The Effect of Isolated Bacteriophage on Multi-Drug Resistant (MDR) Pseudomonas Aeruginosa

Document Type : Original Article (s)

Authors

1 Associate Professor, Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Student of Medicine, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

3 Professor, Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 MSc Student, Department of Microbiology, Islamic Azad University, Falavarjan Branch, Isfahan, Iran

5 MSc Student, Department of Microbiology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Bacterial drug resistance, due to overuse of antibiotics and several mechanisms of resistance by bacteria, is increasing. Multi-drug resistant bacteria (MDR) in different parts of the hospital including the intensive care unit (ICU), cause nosocomial infections and resistance to antibiotics made them difficult to treat. Alternative methods of treatment are one way to solve this problem. Bacteriophages are antibacterial agents that specifically attack their host. In this study, Pseudomonas specific lytic phages isolated from the clinical environment and its effect on multi-drug resistant Pseudomonas aeruginosa was investigated.Methods: In a cross sectional study in 2013, isolates of Pseudomonas aeruginosa from clinical specimens of patients admitted to the intensive care unit were identified via biochemical methods. Then, antibiotic resistance patterns were determined via standard disk diffusion method according to CLSI (Clinical and Laboratory Standards Institute) and were used as indicator hosts to screen phages from water samples.Findings: 42 strains of Pseudomonas aeruginosa wre isolated from the intensive care units. The antibiotic resistant patterns of bacterial isolates were as follows: 88% to amikacin, 90% to cefepime, 85% to ceftazidime, 90% to gentamicin, 75% to imipenem and meropenem and 95% to ciprofloxacin. Lytic bacteriophage was isolated only from hospital wastewater. The isolated bacteriophage had no effect on non- multi-drug resistant Pseudomonas aeruginosa and other Gram-negative bacteria.Conclusion: Bacterial resistance to antibiotics is increasing. New alternative methods, such as phage therapy, would open new insights in treatment of multidrug resistant bacterial infections.

