Advertisement

Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update

  • I. Uçkay
    Correspondence
    Corresponding author. Address: Infection Control Programme, University of Geneva Hospitals, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland. Tel.: +41 22 372 9834; fax: +41 22 372 3987.
    Affiliations
    Infection Control Programme and WHO Collaborating Centre on Patient Safety, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Switzerland

    Orthopaedic Surgery Service, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Switzerland

    Infectious Diseases Service, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Switzerland
    Search for articles by this author
  • P. Hoffmeyer
    Affiliations
    Orthopaedic Surgery Service, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Switzerland
    Search for articles by this author
  • D. Lew
    Affiliations
    Infectious Diseases Service, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Switzerland
    Search for articles by this author
  • D. Pittet
    Affiliations
    Infection Control Programme and WHO Collaborating Centre on Patient Safety, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Switzerland

    Infectious Diseases Service, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Switzerland
    Search for articles by this author
Published:February 18, 2013DOI:https://doi.org/10.1016/j.jhin.2012.12.014

      Summary

      Prevention of surgical site infection in orthopaedic surgery and bone trauma has some hallmarks not shared with other surgical disciplines: low inoculum for implant infections; pathogenicity of coagulase-negative staphylococci and other skin commensals; possible haematogenous origin; and long post-discharge surveillance periods. Only some of the many measures to prevent orthopaedic surgical site infection are based on strong evidence and there is insufficient evidence to show which element is superior over any other. This highlights the need for multimodal approaches involving active post-discharge surveillance, as well as preventive measures at every step of the care process. These range from preoperative care to surgery and postoperative care at the individual patient level, including department-wide interventions targeting all healthcare-associated infections and improving antibiotic stewardship. Although theoretically reducible to zero, the maximum realistic extent to decrease surgical site infection in elective orthopaedic surgery remains unknown.

      Keywords

      Introduction

      Healthcare-associated infections (HCAIs) are relatively rare in orthopaedic and trauma surgery compared with other surgical wards. The current lifelong infection risk for primary hip and knee arthroplasties is around 1% and increases to 2–5% for revision arthroplasties, shoulder arthroplasties, and fracture fixation devices (Table I). By contrast, the risk for surgical site infection (SSI) following colon surgery can be as high as 20%.
      • Rioux C.
      • Grandbastien B.
      • Astagneau P.
      The standardized incidence ratio as a reliable tool for surgical site infection surveillance.
      According to a large French prevalence study, the relative risk of SSI following genitourinary, cardiovascular, gynaecological, and gastrointestinal surgery compared with orthopaedic surgery was 2.1, 2.4, 2.6, 3.4, and 4.8, respectively.
      • Rioux C.
      • Grandbastien B.
      • Astagneau P.
      The standardized incidence ratio as a reliable tool for surgical site infection surveillance.
      SSIs are often associated with a high burden on patients and hospitals in terms of morbidity, mortality, and additional costs.
      • Whitehouse J.D.
      • Friedman N.D.
      • Kirkland K.B.
      • Richardson W.J.
      • Sexton D.J.
      The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost.
      Osteo-articular infections are also difficult to treat and associated with lifelong recurrence risks of around 10–20%, particularly in the case of multi-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA).
      • Teterycz D.
      • Ferry T.
      • Lew D.
      • et al.
      Outcome of orthopedic implant infections due to different staphylococci.
      Table ISurgical site infection in orthopaedic and bone trauma surgery (selected series)
      Adapted from Uçkay et al.4
      Type of orthopaedic surgeryRisk of surgical site infection
      Primary hip and knee arthroplasties0.8% Norwegian Register (73,000 arthroplasties)
      0.9% Finnish Register (4628 arthroplasties)
      0.9% Geneva Register (6101 arthroplasties)
      Elbow arthroplasties3.6% (2458 arthroplasties)
      Femoral osteosynthesis3.9% (541 operations)
      Pin track care7.0% (170 procedures)
      Foot and ankle surgery1.6% (555 operations)
      Hallux valgus (Lapidus procedure)1.3% (61 operations)
      Arthroscopies0.1–0.4% (552,258 procedures)
       Open fractures Gustilo grade I0.9%
       Open fractures Gustilo grade II1.9%
       Open fractures Gustilo grade III12–53%
       Amputation stump5–22%
      a Adapted from Uçkay et al.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      Prevention remains of the utmost importance. SSI prevention in orthopaedic surgery has certain specificities unknown to general surgery: low inocula for implant-related foreign body infections; pathogenicity of skin commensals; a possible haematogenous origin for some infections; and the necessity for a prolonged, post-discharge surveillance period with a minimal follow-up of one year for implant-related surgery.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • Uçkay I.
      • Pittet D.
      • Vaudaux P.
      • Sax H.
      • Lew D.
      • Waldvogel F.
      Foreign body infections due to Staphylococcus epidermidis.
      • Uçkay I.
      • Lübbeke A.
      • Emonet S.
      • et al.
      Low incidence of haematogenous seeding to total hip and knee prostheses in patients with remote infections.
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      Guideline for prevention of surgical site infection, 1999.
      The aim of this review was to focus on specific aspects of SSI prevention in adult orthopaedic and trauma patients and highlight important epidemiological features.

      Methods

      Literature review

      We conducted a literature search including search engines such as Google and electronic resources such as PubMed to identify English, French, and German language publications published before 31 December 2011 using the MeSH terms ‘infection’, ‘orthopaedic’ or ‘orthopedic’, and ‘prevention’ alone and in different combinations. PubMed yielded 1712 reports, and almost a million hits were displayed on Google. Results retrieved by PubMed were screened for pertinence and the presence of redundant information with an emphasis on original evidence-based literature published during the last five years. Older landmark papers were retained when the content was considered still valid. The internet search was restricted to the first 400 Google Scholar hits for every MeSH term.
      Review articles were included only if they summarized specific aspects of SSI prevention. Publications related to general surgery or multiple surgical disciplines were included only if they contained at least a subgroup of orthopaedic patients and patients undergoing clean surgery. Reference lists of identified articles were hand-searched to retrieve additional evidence-based literature. We excluded animal studies, studies with an outcome other than SSI, in vitro studies, and paediatric reports. Sterilization techniques of surgical instruments and issues related to prion diseases were not included as these were outside the scope of this review.

      Changing epidemiology – more resistant pathogens

      MRSA and meticillin-resistant coagulase-negative staphylococci infections (meticillin-resistant Staphylococcus epidermidis: MRSE) are a feared complication of implant-related surgery. Similar to MRSA, MRSE are reportedly increasing as nosocomial pathogens on orthopaedic wards.
      • Uçkay I.
      • Pittet D.
      • Vaudaux P.
      • Sax H.
      • Lew D.
      • Waldvogel F.
      Foreign body infections due to Staphylococcus epidermidis.
      According to the latest United States National Nosocomial Infections Surveillance report, 65% of coagulase-negative staphylococci have become resistant to meticillin during the past two decades.
      • Anonymous
      National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004.
      However, this rise in frequency is not necessarily ubiquitous. For example, we evaluated the epidemiology of osteo-articular infections due to MRSE and meticillin-susceptible coagulase-negative staphylococci at our institution over a 13-year observation period and found no increase in the proportion of MRSE infection.
      • Uçkay I.
      • Harbarth S.
      • Ferry T.
      • et al.
      Meticillin resistance in orthopaedic coagulase-negative staphylococcal infections.
      Hospitals and communities are also facing an increase in resistant Gram-negative colonization and infection.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.

      Pathogenesis of surgical site infections and risk factors

      Most SSIs are believed to be acquired during surgery.
      • Hanssen A.D.
      • Osmon D.R.
      • Nelson C.L.
      Prevention of deep periprosthetic joint infection.
      This is supported by the success of SSI prevention measures directed towards activities in the operating theatre and by reports demonstrating matching strains of pathogens from the surgeon's fingers and postoperative infection.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      To our knowledge, there are currently no data on the actual proportion of SSI acquired in the operating theatre versus postoperative care on wards. Risk factors for orthopaedic, implant-related SSI have been identified through epidemiological studies. Approximately half are endogenous and thus difficult to modify in the immediate pre- and postoperative phase.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      Systemic patient-related factors, such as malnutrition, diabetes mellitus, elevated serum glucose level, anticoagulation, smoking, or iatrogenic immune suppression (steroid therapy or the use of tumour necrosis factor-α inhibitors), play a role in wound-healing and infection risk for surgery in general, and probably also for orthopaedic surgery.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      Some factors can be influenced in the immediate pre- and postoperative period. For example, if possible, preoperative, high-dose corticosteroid therapy should be tapered before elective orthopaedic surgery, and glycaemia and anticoagulation optimized. Smoking cessation before and even after surgery is beneficial in terms of post-surgical complications potentially leading to healthcare-associated infection.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.

