Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.

BACKGROUND: Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. METHODS: Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. RESULTS: Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 µg/mL; 111 (78.7%), MIC = 4 µg/mL; and 28 (19.9%), MIC = 8 µg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 µg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). CONCLUSIONS: Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.

Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016.

BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years. METHODS: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests. RESULTS: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years. CONCLUSIONS: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018.

We describe a gonorrhoea case with combined high-level azithromycin resistance and ceftriaxone resistance. In February 2018, a heterosexual male was diagnosed with gonorrhoea in the United Kingdom following sexual intercourse with a locally resident female in Thailand and failed treatment with ceftriaxone plus doxycycline and subsequently spectinomycin. Resistance arose from two mechanisms combining for the first time in a genetic background similar to a commonly circulating strain. Urgent action is essential to prevent further spread.

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections.

Bacterial sexually transmitted infections are widespread and common, with Neisseria gonorrhoeae (gonorrhea) and Chlamydia trachomatis (chlamydia) being the two most frequent causes. If left untreated, both infections can cause pelvic inflammatory disease, infertility, ectopic pregnancy, and other sequelae. The recommended treatment for gonorrhea is ceftriaxone plus azithromycin (to empirically treat chlamydial coinfections). Antibiotic resistance to all existing therapies has developed in gonorrheal infections. The need for new antibiotics is great, but the pipeline for new drugs is alarmingly small. The aminomethyl spectinomycins, a new class of semisynthetic analogs of the antibiotic spectinomycin, were developed on the basis of a computational analysis of the spectinomycin binding site of the bacterial 30S ribosome and structure-guided synthesis. The compounds display particular potency against common respiratory tract pathogens as well as the sexually transmitted pathogens that cause gonorrhea and chlamydia. Here, we demonstrate the in vitro potencies of several compounds of this class against both bacterial species; the compounds displayed increased potencies against N. gonorrhoeae compared to that of spectinomycin and, significantly, demonstrated activity against C. trachomatis that is not observed with spectinomycin. Efficacies of the compounds were compared to those of spectinomycin and gentamicin in a murine model of infection caused by ceftriaxone/azithromycin-resistant N. gonorrhoeae; the aminomethyl spectinomycins significantly reduced the colonization load and were as potent as the comparator compounds. In summary, data produced by this study support aminomethyl spectinomycins as a promising replacement for spectinomycin and antibiotics such as ceftriaxone for treating drug-resistant gonorrhea, with the added benefit of treating chlamydial coinfections.

Aminoglycoside susceptibility of Pasteurella multocida isolates from bovine respiratory infections in China and mutations in ribosomal protein S5 associated with high-level induced spectinomycin resistance.

Twenty-three isolates of Pasteurella multocida were tested for susceptibility to six aminoglycoside agents and screened by polymerase chain reaction for the presence of aminoglycoside resistance genes. In addition, mutations in the resistance-determining region of strains showing a high level of induced resistance to spectinomycin strains were examined. Susceptibility testing showed that all of the isolates were resistant to at least two types of aminoglycosides, and that the most effective antimicrobial was spectinomycin. The resistance genes aphA1, strB and aacA4 were present in all 23 isolates. In the three induced spectinomycin-resistant strains, a 9-bp deletion in rpsE that encodes ribosomal protein S5 was detected.

New Horizons in Mycoplasma genitalium Treatment.

Mycoplasmagenitalium is an important sexually transmitted pathogen responsible for both male and female genital tract disease. Appreciation of its significance in human disease has been hampered by its slow growth in culture, difficulty in isolating it, and lack of commercial molecular-based tests for rapid detection. Comparatively few in vitro data on antimicrobial susceptibility are available due to the scarcity of clinical isolates and difficulty in performing susceptibility tests to determine minimum inhibitory concentrations for M. genitalium. Antimicrobial agents that inhibit protein synthesis such as macrolides, along with fluoroquinolones that inhibit DNA replication, have been the treatments of choice for M. genitalium infections. Even though international guidelines recommend azithromycin as first-line treatment, rapid spread of macrolide resistance as well as emergence of quinolone resistance has occurred. Increasing rates of treatment failure have resulted in an urgent need for new therapies and renewed interest in other classes such as aminocyclitols, phenicols, and streptogramins as treatment alternatives. Limited data for new investigational antimicrobials such as the ketolide solithromycin suggest that this drug may eventually prove useful in management of some resistant M. genitalium infections, although it is not likely to achieve cure rates >80% in macrolide-resistant strains, in a similar range as recently reported for pristinamycin. However, agents with completely new targets and/or mechanisms that would be less likely to show cross-resistance with currently available drugs may hold the greatest promise. Lefamulin, a pleuromutilin, and new nonquinolone topoisomerase inhibitors are attractive possibilities that require further investigation.

