بررسی شیوع ژنهای int1، sul1، aadA2 و aadB در سویه های اسینتوباکتر بامانی جدا شده از نمونههای بالینی در تهران
محورهای موضوعی : میکروب شناسی مولکولیفرزانه حسینی 1 , زهرا سلیمی زاده 2 , میترا صالحی 3
1 - استادیار، گروه میکروب شناسی، دانشکده علوم زیستی، دانشگاه آزاد اسلامی، واحد تهران شمال، تهران
2 - کارشناس ارشد، گروه میکروب شناسی، دانشکده علوم زیستی، دانشگاه آزاد اسلامی، واحد تهران شمال، تهران
3 - استادیار، گروه میکروب شناسی، دانشکده علوم زیستی، دانشگاه آزاد اسلامی، واحد تهران شمال، تهران
کلید واژه: مقاومت آنتی بیوتیکی, اسینتوباکتر بامانی, اینتگرون کلاس 1,
چکیده مقاله :
سابقه و هدف: اسینتوباکتر بامانی یک کوکوباسیل گرم منفی میباشد که به طور فزایندهای به عنوان یکی از عوامل مهم عفونتهای بیمارستانی گزارش می شود. این مطالعه با هدف تعیین فراوانی اینتگرون کلاس 1 و ژن های کد کننده آنزیم های تغییر دهنده آمینوگلیکوزید ها تیپ های aadA2 وaadB در میان سویههای اسینتوباکتر بامانی انجام شد. مواد و روشها: این مطالعه به صورت مقطعی-توصیفی بر روی 33 نمونه از اسینتوباکتر بامانی جدا شده از بیماران مراجعه کننده به دو بیمارستان بقیه الله الاعظم (عج) و شهید مدرس تهران انجام گردید. مقاومت آنتیبیوتیکی سویهها با استفاده از روش دیسک دیفیوژن و مطابق با دستورالعمل CLSI تعیین شد. حضور ژنهای int-1، sul1، aadA2 وaadB در سویههای بالینی با استفاده از روش PCR مورد بررسی قرار گرفت. یافته ها: فراوانی ژنهای intI1، sul1، aadA2 و aadB در سویههای اسینتوباکتر بامانی به ترتیب معادل 51.5، 51.5، 24.2 و 36.4 درصد گزارش شد. در این مطالعه تمامی سویهها دارای مقاومت چندگانه آنتیبیوتیکی بودند و بیشترین میزان مقاومت نسبت به آنتی بیوتیک های آمپیسیلین، پنیسیلین، سفیکسیم، سفالوتین، سفتیزوکسیم، نالیدیکسیکاسید، کلیندامایسین، کلرامفنیکل، سولفومتاکسازول-تریمتوپریم و استرپتومایسین (100%) وجود داشت. همچنین کمترین میزان مقاومت در آنتی بیوتیک های جنتامایسین (66.7 درصد) و تتراسایکلین (69.7 درصد) مشاهده گردید. نتیجه گیری: ارتباط معنیداری بین حضور اینتگرون کلاس 1 و مقاومت به یک آنتی بیوتیک وجود داشت. با این حال، این ارتباط در بسیاری از سویهها که مقاومت به بقیه آنتیبیوتیکها نشان میدادند قابل توجه نیست. این یافته حاکی از این است که علاوه بر اینتگرونها، دیگر عوامل ایجاد کننده مقاومت مانند ترانسپوزون و پلاسمید نیز ممکن است در ایجاد مقاومت نقش داشته باشند.
Background & Objectives: Acinetobacter baumanniia is a gram-negative coccobacillus which is increasingly reported as the major cause of nosocomial infections. The aim of this study was to determine the frequency of class I integron, and the prevalence of two important aminoglycoside modifying enzymese genes (aadA2 and aadB) in A. baumannii isolates. Materials & Methods: This cross-sectional study was performed on 33 A. baumannii isolated from patients who referred to Baghiatallah Azam and Shahid Modarres Hospitals in Tehran.Antimicrobial susceptibility of isolates was evaluated using disk diffusion method in accordance with CLSI guideline. The presence of intI1, sul1, aadA2 and aadB genes in clinical isolates was investigated by PCR technique. Results: The frequency of intI1, sul1, aadA2, and aadB genes in A. baumannii was observed as 51.5%, 51.5%, 24.2% and 36.4%, respectively. All isolates were multi-drug resistant, and the highest level of antibiotic resistance was shown to ampicillin, cefixime, cephalothin, nalidixic acid, clindamycin, chloramphenicol, sulfamethoxazole-trimethoprim, and streptomycin (100%). Furthermore, the minimum antibiotic resistance was shown to gentamicin (66.7%), and tetracycline (69.7%). Conclusion: A significant correlation was observed between class 1 integrons, and resistance to one antibiotic. However, this association was not remarkable in several other isolates with antibiotics resistance. This may imply that in addition to integrons, other determinants such as transposons and plasmids may also contribute to resistance.
