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Trauma & Orthopaedics Page 1 of 8 Critical review Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery W Jerjes 1,2 *, HB Tan 1 , C Hopper 2 , PV Giannoudis 1 Abstract for diagnosis,

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Critical review

Licensee OA Publishing London 2012. Creative Commons Attribution License (CC-BY)

Competing interests: none declared. Conflict of interests: none declared. All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript. All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure. F : Jerjes W, Tan HB, Hopper C, Giannoudis PV. Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery. Hard Tissue. 2012 Nov 10;1(1):9.

Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery

W Jerjes1,2*, HB Tan1, C Hopper2, PV Giannoudis1

Abstract

Introduction Photodynamic therapy, a minimally invasive oncological modality, has b- een in use for over 20 years. Howev- er, little clinical data is available on its non-oncological efficacy. Several laboratory-based trials on animals have suggested that this technology may be applicable as an antimicrobi- al therapy. In orthopaedics, where i- mplants and metal work are placed in deep tissue planes, a potential ris- k of infection is treated very serious-

ly. Infection not only increases pat-

ient morbidity and mortality but als-

the burden on healthcare system.

Proposing a new modality that can instantly tackle this problem. This critical review discusses surgical site infections subjected to photodynam- ic therapy. Conclusion Surgical care should be state of the art with careful attention to strategi- es that avoid the development of SS-

Is. When SSI does occur, superficial

and deep wound infections can be treated using PDT by applying topic- al photosensitiser to the area follow- ed by light illumination.

Introduction

Surgical site infection (SSI) Nearly all surgical wounds are contaminated by microbes; however, in-nate immunity neutralises this

effect. In few cases, infection may
develop. SSIs account for 10% of

all nosocomial infections. Although there is no international criterion for diagnosis, authorities seem to agree that an infection of the tissues around or within the surgical wound within the first 4 weeks of surgery represents ‘surgical site infection’. SSI significantly increases patient morbidity as well as mortality1–6. Incisional SSIs can be either superfi- cial (i.e. skin and subcutaneous tissue)

r deep (i.e. fascial and muscle layers)
r they can be organ/space SSIs; the

latter may involve anatomical struc- tures that are either unopened or manipulated during the surgery1–6. Several factors have been attributed to cause this surgical setback, including microbial- and host-related factors as well as surgical factors. Host-related factors involve age, medical back- ground, immunodeficiency, malnutri- tion, poor tissue perfusion and poor wound characteristics (such as poor skin, non-viable tissue, foreign body and haematoma). On the other hand, surgical factors include lengthy opera- tion, intraoperative contamination and poor surgical technique. Prolonged hospital stay, immobility and hypother- mia are responsible for majority of nosocomial infections, including SSIs1–6. Simple SSIs usually present as a discharging skin wound, and some- times, a sinus can be identified track- ing to the skin surface from a deeper

source. Involvement of deeper struc-

tures may lead to abscess formation, thereby complicating management (i.e. pelvic and spinal infections)1–6. Management is conventionally via antimicrobials and/or surgical

approach. Surgical wound abscess is

usually managed by incision, debridement and drainage. Deeper wounds are left open to allow healing from the inside out (i.e. healing by secondary inten-tion). Sometimes, long-term antimicrobials are requir- ed, especially when dealing with inf- ections spreading tothe underlying structures (i.e. muscle and bone)1–6. In orthopaedic surgery, SSIs are un- common; however, they can be devas- tating when theydo occur. Optimizing the patient’s general medical condi- tion pre-operatively and eliminating

r diminishing the modifiable risk

factors for infection has been shown to lower the risk of SSIs1–6. Prophylactic antimicrobials and resistance In the 1960s, experimental data dem-

nstrated the value of prophylactic
antimicrobials. According to early

studies at that time, high dose level of antibiotics in blood circulation has to be achieved at the time of first inci- sion in order to preventan infection. Prophylaxis is generally required for clean-contaminated and contaminated

wounds. Most authorities recommend

intravenous administration of pro- phylactic antimicrobials 30 min prior to the first incision7–13. The use of prophylactic antimicro- bials in orthopaedic surgery prior to the first incision has shown to be effective in reducing SSIs, especially in open reduction and internal fixation in trauma surgery, spinal surgery as well as hip and knee surgeries7–13. Staphylococcus aureus is most commonly identified in infected surgical wounds. Other bacteria such ascoagulase-negative staphylococci [including methicillin resistant Staph-ylococcus aureus (MRSA), which is proving to be a menace to modern day surgery], Escherichia coli, Pseudomonas aeruginosa

