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Antibiotic resistance in Neisseria gonorrhoeae: genetics and mechanisms of resistance.

In recent years the emergence and spread of antibiotic resistance in Neisseria gonorrhoeae has increased markedly. Chromosomal resistance to penicillin and tetracycline is due to the effects of one or more mutations and is generally low-level. However, the effects of these mutations are additive. Thus, the level of resistance in strains with several mutations is often high enough to yield significant rates of treatment failure. Resistance to aminoglycosides (e.g., streptomycin and kanamycin) and spectinomycin, an aminocyclitol antibiotic is not due to the inactivation of the antibiotic but to an alteration in the sensitivity of the 30S ribosomal subunit to the drug. At least five beta-lactamase plasmids of N. gonorrhoeae have been described. Some of these plasmids can be mobilized by the 24.5-MDa gonococcal conjugative plasmid and transferred to other gonococcal strains. Gonococci have recently acquired high-level resistance to tetracycline due to the streptococcal tetM determinant. This determinant is located on a 25.2-MDa plasmid that possesses a considerable degree of homology with the 24.5-MDa conjugative plasmid. The 25.2-MDa plasmid has retained the ability to transfer beta-lactamase plasmids as well as to mobilize and transfer itself to suitable recipient strains.

Anti-Bacterial Agents↗

Therapy of uncomplicated gonorrhea due to antibiotic-resistant Neisseria gonorrhoeae.

Antibiotics available to treat uncomplicated anogenital infections due to beta-lactamase-producing Neisseria gonorrhoeae include spectinomycin, ceftriaxone, and clavulanic acid added to aqueous procaine penicillin G or amoxicillin. Important variables in deciding which antibiotic regimen to use include effectiveness against urethral, cervical, pharyngeal, and rectal infections; cost; eradication of coexisting incubating syphilis; adverse effects; efficacy against strains of N. gonorrhoeae with chromosomally mediated resistance to antimicrobial agents; ease of administration; patient acceptance; and the potential for inducing resistance to antimicrobial agents in pathogens other than those causing sexually transmitted diseases. This review outlines the advantages and disadvantages of the various regimens.

Anti-Bacterial Agents↗

Chromosomal resistance to antibiotics in gonococci from Bahrain.

Ninety-one isolates of non-penicillinase-producing Neisseria gonorrhoeae from patients in Bahrain were tested for serotype, auxotype, and antibiotic susceptibility. Ten serovars and three auxotypes were found. Of the 91 isolates, 49 (54%) were serovar IB-5/7, 59 (65%) had a penicillin MIC greater than or equal to 1 mg/l, 39 (45%) had a cefuroxime MIC greater than or equal to 0.5 mg/l, and 63 (69%) had a tetracycline MIC of greater than or equal to 4 mg/l. No spectinomycin or high-level tetracycline resistance was seen. Seventy of the 91 isolates were tested against ciprofloxacin and ceftriaxone, and 40 (57%) and 26 (37%) had MICs greater than or equal to 0.03 mg/l, respectively. DNA from two penicillin-resistant isolates was capable of transforming recipient strain FA19 to donor level of penicillin and cephalosporin resistance in four steps. The first three steps were indicative of the acquisition of known resistance mutations. The existence of the fourth level transformants, with the ability of donor DNA to transform strain FA140 to higher levels of resistance, suggest the presence of another resistance mutation.

Anti-Bacterial Agents↗

Pattern of sexually transmitted diseases in a Malagasy population.

BACKGROUND: Data concerning the spectrum and antimicrobial susceptibility of STDs in Madagascar are scarce. OBJECTIVES: Improvement of STD patient management in Madagascar. GOAL OF THE STUDY: Assessment of the spectrum of STDs and improvement of therapy. STUDY DESIGN: Etiologic study of 400 patients (169 men, 231 women) under consultation at the major STD service in Antananarivo for one or more of the STD syndromes, urethral discharge, cervicovaginal discharge, genital ulcers, or condylomata according to a fixed diagnostic schedule. RESULTS: Of genital ulcers, syphilis accounted for 46%, lymphogranuloma venereum for 24%, chancroid for 16%, and herpes for 1%. Of the syphilis cases, 51% presented as condyloma lata. Discharge was found in 124 men and 210 women. Counting concomitant infections separately, gonorrhea occurred in 69% of the men and 20% of the women with discharges, chlamydia infection in 42% and 52%, trichomoniasis in 9% and 31%, candidiasis in 12% and 30%. Bacterial vaginosis was found in 37% of the women with discharges. In 32% of male and 71% of female gonorrhea cases, there was concurrent chlamydia infection. Infection with HIV 1 or 2 was not detected. Determination of the antibiotic susceptibility of Neisseria gonorrhoea revealed high efficacy of ampicillin, ciprofloxacin, and spectinomycin; but frequent resistance to tetracycline and cotrimoxazole. CONCLUSIONS: High priority should be given to the management of infections with chlamydia and with Treponema pallidum as well as to educational measures to increase awareness of genital ulcer disease.

