Antimicrobial resistance in Neisseria gonorrhoeae: history, molecular mechanisms and epidemiological aspects of an emerging global threat

ABSTRACT Neisseria gonorrhoeae is the agent of gonorrhea, a sexually transmitted infection with an estimate from The World Health Organization of 78 million new cases in people aged 15-49 worldwide during 2012. If left untreated, complications may include pelvic inflammatory disease and infertility. Antimicrobial treatment is usually effective; however, resistance has emerged successively through various molecular mechanisms for all the regularly used therapeutic agents throughout decades. Detection of antimicrobial susceptibility is currently the most critical aspect for N. gonorrhoeae surveillance, however poorly structured health systems pose difficulties. In this review, we compiled data from worldwide reports regarding epidemiology and antimicrobial resistance in N. gonorrhoeae, and highlight the relevance of the implementation of surveillance networks to establish policies for gonorrhea treatment.

Epidemilogical analysis of Neisseria gonorrhoeae isolates by antimicrobial susceptibility testing, auxotyping and serotyping.

PURPOSE: This study was carried out to analyze the epidemiology of gonorrhea based on antimicrobial susceptibility testing, auxotyping and serotyping in New Delhi, India. METHODS: Sixty gonococcal isolates from males with urethritis, females with endocervicitis and their sexual contacts were studied. The isolates were subjected to antimicrobial susceptibility testing, auxotyping and serotyping for epidemiological characterization. RESULTS: We observed nine antibiotic resistance patterns. Ninety-eight percent of isolates were resistant to ciprofloxacin, while 20% isolates were penicillinase producing N. gonorrhoeae (PPNG) and 18.3% isolates were tetracycline resistant N. gonorrhoeae (TRNG). Eight auxotypes were observed, of which the NR (non-requiring), proline requiring and arginine requiring were most common auxotypes. On the basis of serotyping alone, the gonococcal isolates could be differentiated into three serogroups and 18 serovars. Serogroup WI represented 46.7% and WII/III represented 51.7% of isolates and one strain was WI and WII/WIII serogroup combination. When results of auxotyping and serotyping were combined (A/S) 29 A/S classes could be identified. The most prevalent A/S classes were NR/Aost, NR/Arost, Pro/Aost and Pro/Boprt. CONCLUSIONS: Although A/S typing had the highest discriminatory index, isolates recovered from index case and their sexual contacts were found to be identical by all typing methods.

Serological characterisation of Neisseria gonorrhoeae by co-agglutination technique.

Antibiotic susceptibility pattern in cases of acute gonococcal urethritis, was studied by single disc diffusion technique and minimum inhibitory concentration (MIC) by agar dilution technique were determined for 5 antibiotics, viz penicillin, ampicillin, tetracycline, gentamicin and norfloxacin. All the penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG strains were sensitive to norfloxacin. 72% of the isolates belonged to serogroup WII/WIII by co-agglutination technique.

Auxotyping of Neisseria gonorrhoeae as an additional epidemiological marker.

Auxotypes and penicillin sensitivity of 102 strains of N. gonorrhoeae were studied. Ten distinct auxotypes on the basis of growth requirement to seven amino acids were observed. The commonest pattern seen was zero auxotype (33.3%), followed by auxotype requiring proline (18.6%). MIC of 72 (71.5%) strains ranged from < 0.003 IU/ml to 0.062 IU/ml of benzyl penicillin. MIC of the other 30 (29.5%) strains was found to be > or = 0.125 IU/ml, indicating penicillin resistance. None of the strains were penicillinase producers. A case of reinfection was also detected on the basis of change in auxotype pattern.