      Evidence-based preventive measures

      Several preventive measures are currently considered as very effective with a high level of evidence (grade IA) according to guidelines.
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      Guideline for prevention of surgical site infection, 1999.
      National Institute for Health and Clinical Excellence
      Prevention and treatment of surgical site infection. Guideline CG74.
      These include surgical hand preparation, antibiotic prophylaxis, multimodal interventions and, with some limitations, the surgeon's skill, and postponing an elective operation in the case of active remote infection.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      Guideline for prevention of surgical site infection, 1999.
      • Widmer A.F.
      • Rotter M.
      • Voss A.
      • et al.
      Surgical hand preparation: state-of-the-art.
      • Meehan J.
      • Jamali A.A.
      • Nguyen H.
      Prophylactic antibiotics in hip and knee arthroplasty.
      • Prokuski L.
      Prophylactic antibiotics in orthopaedic surgery.
      These items are often combined as multimodal intervention bundles (Table II).
      Table IIMain measures to prevent orthopaedic surgical site infection
      Adapted from Uçkay et al.4 and Mangram et al.7
      MeasureRelative surgical site infection reductionEvidence grading
      High impact
       Active post-discharge surveillance33%, FranceIA
       Multimodal intervention87%, The Netherlands

      65%, Houston, TX, USA

      10%, Madrid, Spain
      IA
       Adequate antibiotic prophylaxis73%, among orthopaedic patients in the USA

      81%, review of the literature
      IA
      Promising impact, needs further studies
       Nasal mupirocin, S. aureus decolonization43%, Pittsburgh, PA, USAIB
      a Adapted from Uçkay et al.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      and Mangram et al.
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      Guideline for prevention of surgical site infection, 1999.

      Surgical hand preparation

      Surgical hand preparation is probably the most important strategy for the prevention of orthopaedic SSI infections.
      • Widmer A.F.
      • Rotter M.
      • Voss A.
      • et al.
      Surgical hand preparation: state-of-the-art.
      For obvious ethical reasons, no randomized, controlled study has been conducted to compare surgery with and without previous surgical hand preparation sensu stricto and hygiene remains its counterpart on the wards. A cluster-randomized, cross-over trial reported the equivalence of surgical hand preparation with non-medicated soap and water versus alcohol-based hand rub on postoperative SSI rates.
      • Tanner J.
      • Swarbrook S.
      • Stuart J.
      Surgical hand antisepsis to reduce surgical site infection.
      Hand-rubbing with an alcohol-based formulation is considered as effective as scrubbing, for which the ideal duration remains unknown, although it is probable that the minimum duration is 2–3 min for both techniques.
      • Widmer A.F.
      • Rotter M.
      • Voss A.
      • et al.
      Surgical hand preparation: state-of-the-art.
      • Dharan S.
      • Pittet D.
      Environmental controls in operating theatres.
      In resource-poor areas, the rapid antimicrobial action, wider spectrum of activity, lower side-effects, and the absence of the risk of hand contamination by rinsing water might favour alcohol-based formulations.
      • Widmer A.F.
      • Rotter M.
      • Voss A.
      • et al.
      Surgical hand preparation: state-of-the-art.

      Antibiotic perioperative prophylaxis

      The effectiveness of preoperative antibiotic agents is taken for granted for most orthopaedic interventions, including bone trauma.
      • Meehan J.
      • Jamali A.A.
      • Nguyen H.
      Prophylactic antibiotics in hip and knee arthroplasty.
      • Matar W.Y.
      • Jafari S.M.
      • Restrepo C.
      • Austin M.
      • Purtill J.J.
      • Parvizi J.
      Preventing infection in total joint arthroplasty.
      • Gatell J.M.
      • Garcia S.
      • Lozano L.
      • Soriano E.
      • Ramon R.
      • SanMihuel J.G.
      Perioperative cefamandole prophylaxis against infections.
      Eventual exceptions are the removal of implant material where the number needed to prevent one SSI episode might be too small to justify routine administration. Antimicrobial prophylaxis for orthopaedic implant surgery helps to reduce SSI rates to 1–3% compared with 4–8% without antibiotics. Successful surgical antibiotic prophylaxis depends on a number of key principles.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • (i)
        The individual patient history of (pseudo)allergy must be considered.
      • (ii)
        First- or second-generation parenteral cephalosporins are sufficient; in the case of skin colonization with meticillin-resistant staphylococci, a glycopeptide antibiotic is recommended.
        • Uçkay I.
        • Harbarth S.
        • Peter R.
        • Lew D.
        • Hoffmeyer P.
        • Pittet D.
        Preventing surgical site infections.
        • Mangram A.J.
        • Horan T.C.
        • Pearson M.L.
        • Silver L.C.
        • Jarvis W.R.
        Guideline for prevention of surgical site infection, 1999.
        • Prokuski L.
        Prophylactic antibiotics in orthopaedic surgery.
        However, during the current epidemic of virulent Clostridium difficile strains in some parts of the world (e.g. North America or the UK) or local outbreaks due to vancomycin-resistant enterococci, some centres are moving away from cephalosporins that are thought to maintain the epidemic more than other antimicrobials. These are exceptional situations. In our opinion, this approach is certainly not valid for institutions without C. difficile problems.
      • (iii)
        Timing is of the utmost importance and prophylaxis should be given ideally within 30 min to 1 h before incision.
        • Matar W.Y.
        • Jafari S.M.
        • Restrepo C.
        • Austin M.
        • Purtill J.J.
        • Parvizi J.
        Preventing infection in total joint arthroplasty.
      • (iv)
        One dose is sufficient. Redosing may be justified for operating procedures longer than 4 h or in the case of significant blood loss, but it remains unknown whether a repeated administration should use the same or reduced dosage. Some older studies have advocated an improved outcome with duration of antibiotic prophylaxis up to 48 h. For example, Gatell et al. performed a randomized, double-blind trial to compare the efficacy of five doses of cefemandole (335 orthopaedic implant patients) with a single perioperative dose of cefemandole (382 implant patients). These were patients with orthopaedic foreign bodies, but elective arthroplasties were excluded. Fewer infections were observed in the group receiving five doses.
        • Gatell J.M.
        • Garcia S.
        • Lozano L.
        • Soriano E.
        • Ramon R.
        • SanMihuel J.G.
        Perioperative cefamandole prophylaxis against infections.
        However, the implants were different across study groups and the benefit of antibiotic prolongation beyond one dose has not been determined in recent trials or meta-analyses.
        • Slobogean G.P.
        • Kennedy S.A.
        • Davidson D.
        • O'Brien P.J.
        Single-versus multiple-dose antibiotic prophylaxis in the surgical treatment of closed fractures: a meta-analysis.
        It remains unknown whether standard doses should be routinely enhanced for obese patients, i.e. a body mass index >30 kg/m2.
        • Evans R.P.
        Surgical site infection prevention and control: an emerging paradigm.
        Different experts recommend a higher dose for obese patients, but this is an empirical opinion.

      Use of glycopeptide antibiotics in routine prophylaxis

      From an epidemiological standpoint, there is no evidence that a general glycopeptide prophylaxis would be superior to cephalosporins for patients without MRSA carriage.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • Prokuski L.
      Prophylactic antibiotics in orthopaedic surgery.
      A review of four randomized trials comparing the prophylactic use of teicoplanin versus a cephalosporin in settings with a high prevalence of meticillin-resistance among S. epidermidis showed similar infection rates in both groups.
      • Mini E.
      • Nobili S.
      • Periti P.
      Methicillin-resistant staphylococci in clean surgery. Is there a role for prophylaxis?.
      Another review and economic model of switching from non-glycopeptide to glycopeptide antibiotic prophylaxis for surgery in endemic MRSA settings failed to show an increased efficacy for the prevention of SSI due to meticillin-resistant staphylococci.
      • Cranny G.
      • Elliott R.
      • Weatherly H.
      • et al.
      A systematic review and economic model of switching from non-glycopeptide to glycopeptide antibiotic prophylaxis for surgery.

