Citrobacter freundii bacteremia: Risk factors of mortality and prevalence of resistance genes

Abstract

Background/purpose: Multidrug-resistant strains of Citrobacter have emerged, which carry Amp-C β-lactamase (Amp-C), broad-spectrum β-lactamase, extended-spectrum β-lactamase (ESBL), and other resistance mechanisms. These strains are associated with a higher rate of in-hospital mortality. The object of this study is to determine the mortality risk factors, susceptibility pattern to antibiotics, and prevalence of resistance genes in patients with Citrobacter freundii bacteremia. Methods: From January 2009 to December 2014, blood isolates of C. freundii were collected in MacKay Memorial Hospital, Taipei, Taiwan. PCR technique and sequencing were performed for resistance genes. Pulsed-field gel electrophoresis (PFGE) was done using XbaI restriction enzyme. The clinical characteristics and risk factors for mortality are demonstrated. Results: The 36 blood isolates of C. freundii belonged to 32 different PFGE pulsotypes, and 15 isolates (41.7%) were polymicrobial. The most common source of infection was intra-abdominal origin (61.1%), followed by unknown sources (22.2%), the urinary tract (8.3%), intravascular catheter (5.6%), and soft tissue (2.8%). High degree of antibiotic resistance was noted for cefazolin (100%), cefoxitin (97.2%), and cefuroxime (66.7%). The blaTEM-1 resistance gene was present in 16.7% isolates. 72.2% isolates carried blaAmpC and 5.6% isolates carried ESBL genes (blaSHV-12 or blaCTX-M-15). Multivariate analysis indicated that the independent risk factor for 28-day mortality was carrying the blaTEM-1 resistance gene. Conclusion: For patients with C. freundii bacteremia, carrying the blaTEM-1 resistance gene was an independent risk factor for 28-day mortality. Carbapenems, fourth-generation cephalosporins, amikacin, and quinolones are still reliable agents for drug-resistant strains. Keywords: Bacteremia, Citrobacter freundii, Mortality risk factors, Polymicrobial infection, TEM-1 gene