Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2006, vol. 15, nr 2, March-April, p. 279–283

Publication type: original article

Language: English

Bactericidal Effects of the Fotolon (Chlorin e6) on Gram−Negative and Gram−Positive Strains Isolated from Wound Infections

Bakteriobójczy wpływ Fotolonu (chlorinu e6) na Gram−ujemne i Gram−dodatnie szczepy izolowane z zakażonych ran

Zuzanna Drulis−Kawa1,2,, Artur Bednarkiewicz3,, Gabriela Bugla1,, Wiesław Stręk3,, Włodzimierz Doroszkiewicz1,

1 Institute of Genetics and Microbiology, University of Wroclaw, Poland

2 Korczak Children’s Hospital in Wroclaw, Poland

3 Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Wroclaw, Poland

Abstract

Background. Surgical site infections and diabetes foot infections are the very serious therapeutic problem. Because of the alarming bacterial drug resistant level and difficulty in wound infections treatment, an alternative or supportive bactericidal cure have to be developed. One of them is Photo Dynamic Inactivation (PDI) of bacterial strains.
Objectives. Test and discussion of the PDI efficiency using the Fotolon (chlorin e6) against Gram−positive and Gram−negative standard and wild type strains.
Material and Methods. Eight clinical isolates of Pseudomonas sp. and one clinical strain of Acinetobacter baumanii were tested. As references the authors used control strains from American Type Culture Collection: Grampositive: Staphylococcus aureus ATCC 29213, and Gram−negative: Klebsiella pneumoniae ATCC 700601, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. PDI procedure were carried out using photosensitive compound – the Fotolon (chlorin e6) and laser light.
Results. For S. aureus strain fivefold decrease of colony forming units was obtained. For other control bacteria only twice decrease level was observed. The P. putida and P. stutzeri isolates were as sensitive as Gram−positive S. aureus, what is very interesting phenomenon. The remaining Gram−negative strains showed 0.5–2 log of cfu decrease. The authors found that high concentration of the Fotolon in short incubation time gives smaller bactericidal effect than lower concentration in long incubation period.
Conclusion. Both Gram−positive and Gram−negative types of bacteria were sensitive to PDI with Fotolon, however different PDI susceptibility of clinical isolates were observed.

Streszczenie

Wprowadzenie. Zakażenia ran pooperacyjnych oraz infekcje związane ze „stopą cukrzycową” są bardzo poważnym problemem terapeutycznym. Ze względu na alarmujący wzrost oporności drobnoustrojów na antybiotyki oraz trudności w leczeniu zakażeń ran istnieje konieczność rozwoju nowych alternatywnych lub wspomagających metod leczniczych. Jedną z nich może być fotodynamiczna inaktywacja (PDI) szczepów bakteryjnych. Cel. Przebadanie skuteczności PDI w stosunku do Gram−dodatnich i Gram−ujemnych szczepów bakteryjnych, zarówno standardowych, jak i dzikich. Materiały i metody. Przetestowano sześć klinicznych szczepów Pseudomonas sp. i jeden kliniczny izolat Acinetobacter baumanii. Jako kontrole użyto szczepy z kolekcji ATCC (American Type Culture Collection): Gram−dodatni Staphylococcus aureus ATCC 29213 oraz Gram−ujemne: Klebsiella pneumoniae ATCC 700601, Escherichia coli ATCC 25922 i Pseudomonas aeruginosa ATCC 27853. Procedurę fotodynamicznej inaktywacji przeprowadzono za pomocą Fotolonu (chlorinu e6) i światła laserowego.
Wyniki. W przypadku szczepu S. aureus zaobserwowano 5−krotny spadek liczby jednostek tworzących kolonie (cfu). Gram−ujemne szczepy kontrolne wykazywały tylko dwukrotny spadek cfu. Izolaty P. putida i P. stutzeri były tak samo wrażliwe na PDI jak Gram−dodatni S. aureus, co jest bardzo interesującym zjawiskiem. Pozostałe szczepy Gram−ujemne wykazywały spadek cfu w granicach 0,5–2 log. Stwierdzono, że wysokie stężenie Fotolonu zastosowane przy krótkim czasie inkubacji charakteryzowało się mniejszym efektem bakteriobójczym niż niskie stężenie aplikowane przez długi czas.
Wnioski. Zarówno bakterie Gram−dodatnie, jak i Gram−ujemne były wrażliwe na PDI z zastosowaniem Fotolonu, szczepy kliniczne jednak wykazywały zróżnicowaną wrażliwość.

