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Sulphonamides and trimethoprim, although generally well‐tolerated, have been temporally associated with aseptic meningitis. To address its presentation and outcome, a literature search was performed. We retained articles reporting patients with features of acute aseptic meningitis following intake of trimethoprim, sulfamethoxazole or sulfisoxazole. A cerebrospinal fluid investigation in ≥1 episode was a prerequisite for inclusion. Sixty articles reporting on 74 patients experiencing a total of 155 episodes were retained. Forty‐five (61%) patients had one or more recurrences. Median age at first episode was 43 (interquartile range [IQR] 23–61) years. Symptoms presented within 48 (IQR 6–168) hours of intake at the first episode and within 1.3 (IQR 1–5) hours at recurrences (p < .0001). Cerebrospinal fluid analysis revealed a predominantly neutrophilic (82%, IQR 65%–94%) pleocytosis (180, IQR 38–507 106 cells/L), without low glucose or high proteins. Recovery took place within 2 (IQR 1–3) days after stopping the suspected agent. All but one patient completely recovered. [ABSTRACT FROM AUTHOR]

In comparison to the efforts required to bring a new drug or formulation to the clinic, bestowing a name on a medicine is relatively simple. However, if the name we choose causes confusion—by making its contents ambiguous or if it is too alike another drug—it can precipitate clinical errors. This prompted the World Health Organization to set up the International Nonproprietary Naming Committee in the 1970s to select unambiguous names for drugs. Unfortunately, multidrug products—which are becoming increasingly popular—do not fall under the remit of conventional International Non‐proprietary Nomenclature. We have identified 26 combination formulations that have been historically named with the co‐drug format in the United Kingdom. Most of them have also been prescribed in the United Kingdom in the past year, and although several of them are not prescribed very often, 11 were prescribed more than 2000 times. In this paper, we have explored the literature to identify prescribing errors with co‐drug products and found several idiosyncrasies that have caused drug errors in the past. We advocate for a standard nomenclature (state the international nonproprietary name [INN] of each component followed by dose information in the x + y format) for these products on the box and in prescribing resources. We hope that this will enhance clarity and safety during prescribing and administration, particularly for high‐volume drugs like paracetamol + codeine (co‐codamol), amoxicillin + clavulanic acid (co‐amoxiclav) and trimethoprim + sulfamethoxazole (co‐trimoxazole). [ABSTRACT FROM AUTHOR]

Background: Warfarin and Direct Oral Anticoagulant (DOAC) users may have more frequent antibiotic prescriptions than non-users. The aim of this study was to estimate rates of common and resistant infections, and antibiotic prescribing amongst warfarin and DOAC users versus non-users. Methods: This matched retrospective cohort study used data from patients registered with General practices in England contributing to the Clinical Practice Research Datalink GOLD. We included 61,750 adults who initiated warfarin or a DOAC between 1st January 2011 and 31st December 2019, matched 1:1 to non-users. We estimated Incident Rate Ratios (IRR) and 95% Confidence Intervals for three common infections and all-cause antibiotic prescribing. We estimated hazard ratios (HRs) and 95% CIs for the risk of methicillin resistance Staphylococcus aureus (MRSA), other antibiotic-resistant organisms, or Clostridium difficile. We assessed the extent to which any of the effect of warfarin and DOAC use on antibiotic resistant infections or Clostridium difficile was mediated by antibiotic prescribing patterns. Results: 37,143 warfarin users and 24,607 DOAC users were matched 1:1 to non-users. Warfarin and DOAC users had greater relative consultation rates for respiratory, urinary, and skin infections. All-cause antibiotic prescribing was greater in warfarin and DOAC users (warfarin; adjusted IRR 1.47, 95% CI 1.45–1.50, DOAC; adjusted IRR 1.66, 95% CI 1.63–1.69). Largest effect sizes were observed for flucloxacillin (adjusted IRR 2.11, 95% CI 2.01–2.20), and erythromycin (adjusted IRR 2.32, 95% CI 2.00–2.70). Warfarin users had significantly higher risk of MRSA (adjusted HR 1.68, 95% CI 1.38–2.05) and hospital admission with antibiotic resistant infections (adjusted HR 1.91, 95% CI 1.11–3.30). DOAC users had significantly higher risk of MRSA (adjusted HR 1.57, 95% CI 1.20–2.06), hospital admission with antibiotic resistant infections (adjusted HR 2.13, 95% CI 1.61–2.82), and Clostridium difficile (adjusted HR 1.45, 95% CI 1.10–1.92). We found little evidence to suggest that the increased risks of studied outcomes were mediated by rates of antibiotic prescription. Conclusion: Warfarin and DOAC use was associated with greater rates of infection consultations, all-cause antibiotic prescribing, antibiotic resistant infections, and Clostridium difficile, but there was little evidence that antibiotic prescribing rates mediated risk of resistant infections or Clostridium difficile. [ABSTRACT FROM AUTHOR]

