Prevalence of Clinically Isolated Metallo-beta-lactamase-producing Pseudomonas aeruginosa, Coding Genes, and Possible Risk Factors in Iran

Document Type: Review Article


1 Microbiology Depat, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran

2 Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

3 Dept. of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

4 Researcher of Shahrekord University of Medical Sciences, Shahrekored, Iran

5 Microbiology Dept, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran



Background & Objective: The spread of carbapenem-resistant Pseudomonas aeruginosa is a global concern. Metallo-beta-lactamase (MBL) enzymes cause extensive drug resistance among Gram-negative bacteria. The current study aimed at determining the prevalence of MBL-producing P. aeruginosa in Iran.
Methods: A total of 43 studies were found out of which 36 were adopted. Data were collected from Google, Google Scholar, Science Direct, PubMed, Scopus, Embase, and Sciverse. The terms “Pseudomonas aeruginosa”, “metallo-beta-lactamase”, “prevalence”, “carbapenems”, and “Iran” were searched. Data from the isolates not producing MBLs were excluded from the study. Data were analyzed with Graph Pad Prism 6, meta-analysis section.
Results: According to the results of the current study, 36 surveys indicated that 55% of the clinically isolated P. aeruginosa in Iran were resistant to imipenem and meropenem, among which 37.72% were the MBL producers. Among genes encoding MBLs, blaVIM and blaIMP were predominant with the prevalence of 12.91%±11.01% and 12.50%±23.56%, respectively. No report of harboring blaNDM1 and blaSPM1 by P. aeruginosa was found, similar to most of the other countries in Asia. The prevalence of blaVIM and blaIMP from burn settings were 11.50%±3.5% and 24.65%±23%, respectively. Furthermore, the prevalence of these genes was not significantly different among burn and non-burn isolates (P=0.942 and P=0.597, respectively). Moreover, no relationship was observed between the MBL production and patients’ age range.
Conclusion: Approximately half of P. aeruginosa isolates were carbapenem-resistant in Iran, and approximately half were the MBL producers. The blaVIM and blaIMP were the predominantMBLs among P. aeruginosa strains, while other genes were not found in P. aeruginosa. Moreover, there was no significant difference between blaVIM and blaIMPamong burn and non-burn isolates. Due to the multiple drug resistance conferred by MBLs, detection and control of their spread alongside proper therapeutic regimens in hospitals and community settings are essential to prevent infection acquisition.


1.    Lee Y, Kim C-K, Chung H-S, Yong D, Jeong SH, Lee K, et al. Increasing carbapenem-resistant gram-negative bacilli and decreasing metallo-β-lactamase producers over eight years from Korea. Yonsei medical journal. 2015;56(2):572-7.

2.    Davodian E, Sadeghifard N, Ghasemian A, Noorbakhsh S. Presence of bla PER-1 and bla VEB-1 beta-lactamase genes among isolates of Pseudomonas aeruginosa from South West of Iran. Journal of epidemiology and global health. 2016;6(3):211-3.

3.    Davodian E, Sadeghifard N, Ghasemian A, Noorbakhsh S. Molecular detection of bla VEB-1 beta-lactamase encoding gene among extended spectrum B-Lactamase positive wound isolates of Pseudomonas aeruginosa. Archives of Pediatric Infectious Diseases. 2015;3(4).

4.    Yagi H, Tsubaki K. Successful treatment with intravenous colistin of sepsis caused by metallo-beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa in a patient with acute myeloid leukemia. Acta Med Kinki Univ. 2014;39(1):69-73.

5.    Kazmierczak KM, Rabine S, Hackel M, McLaughlin RE, Biedenbach DJ, Bouchillon SK, et al. Multi-year, multi-national survey of the incidence and global distribution of metallo-β-lactamase-producing Enterobacteriaceae and P. aeruginosa. Antimicrobial agents and chemotherapy. 2015:AAC. 02379-15.

6.    Saderi H, Owlia P. Detection of multidrug resistant (MDR) and extremely drug resistant (XDR) P. aeruginosa isolated from patients in Tehran, Iran. Iranian journal of pathology. 2015;10(4):265.

