NeisseriaGonorrhoeae

Low-level resistance to benzylpenicillin (MIC 0.1–2 mg/L) has been increasing in strains of N. gonorrhoeae for several decades, and is now very common. This type of resistance is due to mutational alterations in the penicillin-binding proteins PBP 1 and PBP 2 and to impermeability associated with alteration of PI porin. Alterations in penA genes conferring decreased susceptibility to third-generation oral cephalosporins has been documented in Japan, Hong Kong and the Western Pacific Region. Since 1976, a high-level plasmidmediated type of resistance to penicillin, caused by production of TEM-1 β-lactamase, appeared in South East Asia and West Africa and spread to Western countries. These penicillinase- producing strains of N. gonorrhoeae remain common (30–65%) in many developing countries, but account for only 5–10% of gonococcal isolates in the West. Low-level resistance to tetracyclines is often associated with multiple resistance to penicillin, erythromycin and fusidic acid. It is caused by mutational derepression of the MtrRCDE efflux system. Plasmid-mediated high-level resistance to all tetracyclines, including doxycycline, determined by the ribosomal protection protein TetM carried on a transposon, emerged in 1985.
It has reached a high prevalence, which unfortunately reduces the clinical utility of this group of drugs for the treatment of dual infection with gonococci and chlamydia. Spectinomycin resistance, due to mutational alteration of the 30S ribosomal subunit, remains rare. Resistance to fluoroquinolones, due to GyrA and/or ParC mutational alteration, emerged in several countries during the 1990s and increased globally by clonal spread to reach prevalence rates up to 94% in South East Asia and more than 50% in some European countries. This dramatic increase in resistance has markedly reduced the value of fluoroquinolones for empirical treatment of uretritis.