ObjectivesThe aim of this work was to investigate the activity of ceftazidime–avibactam (CZA) and aztreonam–avibactam (AZA) against bloodstream infections caused by carbapenem-resistant organisms (CROs).MethodsNon-duplicate CROs, including 56 carbapenem-resistant Escherichia coli (CR-Eco), 318 carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), and 65 carbapenem-resistant Pseudomonas aeruginosa (CR-Pae), were collected using the Blood Bacterial Resistant Investigation Collaborative System (BRICS) program in China. The minimum inhibitory concentrations (MICs) of 24 antibiotics were tested. Carbapenemase genes were amplified for CZA-resistant CROs by PCR. The MICs of CZA and AZA were further determined with avibactam at 8 and 16 mg/L, respectively.ResultsThe resistance rate of polymyxin B against CROs was less than 5%. Only one CR-Kpn was resistant to tigecycline. The resistance rates of CZA against CR-Eco, CR-Kpn, and CR-Pae were 75.0%, 12.6%, and 18.5%, respectively. The MIC90 values of AZA against CR-Eco, CR-Kpn, and CR-Pae were 2/4, 1/4, and 64/4 mg/L, respectively. Among the CZA-resistant CROs, 42 (100%) CR-Eco, 24 (60%) CR-Kpn, and 1 (8.3%) CR-Pae isolates harbored metallo-β-lactamase genes. The increase of avibactam concentration enhanced the susceptibility of CZA and AZA against CROs, especially for CR-Eco and CR-Kpn.ConclusionsThe in vitro activity of AZA was superior to that of CZA against CR-Eco and CR-Kpn, whereas CZA showed better effect against CR-Pae.

Ceftazidime/avibactam (CAZ/AVI), a combination of ceftazidime and a novel β-lactamase inhibitor (avibactam) that has been approved by the U.S. Food and Drug Administration, the European Union, and the National Regulatory Administration in China. CAZ/AVI is used mainly to treat complicated urinary tract infections and complicated intra-abdominal infections in adults, as well as to treat patients infected with Carbapenem-resistant Enterobacteriaceae (CRE) susceptible to CAZ/AVI. However, increased clinical application of CAZ/AVI has resulted in the development of resistant strains. Mechanisms of resistance in most of these strains have been attributed to bla KPC mutations, which lead to amino acid substitutions in β-lactamase and changes in gene expression. Resistance to CAZ/AVI is also associated with reduced expression and loss of outer membrane proteins or overexpression of efflux pumps. In this review, the prevalence of CAZ/AVI-resistance bacteria, resistance mechanisms, and selection of detection methods of CAZ/AVI are demonstrated, aiming to provide scientific evidence for the clinical prevention and treatment of CAZ/AVI resistant strains, and provide guidance for the development of new drugs.

Understanding the evolution and dissemination of community-genotype ST72 Staphylococcus aureus isolates is important, as isolates of this lineage have rapidly spread into hospital settings and caused serious health issues. In this study, we first carried out genome-wide analysis of 107 global ST72 isolates to characterize the evolution and genetic diversity of the ST72 lineage.

Purpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the leading causes of healthcare-associated infections (HAIs) and is particularly pervasive in intensive care units (ICUs). This study takes ICU layout as the research object, and integrates clinical data and bacterial genome analysis to clarify the role of separate, small wards within the ICU in controlling the transmission of CRKP.Methods: This study prospectively observed the carriage and spread of CRKP from a long-term in-hospital patient (hereafter called the Patient) colonized with CRKP in the gut and located in a separate, small ward within the ICU. The study also retrospectively investigated CRKP-HAIs in the same ICU. The relationship and transmission between CRKP isolates from the Patient and HAI events in the ICU were explored with comparative genomics. Results:In this study, 65 CRKP-HAI cases occurred during the investigation period. Seven CRKP-HAI outbreaks were also observed. A total of 95 nonrepetitive CRKP isolates were collected, including 32 strains from the Patient in the separate small ward. Phylogenetic analysis based on core genome single-nucleotide polymorphism (cgSNP) showed that there were five possible CRKP clonal transmission events and two clonal outbreaks (A1, A2) during the study. CRKP strains from the Patient did not cause CRKP between-patient transmission or outbreaks in the ICU during the 5-year study period. Conclusion:The presence of a long-term hospitalized patient carrying CRKP and positioned in a separate, small ward did not lead to CRKP transmission or infection outbreaks in the ICU. Combining a small-ward ICU layout with normative HAI control measures for multidrug-resistant pathogen infection was effective in reducing CRKP transmission.

ObjectivesThe addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations.MethodsWe conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs).ResultsA total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively.ConclusionsICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.