7.    Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clinical microbiology reviews. 2009;22(4):582-610.

8.    Cornaglia G, Giamarellou H, Rossolini GM. Metallo-β-lactamases: a last frontier for β-lactams? The Lancet infectious diseases. 2011;11(5):381-93.

9.    Poole K. Pseudomonas aeruginosa: resistance to the max. Front Microbiol. 2011;2(65).

10.  Gladstone P, Rajendran P, Brahmadathan K. Incidence of carbapenem resistant nonfermenting gram negative bacilli from patients with respiratory infections in the intensive care units. Indian journal of medical microbiology. 2005;23(3):189.

11.  Moniri R, Mosayebi Z, Movahedian AH, Mousavi GA. Emergence of multi-drug-resistant Pseudomonas aeruginosa isolates in neonatal septicemia. Journal of Infectious Diseases and Antimicrobial Agents. 2005;22(2):39-44.

12.  Hong DJ, Bae IK, Jang I-H, Jeong SH, Kang H-K, Lee K. Epidemiology and characteristics of metallo-β-lactamase-producing Pseudomonas aeruginosa. Infection & chemotherapy. 2015;47(2):81-97.

13.  Partridge SR, Tsafnat G, Coiera E, Iredell JR. Gene cassettes and cassette arrays in mobile resistance integrons. FEMS microbiology reviews. 2009;33(4):757-84.

14.  Walsh TR, Toleman MA, Poirel L, Nordmann P. Metallo-β-lactamases: the quiet before the storm? Clinical microbiology reviews. 2005;18(2):306-25.

15.  Gutiérrez O, Juan C, Cercenado E, Navarro F, Bouza E, Coll P, et al. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa isolates from Spanish hospitals. Antimicrobial agents and chemotherapy. 2007;51(12):4329-35.

16.  Wright LL, Turton JF, Hopkins KL, Livermore DM, Woodford N. Genetic environment of metallo-β-lactamase genes in Pseudomonas aeruginosa isolates from the UK. Journal of Antimicrobial Chemotherapy. 2015:dkv263.

17.  Malkoçoğlu G, Aktaş E, Bayraktar B, Otlu B, Bulut ME. VIM-1, VIM-2, and GES-5 Carbapenemases Among Pseudomonas aeruginosa Isolates at a Tertiary Hospital in Istanbul, Turkey. Microbial Drug Resistance. 2016.

18.  Shahcheraghi F, Nobari S, Rahmati Ghezelgeh F, Nasiri S, Owlia P, Nikbin VS, et al. First report of New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae in Iran. Microbial Drug Resistance. 2013;19(1):30-6.

19.  Khosravi AD, Mihani F. Detection of metallo-β-lactamase–producing Pseudomonas aeruginosa strains isolated from burn patients in Ahwaz, Iran. Diagnostic microbiology and infectious disease. 2008;60(1):125-8.

20.  Owlia P, Saderi H, Karimi Z, Rad A, Bagher SM, Bahar MA. Phenotypic detection of Metallo-beta-Lactamase producing Pseudomonas aeruginosa strains isolated from burned patients. Iranian Journal of Pathology. 2008;3(1):20-5.

21.  Saderi H, Lotfalipour H, Owlia P, Salimi H. Detection of metallo-β-lactamase producing Pseudomonas aeruginosa isolated from burn patients in Tehran, Iran. Laboratory Medicine. 2010;41(10):609-12.

22.  Bahar MA, Jamali S, Samadikuchaksaraei A. Imipenem-resistant Pseudomonas aeruginosa strains carry metallo-β-lactamase gene bla VIM in a level I Iranian burn hospital. Burns. 2010;36(6):826-30.

23.  Shahcheraghi F, Nikbin VS, Feizabadi MM. Identification and genetic characterization of metallo-beta-lactamase-producing strains of Pseudomonas aeruginosa in Tehran, Iran. The new microbiologica. 2010;33(3):243.

24.  Yousefi S, Farajnia S, Nahaei MR, Akhi MT, Ghotaslou R, Soroush MH, et al. Detection of metallo-β-lactamase–encoding genes among clinical isolates of Pseudomonas aeruginosa in northwest of Iran. Diagnostic microbiology and infectious disease. 2010;68(3):322-5.

