Antibiotics-Basel最新文献

Objectives: This study aimed to clarify the area under the curve (AUC) for obtaining better clinical outcomes and to demonstrate vancomycin dosing for achieving the AUC in haemodialysis (HD). Methods: The vancomycin concentration was measured before the second HD. The AUC_24-48h after the initial HD was assessed to evaluate its correlation with an early clinical response and to determine the dosing regimen, assuming an inter-dialysis interval of 48 h, even if the interval was 72 h. Results: An AUC/MIC ≥ 400 was an independent factor for an early response in treating MRSA infections and infections caused by methicillin-resistant Gram-positive organisms. An AUC of 600-700 μg·h/mL did not increase the incidence of adverse effects compared with that of <600 μg·h/mL. An AUC of 400-700 μg·h/mL was obtained in 90.5% of patients with a loading dose of 30 mg/kg followed by a maintenance dose of 10 mg/kg. Pre-dialysis concentrations were significantly higher than the trough concentration required in non-HD patients to achieve the same AUC category, and AUC_24-48h was strongly correlated with pre-dialysis concentrations (R² = 0.921). In a receiver operating characteristic curve, the cut-off value for an early response was 16.8 μg/mL for the pre-dialysis concentration/MIC. Conclusions: AUC_24-48h after the initial HD/MIC of ≥400 μg/mL improves the clinical outcomes in patients on HD, and the target PK/PD can be achieved with an upper range of the recommended dose. The pre-dialysis concentration may be a reliable surrogate for the AUC, and the vancomycin dose could be adjusted according to this PK target.

Background: Non-Hodgkin lymphoma (NHL) is a malignancy of the immune system that includes several subtypes, most commonly diffuse large B-cell lymphoma and follicular lymphoma. Its etiology is multifactorial, with risk factors such as immunosuppressive therapy, infections, chemical exposure, and advanced age. A key aspect is the bidirectional relationship between lymphoma and immunodeficiency, which increases susceptibility to recurrent infections and complicates disease management. Case presentation: One particularly challenging case during the COVID-19 pandemic involved a patient with a personal history of diffuse B-cell non-Hodgkin lymphoma, diagnosed 5 years earlier, who had undergone eight cycles of rituximab-based chemotherapy. The patient tested positive for SARS-CoV-2 for three consecutive months and experienced repeated urinary tract infections warranting more in-depth investigations. The uniqueness of this case lies in the rare association of non-Hodgkin lymphoma, suspected post-rituximab immunodeficiency, severe COVID-19 infection, and recurrent urinary tract infections, which complicated clinical management. Despite appropriate treatment for both respiratory and urinary infections, as well as eight cycles of chemotherapy, the patient's condition continued to deteriorate significantly, ultimately requiring intravenous immunoglobulin replacement therapy. Following the treatment, the patient presented a remarkable clinical improvement, with resolution of the signs and symptoms, and an absence of further recurrent infections. The patient remained clinically stable under regular immunoglobulin replacement therapy, with sustained infection control and improved quality of life. Conclusions: This case highlights the importance of assessing immune status in patients with a hematological malignancy, especially when recurrent infections persist.

Background/objectives: The mammalian microbiota constitutes a reservoir of antimicrobial resistance genes (ARGs), which can be shaped by environmental and anthropogenic factors. Although bat-associated bacteria have been reported to harbor diverse ARGs globally, the ecological and evolutionary determinants driving this diversity remain unclear.

Methods: To characterize ARG diversity in wildlife exposed to contrasting levels of human influence, we analyzed homologs of resistance mechanisms from the Comprehensive Antibiotic Resistance Database in shotgun metagenomes of bat guano. Samples were collected from a colony exposed to continuous anthropogenic activity in Spain (Salamanca) and from a wild, non-impacted bat community in China (Guangdong). Metagenomic analyses revealed marked differences in taxonomic and resistome composition between sites.

