Changing the definition of treatment success alters treatment outcomes in periprosthetic joint infection: a systematic review and meta-analysis.

Background: Variability in the definition of treatment success poses difficulty when assessing the reported efficacy of treatments for hip and knee periprosthetic joint infection (PJI). To address this problem, we determined how definitions of PJI treatment success have changed over time and how this has affected published rates of success after one-stage and two-stage treatments for hip and knee PJI. Methods: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted to identify one-stage and two-stage revision hip and knee PJI publications in major databases (2006-2021). Definition of treatment success, based on Musculoskeletal Infection Society tier criteria, was identified for each study. Publication year, number of patients, minimum follow-up, and study quality were also recorded. The association of success definitions and treatment success rate was measured using multi-variable meta-regression. Results: Study quality remained unchanged in the 245 publications included. Over time, no antibiotics (tier 1) and no further surgery (tier 3) (40.7 % and 54.5 %, respectively) became the two dominant criteria. After controlling for type of surgery, study quality, study design, follow-up, and year of publication, studies with less strict success definitions (tier 3) reported slightly higher odds ratios of 1.05 [1.01, 1.10] ( p = 0.009 ) in terms of treatment success rates compared to tier 1. Conclusions: PJI researchers have gravitated towards tier-1 and tier-3 definitions of treatment success. While studies with stricter definitions had lower PJI treatment success, the clinical significance of this is unclear. Study quality, reflected in the methodological index for non-randomized studies (MINORS) score, did not improve. We advocate for improving PJI study quality, including clarification of the definition of treatment success.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BACKGROUND: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. METHODS: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. RESULTS: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. CONCLUSIONS: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. LEVEL OF EVIDENCE: III.

Development of Diagnostic Quality Metrics for Prosthetic Joint Infection.

ABSTRACT: Although well-accepted clinical practice guidelines exist for the diagnosis of prosthetic joint infection (PJI), little is known about the quality of diagnosis for PJI. The identification of quality gaps in the diagnosis of PJI would facilitate the development of care structures and processes to shorten time to diagnosis and reduce the significant morbidity, mortality, and economic burden associated with this condition. Hence, we sought to develop valid clinical quality measures to improve the timeliness and accuracy of PJI diagnosis. We convened a nine-member multidisciplinary national panel of PJI experts including orthopedic surgeons, infectious disease specialists, an emergency medicine physician, and a patient previously treated for PJI to review, discuss, and rate the validity of proposed measures using a modification of the RAND-UCLA appropriateness method. In total, 57 permutations of six proposed measures were rated. Populations considered to be at high enough risk for PJI that certain care processes should always be performed were identified by the panel. Among the proposed quality measures, the panel rated five as valid. These novel clinical quality measures could provide insight into care gaps in the diagnosis of PJI.

Clinical and Histological Features of Prosthetic Joint Infections May Differ in Patients With Inflammatory Arthritis and Osteoarthritis.

Background: Patients with inflammatory arthritis are at increased risk of prosthetic joint infections (PJIs), but diagnosis in these patients can be challenging because active inflammatory arthritis produces elevated inflammatory markers that may mimic those seen in PJI. Purpose: In this pilot study, we sought to identify the clinical, microbiologic, and histopathologic features of culture-positive and culture-negative PJI in patients with inflammatory arthritis who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA). We also sought to obtain preliminary data to support a definitive study of optimal methods for PJI diagnosis in patients with inflammatory arthritis. Methods: We performed a retrospective analysis of TKA and THA patients treated for PJI from 2009 to 2018 at a single tertiary care orthopedic institution. Data were extracted from a longitudinally maintained hospital infection database. We reviewed hematoxylin and eosin slides of osteoarthritis and inflammatory arthritis PJI cases matched 3:1, respectively, by age, sex, and culture status. Clinical characteristics were evaluated using the Fisher exact test, χ2 test, Student t test, and Mann-Whitney U test where appropriate. Results: A total of 807 PJI cases were identified (36 inflammatory arthritis and 771 osteoarthritis cases). Patients with inflammatory arthritis presented younger, had a higher Charlson Comorbidity Index, more frequently used glucocorticoids, were more likely women, and had a higher proportion of culture-negative PJI compared with osteoarthritis patients. Of the 88 inflammatory arthritis cases reviewed for histopathology, a higher proportion of culture-positive than culture-negative PJI cases had >10 polymorphonuclear leucocytes per high-power field and met Musculoskeletal Infection Society criteria but presented with less chronic inflammation. Conclusions: This retrospective prognostic study suggests that culture-negative PJI may be more frequent in patients with inflammatory arthritis than in those with osteoarthritis. Chronic infections, antibiotic use, or misdiagnosis may be contributing factors to unclear PJI diagnoses among culture-negative cases. This preliminary work supports the need for further studies to assess the differences in clinical features between culture-negative and culture-positive PJI in patients with inflammatory arthritis and the ability of biological diagnostic markers to discriminate between them in this population.