25.  Peymani A, Nahaei M-R, Farajnia S, Hasani A, Mirsalehian A, Sohrabi N, et al. High Prevalence of Metallo-b-Lactamase-Producing Acinetobacter baumannii in a Teaching Hospital in Tabriz, Iran. Jpn J Infect Dis. 2011;64:69-71.

26.  Fallah F, Borhan RS, Hashemi A. Brief Communication Detection of bla (IMP) and bla (VIM) metallo-β-lactamases genes among Pseudomonas aeruginosa strains. Int J Burn Trauma. 2013;3(2):122-4.

27.  Yazdi HR, Nejad GB, Peerayeh SN, Mostafaei M. Prevalence and detection of metallo-β-lactamase (MBL)-producingPseudomonas aeruginosa strains from clinical isolates in Iran. Annals of microbiology. 2007;57(2):293-5.

28.  Shahcheraghi F, Nikbin VS, Feizabadi MM. Identification and genetic characterization of metallo-beta-lactamase-producing strains of Pseudomonas aeruginosa in Tehran, Iran. New Microbiologica. 2010;33(3):243-8.

29.  Boroumand MA, Anvari MS, Habibi E. Detection of vim-and ipm-type metallo-beta-lactamases in Pseudomonas aeruginosa clinical isolates. Archives of Iranian medicine. 2012;15(11):670.

30.  Doosti M, Ramazani A, Garshasbi M. Identification and characterization of metallo-β-lactamases producing Pseudomonas aeruginosa clinical isolates in University Hospital from Zanjan Province, Iran. Iranian biomedical journal. 2013;17(3):129.

31.  Yousefi S, Nahaei MR, Farajnia S, Aghazadeh M, Iversen A, Edquist P, et al. A multiresistant clone of Pseudomonas aeruginosa sequence type 773 spreading in a burn unit in Orumieh, Iran. Apmis. 2013;121(2):146-52.

32.  Sarhangi M, Motamedifar M, Sarvari J. Dissemination of Pseudomonas aeruginosa producing blaIMP1, blaVIM2, blaSIM1, blaSPM1 in Shiraz, Iran. Jundishapur Journal of Microbiology. 2013;6(7).

33.  Sadeghi A, Rahimi B, Shojapour M. Molecular detection of metallo--lactamase genes blaVIM-1, blaVIM-2, blaIMP-1, blaIMP-2 and blaSPM-1 in Pseudomonas aeruginosa isolated from hospitalized patients in Markazi province by Duplex-PCR. African Journal of Microbiology Research. 2012;6(12):2965-9.

34.  Abiri R, Pantea Mohammadi NS, Rezaei M. Detection and Genetic Characterization of Metallo-β-Lactamase IMP-1 and VIM-2 in Pseudomonas aeruginosa Strains From Different Hospitals in Kermanshah, Iran. Jundishapur journal of microbiology. 2015;8(9).

35.  Hakemi Vala M, Hallajzadeh M, Hashemi A, Goudarzi H, Tarhani M, Sattarzadeh Tabrizi M, et al. Detection of Ambler class A, B and D ß-lactamases among Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates from burn patients. Ann Burns Fire Disasters. 2014;27(1):8-13.

36.  Bahar G, Mazzariol A, Koncan R, Mert A, Fontana R, Rossolini GM, et al. Detection of VIM-5 metallo-β-lactamase in a Pseudomonas aeruginosa clinical isolate from Turkey. Journal of Antimicrobial Chemotherapy. 2004;54(1):282-3.

37.  Iraz M, Duzgun AO, Cicek AC, Bonnin RA, Ceylan A, Saral A, et al. Characterization of novel VIM carbapenemase, VIM-38, and first detection of GES-5 carbapenem-hydrolyzing β-lactamases in Pseudomonas aeruginosa in Turkey. Diagnostic microbiology and infectious disease. 2014;78(3):292-4.

