International Journal of Antimicrobial Agents最新文献

Routinely used kidney biomarkers of injury and function such as serum creatinine and urine albumin to creatinine ratio, are neither sensitive nor specific. Future biomarkers are being developed for clinical use and have already been included in guidance from groups such as the U.S. Food and Drug Administration and the Predictive Safety Testing Consortium. These biomarkers have important implications for early identification of kidney injury and more accurate measurement of kidney function. Many antibiotics are either eliminated by the kidney or can cause clinically significant nephrotoxicity. As a result, clinicians should be familiar with new biomarkers of kidney function and injury, their place in clinical practice, and applications for antibiotic dosing.

Background: Empirical treatment needs to be supported by regional data, but knowledge of interregional differences is currently lacking in China. This study aimed to summarize and map the primary and secondary antibiotic resistance of H. pylori in different regions of mainland China.

Methods: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wanfang databases were systematically reviewed for studies published between January 1st, 2000 and July 15th, 2023. Data related to primary and secondary H. pylori antibiotic resistance rates were included. Random-effects models were used to synthesize the pooled resistance rates.

Results: Ultimately, 74 studies were included in the final analysis. Sixteen provinces reported resistance data. The overall resistance rates of H. pylori in mainland China were 30.72% (95% CI 27.53%-33.99%) to clarithromycin, 70.14% (95% CI 29.53%-37.46%) to metronidazole, and 32.98% (95% CI 28.73%-37.37%) to levofloxacin; for amoxicillin, tetracycline, and furazolidone, the rates were 2.41% (95% CI 1.43%-3.60%), 2.53% (95% CI 1.19%-4.28%) and 1.54% (95% CI 0.28%-3.62%), respectively. Spatial and temporal differences were observed. The resistance rates increased after treatment failure, however, secondary resistance to amoxicillin, tetracycline, and furazolidone were still low across the vast majority of study regions.

Conclusion: Surveillance of the updated prevalence of antibiotic resistance of H. pylori for different regions is warranted, which should factor into clinical decision making and guideline recommendations.

Objectives: This study aimed to investigate interspecies transfer of resistance gene bla_NDM-1 and intraspecies transfer of bla_KPC-2 in Serratia marcescens, and explore the epidemical and evolutionary characteristics of carbapenemase-producing S. marcescens (CPSM) regionally and globally.

Methods: Interspecies and intraspecies transfer of bla_KPC-2- or bla_NDM-1 were identified by antimicrobial susceptibility testing, plasmid conjugation and curing, discovery of transposable units (TUs), outer membrane vesicles (OMVs), qPCR, whole-genome sequencing and bioinformatic analysis. The genomic evolution of CPSM strains was explored by cgSNP and maximum-likelihood phylogenetic tree.

Results: CPSM S50079 strain, co-carrying bla_KPC-2 and bla_NDM-1 on one plasmid, was isolated from the blood of a patient with acute pancreatitis and could generate TUs carrying either bla_KPC-2 or bla_NDM-1. We identified the interspecies transfer of bla_NDM-1-carrying plasmid from Providencia rettgeri P50213, producing the identical bla_NDM-1-carrying TUs, to S. marcescens S50079K, an S50079 variant via plasmid curing, through bla_NDM-1-harboring plasmid conjugation and OMVs transfer. Furthermore, the intraspecies transfer of bla_KPC-2, mediated by IS26 from plasmid to chromosome in S50079, was identified. Likely, in another lung transplant patient, interspecies transfer of bla_NDM-1 carried by IncX3 plasmid was also identified among S. marcescens and Citrobacter freundii as well as Enterobacter hormaechei via plasmid transfer. Furthermore, 11 CPSM from 349 non-repetitive S. marcescens strains were identified in the same hospital and clonal dissemination, with carbapenemase evolution from bla_KPC-2 to both bla_KPC-2 and bla_NDM-1 was found in the 8 CPSM across four years. Finally, the analysis of 236 global CPSM from 835 non-repetitive S. marcescens genomes, retrieved from NCBI database, revealed long-term spread and evolution worldwide, and would cause the convergence of more carbapenemase genes.

