EPIDEMIOLOGY OF POSTSURGICAL INFECTION
The establishment of comprehensive national and international surveillance networks provides powerful epidemiological intelligence for monitoring changes in rates, risk factors and outcomes in patients undergoing orthopaedic surgery. Fourteen European countries participate in the orthopaedic modules within the European Centre for Disease Prevention and Control (ECDC) surgical site infection (SSI) surveillance network, the Healthcare-associated Infections Surveillance Network (HAI-Net). Latest data from the network gives an overall infection rate of 0.7% (95% confidence interval 0.7–0.8) within 1 year of surgery for patients undergoing knee replacement in 2010–2011 (intercountry range 0.2–3.2%) and 1.0% for hip replacement including hip hemiarthroplasty (intercountry range 0.4–11.4%, Fig. 2) . Similar rates are reported from Sweden's hip arthroplasty register, with a cumulative incidence of 0.9% based on data from 2005 to 2008, although based on deep infections and a 2-year follow-up . European SSI rates for hip and knee arthroplasty are in line with previous estimates from the National Healthcare Safety Network of the Centers for Disease Control and Prevention, 0.9% in hip and 1.3% in knee prosthesis from 2006 to 2008 . Although most European countries follow broadly harmonized surveillance methods, differences in intensity of case finding following discharge may explain some of the considerable intercountry variation in rates, particularly for hip replacement (Fig. 2). Differences in approaches to the clinical management of underlying conditions may also explain in part the variation in observed infection rates .
Fewer new studies have reported on infection rates following other types of orthopaedic surgery. A multicentre study in Italy assessed rates of infection in patients undergoing surgery for proximal humeral fracture repair . Of the 452 patients assessed, 4% developed deep infection following surgery. National surveillance data from Public Health England on spinal surgery, incorporating laminectomy, spinal fusion and repair of fractures or deformities, shows a low SSI rate of 1.1% (2009/10–2013/14) [8▪]. Similar SSI rates are reported for laminectomy across European HAI-net participating countries, 0.8% for 2010–2011 (intercountry range 0.2–8.3%) , consistent with earlier US data from National Healthcare Safety Network at 1.0% .
New epidemiological insights
A fascinating and simple study from Philadelphia sought to identify whether there is any seasonal pattern to infections following total joint replacement . Seven hundred and fifty operations conducted by a single surgeon were prospectively monitored to identify signs of infection. Although the total number of infections was small (n = 17) there was a notable seasonal gradient with the highest infection rates in summer, followed by autumn, winter and then spring.
Management of the increasing demand for total joint replacement is stimulating reappraisal of delivery of care to minimize costs and maximized patient benefit. Advances in clinical care have enabled a fall in length of admission for patients undergoing joint replacement over the past two decades, from 8/9 days to 3/4 days. Shorter stays for patients undergoing knee replacement are possible for selected patients . A large-scale observational study in the United States assessed the risk of complications in patients undergoing knee replacement between 1997 and 2009 [11▪]. Over 100 000 patients were studied to compare outcomes up to 2 years after surgery. Risk-adjusted infection rates were found to be higher in patients with extended length of stay (≥5 days) compared with early discharge groups, although there may be an element of reverse causality with the infection causing the extended stay in these patients. Similar infection rates between the day surgery, 1–2 day and 3–4 day stay patients suggests a lack of increased risk of infection in early discharge groups, although short stay surgeries were associated with longer-term increased readmission and revision rates compared with 3–4 day stays.
A spectrum of causative pathogens are responsible for orthopaedic infection, although typically staphylococci are dominant [8▪,12]. Assessing the procedure-specific distribution of pathogens forms the basis for surgical antibiotic prophylaxis strategies and as such warrants periodic or continuous monitoring [13,14▪▪,15▪].