Patterns and predictors of antimicrobial resistance among Staphylococcus spp. from canine clinical cases presented at a veterinary academic hospital in South Africa.

BACKGROUND: Antimicrobial resistance in staphylococci, often associated with treatment failure, is increasingly reported in veterinary medicine. The aim of this study was to investigate patterns and predictors of antimicrobial resistance among Staphylococcus spp. isolates from canine samples submitted to the bacteriology laboratory at the University of Pretoria academic veterinary hospital between 2007 and 2012. Retrospective data of 334 Staphylococcus isolates were used to calculate the proportion of samples resistant to 15 antimicrobial agents. The Cochran-Armitage trend test was used to investigate temporal trends and logistic regression models were used to investigate predictors of antimicrobial resistance in Staphylococcus aureus and Staphylococcus pseudintermedius. RESULTS: Results show that 98.2% (55/56) of the S. aureus isolates were resistant to at least one drug while 42.9% were multidrug resistant. Seventy-seven percent (214/278) of the S. pseudintermedius isolates were resistant to at least one drug and 25.9% (72/278) were multidrug resistant. Resistance to lincospectin was more common among S. aureus (64.3%) than S. pseudintermedius (38.9%). Similarly, resistance to clindamycin was higher in S. aureus (51.8%) than S. pseudintermedius (31.7%) isolates. There was a significant (p = 0.005) increase in S. aureus resistance to enrofloxacin over the study period. Similarly, S. pseudintermedius exhibited significant increasing temporal trend in resistance to trimethoprim-sulphamethoxazole (p = 0.004), clindamycin (p = 0.022) and orbifloxacin (p = 0.042). However, there was a significant decreasing temporal trend in the proportion of isolates resistant to doxycycline (p = 0.041), tylosin (p = 0.008), kanamycin (p = 0.017) and amoxicillin/clavulanic acid (p = 0.032). CONCLUSIONS: High levels of multidrug resistance and the increasing levels of resistance to sulphonamides, lincosamides and fluoroquinolones among Staphylococcus spp. isolates in this study are concerning. Future studies will need to investigate local drivers of antimicrobial resistance to better guide control efforts to address the problem.

Australian Gonococcal Surveillance Programme annual report, 2013.

The Australian Gonococcal Surveillance Programme has continuously monitored antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae from all states and territories since 1981. In 2013, 4,897 clinical isolates of gonococci from public and private sector sources were tested for in vitro antimicrobial susceptibility by standardised methods. Decreased susceptibility to ceftriaxone (MIC value 0.06-0.125 mg/L) was found nationally in 8.8% of isolates, double that reported in 2012 (4.4%). The highest proportions were reported from New South Wales and Victoria (both states reporting 11.8%), with a high proportion of strains also reported from Tasmania but a low number of isolates were tested. In addition, there was a multi-drug-resistant strain of N. gonorrhoeae isolated from a traveller to Australia, with a ceftraixone MIC value of 0.5 mgL-the highest ever reported in Australia. These antimicrobial resistance data from Australia in 2013 are cause for considerable concern. With the exception of remote Northern Territory where penicillin resistance rates remain low (1.3%) the proportion of strains resistant to penicillin remained high in all jurisdictions ranging from 15.6% in the Australian Capital Territory to 44.1% in Victoria. Quinolone resistance ranged from 16% in the Australian Capital Territory to 46% in Victoria. Azithromycin susceptibility testing was performed in all jurisdictions and resistance ranged from 0.3% in the Northern Territory to 5.7% in Queensland. High level resistance to azithromycin (MIC value was > 256 mg/L) was reported for the first time in Australia, in 4 strains: 2 each from Queensland and Victoria. Azithromycin resistant gonococci were not detected in the Australian Capital Territory, Tasmania or from the remote Northern Territory. Nationally, all isolates remained susceptible to spectinomycin.

High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in France, March 2014.

We report the first case in France of a high-level azithromycin-resistant Neisseria gonorrhoeae (minimum inhibitory concentration (MIC) = 96 mg/L) assigned to MLST7363 (NG-MAST ST6360), also resistant to ciprofloxacin and tetracycline but susceptible to ceftriaxone. The patient was a 51 year-old heterosexual man who returned following 1g azithromycin monotherapy. Mechanisms of azithromycin resistance were a C2599T mutation in the four copies of the rrl gene and a novel mutation in the promoter of the mtrR gene.

