Skip to main content

Advertisement

SpringerLink
Log in

A combination of photodynamic therapy and antimicrobial compounds to treat skin and mucosal infections: a systematic review

  • Paper
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Background

Antimicrobial photodynamic therapy (aPDT) is a growing approach to treat skin and mucosal infections. Despite its effectiveness, investigators have explored whether aPDT can be further combined with antibiotics and antifungal drugs.

Objective

To systematically assess the in vivo studies on the effectiveness of combinations of aPTD plus antimicrobials in the treatment of cutaneous and mucosal infections.

Materials and methods

Searches were performed in four databases (PubMed, EMBASE, Cochrane library databases, ClinicaTrials.gov) until July 2018. The pooled information was evaluated according to the PRISMA guidelines.

Results

11 full-text articles were finally evaluated and included. The best aPDT combinations involved 5-aminolevulinic acid or phenothiazinium dye-based aPDT. In general, the combination shows benefits such as reducing treatment times, lowering drug dosages, decreasing drug toxicity, improving patient compliance and diminishing the risk of developing resistance. The mechanism of action may be that first aPDT damages the microbial cell wall or membrane, which allows better penetration of the antimicrobial drug.

Limitations

The number of studies was low, the protocols used were heterogeneous, and there was a lack of clinical trials.

Conclusions

The additive or synergistic effect of aPDT combined with antimicrobials could be promising to manage skin and mucosal infections, helping to overcome the microbial drug resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. D. M. Livermore, Has the era of untreatable infections arrived?, J. Antimicrob. Chemother., 2009, 64(Suppl. 1), i29–i36.

  2. M. Bassetti, M. Merelli, C. Temperoni and A. Astilean, New antibiotics for bad bugs: where are we?, Ann. Clin. Microbiol. Antimicrob., 2013, 12, 22.

    Article  Google Scholar 

  3. S. Santajit and N. Indrawattana, Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens, BioMed Res. Int., 2016, 2016, 2475067.

    Article  Google Scholar 

  4. S. B. Singh, K. Young and L. L. Silver, What is an «ideal» antibiotic? Discovery challenges and path forward, Biochem. Pharmacol., 2017, 133, 63–73.

    Article  CAS  Google Scholar 

  5. H. W. Boucher, G. H. Talbot, D. K. Benjamin, J. Bradley, R. J. Guidos, R. N. Jones, et al., 10 × ‘20 Progress—Development of New Drugs Active Against Gram-Negative Bacilli: An Update From the Infectious Diseases Society of America, Clin. Infect. Dis., 2013, 56(12), 1685–1694.

  6. H. W. Boucher, G. H. Talbot, J. S. Bradley, J. E. Edwards, D. Gilbert, L. B. Rice, et al., Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America, Clin. Infect. Dis., 2009, 48(1), 1–12.

  7. T. Dai, B. B. Fuchs, J. J. Coleman, R. A. Prates, C. Astrakas, T. G. St Denis, et al., Concepts and principles of photodynamic therapy as an alternative antifungal discovery platform, Front. Microbiol., 2012, 3, 120.

    CAS  PubMed  Google Scholar 

  8. V. Pérez-Laguna, A. J. García-Malinis, C. Aspiroz, A. Rezusta and Y. Gilaberte, Antimicrobial effects of photodynamic therapy: an overview, G. Ital. Dermatol. Venereol., 2018, 153(6), 833–846.

  9. H. Abrahamse and M. R. Hamblin, New photosensitizers for photodynamic therapy, Biochem. J., 2016, 473(4), 347–364.

  10. K. O’Riordan, O. E. Akilov and T. Hasan, The potential for photodynamic therapy in the treatment of localized infections, Photodiagn. Photodyn. Ther., 2005, 2(4), 247–262.

  11. T. Dai, Y.-Y. Huang and M. R. Hamblin, Photodynamic therapy for localized infections–state of the art, Photodiagn. Photodyn. Ther., 2009, 6(3–4), 170–188.

  12. G. B. Kharkwal, S. K. Sharma, Y.-Y. Huang, T. Dai and M. R. Hamblin, Photodynamic therapy for infections: clinical applications, Lasers Surg. Med., 2011, 43(7), 755–767.

