the addition of iron ore or manganese ore contributed to the better N removal performance with highest relative abundance of N-transferring bacteria under antibiotics stress. [ABSTRACT FROM AUTHOR]

Two plasmid-encoded dihydrofolate reductase (DHFR) isoforms, DfrA1 and DfrA5, that give rise to high levels of resistance in Gram-negative bacteria were structurally and biochemically characterized to reveal the mechanism of TMP resistance and to support phylogenic groupings for drug development against antibiotic resistant pathogens. Preliminary screening of novel antifolates revealed related chemotypes that showed high levels of inhibitory potency against Escherichia coli chromosomal DHFR (EcDHFR), DfrA1, and DfrA5. Kinetics and biophysical analysis, coupled with crystal structures of trimethoprim bound to EcDHFR, DfrA1 and DfrA5, and two propargyl-linked antifolates (PLA) complexed with EcDHFR, DfrA1 and DfrA5, were determined to define structural features of the substrate binding pocket and guide synthesis of pan-DHFR inhibitors. Critical residue variations in two of the most clinically prevalent DHFR isoforms are identified as a common structural element in trimethoprim-resistant DHFR which impose changes on enzyme catalysis and ligand-cofactor cooperativity. [ABSTRACT FROM AUTHOR]

Background: Human and veterinary antibiotics are typically discharged as parent chemicals in urine or feces and are known to be released into the environment via wastewater treatment plants (WWTPs). Several research investigations have recently been conducted on the removal and bioremediation of pharmaceutical and personal care products (PPCPs) disposed of in wastewater. Results: SiNP-Cu, a chelating matrix, was produced by delaying and slowing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel from functionalized with 3-aminopropyltrimethoxysilane. The prepared sorbent material was characterized using several techniques including BET surface area, FT-IR spectroscopy, Scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nitrogen adsorption–desorption isotherm. The pseudo-second-order model provided the best correlation due to the big match between the experimental and theoretical of different adsorption coefficients. The Langmuir and Freundlich adsorption models were used and the study showed a better match with the Freundlich model with a capacity of removal reached up to 420 mg g−1. The removal capacity was dependent on pH and increased by increasing pH. The removal percentage reached 91;5% at pH = 8. The adsorbent demonstrated a high percentage removal of TMP, reaching more than 94% when increased pH. The sample was simply regenerated by soaking it for a few minutes in 1 N HCl and drying it. The sorbent was repeated five times with no discernible decrease in removal capacity. The thermodynamic study also showed endothermic, increasing randomness and not spontaneous. The free energy was 2.71 kJ/mol at 320 K. The findings of the DFT B3LYP/6–31 + g (d, p) local reactivity descriptors revealed that nitrogen atoms and π-electrons of the benzene and pyrimidine rings in the TMP are responsible for the adsorption process with the SiNP surface. The negative values of the adsorption energies obtained by molecular dynamic simulation indicated the spontaneity of the adsorption process. Conclusion: The global reactivity indices prove that TMP is stable and it can be removed from wastewater using SiNP surface. The results of the local reactivity indices concluded that the active centers for the adsorption process are the nitrogen atoms and the π-electrons of the pyrimidine and benzene rings. Furthermore, the positive value of the maximum charge transfer number (ΔN) proves that TMP has a great tendency to donate electrons to SiNP surface during the process of adsorption. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The objective was to find an alternative treatment to a low-dose antibiotic for the prevention of recurrent urinary tract infections (UTI) and to evaluate the difference in rates of reinfection within 1 year when treated with methenamine hippurate for prophylaxis compared with trimethoprim. Methods: We present a non-blinded randomized trial comparing methenamine hippurate with trimethoprim for the prevention of recurrent UTI at 12 months after starting treatment. Women over 18 who had at least two culture-positive UTI in the prior 6 months or three in the prior year were included. Ninety-two patients met enrollment criteria and were randomized to receive daily prophylaxis with methenamine hippurate or trimethoprim for a minimum of 6 months. Both intent-to-treat and per-protocol analyses if patients received the alternative drug after randomization were analyzed using Student's t test, Mann–Whitney U test, Kaplan–Meier curves, log-rank test, and a logistic and multivariate regression model. The primary outcome of this study was culture-proven UTI recurrence by 12 months after initiating prophylaxis. Results: In the intent-to-treat analysis, we found no difference between groups in recurrent UTI, with a 65% (28 out of 43) recurrence in the trimethoprim group versus 65% (28 out of 43) in the methenamine hippurate group (p = 1.00). In the per-protocol analysis, 65% (26 out of 40) versus 65% (30 out of 46) of patients had UTI recurrences in the trimethoprim group versus the methenamine hippurate group (p = 0.98). Conclusions: Methenamine hippurate may be an alternative for the prevention of recurrent UTI, with similar rates of recurrence and adverse effects to trimethoprim. [ABSTRACT FROM AUTHOR]

