OBJECTIVE: We aimed to quantify the individual risk of antimicrobial resistance among patients with community-acquired Escherichia coli urinary tract infection (UTI) according to their antibiotic exposure over the previous 18 months.
METHODS: French patients were prospectively recruited in two centers in 2015-2017. Resistance of isolates to amoxicillin (AMX), amoxicillin-clavulanate (AMC), third-generation cephalosporins (3GC), trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones (FQ) and fosfomycin (FOS) was analysed according to previous intra-class and inter-class antibiotic exposure documented in health insurance files.
RESULTS: Previous antibiotic exposure was found in 588 (81.4 %) of the 722 UTI cases analysed (564 patients). Recent exposure (three months before UTI) was associated with stronger intra-class impact on E. coli resistance compared to remote exposure (18 months before UTI) for AMX, AMC, FQ and TMP-SMX, with respective adjusted odds ratios [95 % confidence interval] of 1.63 [1.20-2.21], 1.59 [1.02-2.48], 3.01 [1.90-4.77], and 2.60 [1.75-3.87]. AMX, FQ, and TMP-SMX also showed significant inter-class impact. Resistance to 3GC was not significantly associated with intraclass exposure (adjusted OR: 0.88 [0.41-1.90]). FOS resistance was remarkably low (0.4 %). Duration of the antibiotic-free period required for resistance risk to drop below 10 %, the threshold for empirical use in UTI, was modelled as < 1 month for 3GC, >18 months for AMX and TMP-SMX and uncertain for AMC (5.2 months [2.3 to > 18]) and FQ (17.4 months [7.4 to > 18]).
CONCLUSIONS: Resistance of E. coli causing UTI is partially predicted by previous personal antibiotic delivery.

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OBJECTIVE: The association between antibiotic exposure and inflammatory bowel disease (IBD) remains controversial, especially whether there is a dose-response relationship. We aimed to conduct a systematic review and meta-analysis to thoroughly evaluate the risk of new-onset IBD associated with antibiotic exposure.
METHODS: Four databases were searched from their inception to September 30, 2023 for all relevant studies. The risk estimates were pooled together using random-effects models, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, stratified by IBD subtype, age, exposure period, study type, and antibiotic classes. Dose-response relationship between the number of antibiotic prescriptions and IBD risk was assessed using generalized least squares regression analysis.
RESULTS: Twenty-eight studies involving 153,027 patients with IBD were included. Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29-1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08-1.68). This association existed for both Crohn\'s disease and ulcerative colitis, as well as in children and adults for prescription-based studies. The majority of antibiotic classes were associated with an increased IBD risk, with metronidazole (OR, 1.70; 95% CI, 1.38-2.10) and quinolones (OR, 1.56; 95% CI, 1.37-1.77) having relatively higher risk estimates. A positive nonlinear dose-response association was observed between the number of antibiotic prescriptions and IBD risk.
CONCLUSIONS: Antibiotic exposure was significantly associated with an increased risk of new-onset IBD, and a positive nonlinear dose-response relationship was observed. Antibiotic stewardship may be important for reducing IBD risk.

Clostridioides difficile is a Gram-positive bacteria that causes nosocomial infections, significantly impacting public health. In the present study, we aimed to describe the clinical characteristics, outcomes, and relationship between antibiotic exposure and Clostridioides difficile infection (CDI) in patients based on reports from two databases. Thus, we conducted a retrospective study of patients diagnosed with CDI from Sibiu County Clinical Emergency Hospital (SCCEH), Romania, followed by a descriptive analysis based on spontaneous reports submitted to the EudraVigilance (EV) database. From 1 January to 31 December 2022, we included 111 hospitalized patients with CDI from SCCEH. Moreover, 249 individual case safety reports (ICSRs) from EVs were analyzed. According to the data collected from SCCEH, CDI was most frequently reported in patients aged 65-85 years (66.7%) and in females (55%). In total, 71.2% of all patients showed positive medical progress. Most cases were reported in the internal medicine (n = 30, 27%), general surgery (n = 26, 23.4%), and infectious disease (n = 22, 19.8%) departments. Patients were most frequently exposed to ceftriaxone (CFT) and meropenem (MER). Also, in the EV database, most CDI-related ADRs were reported for CFT, PIP/TAZ (piperacillin/tazobactam), MER, and CPX (ciprofloxacin). Understanding the association between previous antibiotic exposure and the risk of CDI may help update antibiotic stewardship protocols and reduce the incidence of CDI by lowering exposure to high-risk antibiotics.

BACKGROUND: Preterm neonates often receive a variety of duration of antibiotic exposure during admission. The aim of the study was to evaluate whether neonatal antibiotic exposure is relevant with longitudinal growth problems in preterm-birth children.
METHODS: This prospective study enrolled 481 infants who were born <32 weeks of gestation, discharged, and longitudinally followed from corrected age (CA) 6-60 months. After excluding 153 infants with blood culture-confirmed bacteremia, necrotizing enterocolitis, severe cerebral palsy, intestinal ostomy, and congenital anomaly, 328 infants were included for analysis. Covariates included perinatal demographics, neonatal morbidities, extrauterine growth restriction, and antibiotic exposure accumulated by term equivalent age. The primary outcome was the anthropometric trajectories in z-score of bodyweight (zBW), body height (zBH), and body mass index (zBMI) from CA 6-60 months.
RESULTS: Antibiotic exposure duration was significantly negatively associated with zBW and zBH at CA 6, 12, and 60 months, and zBMI at CA 60 months. Multivariate generalized estimating equation analyses showed antibiotic exposure duration had significantly faltering z-score increment from CA 6 to 60 months in zBW and zBH (adjusted mean [95% CI]; ΔzBW: -0.021 [-0.041 to -0.001], p = 0.042; ΔzBH: -0.019 [-0.035 to -0.002], p = 0.027) after adjustment. Children with neonatal antibiotic exposure duration >15 days were significantly lower in the mean anthropometric zBW, zBH, and zBMI at CA 6, 12, 24, and 60 months compared with children with neonatal antibiotic exposure ≤15 days (all p < 0.01).
CONCLUSIONS: Growth increments were negatively associated with antibiotic exposure duration in preterm neonates implicating that antibiotic stewardship and growth follow-up for preterm neonates are thus warranted.