      Need for Gram-negative prophylaxis?

      By contrast with mass casualty situations and penetrating bone trauma, orthopaedic surgery is more concerned by patient skin pathogens and less by internal colonization with extended-spectrum beta-lactamase (ESBL)-producing Gram-negative rods, vancomycin-resistant enterococci (VRE), or multi-resistant non-fermenting rods (Pseudomonas aeruginosa, Acinetobacter spp.) compared with urological or visceral surgery.
      • Uçkay I.
      • Sax H.
      • Harbarth S.
      • Bernard L.
      • Pittet D.
      Multi-resistant infections in repatriated patients after natural disasters: lessons learned from the 2004 tsunami for hospital infection control.
      Gram-negative infections in clean orthopaedic surgery are rare and the majority appear to be caused by non-fermenting rods, which are by nature resistant to most beta-lactam antibiotics.
      • Seghrouchni K.
      • van Delden C.
      • Dominguez D.
      • et al.
      Remission after treatment of osteoarticular infections due to Pseudomonas aeruginosa versus Staphylococcus aureus: a case-controlled study.
      To our knowledge, there are no solid data to support a change of routine antibiotic prophylaxis for orthopaedic surgery in the case of colonization by these pathogens.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • Uçkay I.
      • Bernard L.
      Gram-negative versus gram-positive prosthetic joint infections.
      • Vergidis P.
      • Lesnick T.G.
      • Kremers W.K.
      • Razonable R.R.
      Prosthetic joint infection in solid organ transplant recipients: a retrospective case–control study.
      The future may reveal an increasing transplant recipient population undergoing arthroplasty surgery. Preliminary data suggest that SSI with Gram-negative pathogens may be more frequent in these highly immunocompromised patients than immunocompetent individuals.
      • Vergidis P.
      • Lesnick T.G.
      • Kremers W.K.
      • Razonable R.R.
      Prosthetic joint infection in solid organ transplant recipients: a retrospective case–control study.
      However, this is an emerging field of epidemiological research and needs more confirmation of preliminary findings.

      Antibiotic-containing cement for prophylaxis

      Engesaeter et al. reviewed the revision rates for 56,000 cemented and uncemented primary total hip replacements.
      • Engesaeter L.B.
      • Espehaug B.
      • Lie S.A.
      • Furnes O.
      • Havelin L.I.
      Does cement increase the risk of infection in primary total hip arthroplasty? Revision rates in 56,275 cemented and uncemented primary THAs followed for 0–16 years in the Norwegian Arthroplasty Register.
      Prostheses with antibiotic cement were associated with an overall lower revision risk. The benefit of antibiotic-loaded cement was further confirmed in the Finnish arthroplasty register and in large retrospective studies where cost-effective antibiotic cementing was reported to reduce SSI by up to 50%.
      • Jamsen E.
      • Huhtala H.
      • Puolakka T.
      • Moilanen T.
      Risk factors for infection after knee arthroplasty. A register-based analysis of 43,149 cases.
      • Parvizi J.
      • Saleh K.J.
      • Ragland P.S.
      • Pour A.E.
      • Mont M.A.
      Efficacy of antibiotic-impregnated cement in total hip replacement.
      Josefsson et al. studied the prophylactic effect of gentamicin-containing bone cement in a prospective multicentre study of infected total hip prostheses. A total of 812 episodes were randomly assigned to a systemic antibiotic group and 821 to local therapy with gentamicin-loaded cement. Follow-up of one to two years showed fewer infections (three versus 13) in the gentamicin-cement group.
      • Josefsson G.
      • Lindberg L.
      • Wiklander B.
      Systemic antibiotics and gentamicin-containing bone cement in the prophylaxis of postoperative infections in total hip arthroplasty.
      Chiu et al. conducted a prospective, randomized trial including 340 primary arthroplasties; one group was treated with simple cement and the other with cefuroxime-impregnated cement. Both groups received systemic antibiotic prophylaxis. The study showed fewer infections in the cefuroxime-cement group, but a comparison of cement-related antibiotic release versus systemic antibiotic administration failed to show a superiority of either regimen.
      • Chiu F.Y.
      • Chen C.M.
      • Lin C.F.
      • Lo W.H.
      Cefuroxime-impregnated cement in primary total knee arthroplasty: a prospective, randomized study of three hundred and forty knees.

      Open fractures

      Open fractures harbour a high risk of infection ranging from 10% to 50%, particularly Gustilo grade IIIc.
      • Gustilo R.B.
      • Anderson J.T.
      Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses.
      By contrast with the duration of preoperative antibiotic prophylaxis where a single parenteral dose is sufficient, almost no evaluation has been attempted for the ideal or minimal duration for open fractures. Most of the available literature relies on historical controls or is underpowered. To our knowledge, no study has attempted to distinguish between infection due to self-inoculation and potential hospital-acquired pathogens due to surgical interventions and prolonged length of hospital stay. Since surgery takes place in a contaminated site, most clinicians consider antibiotic use as pre-emptive therapy, not as mere prophylaxis.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      It is generally accepted that antibiotic medication should not be administered for more than 24 h for grade I and II fractures.
      • Gustilo R.B.
      • Anderson J.T.
      Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses.
      The minimum duration for grade III fractures ranges between one day and several weeks, but guidelines based on expert opinion and common sense recommend a maximum of 48 h or 72 h.
      • Hauser C.J.
      • Adams Jr., C.A.
      • Eachempati S.R.
      Surgical Infection Society guideline: prophylactic antibiotic use in open fractures: an evidence-based guideline.
      • Barie P.S.
      Breaking with tradition: evidence-based antibiotic prophylaxis of open fractures.
      In a case–control study of 1500 patients conducted at our institution, empirical antibiotic therapy and its duration were not related to infection. The infection risk was dominated by the extent of tissue damage according to the Gustilo grade. When compared with less than three days of a pre-emptive course of antibiotic therapy, more than three days did not show any tendency for protection against infection. Results were similar when stratified separately for grade I–III tibial fractures.

      Dunkel N, Uçkay I, Macedo M, Pittet D. Short duration of antibiotic prophylaxis in Gustilo grade III open extremities fractures does not enhance risk of subsequent infection. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, September 2010 (Abstract). In press.

      Dellinger et al. found no benefit of five days of prophylaxis with cefonicid or cefamandole compared with one day of cefonicid in open extremity fractures.
      • Dellinger E.P.
      • Caplan E.S.
      • Weaver L.D.
      • et al.
      Duration of preventive antibiotic administration for open extremity fractures.
      However, the ideal duration of antibiotic administration or the systematic use of negative pressure wound therapy in open fractures needs further research.
      • Stannard J.P.
      • Volgas D.A.
      • Stewart R.
      • McGwin Jr., G.
      • Alonso J.E.
      Negative pressure wound therapy after severe open fractures: a prospective randomized study.
      It is likely that the future will show an equivalence of shorter prophylactic therapies for open fractures.
      A second controversial issue is the choice of antibiotic agents for pre-emptive therapy in open fractures, especially in the presence of contamination with soil and debris. Most authors maintain the usual recommendations for second-generation cephalosporins. Although some combine these with aminoglycosides, quinolones, or regimens targeting anaerobic pathogens, it remains uncertain whether even a maximum antibiotic coverage may prevent infection, especially in tissues with debris and an inadequate blood supply.
      • Gosselin R.A.
      • Roberts I.
      • Gillespie W.J.
      Antibiotics for preventing infection in open limb fractures.
      Open fractures are contaminated by a panoply of antibiotic-susceptible pathogens, including Pseudomonas aeruginosa and S. aureus.
      • Seghrouchni K.
      • van Delden C.
      • Dominguez D.
      • et al.
      Remission after treatment of osteoarticular infections due to Pseudomonas aeruginosa versus Staphylococcus aureus: a case-controlled study.

      Dunkel N, Uçkay I, Macedo M, Pittet D. Short duration of antibiotic prophylaxis in Gustilo grade III open extremities fractures does not enhance risk of subsequent infection. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, September 2010 (Abstract). In press.

