Cutibacterium acnes (C. acnes), the most abundant microbe of the skin microbiota, has been reported playing a protective role in atopic dermatitis (AD), in contrast to its proinflammatory role in acne. While antibiotic resistance in C. acnes has been extensively studied in acne, little is known about its characteristics in AD. Here, we performed an integrated genomic and functional analysis of 405 AD-derived C. acnes isolates using whole genome sequencing (WGS) and antimicrobial susceptibility testing. The result showed that antibiotic resistance genes (ARGs) were highly clustered within specific individuals and phylogenetic subtypes of C. acnes, with erm(X) being the most prevalent determinant conferring cross-resistance to erythromycin and clindamycin. To verify the high genotype-phenotype concordance (95.45%) of erythromycin and clindamycin resistance of 110 ARGs-carried C. acnes isolates, minimum inhibitory concentration (MIC) was performed. AD isolates exhibited low-level acquired resistance to tetracyclines, chloramphenicol, and fusidic acid, indicating distinct antibiotic exposure pressures in AD patients. Comparative genomic analysis and genome-wide association study both showed that metabolism and quorum sensing related pathways were enriched in pan-genome of ARG-containing strains. These findings suggest that resistance in AD-associated C. acnes is linked to metabolic adaptations that may facilitate survival in the AD skin environment. Together, these findings provide a genomic and functional framework for understanding the antibiotic resistance of AD-associated C. acnes, underscoring the need for careful antibiotic stewardship in AD management.

Macrolides are widely prescribed antibiotics with a well-established risk of QT prolongation, but their broader cardiotoxic profile has not been systematically compared across countries using large-scale real-world data. The aim of this study is to characterize the spectrum, drug-specific signal patterns, and clinical outcomes of macrolide-associated cardiac adverse events (cAEs) through a cross-national comparison using two independent national pharmacovigilance databases. We performed a comprehensive disproportionality analysis of macrolide-associated cardiac adverse events (cAEs) using the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) from 2016 Q1 through 2025 Q4. We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) for signal detection. Time-to-onset (TTO) was characterized using cumulative incidence curves and non-parametric Wilcoxon rank-sum tests across individual macrolides, clinical outcomes, and event types. Among 42,605 macrolide-related reports in FAERS and 4613 in JADER, cAEs accounted for 1415 (3.32%) and 128 (2.77%) reports, respectively. Azithromycin predominated in FAERS (72.3%) and clarithromycin in JADER (66.4%). Erythromycin showed the highest FAERS ROR for long QT syndrome (81.82, 95% CI 45.09-148.46), followed by azithromycin (34.71, 95% CI 25.15-47.91) and clarithromycin (18.11, 95% CI 8.61-38.08); azithromycin and clarithromycin signals were independently confirmed in JADER (ROR 24.42 and 13.17, respectively). Azithromycin was uniquely associated with heart-failure-related signals (acute right ventricular failure ROR 52.48, 95% CI 19.37-142.19), whereas clarithromycin showed the strongest ischemic heart disease signals (myocardial ischemia ROR 6.55, 95% CI 2.94-14.60; JADER coronary artery spasm ROR 10.37, 95% CI 4.25-25.33). Overall mortality among cAE cases was 10.2% in FAERS and 10.4% in JADER, with QT/torsade de pointes (TdP)-related case-fatality rates of 12.5% for clarithromycin and 10.3% for azithromycin. Most cardiac events occurred within the first 2 weeks of therapy (median time to onset, 1 day). Macrolide-associated cardiotoxicity extends beyond QT prolongation/TdP to heart failure and ischemic heart disease, with drug-specific and cross-national differences in signal pattern. As disproportionality signals, these findings are hypothesis-generating rather than causal, but support targeted cardiac monitoring in high-risk patients, particularly during the first 2 weeks of macrolide therapy.

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.

Latency antibiotic therapy is an established component of expectant management after preterm prelabour rupture of membranes (PPROMs). Pooled randomised evidence from 22 trials involving 6872 women and infants shows that antibiotics prolong pregnancy, reduce chorioamnionitis (risk ratio 0.66) and reduce neonatal infection (risk ratio 0.67), without a significant reduction in perinatal mortality. The evidence supporting the therapeutic principle is stronger than the evidence defining how the therapy should be configured. This narrative review examines the three decisions an obstetrician makes at the bedside, namely, which agent, at which dose and route, and for how long, and the comparative evidence behind each. Contemporary practice descends from two protocols: the ampicillin-erythromycin regimen of the NICHD Maternal-Fetal Medicine Units Network trial and the erythromycin arm of ORACLE I. Neither was designed to identify an optimal regimen. Substitution of azithromycin for erythromycin rests predominantly on observational cohorts together with one small open-label randomised comparison that pre-specified no non-inferiority margin and is therefore pragmatic and guideline-permitted rather than confirmed by an adequately powered randomised trial. No randomised dose comparison using clinical endpoints has been performed in PPROM, although randomised pharmacokinetic data exist for azithromycin. The seven-day course derives from a trial protocol rather than from a duration-ranging study, and the two randomised duration comparisons published since 2023 point in opposite directions. Guideline agreement reflects shared historical ancestry rather than independent confirmation of optimality. Adequately powered pragmatic trials, stratified by gestational age, remain the principal unmet need.