* Corresponding author Email: waseem_wk1@yahoo.co.uk

Leeds Institute of Molecular Medicine, Leeds, UK

UCL Department of Surgery, London, UK

Trauma & Orthopaedics

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Licensee OA Publishing London 2012. Creative Commons Attribution License (CC-BY)

Competing interests: none declared. Conflict of interests: none declared. All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript. All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure. F : Jerjes W, Tan HB, Hopper C, Giannoudis PV. Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery. Hard Tissue. 2012 Nov 10;1(1):9. and Enterobacter species have also been identified7–13. There has been an increase in the prevalence

antibiotic-resistant bacterial infectio- ns in clinical settings. This is mainly attributable to an increase in the prescription volume of anti-microbi- als, which in turn is attributable to various factors (Table 1). Antibiotic- resistance usually results from horizontal gene transfer as well as unlinked point mutations; four mec- hanisms have been identified: (1) drug inactivation or modification (i.e. some penicillin-resistant bact- eria), (2) alteration of metabolic pat- hways (i.e. sulphonamide-resistant bacteria), (3) alteration of target sites (i.e. MRSA and other pen- icillin-resistant bacteria), and (4) reduced drug accumulation. The most common of these pathogens are highlighted in Table 27–13. It is only time before the emer- gence of new microbial strains that will be resistant to all known antimicrobial agents. The ability to manage deep surgical wounds via antibiotics may soon come to an end. The only remaining alternative may be surgery that could lead to tissue

r limb loss, the latter being a

significant loss to a patient. Despite attempts to modify and create new antimicrobials which may help tackle this problem, the problem may spersist as new mutant strains will eventually develop resistance to newly developed antimicrobial agents. This possibility was evident during the testing phases of many new anti-microbial agents7–13. Another difficulty with developing new antimicrobials is safety, tolerability and toxicity of potential new drugs to humans. In the field of orthopaedic surgery, there is a need for a new modality that can

vercome/sidestep

the issue

multidrug resistance in bacterial strains, thereby reducing the burden on the patient and healthcare system. Photodynamic therapy (PDT) PDT represents a new modality that has been applied in clinical medicine and surgery for over two decades. This modality employs a photosensi- tiser that can either be introduced topically or systemically prior to tissue illumination with light. The resultant reaction between the light, photosensitiser and oxygen present in the tissues leads to a direct or programmed cell death and vascular shutdown14. PDT has been successfully applied in the management of various tissue pathologies with promising results. Pathological tissues in the brain, head and neck, lungs, gastrointestinal tract and hepatobiliary organs, bladder, skin and even bone tumours have responded well to this modality14. Very few reports have highlighted the effect of PDT as an antimicrobial modality in surgery. However, most of the published literature suggests that this modality may effectively eradicate infections, superficial or even deep seated

nes,

when effectively applied. Several in vitro studies have identified PDT as an effective tool for inactivation of antibiotic-sensitive and antibiotic-resistant microorgan-

isms. This could potentially benefit

those patients who suffer from antibiotic-resistant infections

those who require prolonged antimicrobial therapy15,16. The theory of photodynamic inacti- vation (PDI) necessitates cell exposure to specific wavelength light energy that leads to exogenous or endogenous exci- tation of photosensitiser molecules, resulting in the production of reactive

xygen species (ROS). ROS causes cell

inactivation and death through modifi- cation of intracellular components. Advances in understanding of micro- bial pathophysiology have led to identi- fication of a series of pathways and phenotypes that serve as potentialtar- gets for antimicrobial drug discovery. Investigations of these phenotypic ele- ments in concert with PDT have been reported, which mainly focus on multi- drug efflux systems, biofilms, virulence and pathogenesis determinants. In many instances, the results are encour- aging; however, they are still at prelimi- nary phases and would require further investigations15,16. PDT has been suggested as a new technique to inactivate microorgan- isms as it does not lead to the selec- tion of mutant resistant strains; a clear benefit in contrast to standard antibiotic therapy. This idea was ini- tially presented by Rabb (1900), who described the antimicrobial effect of acridine and light on Paramecium