The key aim of this paper is to suggest a more quantitative approach to designing a dose–response experiment, and more specifically, a concentration–response experiment. The work proposes a departure from the traditional experimental design to determine a dose–response relationship in a developmental toxicology study. It is proposed that a model-based approach to determine a dose–response relationship can provide the most accurate statistical inference for the underlying parameters of interest, which may be estimating one or more model parameters or pre-specified functions of the model parameters, such as lethal dose, at maximal efficiency. When the design criterion or criteria can be determined at the onset, there are demonstrated efficiency gains using a more carefully selected model-based optimal design as opposed to an ad-hoc empirical design. As an illustration, a model-based approach was theoretically used to construct efficient designs for inference in a developmental toxicity study of sea urchin embryos exposed to trimethoprim. This study compares and contrasts the results obtained using model-based optimal designs versus an ad-hoc empirical design. [ABSTRACT FROM AUTHOR]

Introduction: Pneumocystis pneumonia is a common opportunistic infection in patients with HIV/AIDS, and is a leading cause of death in this population. Early selection of effective treatment is therefore critical to reduce mortality. We conducted a clinical trial to compare the effectiveness and safety of three different antifungal treatment regimens in HIV-infected patients with moderate to severe PCP. Methods: Our study was a multicenter, observational prospective clinical trial. We recruited 320 HIV-infected patients with moderate to severe PCP, and stratified these subjects into a trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy group, a TMP-SMX plus clindamycin group, and a TMP-SMX plus caspofungin group. Patients were invited to participate in 12 weeks of follow-up. Outcomes included the difference in overall mortality and the proportion of overall positive response to treatment in the three groups at weeks 4 and 12, the difference in treatment duration, and the proportion of adverse events among the three groups during the study period. Results: The probability of survival not statistically different among three treatment groups. Mortality in the TMP-SMX monotherapy group (group 1) was 15/115 (13.04%) vs. 20/83 (24.10%) in the TMP-SMX plus clindamycin group (group 2) vs. 24/107 (22.43%) in the TMP-SMX plus caspofungin group (group 3) at week 12 (p = 0.092). The overall positive response rate to treatment in the three groups was 24.14%, 34.94%, and 38.32%, respectively, at week 4, and 33.91%, 38.55%, and 44.86%, respectively, at week 12. No significant difference in the overall positive response rate to treatment at either week 4 or week 12 was noted (p = 0.061, p = 0.246). Rates of changes to therapy were 6.50% (8/123) in group 1, 3.40% (3/87) in group 2, and 2.70% (3/110) in group 3, and did not differ significantly among the three groups (p = 0.376). There were also no significant differences in adverse events among the three treatment groups of patients with moderate to severe PCP. Conclusions: Our results indicate that there are no significant statistical differences among the three studied treatment regimens in terms of antifungal effectiveness in HIV-infected patients with moderate to severe PCP. TMP-SMX monotherapy is a convenient, cheap, and effective therapeutic drug regimen to treat HIV-infected patients with moderate to severe PCP, and is an appropriate treatment strategy in resource-limited settings. Clinical Trial Registration: www.ClinicalTrials.gov, ID: ChiCTR1900021195. Registered on February 1, 2019. [ABSTRACT FROM AUTHOR]

Trimethoprim and sulfamethoxazole are prescribed for a broad spectrum of bacteria. However, the use of these medicines is restricted due to the risk of microbial resistance in the body. Nanotechnology is a strategy for overcoming this problem by helping develop novel drug delivery systems. This study aims to assess the ability of Fe3O4/Ag and Fe3O4@SiO2/Ag nanoparticles to improve efficiency of the traditional formulation of trimethoprim and sulfamethoxazole. Fe3O4/Ag and Fe3O4@SiO2/Ag were found to have sphere-like morphologies with average sizes of 33.2 and 35.1 nm, respectively. The values of the zeta potential for the pure sulfamethoxazole and trimethoprim were -30.6 and -10.0 mV, respectively, which increased to zero or even larger positive values after being conjugated with the NPs. The study of the release kinetics showed that 64.7% of the medicines were released from the carriers within 40 days. The values of MIC for sulfamethoxazole, trimethoprim, Fe3O4/Ag/sulfamethoxazole, Fe3O4/Ag/trimethoprim, Fe3O4@SiO2/Ag/sulfamethoxazole, and Fe3O4@SiO2/Ag/trimethoprim against Escherichia coli were calculated to be 12, 9, 4, 4, 4, and 4 μg/mL, respectively. Besides, the relevant values against Staphylococcus aureus were measured to be 12, 9, 4, 4, 3, and 2 μg/mL, respectively. The use of synthesized nanomaterials for the delivery of these antibiotics leads to smaller doses compared to their traditional forms. [ABSTRACT FROM AUTHOR]

