Susceptibility of gonococci isolated in London to therapeutic antibiotics: establishment of a London surveillance programme. London Gonococcal Working Group

OBJECTIVES: To establish the in vitro susceptibility of gonococci isolated in the London area to antibiotics in current therapeutic use and to establish a sentinel surveillance system for monitoring trends in antibiotic resistant gonorrhoea in London. METHODS: Isolates of Neisseria gonorrhoeae from consecutive patients attending genitourinary medicine clinics at 10 hospitals in the London area were collected over a 3 month period, May to July 1997. The susceptibility to penicillin, ciprofloxacin, tetracycline, and spectinomycin was determined for each isolate. Isolates exhibiting either plasmid or chromosomally mediated resistance were additionally tested for susceptibility to agents used as alternative treatments including azithromycin, ceftriazone, and ofloxacin. The resistant isolates were also tested for plasmid profiles (penicillinase producing N gonorrhoeae, PPNG), type of tetM determinant (tetracycline resistant N gonorrhoeae, TRNG), and presence of gyrA and parC mutations (quinolone resistant N gonorrhoeae, QRNG). RESULTS: A total of 1133 isolates were collected which represents > 95% of the total gonococci isolated in the 3 months. Plasmid mediated resistance was exhibited by 48 (4.2%) isolates; six (0.5%) were PPNG, 15 (1.3%) were PP/TRNG, and 27 (2.4%) were TRNG. The majority of PPNG (18 of 20 tested) carried the 3.2 MDa penicillinase plasmid whereas the two types of tetM determinant were more evenly distributed. High level resistance to ciprofloxacin was detected in four (0.4%) isolates and double mutations were found in the quinolone resistance determining region (QRDR) of the gyrA gene in three QRNG with MICs of 16 mg/l and a single mutation in one isolate with a MIC of 1 mg/l to ciprofloxacin. No parC mutations were found. Of the remaining 1081 isolates, 86 (8.0%) were chromosomally mediated resistant N gonorrhoeae (CMRNG). CONCLUSIONS: A unique collection of gonococcal isolates has been established which can be used as a baseline for surveillance of susceptibility to antibiotics and for epidemiological purposes.     

Antimicrobial susceptibility profile of resistance phenotypes of Neisseria gonorrheae in India

BACKGROUND AND OBJECTIVES: Regular monitoring of antimicrobial resistance of Neisseria gonorrheae needs to be established in the country. The aim of the study was to determine the trend of resistance phenotypes of N. gonorrheae in India, and to assess the susceptibility profile of resistance phenotypes. METHODS: Antimicrobial susceptibilities of N. gonorrheae isolates to penicillin, tetracycline, ceftriaxone, ciprofloxacin, and spectinomycin were determined by in terms of minimum inhibitory concentrations using Etest. World Health Organization reference strains were used as control strains. Phenotypic characterization of N. gonorrheae isolates was carried out on the basis of plasmid and chromosomally mediated resistance to penicillin and tetracycline. RESULTS: Of 382 isolates, 172 (45.0%) belonged to 6 resistance phenotype i.e., penicillinase-producing N. gonorrheae (PPNG) (16.5%), tetracycline resistant N. gonorrheae (TRNG) (8.9%), PPNG-TRNG (4.7%), chromosomally mediated tetracycline resistant N. gonorrheae (11.2%), and chromosomally mediated penicillin resistant N. gonorrheae (3.7%). Chromosomally mediated penicillin and tetracycline resistant N. gonorrheae isolates were not detected. Chromosomally mediated penicillin resistant N. gonorrheae and chromosomally mediated tetracycline resistant N. gonorrheae decreased from 2002 to 2006 whereas TRNG strains increased during the study period. Ciprofloxacin resistant and ceftriaxone less sensitive strains were more frequent among the resistance phenotypes. CONCLUSIONS: The high rates of plasmid and chromosomally mediated resistance to penicillin, tetracycline along with high rates of resistance to ciprofloxacin among all the resistance phenotypes underlines the necessity for continuous surveillance of antimicrobial resistance to help in controlling the spread of gonorrhoea.     

Surveillance of antimicrobial susceptibilities in Neisseria gonorrhoeae in Nanjing, China, 1999-2006