Surveillance of antimicrobial susceptibilities of Neisseria gonorrhoeae in Nanning, China, 2000 to 2012.

OBJECTIVES: To monitor the frequency of antibiotic resistance of Neisseria gonorrhoeae (NG) in Nanning, China, between 2000 and 2012. METHODS: The production of ß-lactamase by NG isolates was determined using the paper acidometric testing method. Antimicrobial susceptibility testing was performed for tetracycline, ciprofloxacin, spectinomycin, and ceftriaxone using the agar dilution method. The χ(2) test, t test, and univariate and multivariate analyses were used to analyze the statistical difference of the results. RESULTS: A total of 923 NG isolates were collected in Nanning between 2000 and 2012. Among these, 131 (14.2%) were penicillinase-producing NG, 520 (56.3%) isolates were tetracycline-resistant NG, and 857 (92.9%) isolates were ciprofloxacin-resistant strains. One spectinomycin-resistant strain was identified in 2000. There were 304 (32.9%) isolates with decreased susceptibility to ceftriaxone; the proportion of such isolates increased from 22.8% in 2000 to 2002 to 48.9% in 2006 to 2008 (P < 0.001), followed by a fall to 32.2% in 2009 to 2012 (P = 0.001). Patients' age of 16 to 25 years and isolate collection period of 2008 to 2012 (except 2011) were demonstrated to be risk factors for infection with isolates with decreased susceptibility to ceftriaxone. CONCLUSIONS: Antimicrobial susceptibility of NG isolates obtained from patients in Nanning from 2000 to 2012 was characterized by high occurrence of penicillinase-producing NG, tetracycline-resistant NG, and ciprofloxacin-resistant strains. Spectinomycin and ceftriaxone can be considered drugs of choice for empirical treatment of NG infection in Nanning. Moreover, we recommend a combination of 500 mg or higher dose of intramuscular ceftriaxone and 1 g oral azithromycin be used for the treatment of NG infection in Nanning and possibly in China.

The Russian gonococcal antimicrobial susceptibility programme (RU-GASP)--national resistance prevalence in 2007 and 2008, and trends during 2005-2008.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major problem worldwide. In the former Soviet countries including Russia, the knowledge regarding AMR has been highly limited. However, in 2004 the Russian gonococcal antimicrobial susceptibility programme (RU-GASP) was initiated. The aims of this study were to examine and describe the prevalence of N. gonorrhoeae AMR in 2007 and 2008 in Russia, and reveal trends in the period from 2005 to 2008. Gonococcal isolates (660 in 2007 and 900 in 2008) from 36 surveillance sites were examined using agar dilution method. From 2005 to 2008, the proportion of isolates resistant to spectinomycin increased from 0% to 7.2%, and remained high for those resistant to ciprofloxacin (approximately 49%). The resistance to azithromycin was 2.3% and 0.4% in 2007 and 2008, respectively. All isolates between 2005 and 2008 were susceptible to ceftriaxone. In conclusion, the AMR of N. gonorrhoeae in Russia is high, as in most countries in the European Union, and ceftriaxone should be the first line for treatment. If there is no access to ceftriaxone or in the presence of severe beta-lactam antimicrobial allergy, spectinomycin should be used; however, the resistance to spectinomycin has increased. Regular, quality-assured national and international surveillance of AMR in N. gonorrhoeae is crucial globally for public health.

Neisseria gonorrhoeae antibiotic resistance in Paris, 2005 to 2007: implications for treatment guidelines.

Quinolone-resistant Neisseria gonorrhoeae rates have increased worldwide since 1994. The objective of this study was to appraise: (i) the antimicrobial susceptibility of Neisseria gonorrhoeae in a venereology clinic in Paris, between 2005 and 2007; and (ii) the factors associated with quinolone-resistant N. gonorrhoeae. A prospective study of consecutive cases was performed for the period 2005 to 2007. Susceptibility of N. gonorrhoeae to five antibiotics (ciprofloxacin, ceftriaxone, spectinomycin, penicillin G and tetracycline) was tested systematically. Clinical and epidemiological data were collected using a standardized form. Male-to-female sex ratio was 22.0. Median age was 30.0 years. Of 115 cases, 84 occurred in men having sex with men (72.6%) and 22 involved the anorectal area (19.1%). The rate of quinolone-resistant N. gonorrhoeae was 37.4% (43/115), without significant association with gender, age, sexual behaviour, past history of sexually transmitted diseases and susceptibility to other antibiotics. All N. gonorrhoeae were susceptible to ceftriaxone and spectinomycin. The rate of quinolone-resistant N. gonorrhoeae in Paris has been increasing since 2004. Ceftriaxone remains the gold standard treatment.