Adolescent↗

Single-dose ciprofloxacin for the treatment of uncomplicated gonorrhea: a worldwide summary.

BACKGROUND AND OBJECTIVES: Antibiotic therapy for Neisseria gonorrhoeae infections has evolved owing to the development of resistance to penicillin and tetracycline therapy. A variety of antimicrobials, including the fluoroquinolones, have been proposed as useful alternatives. GOAL OF THE STUDY: To evaluate the efficacy and safety of oral ciprofloxacin as single-dose treatment for urogenital and extragenital gonococcal infections. STUDY DESIGN: 1180 patients with uncomplicated gonococcal infection received single-dose ciprofloxacin regimens ranging from 100 mg to 2000 mg to demonstrate microbiologic efficacy and to determine the minimum effective dose. Eight of 18 studies were randomized, controlled trials with ampicillin/probenecid, amoxicillin/probenecid, ceftriaxone, or spectinomycin as control drugs. RESULTS: Although a ciprofloxacin dose-response was not detected, 250 mg was used in most of the studies. Among 815 patients with 910 infected sites receiving 250 mg of ciprofloxacin, bacteriologic eradication was achieved in 563 (100%) male urethral, 199 (100%) female cervical, 101 (99%) male and female rectal, and 47 (96%) male and female pharyngeal sites. CONCLUSION: Although the World Health Organization and the Centers for Disease Control and Prevention have identified 500 mg of ciprofloxacin as a single-dose treatment regimen for uncomplicated gonorrhea, the clinical data from the multinational studies indicate that a 250-mg single-dose of ciprofloxacin is equally effective in the management of uncomplicated gonorrhea, including extragenital sites of infection.

Adult↗

Susceptibility of isolates of Neisseria gonorrhoeae to penicillin and tetracycline in Brooklyn, 1988-1992.

BACKGROUND AND OBJECTIVES: The aim of this analysis was to determine the rate of resistance of Neisseria gonorrhoeae to penicillin and tetracycline over 5 years. STUDY DESIGN: The authors studied 500 isolates of N. gonorrhoeae. Minimum inhibitory concentrations of various antimicrobial agents, including penicillins, tetracyclines, quinolones, cephalosporins, spectinomycin, and trospectomycin, were determined using agar dilution. Organisms that produced beta-lactamase were classified as penicillinase-producing N. gonorrhoeae, and those with tetracycline minimum inhibitory concentrations > 16 micrograms/ml were considered presumptive high-level tetracycline resistant. Organisms with Minimum inhibitory concentrations > 2.0 micrograms/ml were presumptively considered to have chromosomally mediated resistance to penicillin or tetracycline. Isolates with none of these forms of resistance were considered susceptible to penicillin and tetracycline. RESULTS: Penicillinase-producing N. gonorrhoeae represented 34.7%, 40.7%, and 44.9% of gonococcal isolates in 1988, 1989, and 1990, respectively. Only 14.3% and 15.0% of the isolates in 1991 and 1992 were penicillinase-producing N. gonorrhoeae. In 1988, 1.0% of isolates were chromosomally mediated penicillin resistant. In contrast, chromosomally mediated penicillin resistant gonococci represented 7.5% to 22.4% of isolates from 1989 to 1992. In 1988, 26.0% of isolates were high-level tetracycline resistant. The prevalence of presumptive high-level tetracycline resistant organisms decreased after 1988. From 1989 to 1992, only 8.2% to 14.8% of gonococcal isolates were presumptive high-level tetracycline resistant. No chromosomally mediated tetracycline resistant isolates were identified in 1988. In 1989 and 1990, 11.6% and 10.2%, respectively, of isolates were chromosomally mediated tetracycline resistant. Chromosomally mediated tetracycline resistant N. gonorrhoeae represented 2.0% of isolates in 1991 and 25.0% of isolates in 1992. All isolates tested were susceptible to the other antibiotics. CONCLUSION: Continued surveillance of sensitivity of contemporary gonococci to antimicrobial agents is important.