species. Soukos et al.17 studied the

laser-induced effects of toluidine blue O

n normal human gingival keratino-

cytes and fibroblasts in vitro. The pre- liminary results of this study showed aneradication of Streptococcus san- guis, suggesting that a system for lethal photosensitisation of bacteria causing periodontal diseases could be

developed. This demonstrated the

microbial selectivity of PDT. PDI has Table 1 Antibiotic-resistant bacterial infections In appropriate prescribing: clinicians facing individuals who insist on antj biotj cs In appropriate prescribing: clinicians simply prescribe as they feel they do not have tj me to explain why the antj biotj cs are not necessary In appropriate prescribing: overly cautj

us clinicians for medico–legal reasons

Compliance with once-daily antj biotj cs is betu er than with twice-daily antj biotj cs Prescribing suboptj mum antj biotj c doses Poor hand hygiene by hospital staff

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Competing interests: none declared. Conflict of interests: none declared. All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript. All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure. F : Jerjes W, Tan HB, Hopper C, Giannoudis PV. Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery. Hard Tissue. 2012 Nov 10;1(1):9. Table 2 Most common antibiotic-resistant pathogens Bacterial species Description Frequent location Illnesses caused Greatly-feared strains Staphylococcus aureus Facultatj ve anaerobic, Gram-positj ve coccal bacterium Normal skin and mucosal fl

Range from minor skin infectj

ns to life-threatening

diseases such as pneumonia, meningitj s, osteomyelitj s, endocarditj s, toxic shock syndrome, bacteraemia and sepsis Methicillin- resistant Staphylococcus aureus Streptococcus pyogenes Spherical Gram-positj ve bacterium Normal skin fl

Range from mild superfi cial skin infectj

ns to life-threatening

systemic diseases such as necrotj zing fasciitj s, toxic shock syndrome, rheumatj c fever and acute glomerulonephritj s All produce virulence factors Enterococcus Gram-positj ve cocci Intestj nes Urinary tract infectj

bacteraemia, bacterial endocarditj s, divertj culitj s and meningitj s Multj drug- resistant Enterococcus faecalis and Enterococcus faecium Pseudomonas aeruginosa Gram-negatj ve, aerobic, rod- shaped bacterium Normal skin fl

ra and
pportunistj

c human pathogen Infectj

ns are generalized

infl ammatj

n and sepsis,

pneumonia, septj c shock, urinary tract infectj

gastrointestj nal infectj

n and

skin and sofu tj ssue infectj

Clostridium diffi cile Anaerobic, spore-forming rods (bacilli) Normal gut fl

and opportunistj c gut pathogen Severe diarrhoea and other intestj nal disease-associated diarrhoea and can lead to pseudomembranous colitj s Escherichia coli Gram-negatj ve, rod-shaped bacterium Normal lower intestj ne fl

Gastroenteritj s, urinary tract infectj

ns, and

neonatal meningitj

s. In rarer

cases, virulent strains are also responsible for haemolytj c-uremic syndrome, peritonitj s, mastj tj s, septj caemia and Gram-negatj ve pneumonia Escherichia coli O157:H7 Salmonella Rod-shaped, Gram-negatj ve Zoonotj c facultatj ve intracellular pathogens Enteritj s, meningitj s,

steitj

s and osteomyelitj s. Horny/ paratyphoid Salmonella Acinetobacter baumannii Aerobic Gram-negatj ve bacterium Opportunistj c infectj

Severe pneumonia and infectj

ns
f the urinary tract, bloodstream

and other parts of the body Mycobacterium tuberculosis Aerobic and non-motj le bacteria Mammalian respiratory system Tuberculosis Hyper virulent strains of M. tuberculosis

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Licensee OA Publishing London 2012. Creative Commons Attribution License (CC-BY)

Competing interests: none declared. Conflict of interests: none declared. All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript. All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure. F : Jerjes W, Tan HB, Hopper C, Giannoudis PV. Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery. Hard Tissue. 2012 Nov 10;1(1):9. been studied in bacteria, where PDI of Escherichia coli was prim- arily dependent on genomic DNA photo damage18, while in other studies, cellular envelope appears to be the main component being assaulted by PDT19,20. In a study by Bertoloni et al., two S. aureus strains were subjected to PDT, and the electrophoretic analysis

cytoplasmic membrane proteins and DNA suggested that the mem- brane represented the primary target of the photo process, while the DNA may be a secondary target21. Several studies have reported on the anti-staphylococcal activity of

