Management of Surgical Site Infections

Limited evidence supports the use of medical imagining in the diagnostic evaluation of patients with a suspected organ/space (i.e. bone, joint, and implant) surgical site infection.

Radiography
There was one moderate quality study (Bernard 2004) evaluating the use of radiography for patients with suspected hip and knee prosthesis infection. This study showed poor agreement of radiography with the confirmed infections as both a “rule in” test and a “rule out” test. However Radiography is widely available and inexpensive relative to other imaging modalities, and the consensus of the workgroup is that radiographs be considered as the initial imaging exam for suspected cases of bone and/or implant infection interpreted in combination by a provider with skill and experience in interpretation of musculoskeletal radiographs to assess any and all radiographic features of infection, or other causes of the patient’s symptoms, without commenting on or recommending any single finding or combination of findings.

Radiolabeled Leukocyte Imaging
There were five high quality (Scher 2000, Simonsen 2007, Rand 1990, Pelosi 2004, Joseph 2001) and 10 moderate quality (Pons 1999, Glithero 1993, Kim 2014, Love 2004, Segura 2004, Chik 1996, El Espera 2004, Bernard 2004, Fuster 2011, Wolf 2003) studies evaluating the use of radiolabeled leukocyte imaging (with Indium-111 or Tc-99m hexamethylpropyleneamine oxine) for patients with suspected surgical site infections, predominantly patients with suspected hip and knee prosthesis infection. The duration of time between the initial surgery and the performance of the scan was either unclear or greater than 1 year, on average, for most of these studies. These studies showed inconsistent agreement of radiolabeled leukocyte imaging with the confirmed infections as “rule in” and “rule out” tests. For example, two high quality studies (Scher 2000, Simonsen 2007) showed moderate-strong agreement of radiolabeled leukocyte imaging with the reference standard as a “rule in” test, and weak-moderate agreement as a “rule out” test, for patients with suspected infected hip prostheses. By contrast, two high quality studies (Rand 1990, Scher 2000) showed only weak-moderate agreement of radiolabeled leukocyte imaging with the confirmed infections as a “rule in” test for patients with suspected infected knee prostheses. Stronger agreement with the reference test might be possible in combination with single photon emission computed tomography (Kim 2014) or Tc-99m sulfur colloid bone marrow scintigraphy (Love 2004). The consensus of the workgroup is that radiolabeled leukocyte imaging can be useful as a diagnostic tool (i.e., among other tests) as a “rule in” or “rule out” test for prosthetic joint infection, but its routine use for diagnosis of such infection is not justified, as there may be difficulties diagnosing insidious infections or differentiating infection from aseptic loosening. When radiolabeled leukocyte imaging is performed, the addition of bone marrow scintigraphy can help increase specificity.

Tc-99m-Diphosphonate Skeletal Scintigraphy (“Bone Scan”)
There were three moderate quality studies (Nagoya 2008, Battaglia 2011 and Segura 2004) evaluating the use of skeletal scintigraphy for patients with suspected hip and knee prosthesis infection occurring, on average, greater than one year following surgery. Although one study (Segura 2004) showed strong agreement of two-phase (blood pool and delayed imaging) skeletal scintigraphy with the confirmed infections as a “rule out” test, other studies showed moderate (Nagoya 2008, 3-phase scintigraphy) or weak (Battaglia 2011, unknown number of phases) agreement. Two of the studies (Battaglia 2011, Segura 2004) showed poor agreement of skeletal scintigraphy with the confirmed infections as a “rule in” test, while Nagoya 2008 showed moderate agreement of (3-phase scintigraphy) as a “rule in” test. Skeletal scintigraphy can be useful as a diagnostic tool (i.e., among other tests) as a “rule out” test for delayed (>1 year) prosthetic joint infection if radiolabeled leukocyte imaging is not available, but its role in the diagnosis of such infection is limited.