1. Moradi J, Hashemi FB, Bahador A. Antibiotic resistance of Acinetobacter baumannii in Iran: a systemic review of the published literature. Osong Public Health Res Perspectives. 2015; 6(2): 79-86.
2. Tripathi PC, Gajbhiye SR, Agrawal GN. Clinical and antimicrobial profile of Acinetobacter spp.: An emerging nosocomial superbug. Adv Biomed Res. 2014; 3(1): 13.
3. Aliakbarzade K, Farajnia S, Nik AK, Zarei F, Tanomand A. Prevalence of aminoglycoside resistance genes in Acinetobacter baumannii isolates. Jundishapur J Microbiol. 2014; 7(10): e11924.
4. Bou G, Cerveró G, Dominguez MA, Quereda C, Martínez-Beltrán J. Characterization of a nosocomial outbreak caused by a Multi-resistant Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme: high-level carbapenem resistance in A. baumannii is not due solely to the presence of β-lactamases. J Clin Microbiol. 2000; 38(9): 3299-3305.
5. Peters E, Leverstein-van Hall M, Box A, Verhoef J, Fluit A. Novel gene cassettes and integrons. Antimicrobial Agents Chemother. 2001; 45(10): 2961-2964.
6. Hosseini Pour P, Momtaz H, Serajyan AA, Tajbakhsh E. Investigating class I, II and III integrons in multidrug resistance in Pseudomonas aeruginosa isolated from hospital infections in Ahvaz. Int J Medical Lab. 2015; 2(3): 168-176.
7. Poonsuk K, Tribuddharat C, Chuanchuen R. Class 1 integrons in Pseudomonas aeruginosa and Acinetobacter baumannii isolated from clinical isolates. Southeast Asian J Trop Med Public Health. 2012; 43(2): 376.
8. Huang C, Long Q, Qian K, Fu T, Zhang Z, Liao P. Resistance and integron characterization of Acinetobacter baumannii in a teaching hospital in Chongqing, China. New Microbes New Infect. 2015; 8: 103-108.
9. Nardelli M, Scalzo PM, Ramírez MS, Quiroga MP, Cassini MH, Centrón D. Class 1 integrons in environments with different degrees of urbanization. PloS one. 2012; 7(6): e39223.
10. Fluit A, Schmitz FJ. Resistance integrons and super‐integrons. Clin MicrobiolInfect. 2004; 10(4): 272-288.
11. Mak JK. Integrons, resistance genes and their dissemination (in Gram negative bacteria): School of biotechnology & biomolecular sciences, University of New South Wales. Sydney, Australia; 2009.
12. Stokes Ht, Hall RM. A novel family of potentially mobile DNA elements encoding site specific gene integration functions: integrons. Mol Microbiol. 1989; 3(12): 1669-1683.
13. Odumosu BT, Adeniyi BA, Chandra R. Occurrence of aminoglycoside-modifying enzymes genes (aac (6′)-I and ant (2′′)-I) in clinical isolates of Pseudomonas aeruginosa from Southwest Nigeria. Afr Health Sci. 2015; 15(4): 1277-1281.
14. Quinteira S, Sousa JC, Peixe L. Characterization of In100, a new integron carrying a metallo-β-lactamase and a carbenicillinase, from Pseudomonas aeruginosa. Antimicrobial Agents Chemother. 2005; 49(1): 451-453.
15. Ruiz-Martínez L, López-Jiménez L, Fusté E, Vinuesa T, Martínez J, Viñas M. Class 1 integrons in environmental and clinical isolates of Pseudomonas aeruginosa. Int J Antimicrobial Agents. 2011; 38(5): 398-402.
16. Kamalbeik S, Kouchek M, Baseri Salehi M, Fallah F, Malekan MA, Talaie H. Prevalence of class 2 integrons in multidrug-resistant Acinetobacter baumannii in toxicological ICU patients in Tehran. Iran J Toxicol. 2013; 7(22): 900-906.
17. Rastegar-Lari A, Mohammadi-Barzelighi H, Arjomandzadegan M, Nosrati R, Owlia P. Distribution of class I integron among isolates of Acinetobacter baumannii recovered from burn patients. J Med Bacteriol. 2015; 2(1-2): 1-11.