Combined hip and knee prosthesis surveillance based on procedures undertaken in England in 2013/14 identify 30% of infections detected within 1 year of postoperative follow-up as polymicrobial, primarily Gram-negative and Gram-positive combinations. Of the monomicrobial infections (Fig. 3), 43% were Staphylococcus aureus and 4% specifically methicillin-resistant [8▪]. The relative frequency of methicillin-resistant S. aureus (MRSA) as the cause of infections following hip/knee arthroplasty has decreased over the past decade in England (Elgohari et al., unpublished observation). These decreases may relate to the impact of successive preadmission MRSA screening and decolonization policies in England [16,17].
Coagulase-negative staphylococci (CoNS) are also commonly associated with prosthetic joint infections, in particular late onset infections. However, a study from Sweden based on knee arthroplasty registry data found that CoNS were predominant in both early and late-onset infection [18,19]. Within English surveillance data, they comprised 30% of infections following knee prosthesis and 19% following hip prosthesis. Although Gram-negative bacteria, in particular Enterobacteriaceae and Pseudomonas spp., are typically less frequent causes of SSI in these procedures, worryingly, given their increased antibiotic resistance, the frequency of Enterobacteriaceae in England is increasing (Elgohari et al., unpublished observation), with 17% of hip and knee replacement infection in 2013/14 due to these organisms (Fig. 3). Few countries publish national-level data on the microbiology of SSIs and, as such, comparative recent data from other countries are lacking. A single-centre study from France reported a small change in Enterobacteriaceae as causative pathogens in osteoarticular infections from 13% in 2002 to 15% in 2011 . A further single-site study from Spain based on primary total joint arthroplasties reported a nonsignificant but marked increase in Gram-negative infections, from 21% in 2004 to 67% in 2010 .
Infections following repair of neck of femur (largely comprising hip hemiarthroplasty) follow a similar organism distribution, with S. aureus accounting for 46% of monomicrobial infections in England [8▪]. MRSA, however, accounts for a higher proportion of infections than hip and knee replacement, 20% in total, and may reflect the lack of opportunity for screening and decolonization prior to admission given the high proportion of emergency admissions following trauma [8▪]. Enterobacteriaceae accounted for 22% of cases in this surgical category.
Fewer estimates exist for causative pathogens in infections following spinal surgery. Of the cases identified through surveillance in England, S. aureus was again a dominant pathogen accounting for 44% of cases in 2013/14 followed by CoNS at 24% [8▪].
Recurrent prosthetic joint infections are known to occur in a sizeable proportion of patients who have interventions to manage primary infection . Understanding of the epidemiology of recurring infections, in particular whether they represent failed eradication of the primary episode or a new infectious episode is key to identifying preventive strategies. A study published in the Journal of Arthroplasty assessed 92 patients with recurrent prosthetic joint infection (hip and knee) and compared microbiological findings from repeated cultures to identify whether the same species (with the same antibiogram, if available) were identified from recurrent infections compared with the primary episode [23▪▪]. Twenty-nine of the 92 patients (32%) had evidence of persistent infections, although all barring 1 had additional species identified alongside the original pathogen. Gram-negative pathogens featured strongly among the new species cultured. Predictors of persistence were assessed, and interestingly, infection with S. aureus was the only significant factor once adjustments were made for other comorbid and clinical parameters. This finding has important clinical implications, highlighting the particular challenges for effective treatment of S. aureus infection.
PREVENTION AND CONTROL
There are several known risk factors that play a role in the development of SSIs in the perioperative phases of surgery. Although not all are modifiable, optimizing clinical factors such as antibiotic prophylaxis, hypothermia, blood glucose control, S. aureus nasal decontamination and decolonization, oxygen saturation and skin decontamination have a demonstrable impact on infection rates. Translation of national and international guidelines into quality standards and ward/theatre-level practical checklists also play a key role in assisting healthcare staff to deliver safe care . The UK National Institute for Health and Clinical Excellence produced a set of SSI quality standards in 2013 with seven main interventions hospitals should implement to reduce the risk of SSI based on preexisting guidance [25,26]. Continuous review and reassessment of the evidence base for best practice guidelines is essential given the dynamic nature of hospital epidemiology and new insights from the latest research findings.