Positron Emission Tomography (PET) Imaging
There were four high quality (Chacko 2002, Chryssikos 2008, Aksoy 2014, DeWinter 2003) and 3 moderate quality (Kobayashi 2011, Love 2004, Wenter 2015, 2017) studies evaluating the use of F-18 fluorodeoxyglucose (FDG) PET imaging for patients with suspected surgical site infections, with most patients having suspected infection of orthopaedic implants including joint prostheses. The duration of time between the initial surgery and the performance of the scan was either unclear or greater than one year, on average, for most of these studies. These studies showed inconsistent agreement of PET imaging with the confirmed infections as a “rule in” test. For example, two high quality studies (Chacko 2002, Chryssikos 2008) showed strong agreement of FDG-PET imaging with the confirmed infections as a “rule in” test for prosthetic hip joint infection when uptake at the prosthesis-bone interface was used as the criterion for infection. However, another high-quality study (Aksoy 2014) showed that 39/39 hip and knee prostheses with aseptic loosening also showed increased FDG uptake, resulting in poor agreement with the confirmed infections as a “rule in” test for infection. A couple of high quality studies (Chacko 2002, DeWinter 2003) suggest that FDG-PET imaging may be useful as a “rule out” test, showing strong agreement with the confirmed infections; however, other studies show inconsistent results. Better agreement with the reference test might be possible in combination with computed tomography (Wenter 2015). The presence of metallic implants may also affect the diagnostic ability of FDG PET; one high quality study (DeWinter 2003) evaluating the use of FDG PET imaging for patients with suspected surgical site infections of the spine showed weak agreement of PET with the confirmed infections as a “rule in” test when metallic implants were present, but strong agreement as a “rule in” test when implants were not present. Although FDG-PET can be useful as a diagnostic tool (i.e., among other tests) as a “rule in” or “rule out” test for infection, its availability, expense, and current issues with reimbursement are limiting factors, and its routine use is not justified in this setting.

Cross-Sectional Imaging (Magnetic Resonance Imaging, Computed Tomography, Ultrasonography)
There is a lack of data regarding the use of cross-sectional imaging for the diagnosis of orthopaedic surgical site infection. Two moderate quality studies (Li 2016, Plodkowski 2013) evaluating the use of magnetic resonance imaging (MRI) for patients with suspected knee prosthesis infection showed moderate-strong agreement of MRI with the confirmed infections as a “rule in” test, but poor-moderate agreement as a “rule out” test. However, artifacts caused by metallic implants can be significant and limit detection of adjacent bone and soft tissue infection on MRI as well as on computed tomography (CT). Cross-sectional imaging can potentially be useful as a diagnostic tool in certain patients with suspected surgical site infection (e.g., to identify soft-tissue fluid collections) or to guide aspiration/biopsy procedures in such patients, but the potential value of a given imaging exam should be considered on a case-by-case basis.

Strong evidence supports that synovial fluid and tissue cultures are strong rule-in tests for the diagnosis of infection; negative synovial fluid and tissue cultures do not reliably exclude infection.

RATIONALE
Ten high quality studies were identified that addressed the role of culture in the diagnosis of surgical site infection; notably only two of the studies (Holinka, Puig-Verdie) included patients with infections involving orthopaedic sites other than hip or knee arthroplasties.

SYNOVIAL FLUID CULTURES
Three high quality studies (Gallo, Tomas, Spangehl) evaluated the yield of synovial fluid cultures in the diagnosis of prosthetic joint infection. Two of the studies found strong evidence to support fluid culture in the diagnosis of PJI (Tomas, Spangehl) while one found moderate evidence in support (Gallo).

INTRAOPERATIVE TISSUE CULTURES
Seven high quality studies evaluated the yield of intra-operative tissue cultures in the diagnosis of surgical site infection (Aggarwal, Holinka, Hughes, Panousis, Puig-Verdie, Spangehl, Trampuz). Of these, six of the seven studies revealed strong evidence in support of tissue culture to rule in the diagnosis of infection; one found the evidence to be moderate (Holinka). Additionally, the method by which the organism was grown was relevant. In these seven studies, there was variability in the performance of tissue culture in excluding infection. One high quality study evaluated the value of positive culture only from enrichment broth (Smith). Broth-only positive cultures showed poor correlation as a rule-in or rule-out test for infection. Two high-quality studies evaluated the performance of tissue cultures compared with swab cultures (Aggarwal, Spangehl). Both demonstrated better accuracy of tissue cultures over swab cultures.

