Outbreaks of Multidrug-Resistant Pseudomonas aeruginosa in Community Hospitals in Japan

Abstract

We previously reported an outbreak in a neurosurgery ward of catheter-associated urinary tract infection with multidrug-resistant (MDR) Pseudomonas aeruginosa strain IMCJ2.S1, carrying the 6-N-aminoglycoside acetyltransferase gene [aac(6)-Iae]. For further epidemiologic studies, 214 clinical isolates of MDR P. aeruginosa showing resistance to imipenem (MIC > 16 g/ml), amikacin (MIC > 64 g/ml), and ciprofloxacin (MIC > 4 g/ml) were collected from 13 hospitals in the same prefecture in Japan. We also collected 70 clinical isolates of P. aeruginosa that were sensitive to one or more of these antibiotics and compared their characteristics with those of the MDR P. aeruginosa isolates. Of the 214 MDR P. aeruginosa isolates, 212 (99%) were serotype O11. We developed a loop-mediated isothermal amplification (LAMP) assay and a slide agglutination test for detection of the aac(6)-Iae gene and the AAC(6)-Iae protein, respectively. Of the 212 MDR P. aeruginosa isolates, 212 (100%) and 207 (98%) were positive in the LAMP assay and in the agglutination test, respectively. Mutations of gyrA and parC genes resulting in amino acid substitutions were detected in 213 of the 214 MDR P. aeruginosa isolates (99%). Of the 214 MDR P. aeruginosa isolates, 212 showed pulsed-field gel electrophoresis patterns with >70% similarity to that of IMCJ2.S1 and 83 showed a pattern identical to that of IMCJ2.S1, indicating that clonal expansion of MDR P. aeruginosa occurred in community hospitals in this area. The methods developed in this study to detect aac(6)-Iae were rapid and effective in diagnosing infections caused by various MDR P. aeruginosa clones.Pseudomonas aeruginosa causes nosocomial infections as a result of its ubiquitous nature, ability to survive in moist environments, and resistance to many antibiotics and antiseptics. A serious problem is the emergence of multidrug-resistant (MDR) P. aeruginosa strains resistant to ␤-lactams, aminoglycosides, and quinolones (34,39,46 We previously reported a nosocomial outbreak of catheterassociated urinary tract infection involving new MDR P. aeruginosa strain IMCJ2.S1, which occurred in a neurosurgery ward of a hospital located in the Tohoku area of Japan (46). This strain showed broad-spectrum resistance to aminoglycosides, ␤-lactams, fluoroquinolones, tetracyclines, sulfonamide, and chlorhexidine. We found that IMCJ2.S1 harbored a novel class 1 integron, In113, containing an array of three gene cassettes of the metallo-␤-lactamase (MBL) bla IMP-1 gene, aminoglycoside 6Ј-acetyltransferase aac(6Ј)-Iae gene, and aminoglycoside 3Ј-adenylyltransferase aadA1 gene (46). This strain possessed mutations of the gyrA (83Thr3Ile) and parC (87Ser3Leu) genes involving amino acid substitutions, resulting in high-level resistance to fluoroquinolones.In the geographic area where the MDR P. aeruginosa outbreak occurred (46), hospitals and a commercial clinical laboratory were surveyed for similar organisms. Because 99% of the MDR P. aeruginosa isolates analyzed were found to harbor the aac(6Ј)-Iae gene, we d...

Analysis of integrons and associated gene cassettes of metallo-β-lactamase-positive Pseudomonas aeruginosa in Malaysia

“…Thus, from these results, we suggest that the class 1 integron is the most abundant type of integron present among the clinical isolates in this hospital. Similar observations were also noted in a clinical setting in Japan (Sekiguchi et al, 2007).…”

“…The presence of populations of MDR strains among clinical isolates is a cause for concern for physicians applying empirical treatment, especially in serious cases of P. aeruginosa infections in Asian countries such as Japan (Sekiguchi et al, 2007), Taiwan (Leung et al, 2008), India (Navaneeth et al, 2002) and Iran (Japoni et al, 2006).…”

“…The recent emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa has become a serious problem in healthcare settings worldwide, including in Asian countries (Leung et al, 2008;Raja & Singh, 2007;Sekiguchi et al, 2007). The rapid emergence of antibiotic resistance among clinical isolates of bacteria is due to dissemination of antibiotic resistance genes by horizontal transfer (Leverstein-van Hall et al, 2003).…”

Primary mechanisms mediating aminoglycoside resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7

“…A significant relationship between antibiotic use, for example, aminoglycoside, fluoroquinolone and cefepime, and the incidence of MexXY-overproducing P. aeruginosa has been reported (Hocquet et al, 2008). AMEs are also common determinants of aminoglycoside resistance in P. aeruginosa, except for CF isolates (Vogne et Henrichfreise et al, 2007;Sekiguchi et al, 2007;Samuelsen et al, 2010;Poole, 2011). Each AME has limited substrate specificity, but individual aminoglycoside-resistant P. aeruginosa isolates can carry multiple (2-5) AMEs and thus exhibit broad-spectrum aminoglycoside resistance (Poole, 2005).…”

“…Henrichfreise Sekiguchi et al, 2007;Samuelsen et al, 2010;Poole, 2011). Each AME has limited substrate specificity, but individual aminoglycoside-resistant P. aeruginosa isolates can carry multiple (2-5) AMEs and thus exhibit broad-spectrum aminoglycoside resistance (Poole, 2005).…”