      The major challenge is that the clinician never knows which pathogen (known or hidden) will emerge as the one selected by ongoing antibiotic therapy, independent of the initial choice of the agent. Moreover, certain non-fermenting rods, such as Pseudomonas spp., may develop resistance to a single agent during therapy. To circumvent this danger, a hypothetical, broad, antibiotic coverage including glycopeptides and carbapenems is not feasible and would be very costly when applied to every grade III fracture. A retrospective study investigated the congruence of pre-infection microbiological samples of the first surgical exploration with the pathogen of infection and found very little concordance.
      • Faisham W.I.
      • Nordin S.
      • Aidura M.
      Bacteriological study and its role in the management of open tibial fracture.
      We confirmed these results by conducting a similar study and found zero concordance.

      Dunkel N, Uçkay I, Macedo M, Pittet D. Short duration of antibiotic prophylaxis in Gustilo grade III open extremities fractures does not enhance risk of subsequent infection. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, September 2010 (Abstract). In press.

      In other studies, the proportion of positive pre-infectious cultures ranges from 60% to 83%.
      • Robinson D.
      • On E.
      • Hadas N.
      • et al.
      Microbiologic flora contaminating open fractures: its significance in the choice of primary antibiotic agents and the likelihood of deep wound infection.
      One report advocated a repeat culture one day after debridement and observed that persistence of the same organism predicted a very high risk for future infection.
      • Robinson D.
      • On E.
      • Hadas N.
      • et al.
      Microbiologic flora contaminating open fractures: its significance in the choice of primary antibiotic agents and the likelihood of deep wound infection.
      However, a largely accepted confirmation of this approach is still lacking. Similar to the entire surgical field, the completeness of the surgical excision of contaminated tissue in open fractures is of the utmost importance and certainly more important than any considerations related to antibiotic administration.

      Prophylaxis before dental interventions

      Antibiotic prophylaxis for arthroplasty patients before dental or gingival interventions is a subject of debate among orthopaedic surgeons, doctors, and dentists. Indeed, several opinion leaders, scientific reviews, and cohort studies regularly deny any objective rationale for routine prophylaxis.
      • Uçkay I.
      • Pittet D.
      • Bernard L.
      • Lew D.
      • Perrier A.
      • Peter R.
      Antibiotic prophylaxis before invasive dental procedures in patients with arthroplasties of the hip and knee.
      Berbari et al. performed a prospective study including 339 arthroplasty patients undergoing a high- or low-risk dental procedure without antibiotic prophylaxis compared with 339 arthroplasty controls not undergoing a dental procedure. They showed that antibiotic prophylaxis in high-risk or low-risk dental procedures did not decrease the risk of subsequent total hip or knee joint prosthesis infection.
      • Berbari E.F.
      • Osmon D.R.
      • Carr A.
      • et al.
      Dental procedures as risk factors for prosthetic hip or knee infection: a hospital-based prospective case–control study.
      Infections of total hip or knee replacement due to haematogenous seeding following dental intervention are probably very rare.

      Surgeon's expertise

      Although subjective and difficult to analyse, the surgeon's expertise and surgical technique is certainly very important, but it is almost impossible to perform a randomized trial on this topic.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      However, differences in outcome between low- and high-volume surgeons have been observed after hip fractures: there is a lower mortality risk, lower rates of pneumonia, decubitus, and transfusion requirements in patients operated by experienced surgeons in the same setting.
      • Browne J.A.
      • Pietrobon R.
      • Olson S.A.
      Hip fracture outcomes: does surgeon or hospital volume really matter?.
      An excellent surgical technique is believed to reduce SSI by maintaining effective haemostasis while preserving adequate blood supply, gentle handling of tissue, removal of devitalized tissue, eradication of dead space, and appropriate management of the postoperative incision.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      Finally, the duration of surgery is a strong predictor of SSI − the longer the duration, the higher the risk.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • Matar W.Y.
      • Jafari S.M.
      • Restrepo C.
      • Austin M.
      • Purtill J.J.
      • Parvizi J.
      Preventing infection in total joint arthroplasty.
      • Saadatian-Elahi M.
      • Teyssou R.
      • Vanhems P.
      Staphylococcus aureus, the major pathogen in orthopaedic and cardiac surgical site infections: literature review.

      Other measures with high efficacy

      Active surveillance and multimodal interventions

      Multimodal strategies targeted at SSI prevention are associated with the highest impact. These interventions, sometimes in the form of so-called ‘bundles’ or safety checklists, do not need to cover all potential risk factors. For example, De Lucas-Villarubia et al. implemented admission screening for MRSA carriage, preoperative decolonization, improvement of antibiotic prophylaxis, and post-discharge surveillance.
      • Haynes A.B.
      • Weiser T.G.
      • Berry W.R.
      • et al.
      A surgical safety checklist to reduce morbidity and mortality in a global population.
      With these simple measures and an institution-wide awareness of the facility's MRSA problem, the baseline SSI rate of 10% was reduced to almost zero for 12 months.
      • De Lucas-Villarrubia J.C.
      • Lopez-Franco M.
      • Granizo J.J.
      • De Lucas-Garcia J.C.
      • Gomez-Barrena E.
      Strategy to control methicillin-resistant Staphylococcus aureus post-operative infection in orthopaedic surgery.

      Screening for S. aureus carriage with subsequent decolonization

      Screening and subsequent decolonization of patients before and after surgery remain controversial for general surgery.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      If the orthopaedic literature is considered separately, available data suggest that this may be cost-saving specifically in this group of patients and may allow the eradication of MRSA or meticillin-susceptible S. aureus carriage.
      • Matar W.Y.
      • Jafari S.M.
      • Restrepo C.
      • Austin M.
      • Purtill J.J.
      • Parvizi J.
      Preventing infection in total joint arthroplasty.
      • Rao N.
      • Cannella B.
      • Crossett L.S.
      • Yates Jr., A.J.
      • McGough 3rd, R.
      A preoperative decolonization protocol for Staphylococcus aureus prevents orthopaedic infections.
      • De Lucas-Villarrubia J.C.
      • Lopez-Franco M.
      • Granizo J.J.
      • De Lucas-Garcia J.C.
      • Gomez-Barrena E.
      Strategy to control methicillin-resistant Staphylococcus aureus post-operative infection in orthopaedic surgery.
      It is possible that the lower inoculum needed for implant infections might be one reason for more convincing results compared with other surgical disciplines. Kalmeijer et al. identified nasal carriage of S. aureus as a major risk factor for SSI among orthopaedic patients.
      • Kalmeijer M.D.
      • van Nieuwland-Bollen E.
      • Bogaers-Hofman D.
      • de Baere G.A.
      Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery.
      Wilcox et al. decreased the incidence of MRSA SSI from 2.3% to 0.3% after the introduction of intranasal mupirocin and triclosan showers before orthopaedic surgery.
      • Wilcox M.H.
      • Hall J.
      • Pike H.
      • et al.
      Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections.
      The same experience was repeated by others with nasal mupirocin use alone without concomitant body decolonization.
      • Gernaat-van der Sluis A.J.
      • Hoogenboom-Verdegaal A.M.
      • Edixhoven P.J.
      • Spies-van Rooijen N.H.
      Prophylactic mupirocin could reduce orthopedic wound infections. 1,044 patients treated with mupirocin compared with 1,260 historical controls.
      Kim et al. observed that nasal mupirocin and chlorhexidine showers significantly reduced the SSI risk among identified MRSA carriers hospitalized for elective orthopaedic surgery.
      • Kim D.H.
      • Spencer M.
      • Davidson S.M.
      • et al.
      Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery.
      Rao et al. reported that a preoperative decolonization protocol translated to an adjusted economic gain of US $230,000 to the facility.
      • Rao N.
      • Cannella B.
      • Crossett L.S.
      • Yates Jr., A.J.
      • McGough 3rd, R.
      A preoperative decolonization protocol for Staphylococcus aureus prevents orthopaedic infections.
      In practice, various institutional recommendations reflect different opinions. The more the recommendation is based on expert opinion, the more it favours screening, decolonization, or preoperative bathing.

      Widespread measures with low evidence

      Preoperative bathing or showering

      There is little evidence that preoperative showering with an antiseptic agent reduces SSI rates, although it has been shown to reduce skin colonization.
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      Guideline for prevention of surgical site infection, 1999.
      The US Centers for Disease Control and Prevention (CDC) recommend that patients shower or bathe with an antiseptic agent prior to surgery.
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      Guideline for prevention of surgical site infection, 1999.
      A Cochrane review including six trials with 10,000 participants found no evidence for the superiority of preoperative bathing and showering versus placebo.
      • Webster J.
      • Osborne S.
      Preoperative bathing or showering with skin antiseptics to prevent surgical site infection.