OBJECTIVE: To monitor the frequency and types of antibiotic resistance of Neisseria gonorrhoeae in Nanjing, China, between 1999 and 2006. METHODS: beta-Lactamase production was determined by paper acidometric testing. Minimum inhibitory concentrations (MICs) to penicillin, ceftriaxone, tetracycline, ciprofloxacin, and spectinomycin were determined by agar plate dilution. Plasmid types were determined for TRNG and PPNG isolates by PCR. RESULTS: One-thousand two-hundred and eight N. gonorrhoeae isolates were examined. The rate of PPNG rose from 8.0% (9 of 112) in 1999 to 57.36% (113 of 197) in 2004, and declined to 44.44% (88 of 198) in 2006. Prevalence of TRNG increased from 1.8% (2 of 112) in 1999 to 32.82% (65 of 198) in 2006. 99.23% (258 of 260) of TRNG contained the Dutch-type tetM gene and 2 strains contained the American-type tetM gene. All PPNG examined contained the Asian type plasmid. Among non-PPNG, chromosomally mediated resistance to penicillin varied from 57.84% (59 of 102) to 87.80% (72 of 82). Chromosomal resistance to ciprofloxacin (QRNG) was detected in 83.93% (94 of 112) of the strains in 1999 and 98.99% (196 of 198) in 2006. Eight spectinomycin-resistant N. gonorrhoeae strains were detected between 2001 and 2006. None of the gonococcal isolates tested was resistant to ceftriaxone but decreased susceptibility was observed in some strains. CONCLUSIONS: Among N. gonorrhoeae strains isolated in Nanjing, China, plasmid mediated resistance including PPNG and TRNG increased significantly between 1999 and 2006. Chromosomally mediated resistance to both penicillin and ciprofloxacin was also high during this period. Spectinomycin resistance of N. gonorrhoeae was sporadic. Ceftriaxone and spectinomycin can be considered effective antimicrobial agents for the treatment of gonorrhea in Nanjing at the present time.     

Antimicrobial susceptibility, auxotype and plasmid content of Neisseria gonorrhoeae in northern Tanzania: emergence of high level plasmid mediated tetracycline resistance.

OBJECTIVE--To study the antimicrobial susceptibility, plasmid content, auxotype and serogroup of strains of Neisseria gonorrhoeae isolated from an urban population of STD clinic attenders in Northern Tanzania. METHODS--The minimum inhibitory concentrations of nine common antimicrobial agents were measured by the agar dilution method against 130 strains of Neisseria gonorrhoeae isolated in a free government STD clinic in Mwanza town. The auxotype, plasmid content and serogroup of these strains were also determined by conventional techniques. RESULTS--65 strains (50%) were penicillinase producers (PPNG), and 34 (26%) exhibited chromosomally mediated resistance to penicillin. Seven (5%) were sensitive to tetracycline; 78 (60%) showed intermediate levels of resistance, and 45 (35%) had high level plasmid mediated resistance (TRNG), all of which carried a 25.2 MDa plasmid. 79 strains (61%) showed decreased sensitivity to trimethoprim-sulphamethoxazole, and five (4%) were resistant to this agent. All isolates were fully sensitive to spectinomycin, azithromycin, cefotaxime, cefuroxime, norfloxacin and ciprofloxacin. One hundred and one strains (78%) were of type W11/111, 22 type W1, and seven cross reacting strains. The W1 strains were significantly more likely to be carrying plasmid mediated resistance to both penicillin and tetracycline. Six different auxotypes were present, the major type requiring proline. Plasmid profiles showed the presence of both the 3.2 MDa and the 4.4 MDa beta-lactamase encoding plasmids. CONCLUSION--a high proportion of gonococcal isolates remain resistant to penicillin in this region, and most isolates are now also resistant to tetracycline, with the emergence of plasmic mediated tetracycline resistance. Trimethoprim-sulphonamide sensitivity is also decreasing. The population of strains is heterogeneous, and both African and Asian beta-lactamase encoding plasmids are present.     

A one-year survey of Neisseria gonorrhoeae isolated from patients attending an east London genitourinary medicine clinic: antibiotic susceptibility patterns and patients'' characteristics.

OBJECTIVES--To collect epidemiological data on gonococcal infection in an east London genitourinary medicine (GUM) clinic; to perform antibiotic susceptibility testing on Neisseria gonorrhoeae isolates and relate results to patient data; to assess the efficacy of current first-line antibiotic therapy for treating gonorrhoea. METHODS--Gonococcal isolates were collected from 113 patients attending the GUM clinic at Newham General Hospital over a one year period. Isolates (104) were tested for susceptibility to various antibiotics. Plasmid profiles were obtained for penicillinase producing gonococci (PPNG) and isolates exhibiting high-level tetracycline resistance (TRNG). Epidemiological information was collected from clinic attenders by routine note-taking. RESULTS--PPNG (16) accounted for 15% of isolates tested, only three being acquired outside the United Kingdom (U.K.). Plasmid typing showed three types of beta-lactamase-encoding plasmids were represented (2.9 MDa, 3.2 MDa and 4.4 MDa). Amongst the non-PPNG isolates, high-level chromosomal resistance to penicillin (CMRNG) was found in 3.5%, intermediate resistance in 57.5% and full susceptibility in 39%. One isolate showed decreased susceptibility to ciprofloxacin (MIC = 0.06 mg/l). Three PPNG isolates also possessed a 25.2 MDa plasmid and expressed high-level tetracycline resistance encoded by tetM. All isolates were susceptible to cefixime, cefotaxime, azithromycin and spectinomycin. Most gonorrhoea (90%) was seen in local residents. The male:female case ratio was 2:1 with homosexually-acquired gonorrhoea accounting for only 3.5% of the total. Most patients (96%) had acquired gonorrhoea in the U.K.. A past history of gonorrhoea was more frequent in male patients. Concurrent chlamydial infection was seen in 31% females and 16% males. CONCLUSIONS--The high PPNG rate supports a previous decision to change first-line therapy from amoxycillin with probenecid to ciprofloxacin. There was no evidence of clinical treatment failure with ciprofloxacin. Cefixime, cefotaxime, azithromycin and spectinomycin all appear to be suitable alternative therapies. Acquisition of gonorrhoea abroad was associated with isolates exhibiting penicillin resistance but such isolates were also obtained from patients infected locally and without a history of foreign travel.     