After kidney transplantation, the recipients have been under long-term immunosuppression due to the use of immunosuppressive drugs, and they are high-risk population of Pneumocystis jirovecii pneumonia (PJP). The risk of PJP is the highest within 6 months after kidney transplantation and after intensified anti-rejection therapy. Fever, dry cough, progressive dyspnea and hypoxemia are common clinical manifestations of PJP after kidney transplantation. Trimethoprim-sulfamethoxazole (TMP-SMX) can effectively prevent and treat PJP, and significantly reduce the incidence rate and fatality of PJP. To standardize the diagnosis, treatment and prevention of PJP after kidney transplantation, Branch of Organ Transplantation of Chinese Medical Association organized relevant Chinese experts to formulate the " Guidelines for Clinical Diagnosis and Treatment of Pneumocystis Jirovecii Pneumonia After Kidney Transplantation in China" based on clinical concerns, aiming to provide guidance for the prevention and comprehensive clinical treatment of PJP after kidney transplantation. [ABSTRACT FROM AUTHOR]

(1) Background: Pediatric urinary tract infections (UTIs) pose significant challenges due to drug-resistant Escherichia coli (E. coli) strains. This study utilizes whole-genome sequencing to analyze temporal trends in antibiotic resistance genes (ARGs) in clinical E. coli isolates from pediatric UTI cases in central Vietnam. (2) Methods: We conducted whole-genome sequencing on 71 E. coli isolates collected from pediatric UTI patients between 2018 and 2020. ARGs were identified, and their prevalence over time was analyzed. Statistical tests were used to correlate ARG presence with antibiotic resistance. (3) Results: Of the 47 E. coli isolates with complete data, 40 distinct ARGs were identified, with a median of 10 resistance genes per isolate. A significant increase in the total number of ARGs per isolate was observed over time, from an average of 8.88 before June 2019 to 11.63 after. Notably, the prevalence of the aadA2 gene (aminoglycoside resistance) rose from 0% to 26.7%, and that of the blaNDM-5 gene (beta-lactam and carbapenem resistance) increased from 0% to 23.3%. Key correlations include blaEC with cephalosporin resistance, blaNDM-5 with carbapenem resistance, and sul2 with sulfamethoxazole/trimethoprim resistance. (4) Conclusions: Whole-genome sequencing reveals complex and evolving antibiotic resistance patterns in pediatric E. coli UTIs in central Vietnam, with a marked increase in ARG prevalence over time. Continuous surveillance and targeted treatments are essential to address these trends. Understanding genetic foundations is crucial for effective intervention strategies. [ABSTRACT FROM AUTHOR]

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]

Abstract The current study developed a method for quantifying four drugs—Sulfamethoxazole, Trimethoprim, Isoniazid, and Pyridoxine—in rabbit plasma. The method uses gradient liquid chromatography based on analytical quality by design. To achieve separation, a Eclip Plus C18 (250 mm × 5 mm, 4.6 µm) column with L1 packing was used, and analytes were detected at 254 nm at ambient temperature. The optimized mobile phase consisted of 50 mM potassium dihydrogen phosphate buffer (pH 6.5) and Methanol. The concentration of Methanol was 3% (0–5 min), 15% (5–15 min), 55% (15–27 min), and 3% Methanol until the end of the 30-min runtime, and the flow rate was set at 0.95 mL/min. Control Noise Experimentation was used to screen studies, revealing that flow rate, pH, and Methanol concentration significantly affected the analytical attributes. The study identified critical attributes (resolution and asymmetric factor) and developed a quality target method profile. A central composition design was used to optimize the essential parameters. The method developed for the drugs showed peaks at retention times of 6.990 min for Isoniazid, 7.880 min for Pyridoxine, 15.530 min for Sulfamethoxazole, and 26.890 min for Trimethoprim, respectively. The method was validated with linearity in the range of 10–640 ng ml−1, with R2 of 0.9993, 0.9987, 0.9993, and 0.9992 for Sulfamethoxazole, Trimethoprim, Isoniazid, and Pyridoxine, respectively.