Results: Salamanca samples contained numerous hospital-associated genera (e.g., Mycobacterium, Staphylococcus, Corynebacterium), while Guangdong was dominated by Lactococcus, Aeromonas, and Stenotrophomonas. β-lactamases and MurA transferase homologs were the most abundant ARGs in both datasets, yet Salamanca exhibited higher richness and functional diversity (median Shannon index = 1.5; Simpson = 0.8) than Guangdong (Shannon = 1.1; Simpson = 0.66). Salamanca also showed enrichment of clinically relevant ARGs, including qacG, emrR, bacA, and acrB, conferring resistance to antibiotics critical for human medicine. In contrast, Guangdong exhibited a more restricted resistome dominated by β-lactamase and MurA homologs. Beta diversity analysis confirmed significant compositional differences between resistomes (PERMANOVA, R² = 0.019, F = 1.33, p = 0.001), indicating ecological rather than stochastic structuring.

Conclusions: These findings suggest that anthropogenic exposure enhances the diversity and evenness of resistance mechanisms within bat-associated microbiomes, potentially increasing their role as reservoirs of antimicrobial resistance.

Background: Wildlife is increasingly recognized as an important component in the epidemiology of zoonotic pathogens. Salmonella spp., a leading cause of foodborne disease worldwide, can circulate across human, domestic animal, and environmental interfaces. European hedgehogs (Erinaceus europaeus), a synanthropic species frequently inhabiting urban and peri-urban areas, may act as reservoirs or sentinels for Salmonella.

Objectives: The aim of this study was to investigate the prevalence, serotype distribution, and antimicrobial susceptibility profiles of Salmonella spp. isolated from European hedgehogs admitted to wildlife rehabilitation centers in Italy.

Methods: Fecal samples were collected from 100 European hedgehogs housed in five wildlife rehabilitation centers located in four Italian regions. Salmonella spp. were isolated using standard bacteriological methods, serotyped according to the Kaufmann-White-Le Minor scheme, and tested for antimicrobial susceptibility by broth microdilution for ampicillin, enrofloxacin, and sulfamethoxazole-trimethoprim. Minimum inhibitory concentrations (MICs) were interpreted following CLSI guidelines.

Results: Salmonella spp. was isolated from 30% of the animals sampled. Four serovars were identified, with S. Enteritidis (50%) and S. Typhimurium (36.7%) being the most prevalent, followed by S. Agona (10%) and S. Chester (3.3%). Antimicrobial susceptibility testing revealed a high level of susceptibility, with 90% of isolates sensitive to all tested antibiotics. One S. enteritidis strain showed resistance to enrofloxacin and sulfamethoxazole-trimethoprim, while two isolates exhibited intermediate susceptibility to enrofloxacin.

Conclusions: The detection of Salmonella serovars commonly associated with human infections in European hedgehogs highlights the potential role of this species in the ecology of zoonotic Salmonella. Although antimicrobial resistance levels were low, the presence of resistant and intermediate strains underscores the importance of continued surveillance. Despite some limitations related to the study design and sample representativeness, these results support the need for further large-scale investigations, reinforcing the need for integrated One Health surveillance strategies.

Background: Hospitals are recognized as point sources of antimicrobials in urban wastewater systems; however, comprehensive evaluations of their discharge profiles have not yet been conducted. Methods: This study presents a multi-site investigation of residual antimicrobial concentrations in effluents from five general hospitals and a commercial facility in the metropolitan area of Japan. Over a 12-week period (December 2023-March 2024), extensive sampling was conducted. Fifteen antimicrobials from multiple classes were quantified using high-throughput analysis. Results: The results revealed consistently higher concentrations in hospital effluents, particularly for levofloxacin, vancomycin, and ampicillin, than in non-clinical sites. Distinct facility-specific and temporal patterns suggest strong links between local prescribing practices and the effluent composition. Some compounds, such as clarithromycin and minocycline, showed dual contributions from both hospital and commercial sources. Conclusions: These findings highlight the need for source-targeted monitoring and antimicrobial pollution control strategies and provide a foundation for expanding surveillance efforts and informing environmental policies related to antimicrobial resistance (AMR).