Antimicrobial agents and gonorrhoea: therapeutic choice, resistance and susceptibility testing.

INTRODUCTION: Neisseria gonorrhoeae, the causative agent of gonorrhoea is a particularly well adapted pathogen that has continued to evolve mechanisms to evade treatment with antimicrobial agents. THERAPEUTIC CHOICE: The choice of antibiotic for use in the first-line treatment of gonorrhoea should be made with knowledge of the susceptibility of the isolates of N gonorrhoeae to be encountered. RESISTANCE: High-level resistance to penicillin and tetracycline in N gonorrhoeae is plasmid-mediated and a major therapeutic problem. Penicillinase-producing N gonorrhoeae, first described in 1976, have now spread worldwide and tetracycline-resistant N gonorrhoeae, described in 1985, are becoming increasingly prevalent. Chromosomal resistance to penicillin is low-level and affects a range of antibiotics. High-level resistance to spectinomycin has been sporadic and has not limited its use whereas the emergence of resistance to ciprofloxacin will have a significant impact on its use for gonorrhoea. SUSCEPTIBILITY TESTING: A variety of methods are available including disc diffusion, breakpoint agar dilution technique, E-test and determination of the minimum inhibitory concentration (MIC). The choice of methodology will depend on the number and type of isolates and the facilities available for testing. DISCUSSION: Surveillance programmes to monitor levels of antibiotic resistant isolates are essential to ensure therapeutic success.     

Reduced susceptibility to azithromycin and high percentages of penicillin and tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil, 1998

BACKGROUND: The identification of Neisseria gonorrhoeae isolates resistant to antimicrobial agents currently recommended for the treatment of gonococcal infections continues to escalate globally. Thus, in some areas, resistance to fluoroquinolone drugs is commonplace; several reports document resistance to third-generation cephalosporins, and the sporadic isolation of spectinomycin-resistant isolates continues unabated. Gonococcal resistance to azithromycin, an antibiotic used for the primary treatment of gonococcal infections in some Latin American countries, also has been described. Because the prevalence of resistant isolates is insufficiently documented in many areas of Latin America, the efficacy of locally recommended therapies for gonococcal infections is often unknown. GOAL: To determine the antimicrobial susceptibility and strain types of N gonorrhoeae isolates collected in Manaus, Brazil. These data will establish antimicrobial susceptibility baseline data for the region as a reference point for future surveillance. STUDY DESIGN: Consecutive N gonorrhoeae isolates from urethral and endocervical specimens were collected and examined for identity, antimicrobial susceptibility, and strain type (plasmid content, tetM type, auxotype, and serovar). RESULTS: Most of the isolates (65/81; 85.2%) were resistant to tetracycline, penicillin, or both, with the majority (n = 62) carrying plasmid-mediated resistance to tetracycline (tetracycline-resistant N gonorrhoeae [TRNG]). All of the TRNG contained the Dutch-type tetM plasmid, and 18 were A/S class NR/IA-02. Penicillinase-producing N gonorrhoeae comprised 8.2% (7/81) of the isolates. Of these seven isolates, four also were TRNG, and two carried chromosomal resistance to tetracycline. The isolates were susceptible to ciprofloxacin, spectinomycin, and ceftriaxone. However, 23 isolates were characterized by reduced susceptibility to azithromycin (MIC, 0.25-0.5 microg/ml), and one isolate had reduced susceptibility to ciprofloxacin (MIC, 0.25 microg/ml). CONCLUSIONS: This study supports the continued use of third-generation cephalosporins, spectinomycin, and fluoroquinolone drugs for the primary treatment of gonococcal infections in Manaus. The occurrence of isolates with reduced susceptibility to azithromycin and ciprofloxacin underscores the importance of ongoing antimicrobial susceptibility monitoring to support decisions regarding appropriate drugs for the treatment of gonococcal infections.     