Simultaneous spectrofluorometric method described for the determination of trimethoprim (TMP) and sulfamethoxazole (SMZ) in pure and pharmaceutical preparations using H-point standard addition method (HPSAM) according to the reaction of nanograms of drugs with O-phthaladehyde (OPA) reagent to forms highly fluorescence compounds. The formed fluorophore excitation and emission at 342 and 458 nm, respectively, for OPA-TMP compound, at 424 and 508 nm, respectively, for OPA-SMZ compound under basic condition (pH 9.8) in the presence of 2-mercabtoethanol. A simple and accurate HPSAM is reported to resolve the overlapping in the fluorescence spectrum of these two drugs without prior separation of samples. The linear range was 100–1200 ng/mL for TMP and 100–1100 ng/mL for SMZ. The LOD and LOQ were 16.64 and 36.80 ng/mL, as well as 15.76 and 33.88 ng/mL for TMP and SMZ, respectively. The relative standard deviations and recovery percentages were 0.641% and 101.29% for TMP as well as 0.558% and 100.96% for SMZ, respectively. The procedure has been applied successfully in various pharmaceutical preparations. It was discovered that the experimental F- and t-values at a 95% confidence level were no higher than the theoretical values, showing that the HPSAM method is accurate and valid.

Abstract Background We examined whether the pharmacodynamic drug–drug interaction between esaxerenone and trimethoprim enhances the hyperkalemic effect. Methods A retrospective observational study was conducted to identify patients >18 years undertaking esaxerenone alone or esaxerenone plus trimethoprim at Mie University Hospital from May 2019 to December 2022. We performed propensity score-matching (1:1) to compare between-group differences in the maximum change in serum potassium levels (ΔK) using the Mann–Whitney U test. For esaxerenone plus trimethoprim, Spearman's correlation coefficients were used to examine correlations between ΔK and variables, including changes in blood urea nitrogen (ΔBUN), serum creatinine levels (ΔCr), and weekly trimethoprim cumulative dose. Results Out of propensity score-matched groups (n=8 each), serum potassium levels significantly increased after administration of esaxerenone alone (4.4 [4.2 to 4.7] meq/L to 5.2 [4.7 to 5.4] meq/L, p=0.008) and esaxerenone plus trimethoprim (4.2 [4.0 to 5.1] meq/L to 5.4 [4.7 to 5.5] meq/L, p=0.023). ΔK did not significantly differ between the groups (esaxerenone alone; 0.6 [0.3 to 0.9] meq/L vs. esaxerenone plus trimethoprim; 1.0 [0.4 to 1.3] meq/L, p=0.342). ΔK positively correlated with ΔBUN (r=0.988, p

This study is about making and figuring out what trimethoprim (TM), a popular corrosion inhibitor, is like and then using it as an inhibiting agent to stop corrosion in carbon steel in acid media (HCl solution) through adsorption. TM has also been known as the prevalent anti-corrosive agent. It can be added to a liquid or gas to slow the pace of a chemical reaction (in the case of a material – typically a metal or alloy – that corrodes when it encounters the fluid). Many antibiotic compounds, such as TM derivatives, diiron salt dihydrate, and diiron salt tetrahydrate, have active groups that can stop metal from corroding. Spectroscopic methods like XRD (X-ray difraction), FTIR (Fourier transform infrared spectroscopy), UV-visible (ultraviolet-visible spectroscopy), and TGA (thermogravimetric analysis) were used to study the TM drug. Similarly, the OCP (open circuit voltage) technique was introduced to assess the corrosion resistance and the density of current vs. voltage. Finally, this study revealed that TM drugs could be suggested for introduction as corrosion inhibitors due to their simple production and the fact that they have many active groups that exhibit the ability to coordinate with carbon steel. Our study revealed that changes in inhibitor concentrations, the solution's acidity, and the metal's surface area all contribute to adsorption.

