Antibiotics-Basel最新文献

Background: The outbreak and spreading of antimicrobial resistance (AMR) in a very short time has made most of the old-fashioned antibiotics ineffective, and thus new therapeutic substances have to be developed. The traditional methods of antibiotics discovery are defined by long periods of time, high levels of expenditure, and high rates of failure, which contributes to the necessity of new approaches. Artificial intelligence (AI) has become a disruptive technology that can be used to accelerate and optimize various steps of antibiotic discovery, such as target detection and virtual screening, new molecular design, and early-stage testing.

Methods: This review provides an in-depth discussion of the role of AI methodologies in the form of machine learning, deep learning, natural language processing, and generative models in the discovery of small-molecule antibiotics and antimicrobial peptides (AMPs). The major areas that are discussed include virtual screening, pharmacokinetics optimization, resistance mechanism prediction, and AMPs design, which is accompanied by relevant case studies, including the AI-based discovery of Abaucin.

Results: The article highlights how AI can be used in a synergistic relationship with synthetic biology, nanotechnology, and multi-omics data as a core component in the next generation of antimicrobial approaches, such as personalized therapy and predictive stewardship. The existing issues, i.e., the lack of data, bias in algorithms, and the translational divide between research and clinical use, are addressed, as well as suggested measures of responsible, collaborative, and ethical AI use.

Conclusions: The combination of computational innovation with experimentation validation, AI-driven antibiotic discovery paves the way for a potent and scalable approach in addressing the rising threat of AMR.

Background/Objectives: Severe respiratory infections remain a major cause of morbidity and mortality in critically ill patients admitted to an intensive care unit (ICU), particularly in the context of increasing antimicrobial resistance (AMR). This study aimed to describe the clinical, microbiological and resistance profiles of ICU patients diagnosed with hospital-acquired or ventilator-associated pneumonia. Methods: We conducted a retrospective, single-center observational study including adult ICU patients admitted between January and December 2025, with clinically significant positive endotracheal aspirates. Clinical severity scores (APACHE II, SOFA, SOFA-2), inflammatory biomarkers (neutrophil-to-lymphocyte ratio-NLR, platelets-to-lymphocyte ratio-PLR, C-reactive protein-CRP), microbiological findings, antimicrobial resistance patterns and ICU-related outcomes were analyzed. Results: Out of the 606 endotracheal aspirates collected, 76 (12.5%) were culture-positive and 62 (10.2%) patients met the final inclusion criteria. Ventilator-associated pneumonia accounted for 90% of infections, 25 episodes (44.6%) being classified as early-onset and 31 cases (55.4%) as late-onset, without significant differences in bacterial distribution between the two subtypes. In total, 85.5% of infections were monomicrobial, with Gram-negative bacteria representing 76% of isolates. Acinetobacter baumannii and Pseudomonas aeruginosa were the most frequently isolated pathogens, with high resistance rates. Acute kidney injury occurred in 25.8% of patients and was associated with higher APACHE II, SOFA, and SOFA-2 scores. Conclusions: Severe respiratory infections in critically ill patients were predominantly caused by Gram-negative, frequently drug-resistant pathogens and were associated with high disease severity and poor outcomes. These findings provide insight into the local epidemiology and antimicrobial resistance patterns of severe respiratory infections in critically ill patients.

Background: Antimicrobial resistance (AMR) poses a critical global public health challenge requiring comprehensive intervention strategies, including robust antibiotic stewardship programs. The European Commission's 2017 One Health Action Plan against AMR established guidelines based on WHO's AWaRe classification system, which categorizes antibiotics into Access, Watch, and Reserve groups to promote prudent use. However, the proliferation of substandard and falsified (SF) medical products increasingly undermines these stewardship efforts, with European regulatory agencies, including Belgium's Federal Agency for Medicines and Health Products (FAMHP), reporting rising seizures of SF antibiotics. Objective: To assess the pharmaceutical quality of confiscated antibiotic samples and evaluate their potential contribution to AMR development. Methods: We conducted comprehensive pharmaceutical quality control testing on 40 SF antibiotic samples seized by the FAMHP between early 2024 and late 2025. Results: The analysis revealed significant deficiencies: 35% of samples contained antibiotics listed on international watch lists, while nearly 43% failed quality control testing. Dissolution defects represented the predominant failure mode, accounting for 29% of all samples tested. These defects can severely compromise drug bioavailability, clinical efficiency, and expose bacterial populations to sub-lethal concentrations of active pharmaceutical ingredients-a recognized driver of resistance development. Conclusions: Many seized samples appeared to be unregistered/unlicensed medicines that, while prohibited in the EU, may circulate legally elsewhere. This transnational dimension highlights how substandard products threaten global AMR control initiatives beyond individual patient safety. These findings underscore the urgent need to raise more awareness within the EU and for enhanced pharmaceutical quality assurance systems and much more international regulatory cooperation, particularly in low- and middle-income countries where such products circulate more readily.

