Comparative Evaluation of In-vitro Synergy Testing Methods in Carbapenem-Resistant Acinetobacter Species

Year 2019, Volume: 09 Issue: 01, 23 - 33, 15.03.2019

Ranu Soni Varsha Gupta Priya Datta Satinder Gombar Jagdish Chander

https://doi.org/10.5799/jmid.537162

Abstract

Objective: There is an increasing incidence of Acinetobacter species causing serious
hospital acquired infections such as blood stream infections (BSI), catheter
associated urinary tract infections (CAUTI) and lower respiratory tract
infections(LRTI) with high mortality rate of 30-75% in patients having long
hospital stay especially in critical care units (CCUs). During the past decade,
multi drug resistant Acinetobacter
isolates have presented a real challenge to clinicians and are posing
difficulties in treatment. Carbapenem-resistant Acinetobacter species particularly A. baumannii, represent a growing public health concern, since they
often confer resistance to other critically important antimicrobials.

Methodology: In the present study, various antibiotic combinations
such as colistin + meropenem, imipenem + tigecycline, polymyxin B +
azithromycin and doripenem + sulbactam are used for MDR Acinetobacter infections and tested for in-vitro combination test
by Epsilometric test and Broth Micro dilution and confirmation done by time
kill assay.

Results: We found synergistic results with all three methods
used in study with three combinations significantly (p<0.05) but with one
combination i.e. doripenem+sulbactam, synergy found only with Etest not with
MCB and time kill assay (p~0.069).  

Conclusions: We have also observed
and compared outcome of the patients with respect to the treatment received
during hospital stay, but we did not found significant difference between two
groups, (two drug regimen & three drug regimen) regarding their mortality.  J
Microbiol Infect Dis 2019; 9(1): 23-33.