  13. V. Pérez-Laguna, L. Pérez-Artiaga, V. Lampaya-Pérez, I. García-Luque, S. Ballesta, S. Nonell, et al., Bactericidal Effect of Photodynamic Therapy, Alone or in Combination with Mupirocin or Linezolid, on Staphylococcus aureus, Front. Microbiol., 2017, 8, 1002.

    PubMed  PubMed Central  Google Scholar 

  14. A. Wozniak and M. Grinholc, Combined Antimicrobial Activity of Photodynamic Inactivation and Antimicrobials-State of the Art, Front. Microbiol., 2018, 9, 930.

    Article  Google Scholar 

  15. F. Barra, E. Roscetto, A. A. Soriano, A. Vollaro, I. Postiglione, G. M. Pierantoni, et al., Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections, Int. J. Mol. Sci., 2015, 16(9), 20417–20430.

  16. D. Moher, L. Shamseer, M. Clarke, D. Ghersi, A. Liberati, M. Petticrew, et al., Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement, Syst. Rev., 2015, 4, 1.

    Article  Google Scholar 

  17. L. Shamseer, D. Moher, M. Clarke, D. Ghersi, A. Liberati, M. Petticrew, et al., Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation, Br. Med. J., 2015, 350, g7647.

  18. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. Part 2: General methods for Cochrane reviews. Chapter 8: Assessing risk of bias in included studies [Internet], ed. J. P. T. Higgins and S. Green, The Cochrane Collaboration, 2011 [citado 21 de septiembre de 2018]. Disponible en: http://handbook-5-1.cochrane.org/.

  19. K. Sun, H. Yang, X. Huang, N. Gong, Q. Qin, W. Lu, et al., ALA-PDT combined with antibiotics for the treatment of atypical mycobacterial skin infections: Outcomes and safety, Photodiagn. Photodyn. Ther., 2017, 19, 274–277.

    Article  CAS  Google Scholar 

  20. J. Chibebe Junior, B. B. Fuchs, C. P. Sabino, J. C. Junqueira, A. O. C. Jorge, M. S. Ribeiro, et al., Photodynamic and antibiotic therapy impair the pathogenesis of Enterococcus faecium in a whole animal insect model, PLoS One, 2013, 8(2), e55926.

  21. J. Chibebe Junior, C. P. Sabino, X. Tan, J. C. Junqueira, Y. Wang, B. B. Fuchs, et al., Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella, BMC Microbiol., 2013, 13, 217.

    Article  Google Scholar 

  22. Z. Lu, T. Dai, L. Huang, D. B. Kurup, G. P. Tegos, A. Jahnke, et al., Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections, Nanomed., 2010, 5(10), 1525–1533.

  23. T. L. Collins, E. A. Markus, D. J. Hassett and J. B. Robinson, The effect of a cationic porphyrin on Pseudomonas aeruginosa biofilms, Curr. Microbiol., 2010, 61(5), 411–416.

  24. N. Gong, Y. Tan, M. Li, W. Lu and X. Lei, ALA-PDT combined with antibiotics for the treatment of multiple skin abscesses caused by Mycobacterium fortuitum, Photodiagn. Photodyn. Ther., 2016, 15, 70–72.

    Article  CAS  Google Scholar 

  25. S. W. Kashem and D. H. Kaplan, Skin Immunity to Candida albicans, Trends Immunol., 2016, 37(7), 440–450.

  26. Q. Cai, L.-J. Yang, J. Chen, H. Yang, Z.-Q. Gao and X.-L. Wang, Successful Sequential Treatment with Itraconazole and ALA-PDT for Cutaneous Granuloma by Candida albicans: A Case Report and Literature Review, Mycopathologia, 2018, 183(5), 829–834.

  27. L. M. Giroldo, M. P. Felipe, M. A. de Oliveira, E. Munin, L. P. Alves and M. S. Costa, Photodynamic antimicrobial chemotherapy (PACT) with methylene blue increases membrane permeability in Candida albicans, Lasers Med. Sci., 2009, 24(1), 109–112.

  28. J. P. Lyon, C. R. Carvalho, R. R. Rezende, C. J. Lima, F. V. Santos and L. M. Moreira, Synergism between fluconazole and methylene blue-photodynamic therapy against fluconazole-resistant Candida strains, Indian J. Med. Microbiol., 2016, 34(4), 506–508.

