Antimicrobial susceptibilities of Neisseria gonorrhoeae strains isolated in Surabaya, Indonesia.

Until recently, the only common strains of antimicrobial agent-resistant Neisseria gonorrhoeae detected in Indonesia were penicillinase-producing N. gonorrhoeae (PPNG) strains. Despite the spread of resistance to other antimicrobial agents among N. gonorrhoeae in Southeast Asia, surveillance for such resistance in Indonesia has been limited. We evaluated the in vitro susceptibilities of 86 N. gonorrhoeae isolates from female sex workers in Surabaya, Indonesia, to 13 antimicrobial agents. Of the 86 isolates, 89% were resistant to penicillin (MIC, > or = 2.0 micrograms/ml), 98% were resistant to tetracycline (MIC, > or = 2.0 micrograms/ml), 18.1% were resistant to spectinomycin (MIC, > or = 128.0 micrograms/ml), and 97.7% showed decreased susceptibility to thiamphenicol (MIC, 1 to 2 micrograms/ml). Thus, thiamphenicol and spectinomycin may be approaching the end of their usefulness as the drugs of choice for the treatment of gonococcal infections in Surabaya. While the susceptibilities of N. gonorrhoeae to cephalosporins (ceftriaxone, cefixime, and cefoxitin) and fluoroquinolones (ciprofloxacin and ofloxacin) are universal, these drugs have not been used because they are more expensive in Indonesia than thiamphenicol. We conclude that Surabaya had the highest reported rate of penicillin and tetracycline resistance among the Southeast Asian countries and that cephalosporins or fluoroquinolones should be reasonable alternatives for the treatment of gonorrhea in this locale.     

Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan

The spread of antimicrobial-resistant Neisseria gonorrhoeae worldwide is a critical issue in the control of sexually transmitted infections. The purpose of this study was to clarify recent trends in the susceptibility of N. gonorrhoeae to various antimicrobial agents and to compare these data with our previous data. Minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined in N. gonorrhoeae strains clinically isolated from male gonococcal urethritis. In addition, amino acid sequencing of penicillin-binding protein (PBP) 2, encoded by the penA gene, was analyzed so that genetic analysis of mosaic PBP 2 could clarify the susceptibility of the strains to cefixime and other cephalosporins. The susceptibility rate for ceftriaxone, cefodizime, and spectinomycin, agents whose use is recommended by the guideline of the Japanese Society of Sexually Transmitted Infections (JSSTI), was 100 %. The susceptibility rates of the strains to penicillin G and ciprofloxacin were lower than those in previous reports. Mosaic PBP 2 structures were detected in 51.9 % of the strains and the MICs of the strains with the mosaic PBP 2 to cefixime were much higher than those of the strains without the mosaic PBP 2. In the clinical situation, the treatment regimen recommended by the JSSTI remains appropriate; however, the susceptibility to cephalosporins should be intensively surveyed because strains with mosaic PBP 2 were commonly detected.     

Antimicrobial susceptibility and molecular determinants of quinolone resistance in Neisseria gonorrhoeae isolates from Shanghai

OBJECTIVES: To determine the antimicrobial susceptibility of Neisseria gonorrhoeae from Shanghai and to type the quinolone resistance-determining regions (QRDRs) of ciprofloxacin-resistant isolates. METHODS: N. gonorrhoeae isolates (n = 159) were consecutively collected from male patients in Shanghai and examined for their antimicrobial susceptibilities to penicillin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone. The mutation profiles of the QRDRs of gyrA and parC were determined for 103 isolates including one susceptible isolate and one isolate with intermediate levels of susceptibility to ciprofloxacin. RESULTS: High percentages of the 159 isolates were resistant to ciprofloxacin (98.7%), penicillin (93.1%) and tetracycline (56.5%). Penicillinase-producing N. gonorrhoeae (PPNG, 37.8%) or penicillinase-producing/tetracycline-resistant N. gonorrhoeae (PP/TRNG, 13.8%) accounted for 51.6% of the isolates. Chromosomal resistance to penicillin was observed in 41.5% of the isolates. Tetracycline resistance was noted in 56.5% of the isolates with 20.1% carrying plasmid-mediated resistance and 36.4% being chromosomally resistant. All isolates were susceptible to ceftriaxone and spectinomycin, although a trend to decreased susceptibility was noted. QRDR mutations were observed in the 101 ciprofloxacin-resistant isolates and the one ciprofloxacin-intermediate isolate, in contrast to the ciprofloxacin-susceptible isolate tested. Mutations in the QRDRs comprised four predominant (65.0% of the 103 isolates) patterns of a total of 19 patterns. Mutations in parC were significantly associated with higher MICs of ciprofloxacin. CONCLUSIONS: Spectinomycin and ceftriaxone are currently recommended for the treatment of gonorrhoea in Shanghai. Although the present study indicates that these antimicrobials should remain effective, the identification of isolates with decreased susceptibility underscores the importance of ongoing antimicrobial susceptibility surveillance to monitor and respond to the emergence of resistant isolates.     

