The Involvement of Drug Efflux System in Amikacin Resistance of Multiple Drug Resistant Acintobacter baumannii Isolates in Isfahan, Iran
Abstract
Background: Due to the extensive usage of antibiotics in recent decades, the emergence of multiple drug-resistant (MDR) strains has dramatically increased. In the present study, we studied the distribution and involvement of drug efflux system in conferring resistance to amikacin in MDR isolates of Acinetobacter baumannii isolated from hospitalized patients.
Methods: In this cross-sectional study 80 MDR A. baumannii were isolates isolated from hospitalized patients in Alzahra hospital, Isfahan, Iran. A. baumannii isolates were identified by standard microbiologic procedure and were confirmed by specific PCR primers. Minimum inhibitory concentration (MIC) was determined by agar dilution method according to CLSI guidelines. Carbonyl cyanide 3-chlorophenylhydrazon (CCCP) was used as an efflux pump inhibitor for amikacin susceptibility. The presence of efflux genes was detected by PCR method.
Results: Antibiotic susceptibility results showed that 39 of isolates had MIC ≥32 µg/mL and were amikacin-resistant. Totally, 41 isolates which had an amikacin MIC ≥2 μg/mL were tested for reduction of MIC in presence of 25 μg/mL efflux pumps inhibitor. After the treatment, 25 (61%) isolates had ≥2 fold and 15 (36.6%) isolates had 4 fold reduction in amikacin MIC. The results of PCR-amplifications indicated that the presence rate of AdeA, AdeB, AdeC, AbeM and AdeS genes were 100%, 96.3%, 95%, 98.8%, and 95%, respectively.
Conclusion: In summary, significant involvement of drug efflux system in conferring resistance to amikacin along with high distribution of efflux genes suggests an alternative therapy using antibiotics in combination with efflux inhibitors in the fight against MDR isolates of A. baumannii.
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2. Howard A, O'Donoghue M, Feeney A, et al. Acinetobacter baumannii: an emerging opportunistic pathogen. Virulence 2012; 3(3):243-50.
3. Manchanda V, Sanchaita S, Singh N. Multidrug resistant Acinetobacter. Journal glob infect dis 2010; 2(3):291-304.
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5. Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria: an update. Drugs 2009; 69(12):1555-623.
6. Coyne S, Courvalin P, Perichon B. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 2011; 55(3):947-53.
7. Marchand I, Damier-Piolle L, Courvalin P, et al. Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother 2004; 48(9):3298-304.
8. Turton JF, Woodford N, Glover J, et al. Identification of Acinetobacter baumannii by detection of the blaOXA-51-like carbapenemase gene intrinsic to this species. J Clin Microbiol 2006; 44(8):2974-6.
9. Wayne P. Performance standards for antimicrobial susceptibility testing. Clinical and Laboratory Standards Institute (CLSI) 2015; 25th Informational Supplement. (M100-S25).
10. Filgona J, Banerjee T, Anupurba S. Role of efflux pumps inhibitor in decreasing antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in North India. J Infect Dev Ctries 2015; 9(8):815-20.
11. Sambrook J, Russell DW. Purification of nucleic acids by extraction with phenol:chloroform. CSH Protoc 2006; pii: pdb.prot4455.
12. Lin L, Ling BD, Li XZ. Distribution of the multidrug efflux pump genes, adeABC, adeDE and adeIJK, and class 1 integron genes in multiple-antimicrobial-resistant clinical isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus complex. Int J Antimicrob Agents 2009; 33(1):27-32.
13. Jassim KA, Ghaima KK, Saadedin SMK. AdeABC Efflux pump genes in multidrug resistant Acinetobacter baumannii isolates. Avicenna J Clin Microbiol Infect 2016; 3(4).
14. Qiu ZQ, Zhu LJ, Hou PF. Distribution of carbapenemases and efflux pump in carbopenems-resistance Acinetobacter baumannii. PeerJ Preprints 2016; 4:e2655v1.
15. Asadolah-Malayeri HO, Hakemi-Vala M, Davari K. Role of Aders and OXA23 genes among imipenem resistant acinetobacter baumannii isolates from two hospitals of Tehran, Iran. Iran J Pathol 2016; 11(4):345.
16. Wieczorek P, Sacha P, Hauschild T, et al. Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics. Folia Histochem Cyto 2008; 46(3):257-67.
