Tamma Pranita D, Goodman Katherine E, Harris Anthony D, Tekle Tsigereda, Roberts Ava, Taiwo Abimbola, Simner Patricia J
Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine,
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health.
Clin Infect Dis. 2017 Feb 1;64(3):257-264. doi: 10.1093/cid/ciw741. Epub 2016 Nov 9.
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 (92%), followed by bla (5%) and bla (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.
耐碳青霉烯类肠杆菌科细菌(CRE)与相当高的死亡率相关。由于碳青霉烯类耐药机制具有异质性,基于耐药机制的死亡率是否存在差异尚不清楚。我们试图确定CRE耐药机制的判定是否具有预后指导意义。
我们进行了一项观察性研究,比较产碳青霉烯酶(CP)-CRE患者与非CP-CRE菌血症患者的14天死亡率。收集了所有患者的临床数据。对所有分离株进行了基于DNA微阵列的综合检测,以鉴定β-内酰胺酶编码基因。
在研究期间,共有83例单一微生物CRE菌血症的独特病例:37例(45%)为CP-CRE,46例(55%)为非CP-CRE。大多数CP-CRE分离株携带bla (92%),其次是bla (5%)和bla (3%)。CP-CRE分离株更有可能具有美罗培南最低抑菌浓度(MIC)≥16 μg/mL,而非CP-CRE分离株更有可能具有美罗培南MIC≤1 μg/mL(P值<0.001)。共有18例(22%)患者在14天内死亡,其中CP-CRE组12例(32%),非CP-CRE组6例(13%)。在对菌血症第1天的疾病严重程度、基础疾病以及所给予的抗生素治疗差异进行调整后,CP-CRE菌血症患者在14天内死亡的几率比非CP-CRE菌血症患者高出4倍多(调整后的优势比,4.92;95%置信区间,1.01-24.81)。
我们的研究结果表明,CP-CRE可能比非CP-CRE具有更强的毒力,且与更差的预后相关。这突出了明确CRE潜在耐药机制以指导抗生素治疗决策的额外重要性。