No Difference in the Rate of Periprosthetic Joint Infection in Patients Undergoing the Posterolateral Compared to the Direct Anterior Approach.

BACKGROUND: There remains inconsistent data about the association of surgical approach and periprosthetic joint infection (PJI). We sought to evaluate the risk of reoperation for superficial infection and PJI after primary total hip arthroplasty (THA) in a multivariate model. METHODS: We reviewed 16,500 primary THAs, collecting data on surgical approach and all reoperations within 1 year for superficial infection (n = 36) or PJI (n = 70). Considering superficial infection and PJI separately, we used Kaplan-Meier survivorship to assess survival free from reoperation and a Cox Proportional Hazards multivariate models to assess risk factors for reoperation. RESULTS: Between direct anterior approach (DAA) (N = 3,351) and PLA (N = 13,149) cohorts, rates of superficial infection (0.4 versus 0.2%) and PJI (0.3 versus 0.5%) were low and survivorship free from reoperation for superficial infection (99.6 versus 99.8%) and PJI (99.4 versus 99.7%) were excellent at both 1 and 2 years. The risk of developing superficial infection increased with high body mass index (BMI) (hazard ratio [HR] = 1.1 per unit increase, P = .003), DAA (HR = 2.7, P = .01), and smoking status (HR = 2.9, P = .03). The risk of developing PJI increased with the high BMI (HR = 1.04, P = .03), but not surgical approach (HR = 0.68, P = .3). CONCLUSION: In this study of 16,500 primary THAs, DAA was independently associated with an elevated risk of superficial infection reoperation compared to the PLA, but there was no association between surgical approach and PJI. An elevated patient BMI was the strongest risk factor for superficial infection and PJI in our cohort. LEVEL OF EVIDENCE: III, retrospective cohort study.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Unexpected positive intraoperative cultures (UPIC) at index osseointegration do not lead to increased postoperative infectious events.

Introduction: The most common complication following transcutaneous osseointegration for amputees is infection. Although an obvious source of contamination is the permanent stoma, operative site contamination at the time of implantation may be an additional source. This study investigates the impact of unexpected positive intraoperative cultures (UPIC) on postoperative infection. Methods: Charts were reviewed for 8 patients with UPIC and 22 patients with negative intraoperative cultures (NIC) who had at least 1 year of post-osseointegration follow-up. All patients had 24 h of routine postoperative antibiotic prophylaxis, with UPIC receiving additional antibiotics guided by culture results. The main outcome measure was postoperative infection intervention, which was graded as (0) none, (1) antibiotics unrelated to the initial surgery, (2) operative debridement with implant retention, or (3) implant removal. Results: The UPIC vs. NIC rate of infection management was as follows: Grade 0, 6/8 = 75 % vs. 14/22 = 64 %, p = 0.682; Grade 1, 2/8 = 25 % vs. 8/22 = 36.4 % (Fisher's p = 0.682); Grade 2, 1/8 = 12.5 % vs. 0/22 = 0 % (Fisher's p = 0.267); Grade 3, 0/8 = 0 % vs. 1/22 = 4.5 % (Fisher's p = 1.000). No differences were statistically significant. Conclusions: UPIC at index osseointegration, managed with directed postoperative antibiotics, does not appear to increase the risk of additional infection management. The therapeutic benefit of providing additional directed antibiotics versus no additional antibiotics following UPIC is unknown and did not appear to increase the risk of other adverse outcomes in our cohort.