Vancomycin hypersusceptibility in Neisseria gonorrhoeae isolated from patients involves diverse mutations.

We investigated the genetic determinants of hypersusceptibility to vancomycin and erythromycin found in Neisseria gonorrhoeae strains isolated from patients. In terms of resistance (highest concentration of antibiotic permitting growth), the levels of vancomycin resistance of six strains ranged from 0.2 to 1.0 microgram/ml, and the level of erythromycin resistance of these strains was 0.02 or 0.05 micrograms/ml. DNA from these strains was used to introduce their hypersusceptibility determinants into partially isogenic derivatives of N. gonorrhoeae 89 which initially had wild-type levels of resistance to vancomycin (greater than or equal to 3.0 micrograms/ml) and erythromycin (greater than or equal to 0.1 microgram/ml). The recombination frequencies found in reciprocal transformation tests of six isogenic strains indicated that the mutations responsible for vancomycin hypersusceptibility were located at different sites. The transformants selected for increased resistance to vancomycin were also resistant to erythromycin. This evidence, together with DNA concentration-response curves, indicated that the mutations affected either one gene locus or closely linked loci. The recombination indices obtained in crosses between our hypersusceptible strains and DNAs from reference strains carrying the envelope mutations env-1, env-2, env-3, and env-10 showed that the mutation (designated env-12) responsible for erythromycin hypersusceptibility in one strain (89-954) was located in close proximity to env-2. The determinant of vancomycin hypersusceptibility in strain 89-954 was distinct from env-12, but the two were linked. In the other five isogenic strains, the hypersusceptibilities to both vancomycin and erythromycin could be annulled by spontaneous mutations in a locus provisionally designated vel because of its likely effects on the envelope. Vel+ mutants obtained by selection with either vancomycin alone or erythromycin alone gained increased resistance to both antibiotics.     

Antimicrobial susceptibility of Aeromonas species isolated from patients with diarrhea.

In vitro susceptibility to 17 antimicrobial agents was determined for Aeromonas caviae, A. hydrophila, and A. sobria isolated from feces of patients with diarrhea. The three Aeromonas species shared a similar susceptibility pattern, except to cephalothin. Of the oral antimicrobial agents, the quinolones, followed by chloramphenicol, were most active; trimethoprim-sulfamethoxazole and tetracycline had good but variable activity.     

江苏省淋病奈瑟菌对抗菌药物的敏感性分析

目的检测江苏省淋病奈瑟菌（淋菌）临床分离株对几种抗生素的药敏情况，并初步探讨耐药因素。方法采用琼脂稀释法检测淋菌对青霉素、四环素、环丙沙星、头孢曲松、头孢吡肟、头孢噻肟、大观霉素、左氧氟沙星的MIC。结果淋菌对3种头孢类药物敏感率均为100％，对大观霉素敏感率为94．7％，对四环素敏感率为1．1％，而对青霉素和环丙沙星100％耐药。结论江苏省淋菌临床分离株对青霉素、四环素、环丙沙星耐药严重，对目前的一线药物（头孢类药物和大观霉素）敏感，但应重视大观霉素耐药株的出现。     

Update on antimicrobial susceptibility and genotype of Neisseria gonorrhoeae isolated in Italy

Antimicrobial susceptibilities and genotypes of Neisseria gonorrhoeae collected in 2006-2010 from 6 medical centers located in Italy were compared with those from a previous survey conducted in 2003-2005. Resistance to ciprofloxacin increased from 34.2% to 62% whereas penicillin resistance declined from 25.5% to 14%. Important change in antimicrobial resistance rates and a high genetic variability among N. gonorrhoeae from Italy were observed.     

