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.

Pasteurella multocida is an important bacterial respiratory pathogen of buffaloes and may cause major economic losses in the livestock sector. But there is a lack of data on its prevalence, risk factors, and antimicrobial resistance patterns in Bangladesh. The study was cross-sectional, and a total of 400 buffaloes from seven locations in Bangladesh were included in the nasal swab collection. Isolation was done using culture methods and confirmed by polymerase chain reaction (PCR). Associations between infection and risk factors were explored using logistic regression analysis; antibiotic susceptibility was determined by the disc diffusion method. The co-resistance patterns were assessed by Pearson's correlation analysis. The culture-based prevalence of P. multocida was 12.25%, compared with a PCR-confirmed prevalence of 7.25%; all PCR-positive isolates were capsular type B, with notable regional variation in prevalence. Buffaloes with respiratory symptoms had significantly greater odds of being infected (OR = 8.88, p < 0.001), and the younger group of animals aged 1-3 years had a greater predisposition to infection than the younger ones, but sex was not significantly associated with infection. The isolates exhibited high antibiotic resistance, as demonstrated by antimicrobial susceptibility testing, particularly against ampicillin (96.55%), oxytetracycline (93.10%), and penicillin-G (89.65%). Cefixime (93.10%) and azithromycin (68.96%) remained largely effective by contrast. Positive correlations were identified between resistance to β-lactams, tetracyclines, and aminoglycosides. These findings suggest that multidrug-resistant P. multocida type B is circulating in buffaloes in Bangladesh and highlight the need for increased surveillance, rational use of antimicrobials, and integrated control strategies.

Background/Objectives: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) substantially affect quality of life. Previous studies have not evaluated whether the associations between early-life antibiotic exposure and the risks of ASD and ADHD differ according to the antibiotic agents administered during infancy. Methods: This nationwide case-control study used Taiwan's National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database. The cohort included 1,693,718 term neonates born between 2004 and 2015 and followed through to 2022. For ASD (n = 7265) and ADHD (n = 39,056) cases, antibiotic-exposed children were matched 1:1 with unexposed children based on sex, gestational age, birth weight, and birth year. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results: Oral antibiotic exposure was associated with lower ASD but higher ADHD risk, while parenteral exposure was associated with increased risks of both outcomes. Amoxicillin and erythromycin exposure during the first year of life were associated with lower ASD risk, whereas ampicillin exposure at 4-12 months was associated with higher ASD risk (all p ≤ 0.033). For ADHD, exposure to amoxicillin/clavulanic acid, cefixime, ampicillin, and ampicillin/sulbactam was associated with increased risk, whereas erythromycin, cephalexin, and sulfamethoxazole-trimethoprim were associated with reduced risk (all p < 0.047). Conclusions: Associations between early-life antibiotic exposure and the risks of ASD and ADHD varied according to antibiotic agents, route of administration, and timing of exposure. These findings may help explain inconsistencies among previous studies and inform antibiotic prescribing during infancy.

The emergence of antimicrobial resistance (AMR) due to biofilm-forming S. aureus is a worldwide issue associated with a variety of persistent infections, including mastitis. This study investigated the prevalence and molecular characterization of biofilm-forming S. aureus, risk factors associated with subclinical mastitis (SCM), and simulation-based computational modeling for biofilm-associated protein. Moreover, repurposing of non-steroidal anti-inflammatory drugs as adjunct therapies against biofilm-forming S. aureus was investigated in combination with antibiotics. Overall, 384 camel milk samples were collected and subjected to the California mastitis test (CMT), and 51.30% SCM prevalence was found in sampled animals. Among these, 59.39% of SCM-positive milk isolates were positive for S. aureus, while the prevalence of staphylococcal biofilm-positive isolates by Congo red agar (CRA) and tube method was 41.88% and 31.6%, respectively. Further, on genotypic investigation, 47.86% and 31.62% of isolates were found to have icaA and icaD genes, respectively. After this, biofilm-forming isolates were subjected to phylogenetic assessment, and results exhibited strong sequence identity of local icaA and icaD isolates with neighbouring countries. Moreover, phylogenetic analysis was further validated with simulation-based computational modeling by using different tools, and results depicted a close evolutionary relationship and predominant structural integrity of the icaA protein. Drug susceptibility profiling of biofilm-positive isolates showed high resistance against amoxicillin, trimethoprim+sulphamethoxazole, and cefixime. Furthermore, In-Vitro combination therapy trials showed synergistic effect of amoxicillin and trimethoprim+sulphamethoxazole with flunixin meglumine and cefixime with meloxicam. This study will provide baseline data on biofilm-forming S. aureus persistence in the camel population, along with devising an effective therapy against biofilm-forming S. aureus infections.