Female↗

Etiologic study of genitourinary infections in women of childbearing age in Bobo-Dioulasso, Burkina Faso, 1992.

BACKGROUND AND OBJECTIVES: Genitourinary infections have a major impact on public health, especially in Africa. Relative distribution of the different pathogens is unknown in Bobo-Dioulasso. GOAL: To describe the etiology of genitourinary infections, to establish the sensitivity of Neisseria gonorrhoeae to antibiotics, and to provide epidemiologic and biologic evidence to optimize the treatment of genitourinary infections. STUDY DESIGN: Clinical and biologic diagnoses were performed on 223 women with genitourinary infections. RESULTS: Etiologies found were trichomoniasis (27.8%), chlamydia (26.9%), bacterial vaginosis (19.7%), candidiasis (16.6), and N. gonorrhoeae infection (10.9%). Human immune deficiency virus antibodies were present in 42% of the patients. Spectinomycin or ceftriaxone should be recommended for the treatment of gonorrhoeae in Bobo-Dioulasso. CONCLUSIONS: The prevalence of Chlamydia trachomatis is higher than that of N. gonorrhoeae in Bobo-Dioulasso. This should be taken into account in clinical management of sexually transmitted diseases in this setting.

Adolescent↗

Tetracycline-resistant Neisseria gonorrhoeae. Characteristics of patients and isolates at a London Genitourinary Medicine Clinic.

OBJECTIVES: To compare auxotypes, serovars, and antibiograms of tetracycline-resistant Neisseria gonorrhoeae (TRNG) and non-TRNG isolated from patients attending an East London Genitourinary Medicine (GUM) Clinic. To obtain plasmid profiles for penicillinase-producing gonococci (PPNG) as well as presumptive TRNG. To identify differences in patient characteristics for the TRNG and non-TRNG patient groups. STUDY DESIGN: Gonococcal isolates were collected from 400 patients attending the GUM clinic at the Royal London Hospital GUM Clinic over a 1-year period. Isolates (378) were tested for susceptibility to various antibiotics, auxotyped, and serotyped. Plasmid profiles were obtained for PPNG and isolates exhibiting high-level tetracycline resistance (TRNG). The presence of the tet M determinant was confirmed using the polymerase chain reaction (PCR). The PCR product was digested with the restriction endonuclease (RE) Hpa II and electrophoresed on a 2.5% agarose gel to determine an "RE pattern." Patient data were collected by retrospective case-note review. RESULTS: TRNG (n = 42) accounted for 11% of the 378 isolates tested, and the remaining 336 (89%) isolates were non-TRNG. Non-requiring auxotrophy and P1B-2 serovar expression occurred more frequently among TRNG. PPNG accounted for 31% of TRNG and 5% of non-TRNG. Chromosomal resistance to penicillin (CMRNG) was absent among TRNG but accounted for 11% of non-TRNG. One TRNG isolate showed decreased susceptibility to ciprofloxacin (MIC 0.25 mg/l). All isolates were sensitive to cefotaxime, cefixime, spectinomycin, and azithromycin. All TRNG possessed the 25.2 MDa plasmid and produced a PCR product of appropriate size after tet M gene sequence amplification. RE digests of the PCR product gave a single pattern. None of the TRNG in contrast to 18% of the non-TRNG were acquired homosexually. Ethnic distribution differed between the patients with TRNG and patients without non-TRNG (Afro-Caribbean 81% versus 58%; white 19% versus 36%). Most TRNG were acquired in the United Kingdom. CONCLUSIONS: TRNG differ from the non-TRNG in their auxotype and serovar distribution. PPNG are more common among the TRNG isolates, whereas CMRNG appear absent. TRNG are isolated more commonly from Afro-Caribbean patients and were not represented among homosexually acquired isolates.

Adolescent↗

Antimicrobial susceptibilities of strains of Neisseria gonorrhoeae in Bangkok, Thailand: 1994-1995.

