Background and objectives The Salmonella strains causing bloodstream infection show wide genetic diversity together with different antibiotic resistance profiles worldwide. The response of typhoidal Salmonella to standard antimicrobial treatments has become increasingly concerning during the past few decades. This study was conducted to evaluate the occurrence rate, antibiotic susceptibility patterns, and clinical characteristics of patients with Salmonella bacteraemia in a tertiary care hospital in Pune, Maharashtra, India. Methods A cross-sectional study was conducted from March 2024 to March 2025, analysing blood culture-confirmed cases of enteric fever. All patients with Salmonella-positive cultures were included, and data were gathered from clinical and microbiology records. Results Out of 6,862 blood cultures processed, 42 (0.6%) tested positive for Salmonella species. Of these, 50% were Salmonella Typhi, 36% were Salmonella Paratyphi A, and the remaining 14% included S. Cholerasuis, S. Typhimurium, and S. Gallinarum. All S. Typhi and S. Paratyphi A isolates were fully susceptible to first-line antibiotics, including chloramphenicol, amoxicillin, and co-trimoxazole, as well as to ceftriaxone and cefixime. However, 78.5% of isolates showed reduced susceptibility to ciprofloxacin. Initial disc diffusion testing suggested potential azithromycin resistance in 11 isolates, but confirmatory E-strip testing found none to be resistant based on MIC values. One S. Paratyphi A isolate exhibited a notably high MIC of 24 µg/mL, which is not classified as resistant according to U.S. NARMS guidelines. Interpretation and conclusions The increasing azithromycin MIC values among typhoidal Salmonella indicate potential resistance development, so additional research should assess azithromycin susceptibility patterns in detail.

This study investigated the acute inhibitory impacts of two widely used antibiotics, erythromycin (ERY) and tetracycline (TET), on ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) within an enriched nitrifying culture. For this purpose, a lab-scale wastewater treatment system sustaining enriched nitrifiers was exposed to antibiotic concentrations ranging from 25 to 100 mg L[-1]. Model evaluations of oxygen uptake rate (OUR) evolution, together with ammonia and nitrite oxidation profiles, revealed distinct metabolic disruptions. ERY severely impaired the system, dropping overall nitrification efficiency to as low as 25% and halving the growth rates for both AOB and NOB. In contrast, TET exposure largely maintained overall nitrification performance with slightly reduced NOB activity. Under TET stress, the half-saturation constants for ammonia (KNH) and nitrite (KNO) increased to 32 and 2 mg N L[-][1], respectively, indicating competitive inhibition and decreased substrate affinity. Both antibiotics reduced heterotrophic activity - more severely with ERY-triggering the release and utilisation of hydrolyzable biomass fractions. The results demonstrate that acute antibiotic toxicity and inhibitory impacts are markedly less pronounced in enriched nitrifying systems compared to conventional mixed activated sludge systems.

Background and Objective: Azithromycin is a widely used macrolide antibiotic with broad-spectrum antimicrobial activity; however, its clinical acceptability is limited by poor patient compliance due to its bitter taste. Additionally, the growing threat of antimicrobial resistance necessitates the development of novel derivatives with improved therapeutic performance. This study aimed to synthesize and evaluate novel azithromycin derivatives with dual potential for taste masking and enhanced antibacterial activity. Materials and Methods: Five novel azithromycin derivatives were synthesized by reacting azithromycin with different functional linkers, including N-acetyl benzenesulfonyl chloride, p-nitrobenzoyl chloride, p-toluenesulfonyl chloride, 3,5-dinitrobenzoyl chloride and p-nitrobenzenesulfonyl chloride. The synthesized compounds were characterized using Fourier-Transform Infrared Spectroscopy (FT-IR), nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Prodrug properties were assessed through kinetic stability studies at physiological pH values (2.2, 5.5 and 7.4). Antibacterial activity was evaluated in-vitro using minimum inhibitory concentration (MIC) and Half-Maximal Inhibitory Concentration (IC50) assays against clinically relevant bacterial strains, including Escherichia coli, Pseudomonas aeruginosa, Streptococcus pneumoniae and Staphylococcus aureus. The bacterial strains used in this study were standard ATCC reference strains and were not derived from human or animal subjects. Therefore, ethical approval was not required. All experiments were conducted following standard microbiological laboratory practices. Results: All five azithromycin derivatives were successfully synthesized with satisfactory yields and confirmed structural characteristics. <strong>Compounds 2, 4 and 5</strong> demonstrated favorable prodrug behavior by undergoing pH-dependent hydrolysis and regenerating the parent drug, indicating promising taste-masking potential. Furthermore, <strong>compounds 1 and 3</strong> exhibited superior antibacterial activity against Pseudomonas aeruginosa compared to the parent azithromycin. Conclusion: The synthesized azithromycin derivatives demonstrated promising potential as next-generation therapeutic agents with improved palatability and retained or enhanced antimicrobial efficacy. These findings support their prospective application in overcoming taste-related compliance issues while addressing antimicrobial resistance challenges.