Background: The increasingly indiscriminate use of antibiotic therapy in the neonatal period has led to the emergence of multidrug-resistant organisms (MDROs), which are responsible for sepsis that is increasingly difficult to treat and associated with high morbidity and mortality. Increasingly frequently, in neonatal intensive care units (NICUs), it is necessary to use last-generation antibiotics belonging to the RESERVE group according to the current classification of the World Health Organization (WHO). Methods: Among these drugs, ceftazidime-avibactam, ceftolozane-tazobactam and meropenem-vaborbactam are increasingly used in infections caused by Enterobacterales (i.e., E. cloacae complex, Klebsiella spp.), which are often responsible for late-onset sepsis (LOS) in newborns, especially in preterms. Results: Here, we present the experience of four newborn patients in the city of Palermo, treated over a period of 3 years. Conclusions: The comparison between different diagnostic-therapeutic management approaches and a review of the most recent literature can contribute to identifying more standardized pharmacological schemes, especially in the neonatal period, where scientific evidence about this topic is still very limited.

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) poses significant health risks to poultry and humans, with biofilm formation often complicating treatment by enhancing bacterial persistence and resistance. Understanding the genetic mechanisms underlying this lifestyle transition is crucial for controlling infections. This study aimed to investigate the effect of biofilm formation on the transcriptional expression of specific biofilm- and virulence-associated genes in chicken-derived ExPEC strains.

Methods: Biofilm formation conditions for three strong biofilm-producing chicken-derived ExPEC strains were optimized using an orthogonal experimental design (L₉(3³)), evaluating culture medium, incubation time, and initial inoculum concentration. Biofilm biomass was quantified via crystal violet staining. Subsequently, the transcription levels of 10 biofilm-associated genes and 17 virulence-associated genes were compared between planktonic and biofilm states using Reverse Transcription-quantitative PCR (RT-qPCR).

Results: Optimal culture conditions varied among strains, though nutrient-rich media consistently promoted rapid biofilm formation. Transcriptional analysis revealed significant reprogramming in the biofilm state. Among biofilm-associated genes, flhC, tolA, qseC, mhpB, and bdcR were consistently and significantly upregulated across all strains (p < 0.05). Regarding virulence determinants, the expression of eaeA, LT, fimH, ompF, and iss was significantly upregulated (p < 0.05), whereas Sta levels were significantly reduced (p < 0.05).

Conclusions: Biofilm formation induces a distinct transcriptional shift in chicken-derived ExPEC, simultaneously enhancing the expression of key genes involved in biofilm maintenance and pathogenicity. The conserved upregulation of flhC, tolA, qseC, mhpB, and bdcR suggests these genes are critical drivers of biofilm development. Consequently, they represent potential targets for novel therapeutic strategies aimed at preventing E. coli infections and eradicating biofilms in clinical and agricultural settings.

Antimicrobial stewardship in the neonatal intensive care unit is a critically important tool to optimize clinical outcomes. The ideal duration of antimicrobial treatment is a key area that contains many knowledge gaps. This narrative review has three aims. One, to highlight the existing evidence for empiric and definitive antibiotic treatment durations for infants; two, to focus on clinical situations where further studies are needed; and three, to propose a rational, goal-based approach to clinical studies that provide for infant safety as shorter treatment durations are investigated.

Background/Objectives: The rising prevalence of extended-spectrum beta-lactamase (ESBL)-producing pathogens has emerged as a significant challenge in the treatment of pyelonephritis. This study aims to determine the frequency of ESBL-producing agents in hospitalized patients with pyelonephritis, identify associated risk factors, and assess the appropriateness of empirical antimicrobial therapy. Methods: This prospective study included patients hospitalized with pyelonephritis in the Infectious Diseases Clinic of Ankara Training and Research Hospital between 1 October 2022 and 29 February 2024. Demographic features, comorbidities, urinary system pathologies, history of urinary tract interventions, hospitalization more than one month prior, antibiotic use within the previous three months, and prior urinary tract infections were compared between patients infected with ESBL-producing and non-ESBL-producing organisms. Antimicrobial susceptibility profiles and the appropriateness of empirical treatments were evaluated. Statistical analyses were performed using SPSS version 25.0, with p < 0.05 considered statistically significant. Results: Escherichia coli (n = 142) and Klebsiella spp. (n = 43) were isolated in 180 of 204 patients. ESBL positivity was detected in 95 patients (52.7%). In the multivariate logistic regression analysis, male sex (p = 0.038) and hospitalization more than one month prior (p = 0.016) were identified as independent risk factors for ESBL positivity, while prior antibiotic use in the last three months showed a borderline association (p = 0.055) and did not reach statistical significance. ESBL production was not associated with prolonged hospitalization; however, bacteremia significantly increased length of stay (p < 0.001). Antimicrobial susceptibility rates were markedly lower in the ESBL-positive group. The appropriateness of empirical therapy was also significantly reduced, with piperacillin-tazobactam being the most frequently inappropriate agent due to high resistance rates and unnecessary broad-spectrum use. Conclusions: ESBL-producing pathogens were highly prevalent among hospitalized patients with pyelonephritis. The low appropriateness of empirical therapy in ESBL-positive cases underscores the need for careful evaluation of ESBL risk factors prior to treatment initiation, as ESBL rates may approach 50%.