      Preoperative skin preparation

      Preoperative skin preparation in the operating theatre immediately before surgery is routinely implemented worldwide based on expert opinion.
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      Guideline for prevention of surgical site infection, 1999.
      To our knowledge, there is no consensus on the best antiseptic agent to be used.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • Saltzman M.D.
      • Nuber G.W.
      • Gryzlo S.M.
      • et al.
      Efficacy of surgical preparation solutions in shoulder surgery.
      • Ostrander R.V.
      • Botte M.J.
      • Brage M.E.
      Efficacy of surgical preparation solutions in foot and ankle surgery.
      Indeed, even with optimal preparation, true sterilization of the skin is impossible. A prospective, randomized, non-blinded study revealed a superiority of 2% chlorhexidine combined with 70% isopropyl alcohol versus 10% povidone-iodine for the prevention of SSI after clean-contaminated surgery, while another group found the contrary in a before–after study.
      • Darouiche R.O.
      • Wall Jr., M.J.
      • Itani K.M.
      • et al.
      Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis.
      • Swenson B.R.
      • Hedrick T.L.
      • Metzger R.
      • et al.
      Effects of preoperative skin preparation on postoperative wound infection rates: a prospective study of 3 skin preparation protocols.
      For several decades, povidone–iodine or chlorhexidine have been generally used for skin antisepsis. The development of bacterial resistance (mainly among staphylococci and P. aeruginosa) to mupirocin or chlorhexidine has been recognized and its clinical impact is the subject of ongoing studies.
      • Darouiche R.O.
      • Wall Jr., M.J.
      • Itani K.M.
      • et al.
      Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis.
      • Lee A.S.
      • Macedo-Vinas M.
      • Francois P.
      • et al.
      Trends in mupirocin resistance in meticillin-resistant Staphylococcus aureus and mupirocin consumption at a tertiary care hospital.
      • Milstone A.M.
      • Passaretti C.L.
      • Perl T.M.
      Chlorhexidine: expanding the armamentarium for infection control and prevention.
      At present, many centres have raised the chlorhexidine concentration to 4%. In theory, the recolonization of skin bacteria over time needs to be respected, particularly during long operative procedures. Again, no data are available regarding an eventual re-preparation during ongoing surgery, although this could prove difficult as most patients and adjacent skin areas are under drapes.

      Gloves, gowns, drapes and masks

      Sterile gloves and adhesive drapes are usually used in the operating theatre, but many gloves reveal tiny punctures after use that mostly go unnoticed by the operating team.
      • Widmer A.F.
      • Rotter M.
      • Voss A.
      • et al.
      Surgical hand preparation: state-of-the-art.
      Double-gloving or regular glove-changing might reduce the risk of punctures, but it does not guarantee their absence. A Cochrane review of 26 trials conducted on the practice of double-gloving as a barrier precaution was inconclusive in terms of SSI reduction.
      • Tanner J.
      • Parkinson H.
      Double gloving to reduce surgical cross-infection.
      Routine changing of the outer gloves during lengthy surgery is supported by expert opinion, but is not evidence-based.

      Hair removal

      Hair removal had its firm place in the 1999 CDC guidelines, but it has been questioned in a recent meta-analysis.
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      Guideline for prevention of surgical site infection, 1999.
      • Niel-Weise B.S.
      • Wille J.C.
      • van den Broek P.J.
      Hair removal policies in clean surgery: systematic review of randomized, controlled trials.
      If hair removal is performed, it should be done with clippers, not razors, immediately before surgery and not the previous evening.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • Niel-Weise B.S.
      • Wille J.C.
      • van den Broek P.J.
      Hair removal policies in clean surgery: systematic review of randomized, controlled trials.
      • Maksimovic J.
      • Markovic-Denic L.
      • Bumbasirevic M.
      • Marinkovic J.
      • Vlajinac H.
      Surgical site infections in orthopedic patients: prospective cohort study.

      Laminar airflow and ultraviolet light in the operating theatre

      Earlier studies and expert opinion in the 1970s suggested reduced SSI rates in orthopaedic implant surgery performed in ultraclean air facilities.
      • Lidwell O.M.
      • Lowbury E.J.
      • Whyte W.
      • et al.
      Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee replacement: a randomised study.
      • Ritter M.A.
      • Eitzen H.E.
      • Hart J.B.
      • French M.L.
      The surgeon's garb.
      Many hospitals in resource-rich countries are equipped with relatively expensive, vertical, horizontal, or mixed laminar airflow systems that reduce the bacterial burden in the air.
      • Whyte W.
      • Hodgson R.
      • Tinkler J.
      The importance of airborne bacterial contamination of wounds.
      Actual costs today range from US $60,000−90,000 for the installation of an airflow system into a new operating theatre.
      • Evans R.P.
      Current concepts for clean air and total joint arthroplasty: laminar airflow and ultraviolet radiation: a systematic review.
      Expert opinion considers vertical airflows as superior over horizontal ones regarding air turnover at and away from the surgical wound.
      • Evans R.P.
      Current concepts for clean air and total joint arthroplasty: laminar airflow and ultraviolet radiation: a systematic review.
      Conventional plenum ventilation theatres have air exchange rates of 30 times/h. By contrast, laminar flow theatres exchange the volume >300 times/h at a continuous positive pressure, resulting in a maximum of 10 colony-forming units (cfu)/m3, but with values as low as 1 cfu/m3.
      • Hooper G.J.
      • Rothwell A.G.
      • Frampton C.
      • Wyatt M.C.
      Does the use of laminar flow and space suits reduce early deep infection after total hip and knee replacement?: the ten-year results of the New Zealand Joint Registry.
      Few countries have set bacterial threshold limits for conventionally ventilated operating rooms, although most recommend 20 room air changes/h to obtain 50–150 cfu/m3 of air.
      • Evans R.P.
      Current concepts for clean air and total joint arthroplasty: laminar airflow and ultraviolet radiation: a systematic review.
      Strict attention to laminar airflow protocol is essential to avoid any paradoxical increases in infection rates if these concepts are disregarded.
      • Hooper G.J.
      • Rothwell A.G.
      • Frampton C.
      • Wyatt M.C.
      Does the use of laminar flow and space suits reduce early deep infection after total hip and knee replacement?: the ten-year results of the New Zealand Joint Registry.
      • Brandt C.
      • Hott U.
      • Sohr D.
      • et al.
      Operating room ventilation with laminar airflow shows no protective effect on the surgical site infection rate in orthopedic and abdominal surgery.
      In 1982, Lidwell et al. evaluated the effect of laminar airflow during 6781 hip arthroplasties and 1274 knee arthroplasties in a multicentre, prospective, randomized clinical trial.
      • Lidwell O.M.
      • Lowbury E.J.
      • Whyte W.
      • et al.
      Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee replacement: a randomised study.
      Infection occurred in 1.5% of the control group compared with 0.6% in the ultraclean-air group. Although these results seemed to provide irrefutable evidence for the efficacy of laminar airflow systems, the study design had flaws that included randomization irregularities and lack of patient stratification. Furthermore, there was no control over the use of prophylactic antibiotics. In the presence of prophylactic antibiotics, the independent effect of laminar airflow was a non-significant reduction of SSI prevalence from 0.8% in the control group to 0.3% in the ultraclean-air group.
      • Lidwell O.M.
      • Lowbury E.J.
      • Whyte W.
      • et al.
      Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee replacement: a randomised study.
      Recent clinical studies have already questioned its use in terms of SSI reduction. There is an inconsistent relationship between surface and air bacterial counts, indicating that the measurement of air contamination represents an unhelpful method for the assessment of surgical site contamination in laminar airflow units, including a failure to consider the effect of occlusive clothing. Retrospective nationwide analyses from Germany and New Zealand confirmed the absence of SSI reduction with laminar airflow versus no laminar airflow.
      • Brandt C.
      • Hott U.
      • Sohr D.
      • et al.
      Operating room ventilation with laminar airflow shows no protective effect on the surgical site infection rate in orthopedic and abdominal surgery.
      • Lowell J.D.
      • Kundsin R.B.
      • Schwartz C.M.
      • Pozin D.
      Ultraviolet radiation and reduction of deep wound infection following hip and knee arthroplasty.
      However, absence of scientific proof does not necessarily translate as absence of evidence and further studies are needed.
      Ultraviolet light (UVL) works by killing bacteria in the operative field rather than simply decreasing bacterial counts. Its efficacy has been shown in some studies, but not in others. Studies to date have been retrospective with a comparison of clinical experiences and historical controls.
      • Evans R.P.
      Current concepts for clean air and total joint arthroplasty: laminar airflow and ultraviolet radiation: a systematic review.
      SSI rates of hip arthroplasty fell from 3.1% to 0.53% with the use of UVL at intensities of 25 to 30 μW/s/cm2.
      • Lowell J.D.
      • Kundsin R.B.
      • Schwartz C.M.
      • Pozin D.
      Ultraviolet radiation and reduction of deep wound infection following hip and knee arthroplasty.
      Initial levels of UVL used were based on health and safety concerns, but more recent studies have used intensities of up to 300 μW/s/cm
      • Whitehouse J.D.
      • Friedman N.D.
      • Kirkland K.B.
      • Richardson W.J.
      • Sexton D.J.
      The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost.
      without reporting side-effects.
      • Ritter M.A.
      • Olberding E.M.
      • Malinzak R.A.
      Ultraviolet lighting during orthopaedic surgery and the rate of infection.
      UVL technology is considerably less expensive and easier to install and run than laminar airflow systems.
      • Evans R.P.
      Current concepts for clean air and total joint arthroplasty: laminar airflow and ultraviolet radiation: a systematic review.
      Thus, it may achieve the same objectives at much lower cost. In relation to its benefit, the CDC attribute a potentially unacceptable health risk for staff coupled with high costs and do not recommend its use.
      • Evans R.P.
      Current concepts for clean air and total joint arthroplasty: laminar airflow and ultraviolet radiation: a systematic review.
      In particular, all exposed skin should be protected and it is recommended that the operating team wear two caps, visors, and occlusive clothing.
      • Evans R.P.
      Current concepts for clean air and total joint arthroplasty: laminar airflow and ultraviolet radiation: a systematic review.

