Activity of faropenem tested against Neisseria gonorrhoeae isolates including fluoroquinolone-resistant strains.

Abstract

We evaluated the anti-gonococcal potency of faropenem along with 7 comparator reference antimicrobials against a preselected collection of clinical isolates. The 265 isolates were inclusive of 2 subsets: 1) 76 well-characterized resistant phenotypes of gonococcal strains (53 quinolone-resistant strains--31 with documented quinolone resistance-determining region changes from Japan, 15 strains resistant to penicillin and tetracycline, and 8 strains with intermediate susceptibility to penicillin) and 2) 189 recent isolates from clinical specimens in 2004 from 6 states across the United States where quinolone resistance is prevalent. Activity of faropenem was adversely affected by l-cysteine hydrochloride in IsoVitaleX (4-fold increase in [minimal inhibitory concentration] MIC50; 0.06 versus 0.25 microg/mL). The rank order of potency of the antimicrobials for the entire collection was ceftriaxone (MIC90, 0.06 microg/mL) > faropenem (0.25 microg/mL) > azithromycin (0.5 microg/mL) > cefuroxime (1 microg/mL) > tetracycline (2 microg/mL) > penicillin = ciprofloxacin = levofloxacin (4 microg/mL). Using MIC90 for comparison, faropenem was 4-fold more potent than cefuroxime (0.25 versus 1 microg/mL), but was 4-fold less active than ceftriaxone (0.25 versus 0.06 microg/mL). Although the activity of faropenem was not affected by either penicillinase production (MIC90, 0.12 microg/mL, penicillinase-positive) or increasing ciprofloxacin MIC (0.25 microg/mL, ciprofloxacin-resistant), increasing penicillin MIC was associated with an increase in MIC90 values (0.016 microg/mL for penicillin-susceptible to 0.25 microg/mL for penicillin-resistant strains). Among the recent (2004) clinical gonococcal isolates tested, reduced susceptibility to penicillins, tetracycline, and fluoroquinolones was high (28.0-94.2%). Geographic distribution of the endemic resistance rates of gonococci varied considerably, with 16.7-66.7% of the gonococcal isolates being ciprofloxacin-resistant in Oregon, California, Washington, and Hawaii. Faropenem retained its potency against these recent clinical strains and also quinolone-resistant strains from Japan (MIC90, < or =0.25 microg/mL). In summary, the excellent activity of faropenem against the gonococcal strains analyzed irrespective of the resistance phenotype, along with its beta-lactamase stability, makes it an ideal contender for further development as an oral beta-lactam agent to treat uncomplicated gonococcal infections due to strains emerging with resistant to penicillins, tetracyclines, and fluoroquinolones.

• Authors: Ronald N Jones, Ian A Critchley, William L H Whittington, Nebojsa Janjic, Sudha Pottumarthy
• Journal: Diagnostic microbiology and infectious disease (Diagn Microbiol Infect Dis) Vol. 53 Issue 4 Pg. 311-7 (Dec 2005) ISSN: 0732-8893 [Print] United States
• PMID: 16269221 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Fluoroquinolones
• Lactams
• beta-Lactams
• fropenem
• Cysteine

Topics

• Anti-Bacterial Agents (pharmacology)
• Cysteine (pharmacology)
• Drug Antagonism
• Drug Resistance, Bacterial
• Fluoroquinolones (pharmacology)
• Gonorrhea (microbiology)
• Humans
• Lactams (pharmacology)
• Microbial Sensitivity Tests
• Neisseria gonorrhoeae (drug effects)
• United States
• beta-Lactams