Tigecycline activity against metallo-β-lactamase-producing bacteria

Abstract

Backgound: Treatment of serious life-threatening multi-drug-resistant organisms poses a serious problem due to the limited therapeutic options. Tigecycline has been recently marketed as a broad-spectrum antibiotic with activity against both gram-positive and gram-negative bacteria. Even though many studies have demonstrated the activity of tigecycline against ESBL-producing Enterobacteriaceae, its activity is not well-defi ned against micro-organisms producing metallo-β-lactamases (MBLs), as there are only a few reports and the number of isolates tested is limited. Aims: The aim of the present study was to evaluate the activity of tigecycline against MBL-producing bacterial isolates. Materials and Methods: The isolates were tested for MBL production by (i) combined-disk test, (ii) double disc synergy test (DDST), (iii) susceptibility to aztreonam (30 μg) disk. Minimum inhibitory concentration to tigecycline was determined according to agar dilution method as per Clinical Laboratory Standards Institute (CLSI) guidelines. Disc diffusion susceptibility testing was also performed for all these isolates using tigecycline (15 μg) discs. Results: Among the total 308 isolates included in the study, 99 were found to be MBL producers. MBL production was observed mostly in isolates from pus samples (40.47%) followed by urine (27.4%) and blood (13.09%). MBL production was observed in E. coli (41.48%), K. pneumoniae (26.67%), Proteus mirabilis (27.78%), Citrobacter spp. (41.67%), Enterobacter spp. (25.08%), and Acinetobacter spp. (27.27%). The result showed that tigecycline activity was unaffected by MBL production and it was showed almost 100% activity against all MBL-producing isolates, with most of the isolates exhibiting an MIC ranging from 0.25-8 μg/ml, except 2 MBL-producing E. coli isolates who had an MIC of 8 μg/ml. Conclusion: To conclude, tigecycline was found to be highly effective against MBL-producing Enterobacteriaceae and acinetobacter isolates, but the presence of resistance among organisms, even before the mass usage of the drug, warrants the need of its usage as a reserve drug. The study also found that the interpretative criteria for the disc diffusion method, recommended by the FDA, correlates well with the MIC detection methods. So, the microbiology laboratories might use the relatively easier method of disc diffusion, as compared to the comparatively tedious method of MIC determination.

Keywords

Gram-negative bacteria - metallo-β-lactamases - tigecycline

Publication History

Article published online:
09 August 2021

• References

• 1 Poirel L, Héritier C, Spicq C, Nordmann P. In vivo acquisition of high-level resistance to imipenem in Escherichia coli. J Clin Microbiol 2004;42:3831-3.
• 2 Queenan AM, Bush K. Carbapenemases: The versatile β-lactamases. Clin Microbiol Rev 2007;20:440-58.
• 3 Walsh TR. The emergence and implications of metallo-β-lactamases in Gram-negative bacteria. Clin Microbiol Infect 2005;11 Suppl 6:2-9.
• 4 Poirel L, Nordmann P. Acquired carbapenem-hydrolyzing β-lactamases and their genetic support. Curr Pharm Biotechnol 2002;3:117-27.
• 5 Walsh TR, Toleman MA, Poirel L, Nordmann P. Metallo-β-lactamases: The quiet before the storm? Clin Microbiol Rev 2005;18:306-25.
• 6 Livermore DM. Tigecycline: What is it, and where should it be used? J Antimicrob Chemother 2005;56:611-4.
• 7 Hawkey P, Finch R. Tigecycline: In-vitro performance as a predictor of clinical efficacy. Clin Microbiol Infect 2007;13:354-62.
• 8 Winn WC Jr, Allen SD, Janda WM, Koneman EW, Procop GW, Schreckenberger PC, et al., editors. Chapter 7. In: Koneman′s Color Atlas and Textbook of Diagnostic Microbiology. 6 th ed. Baltimore: Lippincott Williams and Wilkins; 2006. p. 348-9.
• 9 Performance standards for Antimicrobial Susceptibility Testing; Seventeenth Informational Supplement. Clin Lab Stand Inst 2010;29:60-70.
• 10 Franklin C, Liolios L, Peleg AY. Phenotypic detection of carbapenem-susceptible metallo-β-lactamase-producing Gram-negative bacilli in the clinical laboratory. J Clin Microbiol 2006;44:3139-44.
• 11 Manchanda V, Singh NP. Occurrence and detection of AmpC 14. β-lactamases among Gram-negative clinical isolates using a modified three dimensional test at Guru Teg Bahadur Hospital, Delhi, India. J Antimicrob Chemother 2003;51:415-8.
• 12 Jones RN, Ferraro MJ, Reller LB, Schreckenberger PC, Swenson JM, Sader HS. Multicenter studies of tigecycline disk diffusion susceptibility results for Acinetobacter Spp. J Clin Microbiol 2007;45:227-30.
• 13 Brown SD, Traczewski MM. Comparative in vitro antimicrobial activity of tigecycline, a new glycylcycline compound, in freshly prepared medium and quality control. J Clin Microbiol 2007;45:2173-9.
• 14 Rossolini GM. Acquired metallo-β-lactamases: An increasing clinical threat. Clin Infect Dis 2005;41:1557-8.
• 15 Cornaglia G, Akova M, Amicosante G, Cantón R, Cauda R, Docquier JD, et al. Metallo-β-lactamases as emerging resistance determinants in Gram-negative pathogens: Open issues. Int J Antimicrob Agents 2007;29:380-8.
• 16 Walsh TR, Bolmstrom A, Qwarnstrom A, Gales A. Evaluation of a new E-test for detecting metallo- β-lactamases in routine clinical testing. J Clin Microbiol 2002;40:2755-9.
• 17 Dwivedi M, Mishra A, Azim A, Singh RK, Baronia AK, Prasad KN, et al. Ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae carrying multiple metallo-beta-lactamase genes. Indian J Pathol Microbiol 2009;52:339-42.
• 18 Castanheira M, Sader HS, Deshpande LM, Fritsche TR, Jones RN. Antimicrobial activities of tigecycline and other broad-spectrum antimicrobials tested against serine carbapenemase- and metallo-β-lactamase-producing enterobacteriaceae: Report from the SENTRY antimicrobial surveillance program. Antimicrob Agents Chemother 2008;52:570-3.
• 19 Behera B, Das A, Mathur P, Kapil A, Gadepalli R, Dhawan B. Tigecycline susceptibility report from an Indian tertiary care hospital. Indian J Med Res 2009;129:446-50.
• 20 Curcio D. Tigecycline for severe infections: The gap between the warning and the necessity. J Antimicrob Chemother 2011;66:454-6.
• 21 Kelesidis T, Karageorgopoulos DE, Kelesidis I, Falagas ME. Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: A systematic review of the evidence from microbiological and clinical studies. J Antimicrob Chemother 2008;62:895-904.