Comparison of broth microdilution and agar dilution for susceptibility testing of Neisseria gonorrhoeae.

Broth microdilution was compared with agar dilution to test the susceptibilities of 170 clinical isolates of Neisseria gonorrhoeae to several antimicrobial agents. Percents agreement between the two methods within 1 doubling dilution were 98.8% for enoxacin, 94.3% for penicillin G, 93.5% for spectinomycin, and 98.4% for ceftriaxone.     

The effect of media on antimicrobial susceptibility testing of Neisseria gonorrhoeae

We have investigated the effect of four different media on the results of susceptibility tests for clinical and reference strains of Neisseria gonorrhoeae. Diagnostic Sensitivity Test (DST) agar supplemented with 5% lysed horse blood and 1% IsoVitaleX was regarded as the 'standard' and three other media were compared with it--DST plus 5% lysed blood, GC agar supplemented with 1% IsoVitaleX and Proteose agar plus 1% haemoglobin and 1% IsoVitaleX. We found no significant differences between the two DST media when testing penicillin, cefuroxime, tetracycline or erythromycin. Proteose agar compared well with the 'standard' for all antibiotics except erythromycin for which MICs were significantly increased. GC agar showed the poorest agreement with the 'standard' medium. Gonococci appeared more sensitive to tetracycline and less sensitive to erythromycin on this medium. The use of GC agar did not significantly affect susceptibilities to the beta-lactam agents tested, although MICs measured on GC agar did tend to be higher than on the 'standard' DST medium.     

Changing antibiotic susceptibility of Neisseria gonorrhoeae in Franceville, Gabon.

Susceptibilities to penicillin, cefotaxime, kanamycin, tetracycline, and spectinomycin were measured for 5 reference strains and 302 Neisseria gonorrhoeae isolates collected between 1980 and 1985. After an initial rise, the number of penicillinase-producing strains decreased. A gradual decrease in susceptibility to spectinomycin and the appearance of tetracycline-resistant strains were also documented.     

Beta-lactam susceptibility of Neisseria gonorrhoeae isolates from pelvic inflammatory disease.

Gonococci isolated in France from urethral and endocervical cultures in 12 women with pelvic inflammatory disease were similar, in their susceptibility to six beta-lactam antibiotics as determined by an agar dilution procedure, to isolates from patients with uncomplicated anogenital infections (83 patients). These data contrast with earlier study done in the United States.     

Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand.

The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending sexually transmitted disease clinics in Cholburi and Bangkok, Thailand, were determined by agar dilution. Some 28.2% of isolates produced beta-lactamase. A total of 97.9% of beta-lactamase-positive and 51% of beta-lactamase-negative isolates tested were resistant to penicillin (MICs, greater than or equal to 2 micrograms/ml), 70% of isolates tested were resistant to tetracycline (MICs, greater than or equal to 2 micrograms/ml), and 91% of isolates tested were susceptible to spectinomycin (MICs, less than or equal to 64 micrograms/ml). The MICs for 90% of isolates for the other drugs tested were 2 micrograms/ml for erythromycin, 2 micrograms/ml for cefoxitin, 1 micrograms/ml for cefuroxime, 0.125 micrograms/ml for cefpodoxime, 0.06 micrograms/ml for cefotaxime, 0.25 micrograms/ml for ceftazidime, 0.03 micrograms/ml for ceftizoxime, 0.03 micrograms/ml for ceftriaxone, 0.03 micrograms/ml for cefixime, 0.06 micrograms/ml for aztreonam, 0.008 micrograms/ml for ciprofloxacin, 0.125 micrograms/ml for norfloxacin, and 0.075 micrograms/ml for ofloxacin. Fewer than 1.5% of isolates were resistant to the extended-spectrum cephalosporins tested. Some 0.3% or fewer isolates were resistant to broad-spectrum cephalosporins, fluoroquinolones, or the monobactam aztreonam. Antibiotic resistance among N. gonorrhoeae isolates from Cholburi and Bangkok in May 1990 appeared to be primarily limited to penicillin and tetracycline, which are no longer used to control gonorrhea. Spectinomycin, which has been in general use against gonorrhea in Thailand since 1983, has dwindling utility, with resistance at a level of 8.9%.     