38.  Guerin F, Henegar C, Spiridon G, Launay O, Salmon-Ceron D, Poyart C. Bacterial prostatitis due to Pseudomonas aeruginosa harbouring the blaVIM-2 metallo-β-lactamase gene from Saudi Arabia. Journal of Antimicrobial Chemotherapy. 2005;56(3):601-2.

39.  Al-Agamy MH, Shibl AM, Tawfik AF, Elkhizzi NA, Livermore DM. Extended-spectrum and metallo-beta-lactamases among ceftazidime-resistant Pseudomonas aeruginosa in Riyadh, Saudi Arabia. Journal of Chemotherapy. 2013.

40.  Al-Agamy MH, Shibl AM, Zaki SA, Tawfik AF. Antimicrobial resistance pattern and prevalence of metallo--lactamases in Pseudomonas aeruginosa from Saudi Arabia. African Journal of Microbiology Research. 2011;5(30):5528-33.

41.  Zafer MM, Amin M, El Mahallawy H, Ashour MSE-D, Al Agamy M. First report of NDM-1-producing Pseudomonas aeruginosa in Egypt. International Journal of Infectious Diseases. 2014;29:80-1.

42.  Zafer MM, Al-Agamy MH, El-Mahallawy HA, Amin MA, Ashour MSE-D. Antimicrobial resistance pattern and their beta-lactamase encoding genes among Pseudomonas aeruginosa strains isolated from cancer patients. BioMed Research International. 2014;2014.

43.  Touati M, Diene SM, Dekhil M, Djahoudi A, Racherache A, Rolain J-M. Dissemination of class I integron carrying VIM-2 carbapenemase gene in Pseudomonas aeruginosa clinical isolates from intensive care unit of university hospital of Annaba, Algeria. Antimicrobial agents and chemotherapy. 2013:AAC. 00032-13.

44.  Hammami S, Gautier V, Ghozzi R, Da Costa A, Ben‐Redjeb S, Arlet G. Diversity in VIM‐2‐encoding class 1 integrons and occasional blaSHV2a carriage in isolates of a persistent, multidrug‐resistant Pseudomonas aeruginosa clone from Tunis. Clinical Microbiology and Infection. 2010;16(2):189-93.

45.  Jacobson RK, Minenza N, Nicol M, Bamford C. VIM-2 metallo-β-lactamase-producing Pseudomonas aeruginosa causing an outbreak in South Africa. Journal of Antimicrobial Chemotherapy. 2012;67(7):1797-8.

46.  Ktari S, Mnif B, Znazen A, Rekik M, Mezghani S, Mahjoubi-Rhimi F, et al. Diversity of β-lactamases in Pseudomonas aeruginosa isolates producing metallo-β-lactamase in two Tunisian hospitals. Microbial Drug Resistance. 2011;17(1):25-30.

47.  Dong F, Xu X-W, Song W-Q, Lü P, Yu S-j, Yang Y-h, et al. Characterization of multidrug-resistant and metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates from a paediatric clinic in China. Chinese medical journal. 2008;121(17):1611-6.

48.  Qu T-t, Zhang J-l, Wang J, Tao J, Yu Y-s, Chen Y-g, et al. Evaluation of phenotypic tests for detection of Metallo-β-lactamase-producing Pseudomonas aeruginosa strains in China. Journal of clinical microbiology. 2009;47(4):1136-42.

49.  Yu Y-S, Qu T-T, Zhou J-Y, Wang J, Li H-Y, Walsh TR. Integrons containing the VIM-2 metallo-β-lactamase gene among imipenem-resistant Pseudomonas aeruginosa strains from different Chinese hospitals. Journal of clinical microbiology. 2006;44(11):4242-5.

50.  Xiong J, Hynes MF, Ye H, Chen H, Yang Y, M'Zali F, et al. blaIMP-9 and its association with large plasmids carried by Pseudomonas aeruginosa isolates from the People's Republic of China. Antimicrobial agents and chemotherapy. 2006;50(1):355-8.

51.  Fang Z-l, Zhang L-y, Huang Y-m, Qing Y, Cao K-y, Tian G-b, et al. OprD mutations and inactivation in imipenem-resistant Pseudomonas aeruginosa isolates from China. Infection, Genetics and Evolution. 2014;21:124-8.