NUMBER OF INTRAOPERATIVE CULTURES
Multiple tissue cultures should be collected to improve the accuracy of infection diagnosis. One moderate quality study (Atkins) quantified the number of samples needed to confirm the diagnosis of infection. A single positive culture for an organism of limited virulence was shown to have poor predictive value as a rule-in test. Two distinct positive cultures for the same organism provided strong evidence of periprosthetic infection.

DURATION OF CULTURE INCUBATION
One high quality (Schafer) and one moderate quality (Butler-Wu) study reviewed the duration of culture incubation for chronic periprosthetic infection. Both studies demonstrated improved yield when both aerobic and anaerobic cultures were incubated for 14 days.

PRIOR ANTIBIOTIC EXPOSURE
One high quality study evaluated the effect of prior antibiotic therapy on the yield of sonicate and tissue culture. The yield of culture was reduced when antibiotic therapy was administered within 14 days of culture collection.
 

Strong evidence supports that C-reactive Protein is a strong rule-in and rule-out marker for patients with suspected surgical site infections.

Multiple high-quality studies and meta-analysis of the study data support the use of C-reactive protein in the diagnosis of surgical site infection (Bottner et al 2007, Glehr et al 2013, Cipriano et al 2012, Jacovides et al 2011). Several moderate quality studies (Yi et al 2015, Piper et al 2009, 2010, Bedair et al 2011) also support its use. It was found to be both sensitive and specific in detecting periprosthetic infection and served as an accurate screening tool, with a positive or negative value demonstrating the likelihood of the presence or absence of infection. Studies vary with respect to the timing and thresholds used to diagnose infection. Both Yi et al 2015 and Bedair et al 2011 confirmed its utility during the early postoperative period. Despite this variation, it has proven its accuracy across investigations. While cutoff values at which an infection is diagnosed vary between studies, and based on time postoperatively it has been shown to be a superior screening test relative to other serological studies.

Limited strength evidence does not support the use of ESR, alone, to rule in and rule out surgical site infections due to conflicting data.

Multiple high-quality studies (Bottner et al 2007, Cipriano et al 2012, Panousis et al 2005) have demonstrated moderate to weak ability of ESR as a solitary test to diagnose or exclude surgical site infection. It is felt to be too variable with respect to time from surgery and in the presence of other confounding factors (such as inflammatory arthropathy) to be considered an accurate tool in diagnosis alone but may be considered as a tool to be used in conjunction with other tests.

Moderate strength evidence supports that clinical exam (i.e. pain, drainage, fever) is a moderate to strong rule-in test (i.e. high probability of presence of infection, if test is positive) for patients with suspected surgical site infections, but a weak rule-out test.

Patients with suspected surgical site infections should be assessed by a history and physical examination. Specific data were available for a structured history, presence of fever, and persistent wound drainage. One study of moderate evidence by Pons 1999 used a structured interview to evaluate 80 patients undergoing revision total hip arthroplasty of whom 16 patients had proven infection by histology and microbiology culture. A positive clinical examination was the presence of one of the following: current painful joint, history of chronic joint pain; or a history of wound drainage or fever lasting greater than 48 hours in the first month after primary surgery. A positive history had a sensitivity of 0.625 and specificity of 0.98.

One moderate strength study by Bernard 2004 evaluated the presence of fever and persistent drainage against the confirmed infections of positive culture in 230 patients undergoing revision joint surgery. Fever had a sensitivity of 0.53 and specificity of 0.90, and persistent drainage had a sensitivity of 0.53 and specificity of 0.90.

