In vitro and in vivo evaluation of antibiotic combination against colistin resistant Acinetobacter baumannii isolated from patients of a tertiary care hospital, Bangladesh
DOI:
https://doi.org/10.18203/2320-6012.ijrms20242916Keywords:
Acinetobacter baumannii, colistin resistance, combined antibiotic therapy, in vitro and in vivo efficacyAbstract
Background: Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern as these-strain are simultaneously resistant to most antimicrobial agents. Colistin is considered as last resort for treating severe bacterial infections caused by gram negative multidrug resistant bacteria. Since current treatment option for these strains are extremely limited, different antimicrobial combinations were used to see their efficacy against colistin resistant A. baumannii both in vitro and in vivo.
Methods: Cross-sectional study was done in the department of Microbiology, Dhaka Medical College, Bangladesh from July, 2017 to June, 2018. Antibiotic susceptibility was performed by disc-diffusion technique and MIC. Colistin resistance genes were detected by PCR. In vitro activity of colistin, tigecycline, imipenem, amikacin and their combinations were evaluated by agar dilution method. Rat septicemic models were made using the colistin resistant A. baumannii and effectiveness of antibiotic combinations were tested in rats.
Results: Among 32 isolated A. baumannii 12.5% were colistin resistant. All colistin resistant A. baumannii were positive for lpxA, lpxC, pmrA, pmrB genes; 75% were positive for lpxD gene, 50% were positive for pmrC gene. The proportions of synergy observed in colistin-tigecycline, colistin-imipenem, colistin-amikacin and imipenem-amikacin were 75%, 50%, 50% and 25% respectively in vitro. The best in vivo result appeared in group treated with colistin-tigecycline combination where 100% bacterial clearance from rats was observed while colistin-imipenem combination showed 83.33% clearance.
Conclusion: Colistin plus tigecycline or colistin plus imipenem may be alternative treatment option against colistin resistant A. baumannii infection.
Metrics
References
Antunes LC, Visca P, Towner KJ. Acinetobacter baumannii: evolution of a global pathogen. Pathog Dis 2014; 71: 292–301.
Peleg AY, Hooper DC. Hospital-acquired infections due to Gram-negative bacteria. N Engl J Med, 2010; 362: 1804–13.
Clark NM, Zhanel GG, Lynch JP. Emergence of antimicrobial resistant among Acinetobacter species: a global threat. Curr Opin Crit Care, 2016; 22(5): 491-499.
Nowak J, Zander E, Stefanik D, Higgins PG, Roca I, Vila J et al. High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and 486 Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother, 2017; 72: 3277-3282.
Rodriguez CH, De Ambrosio A, Bajuk M, Spinozzi M, Nastro M, Bombicino K et al. In vitro antimicrobials activity against endemic Acinetobacter baumannii multiresistant clones. J Infect Dev Ctries, 2010; 4(3): 164–7.
Bialvaei AZ, Kafil HS. Colistin, mechanisms and prevalence of resistance. Curr Med Res Opin, 2015; 31(4): 707-721.
Zusman O, Avni T, Leibovici L, Adler A, Friberg L, Stergiopoulou T et al. Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems. Antimicrob Agents Chemother, 2013; 57(10): 5104-5111.
Chessbrough M. Microscopical test. In: Chessbrough M, ed. District laboratory Practice in Tropical Countries, Cambridge University Press, UK; 2000: pp.178-195.
Dortet L, Legrand P, Soussy CJ, Cattoir V. Bacterial identification, clinical significance, and antimicrobial susceptibilities of Acinetobacter ursingii and Acinetobacter schindleri, two frequently misidentified opportunistic pathogens. J Clin Microbiol, 2006; 44: 4471-4478.
Clinical and Laboratory Standards Institute (CLSI) performance standards for antimicrobial susceptibility testing; Twenty-seventh informational supplement. CLSI document M100-S27. Wayne, PA: CLSI; 2017.
Khosravi AD, Barazandeh B. Investigation of genetic heterogenecity in Mycobacteriun tuberculosis isolates from tuberculosis patients using DNA fingerprinting. Indian J Med Sci, 2005; 59(6): 253-8.
Gombert ME, Aulicino TM. Synergism of imipenem and amikacin in combination with other antibiotics against Nocardia asteroids. Antimicrob Agents Chemother, 1983; 24(5): 810-811.
Hernandez MJR, Pachon J, Pichardo C, Cuberos L, Martinez JI, Curiel AG et al. Imipenem, doxycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental pneumonia. J Antimicrob Chemother, 2000; 45: 493-501.
Akter S, Shamsuzzaman SM. Distribution of New Delhi metallo-beta-lactamase producing Acinetobacter baumannii in patients with ventilator associated respiratory tract infection. IMC J Med Sci, 2018; 12(1): 37-41.
Pawar SK, Karande GS, Shinde RV, Pawar VS. Emergence of colistin resistant gram- negative bacilli, in a tertiary care rural hospital from western India. Indian J Microbiol Res, 2016; 3(3): 308-313.
Henry R, Vithanage N, Harrison P, Seeman T, Coutts S, Moffatt JH et al. Colistin-resistant, lipopolysaccharide deficient Acinetobacter baumannii responds to lipopolysaccharide loss through increased expression of genes involved in the synthesis and transport of lipoproteins, phospholipids, and poly-β-1, 6-N-acetylglucosamine. Antimicrob Agents Chemother, 2012; 56: 59-69.
Soon RL, Nation RL, Cockram S, Moffatt JH, Harper M, Adler B et al. Different surface charge of colistin-susceptible and resistant Acinetobacter baumannii cells measured with zeta potential as a function of growth phase and colistin treatment. J Antimicrob Chemother, 2011; 66: 126–33.