Neisseria gonorrhoeae strains isolated in Hong Kong: in vitro susceptibility to 13 antibiotics.

Fifty-five Neisseria gonorrhoeae strains isolated in Hong Kong over a period of 6 months were tested for their in vitro susceptibility to 13 antimicrobial agents by the agar dilution method. Six strains were beta-lactamase producing. In addition, five beta-lactamase strains from Singapore were tested. Among the non-beta-lactamase-producing strains, 34 (62%) had intermediate resistance to penicillin, with minimal inhibitory concentrations (MICs) ranging from 0.125 to 0.5 microgram/ml, and 15 strains were fully susceptible to penicillin (MICs, 0.015 to 0.06 microgram/ml). The MICs of penicillin for all beta-lactamase-producing strains were 2 microgram/ml, and the strains were resistant to ampicillin. Although a direct correlation between the MICs for resistance to penicillin and the other antibiotics tested was not observed, the gonococci isolated in Hong Kong were notably more resistant to tetracycline and streptomycin than has been reported elsewhere, with 78% of strains requiring for inhibition an MIC of tetracycline of greater than 2 microgram/ml and 51% of the isolates requiring an MIC of streptomycin of greater than 128 microgram/ml. All strains were susceptible to spectinomycin and kanamycin as well as to sulfamethoxazole-trimethoprim (ratio, 19:1). Among the cephalosporins, the order of effectiveness was cefuroxime, cefamandole, and cefoxitin. The older generation of cephalosporins, cephradine and cephalexin, was the least effective: 45 and 37% of the strains, respectively, required for inhibition MICs of greater than or equal to 8 microgram/ml. Cefotaxime, a new parenteral cephalosporin, was the most active; the median MIC was at least 10-fold lower than that of cefuroxime.     

Comparability of laboratory diagnosis and antimicrobial susceptibility testing of Neisseria gonorrhoeae from reference laboratories in Western Europe

OBJECTIVES: The aim of this study was to obtain information on the comparability of methods for the laboratory diagnosis of bacterial sexually transmitted infections (STIs) that contribute to the surveillance data in the European Union (EU) and Norway. Surveillance of bacterial STIs is important across Europe because of the movement of individuals between countries at a time when STI incidence appears to be increasing in many countries. METHODS: Cross-sectional survey using a questionnaire, to provide information on laboratory methods for the diagnosis of gonorrhoea, and a panel of strains of Neisseria gonorrhoeae, to compare susceptibility testing, was circulated to laboratories in the EU and Norway. RESULTS: The questionnaire revealed marked diversity in the methodologies used for the laboratory diagnosis of gonorrhoea across Europe. Fourteen laboratories participated in an exchange of gonococcal strains to assess the methodology in current use for susceptibility testing. The methods included disc diffusion and determination of the minimum inhibitory concentration (MIC) using agar dilution and/or Etest. There was no common method used, each centre varied from another by at least one procedure. Overall agreement using all methods was >70%, being highest for ceftriaxone and lowest for tetracycline. Disc diffusion gave the lowest agreement with the consensus compared with determination of MIC by either agar dilution or Etest. CONCLUSIONS: A variety of methods were used across the EU and Norway for the laboratory diagnosis and susceptibility testing and resulted in poor concordance between laboratories on the definition of resistant N. gonorrhoeae. This suggests that there is a need for greater standardization of methodology that provides surveillance data in the EU and Norway.     

Antimicrobial susceptibility of Enterobacteriaceae isolated from vegetables.