New ECDC guidance based on a commissioned systematic review concludes that perioperative antimicrobial prophylaxis is one of the most effective measures for the prevention of SSIs . The guidance highlights key modalities shown to improve the compliance of healthcare professionals with appropriate administration (selection and indication), timing, dosage and duration of antimicrobial prophylaxis for the prevention of SSIs. Alongside the modalities are a set of indicators for hospitals to monitor compliance.
In 2013, new guidelines were published in the United States recommending that surgical antibiotic prophylaxis should be redosed intraoperatively at a frequency determined by the half-life of the antibiotic used [14▪▪]. This guidance may have implications for orthopaedic surgery depending on the antimicrobial prescribed in a given facility and their respective half-lives. Further evidence would help support the need for redosing, justifying the move to new practices.
In the United Kingdom, the Scottish Intercollegiate Guideline Network (SIGN) produced new guidance on antibiotic prophylaxis. This update focuses on the prevention of Clostridium difficile associated diseases through antimicrobial stewardship, namely indication for use of prophylactic antimicrobial agents, choice of agent and timing/frequency of administration. The guidance provides evidence for current practice and a framework for audit and economic evaluation [15▪].
The importance of maintaining ‘normothermia’ is emphasized in a new guidance from the Royal College of Anaesthetists. The guidance advises that warming devices should be available for use in the anaesthetic room, operating theatre and emergency department .
A randomized controlled trial from the United States has assessed the role of supplemental oxygen in reducing the risk of SSI. The study found perioperative and postoperative administration of supplemental oxygen reduced SSIs in patients undergoing open fixation of high-energy traumatic lower-extremity fractures . This is consistent with findings for patients undergoing colorectal surgery  but at odds with a systematic review and meta-analysis for caesarean section .
Optimal antiseptic agents for use in skin preparation remains under hot debate with diverging evidence over the relative benefits of povidone-iodine or chlorhexidine. Although earlier studies suggested superiority of 2% chlorhexidine combined with 70% isopropanol over other agents as a means to reduce superficial and deep SSIs, new research suggests the equivalence of chlorhexidine–alcohol and iodine–alcohol [32▪▪].
OBESITY AND POSTSURGICAL INFECTION
The impact of secular population trends in many countries towards increasing obesity rates is stimulating research and innovation across health disciplines. For orthopaedic surgery, the impact on postsurgical infection is multifaceted, affecting both the need for surgery and the risk of complication. The association between obesity and development of osteoarthritis is driving the demand for joint replacement, consequently increasing the pool of surgical patients susceptible to infection and shifting the demographic and comorbid profile of patients undergoing this surgery. Data published by the National Joint Registry for England, Wales and Northern Ireland demonstrate this secular trend with an increasing proportion of patients undergoing hip or knee replacement classed as obese or morbidly obese (BMI ≥ 30 kg/m2) (Fig. 4) .
Assessment of excess infection risk
Data from the United Kingdom quantify the impact of being overweight or obese on the risk of infection in knee and hip replacement, with elevation in SSI rates from 0.4 to 1% . Assessment of the population-attributable risk fraction for the development of SSI associated with BMI has been undertaken by a further recent study in the United Kingdom (Thelwall, unpublished observation). Among the 120 000 hip and knee replacement patients studied, approximately 12% of infections were due to patients being overweight. This provides a helpful measure of the proportion of excess infection risk that is likely to be attributable to obesity.
The impact of obesity on risk of infection following spinal surgery was assessed in a recent meta-analysis of 23 studies from across the globe [35▪]. Pooled odds ratios indicated a doubling in risk of infection associated with obesity. Complications were also more frequent amongst obese patients, with higher risk of thromboembolism and surgical revision.