Strong evidence supports that the following factors are associated with an increased risk of infection: • Anemia • Duration of Hospital Stay • Immunosuppressive Medications • History of Alcohol Abuse • Obesity • Depression • History of Congestive Heart Failure • Dementia • HIV/AIDS

Anemia
There were eight high quality studies on the association of Anemia with the risk of SSI. Of these, five revealed an association between anemia and SSI. Four studies reviewed the risk of PJI and the 5th study reviewed the risk of infection and cervical spine fusion. Determinations were based on regression analyses of large data bases. Greenky et al 2012 identified the significant risk of anemia in PJI of development of SSI.

Duration of Hospital Stay
There were 11 high quality studies that examined the association between the length of hospital stay and the risk of SSI. Of these, seven revealed an association between increased length of stay and the risk of SSI. The studies were a range of multi-variant analysis and regression analysis. Three studies revealed that prolonged preoperative inpatient stays were related to increased risk of infection. Four studies revealed that prolonged post op hospitalization correlated with an increased risk of SSI. Longer hospital stays, including both pre-op and post-op stays correlated with increasing risk of SSI development.

Immunosuppressive Medication
Ten high quality studies were reviewed that looked at the effects of immunosuppressive agents. Of these, seven revealed a strong correlation between the use of immunosuppressive medications and an increased risk of SSI. These studies reviewed the effects of these medications on the risk of SSI associated with total joint replacement, spine surgery and ACL reconstruction. Momohara 2011 identified specifically that infliximab and etanercept combined with prolonged disease duration were associated with increased SSI risk. Giles 2006 identified increased risks of SSI associated with taking Tumor Necrosis Factor medications.

Alcohol abuse
Five high quality articles were reviewed. Three revealed a strong correlation between alcohol abuse and the risk of SSI. The articles used multi-variant analysis and looked a range of orthopaedic procedures and the effect of alcohol abuse on the risk of SSI on these procedures. Large multivariate studies from Cavanaugh 2015, Grammatico 2015 and Jain 2015, surveying thousands of patients, consistently show increased risks associated with increased alcohol consumption.

Obesity
Fourteen high quality studies showed a correlation between obesity and the risk of SSI. These studies used multivariant analysis showing that increasing BMI correlated strongly with the risk of post op infection. All of the studies showed significantly increased risk of SSI that correlate well with increased BMI. Several studies identified additional risks associated with increased BMI over 40. These risks include cardiac, pulmonary and systemic complications in additional to the increased SSI risks.

Depression
Four high quality studies confirmed a correlation between depression and the risk of SSI. All four studies used regression analysis. In each of the multivariate studies a correlation between clinically detected depression and increased risks of surgical site infection was identified.

Congestive Heart Failure
Two high quality studies revealed a strong correlation between the risk of CHF and SSI. These studies were all multi-variant regression analysis studies. Patients with CHF also have a higher risk of other vascular problems.

Dementia
Two large high quality studies using regression analysis revealed a strong correlation between Dementia and the risk of SSI in geriatric fractures patients. Dementia is an independent risk factor for occurrence of a surgical site infection

HIV/AIDS
Four high quality studies revealed a high correlation between the diagnosis of HIV/AIDs and the risks of SSI. There was a strong correlation between the diagnosis of HIV/AIDs and the risk of infection. Boylan revealed an increased risk of SSI of 17%.

Moderate strength evidence supports that patients meeting one or more of the following criteria are at an increased risk of infection after hip and knee arthroplasty: • Chronic Kidney Disease • Diabetes (conflicting evidence) • Tobacco Use/Smoking (conflicting evidence) • Malnutrition (conflicting evidence)

Chronic Kidney Disease
The risk of SSI in patients with chronic kidney disease (CKD) correlates positively with the severity of renal disease. Five high quality studies revealed using multivariate analysis and to identify the increased risk of SSI in patients with CKD. The severity of CKD and the description of dialysis and transplant patients were not identifiable within the studies.