52.  Chen Y, Sun M, Wang M, Lu Y, Yan Z. Dissemination of IMP-6-producing Pseudomonas aeruginosa ST244 in multiple cities in China. European journal of clinical microbiology & infectious diseases. 2014;33(7):1181-7.

53.  Hu Y-y, Gu D-x, Cai J-c, Zhou H-w, Zhang R. Emergence of KPC-2-producing Pseudomonas aeruginosa sequence type 463 isolates in Hangzhou, China. Antimicrobial agents and chemotherapy. 2015;59(5):2914-7.

54.  Khuntayaporn P, Montakantikul P, Santanirand P, Kiratisin P, Chomnawang MT. Molecular investigation of carbapenem resistance among multidrug‐resistant Pseudomonas aeruginosa isolated clinically in Thailand. Microbiology and immunology. 2013;57(3):170-8.

55.  Kanayama A, Kawahara R, Yamagishi T, Goto K, Kobaru Y, Takano M, et al. Successful control of an outbreak of GES-5 extended-spectrum β-lactamase-producing Pseudomonas aeruginosa in a long-term care facility in Japan. Journal of Hospital Infection. 2016;93(1):35-41.

56.  Tojo M, Tada T, Shimojima M, Tanaka M, Narahara K, Miyoshi-Akiyama T, et al. Dissemination in Japan of multidrug-resistant Pseudomonas aeruginosa isolates producing IMP-type metallo-β-lactamases and AAC (6′)-Iae/AAC (6′)-Ib. Journal of Infection and Chemotherapy. 2014;20(9):586-8.

57.  Ryoo NH, Ha JS, Jeon DS, Kim JR. Prevalence of Metallo-β-lactamases in Imipenem-non-susceptible Pseudomonas aeruginosa and Acinetobacter baumannii. Korean Journal of Clinical Microbiology. 2010;13(4):169-72.

58.  Castanheira M, Toleman MA, Jones RN, Schmidt FJ, Walsh TR. Molecular characterization of a β-lactamase gene, blaGIM-1, encoding a new subclass of metallo-β-lactamase. Antimicrobial agents and chemotherapy. 2004;48(12):4654-61.

59.  Valenza G, Joseph B, Elias J, Claus H, Oesterlein A, Engelhardt K, et al. First survey of metallo-β-lactamases in clinical isolates of Pseudomonas aeruginosa in a German university hospital. Antimicrobial agents and chemotherapy. 2010;54(8):3493-7.

60.  Elias J, Schoen C, Heinze G, Valenza G, Gerharz E, Riedmiller H, et al. Nosocomial outbreak of VIM‐2 metallo‐β‐lactamase‐producing Pseudomonas aeruginosa associated with retrograde urography. Clinical Microbiology and Infection. 2010;16(9):1494-500.

61.  Flateau C, Janvier F, Delacour H, Males S, Ficko C, Andriamanantena D, et al. Recurrent pyelonephritis due to NDM-1 metallo-beta-lactamase producing Pseudomonas aeruginosa in a patient returning from Serbia, France, 2012. Euro Surveill. 2012;17(45):20311.

62.  Jovcic B, Lepsanovic Z, Suljagic V, Rackov G, Begovic J, Topisirovic L, et al. Emergence of NDM-1 metallo-β-lactamase in Pseudomonas aeruginosa clinical isolates from Serbia. Antimicrobial agents and chemotherapy. 2011;55(8):3929-31.

63.  Jeannot K, Poirel L, Robert-Nicoud M, Cholley P, Nordmann P, Plésiat P. IMP-29, a novel IMP-type metallo-β-lactamase in Pseudomonas aeruginosa. Antimicrobial agents and chemotherapy. 2012;56(4):2187-90.

64.  Mazzariol A, Mammina C, Koncan R, Di Gaetano V, Di Carlo P, Cipolla D, et al. A novel VIM‐type metallo‐beta‐lactamase (VIM‐14) in a Pseudomonas aeruginosa clinical isolate from a neonatal intensive care unit. Clinical Microbiology and Infection. 2011;17(5):722-4.

