Mortality and Risk Factors of Death in Patients with AmpC β-Lactamase Producing Enterobacterales Bloodstream Infection: A Cohort Study

Ana Sheila Duarte Nunes Silva,1 Natalia Chilinque Zambão da Silva,1 Fernanda Moreth do Valle,2 Jaqueline Abel da Rocha,2 Shelley Ehrlich,3,4 Ianick Souto Martins1,5 1Infection Disease Division, Department of Clinical Medicine, Faculty of Medicine, Fluminense Federal University, Niterói, RJ, Brazil; 2Hospital Universitário Antonio Pedro, Faculty of Medicine, Fluminense Federal University, Niterói, RJ, Brazil; 3Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA; 4Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA; 5Infection Control Division, Hospital Do Câncer I, Instituto Nacional Do Câncer, Rio de Janeiro, RJ, BrazilCorrespondence: Ana Sheila Duarte Nunes Silva, Email [email protected]: ESCPM bacteria include Enterobacter spp, Serratia, Citrobacter spp, Providencia spp, and Morganella spp. These Gram-negative bacilli harbor chromosomally encoded AmpC-type β-lactamases that cause resistance to β-lactam antibiotics, such as penicillins, β-lactam/β-lactamase inhibitors, and first-, second-, and third-generation cephalosporins. Bloodstream infections caused by ESCPM group bacteria (BSI-ESCPM) are difficult to treat.Purpose: To describe 30-day mortality and analyze potential risk factors for death in patients with BSI-ESCPM.Patients and Methods: A cohort study of patients aged ≥ 18 years with BSI-ESCPM was conducted at a University Hospital in Brazil, from January 2013 and December 2018. Potential risk factors for death within 30 days of bloodstream infection BSI diagnosis were analyzed using multivariable logistic regression.Results: Among 138 patients with BSI-ESCPM, 63.0% were males, with a median age of 61 years. Of 155 BSI-ESCPM episodes, 61.3% were hospital-acquired. Primary BSI-ESCPM associated with short-term central venous catheter (37.4%) and BSI-ESCPM secondary to respiratory infection (19.4%) occurred mainly. Mostly, Enterobacter spp. (49.7%) and Serratia spp. (29.0%) were isolated. Multidrug-resistance occurred in 27.7% of BSI-ESCPM episodes, involving Enterobacter spp. (16.1%) and Serratia spp. (7.7%) mainly. The mortality was 24.5%. Developing septic shock within 72 h of BSI-ESCPM diagnosis (OR: 70.26; 95% CI: 16.69– 295.77; P< 0.01) was risk factor for death. Conversely, combined antibiotic therapy (OR: 0.23; 95% CI: 0.05– 0.94; P:0.04), BSI-ESCPM secondary to urinary infection (OR: 0.11; 95% CI: 0.01– 0.99; P:0.05), and Enterobacter spp. BSI (OR: 0.16; 95% CI: 0.05– 0.56; P 0< 0.01) was protective factor against death. Tendency of association between inadequate antibiotic therapy and death (OR: 2.19; 95% CI: 0.51– 9.42; P:0.29) was observed.Conclusion: BSI-ESCPM is severe and has serious outcomes such as sepsis-associated deaths. Combined antibiotic therapy was a protective factor against death in patients with BSI-ESCPM. There is a suggestive association between inadequate antibiotic therapy and mortality. The ESCPM group bacteria that are considered to be at moderate to high risk of clinically significant AmpC production were not associated with death.Keywords: bloodstream infection, Enterobacterales, AmpC β-lactamase, mortality, risk factors of death