BACKGROUND AND OBJECTIVES: Failure of uncomplicated gonococcal infections acquired in the Far East to respond to doses of ciprofloxacin and ofloxacin recommended by the Centers for Disease Control and Prevention have been identified in Australia, the United Kingdom, and the United States. In the Republic of the Philippines, 54.3% of strains exhibited decreased susceptibility to fluoroquinolones; 12% of strains were resistant to ciprofloxacin. This study was undertaken to compare the antimicrobial susceptibilities of gonococcal isolates in Bangkok, Thailand, with those in the Republic of the Philippines. GOAL: To determine the frequency and diversity of antimicrobial resistance, particularly to fluoroquinolones, in gonococcal strains in Bangkok, Thailand. STUDY DESIGN: Strains of Neisseria gonorrhoeae isolated from 101 patients with uncomplicated gonorrhea in Bangkok, Thailand, in July, 1994 (46 strains) and November, 1994 to July, 1995 (55 strains), were characterized by auxotype/serovar class, antimicrobial susceptibilities, and plasmid profile. Susceptibilities were determined to penicillin G, tetracycline, ceftriaxone, cefixime, cefoxitin, ciprofloxacin, ofloxacin, norfloxacin, erythromycin, kanamycin, and thiamphenicol. RESULTS: Of 101 strains, 89.1% (90/101) were resistant to penicillin or tetracycline. Plasmid-mediated resistance to penicillin or tetracycline was identified in 33.7% (34/101) of the isolates: penicillinase-producing Neisseria gonorrhoeae (17.8%; 18/101), tetracycline-resistant Neisseria gonorrhoeae (7.9%; 8/101), and penicillinase-producing/tetracycline-resistant Neisseria gonorrhoeae (7.9%; 8/101). Most penicillinase-producing strains (96.2%; 25/26) possessed the 4.4-megadalton (Md) beta-lactamase plasmid; one strain possessed the 3.2-Md beta-lactamase plasmid. Chromosomally mediated resistance to penicillin and tetracycline was exhibited by 51.5% (52/101) of strains, and 4.0% (4/101) were tetracycline resistant. All strains were susceptible to spectinomycin. Of 21.8% (22/101) strains exhibiting decreased susceptibility to ciprofloxacin (minimal inhibitory concentration [MIC] > or = 0.125 microgram/ml), one strain (ciprofloxacin MIC, 0.5 microgram/ml; ciprofloxacin inhibition zone diameter of 23 mm) had MICs of 2.0 and 8.0 micrograms/ml for ofloxacin and norfloxacin, respectively, indicating resistance to these agents. Decreased susceptibility to ciprofloxacin was identified in strains with chromosomally mediated resistance to penicillin or tetracycline and in penicillinase-producing strains. CONCLUSIONS: In Bangkok, Thailand, gonococcal isolates exhibit resistance to penicillin, tetracycline, kanamycin, and thiamphenicol. Decreased susceptibility to fluoroquinolones is emerging in a variety of strains of N. gonorrhoeae. Thus, all gonococcal infections should be treated with antimicrobial therapies known to be active against all gonococcal strains to reduce the spread of strains exhibiting decreased susceptibilities to fluoroquinolones.

Anti-Bacterial Agents↗

Comparison of E-test with agar dilution methods in testing susceptibility of N. gonorrhoeae to azithromycin.

BACKGROUND AND OBJECTIVES: The antimicrobial susceptibility pattern of Neisseria gonorrhoeae varies from one country to another and may also change with time. To monitor these variations and changes, it is desirable to have a method that is simple and reproducible. This study was undertaken to determine the in vitro susceptibility of N. gonorrhoeae to azithromycin and to assess the reliability of results obtained using E-test methodology for determination of the minimum inhibitory concentration (MIC) of azithromycin. STUDY DESIGN: The MICs for 135 clinical isolates of N. gonorrhoeae were determined by a modified Kirby-Bauer method recommended by the National Committee for Clinical Laboratory Standards against penicillin, cefuroxime, ceftriaxone, norfloxacin, tetracycline, kanamycin, spectinomycin, and azithromycin. The MIC of azithromycin was determined by both the E-test and agar dilution method. All tests were done simultaneously. RESULTS: The MIC of azithromycin to all 135 isolates ranged from 0.078 to 0.25 microgram/ml with the agar dilution method and from 0.016 to 0.50 microgram/ml with the E-test. The MIC50 and MIC90 of azithromycin were 0.064 microgram/ml and 0.125 microgram/ml, respectively, by the agar dilution method, whereas they are slightly higher by the E-test method. Seventy-six of the isolates were beta-lactamase producers and 69 were high-level tetracycline-resistant N. gonorrhoeae. There was no difference in the MIC50 and MIC90 of azithromycin in these groups of isolates. The percentage agreement within the acceptable +/-1 log2 dilution difference between MICs obtained by E-test and those obtained by the agar dilution method was 97.8%. CONCLUSIONS: Azithromycin has a very good in vitro antigonococcal activity, and the E-test is a reliable method to determine the MIC of azithromycin against N. gonorrhoeae.