In this study, we investigated the removal efficiency of a broad-spectrum antimicrobial agent trimethoprim (TMP) in a UV-activated persulfate system (UV/PS). The pseudo-first-order reaction kinetic model based on the steady-state hypothesis was used to explain TMP degradation behavior in UV-activated persulfate system. Due to the low quantum yield and molar absorptivity of TMP at 254 nm, the direct photolysis of TMP was slower. Since the free radicals generated by adding H2O2 or PS to the system can react with TMP, the degradation rate was significantly accelerated, and S O 4 • − played a dominant role in the UV/PS system. k H O • , TMP and k SO 4 • − , TMP were determined by the pseudo-first-order reaction kinetic model to be 6.02×109 and 3.88×109 M−1s−1, respectively. The values were consistent with competitive kinetic measurements. The pseudo-first-order reaction kinetics model can predict and explain the effect of PS concentration, natural organic matter, and chloride ion on the TMP degradation in the UV/PS system. The observed pseudo first-order rate constants for TMP degradation (kobs) increased with the persulfate concentration, but it significantly decreased in the presence of NOM and chloride. S O 4 2 − has no effect on the degradation of TMP, while HC O 3 − promotes the degradation and N O 3 − inhibits the degradation. The common transition metal ion (such as Cu2+, Zn2+, and Co2+) in industrial wastewater has a synergistic effect on the TMP degradation in the UV/PS system, but excessive metal ions will lead to a decrease of the degradation rate. [ABSTRACT FROM AUTHOR]

This work is a study on the occurrence of emerging pollutants in the northeast Ecuadorian Amazon. Emerging contaminants (ECs)—caffeine, triclosan, estradiol, acetaminophen, nicotine, and ibuprofen—were quantified by gas chromatography–mass spectrometry in rivers and streams of the Amazon basin near the city of Tena, Ecuador. For that, a total of 16 natural water samples were taken in 8 locations. Sampling sites included areas impacted by discharges from inefficient sewage networks in urban areas, wastes from fish farming and non-functional landfill, a stream with few threats, tap water, and treated sewage. Caffeine was found in the 38% of the samples studied while trimethoprim and acetaminophen had an occurrence of 13%. Caffeine was detected at two sites receiving untreated sewage and one site receiving treated sewage with mean concentrations that ranged between 19 and 31.5 μg L−1. Acetaminophen (50.4 μg L−1) and trimethoprim (2 μg L−1) were only detected in the river receiving treated sewage effluent. This is the first assessment of emerging contaminants in the upper Ecuadorian Amazon basin, and our observations highlight the need for better sewage treatment and water quality monitoring in Amazonian cities. [ABSTRACT FROM AUTHOR]

The antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in the gene encoding the TMP target, bacterial dihydrofolate reductase (DHFR), in particular mutation L28R. Here, we show that 4'-desmethyltrimethoprim (4'-DTMP) inhibits both DHFR and its L28R variant, and selects against the emergence of TMP-resistant bacteria that carry the L28R mutation in laboratory experiments. Furthermore, antibiotic-sensitive E. coli populations acquire antibiotic resistance at a substantially slower rate when grown in the presence of 4'-DTMP than in the presence of TMP. We find that 4'-DTMP impedes evolution of resistance by selecting against resistant genotypes with the L28R mutation and diverting genetic trajectories to other resistance-conferring DHFR mutations with catalytic deficiencies. Our results demonstrate how a detailed characterization of resistance-conferring mutations in a target enzyme can help identify potential drugs against antibiotic-resistant bacteria, which may ultimately increase long-term efficacy of antimicrobial therapies by modulating evolutionary trajectories that lead to resistance. The efficacy of the antibiotic trimethoprim, which inhibits bacterial dihydrofolate reductase (DHFR), is limited by the rapid emergence of resistant bacteria. Here, Manna et al. show that 4'-desmethyltrimethoprim inhibits DHFR and a common TMP-resistant variant, and impedes evolution of antibiotic resistance by selecting against the emergence of this variant. [ABSTRACT FROM AUTHOR]

This study addresses the growing concern about the high levels of antibiotics in water, outlining an alternative for their removal. The adsorption of four representative antibiotics from commonly used families (fluoroquinolones, β-lactams, trimethoprim, and sulfonamides) was performed over vegetal powdered activated carbon. The evolution of the adsorption was studied during 60 min for different initial antibiotic concentrations, not only individually but also simultaneously to determine competitive adsorption. Moreover, this research studied the adsorption isotherms and kinetics of the process, as well as the pH influence; FTIR of the activated carbon before and after adsorption was carried out. Trimethoprim and sulfadiazine showed more affinity for the adsorbent than amoxicillin and enrofloxacin. This trend might be attributed to their structure, capable of stablishing stronger π-π interactions with the adsorbent, which showed high affinity for the active sites of the adsorbent via FTIR. In addition, the sorption isotherms of trimethoprim followed a Langmuir type isotherm, amoxicillin followed a Freundlich type isotherm, and enrofloxacin and sulfadiazine followed both. The antibiotics followed pseudo-second-order kinetics. Sulfadiazine and amoxicillin gave better performances in acidic conditions. By contrast, the sorption of trimethoprim was favored in basic environments. Variations of pH had a negligible effect on the removal of enrofloxacin. [ABSTRACT FROM AUTHOR]