Antibiotic use in critically ill children requiring respiratory support remains controversial, particularly in the absence of standardized guidelines for patients managed with non-invasive ventilation (NIV). Evidence in this area remains limited, and real-world data are therefore valuable. Objective: This retrospective single-center study aimed to describe antibiotic prescribing patterns and infectious outcomes in pediatric patients admitted to the intensive care unit (PICU) with respiratory failure, according to the type of respiratory support. Methods: Children aged 0-17 years admitted between January 2021 and February 2025 who required oxygen supplementation, NIV, or invasive mechanical ventilation (IMV) were included. Demographic characteristics, underlying conditions, infectious complications, antibiotic exposure, length of PICU stay, and outcomes were analyzed using descriptive statistics and univariate comparisons. Results: Eighty-nine patients were included. Ventilator-associated pneumonia (VAP) occurred exclusively in patients receiving IMV, and infection complications were observed more in this group compared to those receiving NIV (p = 0.005). Pseudomonas aeruginosa was the most frequently isolated pathogen. Antibiotics were administered in 82% of patients, with no significant association between the respiratory support and initiation of antibiotic therapy (p = 0.195). A higher number of antibiotics was administered in patients receiving IMV compared with those receiving oxygen therapy alone. Conclusions: Antibiotic use in children requiring respiratory support in the PICU was common and appears to be driven primarily by underlying disease and illness severity rather than by the ventilation modality alone. Infections specific to invasive ventilation, such as VAP, were more frequent in patients receiving IMV, while infection-related outcomes in non-invasive groups should be interpreted cautiously due to differences in diagnostic definitions. These findings are descriptive and hypothesis-generating and highlight the need for prospective multicenter studies to create evidence-based antibiotic stewardship strategies in pediatric critical care.

Background: Bone and joint infections (BJIs), including osteomyelitis, septic arthritis, and periprosthetic joint infections, typically require prolonged antimicrobial therapy and often involve complex outpatient management. Oritavancin, a long-acting lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections caused by Gram-positive bacteria, has emerged as a potential off-label option for BJIs owing to its favourable pharmacokinetic and pharmacodynamic properties. Objectives: To provide a comprehensive overview of the pharmacological rationale, microbiological activity, and available clinical evidence supporting the use of oritavancin in BJIs. Methods: A comprehensive narrative review of the literature was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL), focusing on publications from 2011 to 2025. Observational studies, case series, and case reports describing the off-label use of oritavancin in BJIs were considered. Results: The available literature primarily consists of observational studies and real-world experiences. Eighteen studies met the inclusion criteria. Oritavancin was most frequently evaluated for osteomyelitis (n = 14 studies), prosthetic joint infections (n = 10) and septic arthritis (n = 5). Multi-dose regimens, typically including a 1200 mg loading dose followed by weekly doses of 800-1200 mg, were the most commonly described strategies. Reported clinical success rates generally ranged from approximately 70% to over 90%. Oritavancin was overall well tolerated, with adverse events being mostly mild and self-limiting. Conclusions: Current evidence suggests that oritavancin may represent an effective and well-tolerated off-label option for selected patients with Gram-positive BJIs. Its use may offer practical advantages, including reduced hospitalization and avoidance of prolonged intravenous antimicrobial therapy, particularly in patients for whom standard treatment approaches are challenging.

Background/Objectives: Antimicrobial resistance (AMR) continues to expand under sustained exposure to conventional antibiotics, contributing to the emergence of multidrug- and pan-resistant bacterial pathogens. There remains a critical need for antimicrobial agents that maintain activity during prolonged selective pressure while minimizing the potential for resistance development. This study aimed to evaluate EVQ-218, a non-ionic silver-based antimicrobial, against World Health Organization-designated ESKAPE pathogens. Methods: EVQ-218 was assessed using extended serial passage experiments performed under both sub- and supra-minimum inhibitory concentration (MIC) conditions. Comparative resistance selection experiments were conducted in parallel using tobramycin and ciprofloxacin, and susceptibility was evaluated through MIC determination and phenotypic analysis. Results: Across extended serial passage experiments, EVQ-218 did not exhibit measurable increases in MIC or phenotypic indicators of adaptive resistance. In contrast, parallel exposure to tobramycin and ciprofloxacin resulted in rapid and sustained MIC elevation. Notably, isolates that acquired resistance to either comparator antibiotic retained susceptibility to EVQ-218, indicating a lack of cross-resistance. Mechanistic analyses were consistent with a non-lytic, intracellular mode of antibacterial activity involving disruption of sulfur-associated biomolecular processes, suggestive of a multi-site mechanism distinct from classical antibiotics. Conclusions: These findings support EVQ-218 as a promising broad-spectrum antimicrobial candidate with resistance-resilient activity and warrant further investigation of its potential role in addressing unmet needs in AMR therapeutics.