a Pneumococcal Diseases Research Unit of the Medical Research Council, National Health Laboratory Service and University of the Witwatersrand, de Korte Street, Hillbrow, Johannesburg 2000, South Africa; b Department of International Health, The Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA
Sir,
Faropenem is a novel ß-lactam antimicrobial agent sharing structural similarities with both the penicillins and cephalosporins. It exhibits a broad spectrum of activity that includes Gram-negative, Gram-positive and some anaerobic bacteria.1,2 The primary mode of action of faropenem is consistent with that of other ß-lactam antibiotics, namely binding to penicillin-binding proteins. Faropenem has been shown to demonstrate high stability to a number of ß-lactamases, including TEM-1, SHV-1 to -5, TEM-3 to -9 and the ß-lactamase produced by Staphylococcus aureus NCTC 11561.3,4
The purpose of this study was to determine the activity of faropenem compared with cefaclor, cefpodoxime, cefixime, erythromycin, telithromycin, clarithromycin, azithromycin, levofloxacin and co-amoxiclav against the respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.
Bacterial strains were obtained from routine specimens collected from hospitals and clinics in South Africa. A total of 300 isolates of S. pneumoniae (100 each were penicillin susceptible, intermediate and resistant), 166 isolates of H. influenzae (100 and 66 were ß-lactamase negative and positive, respectively) and 89 isolates of M. catarrhalis (18 and 71 were ß-lactamase negative and positive, respectively) were evaluated. The following control strains were included: Escherichia coli ATCC 35218, S. aureus ATCC 29213, S. pneumoniae ATCC 49619, M. catarrhalis ATCC 43627 and 43628 and H. influenzae ATCC 49247 and 49766. MICs were determined by the broth microdilution method according to the NCCLS recommendations.5 Antibiotics were purchased from Sigma Chemical Co., St Louis, MO, USA, with the exception of faropenem, which was supplied by Bayer AG (Leverkusen, Germany). ß-Lactamase testing was carried out using the nitrocefin method (Oxoid, Basingstoke, UK), as described previously.6 The bro gene from M. catarrhalis isolates was characterized by restriction endonuclease analysis, as described previously.7
The MIC ranges, MIC50s and MIC90s of the 10 antimicrobial agents tested are shown in the Table. Faropenem was active against penicillin-susceptible and -intermediate S. pneumoniae strains (MIC90 < 0.12 mg/L) and was more active than the other drugs with the exception of telithromycin (MIC90 < 0.12 mg/L). Faropenem remained active against penicillin-resistant S. pneumoniae, albeit with an increased MIC90 of 0.5 mg/L. Other antimicrobial agents with MICs < 1 mg/L against penicillin-resistant pneumococci were levofloxacin (MIC90 0.5 mg/L) and telithromycin (MIC90 < 0.12 mg/L). Co-amoxiclav was highly active against penicillin-susceptible isolates (MIC90 0.12/0.06 mg/L) but its activity was reduced three- and four-fold against penicillin-intermediate (MIC90 1/0.5 mg/L) and penicillin-resistant isolates (MIC90 2/1 mg/L), respectively. The oral cephems and other macrolides exhibited activity against penicillin-susceptible isolates, reduced activity against penicillin-intermediate isolates and little activity against penicillin-resistant isolates.
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Against the M. catarrhalis isolates, all the agents exhibited good activity. Faropenem exhibited good activity against both ß-lactamase-negative and -positive isolates (MIC90s, <0.12 and 0.25 mg/L, respectively). The activity of the oral cephems was better against ß-lactamase-negative isolates (MIC90s < 0.12 mg/L) than against ß-lactamase-positive isolates (MIC90s 0.251 mg/L). Previous studies have demonstrated that strains harbouring BRO-1 ß-lactamases confer higher levels of resistance to the penicillins than strains harbouring BRO-2 ß-lactamases;8,9 however, there was no clinically meaningful increase in the MICs of the agents used in this study for BRO-1-producing isolates.
The data presented here indicate that faropenem displays useful in vitro activity against three respiratory pathogens and may be particularly useful in the treatment of pneumococcal infections caused by strains with decreased susceptibility to penicillin.
Acknowledgements
We thank Bayer AG for their financial support for this study.
Notes
* Corresponding author. Tel: +27-11-489-9335/9; Fax: +27-11-489-9332; E-mail: mignondp{at}hotmail.com
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