18. Peymani AFS, Nahaei MR, Hasani A, Sohrabi N, Abbasi L, Aznari F. Prevalence of class 1 integron among multidrug-resistant Acinetobacter baumannii in Tabriz, northwest of Iran. Polish J Microbiol. 2012; 61(1): 157.
19. Bergogne-Berezin E, Towner K. Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clin Microbiol Rev. 1996; 9(2): 148.
20. Wayne P. Performance standards for antimicrobial susceptibility testing: Twenty-Third informational supplement: Clinical and Laboratory Standards Institute; 2013.
21. Xu H, Su Z, Wang S, Dai X, Chen J, Kong F. Four novel resistance integron gene-cassette occurrences in bacterial isolates from Zhenjiang, China. Current Microbiol. 2009; 59(2): 113-117.
22. Randall L, Cooles S, Osborn M, Piddock L, Woodward M. Antibiotic resistance genes, integrons and multiple antibiotic resistance in thirty-five serotypes of Salmonella enterica isolated from humans and animals in the UK. J Antimicrobial Chemother. 2004; 53(2): 208-216.
23. Hujer KM, Hujer AM, Hulten EA, Bajaksouzian S, Adams JM, Donskey CJ. Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrobial Agents Chemother. 2006; 50(12): 4114-4123.
24. Manchanda V, Sanchaita S, Singh N. Multidrug resistant Acinetobacter. J Global Infect Dis. 2010; 2(3): 291.
25. Karbasizade V, Heidari L, Jafari R. Detection of OXA-type carbapenemase genes in Acinetobacter baumannii isolates from nosocomial infections in Isfahan hospitals, Iran. J Med Bacteriol. 2016; 4(5-6): 31-36.
26. Cambray G, Guerout A-M, Mazel D. Integrons. Ann Rev Genetics. 2010; 44: 141-166.
27. Bayuga S, Zeana C, Sahni J, Della-Latta P, El-Sadr W, Larson E. Prevalence and antimicrobial patterns of Acinetobacter baumannii on hands and nares of hospital personnel and patients: The iceberg phenomenon again. Heart & Lung: J Acute Critical Care. 2002; 31(5): 382-390.
28. Joshi SG, Litake GM, Niphadkar KB, Ghole VS. Multidrug resistant Acinetobacter baumannii isolates from a teaching hospital. J Infection Chemother. 2003; 9(2): 187-190.
29. 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.
30. Amini M, Davati A, Golestanifard M. Frequency of nosocomial infections with antibiotic resistant strains of Acinetobacter spp. in ICU patients. Iran J Pathol. 2012; 7(4): 241-245.
31. Gu B, Tong M, Zhao W, Liu G, Ning M, Pan S. Prevalence and characterization of class I integrons among Pseudomonas aeruginosa and Acinetobacter baumannii isolates from patients in Nanjing, China. J Clin Microbiol. 2007; 45(1): 241-243.
32. Turton JF, Kaufmann ME, Glover J, Coelho JM, Warner M, Pike R. Detection and typing of integrons in epidemic strains of Acinetobacter baumannii found in the United Kingdom. J Clin Microbiol. 2005; 43(7): 3074-3082.
33. Ploy MC, Denis F, Courvalin P, Lambert T. Molecular characterization of integrons in Acinetobacter baumannii: description of a hybrid class 2 integron. Antimicrobial Agents Chemother. 2000; 44(10): 2684-2688.
34. Ribera A, Vila J, Fernández-Cuenca F, Martínez-Martínez L, Pascual A, Beceiro A. Type 1 integrons in epidemiologically unrelated Acinetobacter baumannii isolates collected at Spanish hospitals. Antimicrobial Agents Chemother. 2004; 48(1): 364-365.
35. Xu X, Kong F, Cheng X, Yan B, Du X, Gai J. Integron gene cassettes in Acinetobacter spp. strains from South China. Int J Antimicrobial Agents. 2008; 32(5): 441-445.
36. Mirnejad R, Mostofi S, Masjedian F. Antibiotic resistance and carriage class 1 and 2 integrons in clinical isolates of Acinetobacter baumannii from Tehran, Iran. Asian Pacific J Trop Biomed. 2013; 3(2): 140-145.
37. Asadollahi P, Akbari M, Soroush S, Taherikalani M, Asadollahi K, Sayehmiri K. Antimicrobial resistance patterns and their encoding genes among Acinetobacter baumannii strains isolated from burned patients. Burns. 2012; 38(8): 1198-1203.
38. Farahani Kheltabadi R, Moniri R, Shajari GR, Nazem Shirazi MH, Musavi SGA, Ghasemi A, Aghazadeh Sh. Antimicrobial susceptibility patterns and the distribution of resistance genes among Acinetobacter species isolated from patients in shahid Beheshti hospital, Kashan. Feyz. 2009; 12(4): 61-67.
