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Mutations in gyrA and parC in ciprofloxacin-resistant Neisseria gonorrhoeae in Kuala Lumpur, Malaysia

Karunakaran R, Sam IC

J Antimicrob Chemother, 2007 Apr;59(4):803-4.
PMID: 17329273
Matched MeSH terms: Neisseria gonorrhoeae/drug effects*
Rectal microscopy in men - expensive, time consuming and inappropriate

Waters L, Worthen E, O'mahony C

Int J STD AIDS, 2006 Oct;17(10):710.
PMID: 17059644
Matched MeSH terms: Neisseria gonorrhoeae/drug effects*
Investigation of Polycaprolactone Matrices for Intravaginal Delivery of Doxycycline

Pathak M, Coombes AGA, Turner MS, Palmer C, Wang D, Steadman KJ

J Pharm Sci, 2015 Dec;104(12):4217-4222.
PMID: 26398713 DOI: 10.1002/jps.24652

Polycaprolactone (PCL) matrices loaded with doxycycline were produced by rapidly cooling suspensions of the drug powder in PCL solution in acetone. Drug loadings of 5%, 10%, and 15% (w/w) of the PCL content were achieved. Exposure of doxycycline powder to matrix processing conditions in the absence of PCL revealed an endothermic peak at 65°C with the main peak at 167°C, suggesting solvatomorph formation. Rapid "burst release" of 24%-32% was measured within 24 h when matrices were immersed in simulated vaginal fluid (SVF) at 37°C, because of the presence of drug at or close to the matrix surface, which is further confirmed by scanning electron microscopy. Gradual release of 66%-76% of the drug content occurred over the following 14 days. SVF containing doxycycline released from drug-loaded PCL matrices retained 81%-90% antimicrobial activity compared with the nonformulated drug. The concentrations of doxycycline predicted to be released into vaginal fluid from a PCL matrix in the form of an intravaginal ring would be sufficient to kill Neisseria gonorrhoea and many other pathogens. These results indicate that PCL may be a suitable polymer for controlled intravaginal delivery of doxycycline for the treatment of sexually transmitted infections.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects
Comparison of E-test with agar dilution methods in testing susceptibility of N. gonorrhoeae to azithromycin

Yasin RM, Suan KA, Meng CY

Sex Transm Dis, 1997 May;24(5):257-60.
PMID: 9153733

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.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects*
Serological ecology of Neisseria gonorrhoeae (PPNG and non-PPNG) strains: Canadian perspective

Dillon JR, Bygdeman SM, Sandström EG

Genitourin Med, 1987 Jun;63(3):160-8.
PMID: 3111978

One hundred and thirty eight penicillinase producing Neisseria gonorrhoeae (PPNG) and 239 non-PPNG strains were characterised serologically using a panel of seven monoclonal antibodies directed against protein 1A and seven against protein 1B. An association between serovar and susceptibility to antimicrobial agents, auxotype, and plasmid content was observed. Serogroup WI strains were more sensitive to penicillin, ampicillin, tetracycline, erythromycin, cefoxitin, and cefuroxime. Sixty five (82%) of the 79 WI strains were typed as being serovar Aedgkih, and 47 (72%) of these strains required arginine, uracil, and hypoxanthine for growth (AUH-). Seventy one (44%) of 160 WII/WIII strains were serovar Bacejk, and 42 (59%) of these required proline, citrulline, and uracil for growth (PCU-) and were plasmid free. Serovars Bcgk, Beghjk, Bacjk, and Bajk were associated with resistance to antimicrobial agents. Analysis of PPNG isolates showed a new serovar, Af, which was associated with strains imported from Malaysia and Singapore that required proline and ornithine for growth (Pro-Orn-) and carried the 24.5 megadalton transfer plasmid, the 2.6 megadalton cryptic plasmid, and the 4.5 megadalton penicillinase producing plasmid. Other associations between serovar and geographical location were noted.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects
Treatment of gonorrhea with sulbactam/ampicillin