Conclusions: Interspecies transfer of resistance gene bla_NDM-1 and intraspecies transfer of resistance gene bla_KPC-2 in CPSM were identified. Nosocomial and global dissemination of CPSM were revealed and more urgent surveillance was acquired.

Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV is known to cause conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated hemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JCPyV, on the other hand, is responsible for progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. While VST therapy has shown promise in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with hemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with hemorrhagic cystitis and BKPyV viremia, 32 patients with PML were treated with VST in the literature. The overall response was 82, 33, 35, and 10 complete, partial, non-response, and no-outcome-reported (NA), respectively. In conclusion, this review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasizing the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy.

Objectives: This study aimed to assess the incidence and risk factors of subsequent CRE infection among rectal carriers, and their association with geographic region and age.

Methods: A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to January 31^st, 2024). This study is registered with PROSPERO, CRD42023444420.

Results: Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9-25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2-34.5), followed by Europe (20.9%, 95% CI 12.5-30.8) and Asia (19.8%, 95% CI 12.7-27.9). Children had a greater incidence (26.7%, 95% CI 21.3-32.3) than adults (19.8%, 95% CI 14.9-25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (OR 4.95 95% CI 1.87-13.11). In Europe, admission to ICU was prominent (OR 2.76 95% CI 1.14-6.65). In America, use of a urinary foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to ICU was most notable in adult (OR 3.01 95% CI 1.80-5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39-55.47).

Conclusions: Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help developing more potent prevention and control measures to reduce CRE infection.

Pharmacokinetics and safety studies of innovative drugs is an essential part of drug development process. Previously we have developed novel drug for intravenous administration (lyophilizate) containing modified endolysin LysECD7-SMAP that showed notable antibacterial effect in different animal models of systemic infections. Here we present data on pharmacokinetics of endolysin in mice after single and multiple injections. Time-concentration curves were obtained, pharmacokinetic parameters for preparation (C₀, k_el t_1/2, AUC_0-∞, MRT, Cl_T, V_ss) were calculated. It was shown that although endolysin is rather short-living in blood serum (t_1/2 = 12.5 min) the therapeutic concentrations of LysECD7-SMAP (in degraded and non-degraded form) were detected for 60 min after injection that is sufficient for antibacterial effect. Based on the obtained data, it was proposed that endolysin distributes presumably in murine blood, degrades in blood and liver, and is eliminated via glomerular filtration. Safety profile of the preparation relating to general toxicity, immunotoxicity and allergenicity was assessed in rodents. It was demonstrated that LysECD7-SMAP in potential therapeutic (12.5 mg/kg), 10-fold (125 mg/kg) and 40-fold (500 mg/kg) doses showed no signs of intoxication and significant abnormalities after single and repeated i.v. administrations, preparation was non-immunogenic and induced minor and reversible allergic reaction in animal.

Background: Ventilator-associated pneumonia (VAP) constitutes a considerable challenge for patients in intensive care units (ICUs) and necessitates the development of effective preventive strategies. This study aimed to evaluate the clinical efficacy of inhaled antibiotics for preventing VAP.

Methods: PubMed, Embase, and ClinicalTrials.gov were searched until January 21, 2024. Randomized controlled trials (RCTs) investigating the clinical efficacy of inhaled antibiotics for VAP prevention were included.

Results: Seven RCTs, involving 1465 patients, of whom 734 were classified as the study group receiving inhaled antibiotics and 731 as the control group receiving placebo were included in this meta-analysis. Overall, the occurrence of VAP was significantly lower in the study group than in the control group (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.51 to 0.92). However, there were no significant differences in mortality (RR, 0.90; 95% CI, 0.74 to 1.09), length of stay in ICU (mean difference [MD], 0.10 days; 95% CI, -0.91 to 1.1) and hospital (MD, 0.30 days; 95% CI, -1.82 to 2.43), and mechanical ventilation (MV) duration (MD, 0.45 days; 95% CI, -0.45 to 1.35) between groups.