Diabetes
26 high quality studies were reviewed. 13 of the studies showed a correlation between diabetes and the risk of SSI. 13 studies showed no correlation between diabetes and the risk of SSI. The strength of the recommendation was classified as “moderate” due to the divergence between the study findings. The impact of quality diabetic control could not be determined on the outcomes of the studies.

Tobacco Use
22 high quality studies were reviewed. 9 studies showed an association between tobacco use and increased risk of SSI. 12 studies showed no statistically significant differences between smokers and nonsmokers regarding associated risk of SSI. Many of the studies do not define the amount of tobacco
used, description of current versus former smokers, or the length of time for use of tobacco. While tobacco use is widely accepted as a risk factor for increasing the risk of SSI, of 22 HQ studies, 9 confirmed the correlation and 12 failed to confirm the correlation, and one showed a negative association with smoking and risk of SSI. This may be due to the definition of magnitude, effect size, heterogeneity of populations between studies.

Malnutrition
Malnutrition is a known risk factor for patients undergoing surgical procedures. Patients with malnutrition can suffer from a range of poor outcomes including increased risk of death, sepsis and poor wound healing. Six high quality articles were reviewed. Of these, three articles identified a correlation with increased risk of SSI. Bohl et al 2016 identified significantly increased risks of SSI associated with hypoalbuminemia. Grammatico et al 2015 also showed higher risks of SSI due to malnutrition.
 

Limited strength evidence supports that patients meeting one or more of the following criteria are at an increased risk of infection after hip and knee arthroplasty: • Cancer • Hypertension (conflicting evidence) • Liver Disease (conflicting evidence)

Cancer
Two high quality studies showed a correlation between cancer and the risk of SSI. Many of the studies did not specify the type of cancer or the staging of the cancer, which is why this recommendation was downgraded to “limited”. Cancer encompasses a wide variety of disorders, tissues and severity.

Hypertension
Seven high quality studies were reviewed. Four of the studies showed no correlation between hypertension and risk of surgical site infection. The magnitude of the effect of hypertension on the risk of SSI could not be determined from the included studies.

Liver Disease
Five studies reviewed the correlation between unspecified liver disease, cirrhosis and SSI. Three of the studies showed a correlation between liver disease and SSI in larger multivariant studies.

Moderate evidence supports that, in the setting of retained total joint arthroplasty, antibiotic protocols of 8 weeks do not result in significantly different outcomes when compared to protocols of 3 to 6-month duration.

The optimal duration of antibiotic therapy is not known. There was one high quality study (Lora-Tamayo 2016) and two low quality (Puhto 2012, Siqueira 2015) studies that evaluated short term antibiotics vs long term antibiotics in the setting of infected total joint arthroplasties. Both studies showed no significant difference in resolution of infection according to treatment duration.

In the study by Lora-Tamayo 2016, patients with staphylococcal infection were treated with debridement and implant retention and then randomized to either eight weeks or three (hips) or six (knees) months of antibiotic therapy. Resolution of infection was similar in both groups.

In the Puhto 2012 study, which included patients with a variety of microbes, they compared short term (two months total for hips and three months for knees) to their previously used long term (three months for hips and six months for knees). Again, they found no difference in success.

While antibiotic duration may not impact likelihood of cure, long term suppression may reduce the risk of relapse for patients who are not cured (Siqueira 2015). The benefit of chronic antibiotic suppression in this low-quality study was only seen for patients with Staphylococcus aureus infection managed with implant retention.

Moderate evidence supports that rifampin, as a second antimicrobial, increases the probability of treatment success for staphylococcal infections in the setting of retained orthopaedic implants.

Very few high quality studies were identified regarding the optimal antibiotic treatment regarding specific microbes. One high quality study (Zimmerli 1998) and one low-quality studies (El Helou 2010) addressed the addition of Rifampin and its effect on infection resolution in the setting of debridement and implant retention.

In the high quality study Zimmerli 1998 examined the role of rifampin in the setting of a retained fracture fixation implants and total joint prostheses with Staphylococcal infections. Patients who were randomized to receive rifampin as part of their treatment regimen had a lower risk of treatment failure.