Background/Objectives:Streptococcus parasuis is an under-recognized member of the Streptococcus suis complex that can be misidentified by routine diagnostic methods. Human clinical isolates remain sparsely characterized. This study investigated the antimicrobial phenotype, genomic features, population position, and larval pathogenicity of a human pleural-fluid isolate. Methods: Strain HUGSPH was recovered during the care of a patient with pneumonia. Hybrid whole-genome sequencing (WGS), average nucleotide identity analysis, multilocus sequence typing (MLST), core-genome phylogenetics, comparative pan-genomics, and an exploratory host-origin association analysis were performed. Minimum inhibitory concentrations (MICs) were determined using the VITEK 2 Compact system with an AST-ST03 card, and virulence was evaluated in Galleria mellonella larvae. Results: Genome-based analysis confirmed HUGSPH as S. parasuis and assigned it to the novel sequence type (ST) 181. The isolate clustered within a predominantly human-origin phylogenetic clade. Because species-specific clinical breakpoints are unavailable, the MICs were interpreted provisionally using explicitly stated surrogate Clinical and Laboratory Standards Institute (CLSI) criteria; erythromycin, clindamycin, and levofloxacin were categorized as resistant under those criteria. Several predicted antimicrobial-resistance-associated genes were detected. In a restricted comparison of seven human-origin and nine swine-origin genomes, eight genes were present in all included human-origin isolates and absent from all included swine-origin isolates, whereas metQ, metP, and metN showed the reciprocal pattern. HUGSPH caused dose-dependent larval mortality, reaching 100% at 107 colony-forming units (CFU) by 96 h. Conclusions: HUGSPH expands the genomic record of human clinical S. parasuis and highlights the diagnostic and surveillance relevance of antimicrobial resistance in this species. The susceptibility categories, source-associated genes, and larval phenotype require validation by reference susceptibility testing, broader phylogenetically balanced collections, comparative strains, and mammalian models.

Background/Objectives: The increasing prevalence of antimicrobial resistance has reduced the effectiveness of conventional antibiotics, highlighting the need for alternative or adjunct antimicrobial agents. This study aimed to investigate the antibacterial, synergistic, and antibiofilm activities of Liquidambar orientalis Mill. essential oil against clinically relevant bacterial pathogens, using 24 bacterial strains representing 12 bacterial species. Methods: The volatile constituents of L. orientalis essential oil obtained by hydrodistillation of storax balsam were characterized by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID). Antibacterial activity was evaluated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), disk diffusion, and agar well diffusion assays against a panel of Gram-positive and Gram-negative bacterial pathogens. Synergistic interactions with erythromycin, amoxicillin, gentamicin, and enrofloxacin were assessed using fractional inhibitory concentration index (FICI) analysis. Antibiofilm activity was also evaluated against representative biofilm-forming strains. Results: A total of 90 volatile constituents were identified by GC-MS, of which styrene was the most abundant (68.6%), followed by (E)-ethyl cinnamate (6.8%), α-pinene (5.9%), and β-pinene (2.9%). The essential oil exhibited broad-spectrum antibacterial activity, with an overall inhibition rate of 60.4%. Activity was higher against Gram-positive (77.77%) than Gram-negative (73.33%) bacteria. MIC and MBC values ranged from 15.62 to 250 µg/mL and 31.25 to 250 µg/mL, respectively. FICI analysis revealed strain- and antibiotic-dependent interactions, ranging from synergistic to antagonistic effects. Variable antibiofilm activity was observed, with the strongest inhibition against Brucella melitensis and the weakest against Pseudomonas aeruginosa. No significant differences in MIC or MBC values were observed between bacterial groups (p > 0.05). Conclusions:L. orientalis essential oil demonstrated in vitro antibacterial activity against several clinically relevant pathogens, with particularly notable activity against B. melitensis. The essential oil also showed synergistic interactions with selected antibiotics and variable antibiofilm effects. These findings suggest that L. orientalis essential oil may have potential as an antibacterial agent or adjunct to antibiotic therapy; however, further in vivo and clinical studies are required to confirm its therapeutic applicability.

