Antimicrobial Resistance of Neisseria gonorrhoeae and Emerging Ciprofloxacin Resistance in The Netherlands, 1991 to 1998

Abstract

Surveillance of antibiotic resistance in Neisseria gonorrhoeae showed a decrease in the percentage of ␤-lactamase-producing isolates but an increase in intermediately penicillin-resistant strains and strains resistant to a high level of tetracycline. MICs for the ciprofloxacin-resistant isolates that emerged increased, and these isolates had mutations in gyrA and parC similar to those observed in the Far East.Since 1991 five sentinel laboratories in The Netherlands have participated in a surveillance of antibiotic resistance in Neisseria gonorrhoeae. The laboratories are located in Amsterdam, Rotterdam, and The Hague and account for approximately 70% of the gonococcal isolates from The Netherlands (6). They forwarded all isolates of N. gonorrhoeae to the National Institute of Public Health and the Environment 1 month per quarter. Here we report the results of this survey in the period 1991 to 1998. ␤-Lactamase production was detected using nitrocefin (Oxoid, Basingstroke, United Kingdom). The susceptibility to antibiotics was determined by the agar dilution method using Iso-Sensitest agar (Oxoid) with 5% horse blood and multipoint inoculation. The inoculum was 10 6 CFU/spot. The plates were incubated for 18 h at 35°C and 5% CO 2 . N. gonorrhoeae ATCC 49226 was used as the reference strain. The MICs for this strain were 0.5 g of penicillin, 1 g of tetracycline, 0.002 g of ciprofloxacin, 0.008 g of ceftriaxone, and 0.25 g of azithromycin/ml.Resistance to quinolones is known to be related to specific point mutations in the quinolone resistance-determining regions of genes gyrA and parC. The DNA regions of gyrA (GenBank accession no. U08817) encoding amino acids 44 to 156 and of parC (GenBank accession no. U08907) encoding amino acids 54 to 239 were amplified by PCR and sequenced directly using the ABI PRISM Big Dye cycle sequencing ready reaction kit on a 377 DNA sequencer (Perkin-Elmer, Applied Biosystems, Foster City, Calif.).The total number of gonococcal isolates forwarded by the participating laboratories decreased from 967 in 1991 to 1992 to 449 in 1997 to 1998 (Table 1). This decrease may have been due to the implementation of prevention measures against human immunodeficiency virus infection (2). The MIC distributions of azithromycin (MIC at which 50% of isolates tested are inhibited [MIC 50 ], 0.12 g/ml; MIC 90 , 0.25 g/ml) and ceftriaxone (MIC 50 , 0.002 g/ml; MIC 90 , 0.008 g/ml) did not change in the investigated period. The majority (362 of 374) of the isolates resistant to high levels of penicillin produced ␤-lactamase. In contrast 1,124 of 1,183 isolates intermediately resistant to penicillin were ␤-lactamase negative. Although the frequency of ␤-lactamase-producing strains declined from a maximum of 24% in

Gonorrhoea Surveillance System in France: 1986–2000

“…30 Resistance to ciprofloxacin, which first appeared in the RENAGO surveillance system in a strain isolated in the Paris area in 1997, has increased regularly every year to reach 2% in 1998 to 2000. The proportion of ciprofloxacin resistance in the RENAGO surveillance system is consistent with those observed in the United Kingdom, (1.8%), 31 in The Netherlands, (2.2%), 32 or in the United States (0.7%) 33 and remained much lower than those observed in China (34.2%) 34 or in Japan (24.4%). 35 The increased proportion of ciprofloxacin resistance during the last study period needs to be carefully monitored, particularly in France where single-dose treatments are widely used.…”

Update on quinolone resistance in Neisseria gonorrhoeae

“…Similar gyrA mutation patterns at codons 91 and 95 were seen in Greece [10], the Netherlands [11], and Australia [12]. In a surveillance study of 331 isolates in Greece between 1996 and 1999, 11.9% demonstrated decreased susceptibility to ciprofloxacin, with the highest proportion of resistant isolates (20%) seen in homosexual men.…”

“…All of the isolates had mutations in grA at codons 91 and 95. In the Dutch study [11], QRNG was detected by susceptibility determinations and sequencing PCR of the mutations occurring for gyrA and parC. Most of the early isolates with low levels of decreased susceptibility had mutations in gyrA.…”

Increasing trend in gonococcal resistance to ciprofloxacin in The Netherlands, 2006-8

“…National surveillance of antimicrobial resistance in gonococci was conducted in The Netherlands from 1976 until 1999, the period in which reporting the disease was mandatory. Since then, national insight into its incidence, and also into resistance patterns of gonococci, has been lacking, despite signs of increases in gonorrhoea infections and in resistance to fluoroquinolones such as ciprofloxacin 4 5…”