The changing pattern of antibiotic resistance of Neisseria gonorrhoeae.

The World Health Organisation has just issued the conclusions of a consultation on sexually transmitted diseases treatment strategies. ' This replaces the previous consultative report issued in 1983.2 The recommendations for the treatment of gonorrhoea in these two reports are very different. In 1983 the recommended regimen was either single dose therapy with an injectable or oral penicillin combined with probenecid, or a course of a tetracycline. Spectinomycin or cefoxitin were recommended as alternatives where penicillinase producing Neisseria gonorrhoeae (PPNG) or other resistant gonococci were known to be prevalent. Resistance was treated very much as an emergency issue with some recognised problem areas in South East Asia and Africa. Now, seven years later gonococcal resistance to antibiotics is a problem in many parts of the world. The new recommended standard regimens are single dose ceftriaxone 250 mg i.m. , ciprofloxacin 500 mg oral, or spectinomycin 2 g i.m. Tetracyclines and oral or injectable penicillins are now only recommended where the level of resistance to these agents is known to be low. Despite their relatively high initial cost, these three regimens were proposed on the principle that the overall cost of cheaper, less effective regimens (including relapse, complications, further spread and increasing resistance) would in fact be greater. The ceftriaxone and ciproflaxacin doses are higher than those used in some quarters, but it was felt that the higher doses would be more effective in preventing the emergency and spread of resistance to both agents. Antimicrobial resistance in N gonorrhoeae may be controlled by genes on either plasmid or chromosome. Clinically significant chromosomal resistance to penicillins and tetracyclines results from the additive effect of mutations at several resistance loci, for example, pen A, pen B, tet, mtr.34 With penicillins chromosomal resistance is expressed through changes to the gonococcal cell envelope. ' Unfortunately there is no simple rapid test for detecting such resistance. Resistance to other useful antigonococcal compounds is also controlled by chromosomal genes. These include cephalosporins, spectinomycin, thiamphenicol and earlier quinolones such as rosoxacin. ' Resistance to the newer quinolones such as enoxacin and ciprofloxacin is now being seen. ' This too is presumed to be under chromosomal control. In general chromosomal resistance spreads more slowly than plasmid-mediated resistance. Nevertheless penicillin and tetracycline resistance is now common in many parts of the world with spectinomycin resistance posing a problem in some parts of the Pacific. Plasmid-mediated resistance to penicillins was first reported in 1976.9` Two plasmids of 3.2 and 4 4 megadaltons were involved originally, those appearing to originate in gonococcal strains from West Africa and the Far East respectively. Although these remain the most common, other penicillinase controlling plasmids have since been described. None is self-transmissable, requiring the presence of a 24.5 megadalton conjugative plasmid to enable them to move between strains. All control the production of the same TEM-1 beta lactamase. Fortunately gonococcal beta lactamase can be detected simply and rapidly. This makes screening for penicillinase producing Ngonorrhoeae (PPNG) easy and facilitates epidemiological monitoring of these strains. In 1985 a second form of plasmid-mediated antibiotic resistance was found to give rise to high level tetracycline resistant N gonorrhoeae (TRNG). The tetracycline resistance plasmid is large, 25.2 megadaltons, and self-transmissable. " Although TRNG were first encountered in the United States, similar strains have been found in Britain, the Netherlands and parts of Africa. '"'4 Given the capacity of the 25-2 megadalton plasmid for self transmission (in contrast to the betalactamase plasmids), such resistance is likely to disseminate rapidly. The plasmid had been thought to originate from the 24-5 megadalton conjugal gonococcal plasmid into which had been inserted the tet M tetracycline resistance determinant. " However, this view has been challenged recently. " The speed with which PPNG and TRNG have disseminated illustrates a major difference between the impact of plasmid and chromosomal antibiotic resistance in the gonococcus. Even where tetracyclines are not used to treat gonorrhoea, their use in chlamydial infections and pelvic inflammatory dis55