Antimicrobial resistance (AMR) in invasive Salmonella infections remains a global public health concern, and enhanced high-quality genomic surveillance is essential to inform guidelines and policies. Here, we aimed to describe clinically key antibiotic resistance trends in invasive Salmonella infections using 7691 isolates derived from national surveillance and publicly available datasets between 1954 and 2024. 29 (37.7%) of 77 countries identified at least one isolate with resistance or decreased susceptibility to ciprofloxacin, 25 (32.5%) and 29 (37.7%) countries resistance or decreased susceptibility to ceftriaxone and cefixime, 8 (10.4%) countries resistance to azithromycin, 15 (19.5%) countries resistance to fosfomycin, 10 (13.0%) countries resistance to colistin. Overall, 7.39% of 7691 isolates were resistant or decreased susceptibility to ciprofloxacin, 7.91% reported resistance or decreased susceptibility to 3GCs, 4.23% reported resistance to fosfomycin, and 0.79% reported resistance to azithromycin. Globally, azithromycin resistance is increasing, as is resistance or decreased susceptibility to ciprofloxacin, 3GCs, and 4GCs. However, surveillance levels remain inadequate in African and South American regions. We generated a global map of clinically key antibiotic resistance genes in invasive Salmonella infections worldwide. This retrospective, global, longitudinal genomic epidemiology study on invasive Salmonella provides evidence-based data for clinical guidelines, genomic surveillance, AMR control, and public health policies.

Emerging infectious diseases (EIDs) pose a critical threat to global biosecurity. Integrating bio/chemical information and artificial intelligence would bring new strategies for antimicrobial drug discovery. Herein, the Human Pathogenic Microorganisms Chemogenomics Knowledgebase (HPM-CKB) is presented as the largest domain-specific resource, consolidating chemical, genetic, and proteomic data on human-transmissible pathogens, together with multiple computational functional modules. The current release covers 7876 pathogenic proteins from 267 microorganisms (including 13,914 protein 3D structures) and 234,287 associated with bioactive molecules. HPM-CKB enables large-scale virtual screening, target identification, and drug repurposing, and integrates a large language model (LLM) for interactive queries. The computational prediction performance of HPM-CKB is corroborated by known inhibitors targeting SARS-CoV-2 replicase polyprotein 1ab. In wet-lab validations, four approved drugs (cefixime, ceftazidime, saquinavir, and rilapladib) identified via virtual screening show binding activity to SARS-CoV-2 nucleoprotein in affinity assays and inhibit SARS-CoV-2 replication in Vero E6 cells, demonstrating HPM-CKB's potential in drug repurposing. Meanwhile, two anti-Staphylococcus aureus lead compounds with novel scaffolds (CYC-HXL-9124 and CYC-HXL-9126) are identified via deep learning, and the potential target protein, cell division protein FtsZ, is subsequently prioritized using HPM-CKB (http://cgai.asia/g/pathogenDB) and experimentally validated by affinity assays. Collectively, these findings establish HPM-CKB as both a chemogenomic knowledgebase and a systematic drug development platform against EIDs.