_||_1. Moradi J, Hashemi FB, Bahador A. Antibiotic resistance of Acinetobacter baumannii in Iran: a systemic review of the published literature. Osong Public Health Res Perspectives. 2015; 6(2): 79-86.
2. Tripathi PC, Gajbhiye SR, Agrawal GN. Clinical and antimicrobial profile of Acinetobacter spp.: An emerging nosocomial superbug. Adv Biomed Res. 2014; 3(1): 13.
3. Aliakbarzade K, Farajnia S, Nik AK, Zarei F, Tanomand A. Prevalence of aminoglycoside resistance genes in Acinetobacter baumannii isolates. Jundishapur J Microbiol. 2014; 7(10): e11924.
4. Bou G, Cerveró G, Dominguez MA, Quereda C, Martínez-Beltrán J. Characterization of a nosocomial outbreak caused by a Multi-resistant Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme: high-level carbapenem resistance in A. baumannii is not due solely to the presence of β-lactamases. J Clin Microbiol. 2000; 38(9): 3299-3305.
5. Peters E, Leverstein-van Hall M, Box A, Verhoef J, Fluit A. Novel gene cassettes and integrons. Antimicrobial Agents Chemother. 2001; 45(10): 2961-2964.
6. Hosseini Pour P, Momtaz H, Serajyan AA, Tajbakhsh E. Investigating class I, II and III integrons in multidrug resistance in Pseudomonas aeruginosa isolated from hospital infections in Ahvaz. Int J Medical Lab. 2015; 2(3): 168-176.
7. Poonsuk K, Tribuddharat C, Chuanchuen R. Class 1 integrons in Pseudomonas aeruginosa and Acinetobacter baumannii isolated from clinical isolates. Southeast Asian J Trop Med Public Health. 2012; 43(2): 376.
8. Huang C, Long Q, Qian K, Fu T, Zhang Z, Liao P. Resistance and integron characterization of Acinetobacter baumannii in a teaching hospital in Chongqing, China. New Microbes New Infect. 2015; 8: 103-108.
9. Nardelli M, Scalzo PM, Ramírez MS, Quiroga MP, Cassini MH, Centrón D. Class 1 integrons in environments with different degrees of urbanization. PloS one. 2012; 7(6): e39223.
10. Fluit A, Schmitz FJ. Resistance integrons and super‐integrons. Clin MicrobiolInfect. 2004; 10(4): 272-288.
11. Mak JK. Integrons, resistance genes and their dissemination (in Gram negative bacteria): School of biotechnology & biomolecular sciences, University of New South Wales. Sydney, Australia; 2009.
12. Stokes Ht, Hall RM. A novel family of potentially mobile DNA elements encoding site specific gene integration functions: integrons. Mol Microbiol. 1989; 3(12): 1669-1683.
13. Odumosu BT, Adeniyi BA, Chandra R. Occurrence of aminoglycoside-modifying enzymes genes (aac (6′)-I and ant (2′′)-I) in clinical isolates of Pseudomonas aeruginosa from Southwest Nigeria. Afr Health Sci. 2015; 15(4): 1277-1281.
14. Quinteira S, Sousa JC, Peixe L. Characterization of In100, a new integron carrying a metallo-β-lactamase and a carbenicillinase, from Pseudomonas aeruginosa. Antimicrobial Agents Chemother. 2005; 49(1): 451-453.
15. Ruiz-Martínez L, López-Jiménez L, Fusté E, Vinuesa T, Martínez J, Viñas M. Class 1 integrons in environmental and clinical isolates of Pseudomonas aeruginosa. Int J Antimicrobial Agents. 2011; 38(5): 398-402.
16. Kamalbeik S, Kouchek M, Baseri Salehi M, Fallah F, Malekan MA, Talaie H. Prevalence of class 2 integrons in multidrug-resistant Acinetobacter baumannii in toxicological ICU patients in Tehran. Iran J Toxicol. 2013; 7(22): 900-906.
17. Rastegar-Lari A, Mohammadi-Barzelighi H, Arjomandzadegan M, Nosrati R, Owlia P. Distribution of class I integron among isolates of Acinetobacter baumannii recovered from burn patients. J Med Bacteriol. 2015; 2(1-2): 1-11.
18. Peymani AFS, Nahaei MR, Hasani A, Sohrabi N, Abbasi L, Aznari F. Prevalence of class 1 integron among multidrug-resistant Acinetobacter baumannii in Tabriz, northwest of Iran. Polish J Microbiol. 2012; 61(1): 157.
