Antibiotics-Basel最新文献

Background/Objectives: Carbapenemase-producing Escherichia coli (CP-Ec) has emerged as an important contributor to the global crisis of antimicrobial resistance. Although less prevalent than carbapenemase-producing Klebsiella pneumoniae, CP-Ec exhibits marked genomic plasticity, efficient plasmid-mediated dissemination, and increasing involvement in bloodstream infections. This comprehensive review summarizes the global epidemiology, molecular features, treatment options, clonal structure and transmission dynamics of CP-Ec. Particular attention is given to the expanding repertoire of NDM, OXA-48-like, and KPC carbapenemases and their associated plasmid backbones. Key high-risk clones, including ST410, ST167 and ST131, are highlighted as drivers of international spread. Conclusions and Future Directions: CP-Ec bloodstream infections represent a growing clinical challenge, often associated with severe outcomes and limited therapeutic options, particularly for NDM producers. The emergence of treatment failures with last-resort agents further underscores the need for improved management strategies. Strengthened global surveillance, integration of genomic epidemiology, optimized antimicrobial stewardship, and targeted infection control measures are essential to limit the dissemination of CP-Ec and mitigate its impact on human health.

Introduction: Infections attributed to multidrug-resistant organisms have resulted in a significant clinical burden, high mortality, and excessive costs. Identifying the most appropriate and efficacious treatments will aid in reducing these burdens. Imipenem/cilastatin + relebactam (I/R) is used against multidrug-resistant infections providing an alternative option which may support patients where traditional treatments are no longer effective. Objective: The objective was to evaluate the efficacy of I/R for complicated urinary tract infections, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia, based on data aggregated from randomized controlled trials. Method: Two systematic literature reviews were conducted to include randomized controlled trials which aligned with the inclusion criteria reporting on the efficacy of I/R against placebo or other comparators such as piperacillin/tazobactam or colistin. The outcomes of interest were mortality, clinical response, and microbiological response. Results: The results found reduced mortality and comparable clinical and microbiological response with I/R versus its comparators. I/R displayed the largest favorable clinical and microbiological responses within high-risk populations, including those with severe renal impairment when compared with piperacillin/tazobactam. Conclusions: These findings support the efficacy of I/R for key Gram-negative infections, particularly within vulnerable patient populations. Despite the favorable outcomes reported, there is a need for further real-world evidence generation to support the efficacy of I/R to aid in standardizing treatment guidelines and reducing the clinical and economic burden associated with multidrug-resistant bacterial infections.

Background/Objectives: Granulicatella adiacens infective endocarditis is conventionally managed with penicillin, ampicillin, or ceftriaxone in combination with gentamicin, although double beta-lactam regiments have been proposed a safer alternative to reduce aminoglycoside-associated nephrotoxicity. To date, the High-Molecular-Mass Penicillin-Binding Proteins (HMM-PBPs) of G. adiacens and their affinities for beta-lactam antibiotics have not been previously characterized. This study investigated the HMM-PBP profile of G. adiacens, with particular interest on sequence alterations and beta-lactam binding properties, both as single agents and in combination. Methods: Beta-lactam activity, synergistic interactions and PBP binding affinities were evaluated in a clinical isolate (IS 48) and compared with those in the reference strain ATCC 49175. Binding of PBPs to ampicillin, ceftriaxone, and ceftobiprole, alone or in combination, was investigated by Bocillin-FL labeling. PBP homology and conserved active-sites motifs were assessed by sequence alignment, and pbp gene mutations were identified by whole-genome sequencing. Results: The clinical isolate was non-susceptible to ampicillin, resistant to ceftriaxone and exhibited higher minimum inhibitory concentrations (MICs) for ceftobiprole relative to the fully susceptible ATCC reference strain. Five HMM PBPs with high enterococcal homology, were identified. In the IS 48 isolate, the class A PBP showed distinct amino acid substitutions in proximity to the catalytic centers. Despite these alterations, PBP1A and PBP2A were strongly inhibited by the tested beta-lactams, whereas PBP2 and PBP2B demonstrated low acylation rates. Combination of ampicillin with either ceftobiprole or ceftriaxone resulted in enhanced acylation of the three bifunctional HMM PBPs compared with monotreatment. IC₅₀ values were consistently higher for the IS 48 clinical isolate, suggesting decreased target availability and/or reduced beta-lactam affinity under clinical conditions. Conclusions: The resistance phenotype of G. adiacens clinical isolate appears to be primarily associated with altered PBP beta-lactam interactions. Nonetheless, beta-lactam combination regimes remain effective by achieving substantial inhibition of key HMM-PBPs involved in peptidoglycan synthesis, thereby supporting the rationale for dual beta-lactam therapy in this setting.

