In vitro and in vivo Evaluation of Antibiotic Combination against Imipenem Resistant Acinetobacter baumannii Strains Isolated from Bangladeshi Patients

Bhuiyan Mohammad Mahtab Uddin¹, Ritu Saha^2, , Zubair Ahmed Ratan^{3, 4}, Surovi Era Suchi⁵ and S. M. Shamsuzzaman⁶

¹Department of Microbiology, Enam Medical College, Dhaka, Bangladesh,

²Department of Microbiology, Bashundhara Ad-din Medical College, Dhaka, Bangladesh,

³School of Health and Society, University of Wollongong, Australia,

⁴Department of Biomedical Engineering, Khulna University of Engineering and Technology, Khulna, Bangladesh,

⁵Department of Microbiology, Ad-din Sakina Women’s Medical College, Jeshore, Bangladesh

⁶Department of Microbiology, Dhaka Medical College, Dhaka, Bangladesh

Cite this paper:
Bhuiyan Mohammad Mahtab Uddin, Ritu Saha, Zubair Ahmed Ratan, Surovi Era Suchi and S. M. Shamsuzzaman. In vitro and in vivo Evaluation of Antibiotic Combination against Imipenem Resistant Acinetobacter baumannii Strains Isolated from Bangladeshi Patients. American Journal of Infectious Diseases and Microbiology. 2020; 8(2):83-87. doi: 10.12691/ajidm-8-2-6

Abstract

Acinetobacter baumannii is becoming a common etiological agent of nosocomial infections resulting in septicemia, meningitis, endocarditis, pneumonia, wound, and urinary tract infections within the healthcare setting. There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of imipenem, ceftazidime, amikacin and their combinations against imipenem resistant A. baumannii in experimental rat models. We also detected MBL encoding genes such as blaNDM-1, blaVIM and blaIMP and ESBL encoding genes such as blaCTX-M-15 and blaOXA-1 genes by Polymerase chain reaction (PCR). MBL encoding genes such as blaNDM-1 (83.33%), blaVIM (66.67%) and blaIMP (41.67%) and ESBL encoding genes such as blaCTX-M-15 (16.67%) and blaOXA-1 (12.50%) were detected among imipenem resistant Acinetobacter baumannii by PCR. In vitro activities of imipenem, ceftazidime, amikacin, ciprofloxacin, tigecycline and their combinations were tested using agar dilution method. The proportions of synergy observed in imipenem-ceftazidime, imipenem-amikacin, imipenem-ciprofloxacin and amikacin-tigecycline combinations were 25%, 54.17%, 12.50% and 41.67% respectively in vitro. Rat septicaemic models were evaluated using the imipenem resistant A. baumannii strain. Rats were treated with three antimicrobials and their combinations. For the rat model, the efficacies of imipenem, amikacin and imipenem plus ceftazidime and imipenem plus amikacin were assayed. In the septicaemic rat model, compared to the control group, (i) imipenem alone, (ii) ceftazidime alone (iii) imipenem plus ceftazidime (iv) imipenem plus amikacin showed increased sterile blood culture (50%, 16.67%, 66.67% and 83.33%). Imipenem plus amikacin or amikacin plus tigecycline may be appropriate for the treatment against imipenem resistant Acinetobacter baumannii infections.

Keywords:
Acinetobacter baumannii imipenem resistant antibiotic combination in vitro and in vivo efficacy

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References:

[1]	Poirel L., and P. Nordmann, “Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology,” Clin Microbiol Infect, 12: 826-836, 2006.
[2]	Gaynes R., and J. R. Edwards, “Overview of nosocomial infections caused by gram-negative bacilli,” Clin. Infect. Dis, 41:848-854, 2005.
[3]	Koprnova, J., Svetlansky I, Babel A. R., Illinova E, Hanzen J, Zuscakova I. J. et al., “Prospective study of antibacterial susceptibility, risk factors and outcome of 157 episodes of Acinetobacter baumannii bacteraemia in 1990 in Slovakia,” Scand J Infect Dis, 33: 891-895, 2001
[4]	Bergogne-Berezin E., and K. J. Towner, “Acinetobacter spp. as nosocomial pathogens: microbiological, clinical and epidemiological features,’ Clin Microbiol Rev, 9 (2): 148-165, 1996.
[5]	Afzal-Shah, M., and D. M. Livermore, “Worldwide emergence of carbapenem-resistant Acinetobacter spp.” J. Antimicrob. Chemother, 41:576-577, 1998.
[6]	Clinical and Laboratory Standards Institute, “Performance Standards for Antimicrobial Susceptibility Testing: Nineteenth Informational Supplement,” CLSI document M100-S19, CLSI: Wayne, PA, 2009.
[7]	Cheesbrough M, “Summary of the clinical and laboratory features of microorganisms,” In: Cheesbrough M, editor. District Laboratory Practice in Tropical Countries, Part 2. UK: Cambridge University Pre, 157-234,1998.
[8]	Farzana R., Shamsuzzaman SM. and Mamun KZ, “Isolation and moleculer characterization of New Delhi metallo-beta-lactamase-1 producing superbug in Bangladesh,” J infect Dev Ctries 7 (3): 161-168, 2013.
[9]	Franco MR., Caiaffa-Filho HH., Burattini MN., Rossi F., “Metallo-beta-lactamases among imipenem resistant Pseudomonas aeruginosa in a Brazilian university hospital” Clinics 65: 825-829, 2010.
[10]	Gombert, M. E., and Aulicino T. M., “Synergism of imipenem and amikacin in combination with other antibiotics against Nocardia asteroids,” Antimicrob Agents Chemother, 24(5): 810-811, 1983.
[11]	Hernandez, M. J. R., Pachon J, Pichardo C, Cuberos L, Martinez JI, Curiel AG et ai, “Imipenem, doxycycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental pneumonia,” J Antimicrob Chemother, 45: 493-501, 2000.
[12]	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, 44: 4471-4478, 2006.
[13]	Wood, G. C., Hanes, S. D., Croce, M. A. et al., “Comparison of ampicillim-sulbactam and imipenem-cilastatin for the treatment of Acinetobacter ventilator-associated pneumonia,” Clinical Infectious Diseases, 34: 1425-30, 2002.
[14]	Sheng, W. H., Wang J. T., Li S. Y., Lin Y. C., Cheng A, Chen Y. C. et al., “Comparative in vitro antimicrobial susceptibilities and synergistic activities of antimicrobial combinations against carbapenem resistant Acinetobacter species: Acinetobacter baumannii versus Acinetobacter genospecies 3 and 13TU, ” Diagn Microbiol Infect Dis, 70 (3): 380-6, Jul.2011.
[15]	Jimenz-Mejias, M. E., Becerril, B., Marquez- Rivas, F. J. et al., “Successful treatment of multidrug-resistant Acinetobacter baumannii meningitis with intravenous colistin sulfomethate sodium,” European Journal of Clinical Microbiology and Infectious Diseases, 19: 970-1, 2000.
[16]	Principe, L., D’Arezzo S, Capone A, Petrosillo N, Visca P, “In vitro activity of tigecycline in combination with various antimicrobials against multidrug resistant Acinetobacter baumanni,” Ann Clin Microbiol Antimicrob, 8:18, 2009.
[17]	Josh, S. G., Litake G. M., Satput M. G, “Clinical and demographic features of infection caused by Acinetobacter species,” Ind J Med Sci, 60: 351-360, 2006.
[18]	Montero A, Ariza J, Corbella X et al., “Antibiotic combinations for serious infections caused by carbapenem resistant Acinetobacter baumannii in a mouse pneumonia model,” J Antimicrob Chemother, 54: 1085–1091, 2004.
[19]	Johnson, D. E., Thompson B, Calia F. M, “Comparative Activities of piperacillin, ceftazidime and Amikacin, Alone and in All possible Combinations, against Experimental pseudomonas aeruginosa Infections in Neutropenic Rats,” Antimicrob Agents chemother,. 27(12) : 735-739, 1985.
[20]	Kumarasamy KK., Toleman MA., Walsh TR., Bagaria J, Butt F, Balakrishnan R et al., “Emergence of a new antibiotic resistance mechanism in India, Pakistan and the UK: a molecular, biological and edpidemiological study,” Lancet Infect Dis, 10 (9): 597-602, 2010.
[21]	Chen Z, Qlu S, Wang Y, Liu S, Wang Z, Du X, Wang L, Guo J, Liu N, Yuan J et al., “Coexistence of blaNDM-1 with the prevalent blaOXA-23 and blaIMP in pan-drug resistant Acinetobacter baumannii isolates in China,” Clin Infect Dis, 52(5): 692-693, 2011.
[22]	Lee K, Lee WG, Uh Y, Ha GY, Cho J, Chong Y, “VIM- and IMP-type metallo-beta lactamase-producing Pseudomonas spp. and Acinetobacter spp. in Korean hospitals,” Emerg Infect Dis, 9 (7): 868-871, 2003.
[23]	Toleman MA., Biedenbach D, Bennett DM., Jones RN., Walsh TR., “Italian metallo-beta-lactamases: a national problem? Report from the SENTRY Antimicrobial Surveillance Programme,” J Antimicrob Chemother, 55(1): 61-70, 2005.
[24]	Tsakris A, Ikonomidis A, Pournaras S, Tzouvelekis LS., Sofianou D, Legakis NJ., Maniatis AN., “VIM-1 Metallo- beta-lactamase in Acinetobacter baumannii,”. Emerg Infect Dis, 12(6): 981-983, 2006.