Factors Associated With an Intra-articular Infection After Anterior Cruciate Ligament Reconstruction: A Large Single-Institution Cohort Study.

BACKGROUND: An intra-articular infection after anterior cruciate ligament (ACL) reconstruction (ACLR) is a rare complication but one with potentially devastating consequences. The rare nature of this complication raises difficulties in detecting risk factors associated with it and with worse outcomes after one has occurred. PURPOSE: To (1) evaluate the association between an infection after ACLR and potential risk factors in a large single-center cohort of patients who had undergone ACLR and (2) assess the factors associated with ACL graft retention versus removal. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: All ACLR procedures performed at our institution between January 2010 and December 2018 were reviewed; a total of 11,451 procedures were identified. A retrospective medical record review was performed to determine the incidence of infections, patient and procedure characteristics associated with an infection, infection characteristics, incidence of ACL graft retention, and factors associated with the retention versus removal of an ACL graft. Multivariable logistic regression analysis was used to identify potential risk factors for an infection after ACLR. RESULTS: Of the 11,451 ACLR procedures, 48 infections were identified (0.42%). Multivariable logistic regression analysis revealed revision ACLR (odds ratio [OR], 3.13 [95% CI, 1.55-6.32]; P = .001) and younger age (OR, 1.06 [95% CI, 1.02-1.10]; P = .001) as risk factors for an infection. Compared with bone-patellar tendon-bone autografts, both hamstring tendon autografts (OR, 4.39 [95% CI, 2.15-8.96]; P < .001) and allografts (OR, 5.27 [95% CI, 1.81-15.35]; P = .002) were independently associated with an increased risk of infections. Overall, 15 ACL grafts were removed (31.3%). No statistically significant differences besides the number of irrigation and debridement procedures were found for retained versus removed grafts, although some trends were identified (P = .054). CONCLUSION: In a large single-center cohort of patients who had undergone ACLR and those with an infection after ACLR, patients with revision cases and younger patients were found to have a higher incidence of infection. The use of bone-patellar tendon-bone autografts was found to be associated with the lowest risk of infection after ACLR compared with both hamstring tendon autografts and allografts. Larger cohorts with a larger number of infection cases are needed to determine the factors associated with graft retention versus removal.

History of COVID-19 Was Not Associated With Length of Stay or In-Hospital Complications After Elective Lower Extremity Joint Replacement.

BACKGROUND: The impact of previous SARS-CoV-2 infection on the morbidity of elective total joint arthroplasty (TJA) is not fully understood. This study reports on the association between previous COVID-19 disease, hospital length of stay (LOS), and in-hospital complications after elective primary TJA. METHODS: Demographics, comorbidities, LOS, and in-hospital complications of consecutive 340 patients with a history of COVID-19 were compared with those of 5014 patients without a history of COVID-19 undergoing TJA. History of COVID-19 was defined as a positive IgG antibody test for SARS-CoV-2 before surgery. All patients were given both antibody and polymerase chain reaction tests before surgery. RESULTS: Patients with a history of COVID-19 were more likely to be obese (43.8% vs 32.4%, P < .001), Black (15.6% vs 6.8%, P < .001), or Hispanic (8.5% vs 5.4%, P = .028) than patients without a history of COVID-19. COVID-19 treatment was reported by 6.8% of patients with a history of COVID-19. Patients with a history of COVID-19 did not have a significantly longer median LOS after controlling for other factors (for hip replacements, median 2.9 h longer, 95% confidence interval = -2.0 to 7.8, P = .240; for knee replacements, median 4.1 h longer, 95% confidence interval = -2.4 to 10.5, P = .214), but a higher percentage were discharged to a post-acute care facility (4.7% vs 1.9%, P = .001). There was no significant difference in in-hospital complication rates between the 2 groups (0/340 = 0.0% vs 22/5014 = 0.44%, P = .221). CONCLUSIONS: We do not find differences in LOS or in-hospital complications between the 2 groups. However, more work is needed to confirm these findings, particularly for patients with a history of more severe COVID-19. LEVEL OF EVIDENCE: II.