Antimicrobial susceptibilities of Neisseria gonorrhoeae strains isolated in Java,Indonesia

BACKGROUND: Despite the rapid spread of antibiotic resistance in gonococci all over Southeast Asia, there is only limited surveillance for antibiotic susceptibility in Indonesia. GOAL: This study was undertaken to determine the frequency and diversity of antimicrobial resistance in gonococcal isolates from cohorts of female commercial sex workers in Bandung and Jakarta, Indonesia, and to characterize the Tet M plasmid among the tetracycline-resistant strains N gonorrhoeae. STUDY DESIGN: The antimicrobial susceptibility of 267 strains (85 strains from Bandung and 182 from Jakarta) to penicillin, spectinomycin, tetracycline, ciprofloxacin, cefotaxime, thiamphenicol, kanamycin, azithromycin, and trimethoprim-sulfamethoxazole (TMP-SMZ) was determined by agar dilution. Typing of the Tet M plasmid in tetracycline-resistant isolates was performed by PCR. RESULTS: Prevalence of penicillin and tetracycline resistance was extremely high: 60.0% of the isolates from Bandung and 70.9% of the isolates from Jakarta were resistant to penicillin. Of these, 60.0% and 62.1%, respectively, were penicillinase-producing N gonorrhoeae (PPNG). All the isolates from Bandung and 98.4% from Jakarta were resistant to tetracycline. All tetracycline-resistant isolates from Bandung and 97.8% from Jakarta carried a PCR fragment characteristic of the "Dutch" type Tet M plasmid. One isolate from Jakarta showed chromosomal resistance to tetracycline (0.6%). Chromosomal resistance to thiamphenicol (MIC, >/=2.0 microg/ml) was significantly higher in Jakarta than in Bandung (P < 0.05). All gonococcal isolates were susceptible to kanamycin, spectinomycin, cefotaxime, ciprofloxacin, and azithromycin. CONCLUSION: Spectinomycin, fluoroquinolones, and azithromycin are still useful primary drugs for treatment of gonococcal infections in Indonesia. Continued surveillance of antimicrobial susceptibility should be part of gonorrhea control in Indonesia.     

Fluoroquinolone-resistant Neisseria gonorrhoeae in Bali, Indonesia: 2004

OBJECTIVES: In the mid-1990s, fluoroquinolones were introduced in Indonesia for the management of gonorrhea and are now part of the national recommended treatment guidelines. We recently documented introduction of ciprofloxacin-resistant Neisseria gonorrhoeae strains in female sex workers (FSWs) in Timika, Indonesia, 5 years after treating gonococcal cervicitis with ciprofloxacin and periodically monitoring antimicrobial susceptibility of isolates. To assess the importance of this observation, we determined antimicrobial susceptibilities and strain types of N. gonorrhoeae isolates from FSWs seen in a sexually transmitted infection (STI) clinic in Denpasar, Bali, Indonesia. GOAL: The goal of this study was to determine antimicrobial susceptibilities and strain types among N. gonorrhoeae isolated from FSWs in Denpasar, Bali. STUDY DESIGN: FSWs in Denpasar were screened for N. gonorrhoeae by standard culture. Endocervical isolates were frozen in Microbank tubes and sent to the University of California at San Francisco on dry ice. Antimicrobial susceptibility testing using a Clinical Laboratory Standards Institute-recommended agar dilution method was performed at the Centers for Disease Control and Prevention. Isolates were characterized by beta-lactamase production, antimicrobial resistance phenotypes, and auxotype/serovar class. RESULTS: One hundred forty-seven N. gonorrhoeae isolates were characterized. All isolates were highly resistant to tetracycline (minimum inhibitory concentration, >or=16.0 microg/mL): 117 (79.1%) were beta-lactamase-positive (PP-TR), 3 (2.0%) exhibited chromosomally mediated resistance to penicillin (PenR-TRNG), and 27 (18.2%) were susceptible to penicillin (TRNG). All isolates were susceptible to ceftriaxone, cefixime, and spectinomycin; lack of interpretive criteria do not allow interpretation of susceptibilities of cefoxitin, cefpodoxime, or azithromycin. Fifty-nine (40.1%) isolates were ciprofloxacin-resistant; 35 (59.3%) of the ciprofloxacin-resistant isolates exhibited high-level resistance to ciprofloxacin (Cip-HLR; minimum inhibitory concentration, >or=4.0 microg/mL of ciprofloxacin). Three (2.0%) isolates were intermediate to ciprofloxacin. Twenty-two strain types were identified among these isolates; small clusters were identified with 3 strain types. CONCLUSIONS: N. gonorrhoeae isolates from FSWs in Denpasar were resistant to penicillin and tetracycline; 40.1% of the isolates were fluoroquinolone-resistant. With gonorrhea prevalence of 35% at this clinic (by nucleic acid amplified tests), ongoing surveillance for antimicrobial resistance will be needed to appropriately choose treatment for infections caused by these resistant organisms.     

