Research on gonococcal resistance to antibiotics including new quinolone

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I. Prevalence of antibiotic-resistant Neisseria gonorrhoeae : We determined the MIC for 208 N. gonorrhoeae isolates in 2001 in Fukuoka city. The prevalence rates of quinolone resistance (CPFX MIC≧1 μg/ml), penicillin resistance (PCG MIC≧2 μg/ml), and tetracycline resistance (TC MIC≧2 μg/ml) in those isolates were 64.4%, 13.4%, and 13.9%, respectively. The prevalence rate of penicillinase-producing N. gonorrhoeae (PPNG) was only 1.4% in those isolates. There were no isolates resistant to spectinomycin (SPCM MIC≧128 μg/ml) or intermediately resistant to cefixime (CFIX MIC≧0.5 μg/ml) in those isolates. However, the prevalence rate of reduced susceptibility to CFIX with MIC of 0.125 to 0.25 μg/ml was relatively higher (23.6%) in 2001 as compared with that (1.6%) in 1995-96. These results indicate that the prevalence rate of quinolone resistance in the isolates in 2001 was remarkably high and that the isolates in 2001 showed reduced susceptibility to CFIX.II. Mechanism of resistance to cefi … More xime : We examined the genetic mechanisms of chromosomally mediated resistance to CFIX. Chromosomally mediated penicillin (a variety of β-lactam antibiotics) resistance in N. gonorrhoeae occurs in part through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. The first step in transformation to high-level penicillin resistance is mediated by the penA gene, which encodes altered forms of PBP2. Therefore, we analyzed mutations in the penA gene of the 6 gonococcal isolates intermediately resistant (CFIX MIC=0.5 μg/ml) and 3 susceptible (CFIX MIC; ≦0.001 to 0.004 μg/ml) to CFIX, PCR and direct DNA sequencing were performed to identify mutations in a region including the transpeptidase domain of the penA gene. All 6 isolates intermediately resistant to CFIX had same 33 amino acid substitutions through position 323 to 480 within the region of the transpeptidase domain of PBP2. However, no single alteration was identified in the same region of the PBP2 of the 3 susceptible isolates. Our data suggest that multiple alterations in PBP2 play an essential role in conferring cefixime resistance to N. gonorrhoeae. Less