Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify β-lactamase-encoding genes. There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were bla KPC (92%), followed by bla NDM (5%) and bla OXA-48-type (3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ≤1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01-24.81). Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.

Tamma PD ，Goodman KE ，Harris AD ，Tekle T ，Roberts A ，Taiwo A ，Simner PJ ... -  《-》

Comparing mortality in patients with carbapenemase-producing carbapenem resistant Enterobacterales and non-carbapenemase-producing carbapenem resistant Enterobacterales bacteremia.

Carbapenem-resistant Enterobacterales (CRE) are classified as either carbapenemase-producing CRE (CP-CRE) or non-carbapenemase-producing CRE (non-CP-CRE) based on their mechanism of carbapenem resistance. Few studies have compared outcomes associated with each type of infection. We attempted to determine if either CRE subset is associated with increased mortality. We performed a retrospective observational study to collect demographic, clinical and outcomes data to compare patients with CP-CRE and non-CP-CRE bacteremia. Of 146 cases analyzed, 88/146 (60%) were CP-CRE and 58/146 (40%) were non-CP-CRE. Patients with CP-CRE bacteremia were less likely to receive active empiric or targeted antibiotic therapy. Non-CP-CRE bacteremia was associated with a 2.4 times higher hazard of death at 30 days after bacteremia onset compared to CP-CRE (HR, 2.4; 95% CI, 1.2, 4.6). Patients with non-CP-CRE bacteremia had a higher hazard of death at 30 days after bacteremia onset compared to those with CP-CRE bacteremia.

Hovan MR ，Narayanan N ，Cedarbaum V ，Bhowmick T ，Kirn TJ ... -  《-》

Role of Double-Carbapenem Regimen in the Treatment of Infections due to Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae: A Single-Center, Observational Study.

Cancelli F ，Oliva A ，De Angelis M ，Mascellino MT ，Mastroianni CM ，Vullo V ... -  《-》

In vitro activity of meropenem/vaborbactam and characterisation of carbapenem resistance mechanisms among carbapenem-resistant Enterobacteriaceae from the 2015 meropenem/vaborbactam surveillance programme.

The activity of meropenem/vaborbactam was evaluated against 11 559 Enterobacteriaceae isolates, including 330 carbapenem-resistant phenotypes (CRE) and carbapenemase genotypes collected worldwide during 2015. Antimicrobial susceptibility testing for meropenem/vaborbactam (inhibitor at 8 mg/L) and comparators was performed by the reference broth microdilution method. CRE isolates were screened for the presence of genes encoding carbapenemases, and 292 (88.5%) of the CRE isolates carried these resistance genes. A total of 209 isolates (63.3% of the CRE; 1.8% of the overall Enterobacteriaceae population) carried blaKPC, including genes encoding KPC-2 (90 isolates), KPC-3 (117 isolates) and KPC-17 (2 isolates). Overall, meropenem/vaborbactam (vaborbactam at 8 mg/L) inhibited 99.3% of all Enterobacteriaceae isolates at the US-FDA susceptibility breakpoint of ≤4/8 mg/L. Meropenem alone inhibited 96.9% of the isolates at the current CLSI susceptibility breakpoint of ≤2 mg/L. Susceptibility rates for comparator antimicrobial agents tested against Enterobacteriaceae isolates ranged from 82.1-98.2% applying the CLSI breakpoints. Against CRE isolates, meropenem/vaborbactam displayed MIC50/90 values at 0.5/32 mg/L, whereas meropenem MIC50/90 values were 16/>32 mg/L. Meropenem/vaborbactam was very active against KPC-producers, and 99.5% of these isolates were inhibited by ≤4/8 mg/L. The single resistant isolate was shown to harbour an outer membrane porin alteration. Meropenem/vaborbactam had limited activity against MBL-producing isolates (including 49 NDM-, 1 IMP-64- and 2 VIM-producers) and/or oxacillinases (47 OXA-48/-232) that were detected mainly in European countries. Meropenem/vaborbactam was active against contemporary CRE and wild-type Enterobacteriaceae collected worldwide and this combination demonstrated enhanced activity compared with meropenem and most comparator agents against CRE and KPC-producers.

Pfaller MA ，Huband MD ，Mendes RE ，Flamm RK ，Castanheira M ... -  《-》

Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: treatment and survival.

Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes. The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case-control study of surviving and non-surviving patients was conducted. Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2-52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p=0.015) and prolonged neutropenia (p=0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p=0.001 and p=0.001, adjusted r(2)=0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p<0.001). Time to active treatment had a significant effect on the course of infection (p=0.014). Earlier active treatment with colistin based regimens and microbiological and clinical response within 7 days are major predictors of survival in cases of BSIs due to CRE. Rectal screening offers the advantage of earlier recognition and prompt empirical treatment.

Balkan II ，Aygün G ，Aydın S ，Mutcalı SI ，Kara Z ，Kuşkucu M ，Midilli K ，Şemen V ，Aras S ，Yemişen M ，Mete B ，Özaras R ，Saltoğlu N ，Tabak F ，Öztürk R ... -  《-》