Background/Objectives: Despite its hostile physicochemical environment characterized by high osmotic pressure, acidic pH, and low water activity, honey serves as a unique ecological niche for resilient microorganisms. This study aimed to recover bacterial isolates from honeys of different botanical origins and to characterize the probiotic-associated properties of a honey-derived Bacillus licheniformis isolate. Methods: A total of 20 bacterial isolates were recovered from four honey samples, including two blossoms and two honeydew honeys. 16S rRNA gene sequence analysis showed that the recovered isolates had taxonomic assignments consistent with Bacillus licheniformis. Because 16S rRNA sequencing does not provide sufficient resolution to establish strain-level diversity or clonality, one isolate, designated Blhoney, was selected for subsequent molecular and functional characterization. Results: In vitro assays revealed that Blhoney exhibits robust tolerance to simulated gastrointestinal stress, including extreme acidity (pH 1-3), bile salts (0.3-1%), pepsin, and pancreatin, maintaining viability for up to 24 h. Phenotypic antimicrobial testing demonstrated measurable inhibition zones for erythromycin, kanamycin, chloramphenicol, ampicillin, tetracycline, gentamicin, streptomycin, and spectinomycin, whereas no measurable inhibition zones were observed for penicillin G, rifampicin, ciprofloxacin, or ceftazidime. However, MIC determination and standardized breakpoint interpretation were not performed; therefore, these findings were interpreted solely as preliminary phenotypic inhibition-zone observations. Although the isolate did not display direct antagonistic activity against the tested bacterial pathogens under experimental conditions, its persistence under the tested gastrointestinal stress conditions supports further investigation of its probiotic-associated characteristics. Conclusions: Overall, these findings indicate that the honey-derived Blhoney isolate exhibits preliminary probiotic-associated characteristics under the tested in vitro conditions. However, further strain-level genomic and safety characterization is required before its potential probiotic application can be established.

Staphylococcus aureus is a major human pathogen causing infections ranging from mild skin infections to life-threatening systemic conditions. Clindamycin has long been used to treat serious Staphylococcus aureus infections due to its pharmacokinetic profile and ability to inhibit toxin production. However, inducible resistance to clindamycin via erythromycin ribosomal methylases encoded by erm genes poses a significant clinical challenge; it often leads to treatment failure and remains undetected by routine antimicrobial susceptibility testing. This cross-sectional study analyzed 120 non-duplicate clinical Staphylococcus aureus isolates from the University Hospital Center of Fez, Morocco. Identification followed standard microbiological methods, and susceptibility testing adhered to the European Committee on Antimicrobial Susceptibility Testing (EUCAST/CA-SFM) 2024 guidelines. Inducible clindamycin resistance was assessed using the D-test, while methicillin resistance was determined by the cefoxitin disk diffusion method. Of the 120 isolates, 50 (41.67%) were resistant to erythromycin. Constitutive macrolide-lincosamide-streptogramin B (MLSB) resistance was detected in 31 isolates (25.83%), inducible MLSB (iMLSB) resistance in 5 isolates (4.17%), and the macrolide-streptogramin B (MS) phenotype in 14 isolates (11.66%). All isolates with inducible clindamycin resistance or the MS phenotype were methicillin-susceptible Staphylococcus aureus (MSSA), while constitutive MLSB resistance was more frequent among methicillin-resistant Staphylococcus aureus (MRSA). Inducible clindamycin resistance, though less prevalent, remains clinically significant and can be readily detected using the D-test. Routine use of the D-test is essential to guide appropriate antimicrobial therapy and prevent clindamycin treatment failure.

Due to Pseudomonas aeruginosa (P. aeruginosa)'s inherent resistance to many antibiotics and the increasing incidence of multidrug-resistant (MDR) organisms, P. aeruginosa infection has become a growing global threat to humanity. Azithromycin (AZM) does not have prominent antibacterial activity against P. aeruginosa at a clinically reasonable level because of the bacteria's outer membrane and efflux pump system; however, it does demonstrate other properties, including reduction of inflammation and suppression of P. aeruginosa virulence. With the promising potential of AZM as an anti-P. aeruginosa active compound, we proposed the application of a Trojan horse strategy to the synthesis of AZM derivatives. In this study, we designed and synthesized catechol-conjugated AZM derivatives and evaluated their anti-P. aeruginosa activity. One of the derivatives showed superior antibacterial activity to AZM, even against MDR P. aeruginosa clinical isolates.

