Accurate diagnosis of orthopedic infection is crucial in guiding both antimicrobial therapy and surgical management in order to optimize patient outcomes. A variety of microbiological and nonmicrobiological methods are used to establish the presence of a musculoskeletal infection. In this minireview, we examine traditional culture-based and newer molecular methodologies for pathogen detection, as well as systemic and localized assays to assess host response to maximize diagnostic yield.

BACKGROUND: Evidence for the management of periprosthetic joint infection (PJI) after total elbow arthroplasty is sparse, particularly in regard to débridement, antibiotics, and implant retention (DAIR). This study explored the outcomes of DAIR and analyzed risk factors for failure. METHODS: A retrospective cohort study of patients 18 years or older diagnosed with elbow PJI and managed with DAIR between January 1, 2003, and December 31, 2018, at a single institution was performed. Twenty-six elbows met the inclusion criteria during the study period. All DAIR procedures included in this study represented an attempt to manage an acute PJI with surgical irrigation and débridement without removal of the elbow arthroplasty components, followed by long-term systemic antimicrobial therapy. DAIR failure was defined as recurrence of PJI, unplanned re-operation for infection, or death secondary to infection. A Cox proportional hazards model was used to identify possible risk factors for failure. RESULTS: DAIR failed in 17 cases of elbow PJI with a failure rate of 65% at 2 years (95% confidence interval: 41.3%-79.6%). The median time to failure from DAIR was 43 days (interquartile range: 27-114). We found that DAIR failed in all cases with sinus tracts or negative cultures. The group with favorable outcomes had a shorter median duration of symptoms (5 vs. 18 days, P = .65) and a higher proportion of monomicrobial infections (58.8% vs. 88.9%, P = .19) compared to those with unfavorable outcomes. However, with the numbers available, none of the possible risk factors analyzed for association with failure reached statistical significance. CONCLUSION: DAIR for elbow PJI was associated with high rates of failure. Possible risk factors for failure may include the presence of sinus tract, longer duration of symptoms, and culture-negative infection. Although the relatively low morbidity of DAIR compared with total elbow arthroplasty implant resection for a one-stage or two-stage reimplantation is attractive, patients considered for DAIR must know that the chance of success is limited to approximately 35%.

Background Cutibacterium acnes can cause spinal implant infections. However, little is known about the optimal medical management and outcomes of C. acnes spinal implant infections (CSII). Our study aims to describe the management of patients with CSII and evaluate the clinical outcomes. Methods We performed a retrospective cohort study of patients aged 18 years or older who underwent spinal fusion surgery with instrumentation between January 1, 2011, and December 31, 2020, and whose intraoperative cultures were positive for C. acnes. The primary outcome was treatment failure based on subsequent recurrence, infection with another organism, or unplanned surgery secondary to infection. Results There were 55 patients with a median follow-up (interquartile range) of 2 (1.2–2.0) years. Overall, there were 6 treatment failures over 85.8 total person-years, for an annual rate of 7.0% (95% CI, 2.6%–15.2%). Systemic antibiotic treatment was given to 74.5% (n = 41) of patients for a median duration of 352 days. In the subgroup treated with systemic antibiotics, there were 4 treatment failures (annual rate, 6.3%; 95% CI, 1.7%–16.2%), all of which occurred while on antibiotic therapy. Two failures occurred in the subgroup without antibiotic treatment (annual rate, 8.8%; 95% CI, 1.1%–31.8%). Conclusions Our study found that the estimated annual treatment failure rate was slightly higher among patients who did not receive antibiotics. Of the 6 failures observed, 4 had recurrence of C. acnes either on initial or subsequent treatment failures. More studies are warranted to determine the optimal duration of therapy for CSII.

Background The optimal duration of antibiotic therapy after debridement and implant retention (DAIR) for periprosthetic joint infections (PJIs) is debated. Furthermore, the best antibiotic regimens for staphylococcal PJI are also unclear. In this study, we evaluated the impact of antibiotic therapy duration on the risk of failure. We assessed the utility of rifampin-based regimens for staphylococcal PJI managed with DAIR. Methods We performed a retrospective cohort study of patients 18 years and older diagnosed with hip and knee PJI who underwent DAIR between January 1, 2008 and 31 December 31, 2018 at Mayo Clinic, USA. The outcome was failure of DAIR. For statistical analysis, joint-stratified Cox regression models adjusted for age, sinus tract, symptom duration, and primary/revision arthroplasty were performed. Results We examined 247 cases of PJI with a median follow-up of 4.4 years (interquartile range [IQR], 2.3–7) after DAIR. The estimated 5-year cumulative incidence of failure was 28.1% (n = 65). There was no association between the duration of intravenous (IV) antibiotics (median 42 days; IQR, 38–42) and treatment failure (P = .119). A shorter duration of subsequent oral antibiotic therapy was associated with a higher risk of failure (P = .005; eg, 90-day vs 1-year duration; hazard ratio [HR], 3.50; 95% confidence interval [CI], 1.48–8.25). For staphylococcal knee PJI, both the use and longer duration of a rifampin-based regimen were associated with a lower risk of failure (both P = .025). There was no significant association between fluoroquinolone (FQ) use and failure (HR, 0.62; 95% CI, .31–1.24; P = .172). Conclusions The duration of initial IV antibiotic therapy did not correlate with treatment failure in this cohort of patients. Rifampin use is recommended for staphylococcal knee PJI. There was no apparent benefit of FQ use in staphylococcal PJI.