Background: Early administration of antibiotics is commonly recommended for pneumonia in intensive care unit (ICU) patients. However, the clinical benefit of very early empirical treatment remains uncertain and may reflect differences in illness severity, baseline risk, or care pathways, particularly in non-septic or hemodynamically stable ICU populations. Methods: We performed a retrospective cohort study using the Medical Information Mart for Intensive Care IV (v2.2) database to evaluate the observational association between antibiotic timing and in-hospital mortality among adult ICU patients with pneumonia. Patients were categorized as receiving early (<3 h) or delayed (≥3 h) antibiotic therapy after ICU admission. A multivariable logistic regression model adjusted only for age and sex. Given the absence of detailed severity-of-illness measures, no causal inference was intended, and all analyses were considered hypothesis-generating. Additional analyses exploring antibiotic class, dosing frequency, and combination therapy were conducted in an exploratory manner, given substantial variation in sample sizes and a high risk of confounding by indication, misclassification, immortal-time, and survivorship bias. Results: Among 7569 ICU patients with pneumonia, 56.5% received antibiotics within three hours of ICU admission. Early antibiotic initiation was associated with higher in-hospital mortality than delayed therapy (26.1% vs. 21.5%; OR 1.30, 95% CI 1.16-1.44; p < 0.001). Because validated severity-of-illness measures were unavailable, residual confounding and confounding by indication are likely and may largely explain this association. A potential signal of increased mortality was observed in patients receiving ≥3 doses of levofloxacin (OR 4.39, 95% CI 1.13-17.02); however, this subgroup was small and the finding is highly susceptible to survivorship and indication bias. Mortality appeared lower in patients receiving two or three antibiotics compared with monotherapy, but marked group imbalances, lack of restriction or stratification, and clinical selection effects limit interpretability. Regimens involving ≥4 agents were rare and primarily associated with prolonged ICU length of stay rather than a clear mortality difference. Conclusions: In this large retrospective ICU cohort, very early antibiotic administration for pneumonia was observationally associated with higher in-hospital mortality. Causality cannot be inferred, and early treatment likely represents a marker of higher baseline risk or clinical urgency rather than a harmful exposure. These findings challenge the assumption that earlier antibiotic initiation is uniformly beneficial and underscore the importance of individualized, stewardship-aligned, and context-dependent decision-making regarding antimicrobial timing and intensity in critically ill patients.

Background: Antimicrobial resistance (AMR) is a major global health threat, and Cyprus reports one of the highest levels of community antibiotic consumption in the EU. Despite their central role in antibiotic access and counselling, the stewardship practices and perspectives of community pharmacists in this regulated setting are not well documented. Methods: We conducted semi-structured qualitative interviews with 20 community pharmacists to explore their perspectives on antibiotic use and AMR. Results: We analysed the data using reflexive thematic analysis, revealing five key themes: regulation and control of dispensing; pharmacist-patient interaction and misuse; antimicrobial stewardship and public education; safety and professional responsibility; and systemic barriers. Pharmacists reported strict adherence to prescription-only rules, and described regulation and e-prescribing as a practical 'shield' that legitimised refusals and redirected some misuse from overt non-prescription requests towards attempts to reuse, extend, or 'top up' prior prescriptions and household leftovers. They described managing frequent patient demands for antibiotics for self-limiting conditions and using brief counselling scripts, written aids, and symptomatic alternatives to promote appropriate use. Participants emphasised the risks of antibiotic-related harms, including AMR and other health consequences, while also highlighting workload, access constraints, and communication difficulties as barriers to effective counselling. Overall, the findings indicate that community pharmacists in Cyprus function as front-line antimicrobial stewards. Conclusions: These accounts position community pharmacists in Cyprus as front-line antimicrobial stewards. Policy should consider supporting this function by providing enhanced communication tools, improving access pathways for timely prescriber review (including outside routine hours), and strengthening links between community pharmacy and national AMR action plans.