Clinical management of obese surgical patients
Obesity-related knee osteoarthritis often affects both knees resulting in the need for prosthetic replacement of both knee joints. This is variously undertaken bilaterally, either sequentially by the same surgical team or in parallel by two teams, or as a two-stage unilateral procedure. Given the potential benefits of a simultaneous bilateral procedure, an observational retrospective study conducted over a 10-year period in Ohio compared the clinical outcomes of morbidly obese (BMI ≥ 40 kg/m2) patients undergoing simultaneous (two team) bilateral (n = 42) vs. unilateral (n = 35) knee replacement . Although the small sample size and observational nature of the study limit interpretation of results, the infection risk was equivalent in both groups, although there was some evidence of increased clinical complications in the bilateral group (in particular, blood loss). As such, further evidence is needed to conclude whether the benefits of a bilateral procedure, both for the patient and for the healthcare provider, outweigh any potential risks.
IMPACT OF INFECTION
Research continues in an attempt to quantify the impact of infections associated with orthopaedic surgery. As low-risk events, such studies by necessity require large sample sizes limiting the settings in which such research can be undertaken. National registries provide a valuable source of data on complications from surgery, in particular surgical revisions for the management of infection. Latest data from the National Joint Registry for England, Wales and Northern Ireland indicate 23% of revisions following knee replacement to be due to infection . A smaller yet sizeable proportion of hip revisions is also due to infection, 3% of single-stage and 82% of two-stage revisions in 2013.
A 5-year cohort study conducted in a specialist tertiary referral centre in USA assessed the impact of deep incisional/joint infections on healthcare utilization in patients undergoing primary total knee arthroplasty [37▪▪]. Compared with matched counterparts, patients undergoing two-stage revision for management of infection (n = 22) had longer total length of stay in hospital within 1 year of surgery (24 vs. 3 days). The mean total costs of hospitalization, further surgery and allied treatments in patients with infection were calculated at just over $116 000. Compared with the mean $28 000 for primary procedures not complicated by infection, this represents a substantial additional financial burden.
Few studies have robustly measured the impact of prosthetic joint infections on patient mortality. As such, the addition of findings from Zmistowski et al.[38▪▪] in the United States are a welcome addition to the literature. Their study compared patient mortality up to 5 years after revision of joint replacement according to indication for surgery. The authors found clear evidence of excess mortality in patients undergoing revision for management of infection compared with aseptic revision arthroplasty, with crude case fatality rates of 26 vs. 13%. With adjustment for comorbid, clinical and demographic factors, a five-fold excess mortality rate in patients with infection was found in the study.
The increasing rates of knee and hip replacement across many countries emphasize the importance of implementing strategies to minimize the risk of infection [1,39]. Although not all factors which increase risk of SSI are amenable to modification, identifying and understanding the interplay between them is critical to the formulation of prevention strategies. The staggering population rise in obesity is a good case in point, with research published in the last year emphasizing the excess risk of orthopaedic infection associated with obesity. Strategies to optimize clinical outcomes in overweight patients, including reducing infection risk, are urgently needed given the projected trends for population obesity.
Emerging trends from surveillance and research studies are indicating an increase in Enterobacteriaceae as a cause of orthopaedic infection. This is of particular concern given the antimicrobial resistance associated with these pathogens. Monitoring these aetiological changes, including antimicrobial resistance patterns, will become increasingly important as a means to inform local and national policies on first-line prophylactic agents for surgery.
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Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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8▪. Public Health England. Surveillance of surgical site infections in NHS hospitals in England 2013/14. London: Public Health England; 2014.
National surveillance data from acute hospitals in England showing trends in cumulative SSI incidence in orthopaedic surgery, microbial cause and procedure-specific distribution of pathogens in 2013/14. The report highlights the rise in Enterobacteriaceae.
9. Kane P, Chen C, Post Z, et al. Seasonality of infection rates after total joint arthroplasty. Orthopedics 2014; 37:e182–e186.