Key words

photodynamic inactivation, Fotolon (chlorin e6), Gram−positive bacteria, Gram−negative bacteria

Słowa kluczowe

fotodynamiczna inaktywacja, Fotolon (chlorin e6), bakterie Gram−dodatnie, bakterie Gram−ujemne

References (27)

  1. Emori TG, Gaynes RP: An overview of nosocomial infections, including the role of microbiology laboratory. Clin Microb Rev 1993, 4, 428–442.
  2. Mayon−White RT, Ducel G, Kereselidze T: An international survey of the prevalence of hospital−aquired infection. J Hosp Infect 1988, 2, 11 Suppl A: 43–48.
  3. NNIS System: National Nosocomial Infections Surveillance (NNIS) report, data summary from October 1986–April 1996, issued May 1996. A report from the National Nosocomial Infections Surveillance (NNIS) System. Am J Infect Control 1996, 5, 380–388.
  4. Revathi G, Puri J, Jain BK: Bacteriology of burns. Burns 1998, 4, 347–359.
  5. Siami G, Christou N, Eiseman I, Tack KJ and the Clinafloxacin Severe Skin And Soft Tissue Infections Study Group: Clinafloxacin versus Piperacillin−Tazobactam in Treatment of Patients with Severe Skin and Soft Tissue Infections. Antimicrob. Agents Chemother 2001, 45, 525–531.
  6. Carmeli Y, Castro J, Eliopoulos GM, Samore MH: Clinical Isolation and Resistance Patterns of and Superinfection with 10 Nosocomial Pathogens after Treatment with Ceftriaxone versus Ampicillin−Sulbactam. Antimicrob. Agents Chemother 2001, 45, 275–279.
  7. Bell JM, Turnidge JD and SENTRY APAC Participants: High Prevalence of Oxacillin−Resistant Staphylococcus aureus Isolates from Hospitalized Patients in Asia−Pacific and South Africa: Results from SENTRY Antimicrobial Surveillance Program, 1998–1999. Antimicrob. Agents Chemother 2002, 46, 879–881.
  8. Harbarth S, Cosgrove S, Carmeli Y: Effects of Antibiotics on Nosocomial Epidemiology of VancomycinResistant Enterococci. Antimicrob. Agents Chemother 2002, 46, 1619–1628. Fig. 1. Cfu parameter for all strains examined within the two kinds of experiments. The data are normalized to the cfu of respective control group: tinc – incubation time; ce6 – chlorin e6; cfu – colony forming units Ryc. 1. Wskaźnik cfu dla wszystkich badanych szczepów w dwóch rodzajach eksperymentów. Dane zostaly znormalizowane w stosunku do cfu odpowiedniej grupy kontrolnej: tinc – czas inkubacji; ce6 – chlorin e6; cfu – jednostki tworzące kolonie inc t = 120', c = 50 μg/ml cfu Staphylococcus aureus Klebsiella pneumoniae
  9. Livermore DM, Woodford N: Carbapenemases: a problem in waiting? Curr Opin Microbiol 2000, 3, 489–495.
  10. Livermore DM: Of Pseudomonas, porins, pumps and carbapenems. J Antimicrob Chemother 2001, 47, 247–250.
  11. Quinn JP, Dudek EJ, DiVincenzo CA, Lucks DA, Lerner SA: Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. J Infect Dis 1986, 154, 289–294.
  12. Senda K, Arakawa Y, Nakashima K, Ito H, Ichiyama S, Shimokata K, Kato N, Ohta M: Multifocal outbreaks of metallo−—lactamase−producing Pseudomonas aeruginosa resistant to broad−spectrum β−lactams, including carbapenems. Antimicrob Agents Chemother 1996, 40, 349–353.