Background: Carbapenem-resistant Escherichia coli (CREC) producing OXA-48-like carbapenemase was first detected in Hungary in 2022. The aim of the present study was to characterize such strains isolated in 2022-2025 in Baranya County, Hungary. Methods: Antibiotic susceptibility and the whole-genome sequence (WGS) of E. coli isolates, identified as OXA-48-like carbapenemase producers using the CARBA-5 NG test, were established. The transferability of bla_OXA-48-like plasmids was tested by conjugation. Results: Of the 6722 non-repeat E. coli isolates, 6 produced an OXA-48-like carbapenemase. They exhibited variable resistance to ertapenem and were susceptible to imipenem and meropenem. WGS revealed that all OXA-48-like producer E. coli belonged to high-risk clones: two clonally related OXA-181-producer E. coli ST405 were isolated in Hospital A, three OXA-244-producing E. coli ST38 (two identical via cgMLST from Hospital B), and an OXA-48-producing E. coli ST69. The bla_OXA-48 and bla_OXA-244 genes were chromosomally located, while bla_OXA-181 was on a non-conjugative IncFIB-IncFIC plasmid. So far, the bla_OXA-181-bearing plasmid of this incompatibility type has only been described in Ghana, but all bla_OXA-48-like gene-carrying transposons in this study have already been identified in Europe and other continents. The E. coli ST38 isolates, showing close association based on core genome SNP distances to European and Qatari strains, belonged to Cluster A and harbored bla_CTX-M-27. All but the E. coli ST69 isolate had cephalosporinase gene(s). Conclusions: This study describes small-scale intra-hospital transfers of OXA-48-like carbapenemase-producer E. coli. Interestingly, E. coli ST405 of Hungary carried bla_OXA-181 on an IncFIB-IncFIC plasmid, which has only been reported from Africa so far.

Background: This research aimed to investigate the antifungal and antibiofilm action of Lavandula angustifolia essential oil (LaEO) against certain Candida species and its toxicity on human keratinocytes. Methods: The minimum inhibitory concentration (MIC) and sessile minimum inhibitory concentration (SMIC) of LaEO were both determined by broth microdilution assays. The influence of LaEO treatment on the ultrastructural morphology of the biofilm and germ tubes was evaluated by scanning electron microscopy (SEM) and light microscopy. In vitro cytotoxicity studies were conducted using human HaCaT epidermal keratinocytes. Results: LaEO showed fungicidal action for all Candida species (125-4000 μg/mL). The SMIC_>90 (C. albicans) ranged between 10,000 and 20,000 μg/mL and resulted in quantitative and qualitative cellular changes. LaEO also inhibited the developmental germ tube kinetics of C. albicans. The 50% cytotoxic concentration (CI₅₀) for HaCaT cells was estimated at 420 μg/mL of LaEO, resulting in a selectivity index (SI) of 0.376 to 5.753 for planktonic cells and 0.056 to 0.321 for biofilm phases. Conclusions: LaEO was found to have antifungal action against Candida species and inhibited the pathogenic morphology of C. albicans. Its antibiofilm effects are comparable to the antifungal agent nystatin, and it can become an important component for the development of natural products applicable to alternative and complementary medicine and dentistry.

Background: The emergence of antibiotic-resistant bacteria is one of the top health concerns. Escherichia coli is a Gram-negative bacterium that commonly causes severe infections. However, this research exposed its antibiotic-producing potential.

Methods: Rifampicin-resistant mutants of E. coli C91 were generated to activate cryptic BGCs. Mutants (C91-R1, R2 and R3) were tested for antimicrobial production using agar-well diffusion assays. Metabolite profiling was performed by LC-MS/MS. Siderophore production was tested by construction of a Δycao deletion mutant. Growth of this mutant was assessed under iron-limited conditions versus iron-rich conditions using dipyridyl. qRT-PCR was used to analyze gene expression entB, mcmA and mchF. Genome mining was performed using antiSMASH and BAGEL4.

Results: Compared to the wild type, Mutant C91-R1(S531L) displayed clear antibacterial activity against Staphylococcus aureus. LC-MS/MS revealed unique metabolites, including a novel peak at m/z 410.5, specific to the mutant C91-R1. A reduction in siderophore production of 61% was demonstrated in the Δycao mutant, and downregulation of entB, mcmA and mchF. Conclusions: Genome mining predicted non-ribosomal peptide, thiopeptide and polyketide BGCs. E. coli C91 offers antibiotic-producing potential that can be activated through ribosome-engineering-type approaches. Moreover, E. coli C91-R1 has unique metabolites and is considered as a promising candidate for novel antibiotic discovery.