Abstract. The data on long-term antibiotic use following debridement, antibiotics, and implant retention (DAIR) for treatment of periprosthetic joint infections are limited. In this single-center retrospective study, we show that patients with eventual cessation of antibiotic suppression after DAIR had similar outcomes to those who remained on chronic antibiotic suppression.

Background Image-guided biopsies in patients with suspected native vertebral osteomyelitis (NVO) are recommended to establish the microbiological diagnosis and guide antibiotic therapy. Despite recent advances, the microbiological yield of this procedure remains between 48% and 52%. A better understanding of factors associated with this low yield may lead to improved microbiological diagnosis. Methods We retrospectively identified patients with suspected NVO undergoing image-guided biopsies from January 2011 to June 2021 at our institution. Two hundred nine patients undergoing 248 percutaneous biopsies were included. Demographic data, biopsy and microbiologic techniques, clinical characteristics, and antibiotic use were collected. Multivariable logistic regression analysis was conducted to determine factors associated with microbiological yield. Results A total of 110 of 209 (52.6%) initial image-guided biopsies revealed positive microbiological results. This number increased to 121 of 209 (57.9%) when repeat image-guided biopsies were included. In multivariable analysis, aspiration of fluid was associated with a 3-fold increased odds of yielding a positive result (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.39–7.04; P = .006), whereas prior antibiotic use was associated with a 3-fold decreased yield (OR, 0.32; 95% CI, .16–.65; P = .002). A univariate subgroup analysis revealed a significant association between the length of the antibiotic-free period and microbiological yield, with the lowest rates of pathogen detection at 0–3 days and higher rates as duration increased (P = .017). Conclusions Prior antibiotic use in patients with suspected NVO was associated with a decrease in the microbiological yield of image-guided biopsies. An antibiotic-free period of at least 4 days is suggested to maximize yield. Successful fluid aspiration during the procedure also increases microbiological yield.

Background Native joint septic arthritis (NJSA) is definitively diagnosed by a positive Gram stain or culture, along with supportive clinical findings. Preoperative antibiotics are known to alter synovial fluid cell count, Gram stain and culture results and are typically postponed until after arthrocentesis to optimize diagnostic accuracy. However, data on the impact of preoperative antibiotics on operative culture yield for NJSA diagnosis are limited. Methods We retrospectively reviewed adult cases of NJSA who underwent surgery at Mayo Clinic facilities from 2012-2021 to analyze the effect of preoperative antibiotics on operative culture yield through a paired analysis of preoperative culture (POC) and operative culture (OC) results using logistic regression and generalized estimating equations. Results Two hundred ninety-nine patients with NJSA affecting 321 joints were included. Among those receiving preoperative antibiotics, yield significantly decreased from 68.0% at POC to 57.1% at OC (p < .001). In contrast, for patients without preoperative antibiotics there was a non-significant increase in yield from 60.9% at POC to 67.4% at OC (p = 0.244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (OR = 2.12; 95% CI = 1.24-3.64; p = .006). Within the preoperative antibiotic group, additional antibiotic doses and earlier antibiotic initiation were associated with lower OC yield. Conclusion In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in whom antibiotic therapy was held prior to obtaining operative cultures.

Background Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown. Methods This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality. Results Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P < .001) in TKA infections. There was no significant difference in severe ADEs between FQ and non-FQ regimens in both THA and TKA infections. The overall rate of nonsevere ADEs in FQ compared with non-FQ regimens was 43.3% vs 6.1% (P < .001). FQs were associated with tendinopathy, myalgia, arthralgia, and nausea. Conclusions A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs.

Background Debridement, antibiotics, irrigation, and implant retention (DAIR) is the first-line management strategy for acute periprosthetic joint infections (PJI). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny. Methods We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee and treated with DAIR in centers from Europe and the USA. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or lost to follow-up within 12 weeks were excluded from the analysis. Results The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (HR 1.37, 95% CI 0.79-2.39, p=0.27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the USA cohort (HR 0.36, 95% CI 0.11-1.15, p=0.09) which also had the highest risk of treatment failure. Conclusion The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies.

Background Prosthetic joint infection (PJI) is a potentially limb-threatening complication of total knee arthroplasty. Phage therapy is a promising strategy to manage such infections including those involving antibiotic-resistant microbes, and to target microbial biofilms. Experience with phage therapy for infections associated with retained hardware is limited. A 62-year-old diabetic man with a history of right total knee arthroplasty 11 years prior who had suffered multiple episodes of prosthetic knee infection despite numerous surgeries and prolonged courses of antibiotics, with progressive clinical worsening and development of severe allergies to antibiotics, had been offered limb amputation for persistent right prosthetic knee infection due to Klebsiella pneumoniae complex. Intravenous phage therapy was initiated as a limb-salvaging intervention. Methods The patient received 40 intravenous doses of a single phage (KpJH46Φ2) targeting his bacterial isolate, alongside continued minocycline (which he had been receiving when he developed increasing pain, swelling, and erythema prior to initiation of phage therapy). Serial cytokine and biomarker measurements were performed before, during, and after treatment. The in vitro anti-biofilm activity of KpJH46Φ2, minocycline and the combination thereof was evaluated against a preformed biofilm of the patient’s isolate and determined by safranin staining. Results Phage therapy resulted in resolution of local symptoms and signs of infection and recovery of function. The patient did not experience treatment-related adverse effects and remained asymptomatic 34 weeks after completing treatment while still receiving minocycline. A trend in biofilm biomass reduction was noted 22 hours after exposure to KpJH46Φ2 (P = .063). The addition of phage was associated with a satisfactory outcome in this case of intractable biofilm-associated prosthetic knee infection. Pending further studies to assess its efficacy and safety, phage therapy holds promise for treatment of device-associated infections.