Antibiotic-Resistant Neisseria gonorrhoeae: The Calm before Another Storm?

Since the beginning of the modern chemotherapeutic era, the treatment of gonorrhea has been dogged by the shifting antimicrobial susceptibility of Neisseria gonorrhoeae. The sulfonamides, penicillins, tetracyclines, and erythromycin all fell by the wayside as strains of N. gonorrhoeae with relative or absolute resistance to antimicrobial agents evolved and spread; by 1988, approximately one third of all gonococcal isolates in the United States had one form of resistance or another [1, 2]. This led the Centers for Disease Control and Prevention (CDC) to recommend single-dose therapy with a broad-spectrum cephalosporin (cefixime or ceftriaxone) or a fluoroquinolone (ciprofloxacin or ofloxacin) for uncomplicated gonorrhea [3]. The past decade has been a period of relative stability in the pattern of antimicrobial susceptibility of N. gonorrhoeae and recommended treatments for gonorrhea in the United States. But this may soon change.

The fluoroquinolones represented an important advance in antigonococcal therapy. They have a unique mechanism of action and therefore have little cross-resistance with other antibiotic agents. Single oral doses of these drugs are effective against uncomplicated gonorrhea of any anatomical site, are well tolerated, are relatively inexpensive, and were initially active against almost all gonococci, including those with previously documented types of resistance [2, 4]. From the beginning, however, theoretical concerns were raised about the potential of gonococci to develop resistance to fluoroquinolones. Resistance of N. gonorrhoeae and other pathogens could be readily induced in the laboratory, and clinical resistance of some previously susceptible pathogens was documented almost immediately [5, 6]. Gonococcal strains with reduced susceptibility to one or more fluoroquinolones were first …