Ngeow YF, Ramachandran S, Cheong YM

Sex Transm Dis, 1991 7 1;18(3):192-4.
PMID: 1948519

Between January and August, 1989, 36 men and 28 women with uncomplicated lower genital tract infections by Neisseria gonorrhoeae were given single intramuscular injections of sulbactam (500 mg)/ampicillin (1000 mg) together with 1 g oral probenecid. Cure rates that were obtained were 100% for women, 97.2% for men, 100% for patients with penicillinase-producing Neisseria gonorrhoeae (PPNG), and 98.4% for patients with non-PPNG. No serious side effects were encountered, and patient acceptance of the drug was good. A high proportion of patients had concurrent chlamydial infection. Sulbactam/ampicillin was found to be effective against gonococcal urethritis and cervicitis by both PPNG and non-PPNG but have little effect on concomitant chlamydial infections, especially in women.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects
Penincillin-resistant gonorrhoea. A report from University Hospital, Kuala Lumpur

Ngeow YF, Thong ML

Med J Malaysia, 1979 Mar;33(3):252-8.
PMID: 118322
Matched MeSH terms: Neisseria gonorrhoeae/drug effects*
Auxotypes and serogroups of tetracycline-resistant Neisseria gonorrhoeae isolated in Malaysia

Koay AS, My R, Cheong YM

J Clin Microbiol, 1996 Jul;34(7):1863-5.
PMID: 8784614

Between 1992 and 1994, 253 tetracycline-resistant Neisseria gonorrhoeae (TRNG) strains were isolated and characterized by auxotype and serogroup (A/S) classes to study TRNG prevalence in different years. TRNG accounted for 28.1, 42.5, and 51.9% of the strains isolated in 1992, 1993, and 1994, respectively, showing a significant increase in each successive year (chi square = 26.7, P < 0.001). There was no significant increase in penicillinase-producing TRNG, which accounted for 53.1, 53.8, and 63.2% of the TRNG isolates. The 253 TRNG isolates belonged to 53 A/S classes. Eighteen A/S classes not observed in 1992 were detected in 1993, and 11 A/S classes not observed in 1992 and 1993 were isolated in 1994, indicating dissemination of the tetracycline resistance gene among the N. gonorrhoeae strains in Malaysia. Its emergence and subsequent rapid spread are alarming. The plasmid is capable of self-transfer (S.A. Morse, S.R. Johnson, J.W. Biddle, and M.C. Roberts, J. Infect. Dis. 155:819-822, 1987), allowing further dissemination of tetracycline resistance.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects*
Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region, 2005

WHO Western Pacific Gonococcal Antimicrobial Surveillance Programme

Commun Dis Intell Q Rep, 2006;30(4):430-3.
PMID: 17330383

The World Health Organization Western Pacific Region Gonococcal Antimicrobial Surveillance Programme examined about 8,700 isolates of Neisseria gonorrhoeae from 15 countries for resistance to antibiotics in 2005. High to very high rates of resistance to penicillins and quinolones persisted in most centres. Increasing numbers of gonococci with decreased susceptibility to third generation cephalosporins were found in several countries. There were infrequent instances of spectinomycin resistance.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects*
Resistance in gonococci isolated in the WHO Western Pacific Region to various antimicrobials used in the treatment of gonorrhoea, 1997. WHO Western Pacific Gonococcal Antimicrobial Surveillance Programme-WHO WPR GASP

Commun. Dis. Intell., 1998 Dec 24;22(13):288-91.
PMID: 9893340

The World Health Organization Western Pacific Region Gonococcal Antimicrobial Surveillance Programme (WHO WPR GASP) is a multicentric long term programme of continuous surveillance of the antibiotic susceptibility of Neisseria gonorrhoeae. In 1997 the programme examined the susceptibility of 8,594 isolates of gonococci to various antimicrobials in 15 focal points. The trend toward increased antimicrobial resistance noted in earlier years continued. The proportion of quinolone resistant gonococci reported from most centres was either maintained or else increased. More than half of the isolates tested in China-Hong Kong, China, Japan, Korea, and the Philippines had altered quinolone susceptibility and increases in the number and percentage of quinolone resistant strains were noted in most, but not all, of the other centres. Resistance to the penicillins was again widespread, and chromosomally mediated resistance was a significant factor. Penicillinase-producing Niesseria gonorrhoeae (PPNG) were present in all centres. All isolates were sensitive to the third generation cephalosporins and only a very few isolates in China were spectinomycin resistant. High level tetracycline resistance was concentrated in a number of centres including Singapore, Malaysia, the Philippines and Vietnam. The proportion of tetracycline resistant Neiserria gonorrhoeae (TRNG) in most of the remaining centres was less than 10 per cent.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects*
Antineoplastic agents. 522. Hernandia peltata (Malaysia) and Hernandia nymphaeifolia (Republic of Maldives)

Pettit GR, Meng Y, Gearing RP, Herald DL, Pettit RK, Doubek DL, et al.