Association between auxotypes, serogroups, and antibiotic susceptibilities of Neisseria gonorrhoeae isolated from women in Mumbai (formerly Bombay), India.

OBJECTIVES: Gonococcal isolates were differentiated based on susceptibility pattern, penicillinase production (PPNG or non-PPNG), serogroup, auxotype, protein, and plasmid profile. The association between serogroup and auxotype and PPNG was determined. STUDY DESIGN: Women attending tertiary level health centers and the sexually transmitted disease (STD) clinic in Mumbai, India, were screened for Neisseria gonorrhoeae. Minimal inhibitory concentration testing was performed according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines. Auxotypes, serogroups, protein profile, and plasmid content were also studied. RESULTS: Of the 33 isolates, 16 (48.5%) were resistant to penicillin, and 28 (84.8%) showed a chromosomally mediated resistance to tetracycline. Five (15.2%) isolates showed resistance to ciprofloxacin, whereas 12 (36.4%) showed a reduced susceptibility. Twenty-seven (81.8%) isolates belonged to the WI serogroup, and 15 (46.7%) were penicillinase producers (PPNG). Seventeen (51.5%) isolates were of the nonrequiring auxotype, whereas seven (21.2%) were proline requiring. Fifteen (55.6%) of the isolates belonged to the nonrequiring-WI auxotype/serogroup (A/S) class. Ten of the PPNG isolates possessed the 4.4 MDa plasmid, whereas four had the 3.2 MDa plasmid. Increases in the molecular weight of the major outer membrane protein were observed. CONCLUSION: A high prevalence of chromosomal resistance to penicillin and tetracycline was observed. The 4.4 MDa plasmid was the most prevalent among the PPNG isolates. We observed ciprofloxacin resistance, which has not been reported in previous studies in India. The nonrequiring auxotype was the most prevalent, followed by the proline requiring auxotype. WI serogroup was the most commonly observed among the isolates studied. The nonrequiring/WI A/S class was the most prevalent among the PPNG.     

Antibiotic susceptibility of Neisseria gonorrhoeae in Arkhangelsk, Russia

OBJECTIVES: To characterise comprehensively the antibiotic susceptibility of Neisseria gonorrhoeae in Arkhangelsk, Russia, and to investigate whether the recommended treatment guidelines are updated and effective. METHODS: The susceptibility of N gonorrhoeae isolates, cultured during June-November 2004 mainly from consecutive patients with gonorrhoea (n = 76) in Arkhangelsk, to penicillin G, ampicillin, cefixime, ceftriaxone, ciprofloxacin, erythromycin, azithromycin, kanamycin, spectinomycin and tetracycline was analysed using Etest. Nitrocefin discs were used for beta-lactamase detection. RESULTS: The levels of intermediate susceptibility and resistance to the different antibiotics were as follows: penicillin G 76%, ampicillin 71%, cefixime 0%, ceftriaxone 3%, ciprofloxacin 17%, erythromycin 54%, azithromycin 14%, kanamycin 49%, spectinomycin 0% and tetracycline 92%. Of the isolates 55 (72%) were determined as multiresistant--that is, they showed intermediate susceptibility or resistance to three or more classes of antibiotics. However, none of the isolates were beta-lactamase producing. CONCLUSIONS: In Arkhangelsk, and presumably in many other areas of Russia, penicillins, ciprofloxacin, erythromycin, azithromycin, kanamycin and tetracycline should not be used in the treatment of gonorrhoea if the results of antibiotic susceptibility testing are not available. In Russia, optimised, standardised and quality-assured antibiotic susceptibility testing needs to be established in many laboratories. Subsequently, continuous local, regional and national surveillance of antibiotic susceptibility is crucial to detect the emergence of new resistance, monitor changing patterns of susceptibility and be able to update treatment recommendations on a regular basis.     

High percentages of resistance to tetracycline and penicillin and reduced susceptibility to azithromycin characterize the majority of strain types of Neisseria gonorrhoeae isolates in Cuba, 1995-1998

