Detection and spread of carbapenem-resistant Citrobacter freundii in a teaching hospital in China

Background: We examined the detection and spread of carbapenem-resistant Citrobacter freundii in Huashan Hospital, Shanghai, China between 2005 and 2008. Methods: Twenty-three isolates of carbapenem-resistant C freundii collected in our hospital underwent resistant gene amplification by polymerase chain reaction, followed by minimal inhibitory concentration (MIC) analysis. Molecular epidemiologic analyses included pulsed-field gel electrophoresis and case study. Results: Analysis of MICs with amikacin, gentamicin, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, ertapenem, cefoxitin, piperacillin-tazobactam, and ciprofloxacin characterized the isolates as highly resistant to antimicrobials. Colistin, tigecycline, minocycline, and doxycycline to all C freundii isolates had lower MICs than the other antimicrobials tested, with MIC(50)/MIC(90) values of 0.5/1, 1/1, 4/8, and 4/4 mg/L, respectively. Molecular typing using pulsed-field gel electrophoresis classified the isolates into 4 groups, of which 15 isolates belonged to a single clone. In total, all of the isolates produced KPC-2-type carbapenemase, of which most were likely to couple with CTX-M-type extended-spectrum beta-lactamases and plasmid-mediated CMY-2-type AmpC enzyme. Subsequent clinical investigations involving the general status of patients, the ward, and antimicrobial and therapeutic outcomes showed that a carbapenem-resistant clone had spread critically in the Department of Neurosurgery. Potential risk factors were identified, including invasive procedures, surgical operations, use of indwelling urine catheters, and number of sickbed changes. Conclusion: The spread of carbapenem-hydrolyzing C freundii isolates has emerged in regional hospitals in China. Multidrug-resistant mechanisms of strains severely hamper control efforts. Our findings should alert clinicians to issues involved with preventing the spread of carbapenem-resistant C freundii.