Teniposide

Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains. Antimicrobial susceptibility testing, whole-genome sequencing, carbapenem-hydrolysing activity and the expression of carbapenemase genes were determined. In total, 18.8% of CRE strains were ETP-mono-resistant, with relatively low ertapenem MIC values. ETP-mono-resistant strains exhibited enhanced susceptibility to β-lactams, β-lactam/β-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin and polymyxin than MEM/IPM-resistant strains (P < 0.05). Phylogenetic analysis revealed high genetic diversity among ETP-mono-resistant strains. Extended-spectrum β-lactamases (ESBLs) and/or AmpC, as well as porin mutations, were identified as potential major mechanisms mediating ETP-mono-resistance, while the presence of carbapenemases was found to be the key factor distinguishing the carbapenem-resistant phenotypes between the two groups (P < 0.001). Compared with the MEM/IPM-resistant group, limited carbapenemase-producing CRE (CP-CRE) strains in the ETP-mono-resistant group showed a significantly lower prevalence of ESBLs and porin mutations, along with reduced expression of carbapenemase. Remarkably, spot assays combined with modified carbapenem inactivation method indicated that ETP-mono-resistant CP-CRE isolates grew at meropenem concentrations eightfold above their corresponding MIC values, accompanied by rapidly enhanced carbapenem-hydrolysing ability. These findings illustrate that ETP-mono-resistant CRE strains are relatively prevalent and that caution should be exercised when using meropenem alone for treatment. The detection of carbapenemase should be prioritized.

This systematic review and network meta‐analysis compared various antibiotic treatments with surgical treatment for acute appendicitis.

We searched PubMed, Embase, Cochrane Library, and Wanfang databases for randomized controlled trials (RCTs) that met the prespecified inclusion criteria up to July 2023. The interventions included various antibiotics and surgery. The outcomes measured were initial treatment success, treatment success at 1‐year follow‐up, and treatment‐related complications. Meta‐analysis was conducted using R software with the gemtc package. Surfaces under the cumulative ranking curves (SUCRA) were used to rank the interventions.

Thirteen RCTs involving nine treatments (cefotaxime [CTX] + tinidazole [TNZ], CTX + metronidazole [MTZ], ampicillin [AMP] + gentamicin [GEN] + MTZ, amoxicillin/clavulanate [AMC] + GEN, meropenem [MEM] + MTZ, AMC, ertapenem [ETP] + MTZ, ETP, and surgery) were included in this network meta‐analysis. In head‐to‐head comparisons, no statistically significant difference was found between any two interventions for initial treatment success (p > 0.05). The SUCRA indicated that surgery ranked first (SUCRA, 66.5%) for initial treatment success. Surgery was associated with an increased treatment success rate at 1‐year follow‐up compared to AMC (OR = 0.01, 95% CrI = 0.00–0.14, p < 0.05), MEM + MTZ (OR = 0.06, 95% CrI = 0.00–0.42, p < 0.05), and AMP + GEN + MTZ (OR = 0.02, 95% CrI = 0.00–0.23, p < 0.05). No statistically significant differences were found between any two interventions regarding complications (p > 0.05).

Our network meta‐analysis suggests that surgery ranks highest for initial treatment success and treatment success at 1‐year follow‐up. However, surgery may increase the complication rate.