Antibiotics-Basel最新文献

Background: Empirical antibacterial therapy for febrile neutropenia requires adaptation to local epidemiology, a process that is often complex, time-consuming, and prone to human error. This study aims to address this challenge by developing a practical, data-driven tool to efficiently evaluate and adapt treatment protocols. Methods: We developed a novel, open-source computational script in Python (version 3.10), aided by large language models for code revision, to analyze antibiotic susceptibility data. The script was validated using a retrospective dataset of 237 Gram-negative bloodstream infections (BSIs) from 2015 to 2024 in cancer or hematopoietic stem cell transplant recipients at a tertiary care pediatric hospital in Italy. The script calculates efficacy metrics for both single agents and two-drug combinations. Results: Among the Gram-negative BSI strains analyzed, meropenem monotherapy demonstrated the highest efficacy (median 95.4%). In contrast, piperacillin/tazobactam and cefepime showed lower efficacy (80.3% and 81.8%, respectively). On the contrary, combination therapy, particularly with amikacin, significantly increased the efficacy of beta-lactams, elevating their effectiveness to a level comparable to meropenem. Conclusions: The developed script is a valuable tool for antimicrobial stewardship programs, offering a rapid and accessible method to validate international guidelines against local epidemiological data. While meropenem shows high efficacy, its broad use should be limited to prevent resistance. The combination of piperacillin-tazobactam and amikacin is identified as a robust and effective empirical treatment choice.

Objective: This study addresses antimicrobial resistance (AMR), a growing public health threat, by evaluating the role of chicken carcasses as possible vehicle for the spread of Escherichia coli O157:H7 and antimicrobial resistance genes (ARGs), with the aim of analyzing the association between bacterial load and the relative abundance of ARGs in samples obtained from an open and an enclosed market in Lima, Peru. Methods: SYBR Green qPCR was used to analyze 28 chicken carcasses from two local markets in the Lima metropolitan area (Enclosed market n = 13, and Open Market n = 15), detecting Escherichia coli O157:H7 and ARGs like bla_CTX-M, bla_TEM, and strA. Results: The bacterial load was higher in the enclosed market (5.062 log CFU/mL) than in the open market (3.875 log CFU/mL). E. coli O157:H7 was detected in 76.9% and 86.6% of samples, with average loads of 1.676 and 1.251 log CFU/mL, respectively. The relative abundance of bla_CTX-M and bla_TEM showed greater dispersion in the open market, whereas strA was more homogeneous in both markets. Significant positive correlation was found between E. coli load and ARGs abundance, stronger in the enclosed market (r = 0.904-0.945) and moderate to high in the open market (r = 0.794-0.920). Conclusions: The results demonstrate a significant correlation between E. coli O157:H7 load and ARGs, highlighting the need for a comprehensive approach within the framework of the "OneHealth" initiative.

Background/Objective: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia has limited treatment options, and sulbactam MIC interpretation varies with the antimicrobial susceptibility testing (AST) method. This study compared sulbactam MICs determined using broth microdilution (BMD) and the E-test and examined their associations with 28-day mortality. Methods: This secondary analysis used data from a randomized controlled trial comparing colistin plus sulbactam at 9 g/day versus 12 g/day in adults with CRAB pneumonia. The sulbactam MICs of 134 isolates were determined using BMD and the E-test. The agreement between methods across MIC ranges and associations between MICs, dosing, and 28-day mortality were analyzed. Results: Sulbactam MICs determined using BMD were lower than those obtained with the E-test (MIC50/90: 32/128 µg/mL vs. 96/≥256 µg/mL). Overall, agreement between methods was limited and depended on MIC level, with better agreement at lower MICs and marked discrepancies at higher MICs, where the E-test frequently overestimated the MICs. Using the IDSA breakpoint (MIC ≤ 4 µg/mL), susceptibility was identified in 6% of isolates with BMD and 3% with the E-test. A significant survival benefit with high-dose sulbactam (12 g/day) was observed in patients with BMD-determined MICs ≥ 128 µg/mL (HR 0.27; 95% CI, 0.077-0.956; p = 0.042), whereas no mortality association was seen when MICs were categorized using the E-test results. Conclusions: AST method selection substantially affects sulbactam MIC interpretation in CRAB pneumonia. BMD shows stronger correlation with clinical outcomes than the E-test, particularly at high MIC levels. High-dose sulbactam may benefit patients with highly resistant isolates, underscoring the need for accurate and standardized AST methods.

