This chapter focuses on periprosthetic total hip infection in the early postoperative period, defined as within 6 weeks from surgery. Yi et al. [1] reviewed 6033 consecutive primary THAs and identified 73 patients (1.2%) who underwent reoperation for any reason within the first 6 weeks postoperatively. Thirty-six (0.59%) of these patients were infected according to modified Musculoskeletal Infection Society criteria. Studying PJI in the early postoperative period did not have the same share as did chronic PJI in the literature.

Total hip arthroplasty (THA) is considered one of the most successful operations in modern medicine and has positively impacted the life of many patients, providing mobility and relief from pain for a wide range of hip conditions. One of the biggest threats to the success of this procedure is periprosthetic joint infection (PJI), which can convert a highly beneficial procedure into one of frustration and disability for the patient. Over 50 years ago, PJI rates were reported to be as high as 7% [2]. Improvements in surgical technique, operating room environment, body exhaust systems, as well as perioperative care (including skin preparation, antibiotic prophylaxis, and wound management) have led to substantial reductions in the risk of PJI. Currently, the risk is approximately 1–2%; however this rate has not changed substantially in decades [3] and represents thousands of cases each year. The cost of treatment for such cases is much higher than treatment for other complications of THA, up to $50,000 more per case, thus imposing a huge strain on the already struggling healthcare system [4].

Internationally, there are similar reports of PJI complicating total hip arthroplasty from the UK, France, Germany, and Australia [5]. In the UK, 12–15% of hip revisions are secondary to PJI [5]. An in-depth study from France measured the direct costs due to revisions of infected THAs, and calculated these at just over 32,000 Euros per patient, representing 3.6 times the cost of the primary procedure and 2.6 times the cost of revisions for other indications [6]. A small study from Australia assessed the longer term impact of infection on several quality-of-life measures in patients undergoing hip and knee replacement and found substantial detriments to mobility, independent living, and psychological health in patients whose surgery was complicated by infection [7]. In the United States, PJI complicates 1.63% of primary THAs within the first 2 years in the Medicare population. The Mayo Clinic reported a 1.7% infection rate in primary THAs over a 28-year period (1969–1996) [8].

Understanding the incidence of causative organisms is key to prophylactic antibiotic choice. Parvizi et al. [9] reviewed 9245 primary joint replacements. The most commonly isolated organisms in the order of frequency were methicillin-resistant Staphylococcus aureus (MRSA) (19%), methicillin-sensitive Staphylococcus aureus (19%), methicillin-resistant Staphylococcus epidermidis (11%), and methicillin-sensitive Staphylococcus epidermidis (8%). Fifty-three percent of the Staphylococcal organisms were resistant to methicillin. Gram-negative organisms were isolated in 11%, with Escherichia coli and Klebsiella pneumoniae being the most common. Polymicrobial infection occurred in four patients (5%) [9].

Although modern surgical techniques and antibiotic prophylaxis have significantly lowered the incidence of PJI, it has not been eliminated. Therefore, identifying and modifying the preoperative risk factors can help mitigate the incidence of PJI. These risk factors can be divided into host-related factors and hospital-related factors.

Host factors are related to both general health and local conditions of the tissues. General health concerns are variable, but they all share one common effect, which is decreasing or modifying the host immunity. Obesity increases infection risk by 3–4.2-fold, with every 1 kg/m² increase in body mass index. In another study, obesity and morbid obesity increased PJI by 2.6- and 9.1-fold, respectively. Diabetes mellitus has been identified as an independent risk factor for PJI, with an 11% increased infection rate associated with perioperative poor glycemic control [10]. This study suggests that tight perioperative glycemic control can reduce PJI after THA. Metabolic syndrome includes the presence of increased waist circumference, hypertension, diabetes mellitus, and dyslipidemia. Forty percent of the population over 60 years of age in the United States has metabolic syndrome with the incidence likely higher among the joint replacement population [11]. Metabolic syndrome is associated with increased systemic levels of acute-phase response cytokines and cortisol, suggesting a miss-regulated immune response with an inability to mount an effective attack against infectious organisms. It is interesting that the risk of postoperative complications in patients with metabolic syndrome was greater than the sum of each individual component, suggesting synergistic effect of its concomitant elements [12]. Malnutrition is also associated with an increased risk of both chronic and acute PJI [13] and is known to affect innate immunity and normal immune response by altering both humeral and cell-mediated immunity. Malnutrition can be screened for via serum albumin, prealbumin , transferrin, and/or total lymphocyte counts. Paradoxical malnutrition is common among obese and normal-weight patients. If identified preoperatively, malnutrition must be corrected, even if that means delaying the surgery.