Background: Multidrug-resistant bacteria have quadrupled globally, impacting effective treatment of infectious diseases. A growing concern is that many Gram-negative and Gram-positive bacteria harbor genes conferring resistance to various antibiotics including colistin. The alarming emergence of colistin resistance is exacerbated by the growing threat of MDR Salmonella species and Listeria monocytogenes (LMO), which pose an escalating risk to global public health. Materials and Methods: In the present study, red meat samples were collected from randomly selected key retail markets in the Eastern Cape province, South Africa, and were evaluated for the incidence of LMO and the Salmonella species using standard culture-based and molecular methods. The confirmed isolates were subjected to antibiotic susceptibility testing. Results: This study demonstrated the occurrence of multidrug-resistant LMO (62%) and Salmonella species (spp.) (58%) in the red meat specimen. There were high resistance rates in both LMO and Salmonella isolates, with LMO exhibiting resistance to penicillin (89%), colistin (81%), nitrofurantoin (78%), and erythromycin (29%), while Salmonella showed resistance to trimethoprim (96.87%), tetracycline, and colistin (90.62%). Antibiotic resistance genes were also detected including BlaTem, erm, Sul1, Sul2 and mcr 1-6. Notably, Salmonella did not harbor any mcr genes that were screened in this study, whereas Listeria isolates harbored the mcr 2 (10%), 3 (7%), 4 (10%), and 6 (3%), with mcr 5 being the most prevalent with 57%. Conclusions: These findings highlight a threat to food security and public health, emphasizing the need for sturdier food handling procedures to ensure safety, enhanced antimicrobial stewardship, and alternative therapeutic strategies to combat antibiotic-resistant pathogens.

Background/Objectives: Azithromycin is widely recommended as the first-line treatment for pediatric Campylobacter enterocolitis, although supporting evidence is limited and there is a lack of studies evaluating the efficacy of other macrolide antibiotics. This study aims to assess the effectiveness of starting macrolide therapy within three days of symptom onset in pediatric patients with Campylobacter enterocolitis. Methods: Pediatric patients under 19 years of age with a new diagnosis of Campylobacter enterocolitis were enrolled and randomly assigned to receive macrolide antibiotic treatment with either azithromycin or clarithromycin in a 1:1 ratio. Additionally, a retrospective historical cohort of pediatric patients diagnosed with Campylobacter enterocolitis prior to the study period, who did not receive macrolide antibiotics, was retrospectively reviewed for comparison. This dual approach allowed for the evaluation of macrolide therapy's effectiveness against untreated cases. Results: The study included 27 patients in the macrolide group and 37 patients in the non-macrolide group. Baseline demographic and clinical characteristics were comparable between groups. Early macrolide therapy was associated with reduced hospital stay (3.8 ± 0.7 vs. 4.5 ± 0.9 days), shorter duration of diarrhea (1.8 ± 1.2 vs. 3.4 ± 0.7 days, p < 0.001), and shorter duration of fever (1.1 ± 0.6 vs. 2.8 ± 1.0 days, p < 0.001). No significant difference was observed in the duration of vomiting (p = 0.061). Conclusions: Early initiation of macrolide antibiotics in children with Campylobacter enterocolitis significantly accelerated complete clinical resolution and shortened hospitalization, particularly by hastening the resolution of diarrhea, fever, and abdominal pain. These findings support the use of early macrolide therapy for pediatric Campylobacter enterocolitis.