Ventilator-induced lung injury (VILI) is a significant complication of mechanical ventilation, contributing to morbidity and mortality in critically ill patients. Excessive mechanical stress triggers an inflammatory cascade, leading to lung damage, pulmonary oedema, and systemic complications. While macrolide antibiotics such as azithromycin (AZM) have demonstrated anti-inflammatory and epithelial barrier strengthening effects, their use is limited by concerns regarding antibiotic resistance. EP317, an azithromycin-derived compound with negligible antibacterial activity, was designed to retain the immunomodulatory and epithelial barrier enhancing effects of AZM while mitigating the risk of bacterial resistance. This study investigated the effects of AZM and EP317 in a rat model of VILI. Forty-eight rats were divided into six groups (N = 8 per group), receiving either placebo, AZM, or EP317 (5 mg/kg daily for seven days), with half of the animals subjected to mechanical ventilation with peak airway pressure at 35 cmH2O. Both compounds attenuated ventilation-induced pulmonary oedema, reflected in a smaller increase in lung wet/dry ratio, whereas ventilation-induced increases in total protein in bronchoalveolar lavage fluid (BALF) were not significantly reduced by either treatment. Cytokine profiling in plasma (L-Selectin, PAI-1, RANTES, MCP-3, IL-6, SCF, IL-17a, RAGE, MIP-3α, IL-13, G-CSF, IL-10, M-CSF, IFN-γ, GRO-KC and MMP9) revealed that both treatments attenuated inflammatory responses, while cytokine levels in BALF in ventilated animals were either unchanged or increased. Survival rates were improved in the treatment groups. Histological analysis indicated increased oedema in ventilated animals, likely due to the high-pressure ventilation, while drug-treated groups exhibited reduced oedema. Global gene expression profiling by RNA sequencing revealed robust upregulation of inflammatory and stress-response pathways in ventilated animals, with partial attenuation following AZM or EP317 pre-treatment. These findings suggest that EP317 and AZM offer protective effects against VILI. EP317 presents a promising alternative to conventional macrolide therapy by circumventing antibiotic resistance concerns.

Methicillin-resistant Staphylococcus aureus (MRSA) poses challenges in healthcare settings, contributing to antimicrobial resistance and complicating treatment of staphylococcal infections. In resource-limited settings such as Zambia, staphylococcal infections are treated empirically with clindamycin or co-trimoxazole due to limited susceptibility testing. However, MRSA and multidrug resistance are reducing treatment effectiveness. This study aimed to determine the prevalence and antimicrobial susceptibility of MRSA at Mansa General Hospital, Zambia. A retrospective cross-sectional study was conducted on 266 clinical S. aureus isolates from 2020-2024. Bacterial identification was performed using microbiological methods (Mannitol Salt Agar, catalase, coagulase, DNase tests). MRSA detection and antimicrobial susceptibility testing (AST) using the Kirby-Bauer disk diffusion- method with cefoxitin (30 µg) as a surrogate marker, interpreted according to CLSI M100 34th Edition guidelines. Multivariable logistic regression identified factors associated with MRSA. Among 266 S. aureus isolates, the overall MRSA prevalence was 31.6% (84/266). MRSA demonstrated significantly lower susceptibility than MSSA to non-beta-lactam antibiotics: clindamycin (46.2% vs. 67.7%), erythromycin (50.0% vs. 79.5%), ciprofloxacin (58.2% vs. 91.4%), and tetracycline (58.3% vs. 81.9%). Chloramphenicol (86.5% vs. 100%) and linezolid (81.8% vs. 97.9%) retained activity. MDR prevalence was 28.6% (76/266), with higher MDR (57.1%, 48/84) than MSSA (15.4%, 28/182). Older age was independently associated with MRSA: adults aged 45-59 years (AOR 2.77; 95% CI 1.09-7.01; p = 0.032) and ≥60 years (AOR 4.53; 95% CI 1.45-14.1; p = 0.009) had higher odds compared to children. Sex, patient type and specimen source were not significant predictors. This study highlights the high prevalence of MRSA at Mansa General Hospital, reduced susceptibility to used oral antibiotics and a burden of multidrug resistance. Empirical use of clindamycin and erythromycin for suspected staphylococcal skin and soft tissue infections should be reconsidered and guided by local antimicrobial susceptibility whenever available. Continued local surveillance and multicenter studies are needed to inform empirical treatment guidelines across Zambia.