65.  Holmgaard DB, Hansen F, Hasman H, Justesen US, Hammerum AM. Characterisation of a novel bla IMP gene, bla IMP-58, using whole genome sequencing in a Pseudomonas putida isolate detected in Denmark. Diagnostic microbiology and infectious disease. 2016.

66.  Lolans K, Queenan A, Bush K, Sahud A, Quinn J. First nosocomial outbreak of Pseudomonas aeruginosa producing an integron-borne metallo-β-lactamase (VIM-2) in the United States. Antimicrobial agents and chemotherapy. 2005;49(8):3538-40.

67.  Rasheed JK, Kitchel B, Zhu W, Anderson KF, Clark NC, Ferraro MJ, et al. New Delhi metallo-β-lactamase-producing enterobacteriaceae, United States. Emerg Infect Dis. 2013;19(6):870-8.

68.  Sader HS, Reis A, Silbert S, Gales AC. IMPs, VIMs and SPMs: the diversity of metallo‐β‐lactamases produced by carbapenem‐resistant Pseudomonas aeruginosa in a Brazilian hospital. Clinical Microbiology and Infection. 2005;11(1):73-6.

69.  Brink AJ, Coetzee J, Clay CG, Sithole S, Richards GA, Poirel L, et al. Emergence of New Delhi metallo-beta-lactamase (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC-2) in South Africa. Journal of clinical microbiology. 2012;50(2):525-7.

70.  Hawkey PM, Jones AM. The changing epidemiology of resistance. Journal of Antimicrobial Chemotherapy. 2009;64(suppl 1):i3-i10.

71.  Geebelen W, Vangronsveld J, Adriano DC, Van Poucke LC, Clijsters H. Effects of Pb‐EDTA and EDTA on oxidative stress reactions and mineral uptake in Phaseolus vulgaris. Physiologia Plantarum. 2002;115(3):377-84.

72.  Nordmann P, Poirel L. The difficult‐to‐control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clinical Microbiology and Infection. 2014;20(9):821-30.

73.  Hong JS, Kim JO, Lee H, Bae IK, Jeong SH, Lee K. Characteristics of metallo-β-lactamase-producing Pseudomonas aeruginosa in Korea. Infection & chemotherapy. 2015;47(1):33-40.

74.  Rojo-Bezares B, Estepa V, Cebollada R, de Toro M, Somalo S, Seral C, et al. Carbapenem-resistant Pseudomonas aeruginosa strains from a Spanish hospital: characterization of metallo-beta-lactamases, porin OprD and integrons. International Journal of Medical Microbiology. 2014;304(3):405-14.

75.  Martinez E, Pérez JE, Buelvas F, Tovar C, Vanegas N, Stokes H. Establishment and multi drug resistance evolution of ST235 Pseudomonas aeruginosa strains in the intensive care unit of a Colombian hospital. Research in microbiology. 2014;165(10):852-6.

76.  Wendel AF, Brodner AH, Wydra S, Ressina S, Henrich B, Pfeffer K, et al. Genetic characterization and emergence of the metallo-β-lactamase GIM-1 in Pseudomonas spp. and Enterobacteriaceae during a long-term outbreak. Antimicrobial agents and chemotherapy. 2013;57(10):5162-5.

77.  El Salabi A, Toleman MA, Weeks J, Bruderer T, Frei R, Walsh TR. First report of the metallo-β-lactamase SPM-1 in Europe. Antimicrobial agents and chemotherapy. 2010;54(1):582-.

78.  Pollini S, Maradei S, Pecile P, Olivo G, Luzzaro F, Docquier J-D, et al. FIM-1, a new acquired metallo-β-lactamase from a Pseudomonas aeruginosa clinical isolate from Italy. Antimicrobial agents and chemotherapy. 2013;57(1):410-6.

79.  Kumar SH, De AS, Baveja SM, Gore MA. Prevalence and risk factors of metallo β-lactamase producing Pseudomonas aeruginosa and Acinetobacter species in burns and surgical wards in a tertiary care hospital. Journal of laboratory physicians. 2012;4(1):39.