In the absence of reliable evidence, it is the opinion of the work group that adjunctive treatment is of limited value in the management of surgical site infections.

1. There is consensus opinion that local delivery of antibiotics could be beneficial in the management of surgical site infections.
2. In the absence of available evidence, there is no benefit in the use of topically applied antibiotics.
3. The workgroup believes that there is lack of quality evidence for or against the use of negative pressure wound therapy in the treatment of surgical site infections.
4. The consensus of the workgroup is that there is no benefit in the use of antibiotics or antiseptics in irrigation solution in the management of these infections.
5. There is consensus opinion that appropriate soft-tissue coverage of open wounds is advantageous in the treatment of surgical site infections.
6. The workgroup believes that there is no quality literature that supports the use of adjuvant hyperbaric oxygen therapy in the treatment of patients with surgical site infections.
7. Further research is required to develop high-quality evidence to support the use of these adjuvant treatments.

In the absence of reliable evidence, it is the opinion of the work group that the definitive strategy to successfully treat surgical site infections is thorough debridement.

Risks/Harms
Barring the inherent risks of any surgery, there are no known harms associated with implementation of this recommendation.

Future Research
Although percutaneous drainage is an established first-line therapeutic consideration for a variety of infected fluid collections, there is a paucity of data supporting its use for fluid collections following orthopaedic surgical procedures. Future research may explore the value of percutaneous drainage of infected fluid collections in the setting of orthopaedic surgical site infection.

In the absence of reliable evidence, it is the opinion of the work group that irrigation and debridement are the cornerstones of successful management of surgical site infections and timely management is crucial, especially in the setting of orthopaedic implants.

Risks/Harms
The work group acknowledges the inherent risks of any surgery.

Future Research
Future higher quality research is necessary to explore the relationship between infection and surgical management especially regarding the optimal timing for successful outcome.

In the absence of reliable evidence, it is the opinion of the work group that implants should be removed if clinically safe and feasible due to the development of biofilm creating a barrier to successful treatment.

Regarding the role of implant removal associated with SSI, there is a paucity of research and evidence regarding the optimal implant management. The decision to retain or remove implants based on the clinical situation balancing morbity of removal with clearance of infection. While implant retention may be necessary in many cases, it is the recommendation of this committee that implants should be removed if clinically appropriate and feasible due to the development of biofilm as a barrier to successful treatment.

Risks/Harms
There are no know harms associated with implementation of this recommendation.

Future Research
The literature is lacking in quality evidence addressing the risks of retained implants. The total joint literature is attempting to address this question regarding prosthesis, but there remains a void in the research regarding other orthopaedic implants. Future studies should address this knowledge gap and attempt to identify the optimal timing and method of implant hardware exchange.

In the absence of reliable evidence, it is the opinion of the work group that patients with surgical site infections are optimally managed by a multidisciplinary team with expertise in the management of musculoskeletal infections. In addition to individual patient care management, multidisciplinary orthopaedic infection teams may strive to improve diagnostic capabilities, streamline care, create and maintain care pathways, coordinate discharge planning efforts, facilitate quality improvement efforts and improve patient education.

The composition of a multidisciplinary team will depend upon local resources; optimally the team should include orthopaedic surgeons and infectious disease experts. Others whose input would be valuable in some settings: include plastic surgeons and other wound care experts, pharmacists, nursing personnel, pathologists, microbiologists, radiologists, discharge planners, and home health providers. Infectious disease experts aid in the interpretation of diagnostic tests, selection of optimal antimicrobials based on microbial and host factors, and facilitation of safe antimicrobial administration oversight. Surgeons with soft tissue coverage expertise may be helpful. Physical therapists provide modalities to mitigate lost range of motion in associated joints, degreased muscle strength, general deconditioning and to control edema. Hospitalist medicine specialists and primary care providers are often necessary for optimization of patients’ overall health. Laboratory personnel can assure proper acquisition, handling, and testing of specimens. Early planning for discharge is coordinated by discharge planning staff, pharmacy technicians, and home health care services.