New compounds series of [M(TMP)(en)]X·nH2O and [M(TMP)(PD)]X·nH2O, where M = Ni2+, Cu2+, Zr4+, Ag+, Cd2+, TMP = trimethoprim, en = ethylenediamine, PD = o-phenylene and X= Cl− or NO3−, were prepared. The compounds were characterized using techniques including melting points, conductance, elemental analysis, FTIR, NMR, and mass spectroscopy. FTIR spectra indicated TMP acted like a bi-dentate ligand, combining via the nitrogen atoms of azomethine and pyrimidine amino groups. Diamine ligands (en or o-PD) are coordinated via two nitrogen atoms. Prepared compounds showed monomeric behavior and adopted a 6-coordinate octahedral geometry based on magnetic susceptibility and UV spectra. Conductivity measurements revealed Zr(IV) compounds were 1:2 conductive, while Ag+ and Cd2+ were 1:1 conductive; Ni2+ and Cu2+ compounds were non-conductive. Antibacterial tests on compounds and ligands against Bacillus subtilis and Staphylococcus aureus demonstrated broad-spectrum antibacterial activity. The mixed metal compounds revealed an observable tendency of antibacterial activity in the order Zr > Cd = Ag > Cu, making Zr(IV) compounds the most biologically active among them against S. aureus (Gram-positive) while the same compounds showed less antibacterial activity against B. subtilis (Gram-negative) than the free ligand.

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]

Nanoparticles exhibit distinct physical and chemical characteristics and are becoming increasingly significant in the production of innovative nanodevices for many applications in physics, biology, biomedicine, and pharmaceuticals. The aim of this research work is to synthesize Fe (II) and Cu (II) nano-sized complexes of trimethoprim (TMP) using the sonication method, characterize them using physical and spectroscopic methods, and carry out ADMET studies on the synthesized complexes. The spectroscopic and physical studies showed a change in colour and an increase in melting point due to coordination. The novel compounds were slightly soluble in water. The XRD tests revealed that the new nanocomplexes were crystalline. The Fe (II) nanocomplexes had a size of 57.56 nm and the Cu (II) nanocomplexes had a size of 69.88 nm. These values were found using Debye-Scherrer’s equation. The FTIR results of the TMP, Fe (II), and Cu (II) nanometal complexes showed a shift of the amino group band from 3317 to 3295 and 3202 cm−1 and the azomethine band from 1633 to 1625 and 1592 cm−1 in the complexes. In the complexes, the proton NMR spectra revealed an upfield shift of the amine proton. The carbon-13 NMR spectra showed that CH2 was involved in coordination with the metal ions. The spectra studies indicated that TMP coordinated with the metal ions through the methylene and amino groups. A trigonal bipyramid structure was proposed for the complexes. The results of the Rule of 5 studies indicated that the test compounds had a good drug-likeness prediction, with only one violation. The ADMET prediction showed that all of the compounds demonstrated improved pharmacokinetic characteristics and adhered to the RO5 requirement. These findings highlight the therapeutic potential of Fe (II) and Cu (II) nano-sized TMP complexes as bioactive compounds that warrant further investigation for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Antibiotic contamination of water sources is a significant environmental and public health concern. This contamination is classified among the most dangerous types of pollution currently because of their harmful effects. Therefore, it is essential to identify effective and environmentally friendly ways to deal with those dangerous compounds. Within this context, this work looked into whether soils made from volcanic ash could be used as cost-effective adsorbents to remove the antibiotic trimethoprim (TRM) from aqueous solutions. To examine the impacts of the main operating parameters on TRM removal, which are the initial antibiotic concentration (C), contact time (t), stirring speed (S), and solid-to-liquid ratio (R), a Central Composite Design (CCD) based on the Response Surface Methodology (RSM) was employed. Full quadratic polynomial models were used to correlate the experimental data, allowing for the estimation of each factor's influence. With a predicted removal efficiency of 77.59%, the removal process optimization yielded the following set of optimal conditions: C = 4.5 mg/L, t = 45.5 min, S = 747 rpm, and R = 0.04 g/mL. Experiments conducted under predicted ideal conditions supported both the result and the previously developed model's capacity for prediction. Additionally, the adsorption mechanism was also proposed based on the characterization of the adsorbent before and after the treatment. The study's findings provide the possibility of using soils formed from volcanic ash as a cost-effective adsorbent material for the removal of TRM and likely other similar pollutants from contaminated waters. [ABSTRACT FROM AUTHOR]

Background: Acne is the most common skin disorder which is known as a chronic inflammatory disease with psychological burden and reduced quality of life. Objective: The objective of this study is to determine, in a real-world effectiveness and clinical experience in treating acne scars which includes evaluating reduction in depth, diameter, erythema and pigmentation, with an acne scar gel, and to evaluate the effect of the product on quality of life. Methods: Overall, 435 patients were assessed for 90 days. The acne scars were counted and classified as mild, moderate or severe and the type of acne scar was registered. The study participants had gone through both oral and topical treatment for a time range of 1 week to over a month depending on the severity of the scars. They had also gone through medical procedures as per the requirement. The results were assessed at an interval of 30 days to 90 days and were graded between 1-5. Results: Overall facial appearance of atrophic acne scars improved after treatment with acne scar gel. Clinical experience with acne scar gel (in terms of reduction of scar depth, diameter, erythema, and pigmentation), and subject satisfaction (happiness and confidence) score along with the sensation and perception of the skin improved in most subjects. Conclusions: Acne scar gel was effective and safe for treatment of moderate-to-severe acne scars. The acne scar gel can be used as topical treatment for acne scars, thereby reducing the need of procedural treatment for acne scars. [ABSTRACT FROM AUTHOR]