BACKGROUND: In many regions the susceptibility of Neisseria gonorrhoeae isolates to antimicrobial agents is rarely tested. The Gonococcal Antimicrobial Surveillance Program (GASP) in Cuba was established as part of a larger regional GASP program to facilitate the collection and reporting of antimicrobial susceptibility data for N gonorrhoeae isolates. GOAL: The goal was to retrospectively determine the antimicrobial susceptibility and molecular epidemiology of 91 isolates of N gonorrhoeae isolated from 11 centers in Cuba. STUDY DESIGN: Isolates of N gonorrhoeae were collected and presumptively identified from 11 Cuban provincial health centers. They were then forwarded to the National Laboratory of Pathogenic Neisseria Havana for confirmatory identification and were subsequently analyzed at the Center for GASP in Ottawa. Isolates were tested for susceptibility to penicillin, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin, and azithromycin by the agar dilution method. To establish baseline data for molecular epidemiologic profiles, the auxotype (A), serovar (S), plasmid content (P), and TetM type of the isolates were determined. Certain A/S/P classes were further analyzed by pulsed field gel electrophoresis (PFGE). RESULTS: High percentages of the 91 N gonorrhoeae isolates were resistant to penicillin (68%) and tetracycline (83.5%), with 56% being penicillinase-producing (PPNG) and 64% carrying plasmid-mediated tetracycline resistance (TRNG; 50% were PP/TRNG). An additional 14% of the isolates carried chromosomal resistance (CMRNG) to either tetracycline or penicillin or both antibiotics. All isolates were susceptible to spectinomycin, ceftriaxone, and ciprofloxacin. However, nine isolates were resistant to azithromycin (MIC, > or = 1.0 microgram/ml), and 43 other isolates displayed reduced susceptibility to this antibiotic (MIC, 0.25-0.5 microgram/ml). Although a total of 21 different A/S classes were identified, most of the isolates (61) belonged to three A/S classes: NR/IA-6 (35 isolates), NR/IB-1 (15 isolates), and P/IA-6 (11 isolates). Thirty-two of 45 PP/TRNG were A/S class NR/IA-6, and nine of the P/IA-6 isolates were TRNG. By contrast, most of A/S class NR/IB-1 (8) were CMRNG. PFGE analysis following digestion with NheI or SpeI further clustered the isolates into separate groups. CONCLUSIONS: This study demonstrates high percentages of N gonorrhoeae isolates with penicillin and tetracycline resistance in Cuba. As has been noted in other studies in the Caribbean region and Latin America, resistance and reduced susceptibility to azithromycin are developing as emerging problems. Since penicillin and tetracycline continue to be widely used for the treatment of gonococcal infections in Cuba, this study indicates the importance of antimicrobial susceptibility surveillance so that effective antibiotics may be recommended for treatment of gonococcal infections.     

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from three Caribbean countries: Trinidad, Guyana, and St. Vincent

BACKGROUND: The percentage of Neisseria gonorrhoeae isolates resistant to antimicrobial agents commonly used for treatment is unknown in many Caribbean countries. GOAL: To determine the antimicrobial susceptibility of N gonorrhoeae isolates from Trinidad (144 isolates), Guyana (70 isolates), and St. Vincent (68 isolates) so baseline data can be established for further studies, and to assist in establishing effective treatment guidelines. STUDY DESIGN: Consecutive urethral and endocervical specimens from several clinics were collected and identified as N gonorrhoeae. Isolates of N gonorrhoeae were tested for their susceptibility to penicillin, tetracycline, ceftriaxone, ciprofloxacin, spectinomycin, and azithromycin. The presumptive identification of penicillinase-producing N gonorrhoeae and/or tetracycline-resistant N gonorrhoeae isolates based on MIC was confirmed by plasmid and tetM content analysis. RESULTS: High percentages of penicillin and/or tetracycline resistance were observed in N gonorrhoeae isolates from Guyana (92.9%), St. Vincent (44.1%), and Trinidad (42.4%). Isolates from all three countries were susceptible to ceftriaxone, ciprofloxacin, and spectinomycin. One penicillinase-producing N gonorrhoeae/tetracycline-resistant N gonorrhoeae from Guyana had an MIC of 0.5 microg/l to ciprofloxacin. This and nine other isolates from Guyana also were resistant to azithromycin (defined as MIC > or = 2.0 microg/ml) as well as penicillin and tetracycline. A reduced susceptibility to azithromycin was displayed by 16% of the isolates from St. Vincent and 72% of the isolates from Guyana (MIC, 0.25-1.0 microg/ml). Most penicillinase-producing N gonorrhoeae isolates carried Africa-type plasmids (61/90), with 28 of 90 having Toronto-type plasmids and a single isolate carrying an Asia-type plasmid. The tetM determinant in tetracycline-resistant N gonorrhoeae isolates was predominantly of the Dutch type (68/91). CONCLUSIONS: The high prevalence of N gonorrhoeae isolates from 3 of 21 English- and Dutch-speaking Caricom countries in the Caribbean with either plasmid-mediated or chromosomal resistance to penicillin and tetracycline supports international observations that these drugs should not be used to treat gonococcal infections. The detection of isolates with reduced susceptibility to drugs such as azithromycin, which currently are recommended for treatment in the region, attest to the importance of the continued monitoring of gonococcal antimicrobial susceptibility for the maintenance of effective treatment guidelines.     

