Analysis of trends in antimicrobial resistance in Neisseria gonorrhoeae isolated in Australia, 1997 2006.

OBJECTIVES: To analyse trends in antimicrobial resistance (AMR) in Neisseria gonorrhoeae (GC) isolated in Australia between 1997 and 2006 and to identify factors influencing emergence and spread of AMR in GC. METHODS: AMR data were generated in reference laboratories in each state and territory of Australia using the methods of the Australian Gonococcal Surveillance Programme from a comprehensive sample of GC. Trends in the proportion of strains resistant to penicillin, ciprofloxacin, spectinomycin and ceftriaxone or with high-level tetracycline resistance (TRNG) were determined from aggregated national data and were also disaggregated by region. Further analyses of additional AMR, demographic, transmission and antibiotic use data were also performed. RESULTS: More than 36,000 GC were examined. Significant increases in resistance to penicillin and ciprofloxacin and in TRNG occurred in national data and in urban populations. Approximately half of the GC tested in larger urban centres were penicillin and/or ciprofloxacin resistant by 2006. These high rates of resistance arose despite low (penicillin) or absent (ciprofloxacin) exposure. In contrast, in rural and remote areas with very high disease rates and high rates of penicillin use, <5% of GC tested were penicillin (or quinolone) resistant. No spectinomycin-resistant GC were detected. Low numbers of GC with raised MICs of ceftriaxone were present in urban centres each year from 2001 onwards. CONCLUSIONS: Significant increases in AMR in GC occurred in parts of Australia in the 10 years to 2006. The data suggest that the AMR seen in GC in urban populations were the result of their repeated importation into Australia and ultimate introduction into established sexual networks rather than originating de novo or as a result of selection by antibiotic use or misuse.

Increasing resistance to ciprofloxacin and other antibiotics in Neisseria gonorrhoeae from East Java and Papua, Indonesia, in 2004 - implications for treatment.

We examined gonococci isolated in 2004, in East Java and Papua, Indonesia, to review the suitability of ciprofloxacin-based and other treatment regimens. Gonococci from the two provinces were tested in Sydney for susceptibility to penicillin, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin, gentamicin, azithromycin and rifampicin. Of 163 gonococcal isolates from East Java (91) and Papua (72), 120 (74%) of gonococci, 62 (68%) and 58 (80%) from East Java and Papua, respectively, were penicillinase-producing gonococci and 162 displayed high-level tetracycline resistance. Eighty-seven isolates (53%) were ciprofloxacin resistant, 44 (48%) from East Java and 43 (60%) from Papua. All isolates were sensitive to cefixime/ceftriaxone, spectinomycin and azithromycin. Minimum inhibitory concentrations of gentamicin were in the range 0.05-8 mg/L. Sixty-nine gonococci (42%) showed combined resistance, to penicillin, tetracycline and quinolones. Quinolone resistance has now reached unacceptable levels, and their use for the treatment of gonorrhoea in Indonesia should be reconsidered.

Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian regions, 2007-2008.

Long-term surveillance of antimicrobial resistance in Neisseria gonorrhoeae has been conducted in the World Health Organization (WHO) Western Pacific Region (WPR) to optimise antibiotic treatment of gonococcal disease since 1992. In 2007 and 2008, this Gonococcal Antimicrobial Surveillance Programme (GASP) was enhanced by the inclusion of data from the South East Asian Region (SEAR) and recruitment of additional centres within the WPR. Approximately 17,450 N. gonorrhoeae were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea by external quality controlled methods in 24 reporting centres in 20 countries and/or jurisdictions. A high proportion of penicillin and/or quinolone resistance was again detected amongst isolates tested in North Asia and the WHO SEAR, but much lower rates of penicillin resistance and little quinolone resistance was present in most of the Pacific Island countries. The proportion of gonococci reported as 'resistant', 'less susceptible' or 'non-susceptible' gonococci to the third-generation cephalosporin antibiotic ceftriaxone lay in a wide range, but no major changes were evident in cephalosporin minimal inhibitory concentration (MIC) patterns in 2007-2008. Altered cephalosporin susceptibility was associated with treatment failures following therapy with oral third-generation cephalosporins. There is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit a form of plasmid mediated high level resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and from the WHO WPR and SEAR supports the need for gonococcal antimicrobial resistance surveillance programs such as GASP to be maintained and potentially expanded.

The phase-variable allele of the pilus glycosylation gene pglA is not strongly associated with strains of Neisseria gonorrhoeae isolated from patients with disseminated gonococcal infection.

The Neisseria gonorrhoeae pglA gene has two alleles, one of which is phase variable. A previous study reported that all disseminated gonococcal infection (DGI) isolates contained the phase-variable allele and proposed a causal link. In the present study of 81 strains no absolute correlation between DGI and the phase-variable pglA allele was observed.

A cluster of culture positive gonococcal infections but with false negative cppB gene based PCR.