Background: We examined whether the pharmacodynamic drug–drug interaction between esaxerenone and trimethoprim enhances the hyperkalemic effect. Methods: A retrospective observational study was conducted to identify patients >18 years undertaking esaxerenone alone or esaxerenone plus trimethoprim at Mie University Hospital from May 2019 to December 2022. We performed propensity score-matching (1:1) to compare between-group differences in the maximum change in serum potassium levels (ΔK) using the Mann–Whitney U test. For esaxerenone plus trimethoprim, Spearman's correlation coefficients were used to examine correlations between ΔK and variables, including changes in blood urea nitrogen (ΔBUN), serum creatinine levels (ΔCr), and weekly trimethoprim cumulative dose. Results: Out of propensity score-matched groups (n=8 each), serum potassium levels significantly increased after administration of esaxerenone alone (4.4 [4.2 to 4.7] meq/L to 5.2 [4.7 to 5.4] meq/L, p=0.008) and esaxerenone plus trimethoprim (4.2 [4.0 to 5.1] meq/L to 5.4 [4.7 to 5.5] meq/L, p=0.023). ΔK did not significantly differ between the groups (esaxerenone alone; 0.6 [0.3 to 0.9] meq/L vs. esaxerenone plus trimethoprim; 1.0 [0.4 to 1.3] meq/L, p=0.342). ΔK positively correlated with ΔBUN (r=0.988, p<0.001) or ΔCr (r=0.800, p=0.017). There was a trend of correlation of ΔK with a weekly cumulative trimethoprim dose (r=0.607, p=0.110). Conclusions: The hyperkalemic effect of the drug–drug interaction between esaxerenone and trimethoprim is not notable and related to renal function and trimethoprim dosage. [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]

Trimethoprim (TMP) is a bacterial dihydroreductase inhibitor with broad-spectrum antibacterial properties. However, its oral absorption is limited by its low water solubility. Salification is one of the effective methods to solve this problem. This work proposes an efficient method for screening TMP salts using the conductor-like screening model for real solvents (COSMO-RS) model. 200 common compounds were introduced as candidates for screening. As a result, 39 hit compounds were subjected to experimental liquid-assisted grinding (LAG) with TMP, then 25 new solid phases were confirmed by PXRD. The solvent evaporation method was further used to acquire eight single crystals of TMP salts, whose structures were elucidated by single-crystal X-ray diffraction. Power X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier-transform infrared spectroscopy were employed to characterize seven of the TMP salts. Then, atoms-in-molecules was used to analyze intermolecular hydrogen bonding interactions in salts. Finally, we tested the equilibrium solubility and dissolution rate of the salt, which exhibited an increase in solubility. In a word, it is an effective screening method to obtain TMP salts combined with the COSMO-RS model and LAG method, which can be widely applied to other systems for screening of the target salts. [ABSTRACT FROM AUTHOR]

Objective: Thymidine-dependent small-colony variants (TD-SCVs) of Staphylococcus aureus are being isolated with increasing frequency from patients with cystic fibrosis (CF). The aim of this study was to evaluate the relationship between TD-SCV isolation and pulmonary function in patients with CF, as well as to determine whether the emergence of TD-SCVs was associated with trimethoprim-sulfamethoxazole (TMP-SMX) use and with coinfection with other microorganisms. Methods: This was a retrospective casecontrol study including patients with CF who visited the Clinical Hospital Complex of the Federal University of Paraná, in Curitiba, Brazil, between 2013 and 2022. Demographic, clinical, and spirometric data, as well as information on TD-SCVs and other isolated microorganisms, were collected from the medical records of patients with CF and TDSCVs (TD-SCV group; n = 32) and compared with those of a matched group of patients with CF without TD-SCVs (control group; n = 64). Results: Isolation of TD-SCVs was positively associated with TMP-SMX use (p = 0.009), hospitalization (p < 0.001), and impaired pulmonary function (p = 0.04). Conclusions: The use of TMP-SMX seems to contribute to the emergence of TD-SCVs, the isolation of which was directly associated with worse pulmonary function in our sample. [ABSTRACT FROM AUTHOR]

