NIH Response

Ongoing surveillance for antimicrobial resistance is crucial to obtain the information needed to choose effective treatments for gonorrhea.  The decreasing susceptibility of Neisseria gonorrhoeae to fluoroquinolones has raised questions about the use of these antibiotics to treat uncomplicated gonorrhea in light of the recent reports of antimicrobial failures and in vitro evidence.  It is important that these future treatments do not inhibit the absorption of fluoroquinolones, since this can greatly effect therapeutic outcomes, not allowing for optimal therapy (CTR, 1997).

Bambeke and Tulkens (1999) recommend the following when considering local epidemiology and the indication of fluoroquinolone use:
The use of the fluoroquinolones should focus on infections in which

• There is a differential benefit over conventional agents in terms of efficacy, safety, or cost;
• in infections for which few alternative treatments exist, or
• against organisms towards which they are sufficiently active to prevent the rapid emergence of resistance.

In 1997, Mroczkowski et al. determined that a single oral dose of grepafloxacin is an effective fluoroquinolone antibiotic used to treat uncomplicated gonorrhea, and proved to be effective even against penicillinase-producing gonococci; this can be added to the list of other fluoroquinolones currently approved by the CDC: ciprofloxacin, ofloxacin, enoxacin and norfloxacin.  The authors stated that it had excellent in vitro activity and is more potent than ofloxacin against penicillin- and tetracycline-resistant strains, and claimed it to be more effective than ceftriaxone and ofloxacin against Chlamydia trachomatis and penicillinase-producing N. gonorrhoeae (Mroczkowski, et al., 1997).

Grepafloxacin Effectiveness

Trovafloxacin Response

In 1998, Jones et al. determined that a new quinolone antibiotic, trovafloxacin, is highly active in vitro against uncomplicated gonorrhea, even against strains that showed mild resistance to ciprofloxacin and ofloxacin.  It is also active against Chlamydia trachomatis, since many individuals with gonorrhea concurrently are infected with chlamydia, along with numerous other Gram positive and Gram negative bacteria.

Jones et al. determined that these resistance phenotypes included ones that were pencillin-susceptible; chromosomally mediated resistance to pencillin and tetracycline; penicillinase-producing N. gonorrhoeae and those strains with plasmid-mediated resistance because of the TetM determinant; and plasmid-mediated resistance to tetracycline.

As of 1999, no clinically significant resistance to the broad-spectrum cephalosporins have been identified, and fluoroquinolone-resistant gonococcal strains are now prevalent in Australia and much of the Far East (Fox and Knapp, 1999).

Due to the convenience of single oral doses, effectiveness in males and females, safety profile, and relatively low cost, trovafloxacin and ofloxacin remain the preferred quinolone treatments for uncomplicated gonorrhea when compared to ceftriaxone, an effective but costly injectible (Jones et al., 1998).  However, grepafloxacin did have a higher percentage of adverse side-effects with 25.7% (Mroczkowski, et al., 1997) compared to the findings of Jones et al. which was 10% lower for each antibiotic.

It is yet to be seen whether these two fluoroquinolones, grepafloxacin and trovafloxacin, will be useful for a significant period of time.  Nonetheless, the research and development of new fluoroquinolone antimicrobial agents is imperative for the treatment of N. gonorrhoeaea, and other Gram positive cocci, such as S. pneumoniae and methicillin-sensitive S. aureus, as well as atypical pathogens of the respiratory system like Chlamydia, Legionella, and Mycoplasma (File and Slama, 2000).

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