19. Bergogne-Berezin E, Towner K. Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clin Microbiol Rev. 1996; 9(2): 148.
20. Wayne P. Performance standards for antimicrobial susceptibility testing: Twenty-Third informational supplement: Clinical and Laboratory Standards Institute; 2013.
21. Xu H, Su Z, Wang S, Dai X, Chen J, Kong F. Four novel resistance integron gene-cassette occurrences in bacterial isolates from Zhenjiang, China. Current Microbiol. 2009; 59(2): 113-117.
22. Randall L, Cooles S, Osborn M, Piddock L, Woodward M. Antibiotic resistance genes, integrons and multiple antibiotic resistance in thirty-five serotypes of Salmonella enterica isolated from humans and animals in the UK. J Antimicrobial Chemother. 2004; 53(2): 208-216.
23. Hujer KM, Hujer AM, Hulten EA, Bajaksouzian S, Adams JM, Donskey CJ. Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrobial Agents Chemother. 2006; 50(12): 4114-4123.
24. Manchanda V, Sanchaita S, Singh N. Multidrug resistant Acinetobacter. J Global Infect Dis. 2010; 2(3): 291.
25. Karbasizade V, Heidari L, Jafari R. Detection of OXA-type carbapenemase genes in Acinetobacter baumannii isolates from nosocomial infections in Isfahan hospitals, Iran. J Med Bacteriol. 2016; 4(5-6): 31-36.
26. Cambray G, Guerout A-M, Mazel D. Integrons. Ann Rev Genetics. 2010; 44: 141-166.
27. Bayuga S, Zeana C, Sahni J, Della-Latta P, El-Sadr W, Larson E. Prevalence and antimicrobial patterns of Acinetobacter baumannii on hands and nares of hospital personnel and patients: The iceberg phenomenon again. Heart & Lung: J Acute Critical Care. 2002; 31(5): 382-390.
28. Joshi SG, Litake GM, Niphadkar KB, Ghole VS. Multidrug resistant Acinetobacter baumannii isolates from a teaching hospital. J Infection Chemother. 2003; 9(2): 187-190.
29. 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.
30. Amini M, Davati A, Golestanifard M. Frequency of nosocomial infections with antibiotic resistant strains of Acinetobacter spp. in ICU patients. Iran J Pathol. 2012; 7(4): 241-245.
31. Gu B, Tong M, Zhao W, Liu G, Ning M, Pan S. Prevalence and characterization of class I integrons among Pseudomonas aeruginosa and Acinetobacter baumannii isolates from patients in Nanjing, China. J Clin Microbiol. 2007; 45(1): 241-243.
32. Turton JF, Kaufmann ME, Glover J, Coelho JM, Warner M, Pike R. Detection and typing of integrons in epidemic strains of Acinetobacter baumannii found in the United Kingdom. J Clin Microbiol. 2005; 43(7): 3074-3082.
33. Ploy MC, Denis F, Courvalin P, Lambert T. Molecular characterization of integrons in Acinetobacter baumannii: description of a hybrid class 2 integron. Antimicrobial Agents Chemother. 2000; 44(10): 2684-2688.
34. Ribera A, Vila J, Fernández-Cuenca F, Martínez-Martínez L, Pascual A, Beceiro A. Type 1 integrons in epidemiologically unrelated Acinetobacter baumannii isolates collected at Spanish hospitals. Antimicrobial Agents Chemother. 2004; 48(1): 364-365.
35. Xu X, Kong F, Cheng X, Yan B, Du X, Gai J. Integron gene cassettes in Acinetobacter spp. strains from South China. Int J Antimicrobial Agents. 2008; 32(5): 441-445.
36. Mirnejad R, Mostofi S, Masjedian F. Antibiotic resistance and carriage class 1 and 2 integrons in clinical isolates of Acinetobacter baumannii from Tehran, Iran. Asian Pacific J Trop Biomed. 2013; 3(2): 140-145.
37. Asadollahi P, Akbari M, Soroush S, Taherikalani M, Asadollahi K, Sayehmiri K. Antimicrobial resistance patterns and their encoding genes among Acinetobacter baumannii strains isolated from burned patients. Burns. 2012; 38(8): 1198-1203.
38. Farahani Kheltabadi R, Moniri R, Shajari GR, Nazem Shirazi MH, Musavi SGA, Ghasemi A, Aghazadeh Sh. Antimicrobial susceptibility patterns and the distribution of resistance genes among Acinetobacter species isolated from patients in shahid Beheshti hospital, Kashan. Feyz. 2009; 12(4): 61-67.