Anti-Bacterial Agents↗

Antimicrobial susceptibility and types of Neisseria gonorrhoeae in Greece. Data for the period 1990 to 1993.

BACKGROUND: Surveillance of the rapidly changing patterns of antimicrobial resistance of Neisseria gonorrhoeae is imperative for monitoring gonococcal infection. GOAL: To describe the types and the antimicrobial susceptibility profile of a representative samples of gonococci isolated in Greece between 1990 and 1993. STUDY DESIGN: The antimicrobial susceptibilities, serovar/auxotypes classes, and plasmid contents of 263 consecutive isolates of N. gonorrhoeae, recovered from cases of male gonococcal urethritis, were determined. RESULTS: Penicillinase-producing N. gonorrhoeae (PPNG) were isolated at a rate of 6.1% and were mostly from imported cases of infection. Six (2.3%) of the isolates (one PPNG and five non-PPNG) were highly resistant to tetracycline, and one PPNG strain was resistant to norfloxacin and ciprofloxacin. Strains with chromosomal resistance to penicillin, tetracycline, erythromycin, and chloramphenicol accounted for 18.5%, 12.5%, 19%, and 16% of the isolates, respectively; much higher proportions of strains were intermediately susceptible to these antibiotics. Spectinomycin and cefotaxime were active against all gonococci studied. A shift to IB serovars and to sporadic types of strains was noted from previous years among the non-PPNG isolates. This is compatible with the marked increase in the rate of imported cases of infection caused by n on-PPNG strains. CONCLUSIONS: The emergence of high-level resistance to tetracycline and resistance to fluoroquinolones was ascertained. At the present, however, the main problem with gonococcal resistance in Greece seems to ensue from the increasing rates of chromosomally resistant strains. Moreover, the increasing frequency of imported gonococci underlines the necessity for continuous epidemiologic surveillance.

Drug Resistance, Microbial↗

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.

Drug Resistance, Microbial↗

Plasmid-mediated resistance of Neisseria gonorrhoeae strains isolated from female sex workers in North Sumatra, Indonesia, 1996.

BACKGROUND: Sentinel surveillance of the antimicrobial resistance of strains isolated from female sex workers in North Sumatra, Indonesia, has been carried out since 1975. In 1996 a high prevalence of strains with plasmid-mediated resistance to tetracycline and penicillin was observed. GOAL: The goal was to further characterize strains isolated from a core group of patients in Indonesia with sexually transmitted infections in 1996. STUDY DESIGN: The strains were characterized by antimicrobial susceptibility testing, plasmid analysis, subtype of the determinant, and analysis of genomic DNA by pulsed-field gel electrophoresis (PFGE). RESULTS: A total 161 strains obtained from 592 female sex workers in 10 different places in North Sumatra, Indonesia, in 1996 were investigated. All strains exhibited plasmid-mediated resistance to penicillin (PPNG: penicillinase-producing ) and/or tetracycline (TRNG: tetracycline-resistant ); 115 strains were PPNG/TRNG (71%), 45 were TRNG (28%), and 1 was PPNG. All strains were susceptible to ceftriaxone, ciprofloxacin, kanamycin, and spectinomycin. All PPNG strains tested carried the 7.2-kb (Asian type) plasmid except one, which carried the 4.9-kb (Toronto type) plasmid. All TRNG strains except one contained the Dutch-type gene. PFGE analysis of 156 strains documented that a diversity of strains existed and that certain genotypes had spread in a defined area or between different areas in North Sumatra. CONCLUSION: Our results underline the importance of continuous surveillance of the changing patterns of antimicrobial resistance of in high-risk populations.

Anti-Bacterial Agents↗

Gonorrhoea surveillance system in France: 1986-2000.