      Other measures

      There are several SSI preventive measures with promising results for visceral surgery, which have not yet been investigated formally in orthopaedic patients.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      These include supplemented oxygen during surgery, avoidance of intraoperative hypothermia, and hyperglycaemia, although the evidence for the latter is mixed.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      • Melling A.C.
      • Ali B.
      • Scott E.M.
      • Leaper D.J.
      Effects of preoperative warming on the incidence of wound infection after clean surgery: randomised controlled trial.
      Nevertheless, glycaemic control is used as a cornerstone of SSI prevention in many trials or settings.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.
      For example, Karunakar et al. showed that patients with mean serum glucose levels >220 mg/L carried a seven-fold increase for the risk of SSI following orthopaedic trauma than patients below this threshold.
      • Karunakar M.A.
      • Staples K.S.
      Does stress-induced hyperglycemia increase the risk of perioperative infectious complications in orthopaedic trauma patients?.
      By contrast, insulin should not be given routinely to reduce the SSI risk.
      • Uçkay I.
      • Harbarth S.
      • Peter R.
      • Lew D.
      • Hoffmeyer P.
      • Pittet D.
      Preventing surgical site infections.

      Behavioural aspects

      An emerging field of research is the change of routine and behavioural aspects in the operating theatre, often in collaboration with nurses.
      • Lee-Smith J.
      Can the orthopaedic team reduce the risk of infection?.
      • Woodhead K.
      • Taylor E.W.
      • Bannister G.
      • Chesworth T.
      • Hoffman P.
      • Humphreys H.
      Behaviours and rituals in the operating theatre.
      Epidemiological studies have identified noise provoked by the operating staff as an independent risk factor for SSI, and the first interventional studies equally incorporate behavioural aspects in their multimodal interventions.
      • Beldi G.
      • Bisch-Knaden S.
      • Banz V.
      • et al.
      Impact of intraoperative behavior on surgical site infections.
      To our knowledge, this research concerns general surgery so far and it has not been fully extended yet to orthopaedic surgery with one exception.
      • Beldi G.
      • Bisch-Knaden S.
      • Banz V.
      • et al.
      Impact of intraoperative behavior on surgical site infections.
      Douglas et al. experienced a 30% drop in SSI rates by implementing a multimodal programme consisting of a dedicated hospital hygiene team, elaboration of guidelines, staff education, avoidance of urinary catheter, active post-discharge surveillance, and limitation of traffic flow in the operating theatre.
      • Douglas P.
      • Asimus M.
      • Swan J.
      • Spigelman A.
      Prevention of orthopaedic wound infections: a quality improvement project.

      Post-surgical wound care

      There is a paucity of literature on surgical wound care and SSI prevention. Most importantly, the proportion of SSI acquired postoperatively on the ward by direct inoculation remains unknown. Experts suggest that this proportion may be as high as 10%, but there are no studies to support this at present. More than contributing to a mere decrease of SSI, dressings might influence the avoidance of blistering.
      • Cosker T.
      • Elsayed S.
      • Gupta S.
      • et al.
      Choice of dressing has a major impact on blistering and healing outcomes in orthopaedic patients.
      A Cochrane review assessed the effectiveness of various dressings and topical agents on surgical wound healing and infection and concluded that the quality of the trials was insufficient to determine any superiority of one protocol or one topical agent over another.
      • Vermeulen H.
      • Ubbink D.
      • Goossens A.
      • et al.
      Dressings and topical agents for surgical wounds healing by secondary intention.
      Other randomized studies comparing occlusive versus gauze dressings failed equally to detect superiority in terms of SSI reduction or wound-healing.
      • Shinohara T.
      • Yamashita Y.
      • Satoh K.
      • et al.
      Prospective evaluation of occlusive hydrocolloid dressing versus conventional gauze dressing regarding the healing effect after abdominal operations: randomized controlled trial.
      • Ubbink D.T.
      • Vermeulen H.
      • Goossens A.
      • et al.
      Occlusive vs gauze dressings for local wound care in surgical patients: a randomized clinical trial.
      • Wynne R.
      • Botti M.
      • Stedman H.
      • et al.
      Effect of three wound dressings on infection, healing comfort, and cost in patients with sternotomy wounds: a randomized trial.
      To our knowledge, the potential preventive role of silver-coated antimicrobial barrier dressings for non-infected surgical wounds is currently unknown.

      Conclusion

      All healthcare-associated infections must be targeted to reduce their incidence. This requires multidisciplinary commitment, dedicated teams, surveillance networks, and an optimum policy concerning the reduction of antimicrobial use to actual evidence-based levels. From an academic standpoint, we still lack a complete understanding of exactly when the surgical site starts to develop infection and the premises that drive microbial colonization to infection. There is certainly a need to improve the work-up of the pathogenesis, material development, and search for hidden risk factors inside large databases, including the implementation of well-designed and conducted randomized studies to help improve patient safety.

      Acknowledgement

      We thank R. Sudan for editorial assistance.

      Conflict of interest statement

      None declared.

      Funding sources

      None.