Quantification of antibiotic utilization is an essential component of antibiotic stewardship programs. In this multicentric study, we used different metrics to evaluate inpatient antibiotic use in children. The study objectives were to describe point prevalence of antibiotic use by indication and patient characteristics, to evaluate DOTs, LOTs and PDDs, and to compare PDDs to DDDs, which assume average maintenance dose per day in adults. All children hospitalized on the days of the study were included. Trained personnel collected demographic and clinical data from patients' clinical records. We recorded information about antibiotics administered on the date of data collection, and in the previous 30 days of hospitalization. Of 810 patients, 380 (46.9%; CI 95%: 43.4–50.4) received one or more antibiotics; prevalence of use was 27.0% for prophylaxis (219/810), and 20.7% (168/810) for treatment. Overall, 587 drugs were issued to the 380 patients receiving antibiotics (1.5 antibiotic per patient). When considering treatments, DOT and LOT per 100 patient-days were 30.5 and 19.1, respectively, resulting in a DOT/LOT ratio of 1.6. PDDs increased with age and approached DDDs only in children aged ≥ 10 years; the ratio between PDDs estimated in children aged ≥ 10 years and in 0–11 month-old infants ranged from 2 for sulfamethoxazole and trimethoprim, to 25 for meropenem. Our results confirm that DOT, LOT and PDD are better alternatives to DDD in children. [ABSTRACT FROM AUTHOR]

Gene therapies that chronically suppress vascular endothelial growth factor (VEGF) represent a new approach for managing retinal vascular leakage and neovascularization. However, constitutive suppression of VEGF in the eye may have deleterious side effects. Here, we developed a novel strategy to introduce Flt23k, a decoy receptor that binds intracellular VEGF, fused to the destabilizing domain (DD) of Escherichia coli dihydrofolate reductase (DHFR) into the retina. The expressed DHFR(DD)-Flt23k fusion protein is degraded unless "switched on" by administering a stabilizer; in this case, the antibiotic trimethoprim (TMP). Cells transfected with the DHFR(DD)-Flt23k construct expressed the fusion protein at levels correlated with the TMP dose. Stabilization of the DHFR(DD)-Flt23k fusion protein by TMP was able to inhibit intracellular VEGF in hypoxic cells. Intravitreal injection of self-complementary adeno-associated viral vector (scAAV)-DHFR(DD)-Flt23k and subsequent administration of TMP resulted in tunable suppression of ischemia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy (OIR). Hence, our study suggests a promising novel approach for the treatment of retinal neovascularization. Schematic diagram of the tunable system utilizing the DHFR(DD)-Flt23k approach to reduce VEGF secretion. a The schematic shows normal VEGF secretion. b Without the ligand TMP, the DHFR(DD)-Flt23k protein is destabilized and degraded by the proteasome. c In the presence of the ligand TMP, DHFR(DD)-Flt23k is stabilized and sequestered in the ER, thereby conditionally inhibiting VEGF. Green lines indicate the intracellular and extracellular distributions of VEGF. Blue lines indicate proteasomal degradation of the DHFR(DD)-Flt23k protein. Orange lines indicate the uptake of cell-permeable TMP. TMP, trimethoprim; VEGF, vascular endothelial growth factor; ER, endoplasmic reticulum. [ABSTRACT FROM AUTHOR]

Background Co-trimoxazole is an antibiotic combination used for the treatment of Pneumocystis jirovecii pneumonia, amongst others. Co-trimoxazole is known to increase serum potassium. For this reason, Dutch guidelines advise serum potassium monitoring in high-risk patients. Objective This study aimed to determine average serum potassium rise after administration of intravenous co-trimoxazole in hospitalized patients, compared to intravenous ceftriaxone. This study also aimed to determine adherence to Dutch guidelines by measuring the incidence of serum potassium monitoring in these patients. Setting Data was collected retrospectively from patients in five departments of the Canisius Wilhelmina Hospital, a teaching hospital in Nijmegen, the Netherlands. Method Data was collected and compared from patients that received intravenous co-trimoxazole (n = 66) and intravenous ceftriaxone (n = 132) in the period of November 2008–November 2017. For each patient using co-trimoxazole, two patients using ceftriaxone were included in a paired fashion. Baseline and follow-up potassium were collected, if available. Additionally, it was tested if serum potassium was measured around the initiation of antibiotic therapy. Main outcome measure Changes in serum potassium where obtainable in 30 patients using cotrimoxazole and 40 patients using ceftriaxone. When compared to ceftriaxone, administration of intravenous co-trimoxazole was associated with a significant mean increase in serum potassium (+0.55 mmol/l, 95% CI 0.29–0.80, p < 0.001). After correction for confounders (baseline potassium, estimated glomerular filtration rate 30 ≤ 60, the presence of haematological malignancies and the usage of corticosteroids), this effect shrunk noticeably, but remained significant (+0.28 mmol/l, 95% CI 0.03–0.53, p = 0.031). Results The incidence of hyperkalemia at follow-up was 20% in the cotrimoxazole group, compared to 5% in the ceftriaxone group. Despite this, serum potassium was often not measured in patients using intravenous cotrimoxazole, being 76% at baseline and 55% in the period of 48–120 h after antibiotic therapy initiation, compared to 87% and 34% in the ceftriaxone group respectively. Conclusion Adherence to Dutch guidelines was poor as serum potassium monitoring was often not performed. As intravenous co-trimoxazole usage is associated with a significant increase in mean serum potassium, monitoring is strongly recommended. [ABSTRACT FROM AUTHOR]