OBJECTIVE: The objectives of this study were to monitor epidemiologic trends in Neisseria gonorrhoeae (NG) infections and to assess antimicrobial resistance patterns of NG. METHODS: RENAGO, a voluntary-based laboratory surveillance system, including private and public laboratories, was set up in France in 1986. Every NG strain isolated by the participating laboratories was sent to the National Reference Center, Institut Alfred Fournier, Paris, where susceptibility to 6 antibiotics was tested. These laboratories reported monthly numbers of positive NG isolates and associated epidemiologic data. Because the number of laboratories varied every year, the average number of NG isolates per laboratory per year was computed to monitor annual trends in gonorrhea incidence. RESULTS: The average number of NG isolated per laboratory per year decreased steadily from 10.6 in 1986 to 0.6 in 1997 but then yearly increased and reached 1.9 in 2000. Increasing gonorrhea was observed mostly in men and in the Paris area. The proportion of rectal strains increased significantly from 0.9% in 1986 to 9.2% in 2000. From 1998 to 2000, 5.3% of the isolates had reduced susceptibility or were resistant to ciprofloxacin, 7.3% were PPNG strains and 27.4% were resistant to tetracycline, 18.5% had a reduced susceptibility to thiamphenicol, and 1 strain was resistant to the latter. Neither strain was resistant to ceftriaxone or to spectinomycin. CONCLUSION: From 1998 to 2000, gonorrhea markedly increased in France and seemed to affect mainly gay men in Paris, which suggests relapses to risky sexual behaviors and highlights the need for strengthening prevention. During the same period, NG ciprofloxacin resistance has sharply increased and should be carefully monitored because of the wide use of ciprofloxacin single-dose treatment.

Adult↗

Challenges in the control of gonorrhea in South America and the Caribbean: monitoring the development of resistance to antibiotics.

OBJECTIVE: : The objective of this study was to ascertain the antimicrobial susceptibility of Neisseria gonorrhoeae isolates from 6 South American and 13 Caribbean countries participating in the Gonococcal Antimicrobial Surveillance Program (GASP) from 1990 to 1999. STUDY: : A GASP network of laboratories was launched in the Americas and the Caribbean during the 1990s. Standardized methods and interpretative criteria were established for the isolation of N. gonorrhoeae, strain identification, and determination, and quality control of antimicrobial susceptibility. RESULTS: : Two countries (Argentina and Uruguay) maintained continuous surveillance during the study period. Some countries gathered data periodically and several others were unable to initiate antimicrobial surveillance as a result of lack of resources. The percentage of penicillin-resistant N. gonorrhoeae isolated in the region over the decade varied considerably (1.0-11.9% carried chromosomal resistance and 17.9-38.8% produced beta-lactamase) with an overall trend to declining numbers of penicillin-resistant isolates. For tetracycline, 7.4% to 36.3% carried chromosomal resistance, whereas 12.0% to 27.4% carried plasmid-mediated resistance. There were no reports of ciprofloxacin-resistant isolates, although N. gonorrhoeae with decreased susceptibility to ciprofloxacin and azithromycin as well as spectinomycin-resistant isolates were identified in some countries.

Anti-Bacterial Agents↗

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.

Anti-Bacterial Agents↗

Plastid engineering in land plants: a conservative genome is open to change.

We have developed efficient transformation protocols to modify each of the 500-10,000 plastid genome copies in a tobacco cell. The transforming DNA is introduced on the surface of microscopic tungsten particles by the biolistic process. Selection for transplastomes is by spectinomycin resistance based on expression of aminoglycoside-3"-adenyltransferase from a chimeric aadA gene in the transforming DNA. Manipulations that are now feasible include replacement of endogenous plastid genes with DNA sequences modified in vitro, targeted gene disruption, and insertion of reporter genes into the plastid genome. Alternative methods for plastid genome manipulations may be developed utilizing an extrachromosomal element which was identified during the transformation studies. Introduction of foreign genes under control of plastid gene expression elements results in duplication of endogenous regulatory sequences. A sensitive somatic assay to detect deletions via such direct repeats confirmed that these sequence duplications do not result in significant genome instability. The ability to transform plastids will facilitate the study of plastid gene regulation, and the application of genetic engineering to crop improvement.

Base Sequence↗

Increases in the mutation frequency at which fusidic acid-resistant Staphylococcus aureus arise with salicylate.

Salicylate was shown to increase the frequency at which a fusidic acid-susceptible strain of Staphylococcus aureus underwent mutation to become fusidic acid-resistant. These fusidic acid-resistant mutants had alterations in spectinomycin and kanamycin resistance levels indicative of mutations in fusA, the gene that encodes elongation factor-G, the target of fusidic acid.

Anti-Bacterial Agents↗