Background/Objectives: Oral infections are caused by a wide spectrum of bacterial and fungal species and remain clinically challenging, particularly against the background of increasing antimicrobial resistance and efforts to reduce antibiotic use in dentistry. Platelet concentrates are widely applied in periodontal and oral surgery due to their regenerative and immunomodulatory properties, and accumulating evidence suggests additional antimicrobial effects. This study evaluated the antimicrobial activity of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and injectable PRF (i-PRF) against clinically relevant oral microorganisms. Methods: PRP, PRF, and i-PRF were prepared from venous blood of five healthy donors and evaluated using diffusion-dependent, qualitative-semiquantitative agar diffusion assays against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Staphylococcus aureus, Streptococcus mutans, Streptococcus mitis, Enterococcus faecalis, and Candida albicans, with inhibition zones assessed after species-specific incubation times. Chlorhexidine (2%) and amoxicillin served as positive controls and NaCl (0.9%) as negative control. Inhibition zones were digitally quantified and analyzed using non-parametric statistics (Kruskal-Wallis, Friedmann) due to skewed distributions and frequent zero values. Results: All platelet concentrates demonstrated microorganism-dependent inhibition zones in vitro. Overall, i-PRF demonstrated the strongest inhibitory effect across all pathogens (p < 0.001). Significant differences were detected for E. faecalis and C. albicans, where i-PRF produced markedly larger inhibition zones compared to PRP and PRF. Descriptively, anaerobic periodontal pathogens and S. aureus tended to be more susceptible, while streptococci and C. albicans demonstrated lower inhibition. Conclusions: These findings support a potential adjunctive antimicrobial role of platelet-derived preparations in dental infection management but should be interpreted with caution, as agar diffusion results do not necessarily reflect clinical performance.

Objectives: Acute obstructive pyelonephritis (AOP) is a urological emergency that combines bacterial infection with upper urinary tract obstruction. This retrospective study focuses on the microbial etiology and causes of obstruction, clinical manifestations, antibacterial therapy, drainage type, and outcomes in patients diagnosed with AOP at a tertiary urology center between 1 January 2020 and 30 December 2024. Methods: One hundred patients with a mean age of 61.30 years were included in this retrospective study, which examines demographic data, comorbidities, clinical features, pathogens involved, antimicrobial regimens, and hospital outcomes. Results: Urolithiasis was the most frequent cause of obstruction (62%), followed by ureteral stenosis (14%) and tumors (11%). AOPs were mainly produced by Escherichia coli (58%), followed by Klebsiella spp. (21%); 18% of all identified bacteria were ESBL-producing Gram-negative bacilli, and 29% were MDR bacteria. The most used IV antibiotics were fluoroquinolones (52%), followed by cephalosporins (19%) and carbapenems (18%). Carbapenems were administered to all patients with AOP caused by ESBL-producing pathogens and to 62% of those with MDR bacteria. The duration of antibiotic therapy was individualized based on clinical response. Switch to oral administration was made after 4.3 ± 1.5 days, and the antibiotic treatment lasted 10.8 ± 3.2 days. Conclusions: The results of the present study support integrating evidence-based guidelines with regional patterns of bacterial susceptibility to optimize therapeutic approaches and reduce severe outcomes in patients with AOP, most of whom have multiple comorbidities.

Background/objectives: Recent investigations point to red foxes (Vulpes vulpes) as a very potent sentinel species for monitoring the dissemination of antimicrobial bacteria in wildlife habitats.

Methods: This study investigated antimicrobial resistance in red foxes from 16 hunting grounds (peri-urban and peri-rural) in western Romania, between 2022 and 2024, in order to evaluate the species as "One Health" sentinels at the wildlife-human-animal interface. During this period, 137 bacterial strains previously identified from 216 samples were phenotypically tested using both the Kirby-Bauer disk diffusion method and the Vitek 2 Compact system.

Results: Among the Gram-negative isolates, particularly Escherichia coli and Salmonella enterica, notable antimicrobial resistance and multidrug-resistant (MDR) phenotypes were observed, including resistance to third-generation cephalosporins (ceftazidime) and reduced susceptibility to carbapenems. Resistance patterns observed in Proteus spp. largely reflected intrinsic resistance traits. Methicillin-resistant and MDR staphylococci (Staphylococcus aureus, S. pseudintermedius and S. sciuri) were detected in both peri-urban and peri-rural hunting grounds, with higher frequencies observed in peri-rural areas. Although MDR prevalence was slightly higher in peri-urban compared to peri-rural sites, no statistically significant association was identified between area of isolation and antimicrobial resistance or MDR status. Antimicrobial susceptibility results obtained by disk diffusion and the Vitek 2 Compact system showed a high level of concordance for antibiotics tested in common.