Conclusion: Inhaled antibiotics hold promise for mitigating the risk of VAP among critically ill patients. However, their impact on mortality, length of stay in ICU and hospital, and MV duration was not statistically significant.

Background: The increasing incidence of antibiotic-associated diarrhoea (AAD) is a serious health care problem. Dysbiosis of the gut microbiota is suspected to play a role in the pathogenesis of AAD, but its impact on the clinical outcomes of patients remains unclear.

Methods: Between May and October 2022, 210 patients with AAD admitted to a university hospital and 100 healthy controls were recruited. DNA extraction from stool specimens and shotgun sequencing were performed. Machine learning was conducted to assess profiling at different taxonomic levels and to select variables for multivariable analyses.

Results: Patients were classified into two groups: Clostridioides difficile infection (CDI, n = 39) and non-CDI AAD (n = 171). The in-hospital mortality rate for the patients was 20.0%, but the presence of C. difficile in the gut microbiota was not associated with mortality. Machine learning showed that taxonomic profiling at the genus level best reflected patient prognosis. The in-hospital mortality of patients was associated with the relative abundance of specific gut microbial genera rather than alpha-diversity: each of the five genera correlated either positively (Enterococcus, Klebsiella, Corynebacterium, Pseudomonas, and Anaerofustis) or negatively (Bifidobacterium, Bacteroides, Streptococcus, Faecalibacterium, and Dorea). Genes for vancomycin resistance were significantly associated with in-hospital mortality in patients with AAD (adjusted hazard ratios, 2.45; 95% CI, 1.20-4.99).

Conclusion: This study demonstrates the potential utility of metagenomic studies of the gut microbial community as a biomarker for prognosis prediction in AAD patients.

Background: The use of matrix-assisted laser desorption/ionization-time-of-flight mass spectra (MALDI-TOF MS) with machine learning (ML) has been explored for predicting antimicrobial resistance. This study evaluates the effectiveness of MALDI-TOF MS paired with various ML classifiers and establishes optimal models for predicting antimicrobial resistance and mecA gene existence among Staphylococcus aureus.

Materials and methods: The antimicrobial resistance against tier 1 antibiotics and MALDI-TOF MS of S. aureus were analyzed using data from the Database of Resistance against Antimicrobials with MALDI-TOF Mass Spectrometry (DRIAMS) and one medical center (CS database). Five ML classifiers were used to analyze performance metrics. The Shapley value quantified the predictive contribution of individual feature.

Results: The LightGBM demonstrated superior performance in predicting antimicrobial resistance for most tier 1 antibiotics among oxacillin-resistant S. aureus (ORSA) than all and oxacillin-susceptible S. aureus (OSSA) in both databases. In DRIAMS, MLP encompassed excellent predictive performance, expressed as accuracy/AUROC/AUPR, for clindamycin (0.74/0.81/0.90), tetracycline (0.86/0.87/0.94), and trimethoprim-sulfamethoxazole (0.95/0.72/0.97). In CS database, Ada and LightGBM retained excellent performance for erythromycin (0.97/0.92/0.86) and tetracycline (0.68/0.79/0.86), respectively. Mass-to-charge ratio (m/z) features of 2,411-2,414 and 2,429-2,432 correlated with clindamycin resistance, while 5,033-5,036 was linked to erythromycin resistance in DRIAMS. In CS database, overlapping features of 2,423-2,426, 4,496-4,499, and 3,764-3,767 simultaneously predicted mecA existence and oxacillin resistance.

Conclusion: The predictive performance of antimicrobial resistance against S. aureus using MALDI-TOF MS depends on database characteristics and ML algorithm selected. Specific and overlapping MS features are excellent predictive markers for mecA and specific antimicrobial resistance.