Keywords


  1. Gaynes R, Edwards JR. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 2005; 41(6): 848-54.
  2. Fluit AC, Jones ME, Schmitz FJ, Acar J, Gupta R, Verhoef J. Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Europe from the SENTRY antimicrobial surveillance program, 1997 and 1998. Clin Infect Dis 2000; 30(3): 454-60.
  3. Streit JM, Jones RN, Sader HS, Fritsche TR. Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001). Int J Antimicrob Agents 2004; 24(2): 111-8.
  4. Crouch BS, Wunderink RG, Jones CB, Leeper KV, Jr. Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest 1996; 109(4): 1019-29.
  5. Osmon S, Ward S, Fraser VJ, Kollef MH. Hospital mortality for patients with bacteremia due to Staphylococcus aureus or Pseudomonas aeruginosa. Chest 2004; 125(2): 607-16.
  6. Wiblin RT. Nosocomial pneumonia. In: Wenzel RP, editors. Prevention and control of nosocomial infections.3rd ed. Baltimore, MD: Williams and Wilkins; 1997. p. 807-19.
  7. Pollack M. Pseudomonas aeruginosa. In: Mandell GL, Benett JE, Dolin R, editors. Principles and practice of infectious diseases. 4th ed. New York, NY: Churchill Livingstone; 1995. p. 1980-2003.
  8. Kluytmans J. Surgical infections including burns. In: Wenzel RP, editor. Prevention and control of nosocomial infections. 3rd ed. Baltimore, MD: Williams and Wilkins; 1997. p. 841-65.
  9. Gordon SM, Serkey JM, Keys TF, Ryan T, Fatica CA, Schmitt SK, et al. Secular trends in nosocomial bloodstream infections in a 55-bed cardiothoracic intensive care unit. Ann Thorac Surg 1998; 65(1): 95-100.
  10. Fergie JE, Shema SJ, Lott L, Crawford R, Patrick CC. Pseudomonas aeruginosa bacteremia in immunocompromised children: analysis of factors associated with a poor outcome. Clin Infect Dis 1994; 18(3): 390-4.
  11. Bergen GA, Shelhamer JH. Pulmonary infiltrates in the cancer patient. New approaches to an old problem. Infect Dis Clin North Am 1996; 10(2): 297-325.
  12. Crouch BS, Wunderink RG, Jones CB, Leeper KV, Jr. Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest 1996; 109(4): 1019-29.
  13. Richard P, Le FR, Chamoux C, Pannier M, Espaze E, Richet H. Pseudomonas aeruginosa outbreak in a burn unit: role of antimicrobials in the emergence of multiply resistant strains. J Infect Dis 1994; 170(2): 377-83.
  14. Gorgani N, Ahlbrand S, Patterson A, Pourmand N. Detection of point mutations associated with antibiotic resistance in Pseudomonas aeruginosa. Int J Antimicrob Agents 2009; 34(5): 414-8.
  15. Falagas ME, Koletsi PK, Bliziotis IA. The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa. J Med Microbiol 2006; 55(Pt 12): 1619-29.
  16. Livermore DM. The need for new antibiotics. Clin Microbiol Infect 2004; 10(Suppl 4): 1-9.
  17. Ackermann HW, DuBow MS. Viruses of Prokaryotes: General properties of bacteriophages. Boca Raton, FL:CRC Press; 1987.
  18. Kunisaki H, Tanji Y. Intercrossing of phage genomes in a phage cocktail and stable coexistence with Escherichia coli O157:H7 in anaerobic continuous culture. Appl Microbiol Biotechnol 2010; 85(5): 1533-40.
  19. Clokie MRJ, Kropinski A. Bacteriophages: Methods and protocols, Vol 1: Isolation, characterization, and interactions. New York, NY: Humana Press; 2009. p. 15-23, 69-113.
  20. Jin J, Li ZJ, Wang SW, Wang SM, Huang DH, Li YH, et al. Isolation and characterization of ZZ1, a novel lytic phage that infects Acinetobacter baumannii clinical isolates. BMC Microbiol 2012; 12: 156.
  21. Regal RE, DePestel DD, VandenBussche HL. The effect of an antimicrobial restriction program on Pseudomonas aeruginosa resistance to beta-lactams in a large teaching hospital. Pharmacotherapy 2003; 23(5): 618-24.
  22. Gonlugur U, Bakici MZ, Ozdemir L, Akkurt I, Icagasioglu S, Gultekin F. Retrospective analysis of antibiotic susceptibility patterns of respiratory isolates of Pseudomonas aeruginosa in a Turkish University Hospital. Ann Clin Microbiol Antimicrob 2003; 2: 5.
  23. Niitsuma K, Saitoh M, Kojimabara M, Kashiwabara N, Aoki T, Tomizawa M, et al. Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima Prefecture. Jpn J Antibiot 2001; 54(2): 79-87.
  24. Mohajeri P. Antibiotic susceptibility and resistance patterns of pseudomonas aeruginosa strains isolated from different clinical specimens in patients referred to the teaching hospitals in Kermanshah(2001-2). J Kermanshah Univ Med Sci 2004; 7(4): 11-20. [In Persian].
  25. Azimi, Z, Ghane, M, Heshmatipour, Z. The antibiotic resistance of pseudomonas spp. isolated from different wards of Shahid Rajai Hospital in Tonekabon, 2010-2011. Medica Laboratory Journal. 2013; 7(2): 23-9. [In Persian].
  26. Shahcheraghi F, Nikbin VS, Feizabadi MM. Prevalence of ESBLs genes among multidrug-resistant isolates of Pseudomonas aeruginosa isolated from patients in Tehran. Microb Drug Resist 2009; 15(1): 37-9.
  27. Ranjbar R, Owlia P, Saderi H, Mansouri S, Jonaidi-Jafari N, Izadi M, et al. Characterization of Pseudomonas aeruginosa strains isolated from burned patients hospitalized in a major burn center in Tehran, Iran. Acta Med Iran 2011; 49(10): 675-9.
  28. Kianpour F, Havaei SA, Hosseini MM. Evaluation of Pseudomonas aeroginosa isolated from cutaneous infections and determination of drug resistance pattern in patients of Alzahra hospital in Esfahan. J Isfahan Med Sch 2010; 28(110): 503.
  29. Nahaei MR, Bohloli-Khiavi R, Asgarzadeh M, Hasani A, Sadeghi J, Akbari Dibavar M. Antibiotic resistance and plasmid profile of Pseudomonas aeruginosa strain isolated from hospitalized patients. J Ardabil Univ Med Sci 2007; 7(1): 90-8. [In Persian].
  30. Rahman M, Shamsuzzaman AK, Sirajee A, Miah AG, Hossain MA. Pattern of bacteria and their antimicrobial susceptibility isolated from inanimate objects and hospital personnel. Mymensingh Med J 2003; 12(2): 104-7.
  31. Rolston KV, Bodey GP. Pseudomonas aeruginosa infection in cancer patients. Cancer Invest 1992; 10(1): 43-59.
  32. Richards FF. The genetics of bacteria and their viruses. Yale J Biol Med 1969; 42(2): 120-1.
  33. Mihaljev-Martinov J, Nikolic I. Migraine--diagnostic problems. Med Pregl 1986; 39(7-8): 351-4.
  34. Kutter E, Sulakvelidze A. Bacteriophages: Biology and applications: Molecular biology and applications. Boca Raton, FL: CRC Press; 2005.
  35. Merril CR, Friedman TB, Attallah AF, Geier MR, Krell K, Yarkin R. Isolation of bacteriophages from commercial sera. In Vitro 1972; 8(2): 91-3.
  36. Merril CR. Phage in human vaccines. Science 1975; 188(4183): 8.
  37. Betts A, Vasse M, Kaltz O, Hochberg ME. Back to the future: evolving bacteriophages to increase their effectiveness against the pathogen Pseudomonas aeruginosa PAO1. Evol Appl 2013; 6(7): 1054-63.
  38. Hong SS, Jeong J, Lee J, Kim S, Min W, Myung H. Therapeutic effects of bacteriophages against Salmonella gallinarum infection in chickens. J Microbiol Biotechnol 2013; 23(10): 1478-83.
  39. Trigo G, Martins TG, Fraga AG, Longatto-Filho A, Castro AG, Azeredo J, et al. Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model. PLoS Negl Trop Dis 2013; 7(4): e2183.
  40. Gilmer DB, Schmitz JE, Euler CW, Fischetti VA. Novel bacteriophage lysin with broad lytic activity protects against mixed infection by Streptococcus pyogenes and methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2013; 57(6): 2743-50.