Molecular epidemiology of Neisseria gonorrhoeae exhibiting decreased susceptibility and resistance to ciprofloxacin in Hawaii, 1991-1999.

BACKGROUND: Clinically significant resistance to Centers for Disease Control and Prevention (CDC)-recommended doses of fluoroquinolones (ciprofloxacin and ofloxacin) has been reported for Neisseria gonorrhoeae. In Hawaii, fluoroquinolone-resistant gonococcal isolates were first identified in 1991. GOAL: To assess the diversity, based on phenotypic and genotypic characterization, of gonococcal isolates exhibiting decreased susceptibility (CipI; MICs = 0.125-0.5 microg/ml) or clinically significant resistance (CipR; MICs > or = 1 microg/ml) to ciprofloxacin in Hawaii from 1991 through 1999. STUDY DESIGN: Antimicrobial susceptibilities, auxotype/serovar (A/S) class, GyrA/ParC alteration patterns, and plasmid profiles were determined for gonococci isolated in Honolulu from 1991 through 1999 that exhibited intermediate or clinically significant resistance to ciprofloxacin. Strain phenotypes were defined by A/S class, GyrA/ParC alteration pattern, and penicillin-tetracycline resistance phenotype supplemented with plasmid profiles for beta-lactamase-producing isolates. RESULTS: Altogether, 68 isolates exhibiting intermediate or clinically significant resistance to ciprofloxacin belonged to 23 and 19 strain phenotypes, respectively. Among the CipI and CipR isolates, 4 and 13 GyrA/ParC alterations patterns were identified, respectively. The 91,95/Asp-86 alteration pattern occurred most frequently among CipR isolates. Forty-four strain phenotypes were represented by only one isolate. In addition, seven pairs and two clusters of isolates were identified. CONCLUSIONS: From 1991 through 1997, few gonococcal strains exhibiting intermediate or clinically significant resistance to CDC-recommended doses of fluoroquinolones were identified from Hawaii. Isolates belonged to a large number of phenotypic and genotypic types, suggesting that most cases were imported, with only a few instances in which isolate pairs indicated that secondary transmission of infections had occurred in Hawaii. Beginning in 1998, the number of CipR isolates increased markedly, and more isolates belonged to fewer phenotypic and genotypic types, suggesting either more frequent importation of fewer strain types or the possibility that the endemic spread of a few strains is beginning to occur.

Alterations within the quinolone resistance-determining regions of GyrA and ParC of Neisseria gonorrhoeae isolated in the Far East and the United States.

The genetic mutations within the quinolone resistance-determining regions (QRDRs) of gyrA and parC of 234 Neisseria gonorrhoeae strains isolated in the Far East and the United States, which exhibited either clinically significant ciprofloxacin resistance (CipR) or intermediate ciprofloxacin resistance (CipI) were characterized. A number of GyrA/ParC amino acid alteration patterns were identified, the most prevalent alteration pattern among CipR isolates being GyrA-91,95/ParC-Asp-86- > Asn (91,95/Asp-86- > Asn). Isolates containing 91,95/Asp-86- > Asn belonged to a number of A/S classes, penicillin/tetracycline resistance phenotypes, and plasmid profiles. These results strongly suggest that the continuing emergence of ciprofloxacin-resistant gonococci is not due to the spread of a single or a few strains but to numerous factors such as 'spread of existing strains, importation of new strains and, possibly, de novo development of ciprofloxacin resistance in previously susceptible strains.

Identification of novel mutation patterns in the parC gene of ciprofloxacin-resistant isolates of Neisseria gonorrhoeae.

Of 65 ciprofloxacin-resistant, clinical isolates of Neisseria gonorrhoeae, 5 isolates exhibited ParC mutations previously undescribed in the gonococcus. For isolates containing two ParC mutations (the Ser-87-->Ile and Glu-91-->Gly mutations and the Gly-85-->Cys and Arg116-->Leu mutations) the MICs of ciprofloxacin (8.0 to 64.0 microg/ml) were higher than those for the isolate containing the single ParC mutation (Arg-116-->Leu; MIC, 1.0 microg/ml).