  29. C. Zaugg, M. Monod, J. Weber, K. Harshman, S. Pradervand, J. Thomas, et al., Gene expression profiling in the human pathogenic dermatophyte Trichophyton rubrum during growth on proteins, Eukaryotic Cell, 2009, 8(2), 241–250.

  30. L. M. Baltazar, S. M. C. Werneck, H. C. S. Carneiro, L. F. Gouveia, T. P. de Paula, R. M. D. Byrro, et al., Photodynamic therapy efficiently controls dermatophytosis caused by Trichophyton rubrum in a murine model, Br. J. Dermatol., 2015, 172(3), 801–804.

  31. M. B. L. de Barros, R. de Almeida Paes and A. O. Schubach, Sporothrix schenckii and Sporotrichosis, Clin. Microbiol. Rev., 2011, 24(4), 633–654.

  32. Y. Gilaberte, C. Aspiroz, M. C. Alejandre, E. Andres-Ciriano, B. Fortuño, L. Charlez, et al., Cutaneous sporotrichosis treated with photodynamic therapy: an in vitro and in vivo study, Photomed. Laser Surg., 2014, 32(1), 54–57.

  33. Y. Hu, X. Huang, S. Lu, M. R. Hamblin, E. Mylonakis, J. Zhang, et al., Photodynamic therapy combined with terbinafine against chromoblastomycosis and the effect of PDT on Fonsecaea monophora in vitro, Mycopathologia, 2015, 179(1–2), 103–109.

  34. Y. Yang, Y. Hu, J. Zhang, X. Li, C. Lu, Y. Liang, et al., A refractory case of chromoblastomycosis due to Fonsecaea monophora with improvement by photodynamic therapy, Med. Mycol., 2012, 50(6), 649–653.

  35. F. Queiroz-Telles, Chromoblastomycosis: a neglected tropical disease, Rev. Inst. Med. Trop. Sao Paulo, 2015, 57(Suppl. 19), 46–50.

  36. F. Queiroz-Telles and D. W. Santos, Challenges in the therapy of chromoblastomycosis, Mycopathologia, 2013, 175(5–6), 477–488.

  37. Z.-H. Liu and X.-J. Xia, Successful sequential treatment with itraconazole and ALA-PDT for chromoblastomycosis because of Alternaria alternata, Dermatol. Ther., 2014, 27(6), 357–360.

Download references

Author information

Authors and Affiliations

  1. IIS Aragón, Zaragoza, Spain

    Vanesa Pérez-Laguna, Yolanda Gilaberte & Antonio Rezusta

  2. Department of Dermatology, Hospital Universitario Miguel Servet, 50009, Zaragoza, Spain

    Yolanda Gilaberte

  3. Department of Microbiology, Hospital Universitario Miguel Servet, 50009, Zaragoza, Spain

    María Isabel Millán-Lou & Antonio Rezusta

  4. Institut Quimic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017, Barcelona, Spain

    Montserrat Agut & Santi Nonell

  5. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA

    Michael R. Hamblin

  6. Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA

    Michael R. Hamblin

  7. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA

    Michael R. Hamblin

Authors
  1. Vanesa Pérez-Laguna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yolanda Gilaberte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. María Isabel Millán-Lou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Montserrat Agut
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Santi Nonell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Rezusta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael R. Hamblin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vanesa Pérez-Laguna.

Additional information

Electronic supplementary information (ESI) available: Fig. 1 Simplified diagram of the photodynamic reaction. e−: electron; H2O2: hydrogen peroxide; hv: photons (light);•O2−: superoxide anion; 1O2: singlet oxygen; 3O2: molecular oxygen;•OH: hydroxyl radical; PS: photosensitizer in basal state; 1PS*: photosensitizer in its singlet state; 3PS*: photosensitizer in excited triplet state; ROS: reactive oxygen species. See DOI: 10.1039/c8pp00534f

These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pérez-Laguna, V., Gilaberte, Y., Millán-Lou, M.I. et al. A combination of photodynamic therapy and antimicrobial compounds to treat skin and mucosal infections: a systematic review. Photochem Photobiol Sci 18, 1020–1029 (2019). https://doi.org/10.1039/c8pp00534f

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c8pp00534f

Search

Navigation