a R. M. Alden Research Laboratory, Santa Monica-UCLA Medical Center, 2021 Santa Monica Boulevard, Suite 740, East Santa Monica, CA 90404; b UCLA School of Medicine, Los Angeles, CA 90073, USA
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Abstract |
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Introduction |
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Ertapenem (MK-0826) is a new parenteral carbapenem that is highly resistant to inactivation by a wide variety of ß-lactamases and has been shown to have a broad spectrum of antimicrobial activity against both aerobes and anaerobes.410 These studies have focused on more typical isolates, especially those associated with nosocomial infection and intra-abdominal infections,4,7,8,11 and do not evaluate the in vitro activity against the specific range of bacteria typically found in human and animal bite wound infections. To evaluate the expanded activity of ertapenem, we determined its comparative activity along with 11 other antimicrobial agents against 420 aerobic and anaerobic strains recently isolated from infected skin and soft tissue bite wounds in humans.
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Materials and methods |
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To ensure purity and good growth, frozen cultures of aerobic bacteria were transferred twice on trypticase soy agar (TSA) supplemented with 5% sheep blood, or chocolate agar (Hardy Diagnostics, Santa Maria, CA, USA) and anaerobic bacteria were cultured on Brucella agar supplemented with haemin, vitamin K1 and 5% sheep blood (Anaerobe Systems, Morgan Hill, CA, USA). Susceptibility testing was performed according to NCCLS standards.18,19 Brucella agar supplemented with haemin, vitamin K1 and 5% laked sheep blood was the basal medium used for anaerobic species, and for Eikenella corrodens and Bergeyella zoohelcum. MuellerHinton agar was used for staphylococci, and MuellerHinton agar supplemented with 5% sheep blood was used for the remainder of the organisms.
The agar plates were inoculated with a Steers replicator (Craft Machine Inc., Chester, PA, USA). The inoculum used for aerobic bacteria was 104 cfu/spot, and the inoculum used for E. corrodens and anaerobic bacteria was 105 cfu/spot. Control plates without antimicrobial agents were inoculated before and after each set of drug-containing plates. Plates with aerobic isolates were incubated at 35°C in an aerobic environment for 1820 h and then examined. E. corrodens and streptococci were incubated in 5% CO2 for 4244 h, and plates with anaerobes were incubated in an anaerobic chamber (Anaerobe Systems) at 35°C for 48 h.
The control strains included Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Bacteroides fragilis ATCC 25285 and Bacteroides thetaiotaomicron ATCC 29741. These strains were tested simultaneously with the appropriate plates and environments. The MIC was defined as the lowest concentration of an agent that yielded no growth, or a marked change in the appearance of growth as compared with the growth control plate.
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Results |
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Against anaerobes, ertapenem was active against 170/180 isolates at 0.05 mg/L (overall MIC 90
0.5 mg/L), including strains of Prevotella heparinolytica, other Prevotella spp., Porphyromonas spp., Bacteroides tectum and Peptostreptococcus spp.
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Discussion |
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Wexler et al.10 reported that ertapenem (MK-0826) inhibited 14 strains of Campylobacter gracilis at 0.25 mg/L. However, in our study, the only isolates tested that required
16 mg/L of ertapenem for inhibition were four of five C. gracilis and one of three Campylobacter rectus strains. The reason for this disparity is unclear, as we used the same methods, agar medium and inoculum as Wexler et al.10 Our Campylobacter strains were also resistant to all other ß-lactam agents tested, but susceptible to the fluoroquinolones (levofloxacin, ciprofloxacin) and doxycycline.
As expected, oxacillin was relatively inactive against E. corrodens, EF-4a and EF-4b isolates, Neisseria spp., Moraxella spp. and Veillonella spp., and often 24 mg/L was required to inhibit B. zoohelcum; it also required 14 mg/L of oxacillin to inhibit the various Pasteurella species, making it of limited clinical value in the therapy of bite wound infections. Cefotetan had limited activity against B. zoohelcum and streptococci.
Ertapenem has an excellent broad spectrum of activity and consequently merits further evaluation as a therapeutic alternative in serious animal and human bite wound infections.
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Acknowledgements |
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Notes |
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References |
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2
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Received 9 May 2001; returned 12 July 2001; revised 27 July 2001; accepted 3 August 2001