Clinical efficacy of the various drugs used in the treatment of gonorrhoeae.

BACKGROUND: Gonorrhoea is a purulent inflammation of mucus membrane of the genital tract and is a highly contagious sexually transmitted disease (STD) caused by the bacterium Neisseria gonorrhoae. Both men and women can be infected through a variety of sexual contact behaviours including vaginal, anal or oral intercourses. This comparative study was carried out in New Gulail Polyclinic Jeddah, KSA from Jan 2003 to March 2004 to find the clinical efficacy of ciprofloxacin, ceftriaxone and spectinomycin, the three commonly used drugs, in the treatment of gonorrhoea. METHODS: A total number of 300 patients suffering from gonorrhoea were included in this study. They were randomly divided into 3 groups of 100 patients each. Group-A patients were given Tablet Ciprofloxacin 500 mg, Group-B patients Injection Ceftriaxone 500 mg, and Group-C patients were put on Injection Spectinomycin 2 gm, all in stat dosage. On the 5th day following the treatment, all patients were re-examined and their clinical and laboratory findings were recorded and analysed. RESULTS: On the 5th day following treatment the Group-A (n = 100) showed 9 (9%) partial response and 11 (11%) cases showed no response to Ciprofloxacin. In the Group-B (n = 100), 4 (4%) patients showed partial response and 6 (6%) patients showed no response to Ceftriaxone. In Group-C, out of 100 patients, 4 (4%) cases reported with partial response and 2 (2%) patients showed no response to Spectinomycin. The efficacy of these anti-microbial agents was the same in both the genders. CONCLUSION: Anti-microbial susceptibility of N. gonorrhoeae to various antibiotics is gradually decreasing. In order to ensure full cure, all gonorrhoea patients should be followed-up after a single dosage of any antibiotic. Further research should continue for newer, effective, and preferably oral medication for the treatment of gonorrhoea.

Single-dose treatment of male patients with gonococcal urethritis using 2g spectinomycin: microbiological and clinical evaluations.

The microbiological and clinical efficacies of a single-dose treatment of 2g spectinomycin administered by intramuscular injection were studied in 365 male patients with gonococcal urethritis. A total of 210 patients (57.5%) could be evaluated, in 28 (13.3%) of whom Chlamydia trachomatis was detected in addition to Neisseria gonorrhoeae. A single dose of spectinomycin eradicated N. gonorrhoeae in 203 (96.7%) of the 210 patients. Among patients in whom N. gonorrhoeae was eradicated, pyuria and clinical symptoms, respectively, disappeared in 92.6% (162/175) and 98.9% (173/175) of patients without concomitant C. trachomatis and in 78.6% (22/28) and 71.4% (20/28) with C. trachomatis. Minimal inhibitory concentrations (MICs) were determined for four of seven N. gonorrhoeae strains isolated after spectinomycin treatment. MICs to spectinomycin for three of the four isolates were 16 microg/mL (defined as susceptible) and the MIC of the other isolate was 128 microg/mL, indicating resistance. The resistant isolate was a multidrug-resistant strain with resistance to ciprofloxacin, tetracycline, penicillin and cephalosporins, except for ceftriaxone. The results of this study indicate that a single-dose treatment using 2g spectinomycin is effective in treating patients with urethritis caused by N. gonorrhoeae, even in the era of multidrug-resistant N. gonorrhoeae.

National surveillance of antimicrobial susceptibility in Neisseria gonorrhoeae in 2005-2006 and recommendations of first-line antimicrobial drugs for gonorrhoea treatment in Russia.