There is potential for the normal faecal flora of humans to be augmented by resistant strains of bacteria, acquired from food. The frequency of resistance in the aerobic Gram-negative faecal flora is often very high. The purpose of this study was to find out whether food strains contribute to this resistance. One hundred and thirty-seven vegetable samples were studied, 48 of Finnish origin, and 89 imported. From these samples, 535 different strains of bacteria belonging to the family Enterobacteriaceae were isolated. Enterobacter spp. were most frequent, Escherichia coli was rare. Sensitivity testing was undertaken only for isolates with different biotypes and antibiograms. No resistance was found to cefotaxime, aztreonam, imipenem, gentamicin, nalidixic acid or ciprofloxacin. The frequency of trimethoprim resistance was 0.2%, sulphamethoxazole resistance 1.3%, and tetracycline resistance 5.5%. These frequencies were much lower than those found in faecal flora. Chloramphenicol and cefuroxime resistance was found in 12% and 14% of isolates, respectively. The only statistically significant differences between the Finnish and imported strains were for these two; the Finnish isolates were more resistant to cefuroxime, whereas the imported ones were more resistant to chloramphenicol. Consequently, bacteria from vegetables are not responsible for the high prevalence of resistant Enterobacteriaceae in faecal flora in Finland; they are in fact unusually susceptible to the antibiotics studied. Multiresistance profiles, typical of strains associated with human activities, were not identified in these isolates.     

Trends in susceptibility of Neisseria gonorrhoeae to ceftriaxone from 1985 through 1991.

The antimicrobial susceptibilities of 16,441 gonococcal isolates from Seattle-King County were determined for ceftriaxone, cefoxitin, penicillin G, and tetracycline. From 1985 to 1989, ceftriaxone, in combination with doxycycline, was increasingly used for treatment of gonorrhea, and by 1989, it was used as therapy for > 80% of cases in Seattle-King County. MICs of ceftriaxone correlated significantly (P < 0.001) with those of the other beta-lactam antibodies included in this study. Geometric mean MICs of penicillin G for isolates that did not produce beta-lactamase increased from 1985 to 1991. The geometric mean MICs of cefoxitin, ceftriaxone, and tetracycline began to decline in 1987 but increased in 1990 and 1991. The percentage of strains with decreased susceptibility to ceftriaxone (MIC, 0.06 to 0.25 microgram/ml) rose from 0.3% in 1985 to 5.3% in 1987 but subsequently declined steadily to 2.6% in 1991, despite increased use of ceftriaxone as routine therapy for gonorrhea. Changes in patterns of antimicrobial susceptibility may be related not only to antimicrobial selection pressures but also to less well understood population shifts among Neisseria gonorrhoeae strains within a community.     

Antimicrobial susceptibility of Neisseria gonorrhoeae in Greece: data for the years 1994-2004

OBJECTIVES: Surveillance data concerning antimicrobial susceptibilities of Neisseria gonorrhoeae isolated in Greece during the 11 year period 1994-2004 are presented. METHODS: Antimicrobial susceptibilities of all gonococcal isolates received by the Greek National Reference Center for N. gonorrhoeae during the study period were determined in terms of MICs using Etest. Trends in yearly isolation frequencies by susceptibility category were estimated for defining significant changes in overall susceptibility figures. RESULTS: Cefotaxime and spectinomycin retained undiminished activity against all isolates throughout the study period. High rates of resistance and intermediate susceptibilities were noticed for penicillin, tetracycline and erythromycin, and even for norfloxacin and ciprofloxacin. A substantial portion (16.5%) of the gonococcal samples consisted of multiresistant strains exhibiting resistance to two or more agents of different antibiotic classes. Although annual rates of low-level chromosomal resistance decreased, high-level resistance owing to the presence of penicillin- and tetracycline-resistance plasmids increased. Fluoroquinolone resistance also showed a significant increasing trend after 1996, reaching a peak rate of 11.3% in 2004. CONCLUSION: Third-generation cephalosporins and spectinomycin should be considered as first-choice drugs for the empirical treatment of gonorrhoea in Greece.