Syphilis infection during pregnancy leads to around 390,000 adverse birth outcomes each year and is an important cause of preventable stillbirth. Although benzathine penicillin G is safe and effective during pregnancy for treating maternal and fetal infection, there are frequent global shortages and limited options for people with penicillin allergy. We conducted a review of potential alternatives to penicillin for treating syphilis during pregnancy when penicillin is not available or cannot be used, including ceftriaxone, amoxicillin, doxycycline, cefixime, and linezolid. Despite some efficacy data on their use in non-pregnant adults with syphilis, limited data were available on placental transfer, pharmacokinetics and dosing, efficacy or effectiveness, and safety in pregnancy. Given its favourable preclinical reproductive toxicity data, efficacy data in non-pregnant adults with syphilis, and safety during pregnancy when used for other indications, ceftriaxone could potentially be considered as an alternative treatment for pregnant women with syphilis in cases where penicillin cannot be used, as currently recommended by the World Health Organization. However, evidence about optimal dosing, feasibility, and efficacy/effectiveness for treating syphilis during pregnancy is needed. Several planned and ongoing clinical trials will provide additional data to inform the use of cefixime, amoxicillin, and linezolid in pregnant women with syphilis. Going forward, evaluation of new and existing medications for treating syphilis and preventing congenital syphilis should include a pregnancy investigation plan. Where possible, efforts should be made to ensure that high-quality pregnancy safety and efficacy or effectiveness data on drug candidates are generated in carefully designed studies to ensure that pregnant women and their infants are able to benefit from the full range of treatment options.

Fowl cholera (FC), caused by Pasteurella multocida type A, represents a major threat to poultry production worldwide. Detailed characterization of the genotypic, phenotypic, and antimicrobial resistance profiles is essential for advancing epidemiological surveillance and guiding effective intervention strategies. A total of 80 suspected FC field samples were collected from which P. multocida was isolated and identified through conventional culture techniques, Gram staining, and PCR. Antimicrobial susceptibility testing was performed using the disc diffusion method with 16 antimicrobial drugs. Whole-genome sequencing of a representative isolate was conducted using the Illumina MiSeq platform, and genomic analysis was carried out with multiple bioinformatics tools. P. multocida type A was confirmed in 12 isolates (15%). RAST annotation revealed a genome size of 2,346,689 bp with 2,205 predicted coding sequences, 59 RNA genes, and a GC content of 40.2%. Phenotypic analyses showed resistance to cefixime, ceftriaxone, ertapenem, and meropenem, while the highest sensitivity was observed for ciprofloxacin, doxycycline, tetracycline, and levofloxacin. PathogenFinder predicted the isolate as a potential human pathogen with a probability score of 0.891. Virulence-associated genes identified included wecA, galU, manB, rfaD, rfaE, rfaF, lpxB, lpxC, and msbA, supporting the pathogenic potential of the isolates and suggesting a possible role in host immune evasion. Phylogenetic analysis using MEGA X with the maximum likelihood method revealed that the isolate was clustered within the monophyletic clade and that it showed closest genetic relatedness to strains from Australia, China, and Malaysia. These findings highlight the genomic basis of virulence and antimicrobial resistance in P. multocida type A from Bangladeshi layer for the first time. The isolate characterized in this study provides valuable genomic insights and the selection of targeted antimicrobials to improve fowl cholera control strategies.

Background and Objectives: Antimicrobial resistance in Neisseria gonorrheae threatens the effectiveness of empirical gonorrhoea treatment. Although global surveillance evidence is increasingly available, resistance data are not consistently reported separately for men with urethral or urogenital infection. This review evaluated antibiotic-specific resistance in N. gonorrhoeae isolates from this clinically defined population and examined the geographic and reporting limitations of the available evidence. Materials and Methods: PubMed, Scopus, ScienceDirect, Google Scholar, and relevant WHO GASP/EGASP resources were searched from inception to [updated search date]. Eligible observational or surveillance studies reported categorical resistance classifications or extractable antibiotic-specific resistant counts and denominators for male urethral or urogenital isolates. Antibiotic-specific proportions were synthesized using random-effects meta-analysis where pooling was considered appropriate. Sparse-event outcomes were additionally evaluated using study-specific estimates and aggregate resistant/tested counts. Certainty of evidence was assessed using the GRADE framework adapted for prevalence outcomes. Results: Six studies met the eligibility criteria, including the 2025 multinational EGASP study. Cefixime resistance was reported in 748 of 13,154 isolates, corresponding to an aggregate proportion of 5.69%; however, the random-effects estimate was unstable because three studies reported no resistant isolates and events were concentrated in two large datasets. Ceftriaxone resistance varied from 0% to 5.17%, with a pooled estimate of 0.32% (95% CI 0.05-2.15; I[2] = 97.8%). Resistance was high but heterogeneous for ciprofloxacin (71.84%, 95% CI 7.53-98.77; I[2] = 97.3%) and penicillin (62.47%, 95% CI 36.87-82.58; I[2] = 98.1%). Spectinomycin resistance was 2.57% (95% CI 1.58-4.16; I[2] = 0%), while azithromycin resistance was 6.38% (95% CI 4.38-9.21; I[2] = 94.9%). Certainty of evidence was very low for all outcomes. Conclusions: Evidence specifically reporting resistance in male urethral or urogenital N. gonorrhoeae isolates remains limited and geographically uneven. Contemporary EGASP data demonstrate that ceftriaxone resistance is not uniformly low across surveillance settings. The pooled estimates should be interpreted as exploratory summaries rather than current global prevalence values or an independent basis for treatment selection. Standardized reporting of sex, anatomical site, breakpoints, MIC distributions, and resistant/tested counts is needed to improve future surveillance synthesis.