17. Necati Hakyemez I, Kucukbayrak A, Tas T, et al. Nosocomial Acinetobacter baumannii infections and changing antibiotic resistance. Pak J Med Sci 2013; 29(5):1245-8.
18. Vahdani P, Yaghoubi T, Aminzadeh Z. Hospital acquired antibiotic-resistant Acinetobacter baumannii infections in a 400-bed hospital in Tehran, Iran. Int J Prev Med 2011; 2(3):127-30.
19. Al Samawi MS, Khan FY, Eldeeb Y, et al. Acinetobacter Infections among adult patients in Qatar: A 2-year hospital-based study. Can J Infect Dis Med Microbiol 2016; 2016:6873689.
20. Rahbar M, Mehrgan H, Aliakbari NH. Prevalence of antibiotic-resistant Acinetobacter baumannii in a 1000-bed tertiary care hospital in Tehran, Iran. Indian J Pathol Microbiol 2010; 53(2):290-3.
21. Agarwal S, Kakati B, Khanduri S, et al. Emergence of carbapenem resistant non-fermenting Gram-negative bacilli isolated in an ICU of a tertiary care hospital. J Clin Diagn Res 2017; 11(1):Dc04-dc7.
22. Ntusi NB, Badri M, Khalfey H, et al. ICU-associated Acinetobacter baumannii colonisation/infection in a high HIV-prevalence resource-poor setting. PloS One 2012; 7(12):e52452.
23. Wang Y, Shen M, Yang J, et al. Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China. Exp Ther Med 2016; 12(6):3642-52.
24. Over U, Gur D, Unal S, et al. The changing nature of aminoglycoside resistance mechanisms and prevalence of newly recognized resistance mechanisms in Turkey. Clin Microbiol Infect 2001; 7(9):470-8.
25. Moradi J, Hashemi FB, Bahador A. Antibiotic resistance of Acinetobacter baumannii in Iran: a systemic review of the published literature. Osong Public Health Res Perspect 2015; 6(2):79-86.
26. Aliakbarzade K, Farajnia S, Karimi Nik A, et al. Prevalence of aminoglycoside resistance genes in Acinetobacter baumannii isolates. Jundishapur J Microbiol 2014; 7(10):e11924.
27. Moniri R, Farahani RK, Shajari G, et al. Molecular epidemiology of aminoglycosides resistance in Acinetobacter spp. with emergence of multidrug-resistant strains. Iranian j of public health 2010; 39(2):63-8.
28. Ardebili A, Talebi M, Azimi L, et al. Effect of efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone on the minimum inhibitory concentration of ciprofloxacin in Acinetobacter baumannii clinical isolates. Jundishapur J Microbiol 2014; 7(1):e8691.
29. Azimi L, Ebrahimzadeh Namvar A, Rastegar Lari A, et al. Comparison of efflux pump involvement in antibiotic resistance among Pseudomonas aeruginosa isolates of burn and non-burn patients. Arch Pediatr Infect Dis 2016; 4(3):e36160.
30. Rajamohan G, Srinivasan VB, Gebreyes WA. Novel role of Acinetobacter baumannii RND efflux transporters in mediating decreased susceptibility to biocides. J Antimicrob Chemother 2010; 65(2):228-32.
31. Adabi M, Talebi-Taher M, Arbabi L, et al. Spread of efflux pump overexpressing-mediated fluoroquinolone resistance and multidrug resistance in Pseudomonas aeruginosa by using an efflux pump inhibitor. Infect Chemother 2015; 47(2):98-104.
32. Gholami M, Hashemi A, Hakemi-Vala M, et al. Efflux pump inhibitor phenylalanine-arginine beta-naphthylamide effect on the minimum inhibitory concentration of imipenem in Acinetobacter baumannii strains isolated from hospitalized patients in Shahid Motahari burn hospital, Tehran, Iran. Jundishapur J Microbiol 2015; 8(10):e19048.
33. Wieczorek P, Sacha P, Czaban S, et al. Distribution of AdeABC efflux system genes in genotypically diverse strains of clinical Acinetobacter baumannii. Diagn Microbiol Infect Dis 2013; 77(2):106-9.
34. Jia W, Li C, Zhang H, et al. Prevalence of genes of OXA-23 carbapenemase and AdeABC efflux pump associated with multidrug resistance of Acinetobacter baumannii isolates in the ICU of a comprehensive hospital of northwestern China. Int J Environ Res Public Health 2015; 12(8):10079-92.