Background: Stenotrophomonas maltophilia is an opportunistic, gram-negative bacillus with few therapeutic options due to a high level of intrinsic resistance. Trimethoprim/sulfamethoxazole (SXT) is recommended as the first-line treatment; however, minocycline (MIN) has been shown to have similar clinical outcomes in treating S. maltophilia and addresses concern for increasing resistance to SXT. Objective: The objective of this study is to evaluate the efficacy and safety outcomes of nonurinary, monomicrobial infections due to S. maltophilia in hospitalized patients treated with MIN or SXT. Methods: This was a retrospective study of hospitalized adult patients receiving MIN or SXT for nonurinary monomicrobial S. maltophilia infection from April 1, 2018 to March 31, 2020. The primary outcome was clinical disposition classified as rates of clinical failure, clinical improvement, or clinical success. Results: Eighty-two patients (88.2%) received MIN and 11 patients (11.8%) received SXT initially. Clinical failure occurred in 16 (19.5%) patients in the MIN group and in 4 (36.4%) patients in the SXT group (P = 0.242). Clinical improvement occurred in 11 (13.4%) patients in the MIN group and in 1 (9.1%) patient in the SXT group (P = 1.0). Clinical success occurred in 55 (67.1%) patients in the MIN group and in 6 (54.5%) patients in the SXT group (P = 0.503). Total duration of antimicrobial therapy (P = 0.3198), in-hospital mortality (P = 1.0), hospital length of stay (P = 0.9668), intensive care unit (ICU) length of stay (P = 0.1384), and 30-day readmission (P = 0.686) were similar between groups. Conclusions and Relevance: Rates of clinical failure, clinical improvement, or clinical success were similar between MIN and SXT for nonurinary monomicrobial S. maltophilia infections. [ABSTRACT FROM AUTHOR]

Background: Research on acute cystitis in men is scarce and treatment guidelines differ between countries. Improved antibiotic stewardship is needed. Aim: To analyse antibiotic prescriptions and outcomes of Norwegian men diagnosed with cystitis in primary care. Design & setting: A nationwide retrospective study was undertaken in primary care in Norway. Method: We identified all episodes of acute cystitis in men diagnosed in Norwegian primary care during 2012–2019. Choice of antibiotic (from the Norwegian Prescription Database), treatment failure, re-prescription, and complications were stratified by age, calendar year, and risk factors. We used logistic regression to explore predefined risk factors (diabetes, prostate cancer, benign prostate hyperplasia [BPH], urinary retention, and any cancer) with complications (pyelonephritis, prostatitis, and hospitalisation) and re-prescriptions. Linear regression was used to explore time trends. Results: In total, 108 994 individuals contributed 148 635 episodes. Narrow-spectrum antibiotics were first-choice treatment in 71.0% of the episodes (52.5% of all prescriptions were pivmecillinam). More than 75% of the episodes with narrow-spectrum versus 82.2% of broad-spectrum treatment did not lead to any re-prescription or complication. Complications occurred in 1.8% of all episodes (0.5% prostatitis, 0.7% pyelonephritis, and 0.7% hospitalisation). BPH was associated with increased risk of complications and re-prescription. Diabetes was associated with a lower risk of re-prescriptions. Prostate cancer and urinary retention were associated with a lower risk of both complications and re-prescriptions. Conclusion: Our results support narrow-spectrum antibiotics as first-line treatment. Risk factor analyses warrants further investigation. [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]

Cotrimoxazole, the combined formulation of sulfamethoxazole and trimethoprim, is one of the treatments of choice for several infectious diseases, particularly urinary tract infections. Both components of cotrimoxazole are synthetic antimicrobial drugs, and their combination was introduced into medical therapeutics about half a century ago. In Gram-negative bacteria, resistance to cotrimoxazole is widespread, being based on the acquisition of genes from the auxiliary genome that confer resistance to each of its antibacterial components. Starting from previous knowledge on the genotype of resistance to sulfamethoxazole in a collection of cotrimoxazole resistant uropathogenic Escherichia coli strains, this work focused on the identification of the genetic bases of the trimethoprim resistance of these same strains. Molecular techniques employed included PCR and Sanger sequencing of specific amplicons, conjugation experiments and NGS sequencing of the transferred plasmids. Mobile genetic elements conferring the trimethoprim resistance phenotype were identified and included integrons, transposons and single gene cassettes. Therefore, strains exhibited several ways to jointly resist both antibiotics, implying different levels of genetic linkage between genes conferring resistance to sulfamethoxazole (sul) and trimethoprim (dfrA). Two structures were particularly interesting because they represented a highly cohesive arrangements ensuring cotrimoxazole resistance. They both carried a single gene cassette, dfrA14 or dfrA1, integrated in two different points of a conserved cluster sul2-strA-strB, carried on transferable plasmids. The results suggest that the pressure exerted by cotrimoxazole on bacteria of our environment is still promoting the evolution toward increasingly compact gene arrangements, carried by mobile genetic elements that move them in the genome and also transfer them horizontally among bacteria. [ABSTRACT FROM AUTHOR]