      References

        • Rioux C.
        • Grandbastien B.
        • Astagneau P.
        The standardized incidence ratio as a reliable tool for surgical site infection surveillance.
        Infect Control Hosp Epidemiol. 2006; 27: 817-824
        • Whitehouse J.D.
        • Friedman N.D.
        • Kirkland K.B.
        • Richardson W.J.
        • Sexton D.J.
        The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost.
        Infect Control Hosp Epidemiol. 2002; 23: 183-189
        • Teterycz D.
        • Ferry T.
        • Lew D.
        • et al.
        Outcome of orthopedic implant infections due to different staphylococci.
        Int J Infect Dis. 2010; 14: 913-918
        • Uçkay I.
        • Harbarth S.
        • Peter R.
        • Lew D.
        • Hoffmeyer P.
        • Pittet D.
        Preventing surgical site infections.
        Expert Rev Anti Infect Ther. 2010; 8: 657-670
        • Uçkay I.
        • Pittet D.
        • Vaudaux P.
        • Sax H.
        • Lew D.
        • Waldvogel F.
        Foreign body infections due to Staphylococcus epidermidis.
        Ann Med. 2009; 41: 109-119
        • Uçkay I.
        • Lübbeke A.
        • Emonet S.
        • et al.
        Low incidence of haematogenous seeding to total hip and knee prostheses in patients with remote infections.
        J Infect. 2009; 59: 337-345
        • Mangram A.J.
        • Horan T.C.
        • Pearson M.L.
        • Silver L.C.
        • Jarvis W.R.
        Guideline for prevention of surgical site infection, 1999.
        Infect Control Hosp Epidemiol. 1999; 20: 250-278
        • Anonymous
        National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004.
        Am J Infect Control. 2004; 32: 470-485
        • Uçkay I.
        • Harbarth S.
        • Ferry T.
        • et al.
        Meticillin resistance in orthopaedic coagulase-negative staphylococcal infections.
        J Hosp Infect. 2011; 79: 248-253
        • Hanssen A.D.
        • Osmon D.R.
        • Nelson C.L.
        Prevention of deep periprosthetic joint infection.
        Instr Course Lect. 1997; 46: 555-567
        • National Institute for Health and Clinical Excellence
        Prevention and treatment of surgical site infection. Guideline CG74.
        NICE, London2008
        • Widmer A.F.
        • Rotter M.
        • Voss A.
        • et al.
        Surgical hand preparation: state-of-the-art.
        J Hosp Infect. 2010; 74: 112-122
        • Meehan J.
        • Jamali A.A.
        • Nguyen H.
        Prophylactic antibiotics in hip and knee arthroplasty.
        J Bone Joint Surg Am. 2009; 91: 2480-2490
        • Prokuski L.
        Prophylactic antibiotics in orthopaedic surgery.
        J Am Acad Orthop Surg. 2008; 16: 283-293
        • Tanner J.
        • Swarbrook S.
        • Stuart J.
        Surgical hand antisepsis to reduce surgical site infection.
        Cochrane Database Syst Rev. 2008; 1 (CD004288)
        • Dharan S.
        • Pittet D.
        Environmental controls in operating theatres.
        J Hosp Infect. 2002; 51: 79-84
        • Matar W.Y.
        • Jafari S.M.
        • Restrepo C.
        • Austin M.
        • Purtill J.J.
        • Parvizi J.
        Preventing infection in total joint arthroplasty.
        J Bone Joint Surg Am. 2010; 92: 36-46
        • Gatell J.M.
        • Garcia S.
        • Lozano L.
        • Soriano E.
        • Ramon R.
        • SanMihuel J.G.
        Perioperative cefamandole prophylaxis against infections.
        J Bone Joint Surg Am. 1987; 69: 1189-1193
        • Slobogean G.P.
        • Kennedy S.A.
        • Davidson D.
        • O'Brien P.J.
        Single-versus multiple-dose antibiotic prophylaxis in the surgical treatment of closed fractures: a meta-analysis.
        J Orthop Trauma. 2008; 22: 264-269
        • Evans R.P.
        Surgical site infection prevention and control: an emerging paradigm.
        J Bone Joint Surg Am. 2009; 91: 2-9
        • Mini E.
        • Nobili S.
        • Periti P.
        Methicillin-resistant staphylococci in clean surgery. Is there a role for prophylaxis?.
        Drugs. 1997; 54: 39-52
        • Cranny G.
        • Elliott R.
        • Weatherly H.
        • et al.
        A systematic review and economic model of switching from non-glycopeptide to glycopeptide antibiotic prophylaxis for surgery.
        Health Technol Assess. 2008; 12: 1-168
        • Uçkay I.
        • Sax H.
        • Harbarth S.
        • Bernard L.
        • Pittet D.
        Multi-resistant infections in repatriated patients after natural disasters: lessons learned from the 2004 tsunami for hospital infection control.
        J Hosp Infect. 2008; 68: 1-8
        • Seghrouchni K.
        • van Delden C.
        • Dominguez D.
        • et al.
        Remission after treatment of osteoarticular infections due to Pseudomonas aeruginosa versus Staphylococcus aureus: a case-controlled study.
        Int Orthop. 2012; 36: 1065-1071
        • Uçkay I.
        • Bernard L.
        Gram-negative versus gram-positive prosthetic joint infections.
        Clin Infect Dis. 2010; 50: 795-796
        • Vergidis P.
        • Lesnick T.G.
        • Kremers W.K.
        • Razonable R.R.
        Prosthetic joint infection in solid organ transplant recipients: a retrospective case–control study.
        Transpl Infect Dis. 2012; 14: 380-386
        • Engesaeter L.B.
        • Espehaug B.
        • Lie S.A.
        • Furnes O.
        • Havelin L.I.
        Does cement increase the risk of infection in primary total hip arthroplasty? Revision rates in 56,275 cemented and uncemented primary THAs followed for 0–16 years in the Norwegian Arthroplasty Register.
        Acta Orthop Scand. 2006; 77: 351-358
        • Jamsen E.
        • Huhtala H.
        • Puolakka T.
        • Moilanen T.
        Risk factors for infection after knee arthroplasty. A register-based analysis of 43,149 cases.
        J Bone Joint Surg Am. 2009; 91: 38-47
        • Parvizi J.
        • Saleh K.J.
        • Ragland P.S.
        • Pour A.E.
        • Mont M.A.
        Efficacy of antibiotic-impregnated cement in total hip replacement.
        Acta Orthop Scand. 2008; 79: 335-341
        • Josefsson G.
        • Lindberg L.
        • Wiklander B.
        Systemic antibiotics and gentamicin-containing bone cement in the prophylaxis of postoperative infections in total hip arthroplasty.
        Clin Orthop Relat Res. 1981; 159: 194-200
        • Chiu F.Y.
        • Chen C.M.
        • Lin C.F.
        • Lo W.H.
        Cefuroxime-impregnated cement in primary total knee arthroplasty: a prospective, randomized study of three hundred and forty knees.
        J Bone Joint Surg Am. 2002; 84: 759-762
        • Gustilo R.B.
        • Anderson J.T.
        Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses.
        J Bone Joint Surg Am. 1976; 58: 453-458
        • Hauser C.J.
        • Adams Jr., C.A.
        • Eachempati S.R.
        Surgical Infection Society guideline: prophylactic antibiotic use in open fractures: an evidence-based guideline.
        Surg Infect (Larchmt). 2006; 7: 379-405
        • Barie P.S.
        Breaking with tradition: evidence-based antibiotic prophylaxis of open fractures.
        Surg Infect (Larchmt). 2006; 7: 327-329
      1. Dunkel N, Uçkay I, Macedo M, Pittet D. Short duration of antibiotic prophylaxis in Gustilo grade III open extremities fractures does not enhance risk of subsequent infection. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, September 2010 (Abstract). In press.