35. Jassim KA, Ghaima KK, Saadedin SMK. AdeABC efflux pump genes in multidrug resistant Acinetobacter baumannii isolates. Avicenna J Clin Microbiol Infect 2016; 3(4):e40898.
36. Angoti G, Bandehpour M, Goudarzi H, et al. Detection of efflux pump genes (adeA, adeB, adeC and abeM) in Acinetobacter baumannii isolated from hospitalize patients, North-west of Iran. Infect Epidemiol Microbiol 2016; 2(4):8-11.
2. Howard A, O'Donoghue M, Feeney A, et al. Acinetobacter baumannii: an emerging opportunistic pathogen. Virulence 2012; 3(3):243-50.
3. Manchanda V, Sanchaita S, Singh N. Multidrug resistant Acinetobacter. Journal glob infect dis 2010; 2(3):291-304.
4. Lin MF, Lan CY. Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside. World J Clin Cases 2014; 2(12):787-814.
5. Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria: an update. Drugs 2009; 69(12):1555-623.
6. Coyne S, Courvalin P, Perichon B. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 2011; 55(3):947-53.
7. Marchand I, Damier-Piolle L, Courvalin P, et al. Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother 2004; 48(9):3298-304.
8. Turton JF, Woodford N, Glover J, et al. Identification of Acinetobacter baumannii by detection of the blaOXA-51-like carbapenemase gene intrinsic to this species. J Clin Microbiol 2006; 44(8):2974-6.
9. Wayne P. Performance standards for antimicrobial susceptibility testing. Clinical and Laboratory Standards Institute (CLSI) 2015; 25th Informational Supplement. (M100-S25).
10. Filgona J, Banerjee T, Anupurba S. Role of efflux pumps inhibitor in decreasing antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in North India. J Infect Dev Ctries 2015; 9(8):815-20.
11. Sambrook J, Russell DW. Purification of nucleic acids by extraction with phenol:chloroform. CSH Protoc 2006; pii: pdb.prot4455.
12. Lin L, Ling BD, Li XZ. Distribution of the multidrug efflux pump genes, adeABC, adeDE and adeIJK, and class 1 integron genes in multiple-antimicrobial-resistant clinical isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus complex. Int J Antimicrob Agents 2009; 33(1):27-32.
13. Jassim KA, Ghaima KK, Saadedin SMK. AdeABC Efflux pump genes in multidrug resistant Acinetobacter baumannii isolates. Avicenna J Clin Microbiol Infect 2016; 3(4).
14. Qiu ZQ, Zhu LJ, Hou PF. Distribution of carbapenemases and efflux pump in carbopenems-resistance Acinetobacter baumannii. PeerJ Preprints 2016; 4:e2655v1.
15. Asadolah-Malayeri HO, Hakemi-Vala M, Davari K. Role of Aders and OXA23 genes among imipenem resistant acinetobacter baumannii isolates from two hospitals of Tehran, Iran. Iran J Pathol 2016; 11(4):345.
16. Wieczorek P, Sacha P, Hauschild T, et al. Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics. Folia Histochem Cyto 2008; 46(3):257-67.
17. Necati Hakyemez I, Kucukbayrak A, Tas T, et al. Nosocomial Acinetobacter baumannii infections and changing antibiotic resistance. Pak J Med Sci 2013; 29(5):1245-8.
18. Vahdani P, Yaghoubi T, Aminzadeh Z. Hospital acquired antibiotic-resistant Acinetobacter baumannii infections in a 400-bed hospital in Tehran, Iran. Int J Prev Med 2011; 2(3):127-30.
19. Al Samawi MS, Khan FY, Eldeeb Y, et al. Acinetobacter Infections among adult patients in Qatar: A 2-year hospital-based study. Can J Infect Dis Med Microbiol 2016; 2016:6873689.
20. Rahbar M, Mehrgan H, Aliakbari NH. Prevalence of antibiotic-resistant Acinetobacter baumannii in a 1000-bed tertiary care hospital in Tehran, Iran. Indian J Pathol Microbiol 2010; 53(2):290-3.
21. Agarwal S, Kakati B, Khanduri S, et al. Emergence of carbapenem resistant non-fermenting Gram-negative bacilli isolated in an ICU of a tertiary care hospital. J Clin Diagn Res 2017; 11(1):Dc04-dc7.