Advanced age is another independent, uncorrectable risk factor that decreases patient immunity, exposing them to more risk of PJI [14]. Atrial fibrillation and myocardial infarctions have also been shown to be independent risk factors for PJI in a review of large series, possibly related to aggressive heparin anticoagulation and/or infirm nature of these patients [9, 15]. Autoimmune diseases like rheumatoid arthritis are associated with a 2.6-fold increase in infection rates compared to patients with osteoarthritis [16]. Psoriasis is another autoimmune disease associated with increased infection risk. Organ failure, like chronic renal failure, patients on dialysis, and those with liver, heart, or kidney transplant, are at increased risk for infection. Patients with malignancy and those with human immunodeficiency virus, particularly patients with CD4 counts below 240 cells/mm³, are also at increased risk [17–19]. Patient colonization with MRSA is a growing concern in modern arthroplasty with the prevalence of MRSA in the community found to be 0.6–6% in current hospital screening programs [20]. The presence of urinary tract infection (UTI) after surgery is also associated with increased risk for infection [9]. However, performing preoperative urine screening has been proven to be unnecessary [21, 22]. Smoking has been shown to increase the risk for wound complications and PJI, with a randomized controlled trial from Denmark demonstrating that cessation or at least 50% reduction in smoking decreased wound complications from 30 to 5% (p < 0.001) in patients undergoing total joint replacement [23]. Smoking cessation should be considered for all patients.

Postoperative host factors that increase the risk for PJI include hematoma formation and profuse wound drainage with an odds ratio of 11.8 and 1.32, respectively. The risk of deep infection subsequent to superficial infection is 10%, with the same organism being isolated from both sites in most instances [24].

Revision surgery carries a threefold increase in the risk for infection [25, 26]. Peel et al. [27] have shown that previous PJI increases the risk of infection at the same site by 36-fold, while the incidence of developing PJI in a subsequent joint replacement was 15% [28]. Even after successfully treating a PJI, the relative risk of developing an infection in a subsequent total joint was 21, significantly higher than patients with no such history [29].

Hospital-related risk factors have been studied as a function of the annual volume of THAs. In a review of 5000 Medicare patients, a 69% reduction in the rate of deep infection and dislocation was correlated with hospitals in which more than 100 THAs were performed annually. Factors associated with decreased complication rates included private hospitals, academic institutions, dedicated orthopedic nursing teams, and laminar airflow in the operating room. The most significant determinant is increased surgeon caseload, which in turn affects the duration of surgery, tissue handling, blood loss, need for blood transfusion postoperatively, operating room traffic, and attention to sterility [30, 31].

Prevention of PJI in the early postoperative period (first 4–6 weeks postoperatively) revolves around identifying and if possible eliminating and/or modifying most of the above-mentioned risk factors. The single most important factor in reducing postoperative wound infections is antibiotic prophylaxis. Optimizing antibiotic coverage can protect the local tissue from bacterial colonization at the time of surgery and requires both optimal timing and type of antibiotic used. An effective bactericidal concentration of antibiotic should be present in tissues and serum at the time that surgery begins. The highest serum and bone tissue levels appear to be achieved 35–40 min after intravenous antibiotic injection [32]. For prolonged operations (more than 2.5 h), and/or increased blood loss (more than 1000 cm³), a second dose of IV antibiotic appears to reduce the risk of infection [33]. The duration of postoperative antibiotics has been debated, but multicenter studies have shown no difference between 24 h, 3 days, and 7 days [34, 35]. A shorter course of antibiotic would be more cost effective, and reduce side effects and possible development of resistance to frequently used agents. Since it is very difficult to provide coverage for all organisms causing infections, it is recommended to use an agent with excellent protection against the most common gram-positive organisms (i.e., Staphylococci and Streptococci). The antibiotic of choice also must have a low side effect profile, be well tolerated by patients, be less likely to have resistance development, and possess an appropriate half-life. As such, first-generation cephalosporins (e.g., cefazolin ) is optimal and remains the antibiotic of choice for most patients. In a randomized controlled study, cefazolin use before and after surgery reduced the incidence of PJI from 3.3 to 0.9% compared to placebo [36]. For patients with penicillin allergy, vancomycin or clindamycin can be used as a substitute. Vancomycin combined with an antibiotic covering gram-negative organisms (e.g., gentamicin) can be utilized in patients who are colonized with MRSA. Nasal decolonization with mupirocin has been shown to decrease rates of PJI by 50% among patients who test MRSA positive during the preoperative screening [37].

