JAC Advance Access originally published online on September 8, 2008
Journal of Antimicrobial Chemotherapy 2008 62(6):1463-1464; doi:10.1093/jac/dkn389
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Research letters |
Susceptibility testing of tigecycline against Acinetobacter spp. by disc diffusion method: withdrawing a therapeutic option by varying the Mueller–Hinton agar?
1 Laboratorio de Microbiología, Hospital Alemán, Buenos Aires, Argentina 2 Laboratorio Domingo I Nanni, Paraná, Argentina
* Correspondence address. Colón 128, 3100 Paraná, Entre Rios, Argentina. Tel: +54-343-4310783; Fax: +54-343-4232340; E-mail: cbantar{at}arnet.com.ar
Keywords: tetracyclines , susceptibility tests , antimicrobial resistance
We read with interest the letter published by Thamlikitkul and Tiengrim.1 They found that the susceptibility of several Acinetobacter spp. isolates varied according to the commercial Mueller–Hinton agar (MHA) used in the disc diffusion test, probably as a consequence of the higher content of manganese in the Oxoid MHA, when compared with that from Becton-Dickinson. In fact, they have previously noted the lack of correlation between the disc diffusion and microdilution tests, albeit the MHA employed in that study was not stated.2 To analyse the differences between the two different MHA trademarks, these authors used a correlation model applied to the results yielded by the disc diffusion test performed with both media. It is difficult to see how such an analysis would shed light on the magnitude of the problem. Indeed, even proving a close correlation, both media showed a significant difference in the resistance rate.1 We performed susceptibility testing in 107 isolates of Acinetobacter spp. recovered from patients hospitalized in 20 Argentinean centres. In vitro susceptibility was assayed in parallel by the disc diffusion method with a 15 µg tigecycline disc, as described by the CLSI,3 with three different MHAs: A, Oxoid (Oxoid Ltd, Basingstoke, Hampshire, UK); B, Britania (Laboratotios Britania SA, Buenos Aires, Argentina) and C, Difco (Difco Laboratories, Detroit, MI, USA). In addition, broth microdilution testing was performed (SENSITITRE, Trek Diagnostics, UK). Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 were used as the controls. The mean inhibition zone diameters (mm ± SD) for MHA-A, -B and -C were 18.4 ± 2.7, 19.5 ± 2.6 and 21.1 ± 2.6, respectively. Table 1 shows the frequency of interpretative errors observed with the three MHAs. A comparative analysis was performed adopting the breakpoints suggested by the US Food and Drug Administration (FDA) for Enterobacteriaceae (Tygacil package insert June 2005, Wyeth Pharmaceuticals Inc., Philadelphia, PA, USA) and those suggested by Jones et al.4 for Acinetobacter spp. With the FDA breakpoints and taking into account the minor errors, the worst results were displayed by MHA-A, followed by MHA-B and MHA-C. Of interest, all major errors disappeared when the breakpoint of Jones et al.4 was taken into account, whereas the rank in minor errors remained unchanged. Very major errors were not found in any instance. By splitting the isolates according to the tigecycline MIC; >0.5 mg/L (18 isolates) and 
0.5 mg/L (89 isolates), we observed that all error rates were more pronounced in the group with higher MICs. As an example, by adopting the FDA breakpoint, major errors increased from 0% to 5.6% and to 11.1% with MHA-B and -C, respectively; whereas the corresponding minor errors increased from 50.6% to 77.8% and from 25.8% to 55.6%. Therefore, it appears that disc diffusion is not the optimal method to be used for susceptibility testing of tigecycline against Acinetobacter spp. However, testing this new antibiotic by other techniques is not a simple issue, as the purified drug is not available, thus agar dilution is not possible and tigecycline is not included in the routine commercial microdilution cards. In addition, the tigecycline microdilution panel is still difficult to obtain on a large scale in many countries, so that the diffusion method is routinely used in several countries for testing tigecycline against this pathogen in the clinical setting, where this drug may be the only suitable option for treating severe infections caused by multiresistant Acinetobacter spp. strains.5 Our results enlarge the observation of Thamlikitkul and Tiengrim,1 quantify the magnitude of the problem and demonstrate that its extent may vary according to the adopted breakpoint. Thus, caution should be exerted when testing tigecycline against Acinetobacter spp. by the disc diffusion method, especially when the manganese content in the MHA is unknown. Further studies are required to definitively rule out the influence of this phenomenon on dilution tests.
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No external funding was received for this study.
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L. F. C. has received speaking fees from Wyeth. C. B. has received speaking fees from Wyeth and Laboratorios Bago and a fee for serving on an Advisory Board from Wyeth.
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1 Thamlikitkul V, Tiengrim S. Effect of different Mueller–Hinton agars on tigecycline disc diffusion susceptibility for Acinetobacter spp. J Antimicrob Chemother (2008) 62:847–848.
2 Tiengrim S, Tribuddharat C, Thamlikitkul V. In vitro activity of tigecycline against clinical isolates of multidrug-resistant Acinetobacter baumannii in Siriraj Hospital, Thailand. J Med Assoc Thai (2006) 89(Suppl_5):S102–5.[Medline]
3 Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard M2-A9 (2006) 9th edn. Wayne, PA, USA: CLSI.
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Jones RN, Ferraro MJ, Reller LB, et al. Multicenter studies of tigecycline disk diffusion susceptibility results for Acinetobacter spp. J Clin Microbiol (2007) 45:227–30.
5 Schafer JJ, Goff DA, Stevenson KB, et al. Early experience with tigecycline for ventilator-associated pneumonia and bacteremia caused by multidrug-resistant Acinetobacter baumannii. Pharmacotherapy (2007) 27:980–7.[CrossRef][Web of Science][Medline]
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