JAC Advance Access originally published online on May 11, 2007
Journal of Antimicrobial Chemotherapy 2007 60(1):177-178; doi:10.1093/jac/dkm142
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Correspondence |
Comment on: High tigecycline resistance in multidrug-resistant Acinetobacter baumannii
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
* Corresponding author. Tel/Fax: +66-2-412-5994; E-mail: sivth{at}mahidol.ac.th
Keywords: A. baumannii , glycylcyclines , susceptibility
Navon-Venezia et al.1 recently reported high tigecycline resistance in multidrug-resistant Acinetobacter baumannii. The activity of tigecycline against A. baumannii was determined by disc diffusion method and Etest. The breakpoints for susceptibility were an inhibition zone diameter 
19 mm and MIC 
2 mg/L. They found that 66% of the isolates were resistant to tigecycline and that the MIC50 and MIC90 values of tigecycline were 16 and 32 mg/L, respectively, with a wide MIC range of 1–128 mg/L. All the Etest MIC values measured in the resistance range correlated 100% with inhibition zone diameters using the disc diffusion method with tigecycline discs.
We would like to describe our experiences in conducting in vitro activity of tigecycline against 148 isolates of Acinetobacter spp. isolated from different infected patients hospitalized at Siriraj Hospital, Bangkok, Thailand during 2002–2005. These isolates were resistant to all ß-lactams, aminoglycosides and fluoroquinolones. In vitro susceptibility of Acinetobacter spp. to tigecycline was determined by Kirby–Bauer disc diffusion, Etest and broth microdilution methods. Paper discs containing 15 µg of tigecycline per disc (Becton Dickinson, USA), Etest strips (AB BIODISK, Sweden) and Gram-negative MicroScan MIC panels (Dade Behring Inc., USA) were provided by Wyeth Research. The methodology for susceptibility testing was determined by direct colony suspension according to the guidelines suggested by the CLSI.2 Quality control was performed by testing the susceptibility of Escherichia coli ATCC 25922.
We found that the MIC50 and MIC90 values of tigecycline for Acinetobacter spp. determined by Etests were 2 and 4 mg/L, respectively. The MIC50 and MIC90 values of tigecycline for Acinetobacter spp. determined by the broth microdilution method were 0.5 and 1 mg/L, respectively. If the MIC of tigecycline at 2 mg/L was a breakpoint for tigecycline susceptibility, 97.3% and 72.3% of the isolates were susceptible to tigecycline as determined by the broth microdilution method and Etest, respectively. If the inhibition zone diameter at 19 mm was a breakpoint for tigecycline susceptibility, only 44.6% of the isolates were susceptible to tigecycline, as shown in Table 1. There was a significant correlation between inhibition zone diameters and MICs determined by the broth microdilution method (P < 0.001, r = –0.8) and between MICs of tigecycline determined by the Etest and broth microdilution method (P < 0.001, r = 0.9). The inhibition zone diameter at 13 mm in predicting susceptibility of Acinetobacter spp. to tigecycline determined by the broth microdilution method is the most accurate breakpoint, as shown in Table 1. If the MIC of tigecycline determined by the broth microdilution method at 2 mg/L was considered a breakpoint for tigecycline susceptibility, the inhibition zone diameter at 13 mm had a sensitivity of 99% and a specificity of 100% in predicting the susceptibility of Acinetobacter spp. to tigecycline.
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The MIC50 and MIC90 values of tigecycline for Acinetobacter spp. determined by the broth microdilution method from our study were comparable with the results from the previous studies on the in vitro activity of tigecycline against A. baumannii using the same method.3–5 However, our findings indicated that there was a discrepancy in susceptibility results of tigecycline against Acinetobacter spp. among different methods of testing. The MICs determined by the Etest were usually 4-fold higher than those determined by the broth microdilution method and Etest might not be an accurate method for in vitro susceptibility testing of tigecycline against Acinetobacter spp. Moreover, our study also observed that the US FDA-approved breakpoint of tigecycline against Enterobacteriaceae, an inhibition zone diameter of
19 mm, was not applicable to tigecycline against Acinetobacter spp. The breakpoint for an inhibition zone diameter of 13 mm was more accurate in predicting susceptibility of Acinetobacter spp. to tigecycline with a sensitivity of 99% and a specificity of 100%. Our observations were similar to those reported by Jones et al.6 They tested 103 contemporary clinical Acinetobacter spp., including multidrug-resistant strains, by reference broth microdilution and disc diffusion (15 µg disc content) methods against tigecycline. Applying tigecycline breakpoint at 2 mg/L and disc diffusion breakpoints at 19 and 14 mm (susceptible and resistant) to Acinetobacter spp. led to an unacceptable error rate (23.3%). However, an adjustment of tigecycline disc diffusion breakpoints (susceptible/resistant) to 16/12 mm reduced intermethod errors to an acceptable level (only 9.7%, all minor). Therefore, the interpretative criteria of inhibition zone diameter breakpoint for tigecycline against Acinetobacter spp. should not be 19 mm. The mechanisms for having smaller inhibition zones and lower MICs of tigecycline for Acinetobacter spp. tested by solid agar methods should be explored. The aforementioned observations warrant a clinical study to determine the efficacy of tigecycline for therapy of Acinetobacter spp. infections in order to consider whether such proposed breakpoints and appropriate testing method are valid. A high tigecycline resistance in multidrug-resistant A. baumannii reported by Navon-Venezia et al. could be due to the methods they used, disc diffusion method and Etest. However, they also found a slight variation in tigecycline susceptibility among different pulsotypes of A. baumannii isolates and this might explain a discrepancy in tigecycline susceptibility in A. baumannii isolates from Israel and other countries.
None to declare.
Acknowledgements
We thank Wyeth Research for providing Etest strips and MicroScan Gram-negative panels for tigecycline susceptibility tests, and The Thailand Research Fund for supporting the study.
References
1
Navon-Venezia S, Leavitt A, Carmeli Y. High tigecycline resistance in multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother (2007) 59:772–4.
2 Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Fifteenth Informational Supplement M100-S15 (2005) Wayne, PA, USA: CLSI.
3
Pachon-Ibanez ME, Jimenez-Mejias ME, Pichardo C, et al. Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains, including those resistant to imipenem. Antimicrob Agents Chemother (2004) 48:4479–81.
4 Bouchillon SK, Hoban DJ, Johnson BM, et al. In vitro activity of tigecycline against 3989 Gram-negative and Gram-positive clinical isolates from the United States Tigecycline Evaluation and Surveillance Trial (TEST Program; 2004). Diagn Microbiol Infect Dis (2005) 52:173–9.[CrossRef][Web of Science][Medline]
5 Sader HS, Jones RN, Dowzicky MJ, et al. Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit. Diagn Microbiol Infect Dis (2005) 52:203–8.[CrossRef][Web of Science][Medline]
6 Jones RN, Ferraro MR, Reller LB, et al. Multicenter studies of tigecycline disk diffusion susceptibility results for Acinetobacter spp. J Clin Microbiol (2007) 35:227–30.
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