Keywords

Acinetobacter species, drug synergism, antibiotic sensitivity testing

References

• 1. Bergogne-Bérézin E, Towner KJ. Acinetobacter spp. as nosocomial pathogens: Microbiological, clinical, and epidemiological features. Clin Microbiol Rev 1996; 9:148-165. 2. Balaji V, Jeremiah SS, Baliga PR. Polymyxins: Antimicrobial susceptibility concerns and therapeutic options. Indian J Med Microbiol 2011; 29:230-242. 3. Doi Y, Murray GL, Peleg AY. Acinetobacter baumannii: evolution of antimicrobial resistance-treatment options. Semin Respir Crit Care Med 2015; 36:85-98. 4. Anandan S, Jennifer L, Pragasam AK, et al Synergy Testing between Sulbactam and Meropenem/ Colistin in MDR Acinetobacter baumannii-calcoaceticus Complex Isolated from Ventilator Associated Pneumonia. J Infect Dis Ther 2016; 4:299. 5. Clinical and Laboratory Standards Institute.2016. Performance Standards for Antimicrobial Susceptibility Testing; approved standard. 26th ed. supplement CLSI document M100S. Clinical and Laboratory Standards Institute Wayne, PA, USA. 6. Andrews JM. BSAC Standardized disc susceptibility testing methods version 6. J Antimicrob Chemother 2007; 60:20-41. 7. Sopirala MM, Mangino JE, Gaberyes WA, et al. Synergy testing by Etest, microdilution checkerboard, and time-kill methods for pan-drug-resistant Acinetobacter baumannii. J Antimicrob Chemother 2010; 54:4678-4683. 8. Clinical and Laboratory Standards Institute.2009. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. 8th ed. Supplement CLSI document M07-A8. Clinical and Laboratory Standards Institute Wayne, PA, USA. 9. Garcia, Lynne Shore, Isenberg, Henery D. Microbiological Techniques & methods-Laboratory Manuals. Clinical Microbiology Procedures Handbook-3rd edition, 2007 update Washington, 2007; 2:5.18.1-14. 10. Howard A, O’Donoghue M, Feeney A, Sleator RD. Acinetobacter baumannii An emerging opportunistic pathogen, Virulence 2012; 3:243-250. 11. Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother 2010; 65:233-238. 12. Soudeiha MAH, Dahdouh EA, Azar E, Sarkis DK, Daoud Z. In vitro Evaluation of the Colistin-Carbapenem Combination in Clinical Isolates of A. baumannii, Using the Checkerboard, Etest, and Time-Kill Curve Techniques. Front Cell Infect Microbiol 2017; 7:209. 13. LeMinh V, Nhu NTK, Phat VV, et al. In vitro activity of colistin in antimicrobial combination against carbapenem-resistant Acinetobacter baumannii isolated from patients with ventilator-associated pneumonia in Vietnam. J Med Microbiol 2015; 64:1162-9. 14. Justin RL, Roger LN, Brian TT. Synergistic combinations of polymyxins. Int J Antimicrob Agents 2016; 48:607-613. 15. D'Arezzo S, Capone A, Petrosillo N, et al. Epidemic multidrug resistant Acinetobacter baumannii related to European clonal types I and II in Rome (Italy). Clin Microbiol Infect 2009; 15:347-357. 16. Kuo LC, Yu CJ, Kuo ML, Chen WN, Chang CK, Lin HI. Antimicrobial resistance of bacterial isolates from respiratory care wards in Taiwan: A horizontal surveillance study. Int J Antimicrob Agents 2008; 31:420-426. 17. Lee NY, Wang CL, Chuang YC, Yu WL, Lee HC, Chang CM. Combination carbapenem-ampicillin/sulbactam therapy for critically ill patients with multidrug-resistant Acinetobacter baumannii bacteremia: Four case reports and an in vitro combination synergy study. Pharmacotherapy. 2007; 27:1506-1511. 18. Pachon-Ibanez ME, Jimenez-Mejias ME, Pichardo C, Lianos AC, Pachon J. Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains, including those resistant to imipenem. Antimicrob Agents Chemother 2004; 48:4479-4481. 19. Nageeb W, Metwally L, Kamel M, Zakaria S. In vitro antimicrobial synergy studies of carbapenem-resistant Acinetobacter baumannii isolated from intensive care unit of tertiary care hospital in Egypt J Infect public Health 2015; 8:593-602. 20. Manikal VM, Landman D, Saurina G, Oydna E, Lal H, Quale J. Endemic carbapenem-resistant Acinetobacter species in Brooklyn, New York: citywide prevalence, inter-institutional spread, and relation to antibiotic usage. Clin Infect Dis 2000; 31:101-106. 21. Luber P, Bartelt,E, Genschow E, Wagner J, Hahn H. Comparison of broth microdilution, E Test, and agar dilution methods for antibiotic susceptibility testing of Campylobacter jejuni and Campylobacter coli. J Clin Microbiol 2003; 41:1062-1068. 22. Dinc G, Demiraslan H, Elmali F, Ahmed SS, Alp E, Doganay M. Antimicrobial efficacy of doripenem and its combinations with sulbactam, amikacin, colistin, tigecycline in experimental sepsis of carbapenem-resistant Acinetobacter baumannii. New Microbiol 2015; 38:67-73. 23. Pongpech P, Amornnopparattanakul S, Panapakdee S, et al. Antibacterial activity of carbapenem-based combinations againts multidrug-resistant Acinetobacter baumannii. J Med Assoc Thai 2010; 93:161-171. 24. Keam S.J. Doripenem: a review of its use in the treatment of bacterial infections. Drugs 2008; 68:2021-2057. 25. Fernandez CF, Martinez ML, Conejo MC, Ayala JA, Perea EJ, Pascual A. Relationship between β-lactamase production, outer membrane protein and penicillin-binding protein profiles on the activity of carbapenems against clinical isolates of Acinetobacter baumannii. J Antimicrob Chemother. 2003; 51:565-574. 26. Gerner-Smidt P, Tjernberg I, Ursing J. Reliability of phenotypic tests for identification of Acinetobacter species. J Clin Microbiol 1991; 29:277-282. 27. Viehman JA, Nguyen MH, Doi Y. Treatment Options for Carbapenem-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections. HHS Public Access. Drugs 2014; 74:1315-1333. 28. Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, Tansarli GS. Antibiotic treatment of infections due to carbapenem‑resistant Enterobacteriaceae: Systematic evaluation of the available evidence. Antimicrob Agents Chemother 2014; 58:654‑663. 29. Ghafur A, Devarajan V, Raja T, et al. Monotherapy versus combination therapy against carbapenem-resistant Gram-negative bacteria: A retrospective observational study. Indian J Cancer 2016; 53: 592-594. 30. Saiman L. Clinical utility of synergy testing for multi drug resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis: the motion for. Paediatr Respir Rev 2007; 8:249-255.