J Nat Prod, 2004 Feb;67(2):214-20.
PMID: 14987061

Bioassay (P388 lymphocytic leukemia cell line and human tumor cell lines)-guided separation of the extracts prepared from the tropical and coastal trees Hernandia peltata (Malaysia) and Hernandianymphaeifolia (Republic of Maldives) led to the isolation of a new lignan designated as hernanol (1) and 12 previously known lignans: (-)-deoxypodophyllotoxin (2), deoxypicropodophyllin (3), (+)-epiaschantin (4), (+)-epieudesmin (5), praderin (6), 5'-methoxyyatein (7), podorhizol (8), deoxypodorhizone (9), bursehernin (10), kusunokinol (11), clusin (12), and (-)-maculatin (13). The oxidative cyclization (with VOF(3)) of lignans 8, 9, and 10 resulted in a new and unusual benzopyran (14), isostegane (15), and a new dibenzocyclooctadiene lactone (16), respectively. The structure and relative stereochemistry of hernanol (1) and lignans 3, 7, 8, 9, 10, 11, and 12 were determined by 1D and 2DNMR and HRMS analyses. The structures and absolute stereochemistry of structures 2, 4, 5, 6, 13, 14, 15, and 16 were unequivocally determined by single-crystal X-ray diffraction analyses. Evaluation against the murine P388 lymphocytic leukemia cell line and human tumor cell lines showed podophyllotoxin derivatives 2 and 3 to be strong cancer cell line growth inhibitors and substances 4, 5, 8, and 15 to have marginal cancer cell line inhibitory activities. Seven of the lignans and one of the synthetic modifications (14) inhibited growth of the pathogenic bacterium Neisseria gonorrhoeae.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects
Phenotypic and Genotypic Characterization of Neisseria gonorrhoeae Isolates from New Zealand with Reduced Susceptibility to Ceftriaxone

Jamaludin N, Gedye K, Collins-Emerson J, Benschop J, Nulsen M

Microb Drug Resist, 2019 Sep;25(7):1003-1011.
PMID: 31021281 DOI: 10.1089/mdr.2018.0111

Aim:
To characterize mutations in penA, mtrR, ponA, and porBIB, considered target genes for antimicrobial resistance, in Neisseria gonorrhoeae isolates with elevated minimum inhibitory concentrations (MICs) of ceftriaxone cultured from patients in New Zealand.
Results:
Out of 28 isolates supplied by the Institute of Environmental Science and Research Limited (ESR), Porirua, New Zealand, 14 were found to show reduced susceptibility to ceftriaxone (MIC of 0.06 mg/L) according to criteria used by the ESR and the Australian Gonococcal Surveillance Programme (AGSP) when tested in our laboratory. Rates of resistance to ciprofloxacin, azithromycin, penicillin, and tetracycline were 100% (28/28), 7% (2/28), 36% (10/28), and 25% (7/28), respectively. Ten different penA (Penicillin binding protein 2 [PBP2]) sequences were observed. The most common mosaic penA M-1 resembled mosaic penA XXXIV, which has been associated with ceftriaxone treatment failures in other countries. Four semimosaic PBP2 sequences were observed and may be novel PBP sequences, while four out of five nonmosaic PBP2 sequences were similar to PBP2 sequences reported in Australia. Twenty-one isolates harbored mutations in all 4 genes (penA, mtrR, porBIB, and ponA), and 13 of these exhibited reduced susceptibility to ceftriaxone.
Conclusion:
Mutations in penA, mtrR, porBIB, and ponA observed in this study may have contributed to reduced susceptibility to ceftriaxone among New Zealand gonococcal isolates. Over half (16/22) of mosaic penA sequences from the gonococcal isolates resembled penA XXXIV.

Matched MeSH terms: Neisseria gonorrhoeae/drug effects*