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A large-scale observational study in the United States based on Medicare data assessing risk of complications in >100 000 patients undergoing knee replacement between 1997 and 2009 according to the their length of stay in hospital. The study highlighted the complexity of undertaking outcomes of research using observational data given the fundamental differences in each of the study groups. After comprehensive risk adjustment to compensate for differences in baseline characteristics, patients with extended length of stay (≥5 days) were found to have a higher infection risk than early discharge groups (<5 days).
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In 2013, new guidelines were published in the United States recommending that surgical antibiotic prophylaxis should be redosed intraoperatively at a frequency determined by the half-life of the antibiotic. These guidelines are intended to provide practitioners with a standardized approach to the rational, safe, and effective use of antimicrobial agents for the prevention of SSIs based on currently available clinical evidence and emerging issues.
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Scottish guidelines (SIGN) produced to provide evidence-based recommendations to reduce inappropriate prophylactic antibiotic prescribing, focusing on the timing and administration of the antibiotic. It provides guidance on the indication for use of prophylactic antibiotic therapy for a range of surgical procedures and also includes guidance for the prevention of C. difficile infection.
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Multicentre study from USA assessing pathogen eradication in failed two-stage revision of infected knee arthroplasty (n = 92). Cultures were taken at different stages, and 31.5% of the patients were identified as having a pathogen identical to the original infecting organism. Repeat infections with a new organism were generally ascribed to gram-negative pathogens.
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A retrospective observational study was conducted at a single centre in the Netherlands involving patients who underwent breast, colon or vascular surgery, in which preoperative disinfection of the skin was undertaken with iodine–alcohol or chlorhexidine–alcohol. The result shows no difference in the rate of SSI after an instantaneous protocol change from iodine–alcohol to chlorhexidine–alcohol for preoperative topical antisepsis.
33. National Joint Registry for England, Wales and Northern Ireland. 11th Annual report 2014, surgical data to 31st December 2013. London: National Joint Registry and Healthcare Quality Improvement Partnership; 2014.
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35▪. Jiang J, Teng Y, Fan Z, et al. Does obesity
affect the surgical outcome and complication rates of spinal surgery? A meta-analysis. Clin Orthop Relat Res 2014; 472:968–975.
Meta-analysis assessing the impact of obesity on clinical outcome following spinal surgery. Thirty-two studies involving over 97 300 patients were included in this new assessment. Obesity was found to double the risk of infection (OR 2.33, 95% confidence interval 1.94–2.79).
36. Madsen AA, Taylor BC, Dimitris C, et al. Safety of bilateral total knee arthroplasty in morbidly obese patients. Orthopedics 2014; 37:e252–e259.
37▪▪. Kapadia BH, McElroy MJ, Issa K, et al. The economic impact of periprosthetic infections following total knee arthroplasty at a specialized tertiary-care center. J Arthroplasty 2014; 29:929–932.
Five-year cohort study conducted in a specialist tertiary referral centre in USA assessing the impact of deep incisional/joint infections in patients undergoing primary total knee arthroplasty. Twenty patients who underwent two-stage revisions for management of their infection were matched to an equal number of patients with the same risk profile having the same surgery on the same day performed by the same surgeon but without postoperative infection. Patients with infection had longer initial length of stay in hospital (mean 5 vs. 3 days) and total length of stay within 1 year of surgery (24 vs. 3 days). The mean total costs of hospitalization, further surgery and allied treatments in patients with infection were calculated at just over $116 000 ($28 000 for primary procedures not complicated by infection).
38▪▪. Zmistowski B, Karam JA, Durinka JB, et al. Periprosthetic joint infection increases the risk of one-year mortality. J Bone Joint Surg Am 2013; 95:2177–2184.
This single-centre university hospital study examined predictors of mortality in patients with perisprosthetic joint infection compared with those undergoing aseptic revision. Infection was found to increase 1-year mortality five-fold once causative organism, demography comorbidity, BMI and prior surgery were taken into account.
Keywords:Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
epidemiology; hip prosthesis; knee prosthesis; obesity; surgical wound infection