From an operative standpoint, frequent irrigation of the wound with pulsatile lavage can be helpful [38]. Additional factors to consider include the use of dilute betadine lavage (which has been shown to decrease the risk of infection [39], frequent glove change, and suction tip change). Operative environment control through vertical laminar airflow, body exhaust suites, and reinforced Gore-Tex gowns decrease dissemination of shed bacteria by the surgical team. Limiting operative room personnel and decreasing room traffic also mitigate the risk of infection [40–42].

Acute PJI diagnosis can be challenging with symptoms being easily confused with normal inflammatory response to surgery.

Evaluation of the patient with a possible PJI should include a thorough history and physical examination. Items that should be obtained in the history include the types of prostheses, date of implantation, past surgeries on the joint, history of wound healing problems following prosthesis implantation, remote infections, current clinical symptoms, drug allergies and intolerances, comorbid conditions, prior and current microbiology results from aspirations and surgeries, and antimicrobial therapy for the PJI including local antimicrobial therapy. While being febrile is traditionally associated with infection, it is important to distinguish fever resulting from infection from a normal postoperative course [43, 44]. A recent study of 100 patients undergoing THA and 100 patients undergoing TKA showed that the normal postoperative febrile response peaked on the first postoperative day and normalized by the fifth day. In 19% of patients, the maximum body temperature was between 39 and 39.8 °C [45]. Febrile episodes can be a sign of other complications with significant morbidity and mortality, such as atelectasis, hematoma, urinary tract infection, fat emboli, or deep vein thrombosis [43].

Another concerning finding is a draining wound. The incidence of superficial wound infections progressing to deep PJI is difficult to assess. Gaine et al. [24] reviewed 530 patients with either THAs or TKAs and found an over 15% rate of wound complications. Six patients had deep PJI that required operative debridement, while two patients required removal of their prostheses. The rate of postoperative PJI ranges from 1.3 to 50% in patients with persistent wound drainage. Postoperative drainage correlates to body mass index and type of anticoagulation used. Each day of prolonged drainage is associated with up to 42% increased risk of wound infection in total hip patients [46] Ultimately, PJIs have been shown to highly correlate to superficial surgical site infections but they are a poor predictor of ongoing problems or periprosthetic infection at 1 year post-surgery [47]. As such it is very difficult to make a diagnosis of infection during the early postoperative period. Wound complications in themselves do not confirm the presence of deep infection, and additional studies are often required to define a diagnosis.

While a draining wound can be very tempting to culture, this temptation should be avoided. Tetreault et al. [44] investigated 55 patients draining wounds after total joint arthroplasty with wound swabs and found that only 47% of the wound swabs correlated with deep cultures. The superficial cultures were typically polymicrobial and would have resulted in an antibiotic regimen change in 41.8% of cases. More importantly, superficial cultures yielded microbial growth in 80% of cases deemed negative for deep infection. The authors thus recommended against wound or sinus swabs for diagnosis due to possible overtreatment [48, 49].

Plain radiographs have limited usefulness in the early postoperative period as it is premature to develop or detect bony radiographic changes such as lacy periostitis, osteopenia, endosteal resorption, loosening of the prosthesis, and rapid progression of osteolysis, finding that can be useful in the setting of chronic PJI. However, they are essential to rule out other etiologies that may be contributing to the patient’s symptoms.

Magnetic resonance imaging (MRI) is not widely used. White et al. [50] have described technical modifications to traditional MRIs with the use of a metal artifact reduction sequence (MARS) . This allows for better visualization of the bone-prosthesis interface and adjacent soft tissues, although it is not intended for PJI diagnosis [51].