Background: The coexistence of antibiotic resistance genes (ARGs) and heavy metals in livestock manure poses critical challenges to vermicomposting technology. Objectives: This study aimed to clarify the zinc (Zn)-driven ARG dynamics over 60-day vermicomposting for livestock manure and provide a reference for taking appropriate measures to reduce the spread of ARGs in the environment. Methods: In a vermicomposting system using Eisenia fetida and treated with varying concentrations of Zn, high-throughput sequencing was employed to analyze microbial succession, while quantitative real-time PCR (qPCR) was performed to track the fluctuation patterns of ARG (tet-, erm-, qnr-, str-, chl-, bla-, mcr-ARGs) and mobile genetic element (MGE, intI1 and intI2) abundances over the 60-day treatment period. Results: Generally, sul- (10^-3-10^-1 copies/16S rRNA), tet- (10^-3-10^-2 copies/16S rRNA), and str-ARGs (10^-3-10^-2 copies/16S rRNA) are dominant in dairy manure. Vermicomposting significantly reduced total ARGs (88.62% removal), but Zn stress triggered concentration-dependent shifts. Low Zn (100-250 mg/kg) elevated tet-, erm-, and chl-ARGs via co-selective pressure and disrupted bacterial succession, while high Zn (500-1000 mg/kg) suppressed qnr- and mcr-ARGs but intensified horizontal transfer via cross-resistance. Conclusions: Vermicomposting maintained a greater ARG removal capacity across the Zn gradient (100-1000 mg/kg) than natural composting, proving an effective approach for reducing the threat of antibiotic resistance in bacteria even under high Zn stress. The link between Zn residues and the increased ARG dissemination risks underscores the challenge of co-contaminants, providing essential insights for developing vermicomposting strategies to mitigate ARG risks and ensure sustainable manure management.

Background/Objectives: The COVID-19 period was marked by changes in antibiotic use and in the incidence of bacterial infections. We examined the association between antibiotic use and the proportion of Escherichia coli bloodstream infections (BSI) that were third-generation cephalosporin-resistant (3GC-R), using the COVID-19 period as a natural experiment. Methods: Data for this ecological study came from Israeli national surveillance systems for BSI and antibiotic consumption in 2015-2023. We performed interrupted time series analyses with a 1-year lag to examine the impact of COVID-19 on the proportion of E. coli BSI that were 3GC-R. We used linear regression to test the association between antibiotic use and 3GC resistance. Results: The majority of national antibiotic use was in outpatient settings; it was stable between 2015-2019, dropped by 19.4% in 2020, then increased gradually, but in 2023 remained 10.8% lower than before the pandemic. Incidence of E. coli BSI per 100,000 population increased from 62.6 in 2015 to a peak of 66.0 in 2019, with a small, non-significant change in the proportion of E. coli BSI that were 3GC-R (0.339 in 2015 vs. 0.335 in 2020). In 2020, the incidence of both 3GC-susceptible and 3GC-R E. coli BSI decreased. In 2021, only 3GC-R BSI declined, resulting in the proportion resistant dropping significantly by 0.05 (95% CI: 0.03-0.07). Post-pandemic, BSI incidence rose but remained below the 2019 rate. The proportion resistant after 2021 rose by 0.02 per year relative to the pre-COVID slope (95% CI: 0.02-0.03), such that it was higher in 2023 (0.341) than in 2019 and 2015. There was a significant positive linear relationship between antibiotic use and resistance: the proportion of E. coli BSI that were 3GC-R increased by 0.02 for each increase of one defined daily dose of antibiotic per person (95% CI: 0.001-0.03). Conclusions: Reduced outpatient antibiotic use during COVID-19 was followed by a reduction in the proportion of E. coli BSI that were 3GC-R.

Introduction: The emergence and spread of multidrug-resistant infections has resulted in significant clinical and economic burdens. To address these infections, novel therapy combinations are needed. Ceftolozane/tazobactam is a treatment option that targets multidrug-resistant pathogens and may offer improved patient outcomes compared to traditional antibiotics that are now often ineffective. Objectives: Our objective was to collate findings from comparative efficacy studies to assess the efficacy of ceftolozane/tazobactam for the indications of complex intra-abdominal infection, complex urinary tract infection, ventilated hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Methods: Two systematic literature reviews were conducted, including randomized controlled trials comparing ceftolozane/tazobactam with other interventions for complex intra-abdominal infection, complex urinary tract infection, ventilated hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia indications. The outcomes of interest were mortality, clinical cure and microbiological eradication. Results: Ceftolozane/tazobactam was determined to be non-inferior to comparators for all outcomes of interest. All-cause mortality for ceftolozane/tazobactam displayed non-inferiority to meropenem, with the largest numerical differences in all-cause mortality displayed in susceptible patients, such as those with severe renal impairment. Similarly, the clinical cure and microbiological eradication for ceftolozane/tazobactam demonstrated non-inferiority compared to meropenem or levofloxacin. Conclusions: These reviews support the role of ceftolozane/tazobactam as an alternative option, particularly when MDR pathogens are suspected or documented. Their findings may contribute to the standardization of treatment guidelines, ultimately helping to reduce the clinical and economic burdens associated with these infections.