Antimicrobial susceptibilities of Neisseria gonorrhoeae in Kigali, Rwanda, and trends of resistance between 1986 and 2000

BACKGROUND: Plasmid-mediated and chromosomal-mediated resistance of Neisseria gonorrhoeae to penicillin, tetracycline, thiamphenicol, and trimethoprim-sulfamethoxazole has spread dramatically in Africa. Monitoring of antimicrobial susceptibility is a key element in the control of sexually transmitted diseases. GOAL: To document antimicrobial susceptibilities of gonococci isolated during the past 15 years in Kigali, Rwanda. STUDY DESIGN: Minimal inhibitory concentrations of recently collected gonococcal isolates of eight antimicrobials were determined. The results were compared with data collected for isolates obtained since 1986. RESULTS: In 1986, 35% of the gonococcal isolates were penicillinase-producing N gonorrhoeae. Tetracycline-resistant N gonorrhoeae appeared in 1989. The prevalence of penicillinase-producing N gonorrhoeae and tetracycline-resistant N gonorrhoeae increased significantly to 70.5% and 89.2%, respectively. Chromosomal resistance to penicillin, tetracycline, and thiamphenicol increased temporarily, then decreased significantly. Chromosomal resistance to trimethoprim-sulfamethoxazole appeared in 1988 and increased to 21.6%. All the isolates were susceptible to ceftriaxone, ciprofloxacin, spectinomycin, and kanamycin. CONCLUSIONS: This study illustrated the rapidly increasing frequencies of penicillinase-producing N gonorrhoeae and tetracycline-resistant N gonorrhoeae. Chromosomal resistance to thiamphenicol and trimethoprim-sulfamethoxazole excludes these drugs as alternative treatment. Programs for antimicrobial susceptibility surveillance of N gonorrhoeae should urgently be established in Africa.     

Effectiveness of norfloxacin and ofloxacin for treatment of gonorrhoea and decrease of in vitro susceptibility to quinolones over time in Rwanda.

OBJECTIVE--To study the effectiveness of single-dose norfloxacin and ofloxacin in the treatment of gonococcal urethritis in men, and to monitor in vitro antimicrobial susceptibility to these antibiotics over time. SETTING--Centre Médico-Social de Bilyogo, Kigali, Rwanda. The only clinic in Rwanda using quinolones for the treatment of gonorrhoea. METHODS--As part of a monitoring programme, men with gonococcal urethritis were evaluated after treatment with norfloxacin (800 mg) in 1986 and 1987, and after treatment with ofloxacin (400 mg) in 1989. RESULTS--Neisseria gonorrhoeae was eradicated from the urethra from 96.0% (189/197) and from 97.1% (166/171) men treated with norfloxacin and ofloxacin, respectively. Overall 38.2% of the pretreatment isolates produced penicillinase (PPNG isolates) and 20.4% (44/216) of the tested non-PPNG isolates were chromosomally resistant to penicillin (MIC > or = 2.0 mg/l). Resistance to tetracycline and thiamphenicol was common in both PPNG and non-PPNG and increased considerably in 1989. All isolates were susceptible to kanamycin, spectinomycin, ceftiaxone, norfloxacin, ofloxacin and ciprofloxacin. However, a higher number of isolates recovered in 1989 showed decreased susceptibility to the quinolones. Treatment failure occurred more often in subjects with isolates having MIC values > or = 0.06 mg/L of norfloxacin (p = 0.006). Seven out of 13 patients who did not respond to therapy had no signs nor symptoms of urethritis. CONCLUSION--Quinolone antibiotics are now indicated as a first line treatment of gonorrhoea in countries with a problem of antimicrobial multiresistance. However, antimicrobial susceptibility to the quinolones may decrease rapidly, and close monitoring of the in vitro susceptibility of N gonorrhoeae and the clinical effectiveness of the antibiotics is imperative.     

Antimicrobial susceptibility of Neisseria gonorrhoeae in Cuba (1995-1999): implications for treatment of gonorrhea

BACKGROUND: Antibiotic-resistant strains of Neisseria gonorrhoeae, especially those resistant to penicillin and tetracycline, have spread with remarkable rapidity in many Caribbean countries. GOAL: The goal of the study was to survey the antibiotic susceptibilities of N gonorrhoeae strains isolated from 1995 to 1999 in Cuba and to discuss the impact of antimicrobial resistance on the management of gonorrhea in the country. STUDY DESIGN: Susceptibility of the strains to penicillin, tetracycline, cefuroxime, ceftriaxone, ciprofloxacin, spectinomycin, and azithromycin were determined by an agar dilution method. RESULTS: Penicillin and tetracycline resistance was noted in 60.8% and 54.2%, respectively, of the N gonorrhoeae strains tested. A total of 63.35 (76/120) of the N gonorrhoeae strains exhibited plasmid-mediated resistance to penicillin, tetracycline, or both. Strains with chromosomally mediated resistance to these antibiotics accounted for 10% (12/120) of the strains. The strains were susceptible to ceftriaxone, cefuroxime, spectinomycin, and ciprofloxacin. One strain's ciprofloxacin MIC was 0.125 mircog/ml. Of the 52 strains tested, 23.1% displayed intermediate resistance to azithromycin. CONCLUSIONS: N gonorrhoeae strains exhibited a high frequency of resistance and multiresistance to penicillin and tetracycline. Therefore, these antibiotics should no longer be used to treat gonococcal infections in Cuba and should be substituted with effective drugs such as third-generation cephalosporins, spectinomycin, and fluoroquinolones. The detection of intermediate resistance to azithromycin and ciprofloxacin underlines the importance of periodic surveillance for susceptibility of N gonorrhoeae strains to antimicrobials agents used as primary therapy for gonorrhea.     