An automated sequential injection analysis with spectrometric detection for the determination of trimethoprim and sulfamethoxazole in tablets is proposed. The concentration of sulfamethoxazole is determined by monitoring the absorbance at 540 nm due to the intensively colored complex formed by derivatization reaction of sulfamethoxazole with nitrite and N-(1-naphthyl)ethylenediamine in acidic media. With knowledge of the sulfamethoxazole concentration, the trimethoprim concentration can be calculated from the absorption of the sample solution at 264 nm, where both analytes absorb, and the additivity of individual absorbances according to Beer-Lambert law can be used. The developed method has a linear dynamic range of 0.03–5.0 mg dm−3 and a detection limit of 0.03 mg dm−3 for trimethoprim and a linear dynamic range of 0.1–10.0 mg dm−3 and a detection limit of 0.01 mg dm−3 for sulfamethoxazole. The sampling frequency of the method is 24 h−1. The method was successfully applied on pharmaceutical dosage form of tablets, as the results of the determination are in a good agreement with the official pharmacopoeial method (HPLC). The developed sequential injection analysis is simpler, cheaper, and faster than already published methods and pharmacopoeial assay. So it appears to be suitable for quality control in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Modification of endogenous proteins by drugs and drug metabolites are thought to be a cause of idiosyncratic adverse drug reactions (IADRs). Trimethoprim (TMP) is a commonly prescribed antibiotic that has been implicated in IADRs; however, there is no known mechanism by which this drug or its metabolites modify proteins. This study describes the results of screening trimethoprim and its primary metabolites for the ability to covalently modify human serum albumin (HSA). The first step of the screen was in vitro reactions of the compounds with HSA followed by western blotting with antisera specific to drug-modified proteins. Compounds with positive signal in the western blot were then screened using an untargeted peptide profiling method to discover modified peptides. This strategy identified two sites in HSA that are modified by incubation with a TMP metabolite, α-hydroxy trimethoprim (Cα-OH-TMP). [ABSTRACT FROM AUTHOR]

Results of differential scanning calorimetry studies of phase equilibria in binary systems of a series of sulfanilamides, levofloxacin, and levomycetin in combination with trimethoprim are presented. The studied systems were found to be simple eutectics. The congruent equilibrium compositions and melting points of nine pairs of systems and results of preclinical investigations are reported. The rate of development of microbial resistance to a composition modeling a commercial combination was four times greater than the eutectic composition. The antimicrobial activity of the eutectic mixtures was from 2 to 2000 times greater than those of the individual components. The observed properties could be useful for clinical application of eutectic dispersions as antimicrobial drug delivery systems for more effective achievement of the therapeutic goals. [ABSTRACT FROM AUTHOR]

In recent years, high frequencies of trimethoprim resistance in urinary tract infections (UTIs) caused by E. coli are have been reported. Co-resistance to other antimicrobial drugs may play a role in this increase. Therefore, we investigated whether previous use of other antimicrobial drugs was associated with trimethoprim resistance. We conducted a nested case-control study with urinary cultures with E. coli from participants of the Rotterdam Study sent in by general practitioners to the regional laboratory between 1 January 2000 and 1 April 2016. Multivariable logistic regression analysis was performed to study the association between prior prescriptions of several antimicrobial drug groups and trimethoprim resistance using individual participant data. Urinary cultures of 1264 individuals with a UTI caused by E. coli were included. When adjusted for previous other antimicrobial drug use, a history of > 3 prescriptions of extended-spectrum penicillins (OR 1.68; 95% CI 1.10–2.55) was significantly associated with trimethoprim resistance of E. coli as was the use of > 3 prescriptions of sulfonamides and trimethoprim (OR 2.22; 95% CI 1.51–3.26). The use of > 3 prescriptions of nitrofuran derivatives was associated with a lower frequency of trimethoprim resistance (OR 0.60; 95% CI 0.39–0.92), after adjustment for other antimicrobial drug prescriptions. We found that previous use of extended-spectrum penicillins is associated with trimethoprim resistance. On the contrary, previous nitrofurantoin use was associated with a lower frequency of trimethoprim resistance. Especially in individuals with recurrent UTI, co-resistance should be taken into account and susceptibility testing before starting trimethoprim should be considered. [ABSTRACT FROM AUTHOR]

