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METHICILLIN-RESISTANT S. AUREUS (MRSA) SKIN ABSCESS AND VARIOUS OTHER SKIN CONDITIONS TREATED WITH NON-INVASIVE COLD LASER THERAPY.

Posted on September 1, 2014 at 5:05 PM

INTRODUCTION:

The extensive and inappropriate use of antibiotics in the early 1980s gradually led to the buildup of universal antimicrobial resistance. Penicillin was first widely used in the early 1940s and by 1944 half of all clinical Staphylococci spp isolates were resistant to this proclaimed “miracle drug [1]. In recent times infectious disease has become the second most important killer in the world, number three in developed nations and fourth in the USA [2]. Additionally it is one of the leading cause of death in Europe, mostly in elderly and debilitated populations, and despite existing antibiotic therapies and vaccines, infectious diseases remain the leading cause of mortality and morbidity [3]. Worldwide, 17 million people die each year from bacterial infections [4].In addition to that, five classes of antibiotic-resistant pathogens are emerging as major threats to public health: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), multidrug-resistant mycobacteria, Gram-negative pathogens and fungi [5].

As the efficacy of antibiotics reduces and the end of the “antibiotic era” gets closer, major international research efforts to discover new ways to eradicate bacteria are evolving. Antibiotic therapy failure can result in variants of Staphylococcus aureus that are more resistant to antibiotics and can lead to persistent infections, necessitating the development of more effective antimicrobial strategies to combat small colony variant infections.

CAUSES AND RISK FACTORS FOR MRSA:

S. aureus small colony variants (SCVs) are clinically important owing to their reduced susceptibility to antibiotics. SCVs are commonly auxotroph’s for hemin, menadione or thymidine, resulting in electron transport chain defects and consequently reduced membrane potential and reduced uptake of cationic antibiotics [6]. Resistance to cell wall–active antibiotics such as β-lactams occurs due to the slow growth rate and reduced cell wall metabolism of SCVs [7]. Given their persistent nature and their selection by and resistance to conventional antibiotics, there is a need to identify effective therapies for SCV infections. One relatively new potential novel strategy is high powered non-invasive laser therapy.

STANDARD TREATMENT METHODS FOR MRSA RELATED SKIN CONDITIONS:

Primary topical anti-microbial and antiseptic agents are indicated in both prophylaxis and treatment of superficial skin infections. One advantage of topical application of anti-microbial agents is their low systemic absorption, consequently the reduced exposure of the commensal gastrointestinal flora to these antibiotics and low systemic toxicity [8]. The principles of anti-microbial treatment of infected skin wounds are discussed extensively by Filius et al. [9]. Today topical therapy with antibiotics has become unpopular because of the development of resistance [10].

Colsky and colleagues made a comparison of antibiotic resistance profiles using data collected from 1992 to 1996 from patients with skin wounds and revealed a marked increase in oxacillin and ciprofloxacin resistance in S. aureus and P. aeruginosa. In leg ulcers, an increase from 24% to 50% oxacillin resistance in S. aureus and from 9% to 24% ciprofloxacin resistance in P. aeruginosa. In superficial wounds, an increase from 24% to 36% ciprofloxacin resistance in P. aeruginosa [11, 12]. This study demonstrated the rapid increase of antibiotic resistant bacterial pathogens due to the systemic use of antibiotics in dermatology and highlights the importance of searching for alternatives.

USE OF NON-INVASIVE COLD LASER THERAPY:

In a first report, Hamblin et al. showed the use of a photochemical approach to destroy bacteria infecting a wound in an animal model without damaging the surrounding host tissue [13]. After topical application of achlorin (e6) photosensitizer conjugated with poly-Lysine, E. coli was rapidly killed upon exposure to selected visible light wavelengths.

MECHANISM OF ACTION OF LASER INACTIVATION OF MICROORGANISMS:

Upon irradiation with light from a high powered non-invasive laser using parameters of 1275 nm or 1064 nm wavelength and within the 750 mW to 2.8 watts per cm2range , the photosensitizer (PS) or chromosphere undergoes a transition from a low energy ground state to a higher energy triplet state. This triplet state photosensitizer can react directly with biomolecules to produce free radicals and/or radical ions (type I reaction), or with molecular oxygen to produce highly reactive singlet oxygen (type II reaction) as shown is figure. Various studies showed that there is a difference in susceptibility to anti-bacterial PDT between gram-positive and gram-negative bacteria [14, 15, 16]. Anionic and neutral photosensitizers were found to bind efficiently to gram-positive bacteria to induce growth inhibition or killing by visible light, whereas gram-negative bacteria were not killed. Growth inhibition of E. coli by porphyrin photosensitization was possible only in the presence of membrane disorganizing substances, e.g. the nona-peptide polymyxin or Tris–EDTA [16]. However, direct photo killing of gram-negative bacteria is also possible. In recent years, different chemical classes of positively charged PS, including phthalocyanines and porphyrins, were successfully tested as photo inactivating agents against gram-positive and gram-negative bacteria so far [17, 18, 19, 15, 20]. In general, photosensitizers with an overall cationic charge and meso-substituted cationic porphyrins and water-soluble cationic zinc phthalocyanines can efficiently kill gram negative bacteria by photosensitization even in the absence of additives. This resistance of gram-negative bacteria against efficient killing by anti-bacterial photodynamic therapy is due to the different outer membrane structures of gram-positive and gram-negative bacteria, which is discussed in detail elsewhere [21]. Inactivation of S. aureus, E. coli and P. aeruginosa is accompanied by alterations of the ultra-structure of the cells, e.g. disordered cell wall structure; elongated cells connected together without separation of the daughter cells and different low density areas in the cytoplasm [16, 22].