Pharmaceuticals are widely detected in surface waters, posing significant ecological and human-health risks. China is a major producer and consumer of pharmaceuticals, and widespread contamination has been reported in its surface waters. Regional differences in topography, hydrology, land use, and socioeconomic conditions can shape patterns of pharmaceutical exposure and risk, calling for priority lists tailored to individual river basins. However, previous studies mainly focused on national-scale assessments, selected river basins, or specific pharmaceutical classes. In this study, we systematically reviewed 226 peer-reviewed articles and compiled 8628 occurrence records for 158 pharmaceutical compounds. A multi-criteria prioritization framework that integrated both hazard and exposure potential was used to identify priority pharmaceuticals across nine river basins. Antibiotics were the most frequently detected class of pharmaceuticals, although most had low or moderate priority scores. Erythromycin, roxithromycin, and azithromycin were notable exceptions and ranked highly. Among nonantibiotic pharmaceuticals, estrone and ibuprofen ranked highly in all nine basins. Beyond these shared priorities, several pharmaceuticals showed distinct basin-specific priority pattern. Psychotropic medicines, including diazepam, fluoxetine, sertraline, and citalopram, were identified as priorities in highly urbanized basins, particularly the Haihe and Yangtze River basins. In the Yellow River Basin, the lipid modulator gemfibrozil was prioritized, while in the Pearl River Basin, the veterinary antibiotic salinomycin was prioritized. Combining the rankings with uncertainty estimates showed that high-priority compounds with low uncertainty should be considered for stringent monitoring and control, whereas compounds with high uncertainty require additional occurrence and toxicity data. These findings underscore the importance of basin-scale prioritization in capturing regional differences and provide a basis for tiered monitoring and management in China.

Chronic lung allograft dysfunction (CLAD) is the primary cause of late graft loss after lung transplantation, affecting up to half of lung transplant recipients within 5 years and presenting with heterogeneous phenotypes, most commonly bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome. Prevention and treatment of CLAD are challenging. This European Society for Organ Transplantation (ESOT) clinical practice guideline was developed by a multidisciplinary Task Force, including patient and allied healthcare representation, using systematic reviews and GRADE methodology. Eight key PICO questions addressing prevention and treatment of CLAD were evaluated. In terms of prevention, recommendations are in favor of using tacrolimus over cyclosporine, either mycophenolate or azathioprine, and azithromycin to reduce the risk of CLAD. Regarding treatment, montelukast could be considered in early-stage BOS. Current data are inconclusive in demonstrating benefits of anti-thymocyte globulin, alemtuzumab or extracorporeal photopheresis compared with standard of care, and do not support the use of antifibrotics in BOS. The Task Force emphasizes the urgent need for high-quality clinical trials and standardized care pathways in CLAD management.