Klebsiella pneumoniae, a leading cause of health care-associated infections, increasingly exhibits multidrug-resistant phenotypes, including resistance to carbapenems, the last-resort antimicrobials, and thus compromises treatment options. However, there is a paucity of data on antimicrobial profiles and carbapenemase gene distribution in K. pneumoniae in Rwanda. A cross-sectional study was conducted from February 1 to June 30, 2025, at the University Teaching Hospital of Butare. One-hundred-fifty isolates were analyzed using traditional bacteriological identification with the API 20E system. Antimicrobial susceptibility was assessed by the modified Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute 2024 guidelines, and carbapenemase genes were detected through conventional polymerase chain reaction. Data were analyzed using descriptive and inferential statistical methods, and a P-value less than 0.05 was considered statistically significant. As a result, Klebsiella isolates exhibited high resistance rates to trimethoprim-sulfamethoxazole (78%), cefuroxime (71.3%), cefixime (72%), and ceftriaxone (66.7%). Moderate resistance to ciprofloxacin (30%) and amoxicillin-clavulanate (42.7%) was observed. In contrast, lower resistance to amikacin (9.3%), imipenem (12%), meropenem (13.3%), and ertapenem (14%) was observed. Of the Carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, 8 (38.1%) tested positive for the blaNDM gene, whereas none harbored the blaKPC gene. This study found a high resistance rate in K. pneumoniae to a widely used antibiotic and confirms the presence of blaNDM, highlighting the need for antimicrobial stewardship and strengthened local surveillance.

This study systematically investigated the degradation and abolishment of antibiotic potency and phytotoxicity of 6 sulfonamide antibiotics (sulfadiazine, sulfapyridine, sulfamethoxazole, sulfathiazole, sulfameter, and sulfadimethoxine) and a cephalosporin, cefixime, using purified LAC-48-2 laccase. The LAC-48-2 laccase/tannic acid system showed strong degradation capacity for 6 individual sulfonamides and 2 sulfonamide mixtures. The degradation mechanism and pathways of the LAC-48-2 laccase/tannic acid system for different sulfonamides was further revealed. The LAC-48-2 laccase/tannic acid system also strongly alleviated or abolished the antibiotic potency (bacteriostatic activity toward 3 bacterial strains: Bacillus subtilis, Staphylococcus aureus, and Escherichia coli) of the 6 individual sulfonamides and sulfonamide mixtures. The LAC-48-2 laccase/tannic acid system demonstrated excellent detoxification effects on the phytotoxicity caused by 6 individual sulfonamides and various combinations of sulfonamide mixtures. The LAC-48-2 laccase/ABTS (2,2'-Azino-bis-(3-ethylbenzodihydrothiazoline-6-sulfonic acid) diammonium salt) system can quickly degrade the cephalosporin cefixime, with a degradation efficiency of 99.58% within 5 min. The LAC-48-2 laccase/ABTS system also effectively abolished the antibiotic potency and bacteriostatic activity of cefixime: the high bacteriostatic activity of cefixime decreased greatly or was completely abolished after laccase treatment. The LAC-48-2 laccase/ABTS system also efficiently degraded the sulfonamide + cefixime mixture, as laccase treatment could significantly decrease or even completely abolish the antibiotic potency (bacteriostatic activity) of the sulfonamide + cefixime mixture. Treatment with laccase demonstrated strong detoxification capabilities against the phytotoxicity of this mixed antibiotics.