Conclusions: Overall, these findings support the use of red foxes as effective One Health sentinels for monitoring environmental antimicrobial resistance occurrence across wildlife, domestic animals, and human-impacted habitats.

Background/Objective: To identify the risks and outcomes of extensively drug-resistant Gram-negative bacilli (XDR-GNB) in neonates. Methods: This retrospective case-control study (1995-2024) included neonates with late-onset sepsis (n = 132) and XDR-GNB bacteremia (n = 26) compared with those without XDR-GNB (n = 106). Results: Median gestational age was 31 weeks and birth weight 1540 g. The prevalence of XDR-GNB was 19.7%. The most common XDR-GNB and non-XDR-GNB pathogens were Acinetobacter baumannii and Klebsiella pneumoniae. Sepsis onset occurred earlier in the XDR-GNB group than in the non-XDR-GNB group (7.0 vs. 12.5 days, p = 0.005). In multivariable analysis using Firth's penalized likelihood method, the XDR-GNB group was more likely to have gastrointestinal anomalies (adjusted odds ratio 3.81, 95% confidence interval 1.24-12.01, p = 0.02) and history of umbilical arterial catheterization (adjusted odds ratio 3.04, 95% confidence interval 1.21-7.95, p = 0.02) compared to the non-XDR-GNB group. The XDR-GNB group had higher rates of septic shock (50.0% vs. 18.9%, p = 0.002) and inadequate empiric antimicrobial therapy (34.6% vs. 13.2%, p = 0.02). The non-susceptibility rates to third-generation cephalosporins, gentamicin, carbapenems, amikacin, and colistin were 83.3%, 58.3%, 48.1%, 30.4%, and 4.4%, respectively. Conclusions: Empirical colistin treatment is warranted for neonates in high-XDR environments who exhibit septic shock and have specific risk factors, such as gastrointestinal anomalies or the presence of an umbilical arterial catheter. Multimodal interventions, including antimicrobial stewardship programs, have been used to prevent or reduce the incidence of neonatal XDR-GNB sepsis.

Introduction: Cutibacterium acnes, a component of normal skin flora and a common commensal Gram-positive bacterium, presents a diagnostic challenge for arthroplasty surgeons. While Cutibacterium acnes (C. acnes) as a source of infection has been well characterized in shoulder surgery, its presentation and clinical significance in total hip (THA) and total knee arthroplasty (TKA) remain less understood.

Methods: A retrospective chart review identified patients with C. acnes culture positivity following THA or TKA. Demographics, laboratory values, and microbiologic data were collected. Statistical comparisons were performed using t-tests and chi-squared analysis. One-year outcomes were evaluated using the Musculoskeletal Infection Society Outcome Reporting Tool (MSIS ORT) criteria among patients undergoing further surgical intervention.

Results: Twenty-nine patients with C. acnes-positive cultures were identified (21 THA, 8 TKA); 15 (52%) were polymicrobial. Ten THA patients (47.6%) and seven TKA patients (87.5%) met MSIS criteria for infection at the time of presentation. Mean time to culture positivity was similar between THA (6.8 days) and TKA (7.4 days; p = 0.57). Sonicated cultures were positive in 24% of THA and 12.5% of TKA cases. Mean ESR was 36.4 mm/h for THA and 51.5 mm/h for TKA (p = 0.21); mean C-reactive protein (CRP) was 35.2 and 36.8 mg/dL, respectively (p = 0.95). Mean synovial cell counts were 27,055 for THA and 22,194 for TKA, with polymorphonuclear cells (PMN) percentages of 68% and 73.9% (p = 0.72, 0.70). Monomicrobial infections demonstrated a mean cell count of 24,143 with 58.9% PMNs, compared to 25,903 and 78.8% in polymicrobial cases. At one year, 72% of patients undergoing subsequent surgery achieved successful outcomes. Higher ASA classification was the only significant predictor of failure (mean 3.0 vs. 2.75).

Conclusions: C. acnes-associated THA and TKA infections often present with delayed culture growth, mild inflammatory markers, and frequent polymicrobial involvement. At one-year, patients with available follow-up who undergo surgical management experience favorable outcomes, with 72% achieving MSIS ORT success.