Triterpenoids are a diverse class of naturally occurring compounds with a wide range of pharmacological properties, including anticancer, anti-inflammatory, antimicrobial, and antiviral activities. Among them, ursolic acid (UA), oleanolic acid (OA), and betulinic acid (BA) have emerged as key scaffolds due to their broad therapeutic potential and structural versatility. However, the clinical application of these compounds is often limited by issues such as poor solubility, bioavailability, and selectivity. To address these challenges, research conducted between 2015 and 2025 increasingly focused on the development of triterpenoid-based hybrid molecules, in which the triterpenoid scaffolds are chemically linked to other bioactive pharmacophores. This approach aims to enhance therapeutic efficacy through synergistic action, improved pharmacokinetics, and multitarget interactions. This comprehensive review explores recent advancements in the design, synthesis, and evaluation of hybrid derivatives of selected triterpenoids, particularly UA, OA, and BA. Emphasis is placed on the structure-activity relationships (SARs), biological evaluations, and mechanisms of action of these hybrid compounds across various disease models. The review also highlights current challenges, research gaps, and future perspectives in the rational development of triterpenoid-based hybrids as potential leading candidates in drug discovery.

Background: Antimicrobial consumption (AMC) varies widely across European countries, and cross-national studies have linked this variation to cultural values. However, two critical gaps remain: it is unclear whether these associations differ between community and hospital sectors or across antimicrobial classes. This study directly tests these differences.

Methods: We analysed country-level AMC data from the European Centre for Disease Prevention and Control for EU/EEA countries, combining sector-specific (community, hospital) and Anatomical Therapeutic Chemical (ATC) group-specific data. Spearman's rank correlation coefficients (ρ) were calculated between Hofstede's cultural dimensions and AMC. We compared correlations across sectors within ATC groups, and between community antibacterials for systemic use (J01) and other community medicine classes, using differences in correlations (Δρ). Uncertainty was assessed with non-parametric bootstrap 95% confidence intervals and paired-label permutation tests, with false discovery rate control. Sensitivity analyses included leave-one-country-out checks and replication using Kendall's τ-b.

Results: Cultural values, especially Power Distance Index (PDI) and Uncertainty Avoidance Index (UAI), were more strongly associated with community antibiotic use than with hospital antibiotic use or other community medicine groups. PDI and UAI showed significantly stronger correlations with community J01 use than with hospital J01 use and with several other community ATC groups. These patterns were robust in sensitivity analyses.

Conclusions: The national cultural context appears more closely related to community antibiotic use than to hospital use or other community medicines, particularly for PDI and UAI. This demonstrates that cultural drivers of AMC are context-specific, necessitating stewardship strategies tailored to community settings to address norms around hierarchy and uncertainty.

Background: The emergence of polymyxin-resistant, carbapenem-resistant Klebsiella pneumoniae (CRKP) presents a critical challenge to clinical management. This study aimed to delineate the molecular mechanisms driving the acquisition of polymyxin resistance in CRKP. Methods: We analyzed polymyxin-susceptible and polymyxin-resistant CRKP isolates obtained from a single patient. Antimicrobial susceptibility testing was performed to determine the minimum inhibitory concentrations. Whole genome sequencing was employed to identify variations in two-component systems and to screen for mcr genes, which were involved in polymyxin resistance. Differential gene expression was assessed using RNA sequencing and validated by quantitative real-time PCR. Furthermore, site-directed mutagenesis was utilized to confirm the causal role of specific mutations in conferring the resistant phenotype. Results: An L96P mutation in the PhoQ protein was found in the polymyxin-resistant CRKP isolate. Compared with the PhoQ wild-type, this mutation significantly upregulated expression of phoP/Q, pmrD, and arnBCADTEF operon-related genes. A corresponding L96P mutant was subsequently constructed in the polymyxin-susceptible ATCC 13883 strain via site-directed mutagenesis. Antimicrobial susceptibility testing confirmed that the PhoQ L96P mutation elevates the minimal inhibitory concentrations of colistin and polymyxin B to 64 mg/L and >32 mg/L, respectively, from a baseline of 0.5 mg/L. Conclusions: The PhoQ L96P mutation is a pivotal driver of polymyxin resistance in CRKP, primarily mediated through the upregulation of the arnBCADTEF operon.