OBJECTIVES: To describe the prevalence and characteristics of isolates of Neisseria gonorrhoeae grown from urine samples that produced negative results with nucleic acid amplification assays (NAA) targeting the cppB gene. METHODS: An initial cluster of culture positive, but cppB gene based NAA negative, gonococcal infections was recognised. Urine samples and suspensions of gonococci isolated over 9 months in the Northern Territory of Australia were examined using cppB gene based and other non-cppB gene based NAA. The gonococcal isolates were phenotyped by determining the auxotype/serovar (A/S) class and genotyped by pulsed field gel electrophoresis (PFGE). RESULTS: 14 (9.8%) of 143 gonococci isolated were of A/S class Pro(-/)Brpyut, indistinguishable on PFGE and negative in cppB gene based, but not other, NAA. CONCLUSIONS: This cluster represents a temporal and geographic expansion of a gonococcal subtype lacking the cppB gene with consequent loss of sensitivity of NAA dependent on amplification of this target. Gonococci lacking the cppB gene have in the past been more commonly associated with the PAU-/PCU- auxotype, a gonococcal subtype hitherto infrequently encountered in Australia. NAA based on the cppB gene as a target may produce false positive as well as false negative NAA. This suggests that unless there is continuing comparison with culture to show their utility, cppB gene based NAA should be regarded as suboptimal for use either as a diagnostic or supplemental assay for diagnosis of gonorrhoea, and NAA with alternative amplification targets should be substituted.

Continuing evolution of the pattern of quinolone resistance in Neisseria gonorrhoeae isolated in Sydney, Australia.

BACKGROUND AND OBJECTIVES: Multiple phenotypes of quinolone-resistant Neisseria gonorrhoeae isolated in Sydney since 1984 originated in Asia and increased in number and level of resistance in 1995. GOAL: To study the origins, characteristics, and infection pattern of quinolone-resistant Neisseria gonorrhoeae in Sydney from 1995 to 1997 and to compare these results with prior findings. STUDY DESIGN: Quinolone minimal inhibitory concentrations, phenotype, and geographic source of quinolone-resistant Neisseria gonorrhoeae isolated in Sydney from 1995 to 1997 were analyzed. RESULTS: Two hundred nineteen episodes of infection with quinolone-resistant Neisseria gonorrhoeae from 2,236 gonococcal isolates occurred during 1995 through 1997. The rate of isolation of quinolone-resistant Neisseria gonorrhoeae increased significantly at the end of 1996 and was maintained through 1997. The increase resulted from sustained domestic transmission of a limited number of phenotypes in heterosexual patients. CONCLUSION: The pattern of isolation of quinolone-resistant Neisseria gonorrhoeae in Sydney changed from the sporadic isolation of multiple phenotypes of imported quinolone-resistant Neisseria gonorrhoeae to a higher rate of endemic disease caused by a few subtypes. Alterations in antibiotic treatment regimens in the affected patient group were required.

Failure of azithromycin therapy in gonorrhea and discorrelation with laboratory test parameters.

BACKGROUND: Azithromycin is efficacious in the treatment of chlamydial genital tract infection but less so in gonorrhea. However, MICs of azithromycin for gonococci from previously reported azithromycin treatment failures were consistently below the 'susceptible' MIC level of 2 mg/L. GOAL OF THIS STUDY: To examine gonococci not eliminated with 1 g azithromycin therapy to establish treatment outcome/MIC correlates in gonorrhea. STUDY DESIGN: The MICs and phenotypes of gonococci isolated from five cases of treatment failure after 1 g azithromycin therapy were determined and compared with the MICs of a systematic sample of routine isolates. RESULTS: Azithromycin MICs of gonococci from five cases of failed 1 g azithromycin treatment were 0.125 or 0.25 mg/L, well within the current 'susceptible' MIC range. None of the isolates were of the mtr phenotype. The MIC90 of a systematic sample of 219 gonococcal isolates was 0.25 mg/L. CONCLUSION: The antibiotic MIC/treatment outcome correlates that are usually found in gonorrhea do not apply for azithromycin. Current MIC criteria do not accurately define susceptibility or resistance of gonococci to azithromycin and by themselves do not predict the likely outcome of therapy. Pharmacokinetic factors may decrease the predictive value of MIC data.

High-level quinolone resistance in Neisseria gonorrhoeae: a report of two cases.

BACKGROUND AND OBJECTIVES: Fluoroquinolones are widely used oral agents for treating Neisseria gonorrhoeae. Resistance to these agents is sporadic and usually at a low level. Two instances of high-dose ciprofloxacin regimens failing in the treatment of gonococcal infection, caused by strains with high-level quinolone resistance, are reported. STUDY DESIGN: This is a case report. CONCLUSION: High-level resistance to quinolone antibiotics resulting in treatment failure was observed in two distinct gonococcal isolates from patients infected in the Philippines (ciprofloxacin; minimal inhibitory contribution = 16 mg/l). Continued monitoring of the quinolone sensitivity of Neisseria gonorrhoeae is appropriate and prudent.