  13. Hamblin MR, Zahra T, Contag CH, McManus AT, Hasan T: Optical monitoring and treatment of potentially lethal wound infections in vivo. J Infect Dis 2003, 187, 1717–1725.
  14. Soukos NS, Wilson M, Burns T, Speight PM: Photodynamic effects of toluidine blue on human oral keratinocytes and fibroblasts and Streptococcus sanguis evaluated in vitro. Lasers Surg Med 1996, 18, 253–259.
  15. Embleton ML, Sean PN, Cookson BD, Wilson M: Selective lethal photosensitization of methicillin−resistant Staphylococcus aureus using an IgG−tin (IV) chlorin e6 conjugate. J Antimicrob Chemother 2002, 50, 857–864.
  16. Soncin M, Fabris C, Busetti A, Dei D, Nistri D, Roncucci G, Jori G: Approaches to selectivity in the Zn(II)− phthalocyanine−photosensitized inactivation of wild−type and antibiotic−resistant Staphylococcus aureus. Photochem Photobiol Sci 2002, 10, 815–919.
  17. Ehrenberg B, Malik Z, Nitzan Y: Fluorescence spectral changes of hematoporphyrin derivative upon binding to lipid vesicles Staphylococcus aureus and Escherichia coli cells. Photochem Photobiol 1985, 41, 429–435.
  18. Malik Z, Ladan H, Nitzan Y: Photodynamic inactivation of Gram−negative bacteria Problems and possible solutions. J Photobiol Photochem B: Biol 1992, 1, 262–266.
  19. Bertoloni G, Rossi F, Valduga G, Jori G, van Lier J: Photosensitiseing activity of waterand lipid−soluable phthalocyanines on Escherichia coli. FEMS Microbiol Letters 1990, 59, 149–55.
  20. Nitzan Y, Malik Z, Ehrenberg B: Photosensitization of microbial cells. In Photobiology: the Science and its Applications. Eds.: Riklis E. Plenum Press, New York, 815–820.
  21. Merchat M, Bertoloni G, Giacomoni P, Villanueva A, Jori G: Meso−substituted cationic porphyrins as efficient photosensitizers of Gram−positive and Gram−negative bacteria. J Photochem Photobiol 1996, 32, 153–157.
  22. Hamblin MR, O’Donnell DA, Murthy N, Rajagopalan K, Michaud N, Sherwood ME, HasanT: Polycationic photosensitiser conjugates: effects of chain length and Gram classification on the photodynamic inactivation of bacteria. J Antimicrob Chemother 2002, 49, 941–951.
  23. Minnock A, Vernon DI, Schofield J, Griffiths J, Parish JH, Brown ST: Photoinactivation of bacteria. Use of a cationic water−soluble zinc phthalocyanine to photoinactivate both Gram−negative and Gram−positive bacteria. J Photochem Photobiol B: Biol 1996, 32, 159–164.
  24. Vaara M: Agents that increase the permeability of the outer membrane. Microbiol Rev 1992, 56, 395–411.
  25. Berthiaume F, Reiken SR, Toner M, Tompkins RG, Yarmush ML: Antibody−targeted photolysis of bacteria in vivo. Bio−Technology 1994, 12, 703–706.
  26. Friedberg JS, Tompkins RG, Rakestraw SL, Warren SW, Fischman AJ, Yarmush ML: Antibody−targeted photolysis. Bacteriocidal effects of Sn (IV) chlorin e6−dextran−monoclonal antibody conjugates. Ann NY Acad Sci 1991, 618, 383–393.
  27. Parkhots MV, Knyukshto VN, Isakov GA, Petrov PT, Lepeshkevich SV, Khairullina AY, Dzhagarov BA: Spectral−luminescent studies of the “photolon” photosensitizer in model media and in blood of oncological patients. J App Spectr 2003, 70, 921–926.