Molecular Epidemiology, Risk Factors and Clinical Outcomes of Carbapenem-Nonsusceptible Enterobacter cloacae Complex Infections in a Taiwan University Hospital

The genus Enterobacter is a member of the ESKAPE group, which contains the major resistant bacterial pathogens. Enterobacter cloacae complex (ECC) has emerged as a clinically significant cause of a wide variety of nosocomial infections. Carbapenem-nonsusceptible Enterobacter cloacae complex (CnsECC) has become an emerging threat to public health but there is still a lack of comprehensive molecular and clinical epidemiological analysis. A total of 157 CnsECC isolates were recovered during October 2011 to August 2017. hsp60 gene sequencing and pulsed-field gel electrophoresis (PFGE) were applied to discriminate the species, genetic clusters and clonal relatedness. All the isolates were subjected to polymerase chain reaction (PCR) analysis for carbapenemase, AmpC-type 13-lactamase, and extended spectrum 13-lactamase (ESBL) genes. Clinical data were collected on all patients for comparing clinical risks and outcomes between patients with carbapenemase-producing (CP)-CnsECC compared with non-CP-CnsECC infection. The most commonly identified species was E. hormaechei subsp. hoffmannii (47.1%), followed by E. hormaechei subsp. steigerwaltii (24.8%). Different species of CnsECC isolates showed heterogeneity in resistance patterns to piperacillin/tazobactam, cefepime and levofloxacin. In the present study, we observed that E. hormaechei subsp. hoffinannii was characterized with higher cefepime and levofloxacin resistance rate but lower piperacillin/tazobactam resistance rate relative to other species of CnsECC. CP-CnsECC comprised 41.1% (65 isolates) and all of these isolates carried IMP-8. In this study, 98% of patients had antimicrobial therapy prior to culture, with a total of 57/150 (38%) patients being exposed to carbapenems. Chronic pulmonary disease (OR: 2.51, 95% CI: 1.25-5.06), received ventilator support (OR: 5.54, 95% CI: 225-12.03), steroid exposure (OR: 3.88, 95% CI: 1.91-7.88) and carbapenems exposure (OR: 2.17, 95% CI: 1.10-4.25) were considered risk factors associated with CP-CnsECC infection. The results suggest that CP-CnsECC are associated with poorer outcomes including in-hospital mortality, 30-day mortality and 100-day mortality. Our study provides insights into the epidemic potential of IMP-8-producing E. cloacae for healthcare-associated infections and underscores the importance of understanding underlying resistance mechanisms of CnsECC to direct antibiotic treatment decisions.

Automated summary

The Enterobacter cloacae complex (ECC) has emerged as a significant cause of nosocomial infections, especially with carbapenem-nonsusceptible isolates posing a threat to public health. This study identified the most commonly isolated species was E. hormaechei subsp. hoffmannii, with different species of CnsECC showing heterogeneity in resistance patterns. Carbapenemase-producing CnsECC infections were associated with poorer outcomes, with risk factors including exposure to carbapenems, chronic pulmonary disease, and ventilator support. The findings emphasize the importance of understanding resistance mechanisms to guide antibiotic treatment decisions.