The occurrence and fate of antibiotic compounds in water can adversely affect human and animal health; hence, the removal of such substrates from soil and water is indispensable. Herein, we described the synthesis method of mesoporous carbon (MPC) via the pyrolysis route from a coordination polymer Fe-based MIL-53 (or MIL-53, shortly). The MPC structure was analyzed by several physical techniques such as SEM, TEM, BET, FT–IR, VSM, and XRD. The response surface methodology (RSM) was applied to find out the effects of initial concentration, MPC dosage, and pH on the removal efficiency of trimethoprim (TMP) and sulfamethoxazole (SMX) antibiotics in water. Under the optimized conditions, the removal efficiencies of TMP and SMX were found to be 87% and 99%, respectively. Moreover, the adsorption kinetic and isotherm studies showed that chemisorption and the monolayer adsorption controlled the adsorption process. The leaching test and recyclability studies indicated that the MPC structure was stable and can be reused for at least four times without any considerable change in the removal efficiency. Plausible adsorption mechanisms were also addressed in this study. Because of high maximum adsorption capacity (85.5 mg/g and 131.6 mg/g for TMP and SMX, respectively) and efficient reusability, MPC is recommended to be a potential adsorbent for TMP and SMX from water media. [ABSTRACT FROM AUTHOR]

The in vitro and in vivo antimicrobial activities of dihydrofolate reductase (DHFR) inhibitors are inhibited in the presence of free thymidine in the growth milieu and in rodent efficacy models. However, for thymidine kinase (TK) deficient mutant bacteria, the presence of free thymidine does not impact the activity of DHFR inhibitors, and these mutants were used to assess the in vivo efficacy of the DHFR inhibitor, iclaprim. The efficacies of iclaprim, trimethoprim, and vancomycin were evaluated in a systemic mouse infection model. Female CD-1 mice were infected intraperitoneally (IP) with wild-type Staphylococcus aureus ATCC 25923 (MSSA) or AW 6 (MRSA) or their corresponding isogenic TK-deficient mutant S. aureus strains AH 1246 and AH 1252. Iclaprim showed potent antibacterial activity against both the TK-deficient mutant S. aureus strains, with PD50 values of 1.8 and < 0.5 mg/kg, respectively, for strains AH 1246 and AH 1252. In contrast, poor antibacterial activity was observed against corresponding wild-type (TK competent) S. aureus strains, with PD50 values of 10.8 and 2.2 mg/kg, respectively, for strains ATCC 25923 and AW 6. This study confirms that thymidine plays an important antagonistic role when determining the efficacy of DHFR inhibitors in vivo. This is the first study to show that iclaprim is active against TK-deficient S. aureus strains in a systemic mouse infection model, and that TK-deficient mutants may be used to evaluate iclaprim's activity in rodent models in vivo. [ABSTRACT FROM AUTHOR]

A simple, inexpensive, versatile, and environment-friendly extraction method, using low-temperature partitioning extraction (LTPE), was validated to quantify pharmaceutical-active compounds (PhACs) in surface water samples by high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The PhACs analyzed were acetaminophen, bezafibrate, diclofenac, diltiazem, fluconazole, linezolid, miconazole, ondansetron hydrochloride, and trimethoprim. The detection and quantification limits ranged from 0.15 to 12.30 ng L−1 and 0.43 to 40.60 ng L−1, respectively. Recovery rates ranged from 46 to 135%, and relative standard deviation (RSD%) varied between 0.49 and 6.13%. This method was applied to monitor water contamination by PhACs in the Paraopeba River Basin (PRB), Minas Gerais state, Brazil. All PhACs, except linezolid which was not detected, were found in PRB water samples in concentrations that ranged from 2.6 ng L−1 to 2.62 μg L−1. [ABSTRACT FROM AUTHOR]

Sulphamethoxazole/trimethoprim (SMX/T) is an antimicrobial agent that has been used for decades against both Gram-positive and Gram-negative bacteria as well as protozoa. It is particularly used as prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with acquired immune-deficiency syndrome (AIDS). Its use in dogs with associated adverse reactions has necessitated an experimental study that may enhance clinical management of the toxicities. The study aimed to determine the effects of prolonged treatment with high doses of sulphamethoxazole/trimethoprim on the haematological profile of dogs. Dogs were given SMX/T at 30, 60 and 120 mg/kg body weight at 12-h intervals for 21 days. The packed cell volume (PCV), haemoglobin concentration (HbC), red blood cell (RBC) count and total and differential white blood cell (WBC) counts were performed using standard techniques. Data generated was analysed by one-way analysis of variance (ANOVA). Alopecia, epistaxis and skin eruptions were seen at the dose of 120 mg/kg. There were also dose-dependent decreases in the PCV and RBC count. HbC was significantly (p < 0.05) lower than the control only at the dose of 120 mg/kg. Total WBC count was significantly (p < 0.05) lower than the control only on day 7 of treatment at 30, 60 and 120 mg/kg. Beyond day 7, the white cell response, total and differential WBC counts, were fluctuating with significant depression at the dose of 120 mg/kg. Increase in dose and prolonged use of SMX/T in the dogs decreased the haematological parameters and increased the occurrence of toxic reactions and may outweigh the benefits of treatment with the drug in recommended cases. [ABSTRACT FROM AUTHOR]

