Affiliation:
1. Neisseria Unit, Department of Respiratory Infections, Meningitis and STIs, Statens Serum Institut, Copenhagen, Denmark
Abstract
ABSTRACT
In Denmark surveillance of the in vitro susceptibility to ciprofloxacin of
Neisseria gonorrhoeae
was established in 1990. The proportion of
N. gonorrhoeae
strains with decreased susceptibility or resistance to ciprofloxacin (MIC ≥ 0.06 μg/ml) was low (0.3 to 2.3%) up to 1995. Between 1995 and 1998 the rate of less-susceptible and resistant strains rose from 6.9 to 13.2%. Among ciprofloxacin-resistant strains (MIC ≥ 1 μg/ml), 81% were highly resistant (MIC ≥ 4 μg/ml). Thirty-five
N. gonorrhoeae
strains (40 isolates) for which ciprofloxacin MICs were 4 to 32 μg/ml were investigated for the frequency and patterns of mutations within the
gyrA
and
parC
genes. The quinolone resistance-determining regions of the
gyrA
and
parC
genes were amplified by PCR, and the amplicons were directly sequenced. Alterations at Ser-91 and Asp-95 in GyrA and a single or double alteration in ParC were identified in 32 strains (91%). Ser-91-to-Phe and Asp-95-to-Gly alterations in GyrA were detected in 28 strains (80%). The most common ParC alteration, Asp-86 to Asn, was found in 19 strains (54%). The strains were analyzed for genetic relationship by pulsed-field gel electrophoresis (PFGE). The analysis showed that nine strains with the same mutation pattern in the
gyrA
and
parC
genes, originating from different geographical areas over 3 years, had the same PFGE patterns after
Spe
I as well as
Nhe
I digestion (only one strain with one band difference in the
Nhe
I pattern), suggesting that a resistant clone had spread worldwide. The results from this study strongly suggest that double
gyrA
mutations plus a
parC
mutation(s) play an important role in the development of high-level fluoroquinolone resistance in
N. gonorrhoeae
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
44 articles.
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