Trimethoprim-sulfonamide (TMPS) combinations are widely used to treat a range of infectious diseases in horses, but some equine practitioners are reluctant to use them for treatment of both neonatal and older foals. Considering the emergence of increased antimicrobial resistance, the use of protected antimicrobials commonly prescribed to foals should be avoided and alternative first-line therapy considered, where appropriate. This review examines the characteristics and pharmacokinetics of TMPS and its suitability for treatment of foals. Data regarding dosage and route of administration are reported on the basis of recent publications in foals. The review intends to share significant information about the common infections that are most likely responsive to TMPS treatment in foals and, as such, where TMPS might be considered a suitable first-line therapeutic option. [ABSTRACT FROM AUTHOR]

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a complex and potentially fatal hypersensitivity condition. We present a unique case report and literature review focusing on DRESS syndrome-associated myocarditis resulting from reactivated viral infections in a 21-year-old female. 3 weeks after 5-day oral co-trimoxazole consumption due to acne, she developed symptoms consistent with DRESS syndrome, including a generalized maculopapular rash. Despite prednisolone treatment, the patient developed fatal fulminant myocarditis linked to HHV-6 and CMV reactivation. The patient's death highlights the importance of early recognition and careful management of DRESS syndrome, especially considering the potential viral reactivation that can lead to severe complications. Postmortem investigations revealed that viral reactivation caused myocarditis. Careful consideration must be given to corticosteroid usage in DRESS treatment, as inappropriate prescribing may promote viral reactivation and subsequent complications. While high-dose corticosteroids initiated within the first week effectively suppress HHV-6 reactivation. Conversely, low-dose or late-start high-dose corticosteroids prove ineffective in preventing HHV-6 viremia. Late- onset or low- dose corticosteroids may lead to fatal complications following the primary viral reactivation. [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]

Trimethoprim is predicted to inhibit several thiamine transporters, including the primary thiamine intestinal absorptive transporter, ThTR-2, and the hepatic and renal organic cation transporters, OCT1, OCT2, and MATEs. To investigate the effect of trimethoprim on thiamine absorption, studies were conducted in cells, mice, and healthy volunteers and supported by use of real-world data. In a randomized, crossover clinical study, seven healthy volunteers were given a single oral dose of thiamine or thiamine plus trimethoprim, followed by blood sampling. The thiamine area under the curve (AUC) increased with trimethoprim co-administration (P value = 0.031). Similar results were seen in mice. Trimethoprim appeared to act on thiamine absorption through inhibition of hepatic OCT1 as evidenced from its ability to modulate levels of isobutyrylcarnitine and propionylcarnitine, OCT1 biomarkers identified from metabolomic analyses. Real-world data further supported this finding, showing an association between trimethoprim use and higher levels of triglycerides, LDL cholesterol, and total cholesterol, consistent with OCT1 inhibition (P values: 2.2 × 10-16 , 5.75 × 10-7 , and 5.82 × 10-7 , respectively). These findings suggest that trimethoprim increases plasma levels of thiamine by inhibiting hepatic OCT1. Trimethoprim reduced urinary excretion and clearance of biomarkers for OCT2 and MATEs, consistent with inhibition of renal organic cation transporters. This inhibition did not appear to play a role in the observed increases in thiamine levels. This study highlights the potential for drug-nutrient interactions involving transporters, in addition to transporters' established role in drug-drug interactions.