Adams MD, Nickel GC, Bajaksouzian S, Lavender H, Murthy AR, Jacobs MR et al. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob Agents Chemother, 2009; 53: 3628-34.
Arroyo LA, Herrera CM, Fernandez L, Hankins JV, Trent MS, Hancock RE. The pmrCAB operon mediates polymyxin resistance in Acinetobacter baumannii ATCC 17978 and clinical isolates through phosphoethanolamine modification of lipid A. Antimicrob Agents Chemother, 2011; 55: 3743-51.
Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016; 16: 161-8.
Mostofa HA, Shamsuzzaman SM, Hasan MM. Colistin susceptibility pattern in gram negative bacilli isolated from patients of Dhaka Medical College Hospital with distribution of antibiotic resistance genes among them. Asian Jr. of Microbiol Biotech Env. Sc. 2020; 22(3): 432-437.
Zubair A. Qureshi, Lauren E. Hittle, Jessica A. O’Hara, Jesabel I. Rivera, Alveena Syed, Ryan K. Shields, Anthony W. Pasculle, Robert K. Ernst, and Yohei Doi Colistin-Resistant Acinetobacter baumannii: Beyond Carbapenem Resistance. Clin Infect Dis 2015;60(9):1295–303.
Taneja N, Singh G, Singh M, Sharma M. Emergence of Tigecycline & Colistin resistant Acinetobacter Baumanii in patients with complicated UTI in North India. Indian J Med Res. 2011;133:681-684.
Baadani AM, Thawadi MSI, El-Khizzi NA, Omrani AS. Prevalence of colistin and tigecycline resistance in Acinetobacter baumannii clinical isolates from 2 hospitals in Riyadh Region over a 2-year period. Saudi Med J, 2013; 34(3): 248-253.
Rodriguez CH, Bombicino K, Granados G, Nastro M, Vay C, Famiglietti A. Selection of colistin-resistant Acinetobacter baumannii isolates in postneurosurgical meningitis in an intensive care unit with high presence of heteroresistance to colistin. Diagn Microbiol Infect Dis 2009; 65: 188-191.
Li J, Rayner CR, Nation RL, Owen RJ, Spelman D, Tan KE, et al. Heteroresistance to Colistin in Multidrug-Resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2006; 50: 2946-2950 .
Peleg AY, Adams J, Paterson DL. Tigecycline Efflux as a Mechanism for Nonsusceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother 2007; 51: 2065-2069.
Navon-veneza S, Leavitt A, Carmeli Y. High tigecycline resistance in multidrug-resistant Acinetobacter baumannii. J antimicrobial chemother, 2007; 59; 772-774.
Garbati MA, Abdulhak AB, Baba K, Sakkijha H. Infection due to colistin-resistant Enterobacteriacae in critically-ill patients. J Infect Dev Ctries 2013;7(10):713- 719.
Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev, 2008, 21: 538–582.
Kaur A, Singh S, Gill AK et al. Isolation of Acinetobacter baumannii and it’s Antimicrobial Resistance pattern in an intensive Care Unit (ICU) of a tertiary Care Hospital. Int J Contemp Med Research, 2016;3(6): 1794-1796.
Bae S, Kim MC, Park SJ, Kim HS, Sung H, Kim MN et al. In vitro synergistic activity of antimicrobial agents in combination against clinical isolates of colistin-resistant Acinetobacter baumannii. Antimicrob Agents Chemother, 2016; 60: 6774-6779.
Nastro M, Rodriguez CH, Monge R, Zintgraff J, Neira L, Rebollo M et al. Activity of colistin-rifampicin combination against colistin-resistance carrbapenemase-producing gram-negative bacteria. J Chemother, 2014; 26: 211-216.
Li J, Yang X, Chen L, Duan X, Jiang Z. In vitro activity of various antibiotics in combination with tigecycline against Acinetobacter baumannii: A systematic Review and Meta-Analysis. Microb Drug Resist, 2017; 23(8): 982-993.
Cikman A, Gulhan B, Aydin M, Ceylan MR, Parlak M, Karakecili F et al. In vitro activity of colistin in combination with tigecycline against carbapenem-resistant Acinetobacter baumannii strains isolated from patients with ventilator-associated pneumonia. Int J Med Sci, 2015; 12(9): 695-700.
Bialvaei AZ, Kafil HS. Colistin, mechanisms and prevalence of resistance. Curr Med Res Opin, 2015; 31(4): 707-721.
Petrosillo N, Ioannidou E, Falagas ME. Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies. Clin Microbiol Infect, 2008; 14: 816–827.
Chung ES and Ko KS. Eradication of persister cells of Acinetobacter baumannii through combination of colistin and amikacin antibiotics. J antimicrob Chemother, 2019; 1-7.
Michiels JE, Van den Bergh B, Verstraeten N, Michiels J. Molecular mechanisms and clinical implications of bacterial persistence. Drug Resist Updat, 2016; 29: 76–89.
Poornesh KK, Cho C, Tak Y. Effect of accelerated chemical degradation on the surface roughness parameters and morphology of fuel cell membranes. Am J Mater Sci, 2015; 5: 175-82.
Nazmun Nahar Munny , SM Shamsuzzaman, Tamzeed Hossain. In vitro and in vivo Evaluation of Antibiotic Combination against Multidrug Resistant Enterobacter Species Isolated from Patients of a Tertiary Care Hospital, Bangladesh. Am J Infect Dis Microbiol, 2021,9(3): 98-105.
Kohanski MA, Dwyer DJ, Collins JJ. How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol.2010; 8(6): 423-435.
Downloads
Published
How to Cite
Issue
Section