22. Ntusi NB, Badri M, Khalfey H, et al. ICU-associated Acinetobacter baumannii colonisation/infection in a high HIV-prevalence resource-poor setting. PloS One 2012; 7(12):e52452.
23. Wang Y, Shen M, Yang J, et al. Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China. Exp Ther Med 2016; 12(6):3642-52.
24. Over U, Gur D, Unal S, et al. The changing nature of aminoglycoside resistance mechanisms and prevalence of newly recognized resistance mechanisms in Turkey. Clin Microbiol Infect 2001; 7(9):470-8.
25. Moradi J, Hashemi FB, Bahador A. Antibiotic resistance of Acinetobacter baumannii in Iran: a systemic review of the published literature. Osong Public Health Res Perspect 2015; 6(2):79-86.
26. Aliakbarzade K, Farajnia S, Karimi Nik A, et al. Prevalence of aminoglycoside resistance genes in Acinetobacter baumannii isolates. Jundishapur J Microbiol 2014; 7(10):e11924.
27. Moniri R, Farahani RK, Shajari G, et al. Molecular epidemiology of aminoglycosides resistance in Acinetobacter spp. with emergence of multidrug-resistant strains. Iranian j of public health 2010; 39(2):63-8.
28. Ardebili A, Talebi M, Azimi L, et al. Effect of efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone on the minimum inhibitory concentration of ciprofloxacin in Acinetobacter baumannii clinical isolates. Jundishapur J Microbiol 2014; 7(1):e8691.
29. Azimi L, Ebrahimzadeh Namvar A, Rastegar Lari A, et al. Comparison of efflux pump involvement in antibiotic resistance among Pseudomonas aeruginosa isolates of burn and non-burn patients. Arch Pediatr Infect Dis 2016; 4(3):e36160.
30. Rajamohan G, Srinivasan VB, Gebreyes WA. Novel role of Acinetobacter baumannii RND efflux transporters in mediating decreased susceptibility to biocides. J Antimicrob Chemother 2010; 65(2):228-32.
31. Adabi M, Talebi-Taher M, Arbabi L, et al. Spread of efflux pump overexpressing-mediated fluoroquinolone resistance and multidrug resistance in Pseudomonas aeruginosa by using an efflux pump inhibitor. Infect Chemother 2015; 47(2):98-104.
32. Gholami M, Hashemi A, Hakemi-Vala M, et al. Efflux pump inhibitor phenylalanine-arginine beta-naphthylamide effect on the minimum inhibitory concentration of imipenem in Acinetobacter baumannii strains isolated from hospitalized patients in Shahid Motahari burn hospital, Tehran, Iran. Jundishapur J Microbiol 2015; 8(10):e19048.
33. Wieczorek P, Sacha P, Czaban S, et al. Distribution of AdeABC efflux system genes in genotypically diverse strains of clinical Acinetobacter baumannii. Diagn Microbiol Infect Dis 2013; 77(2):106-9.
34. Jia W, Li C, Zhang H, et al. Prevalence of genes of OXA-23 carbapenemase and AdeABC efflux pump associated with multidrug resistance of Acinetobacter baumannii isolates in the ICU of a comprehensive hospital of northwestern China. Int J Environ Res Public Health 2015; 12(8):10079-92.
35. Jassim KA, Ghaima KK, Saadedin SMK. AdeABC efflux pump genes in multidrug resistant Acinetobacter baumannii isolates. Avicenna J Clin Microbiol Infect 2016; 3(4):e40898.
36. Angoti G, Bandehpour M, Goudarzi H, et al. Detection of efflux pump genes (adeA, adeB, adeC and abeM) in Acinetobacter baumannii isolated from hospitalize patients, North-west of Iran. Infect Epidemiol Microbiol 2016; 2(4):8-11.
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| Issue | Vol 8 No 1-2 (2019) | |
| Section | Original Articles | |
| Keywords | ||
| Acinetobacter baumannii AdeABC genes Amikacin Efflux pumps MDR | ||
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How to Cite
1.
Ostadi Y, Rezai AA, Moghadampour M, Faghri J. The Involvement of Drug Efflux System in Amikacin Resistance of Multiple Drug Resistant Acintobacter baumannii Isolates in Isfahan, Iran. J Med Bacteriol. 2019;8(1-2):13-20.