Background and aims: To examine antimicrobial resistance of commonly isolated pathogens in elderly hospitalized patients.Methods: Data regarding all clinically significant isolates from blood and urine cultures of patients admitted to a multilevel geriatric hospital during March 2015 to April 2016 were collected. Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standard Institute guidelines.Results: Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae were the most common isolates, with proportions of extended spectrum beta-lactamase positivity of 60, 40, and 61% respectively. Adjusted logistic regression models indicated that resistance of Escherichia coli to ceftriaxone [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.5-5.1], ceftazidime (OR 2.8, 95% CI 1.5-5.1), ciprofloxacin (OR 2.2, 95% CI 1.2-4.0), amoxicillin/clavulanic acid (OR 2.3, 95% CI 1.2-4.3), and trimethoprim/sulfamethoxazole (OR 2.4, 95% CI 1.4-4.3) was significantly higher in skilled nursing wards than in acute geriatric wards. Resistance of Proteus mirabilis to ceftriaxone (OR 3.1, 95% CI 1.5-6.4) and Klebsiella pneumoniae to ciprofloxacin (OR 3.2, 95% CI 1.3-7.9) was significantly higher in skilled nursing wards than in acute wards.Conclusions and discussion: Antimicrobial resistance was found to be high in a multilevel geriatric hospital, especially in skilled nursing wards. These findings call for rethinking of the empirical antimicrobial therapy and of the efforts for prevention of nosocomial infection. [ABSTRACT FROM AUTHOR]

Purpose: Escherichia coli urine isolates from patients presenting to the emergency department at a German tertiary care hospital were retrospectively analyzed from January 2015-March 2017 to determine antibiotic resistance patterns and patient risk factors for resistance.Methods: Uncomplicated urinary tract infection (UTI) was defined as UTI in the otherwise healthy patient without relevant co-morbidities and complications. Patients were assumed to have UTI if diagnosis was made by the attending physician with conclusive dipstick results. For subgroup analysis, only patients with symptoms suggestive for UTI documented in their records were included.Results: 228 patients with a UTI diagnosed by the attending physician with E. coli isolated in urine culture were included. 154/228 patients had documented symptomatic UTI, 57/154 had uncomplicated infection, 76/154 patients had cystitis, and 124/154 were female. Resistance rates of uncomplicated UTI in symptomatic patients were: ciprofloxacin 10.5%, cotrimoxazole 15.8%, amoxicillin/clavulanic acid 5.3%, nitrofurantoin 0% (CLSI MICs). Previous hospitalization in the last 3 months (including patients living in a long-term care facility) was significantly correlated with resistance to ciprofloxacin, cotrimoxazole and amoxicillin/clav. Previous hospitalization was a strong predictor of resistance to ciprofloxacin and cotrimoxazole in multivariate analysis also. Other risk factors correlated with resistance were hematological malignancy (for cotrimoxazole) and renal transplantation (for ciprofloxacin).Conclusions: Cotrimoxazole is still an alternative for treating uncomplicated cystitis. Previous hospitalization in the last 3 months was a strong predictor of resistance to cotrimoxazole and ciprofloxacin. Other risk factors which might help guide empirical therapy are hematological malignancy and renal transplantation. [ABSTRACT FROM AUTHOR]

Trimethoprim, a commonly used antibacterial agent, is widely applied in the treatment of variety of infections in human. A few studies have demonstrated an extensive exposure of man to antibiotics, but there is still a lack of data for cytotoxic effects including nephrotoxicity, gastrointestinal toxicity, hematotoxicity, neurotoxicity and ototoxicity. The main purpose behind this study was to determine cytotoxic and genotoxic activities of trimethoprim (1), trimethoprim with maleic acid (2) and trimethoprim in conjugation with oxalic acid dihydrate (3). The cytotoxic effects of these three conjugates were elucidated by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoium bromide (MTT) assay using embryonic rat fibroblast-like cell line (F2408) and H-ras oncogene activated embryonic rat fibroblast-like cancer cell line (5RP7). Additionally, determination of genotoxic activity of these three compounds were studied by using cytokinesis blocked micronucleus assay (CBMN) in human lymphocytes. The results demonstrated that trimethoprim alone and its combination with other compounds are able to induce both cytotoxic and genotoxic damage on cultured cells (F2408, 5RP7, human lymphocytes). [ABSTRACT FROM AUTHOR]

