ROBLIN PM, HAMMERSCHLAG MR; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. F-1674.

SUNY Downstate Medical Center, Brooklyn, NY

BACKGROUND: Peptide deformylase (PDF) is a necessary enzyme in bacterial protein synthesis. The gene encoding PDF (def) is present in all pathogenic bacteria but is not required for mammalian cell growth. Preliminary studies have shown that PDF inhibitors are active against a wide range of respiratory pathogens including Streptococcus pneumoniae, S. pyogenes and Moraxella catarrhalis. Data on activity of these compounds against atypical respiratory pathogens, including Chlamydia pneumoniae and Mycoplasma pneumoniae, are limited. We compared the activity of NVP-PDF386, a new PDF inhibitor, levofloxacin, and clarithromycin against 20 isolates of C. pneumoniae, including TW183, AR-39, CM-1, W6805, and 15 recent clinical isolates from adults with community-acquired pneumonia from the US and one isolate from Japan (J21). METHODS: In vitro susceptibility testing was done in cycloheximide-treated HEp-2 cells grown in 96-well microtiter plates. The minimal inhibitory concentration (MIC) was the lowest antibiotic concentration at which no inclusions were seen. The minimal bactericidal concentration (MBC) was determined by aspirating the antibiotic containing medium, washing wells 2x with PBS and adding antibiotic-free medium. All tests were done in triplicate. RESULTS: NVP-PDF386 was the most active compound tested, the MICs and MBCs ranged from 0.008-0.015microg/ml with an MIC[90] and MBC[90] of 0.015 microg/ml, compared to a range of 0.125-0.25microg/ml (MIC[90] and MBC[90] of 0.25microg/ml) for levofloxacin and a range of 0.015-0.06microg/ml for clarithromycin (MIC[90] and MBC[90] of 0.06microg/ml). CONCLUSIONS: NVP-PDF386 was 5 to10-fold more active in vitro than levofloxacin and clarithromycin against C. pneumoniae. The potential role of NVP-PDF386 or other PDF compounds for the treatment of C. pneumoniae infections will depend on the results of clinical studies utilizing culture to assess microbiologic efficacy.

Publication Types:

• Meeting Abstracts

Keywords:

• Adult
• Amidohydrolases
• Anti-Bacterial Agents
• Bacteria
• Chlamydophila pneumoniae
• Clarithromycin
• Humans
• In Vitro
• Japan
• Microbial Sensitivity Tests
• Mycoplasma pneumoniae
• NVP-PDF386
• Ofloxacin
• Peptides
• Streptococcus pneumoniae
• peptide deformylase

Other ID:

• GWAIDS0028159

UI: 102267783

From Meeting Abstracts