OBJECTIVES: To investigate comprehensively the antimicrobial susceptibility and resistance of Neisseria gonorrhoeae during 2005-2006 in a national survey and to recommend effective antimicrobial drugs for the treatment of gonorrhoea in Russia. METHODS: The susceptibility of N gonorrhoeae isolates, cultured mainly from consecutive gonorrhoea patients (n = 1030) during the period January 2005 to December 2006 in Russia, to penicillin G, ceftriaxone, ciprofloxacin, tetracycline and spectinomycin was analysed using the agar dilution method. Nitrocefin discs were used for beta-lactamase detection. RESULTS: All isolates were susceptible to ceftriaxone. During 2005 and 2006, however, 5%, 50%, 70% and 77% displayed intermediate susceptibility or resistance to spectinomycin, ciprofloxacin, tetracycline and penicillin G, respectively. Furthermore, 4% of the isolates were beta-lactamase producing during these years. The different federal districts of Russia displayed substantial heterogeneities with regard to the prevalence of gonorrhoea and antimicrobial resistance among N gonorrhoeae isolates. CONCLUSIONS: In Russia, penicillins, ciprofloxacin, or tetracycline should definitively not be used in the empirical treatment of gonorrhoea. The recommended first-line antimicrobial drug should be ceftriaxone. If ceftriaxone is not available, spectinomycin ought to be used. Increasing levels of intermediate susceptibility and resistance to spectinomycin have, however, been observed during recent years and, accordingly, great care and monitoring should be undertaken when using this agent. Continuous local, national and international surveillance of N gonorrhoeae antimicrobial susceptibility, in order to reveal the emergence of new resistance, to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis, is crucial.

Antimicrobial susceptibility among Neisseria gonorrhoeae in New Zealand in 2002.

AIM: To estimate the prevalence of antimicrobial resistance among Neisseria gonorrhoeae, and to determine whether the increase in ciprofloxacin resistance observed in Auckland in 2001 had occurred in other parts of the country. METHODS: The antimicrobial susceptibility of N. gonorrhoeae (isolated in New Zealand over a 4-month period between April and August 2002) was tested at either LabPlus, Auckland District Health Board, or at ESR, using the same agar dilution method. RESULTS: The prevalence of resistance to the antimicrobials tested was: ceftriaxone, 0%; ciprofloxacin, 6.8%; penicillin, 9.0%; spectinomycin, 0%; and tetracycline, 27.8%. There were few statistically significant geographical differences in resistance within New Zealand. Gonococcal infections acquired in Asia were more likely to be ciprofloxacin and penicillin resistant than infections acquired in New Zealand. CONCLUSIONS: Ciprofloxacin resistance among N. gonorrhoeae in New Zealand has reached a level where this antibiotic is no longer the most appropriate first-line treatment. In fact, ceftriaxone should now be considered the most reliable option for the treatment and control of gonorrhoea in New Zealand, particularly in the Northland/Auckland region.

Antimicrobial susceptibility of Neisseria gonorrhoeae strains isolated in Guangzhou, China, 1996-2001.

OBJECTIVE: To investigate the in vitro antimicrobial susceptibility and resistant trends of Neisseria gonorrhoeae strains isolated in Guangzhou, from 1996 to 2001. METHODS: The agar dilution method was used to determine the minimum inhibitory concentrations (MICs) to four antimicrobials, penicillin G, ciprofloxacin, ceftriaxone, and spectinomycin. The resistance of all strains to four antibiotics was interpreted according to criteria used in the project of surveillance of gonococcal antibiotic susceptibility in the WHO Western Pacific Region. Penicillinase producing N gonorrhoeae (PPNG) was analysed by the paper acidometric method. RESULTS: 793 consecutive N gonorrhoeae isolates collected in Guangzhou were studied from 1996 to 2001. A total of 55 strains of PPNG were identified and the prevalence rapidly spread from 2% to 21.8%. Of the four antibiotics examined, ceftriaxone and spectinomycin appeared to be the most effective agents although two spectinomycin resistant strains were isolated in 1996. Their MIC(50), MIC(90), and geometric mean MIC (MICmean) were all between the sensitive ranges of the interpretative criteria and remained stable over the years. However, resistance increased continuously to penicillin G and dramatically to ciprofloxacin. In 1996-2001, MIC(50), MIC(90), and MICmean of penicillin G increased from 1 micro g/ml to 2 micro g/ml, 4 micro g/ml to 32 micro g/ml, and 0.68 micro g/ml to 2.35 micro g/ml, respectively; those of ciprofloxacin steeply increased from 0.12 micro g/ml to 4 micro g/ml, 2 micro g/ml to 32 micro g/ml, and 0.14 micro g/ml to 2.62 micro g/ml in 1996-9, respectively, and then declined slightly in 2000-1. The prevalence of resistant isolates spread from 57.2% to 81.8% for penicillin G and from 17.6% to 72.7% for ciprofloxacin over the 6 years. CONCLUSION: Resistance to penicillin and ciprofloxacin increased greatly during 1996-2001. Ceftriaxone and spectinomycin should be used as the first line agents in treating gonorrhoea. It is of great importance to continuously survey the susceptibilities of N gonorrhoeae to antibiotics in controlling the spread of gonococcal infections.