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.     

Temporal trends in gonococcal antibiotic resistance in Baltimore.

Each month from August 1986 through July 1990, clinical and laboratory data were evaluated for the first 25 urethral isolates of Neisseria gonorrhoeae from men attending a Baltimore sexually transmitted disease (STD) clinic as part of an effort to understand factors that contribute to changes in gonococcal antimicrobial susceptibility. During the 48-month study period, 1193 gonococcal isolates were evaluated; the proportion of penicillinase-producing N. gonorrhoeae (PPNG) isolates steadily increased, the prevalence of tetracycline-resistant N. gonorrhoeae (TRNG) remained relatively stable, and chromosomally mediated penicillin resistance increased steadily during the first 5 6-month intervals, then decreased, only to increase again during the final 2 6-month intervals. Changes in antibiotic treatment regimens for gonorrhea were associated with changes in the prevalence of chromosomally mediated penicillin resistance. In a supplementary study to characterize patterns of antibiotic use among men and women attending the STD clinics, 9% of patients reported antibiotic use in the 2 weeks prior to clinic visit. Antibiotics were taken prior to clinic attendance by 65% of patients reporting antibiotic use, because of concerns regarding possible STD or STD exposure. These patients were significantly less likely to be culture positive for N. gonorrhoeae when compared with patients who did not report antibiotic use. Temporal trends in N. gonorrhoeae antibiotic resistance appear to be influenced by many factors, including treatment regimens and self medication.     

Antimicrobial susceptibility and biochemical patterns of Neisseria gonorrhoeae strains in Vejle area, Denmark

Background  Strains of Neisseria gonorrhoeae resistant to penicillin and ciprofloxacin have been isolated worldwide. Increasing number of N. gonorrhoeae that lack the enzyme proline aminopeptidase (proA-negative N. gonorrhoeae ) have been detected in many countries all over the world.
Objectives  This study aims to assess the resistance profiles of N. gonorrhoeae isolates sent to the Department of Clinical Microbiology in Vejle, Denmark, between 2003 and 2007, and to analyse their biochemical patterns.
Methods  Sixty-two strains of N. gonorrhoeae were retrospectively analysed for their susceptibility to penicillin, ciprofloxacin and ceftriaxone. The identification of isolated strains was confirmed using both biochemical and immunological tests.
Results  Twenty-one (33.9%) N. gonorrhoeae isolates were resistant to penicillin and 30 (48.4%) were resistant to ciprofloxacin. All strains were susceptible to ceftriaxone. Fifty-six (90.3%) N. gonorrhoeae strains showed API NH biochemical code 10 010 (produced acid from glucose and proline aminopeptidase). Six strains showed code 10 000 that lack the enzyme proline aminopeptidase (proA-negative N. gonorrhoeae ).
Conclusions  Ceftriaxone should be used as the first-line treatment of gonorrhoea in Vejle community area, Denmark, both for infections with proA-producing and proA-negative N. gonorrhoeae isolates, which circulate in the region.     

Surveillance of antibiotic resistance of Neisseria gonorrhoeae isolates in China, 1993-1998

BACKGROUND: The prevalence of sexually transmitted diseases (STDs) has been increasing in China since the 1980s. Because gonorrhea is the most frequently reported STD there, information on the antimicrobial susceptibility of Neisseria gonorrhoeae will aid in its control. GOAL: To investigate the antimicrobial susceptibility of N gonorrhoeae isolates in China and to provide data for formulation of treatment guidelines and control policies. METHODS: The agar dilution technique was used to determine antimicrobial susceptibility, and acidimetric method was used to test for penicillinase-producing N gonorrhoeae. RESULTS: A total of 3186 gonococcal isolates were tested during the 6-year study period. The rate of resistance to penicillin was 66.70%; 8.14% of isolates were penicillinase-producing N gonorrhoeae. The percentage of tetracycline-resistant isolates was 92.03%, and that of highly tetracycline-resistant isolates was 4.65%. The rate of resistance to ciprofloxacin was also relatively high (34.25%). The rates of resistance to spectinomycin and ceftriaxone were 0.44% and 0.57%. CONCLUSIONS: The gonococcal isolates in China are relatively highly resistant to penicillin, tetracycline, and ciprofloxacin, but most of them are still susceptible to spectinomycin and ceftriaxone. Standardized treatment of gonorrhea is needed to prevent further spread of resistant gonococcal strains.