A technetium-Tc99m (99MTc) isotope bone scan can be performed in the assessment of a failed THA. Although it has a high sensitivity, the low specificity for infection limits its use [52]. Indium-111-labeled white cell scans have a much higher sensitivity in infection, which has been found to be 77%, with specificity of 86%, a positive predictive value of 54%, and a negative predictive value of 95% [13]. However, this test is expensive and time consuming and its utility in the acute postoperative period is unknown [53]. Other isotopes have been investigated but none has demonstrated clinically useful sensitivity or specificity. The use of radioactive immunoglobulin G has also been described but has not become common , as its sensitivity and specificity were similar to those of standard laboratory investigations [54, 55].

After a complete history, physical examination , and review of radiographs, the next step should be to measure serological inflammatory markers, specifically C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) . These markers are strongly recommended for every painful or failed THA, regardless of cause of failure, as multiple modes of failure can coexist.

Both ESR and CRP are normally elevated during the early postoperative period [56, 57]. Interpreting the results of these markers during the early postoperative period is based on their behavior curve. Following uncomplicated surgery, the ESR has been shown to peak approximately 5 days postoperatively, and remain elevated for several months; the CRP has been shown to peak approximately 2 days postoperatively, and should return to normal within 21 days [57]. More importantly, CRP response is not correlated with type of anesthesia, estimated blood loss, operative time, transfusions, medications , age, or gender. As such, any late reversal of downtrend should raise suspicion of, and be concerning for, infection. The CRP level, therefore, is more helpful in the evaluation of acute postoperative infection, especially if it continues to increase after the third postoperative day. The optimal cutoff CRP level for acute postoperative infection has been studied in acute postoperative THA infections confirmed with culture or intraoperative purulence by Yi et al. [1], with the optimal diagnostic cutoff for infection as measured by CRP found to be 93 mg/L (AUC of 93%). Given these findings, in the patient with any suspicion of infection, we obtain a serum CRP and if near or over 100 mg/L, an aspiration of the hip is obtained [1, 58].

When the history, physical examination , and inflammatory markers yield a high suspicion of acute PJI, aspiration of the joint fluid is indicated. Arthrocentesis should be done under ultrasound or fluoroscopy to confirm position. In addition, the patient should be off antibiotics for at least 2 weeks to avoid false-negative culture results. Synovial fluid is sent for WBC count, differential, and culture. Yi et al. reviewed 6033 consecutive primary THAs and identified 73 patients (1.2%) who underwent reoperation for any reason within the first 6 weeks postoperatively. Thirty-six of these patients were infected according to modified Musculoskeletal Infection Society criteria. The best test for the diagnosis of PJI in the early postoperative period after THA was the synovial fluid WBC count (AUC = 98%; optimal cutoff value 12,800 cells/μL), and synovial fluid differential (AUC = 91%; optimal cutoff value 89% PMN) [59]. It is important to note that these thresholds are quite different than the recommended value of 3000 WBC/μL used for the diagnosis of chronic PJI. Synovial fluid cell count can be adjusted for synovial red blood cell (RBC), serum RBC, and serum WBC counts according to a formula proposed by Ghanem et al. [60]. Phagocytosed metal debris within monocytes may be read as neutrophils by automated hematology instruments resulting in falsely elevated cell counts. In these settings, a manual count should be obtained [61, 62].

Newer tests for PJI of the synovial fluids have emerged such as leukocyte esterase test and alpha-defensin peptide. The utility of these tests in the acute postoperative period is not known [63, 64].

Organism identification is paramount for antimicrobial treatment plan. Routine cultures should be maintained for 14 days. Extending the incubation period to 2 weeks will significantly increase culture yield particularly in patients who may be infected with low-virulence organisms [65, 66]. In a study from Mayo Clinic of 897 PJI cases (from 1990 to 1999), 60 cases (7%) were culture-negative periprosthetic joint infections (CN-PJI) . Prior antimicrobial use has been shown by prior investigators to reduce the sensitivity of periprosthetic tissue cultures [67].

Frozen section and histology have been used as part of the intraoperative evaluation with the criterion value of the histologic diagnosis of infection reported to be either five or ten neutrophils per high-power field. The sensitivity for the cutoff of five neutrophils has been 100%, with a specificity of 96%. Using a cutoff criterion of ten neutrophils per high-power field did not change the sensitivity, but the specificity increased to 99% [68]. The utility of these tests in the acute postoperative phase , however, has not been studied.

In the vast majority of cases, surgical management is deemed necessary for the treatment of acute PJI.