PDT. In vitro studies using various

photosensitisers have shown a com- plete bactericidal effect on various bacteria, including MRSA22–30. Other Gram-positive bacteria have been investigated to a lesser extent; how- ever, they, including Propionibacterium acnes31,32 and Listeria monocytogenes33, have been reported to respond equally well to PDT. The in vitro bactericidal effect of PDT

n Gram-negative bacteria was also

investigated and it was found to have a high bactericidal effect on Haemophilus parainfluenzae34, Prevotella and Por- phyromonas species35–37, Helicobacter mustelae38, E. coli B, Acinetobacter bau- mannii, and P. aeruginosa39,40. PDT of Gram-positive and Gram-negative bac- teria in animal models hasproven to be as successful as in in vitro studies in inactivating the causative bacteria41–46. As yet, clinical PDT for infections has been mainly in the field of derma- tology using 5-aminolevulanic acid (5-ALA) and in dentistry using pheno- thiazinium dyes—a study concluded after peer-reviewing the published literature between 1960 and 2011. The authors expected to observe the applications of PDT to more challeng- ing infections using advanced antimi- crobial photosensitisers targeted to microbial cells in the years to

come16. Except for E. coli, there was a

significant decrease in the survival of Staphylococcus intermedius, Strept-

coccus canis and P. aeruginosa fo-

llowing ALA-PDT. A single treatme- nt required 2–3 h of light exposur-

e. The data from this particular st-

udy suggested that PDT may be a possible treatment option for wou- nd infections, but repeated treatm- ents or alterations in the photosen- sitiser or its carrier may be required to decrease treatment times41. The aim of this critical review is to discuss surgical site infections in

rthopaedic surgery.

Discussion

Application of PDT to surgical wounds The literature reports significant advances in the application of PDT as an antimicrobial modality that targets those pathological microorganisms which cause wound infections. If this antimicrobial modality is applied properly using an appropriate photo- sensitiser and matching light proper- ties, a high bactericidal rate can be

achieved. However, the efficacy and

safety of PDT on surgical wounds re- quires confirmation by appropriately designed human clinical trials. With all this overwhelming evidence, there is no doubt that we are entering an age of human clinical trials when it comes to the inactivation of microor- ganisms using PDT16,41. The issue of photosensitiser selec- tivity has been raised at a very early stage prior to clinical trials. Hamblin and Dai47 highlighted a crucial point with regard to selectivity—a photo- sensitiser that binds to microbial cells versus the one that binds to all other components in a complex milieu. According to these authors, theoreti- cally, 100 times more PDT is required to achieve the same high bactericidal effect that was achieved in in vitro and in vivo animal models. This was explained by an increase in the likeli- hood that the photosensitiser may bind to other components in a com- plex milieu, thereby reducing its availability for stronger PDT effect. Furthermore, the photosensitiser and light penetration may be affecte- d by thick pus and dead tissue. It is expected that each wound should be

pened and pus drained and that

debridement and washout should be performed prior to the application

f PDT in order to maximise the

penetration of the photosensitiser and light. This would theoretically increase the efficacy of PDT. Challenges

Education to surgeons: an editorial

highlighted the fact that surgeons do not possess the adequate knowl- edge when it comes to PDT and its potential applications47,48.

Translation from laboratory science

to human clinical trials: several factors need to be assessed and

reviewed. These include elimina-

tion of pathogens, selectivity, inflam- matory and immune processes of human tissues, collateral damage and systemic effect47,48.

PDT effect on the local vessels may

causeischaemia; this may poten- tially affect wound healing, leading to re-infection47.

Vascular and cellular mechanisms
f the treated infective inflamma-

tion may allow the involved tissue to defend and protect itself48.