A novel strain capable of degrading triclosan was isolated from the acclimated activated sludge and identified to be Dyella sp. WW1 based on 16S rDNA analysis. The effect of initial concentration of triclosan (0.2, 1, 5, and 10 mg/L), temperature (15, 25, and 35 °C), pH (5, 7, and 9), and additional carbon source on the degradation of triclosan was investigated in a mineral medium. The results showed that Dyella sp. WW1 can use triclosan as sole carbon source and degrade it when initial triclosan concentration was in the range of 0.2–10 mg/L. The optimal condition for Dyella sp. WW1 to degrade triclosan was 15 °C and pH 7. TOC removal efficiency was more than 90%. Dyella sp. WW1 can degrade 3,5-dichloro-4-hydrobenzoic via co-metabolism in the presence of triclosan, but cannot degrade trimethoprim, sulfamethoxazole, carbamazepine, and diclofenac. In the presence of glucose, Dyella sp. WW1 firstly utilized glucose to synthesize the biomass and then degraded triclosan. When triclosan concentration decreased to an extent (1.2 mg/L in this study), Dyella sp. WW1 started to use glucose again. The wastewater components did not significantly affect the activity of Dyella sp. WW1 to degrade triclosan. During the biodegradation process, six metabolite products were identified. Based on the metabolites, two degradation pathways were tentatively proposed. In summary, Dyella sp. WW1 could be used for degrading triclosan in the real wastewater. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia (SM) has emerged as an important nosocomial pathogen with high morbidity and mortality. Because of its unique antimicrobial susceptibility pattern, appropriate antimicrobial therapy for SM bacteremia is still challenging, especially in immunocompromised patients. The present study was performed to assess clinical predictors of SM bacteremia in adult patients with hematologic malignancy. From 2006 through 2016, a case-control study was performed at a tertiary-care hospital. Case patients were defined as SM bacteremia in patients with hematologic malignancy. Date- and location-matched controls were selected from among patients with gram-negative bacteremia (GNB) other than SM. A total of 118 cases of SM bacteremia were identified and compared to 118 controls. While pneumonia was the most common source of SM bacteremia, centralline-associated infection was most common in the controls. The overall 30-day mortality rate of cases with SM bacteremia was significantly higher than that of the controls (61.0 and 32.2%, respectively; P < 0.001). A multivariable analysis showed that polymicrobial infection, previous SM isolation, the number of antibiotics previously used ≥ 3, and breakthrough bacteremia during carbapenem therapy were significantly associated with SM bacteremia (all P < 0.01). Previous use of trimethoprim/sulfamethoxazole (TMP/SMX) was negatively association with SM bacteremia (P = 0.002). Our data suggest that SM is becoming a significant pathogen in patients with hematologic malignancy. Several clinical predictors of SM bacteremia can be used for appropriate antimicrobial therapy in hematologic patients with suspected GNB. [ABSTRACT FROM AUTHOR]

Antibiotic contamination of aqueous environment due to pharmaceutical sewage may lead to development of antibiotic-resistant bacteria strain. In this research, elimination of antibiotics from synthetic wastewater was investigated. For this purpose, sulfamethoxazole and trimethoprim were treated by a pilot scale of net-like rotating biological contactor with three compartments, 48 plastic discs with total volume of 78.75 L. This system was continuously operated for about one year at various organic loading rates with different antibiotic dosages. The obtained results indicated that by increasing hydraulic retention time, the chemical oxygen demand (COD) removal was gradually increased. The optimal hydraulic retention time for desired rate of COD removal was 36 h. In addition, the effect of hydraulic retention time, organic load rate and sulfamethoxazole concentration in the removal of sulfamethoxazole and organic matter was assessed. Moreover, the results demonstrated that with increasing in organic load rate, sulfamethoxazole elimination was enhanced. In the next step, simultaneous removal of both antibiotics for constant inlet COD concentration of 8000 mg/L at optimum hydraulic retention time was analysed. The results showed that trimethoprim removal efficiency was approximately 100%, even at high concentration of trimethoprim (50 mg/L). For observation of dominant microorganism, samples of the developed biofilm on rotating biological contactor discs were scanned by scanning electron microscopy. In the first compartment where biomass was exposed to highest concentration of antibiotics, fungus strains were the dominant organism. In the second and third compartment antibiotic-resistant bacteria were the dominant attached living organisms. [ABSTRACT FROM AUTHOR]

Polymorphic transformation in Trimethoprim (TMP) drug has been studied employing differential scanning calorimetry (DSC), TG/DSC, X-ray diffraction and FTIR techniques. To obtain a better understanding of the thermal events for the TMP polymorphs, a series of increasing heating rates and different mass were used. DSC of the Trimethoprim indicated that the as-received sample was crystalline (Form A). The molten Trimethoprim on cooling, however, produced a glassy amorphous mass. The sample obtained after heating at 100 °C for 1 h transformed to Trimethoprim (Form B).The glass transition observed in the second heating at 61 °C was followed by crystallization of the product at 81 °C. Form B of this study is probably a novel TMP polymorph. [ABSTRACT FROM AUTHOR]