ABSTRACT: Sulfonamides (S) are old bacteriostatic antibiotics which are widely prescribed in combination with trimethoprim (TMP) for the treatment of various diseases in food-producing animals such as poultry. Nowadays, the 1:5 dose ratio of TMP/S used in broilers is a direct transposition of the ratio determined in Human decades ago for TMP/sulfamethoxazole (SMX), aiming to obtain a supposed synergistic plasma concentration ratio of 1:19. However, major pharmacokinetics (PK) differences exist according to the sulfonamide used in the combination. Here, we generated new PK data in broilers after a cross-over design with IV and the oral administration of 2 major sulfonamides, sulfadiazine (SDZ) and SMX, in combination with TMP, and analyzed the data via a population pharmacokinetic (popPK) modeling approach. Results showed that TMP has a greater plasma to tissue distribution than both sulfonamides with a higher volume of distribution (0.51 L/kg for SDZ, 0.62 L/kg for SMX and 3.14 L/kg for TMP). SMX has the highest elimination half-life (2.83 h) followed by SDZ and TMP (2.01 h and 1.49 h, respectively). The oral bioavailability of the 3 molecules was approximately 100%. Bodyweight could explain some of the inter-individual variability in the volume of distribution of SDZ and SMX and the clearance of SDZ and TMP, as heavier broilers have higher typical values. Monte Carlo simulations of a large virtual broiler population (n = 1,000) showed that the targeted plasma ratio of TMP:S of 1:19 was rarely or never reached at the individual level for both combinations at the marketed doses and greatly varies over time and between individuals, questioning the relevance of the 1:5 dose ratio for current formulations of TMP/S.

A Novel bioanalytical detector based on Poly(Diaquabis(1,10-phenanthroline copper (II) Iodide) (poly([Cu(H2O)2P2]I2)/GCE) has been fabricated by potentiodynamic polymerization of [Cu(H2O)2P2]I2. The synthesized complex and the fabricated electrodes showed a promising electrocatalytic behavior towards the electrooxidation of Trimethoprim (TPM). Based on the regression coefficient value of scan rate with peak current and square root of peak current, the oxidation of TMP at poly([Cu(H2O)2P2]I2)/GCE was dominated by diffusion. Under the optimized experimental conditions and square wave voltammetric parameters, the poly([Cu(H2O)2P2]I2)/GCE revealed very wide responses in the range of concentration of 500 nM–160 μM with a limit of detection of 3.91 nM and a Limit of quantification of 13.02 nM with the relative standard deviation below 1.75 %. The valuable applicability of the fabricated sensor for the determination of TMP in real samples, including cow's milk, blood serum, and human urine, was successfully investigated. The electroanalysis results from the spike recovery and interference study provided an excellent range of recovery with an error percent of below 3.0 % in the combination effect with the potential interferents. The sensor exhibited excellent reproducibility, sensitivity, long-term stability, high accuracy, and fast response. The developed bioanalytical sensor revealed the best application prospect for biomedicine and environmental monitoring activities.

ABSTRACT Antimicrobial resistance (AMR) is a public health threat worldwide. Next-generation sequencing (NGS) has opened unprecedented opportunities to accelerate AMR mechanism discovery and diagnostics. Here, we present an integrative approach to investigate trimethoprim (TMP) resistance in the key pathogen Streptococcus pneumoniae. We explored a collection of 662 S. pneumoniae genomes by conducting a genome-wide association study (GWAS), followed by functional validation using resistance reconstruction experiments, combined with machine learning (ML) approaches to predict TMP minimum inhibitory concentration (MIC). Our study showed that multiple additive mutations in the folA and sulA loci are responsible for TMP non-susceptibility in S. pneumoniae and can be used as key features to build ML models for digital MIC prediction, reaching an average accuracy within ±1 twofold dilution factor of 86.3%. Our roadmap of in silico analysis—wet-lab validation—diagnostic tool building could be adapted to explore AMR in other combinations of bacteria–antibiotic.IMPORTANCEIn the age of next-generation sequencing (NGS), while data-driven methods such as genome-wide association study (GWAS) and machine learning (ML) excel at finding patterns, functional validation can be challenging due to the high numbers of candidate variants. We designed an integrative approach combining a GWAS on S. pneumoniae clinical isolates, followed by whole-genome transformation coupled with NGS to functionally characterize a large set of GWAS candidates. Our study validated several phenotypic folA mutations beyond the standard Ile100Leu mutation, and showed that the overexpression of the sulA locus produces trimethoprim (TMP) resistance in Streptococcus pneumoniae. These validated loci, when used to build ML models, were found to be the best inputs for predicting TMP minimal inhibitory concentrations. Integrative approaches can bridge the genotype-phenotype gap by biological insights that can be incorporated in ML models for accurate prediction of drug susceptibility.