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 Xba I 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.