Biodiversity loss resulting from environmental pollution is a global concern. While interspecific interactions are central to ecology, the impact of environmental pollution on predator-prey interactions and its ecological consequences, such as extinction and biodiversity loss, remain unclear. To investigate the effects of antibiotic exposure on predation strength and the resulting ecological consequence, the Didinium-Paramecium was utilized as a predator-prey model and exposed to nitrofurazone or erythromycin, two common pollutants, respectively. Initially, we determined prey population growth dynamics, body size, and predator numerical-functional responses. Subsequently, these above parameters were integrated into a mathematical model of predator-prey predation. Then both the long time-series data and phase portraits obtained through model simulation were used to estimate interaction strength and to predict the outcome of predator-prey coexistence. Our results revealed that exposure to either antibiotic significantly reduced prey population growth parameters (e.g., μmax and K) while increasing individual body size. The combined effects of antibiotic exposure and predation pressure on population growth inhibition or body size promotion were variable, mostly additive, with a few cases of synergy and extremely rare antagonism, depending on antibiotic exposure concentration. As antibiotic exposure concentration increased, the predator rmax generally declined, while functional responses varied depending on specific parameters, implying a decrease in predator-prey interaction strength. Analyses of phase portrait features showed that the population oscillation amplitude decreased with increasing antibiotic exposure concentrations, the cycle length of adjacent peaks increased, and prey extinction occurred earlier. In conclusion, antibiotic exposure reduced both predator and prey fitness, underlying the reason antibiotics reduces the strength of predator-prey interaction. Despite the indirect benefits of prey gain from this, the presence of predators can expedite the process of prey extinction caused by antibiotic exposure.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab.
METHODS: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS).
RESULTS: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS.
CONCLUSIONS: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Marine periphytic ciliates play a pivotal role in shaping coastal ecosystems dynamics, thereby acting as robust biological indicators of aquatic ecosystem health and functionality. However, the understanding of the effects of veterinary antibiotics on composition and structure of periphytic ciliate communities remains limited. Therefore, this research investigates the influence of the veterinary antibiotic nitrofurazone on the community dynamics of marine periphytic ciliates through bioassay experiments conducted over a one-year cycle. Various concentrations of nitrofurazone were administered to the tested ciliate assemblages, and subsequent changes in community composition, abundance, and diversity were quantitatively analyzed. The research revealed significant alterations in periphytic ciliate communities following exposure to nitrofurazone. Concentration-dependent (0-8 mg L-1) decrease in ciliates abundance, accompanied by shifts in species composition, community structure, and community patterns were observed. Comprehensive assessment of diversity metrics indicated significant changes in species richness and evenness in the presence of nitrofurazone, potentially disrupting the stability of ciliate communities. Furthermore, nitrofurazone significantly influenced the community structure of ciliates in all seasons (winter: R2 = 0.489; spring: R2 = 0.666; summer: R2 = 0.700, autumn: R2 = 0.450), with high toxic potential in treatments 4 and 8 mg L-1. Differential abundances of ciliates varied across seasons and nitrofurazone treatments, some orders like Pleurostomatida were consistently affected, while others (i.e., Strombidida and Philasterida) showed irregular distributions or were evenly affected (e.g., Urostylida and Synhymeniida). Retrieved contrasting patterns between nitrofurazone and community responses underscore the broad response repertoire exhibited by ciliates to antibiotic exposure, suggesting potential cascading effects on associated ecological processes in the periphyton community. These findings significantly enhance the understanding of the ecological impacts of nitrofurazone on marine periphytic ciliate communities, emphasizing the imperative for vigilant monitoring and regulation of veterinary antibiotics to protect marine ecosystem health and biodiversity. Further research is required to explore the long-term effects of nitrofurazone exposure and evaluate potential strategies to reduce the ecological repercussions of antibiotics in aquatic environments, with a particular focus on nitrofurazone.

Understanding the source of methane (CH4) is of great significance for improving the anaerobic fermentation efficiency in bioengineering, and for mitigating the emission potential of natural ecosystems. Microbes involved in the process named direct interspecies electron transfer coupling with CO2 reduction, i.e., electrons released from electroactive bacteria to reduce CO2 into CH4, have attracted considerable attention for wastewater treatment in the past decade. However, how the synergistic effect of microbiota contributes to this anaerobic carbon metabolism accompanied by CH4 production still remains poorly understood, especial for wastewater with antibiotic exposure. Results show that enhancing lower-abundant acetoclastic methanogens and acetogenic bacteria, rather than electroactive bacteria, contributed to CH4 production, based on a metagenome-assembled genomes network analysis. Natural and artificial isotope tracing of CH4 further confirmed that CH4 mainly originated from acetoclastic methanogenesis. These findings reveal the contribution of direct acetate cleavage (acetoclastic methanogenesis) and provide insightsfor further regulation of methanogenic strategies.