Rapid Detection and Evaluation of Clinical Characteristics of Emerging Multiple-Drug-Resistant Gram-Negative Rods Carrying the Metallo-β-Lactamase Gene bla IMP

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Abstract
Gram-negative rods (GNR) carrying the transferable carbapenem resistance gene bla IMP , including Pseudomonas aeruginosa and Serratia marcescens , have been isolated from more than 20 hospitals in Japan. Although the emergence of such multiple-drug-resistant bacteria is of utmost clinical concern, little information in regard to the distribution of bla IMP -positive GNR in hospitals and the clinical characteristics of infected patients is available. To address this, a system for the rapid detection of the bla IMP gene with a simple DNA preparation and by enzymatic detection of PCR products was developed. A total of 933 ceftazidime-resistant strains of GNR isolated between 1991 and 1996 at Nagasaki University Hospital, Nagasaki, Japan, were screened for the bla IMP gene; 80 isolates were positive, including 53 P. aeruginosa isolates, 13 other glucose-nonfermenting bacteria, 13 S. marcescens isolates, and 1 Citrobacter freundii isolate. Most of the patients from whom bla IMP -positive organisms were isolated had malignant diseases (53.8%). The organisms caused urinary tract infections, pneumonia, or other infections in 46.3% of the patients, while they were just colonizing the other patients evaluated. It was possible that bla IMP -positive P. aeruginosa strains contributed to the death of four patients, while the other infections caused by GNR carrying bla IMP were not lethal. DNA fingerprinting analysis by pulsed-field gel electrophoresis suggested the cross transmission of strains within the hospital. The isolates were ceftazidime resistant and were frequently resistant to other antibiotics. Although no particular means of pathogenesis of bla IMP -positive GNR is evident at present, the rapid detection of such strains is necessary to help with infection control practices for the prevention of their dissemination and the transmission of the resistance gene to other pathogenic bacteria.