        • Dellinger E.P.
        • Caplan E.S.
        • Weaver L.D.
        • et al.
        Duration of preventive antibiotic administration for open extremity fractures.
        Arch Surg. 1988; 123: 333-339
        • Stannard J.P.
        • Volgas D.A.
        • Stewart R.
        • McGwin Jr., G.
        • Alonso J.E.
        Negative pressure wound therapy after severe open fractures: a prospective randomized study.
        J Orthop Trauma. 2009; 23: 552-557
        • Gosselin R.A.
        • Roberts I.
        • Gillespie W.J.
        Antibiotics for preventing infection in open limb fractures.
        Cochrane Database Syst Rev. 2004; 1 (CD003764)
        • Faisham W.I.
        • Nordin S.
        • Aidura M.
        Bacteriological study and its role in the management of open tibial fracture.
        Med J Malaysia. 2001; 56: 201-206
        • Robinson D.
        • On E.
        • Hadas N.
        • et al.
        Microbiologic flora contaminating open fractures: its significance in the choice of primary antibiotic agents and the likelihood of deep wound infection.
        J Orthop Trauma. 1989; 3: 283-286
        • Uçkay I.
        • Pittet D.
        • Bernard L.
        • Lew D.
        • Perrier A.
        • Peter R.
        Antibiotic prophylaxis before invasive dental procedures in patients with arthroplasties of the hip and knee.
        J Bone Joint Surg Br. 2009; 90: 833-838
        • Berbari E.F.
        • Osmon D.R.
        • Carr A.
        • et al.
        Dental procedures as risk factors for prosthetic hip or knee infection: a hospital-based prospective case–control study.
        Clin Infect Dis. 2010; 50: 8-16
        • Browne J.A.
        • Pietrobon R.
        • Olson S.A.
        Hip fracture outcomes: does surgeon or hospital volume really matter?.
        J Trauma. 2009; 66: 809-814
        • Saadatian-Elahi M.
        • Teyssou R.
        • Vanhems P.
        Staphylococcus aureus, the major pathogen in orthopaedic and cardiac surgical site infections: literature review.
        Int J Surg. 2008; 6: 238-245
        • Haynes A.B.
        • Weiser T.G.
        • Berry W.R.
        • et al.
        A surgical safety checklist to reduce morbidity and mortality in a global population.
        N Engl J Med. 2009; 360: 491-499
        • De Lucas-Villarrubia J.C.
        • Lopez-Franco M.
        • Granizo J.J.
        • De Lucas-Garcia J.C.
        • Gomez-Barrena E.
        Strategy to control methicillin-resistant Staphylococcus aureus post-operative infection in orthopaedic surgery.
        Int Orthop. 2004; 28: 16-20
        • Rao N.
        • Cannella B.
        • Crossett L.S.
        • Yates Jr., A.J.
        • McGough 3rd, R.
        A preoperative decolonization protocol for Staphylococcus aureus prevents orthopaedic infections.
        Clin Orthop Relat Res. 2008; 466: 1343-1348
        • Kalmeijer M.D.
        • van Nieuwland-Bollen E.
        • Bogaers-Hofman D.
        • de Baere G.A.
        Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery.
        Infect Control Hosp Epidemiol. 2000; 21: 319-323
        • Wilcox M.H.
        • Hall J.
        • Pike H.
        • et al.
        Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections.
        J Hosp Infect. 2003; 54: 196-201
        • Gernaat-van der Sluis A.J.
        • Hoogenboom-Verdegaal A.M.
        • Edixhoven P.J.
        • Spies-van Rooijen N.H.
        Prophylactic mupirocin could reduce orthopedic wound infections. 1,044 patients treated with mupirocin compared with 1,260 historical controls.
        Acta Orthop Scand. 1998; 69: 412-414
        • Kim D.H.
        • Spencer M.
        • Davidson S.M.
        • et al.
        Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery.
        J Bone Joint Surg Am. 2010; 92: 1820-1826
        • Webster J.
        • Osborne S.
        Preoperative bathing or showering with skin antiseptics to prevent surgical site infection.
        Cochrane Database Syst Rev. 2007; 2 (CD004985)
        • Saltzman M.D.
        • Nuber G.W.
        • Gryzlo S.M.
        • et al.
        Efficacy of surgical preparation solutions in shoulder surgery.
        J Bone Joint Surg Am. 2009; 91: 1949-1953
        • Ostrander R.V.
        • Botte M.J.
        • Brage M.E.
        Efficacy of surgical preparation solutions in foot and ankle surgery.
        J Bone Joint Surg Am. 2005; 87: 980-985
        • Darouiche R.O.
        • Wall Jr., M.J.
        • Itani K.M.
        • et al.
        Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis.
        N Engl J Med. 2010; 362: 18-26
        • Swenson B.R.
        • Hedrick T.L.
        • Metzger R.
        • et al.
        Effects of preoperative skin preparation on postoperative wound infection rates: a prospective study of 3 skin preparation protocols.
        Infect Control Hosp Epidemiol. 2009; 30: 964-971
        • Lee A.S.
        • Macedo-Vinas M.
        • Francois P.
        • et al.
        Trends in mupirocin resistance in meticillin-resistant Staphylococcus aureus and mupirocin consumption at a tertiary care hospital.
        J Hosp Infect. 2011; 77: 360-362
        • Milstone A.M.
        • Passaretti C.L.
        • Perl T.M.
        Chlorhexidine: expanding the armamentarium for infection control and prevention.
        Clin Infect Dis. 2008; 46: 274-281
        • Tanner J.
        • Parkinson H.
        Double gloving to reduce surgical cross-infection.
        Cochrane Database Syst Rev. 2006; (3):CD003087
        • Niel-Weise B.S.
        • Wille J.C.
        • van den Broek P.J.
        Hair removal policies in clean surgery: systematic review of randomized, controlled trials.
        Infect Control Hosp Epidemiol. 2005; 26: 923-928
        • Maksimovic J.
        • Markovic-Denic L.
        • Bumbasirevic M.
        • Marinkovic J.
        • Vlajinac H.
        Surgical site infections in orthopedic patients: prospective cohort study.
        Croat Med J. 2008; 49: 58-65
        • Lidwell O.M.
        • Lowbury E.J.
        • Whyte W.
        • et al.
        Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee replacement: a randomised study.
        BMJ. 1982; 285: 10-14
        • Ritter M.A.
        • Eitzen H.E.
        • Hart J.B.
        • French M.L.
        The surgeon's garb.
        Clin Orthop Relat Res. 1980; 153: 204-209
        • Whyte W.
        • Hodgson R.
        • Tinkler J.
        The importance of airborne bacterial contamination of wounds.
        J Hosp Infect. 1982; 3: 123-135
        • Evans R.P.
        Current concepts for clean air and total joint arthroplasty: laminar airflow and ultraviolet radiation: a systematic review.
        Clin Orthop Relat Res. 2011; 469: 945-953
        • Hooper G.J.
        • Rothwell A.G.
        • Frampton C.
        • Wyatt M.C.
        Does the use of laminar flow and space suits reduce early deep infection after total hip and knee replacement?: the ten-year results of the New Zealand Joint Registry.
        J Bone Joint Surg Br. 2011; 91: 85-90
        • Brandt C.
        • Hott U.
        • Sohr D.
        • et al.
        Operating room ventilation with laminar airflow shows no protective effect on the surgical site infection rate in orthopedic and abdominal surgery.
        Ann Surg. 2008; 248: 695-700
        • Lowell J.D.
        • Kundsin R.B.
        • Schwartz C.M.
        • Pozin D.
        Ultraviolet radiation and reduction of deep wound infection following hip and knee arthroplasty.
        Ann NY Acad Sci. 1980; 353: 285-293
        • Ritter M.A.
        • Olberding E.M.
        • Malinzak R.A.
        Ultraviolet lighting during orthopaedic surgery and the rate of infection.
        J Bone Joint Surg Am. 2007; 89: 1935-1940
        • Melling A.C.
        • Ali B.
        • Scott E.M.
        • Leaper D.J.
        Effects of preoperative warming on the incidence of wound infection after clean surgery: randomised controlled trial.
        Lancet. 2001; 358: 876-880
        • Karunakar M.A.
        • Staples K.S.
        Does stress-induced hyperglycemia increase the risk of perioperative infectious complications in orthopaedic trauma patients?.
        J Orthop Trauma. 2010; 24: 752-756
        • Lee-Smith J.
        Can the orthopaedic team reduce the risk of infection?.
        J Orthopaedic Nurs. 1999; 3: 95-98
        • Woodhead K.
        • Taylor E.W.
        • Bannister G.
        • Chesworth T.
        • Hoffman P.
        • Humphreys H.
        Behaviours and rituals in the operating theatre.
        J Hosp Infect. 2002; 51: 241-255
        • Beldi G.
        • Bisch-Knaden S.
        • Banz V.
        • et al.
        Impact of intraoperative behavior on surgical site infections.
        Am J Surg. 2009; 198: 157-162
        • Douglas P.
        • Asimus M.
        • Swan J.
        • Spigelman A.
        Prevention of orthopaedic wound infections: a quality improvement project.
        J Qual Clin Pract. 2001; 21: 149-153
        • Cosker T.
        • Elsayed S.
        • Gupta S.
        • et al.
        Choice of dressing has a major impact on blistering and healing outcomes in orthopaedic patients.
        J Wound Care. 2005; 14: 27-29
        • Vermeulen H.
        • Ubbink D.
        • Goossens A.
        • et al.
        Dressings and topical agents for surgical wounds healing by secondary intention.
        Cochrane Database Syst Rev. 2004; (2):CD003554
        • Shinohara T.
        • Yamashita Y.
        • Satoh K.
        • et al.
        Prospective evaluation of occlusive hydrocolloid dressing versus conventional gauze dressing regarding the healing effect after abdominal operations: randomized controlled trial.
        Asian J Surg. 2008; 31: 1-5
        • Ubbink D.T.
        • Vermeulen H.
        • Goossens A.
        • et al.
        Occlusive vs gauze dressings for local wound care in surgical patients: a randomized clinical trial.
        Arch Surg. 2008; 143: 950-955
        • Wynne R.
        • Botti M.
        • Stedman H.
        • et al.
        Effect of three wound dressings on infection, healing comfort, and cost in patients with sternotomy wounds: a randomized trial.
        Chest. 2004; 125: 4349