Long term effect of PDT exposure
n human tissues.
Continued local and systemic influ-

ence of PDT once actual therapy has ceased. Proposing a trial A human clinical trial is a step in the right direction. We propose an

pen, phase I, dose-escalating and de-

escalating study to evaluate the safety and efficacy of porphyrin- or ALA- based photosensitiser-based PDT in patients suffering from deep SSIs following trauma and orthopaedic

perations. The primary objective of

this study will be to assess the safety and efficacy of the porphyrin- or ALA-based photosensitiser and determine the maximal tolerated dose;

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Licensee OA Publishing London 2012. Creative Commons Attribution License (CC-BY)

Competing interests: none declared. Conflict of interests: none declared. All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript. All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure. F : Jerjes W, Tan HB, Hopper C, Giannoudis PV. Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery. Hard Tissue. 2012 Nov 10;1(1):9. Table 3 The design of the proposed human trial Study design An open, phase I, dose-escalatj ng and de-escalatj ng study to evaluate the safety and effi cacy

f porphyrin- or ALA-based photosensitj

ser-based PDT in patj ents suff ering from deep SSIs post-trauma and orthopaedic operatj

ns. There will be a comparatj

ve arm. Product Porphyrin-or ALA-based photosensitj ser Centres University Teaching Hospital Key dates Antj cipated start of patj ent recruitment: June 2012 Antj cipated end of patj ent recruitment: December 2013 Antj cipated end of patj ent follow-up: January 2014 Primary objectj ve To assess the safety and effi cacy of the porphyrin- or ALA-based photosensitj ser and determine the maximal tolerated dose Secondary objectj ve To evaluate toxicity, including skin photosensitj vity To determine the pharmacokinetj cs of the drug in humans To document the antj bacterial actj vity Eligible patj ents Eligible patj ents will be included in 5 cohorts. The initj al interventj

n will involve incision and

drainage of the abscess, followed by the applicatj

n of the photosensitj
ser. The initj

al startj ng dose will be 2 mg/kg. The drug will be administered as a topical solutj

n to washout the infected wound.

The illuminatj

n will follow afu

er 60 min. The illuminatj

n will be with red light (laser 630 nm),

fl uence of 100–200 J/cm2 and fl uence rate of 10 mW/cm2. No antj bacterial cover will be administered afu er the interventj

Comparatj ve arm Eligible patj ents will have incision, debridement and drainage of the deep surgical site abscess with antj bacterial cover as indicated in the local hospital microbiology guidelines. Dose escalatj

Will proceed according to a modifi catj

n of Simon’s accelerated tj

tratj

n design. The number
f patj

ents recruited will depend on the dose limitj ng toxicity (DLT) experienced. A total of 10 patj ents will be included at each dose level if no more than 1 patj ent experiences DLT. Dose de-escalatj

Additj

nal cohorts may be added pending the outcome of the previous cohorts and discussions

between the investj gators. Discontj nuatj

from the study The discontj nuatj

n of a patj

ent from the study will occur in an event of infectj

n progression or DLT.

Target populatj

Patj ents with SSIs requiring incision, debridement and drainage post-trauma and orthopaedic

peratj
ns. SSIs to be subjected to PDT and verifi

ed by microbiological investj gatj

ns include

infectj

ns caused by Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, non-life

threatening Streptococcus pyogenes and Pseudomonas aeruginosa. Safety An assessment of all adverse events experienced since treatment visit and assignment of CTCAE grades to all those considered to be drug related will be done at all visits. Adverse events will be followed untj l resolved. Blood sampling will be performed to check standard haematological and biochemical parameters and vital signs. Fluorescence and skin photosensitj vity will be measured and followed untj l values return to normal. Study duratj

Patj ent enrolment is estj mated to take 4 weeks. The study is expected to last for 19 months. debridement and drainage post- trauma and orthopaedic operatio-

ns. SSIs to be subjected to PDT

and verified by microbiological investigations will include infecti-

ns caused by S. aureus, MRSA,

non-life threatening Streptococcus pyogenes and P. aeruginosa. Patients will be enrolled for a period of 4 weeks and performance status will be recorded pre- and post- intervention. Each patient in the in-tervention and control groups will undergo incision and

drainage. Topical photosensitiser

will be administered the secondary objective will be to evaluate the toxicity, including skin photosensitivity, in

rder

to determine the pharmacokinetics of the drug in humans and to document the antibacte-rial activity (Table 3). The target population will include patients with SSIs requiring incision

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Licensee OA Publishing London 2012. Creative Commons Attribution License (CC-BY)