This study reports the genomic insights into a Streptococcus pneumoniae serotype 17F isolate in Malaysia (IMRCC/SS430/25), collected from an adult patient with aspiration pneumonia in 2025. Phenotypic identification revealed characteristic alpha-haemolytic colonies and optochin susceptibility. Species identity as S. pneumoniae was further verified by bile solubility testing and the 17F serotype was confirmed using the Quellung reaction. The isolate was subjected to whole-genome sequencing using the Oxford Nanopore platform. The assembly yielded a highly accurate, single circular contig of 2,065,967 bp with 100% completeness and 48× coverage. In silico typing assigned the genome to ST2355 within the globally disseminated GPSC10 cluster. Antimicrobial susceptibility testing demonstrated resistance to erythromycin, azithromycin, clindamycin, and tetracycline. This phenotypic profile was concordant with genomic screening which identified the ermB and tetM_8 genes responsible for macrolide-lincosamide-streptogramin B (MLSB) and tetracycline resistance respectively. The penicillin-binding protein allelic profile (pbp1a: 79, pbp2b: 26, pbp2x: 194) predicted uniform susceptibility to beta-lactam antibiotics shown by phenotypic testing of amoxicillin-clavulanate and penicillin. Phylogenomic characterization identified the Malaysian isolate within the predominant global ST2355 clade of GPSC10, clustering alongside isolates from Nepal, the United Kingdom, Bangladesh, and the United States. This study demonstrates the utility of combining routine clinical microbiology with high-resolution genomic surveillance to resolve lineage relationship, reveal underlying resistance mechanisms, and confirm genotype-phenotype concordance.

Multidrug resistant tuberculosis (MDR-TB) poses a serious global health concern. The development of drug-resistant mycobacterial strains is likely influenced by efflux transporters. In this study we created a deletion mutant of MSMEG_3118, a hypothetical efflux pump protein in Mycobacterium smegmatis, and characterized the mutant. It is shown that MSMEG_3118 acts as an efflux pump, and its deletion results in enhanced accumulation of the ethidium bromide. The MSMEG_3118 deletion mutant exhibited noticeable changes in colony morphology, slower growth rates, and reduced biofilm formation, indicating a larger role of this protein in mycobacterial physiology. Lipids profile showed elevated levels of menaquinone in the mutant. Interestingly, the mutant showed increased sensitivity to clofazimine and the proton motive force inhibitor CCCP but rendered higher resistance to several first- and second-line anti-tubercular drugs, such as rifampicin, isoniazid, streptomycin, vancomycin and erythromycin. All the changes in the mutant phenotypes were duly restored in the complemented mutant strain, suggesting a larger role of this protein in addition to an efflux pump transporter. Summarily, these results highlight a complex regulatory network that contributes to the multidrug resistance in mycobacteria.

Ribosome stalling is a major problem in all domains of life. When a ribosome stalls, trailing ribosomes may catch up to and collide with the stalled ribosome, depleting protein synthesis capacity. Here, we describe a novel pathway used by Gram-positive bacteria to rescue ribosome collisions. We used the ATPase defective ABCF protein YdiF(EQ2) to induce ribosome stalling and collisions in Bacillus subtilis. Ribosome profiling (Ribo-seq) of YdiF(EQ2)-expressing cells revealed that collided ribosomes are enriched for tmRNA, a functional RNA involved in trans-translation. We confirmed that tmRNA tagging activity is globally increased upon expression of any ATPase defective ABCF as well as in cells treated with the collision-inducing antibiotic erythromycin, suggesting this is a generalizable mechanism to rescue stalled and collided ribosomes. The global increase in tmRNA tagging that occurred in response to both erythromycin and YdiF(EQ2) induced collisions was dependent on the Rae1 endonuclease. Loss of trans-translation in cells experiencing widespread ribosome collisions leads to a severe fitness defect, consistent with the importance of this pathway in rescuing ribosomes stalled on truncated mRNAs that result from ribosome collisions. Altogether, our work supports a model in which Rae1 cleaves mRNA on collided ribosomes, thereby generating a truncated mRNA substrate for trans-translation and leading to rescue and recycling of the collided ribosomes. We term this mechanism Collision-Associated Rae1-induced t rans-Translation (CART). CART broadens the repertoire of tools that bacteria use to manage ribosome collisions.