In vitro susceptibility of ertapenem by BSAC standardized methodology

J. M. Andrews*, J. P. Ashby, G. Jevons and R. Wise

Department of Microbiology, City Hospital, Dudley Road, Birmingham B18 7QH, UK

Sir,

Ertapenem is a synthetic, parenteral, 1-ß methyl-carbapenem that is structurally related to ß-lactam antibiotics and has in vitro activity against Gram-positive and Gram-negative aerobic and anaerobic organisms.1 In this communication, we describe a method for assessing the susceptibility of ertapenem based on the British Society for Antimicrobial Chemotherapy (BSAC) standardized methods for determining MIC2 and disc susceptibility testing.3 Detection of ß-lactam resistance (including penicillins, cephalosporins, carbapenems and combinations of ß-lactam and ß-lactamase inhibitors) in staphylococci is best achieved by using methicillin, oxacillin or cefoxitin as an indicator antibiotic, not by testing the ß-lactam antibiotic that is to be used therapeutically.3 Staphylococci were therefore not included in the study.

A total of 893 organisms were studied (see Table 1), including appropriate ATCC and NCTC strains (Escherichia coli NCTC 10418; E.coli ATCC 25922; Haemophilus influenzae NCTC 11931; H. influenzae ATCC 49247; Streptococcus pneumoniae ATCC 49619; Bacteroides fragilis NCTC 9343). MIC determinations and disc susceptibility testing were undertaken using the BSAC methodology.24 Data were analysed using the BSAC susceptible breakpoints5 shown in Table 1.


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Table 1. Criteria for interpreting the susceptibility of ertapenem by BSAC methodology
 
For Enterobacteriaceae, Moraxella catarrhalis and ß-haemolytic streptococci, ertapenem MICs for the ‘wild susceptible’ populations were 0.004–0.25, 0.004–0.03 and 0.004–0.12 mg/L, respectively. Among the Enterobacter cloacae tested, there were six organisms with ertapenem MICs between 1–8 mg/L. When ertapenem and ceftazidime MICs were repeated in combination with clavulanic acid, no reduction in MIC was observed. These isolates are undergoing further tests to elucidate the mechanism of resistance. For S. pneumoniae, ertapenem MICs ranged between 0.008–0.03 mg/L, except for the 20 isolates of S. pneumoniae with reduced susceptibility to penicillin. These organisms had corresponding ertapenem MICs of 0.12–1 mg/L. In the case of H. influenzae, MICs for the ß-lactamase-negative, ampicillin-susceptible population were between 0.015–0.12 mg/L. In comparison, for the ß-lactamase-positive and the ß-lactamase-negative ampicillin-resistanct (BLNAR) organisms, MICs ranged between 0.03–0.12 mg/L and 0.06–0.5 mg/L, respectively. For B. fragilis, MICs for the susceptible population were between 0.12–0.5 mg/L. For the five clinical isolates with reduced susceptibility to ertapenem, MICs were between 1–4 mg/L.

The susceptibility of each organism was categorized by comparing the ertapenem MIC with the MIC range for the ‘wild susceptible’ population. This information was then used to analyse the zone diameter data. Table 1 summarizes the MIC and zone diameter breakpoints (BPs) for each of the organism groups tested. MIC and zone diameter ranges for the control strains were: E.coli NCTC 10418, 0.004–0.015 mg/L (35–41 mm); E.coli ATCC 25922, 0.008–0.03 mg/L (35–39 mm); H. influenzae NCTC 11931, 0.06–0.25 mg/L (30–38 mm); H. influenzae ATCC 49247, 0.25–1 mg/L (25–34 mm); S. pneumoniae ATCC 49619, 0.06–0.25 mg/L (35–40 mm); B. fragilis NCTC 9343, 0.12–0.5 mg/L (35–39).

All of the E. cloacae, S. pneumoniae and B. fragilis with ertapenem MICs higher than the ‘wild susceptible’ population were detected by disc susceptibility testing using the interpretative criteria recommended.

This study has shown that a 10 µg ertapenem disc is suitable for testing by BSAC methodology, and those organisms with reduced susceptibility can be detected using the criteria suggested. However, the large zones of inhibition observed for the susceptible population may preclude multiple disc testing on one plate.

Footnotes

* Corresponding author. Tel: +44-121-507-5693; Fax: +44-121-551-7763; E-mail: jenny.andrews{at}swbh.nhs.uk Back

References

1 . INVANZ annotated prescribing information. Merck & Co. Incorporated, Hoddesdon, UK.

2 . Andrews, J. M. (2001). Determination of minimum inhibitory concentrations. Journal of Antimicrobial Chemotherapy 48, Suppl. S1, 5–16.[Abstract/Free Full Text]

3 . Andrews, J. M. (2001). BSAC standardized disc susceptibility testing method. Journal of Antimicrobial Chemotherapy 48, Suppl. S1, 43–57.[Abstract/Free Full Text]

4 . King, A. (2001). Recommendations for susceptibility tests on fastidious organisms and those requiring special handling. Journal of Antimicrobial Chemotherapy 48, Suppl. S1, 77–80.[Abstract/Free Full Text]

5 . British Society for Antimicrobial Chemotherapy. (2003). BSAC disc diffusion method for antimicrobial susceptibility testing. Version 2.1.4 May 2003. [Online.] http://www.bsac.org.uk (29 July 2003, date last accessed).





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