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

Abstract

Gram-negative rods (GNR) carrying the transferable carbapenem resistance gene blaIMP, includingPseudomonas 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 ofblaIMP-positive GNR in hospitals and the clinical characteristics of infected patients is available. To address this, a system for the rapid detection of theblaIMP 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 theblaIMP 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 blaIMP-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 blaIMP-positive P. aeruginosa strains contributed to the death of four patients, while the other infections caused by GNR carryingblaIMP 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 ofblaIMP-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.

Clinical efficacy of intravenous ciprofloxacin in patients with biliary tract infection: a randomized controlled trial with carbapenem as comparator

“…For empirical antimicrobial therapy for biliary tract infection in Japan, beta-lactams, such as third-or fourthgeneration cephems or carbapenems, are widely used. However, extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli resistant to third-or fourthgeneration cephems and Pseudomonas aeruginosa carrying bla IMP , which hydrolyzes even carbapenems, have recently been more frequently isolated, and resistance to drugs is becoming a serious problem [3,4]. Against this backdrop, clinical use of an intravenous fluoroquinolone for biliary tract infection was allowed in 2000, and its characteristics have raised hopes for high clinical efficacy in Japan.…”

?-Laktamasen mit breitem Wirkungsspektrum

“…Mit der Einfüh-rung der Chip-Technologie mit captureprobes für die einzelnen Allele der β-Laktamase-Gene wird dann aber eine schnelle Detektion bestimmter ESBL-Typen möglich sein.Für die Unterscheidung der 6 häufigsten Familien plasmidkodierter AmpC-Enzyme wurde eine Multiplex-PCR etabliert [36]. Auch das Erkennen von Metallo-β-Laktamasen der Gruppe B ist durch PCR möglich [37].…”

Nosocomial infectious potency of imipenem-resistant Pseudomonas aeruginosa isolated from obstetric and gynecologic infections

“…1 However, clinical carbapenem-resistant isolates, including Enterobacteriaceae and Pseudomonas aeruginosa, have recently been increasing in Japan. 2,3 The mechanism of the resistance has been associated with the production of the metallo--lactamase (IMP-1) enzyme encoded by the transferable metallo--lactamase gene, bla imp . The metallo--lactamase gene, bla imp was found to be carried on mobile gene cassettes inserted in plasmid or chromosome-borne integrons.…”

“…P. aeruginosa, followed by Serratia marcescens and Pseudomonas putida, is identified in 66.7% of bla imppositive isolates among gram-negative rods. 2 While the occurrence of resistance is diverse in each hospital, antimicrobial agents are ineffective against IPM-resistant P. aeruginosa, which often has multidrug-resistance. In our hospital, no strain of P. aeruginosa had both the bla imp and aac (6Ј)-Ib genes.…”

“…aeruginosa is one of the microorganisms involved in nosocomial infections, and acquires resistance to chemotherapeutic agents in various hospitals. 2 The intrinsic antibiotic resistance of P. aeruginosa is determined mainly by three factors: [13][14][15] the instability of antimicrobial agents against antibiotic-modifying enzymes, e.g., metallo--lactamase; 13 the permeability barrier at the outer membrane (among the dipolar ionic -lactëms, ŸhM aˆd meropenem diffuse mainly through protein D2 pores. 14 A defect of D2 porin causes the resistance to carbapenems.…”