Title : Clinical outcomes and choice of antibiotics in AmpC beta-lactamase hyperproducing Enterobacterales bacteremia: A single-centre study
Abstract:
Background: AmpC β-lactamase hyperproducing Enterobacterales (ABLHE) are significant causes of bloodstream infections, often associated with multidrug resistance and high mortality. This study aimed to determine the 30-day all-cause mortality rate and its risk factors, to describe the epidemiology, clinical outcomes, and treatment of ABLHE bacteremia.
Methods: A retrospective single-centre study was conducted at Hospital Canselor Tuanku Muhriz (HCTM) from January 2015 to December 2022. This study primarily aimed to determine the 30-day all-cause mortality rate among patients with AmpC β-lactamase– hyperproducing Enterobacterales (ABLHE) bacteremia. Secondary objectives included describing empirical and definitive antimicrobial therapies, evaluating their association with length of hospitalization, and identifying risk factors for 30-day all-cause mortality. The sources of infection, patterns of community- versus nosocomial-acquired cases, and the prevalence of Enterobacter cloacae, Klebsiella aerogenes, and Citrobacter freundii were also analysed.
Results: A total of 196 patients with blood culture-confirmed ABLHE bacteremia (Enterobacter cloacae, Klebsiella aerogenes, and Citrobacter freundii) were included. The overall 30-day mortality rate was 32.7%. The commonest microorganism was Enterobacter cloacae at 71.4%. Klebsiella aerogenes and Citrobacter freundii accounted for 23.5% and 5.1% respectively. Nosocomial acquired bacteremia accounted for 40.3% . ABLHE bacteremia was mainly acquired via respiratory tract infection at 27.0% followed by catheter-related bloodstream infection, at 23.5%. The commonest empirical antibiotic used in this study was piperacillin- tazobactam at 43.4% where else the commonest definitive antibiotic was cefepime accounting for 55.1%. Independent predictors of 30-day mortality included Pitt Bacteremia score (aHR: 6.533, 95% CI: 2.066–19.532, p = 0.001), septic shock (aHR: 2.532, 95% CI: 1.448–4.428, p = 0.001), mechanical ventilation (aHR: 3.381, 95% CI: 1.703–6.712, p <0.001) and inappropriate definitive antibiotic therapy (aHR: 2.435, 95% CI: 1.240–4.781, p = 0.010). Cefepime had a shorter length of stay (aHR: 0.982, 95% CI: 0.968–0.995, p = 0.007). There was no difference in the 30-day all-cause mortality in definitive cefepime and carbapenem treatment group (aHR: 0.908, 95% CI: 0.499 – 1.652, p = 0.753).
Conclusion: ABLHE bacteremia was associated with high mortality, particularly among patients with severe illness and inappropriate definitive antibiotics therapy. The 30-day allcause mortality between cefepime and carbapenem groups was comparable in ABLHE bacteremia. These findings emphasize the importance of appropriate intensive management in managing ABLHE bacteremia especially in this high risk group.
Keywords: AmpC β-lactamase hyperproducing Enterobacterales bacteremia, 30-day all-cause mortality, cefepime, carbapenem, antibiotics therapy.