CONCLUSION:

The current research work provides sufficient evidence that cold laser therapy can be an effective tool in the management of non-healing MRSA abscess or related skin conditions. Such results prove that there is still hope for the cure and even prevention of MRSA infection complications. The research to develop a standard guideline for the use of such laser therapy should be continued and promoted so that a larger number of patients can benefit from laser therapy.

REFERENCES:

1. Livermore DM. Antibiotic resistance in staphylococci. Int J Antimicrob Agents 2000; 16:3-10; PMID:11137402; http://dx.doi.org/10.1016/S0924- 8579(00)00299-5.

2. Kraus CN. Low hanging fruit in infectious disease drug development. Curr Opin Microbiol 2008; 11:434-8; PMID:18822387;http://dx.doi.org/10.1016/j.mib.2008.09.009.

3. Vicente M, Hodgson J, Massidda O, Tonjum T,Henriques-Normark B, Ron EZ. The fallacies of hope: will we discover new antibiotics to combat pathogenic bacteria in time? FEMS Microbiol Rev 2006; 30:841-52; PMID:17064283; http://dx.doi. org/10.1111/j.1574-6976.2006.00038.x.

4. Butler MS, Buss AD. Natural products—the future scaffolds for novel antibiotics? Biochem Pharmacol 2006; 71:919-29; PMID:16289393; http://dx.doi. org/10.1016/j.bcp.2005.10.012.

5. Nicolau DP. Current challenges in the management of the infected patient. Curr Opin Infect Dis 2011; 24:1-10; PMID:21200179; http://dx.doi.org/10.1097/01. qco.0000393483.10270.ff.

6. Proctor RA, von Eiff C, Kahl BC, Becker K, McNamara P, Herrmann M, et al:Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 2006, 4:295–305.

7. Proctor RA, Kahl B, von Eiff C, Vaudaux PE, Lew DP, Peters G:Staphylococcal small colony variants have novel mechanisms for antibiotic resistance. Clin Infect Dis 1998, 27(suppl 1):S68–S74.

8. Kaye ET (2000) Topical antibacterial agents: role in prophylaxis and treatment of bacterial infections. Curr Clin Top Infect Dis 20:43–62.

9. Filius PM, Gyssens IC (2002) Impact of increasing antimicrobial resistance on wound management. Am J Clin Dermatol 3:1–7.

10. Wyatt TD, Ferguson WP, Wilson TS, McCormick E (1977) Gentamicin resistant Staphylococcus aureus associated with the use of topical gentamicin. J Antimicrob Chemother 3:213–217.

11. Colsky AS, Kirsner RS, Kerdel FA (1998) Analysis of antibiotic susceptibilities of skin wound flora in hospitalized dermatology patients. The crisis of antibiotic resistance has come to the surface. Arch Dermatol 134:1006–1009.

12. Colsky AS, Kirsner RS, Kerdel FA (1998) Microbiologic evaluation of cutaneous wounds in hospitalized dermatology patients. Ostomy Wound Manage 44:40–42, 44, 46.

13. Hamblin MR, O’Donnell DA, Murthy N, Contag CH, Hasan T(2002) Rapid control of wound infections by targeted photodynamic therapy monitored by in vivo bioluminescence imaging. Photochem Photobiol 75:51–57.

14. Merchat M, Bertolini G, Giacomini P, Villanueva A, Jori G(1996) Meso-substituted cationic porphyrins as efficient photosensitizers of gram-positive and gram-negative bacteria.J Photochem Photobiol B 32:153–157.

15. Minnock A, Vernon DI, Schofield J, Griffiths J, Parish JH,Brown ST (1996) Photoinactivation of bacteria. Use of a cationic water-soluble zinc phthalocyanine to photoinactivate both gram-negative and gram-positive bacteria. J PhotochemPhotobiol B 32:159–164.

16. Nitzan Y, Gutterman M, Malik Z, Ehrenberg B (1992) Inactivation of gram-negative bacteria by photosensitized porphyrins. Photochem Photobiol 55:89–96.

17. Maisch T, Bosl C, Szeimies RM, Lehn N, Abels C (2005).Photodynamic effects of novel XF porphyrin derivatives on prokaryotic and eukaryotic cells. Antimicrob Agents Chemother 49:1542–1552.

18. Merchat M, Spikes JD, Bertoloni G, Jori G (1996) Studies on the mechanism of bacteria photosensitization by meso-substitutedcationic porphyrins. J Photochem Photobiol B 35:149–157.

19. Minnock A, Vernon DI, Schofield J, Griffiths J, Parish JH,Brown SB (2000) Mechanism of uptake of a cationic watersoluble pyridinium zinc phthalocyanine across the outer membrane of Escherichia coli. Antimicrob Agents Chemother44:522–527.

20. Segalla A, Borsarelli CD, Braslavsky SE, Spikes JD, Roncucci G, Dei D, Chiti G, Jori G, Reddi E (2002) Photophysical,photochemical and antibacterial photosensitizing properties of a novel octacationic Zn(II)-phthalocyanine. Photochem Photobiol Sci 1:641–648.

21. Maisch T, Szeimies RM, Jori G, Abels C (2004) Antibacterial photodynamic therapy in dermatology. Photochem PhotobiolSci 3:907–917.

22. Malik Z, Faraggi A, Savion N (1992).Ultrastructural damage in photosensitized endothelial cells: dependence on hematoporphyrin delivery pathways. J Photochem Photobiol B 14:359–368.

 

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