In vitro activity of faropenem against 5460 clinical bacterial isolates from Europe

Dana Milatovic*, Franz-Josef Schmitz, Jan Verhoef and Ad C. Fluit

Eijkman-Winkler Institute for Medical Microbiology, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands

Sir,

Faropenem is a new member of the penem class intended for oral administration. Penems share structural similarities with both penicillins and cephalosporins. Preliminary reports indicate that faropenem has a broad spectrum of activity against Gram-positive and -negative bacteria, and is also bactericidal.1,2

The purpose of the present study was to evaluate the in vitro activity of faropenem against a large number of recent clinical isolates from various European countries and to compare its activity with that of other orally administered compounds, such as co-amoxiclav, cefuroxime, cefpodoxime, cefdinir, cefixime, ceftibuten and co-trimoxazole. Clarithromycin, telithromycin and ABT-773 were included as comparators for Gram-positive bacteria only, because of their limited antibacterial spectrum.

A total of 5460 bacterial strains were tested, which had been isolated between 1998 and 2001 from patients in 33 hospitals from 17 European countries. Only one isolate per patient, which was deemed clinically significant according to local criteria, was studied. Strains were identified using a combination of standard methods and either the VITEK or API system. Susceptibility testing was performed by the microdilution method according to NCCLS guidelines.3 The results of susceptibility testing are presented as ranges of MIC, MIC50s and MIC90s (Table 1).


View this table:
[in this window]
[in a new window]
 
Table 1.  Susceptibility of 5460 clinical isolates to faropenem and comparators
 
Faropenem was very active against methicillin-susceptible Staphylococcus aureus (MIC90 0.12 mg/L) and was eight- to 32-fold more active than the other ß-lactams tested. Except for co-trimoxazole, none of the agents tested showed any activity against methicillin-resistant S. aureus. Corresponding results were observed for methicillin-susceptible and -resistant coagulase-negative staphylococci.

Against Enterococcus faecalis, faropenem and the remaining comparators were less potent than co-amoxiclav (MIC50/MIC90 1/8 and 1/1 mg/L, respectively) and none of the agents showed activity against Enterococcus faecium.

Faropenem was highly active against group A and B ß-haemolytic streptococci and Streptococcus milleri, all strains being inhibited at <=0.12 mg/L, including those strains exhibiting macrolide resistance (8.6%, 4.9% and 7.9%, respectively, of the isolates tested).

Against viridans streptococci faropenem was very active, all strains being inhibited at 1 mg/L except for those isolates resistant to penicillin.

Faropenem exhibited very good activity against the three major pathogens associated with community-acquired respiratory infections (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis). Against S. pneumoniae it was the most active agent among the ß-lactam antibiotics tested. Although the MICs of faropenem for penicillin-intermediate and -resistant strains were higher than those for penicillin-susceptible strains, 96% of the penicillin-resistant strains were inhibited by faropenem at a concentration of 1 mg/L. Among all agents tested, the two ketolide compounds telithromycin and ABT-773 exhibited the highest in vitro activity against all streptococcal isolates.

Against H. influenzae, including ß-lactamase-positive strains, the activity of faropenem (MIC50/MIC90 0.5/1 mg/L) was two-fold higher than that of cefuroxime and comparable to that of co-amoxiclav; the third generation cephalosporins were more active than faropenem. At a faropenem concentration of 1 mg/L, 93.7% of the isolates were inhibited. There was no difference in faropenem MIC distribution between ß-lactamase-positive and -negative strains.

This new penem was also highly active against all M. catarrhalis isolates (MIC50/MIC90 0.12/0.5 mg/L), including ß-lactamase-producing strains. It was two- to eight-fold more active than cefuroxime, cefpodoxime and ceftibuten and was as active as cefixime and cefdinir.

Faropenem showed good activity against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Citrobacter koseri with MIC50s and MIC90s of 0.5 and 1–2 mg/L, respectively. Against Proteus spp., Morganella morganii, Providencia spp., Serratia spp. and Enterobacter spp. faropenem exhibited reduced activity (MIC50 2–8 mg/L and MIC90 4–32 mg/L). Except for the Proteus spp. faropenem was at least four times more active than co-amoxiclav and cefuroxime against the Enterobacteriaceae tested. In comparison with the third generation cephalosporins tested, faropenem was more active against Citrobacter freundii and Enterobacter spp. and equally as active as cefpodoxime and cefixime against E. coli. Except for C. freundii and Enterobacter spp., ceftibuten was the most active agent against the Enterobacteriaceae.

Neither faropenem nor any of the ß-lactam antibiotics tested was active against Pseudomonas aeruginosa and the other non-fermenters.

In summary, our results display a broad spectrum of antibacterial activity of faropenem as shown by others.1,4,5 In particular, faropenem exhibited very good activity against S. pneumoniae, H. influenzae and M. catarrhalis, including penicillin non-susceptible pneumococci and ß-lactamase-producing strains of the latter two species. Its high potency against a variety of common community pathogens recommends faropenem for the treatment of various community-acquired infections, especially those of the respiratory tract.

Acknowledgements

We thank Alice Florijn, Miriam Klootwijk, Karlijn Kusters and Stefan de Vaal for their expert technical assistance and the following colleagues for referring isolates: H. Mittermayer, M. Struelens, F. Goldstein, V. Jarlier, J. Etienne, R. J. Courcol, F. Daschner, U. Hadding, N. Legakis, G. C. Schito, G. Raponi, W. Hryniewicz, P. Heczko, D. Costa, E. Perea, F. Baquero, R. M. Alvarez, J. Bille, G. French, S. Unal, D. Gür, V. Korten, J. M. Andrews, J. K. Moller, K. Elzenaar, A. van Belkum, A. R. Jansz, H. Miorner, M. Vaara, R. Jureen, E. Ijzerman. This work was funded by Bayer AG, Leverkusen.

Footnotes

* Corresponding author. Tel: +31-30-2507625; Fax: +31-30-2541770; E-mail: d.milatovic{at}azu.nl Back

References

1 . Woodcock, J. M., Andrews, J. M., Brenwald, N. P., Ashby, J. P. & Wise, R. (1997). The in vitro activity of faropenem, a novel penem. Journal of Antimicrobial Chemotherapy 39, 35–43.[Abstract]

2 . Boswell, F. J., Andrews, J. M. & Wise, R. (1997). Pharmacodynamic properties of faropenem demonstrated by studies of time–kill kinetics and post-antibiotic effect. Journal of Antimicrobial Chemotherapy 39, 415–8.[Abstract]

3 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: Approved Standard M7-A5. NCCLS, Wayne, PA.

4 . Marchese, A., Debbia, E. A., Bryskier, A. & Schito, G. C. (1999). Antimicrobial activity of faropenem, a new oral penem, against lower respiratory tract pathogens. Clinical Microbiology and Infection 5, 282–7.[Medline]

5 . Cormian, M. G. & Jones, R. N. (1995). Evaluation of the in vitro activity of furopenem (SY5555 or SUN5555) against respiratory tract pathogens and ß-lactamase producing bacteria. Journal of Antimicrobial Chemotherapy 35, 535–9.[Abstract]





This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (1)
Disclaimer
Request Permissions
Google Scholar
Articles by Milatovic, D.
Articles by Fluit, A. C.
PubMed
PubMed Citation
Articles by Milatovic, D.
Articles by Fluit, A. C.