Competing interests: none declared. Conflict of interests: none declared. All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript. All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure. F : Jerjes W, Tan HB, Hopper C, Giannoudis PV. Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery. Hard Tissue. 2012 Nov 10;1(1):9. Table 4 Patient recruitment and follow-up in the proposed trial VISIT NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 VISIT DAY Day

Day Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day 10 Day 11 Day 12 Day 13 Day 14 Day 21 Day 28 Patj ent demographics √ Informed consentj ng √ Inclusion/ exclusion √ Medical background √ √ √ √ √ Current medicatj

√ √ √ √ √ Pregnancy test √ Eye examinatj

√ √ √ √ √ Stop antj bacterial Rx √ Enrolment √ Bacterial strain √ √ √ √ √ Performance status √ √ √ √ √ √ Booked for surgery √ I&D performed √ Photosensitj ser administered √ Illuminatj

√ Pain scoring √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ Vital signs √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ Blood screening √ √ √ √ √ √ √ √ √ √ √ √ √ Blood and urine test PK √ √ √ √ √ √ √ √ √ √ √ Microassessment √ √ √ √ √ √ √ Photography √ √ √ √ √ √ √ √ √ √ √ √ √ Fluorescence √ √ √ √ √ √ √ √ √ √ √ √ √ Skin sensitj vity testj ng √ √ √ √ √ √ √ √ √ √ √ √ Bioluminescence √ √ √ √ √ √ √ √ √ √ √ √ √ Wound check √ √ √ √ √ √ √ √ √ √ √ √ √ Bactericidal eff ect √ √ √ √ Adverse events √ √ √ √ √

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Licensee OA Publishing London 2012. Creative Commons Attribution License (CC-BY)

Competing interests: none declared. Conflict of interests: none declared. All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript. All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure. F : Jerjes W, Tan HB, Hopper C, Giannoudis PV. Surgical site infections subjected to photodynamic therapy: a potential application in orthopaedic surgery. Hard Tissue. 2012 Nov 10;1(1):9. at the site

the infected surgical wounds in the intervent- ion groups, and illumination will follow within 30 min. Pain scor- ing, vital signs, blood screening, blood and urine PK and microb- iological assessment will be perf-

rmed on a regular basis. Asses-

sment of the outcome will be do- cumented through clinical photogra- phy, fluorescence and skin sensitivity testing, bioluminescence, wound check and assessment of the bacteri- cidal effect. Adverse events will be documented and subsequently re- ported (Table 4).

Conclusion

In an ideal world, surgical care should be state of the art with careful attention to strategies that avoid the develop- ment of SSIs. As mentioned previously,

ptimisation of patient medical status

(Table 5), appropriate aseptic tech- niques and surgical site preparation should help in preventing complica-

tions. Intraoperatively, application of

good basic surgical skills, accurate tis- sue dissection, suitable selection of suture materials and appropriate wound closure is paramount. However, when SSI does occur, the wound should be immediately open- ed, pus evacuated and debridement and washout of the dead tissue and debris should be performed. During this time, antimicrobial When resistance develops, a surge-

n usually seeks input from a local

microbiology department, which may suggest another medical ther- apy as guided by microscopy, cult- ure and sensitivity of the infected inflammatory sample acquired from the surgical wound. The new therapy is most likely to cover a wide spec- trum of pathogens, increasing the chance of developing multidrug- resistant strains. If the wound con- tinues to deteriorate, further surgical debridement may be indicated. Superficial and deep wound infec- tions can be treated using PDT by applying topical photosensitiser to the area followed by light illumination. For example, in burn infections which carry high mortality, Gram-positive bacteria, especially S. aureus, colonize these wounds at an early stage and are known to develop multidrug-resistance. These can be inactivated by PDT in in vitro and in vivo animal models.

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Table 5 Optimisation of patient medical status Maintaining close regulatj

n of blood sugar

Maintaining normal intraoperatj ve core body temperature Maintaining or increasing oxygen delivery to the wound by increasing the inspired oxygen concentratj

n administered to the patj

ent perioperatj vely Identj fying epidemics by common or uncommon microorganisms Establishing the correct use of prophylaxis Documentj ng costs, risk factors, and readmission rates Monitoring post-discharge infectj

ns and secondary consequences

Ensuring patj ent safety Preventj ng emergence of resistance cover is a requirement which will be guided by clinical wound healing and inflammatory markers.

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Critical review

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