Identification of the causative organism(s) in periprosthetic joint infection (PJI) is a challenging task. The shortcomings of traditional cultures have been emphasized in recent literature, culminating in a clinical entity known as “culture-negative PJI.” Amidst the growing burden of biofilm infections that are inherently difficult to culture, the field of clinical microbiology has seen a paradigm shift from culture-based to molecular-based methods. These novel techniques hold much promise in the demystification of culture-negative PJI and revolutionization of the microbiology laboratory. This article outlines the clinical implications of culture-negative PJI, common causes of this diagnostic conundrum, established strategies to improve culture yield, and newer molecular techniques to detect infectious organisms.

The isolation of an infective pathogen can be challenging in some patients with active, clinically apparent infectious diseases. Despite efforts in the microbiology lab to improve the sensitivity of culture in orthopedic implant-associated infections, the clinically relevant information often falls short of expectations. The management of peri-prosthetic joint infections (PJI) provides an excellent example of the use and benefits of newer diagnostic technologies to supplement the often-inadequate yield of traditional culture methods as a substantial percentage of orthopedic infections are culture-negative. Next-generation sequencing (NGS) has the potential to improve upon this yield. Bringing molecular diagnostics into practice can provide critical information about the nature of the infective organisms and allow targeted therapy in these otherwise challenging situations. This review article describes the current state of knowledge related to the use and potential of NGS to diagnose infections, particularly in the setting of PJIs.

Aims The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. Methods A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. Results Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. Conclusion This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3–9.

Background: A 2-stage approach is most commonly used to treat periprosthetic joint infection (PJI). Some successful studies of the 1-stage approach were underpowered, lacked a 2-stage comparative group, and excluded patients with draining sinuses, comorbidities, and/or antibiotic-resistant organisms. Given the morbidity and expense associated with 2-stage treatment, we conducted a prospective, multicenter, randomized trial to compare the results of 1- and 2-stage PJI treatment, specifically including patients with draining sinuses, comorbidities, and resistant organisms. Methods: Patients presenting for surgical treatment of a chronic PJI with a known organism following primary total hip or knee arthroplasty were included (with infection defined by Musculoskeletal Infection Society [MSIS] criteria). Patients with prior revision, culture-negative infection, or fungal infection, or who were immunosuppressed or had soft-tissue involvement precluding wound closure, were excluded. Patients were classified according to the McPherson host staging system. Clinical success was defined as (1) no clinical failure or reinfection with the same or new organism; (2) no reoperation for PJI; and (3) no PJI-related death. A double-instrument setup was used for all patients, as were similar irrigation and antibiotic protocols. A total of 323 patients (166 one-stage; 157 two-stage) were randomized. Groups were similar with respect to demographics and host classification. After excluding patients who died or were lost to follow-up, 258 of the 323 patients had 2-year follow-up (135 one-stage and 123 two-stage). The rate of patient loss to follow-up was similar between the treatment groups. Results: Sixteen patients in the 1-stage group and 9 patients in the 2-stage group died prior to 2-year follow-up. Overall, the 2-year success rate of 1-stage treatment was 97% (131 of 135), while the success of 2-stage treatment was 91% (112 of 123) (p = 0.04). Compared with the 2-stage group, the 1-stage group had 3-times the odds of overall success in a regression analysis (unadjusted odds ratio = 3.22 [95% confidence interval = 1.0 to 10.38]). After adjusting for specific variables (McPherson host grade, resistant organism, and draining sinuses), 1-stage treatment also had 3-times the odds of success. Conclusions: The results of this prospective randomized trial indicated that 1-stage treatment (97% success) was statistically noninferior to 2-stage treatment (91% success) when treating chronic PJI following primary total hip or knee arthroplasty, provided the protocols described here are explicitly followed. Extrapolation to other patient cohorts and clinical situations should be avoided.

Abstract Background Rifampin is generally advised in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin remains a matter of debate. We evaluated the outcome of patients treated with and without rifampin, and analyzed the influence of timing, dose and co-antibiotic. Methods Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death or the need for suppressive antimicrobial treatment. Results A total of 669 patients were analyzed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P < .001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P < .001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 – 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone or clindamycin (OR 10.1, 95% CI 5.65 – 18.2) and the start of rifampin within 5 days after surgical debridement (OR 1.96, 95% CI 1.08 – 3.65) were predictors of treatment failure. The dosing of rifampin had no effect on outcome. Conclusions Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged, but requires further investigation.

Background The success of debridement, antibiotics, and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to the time after index arthroplasty. Methods We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements, and a follow-up <1 year were excluded. Treatment failure was defined as (1) any further surgical procedure related to infection; (2) PJI-related death; or (3) use of long-term suppressive antibiotics. Results We included 769 patients. Treatment failure occurred in 294 patients (38%) and was similar between time intervals from index arthroplasty to DAIR: the failure rate for Week 1–2 was 42% (95/226), the rate for Week 3–4 was 38% (143/378), the rate for Week 5–6 was 29% (29/100), and the rate for Week 7–12 was 42% (27/65). An exchange of modular components was performed to a lesser extent in the early post-surgical course compared with the late course (41% vs 63%, respectively; P < .001). The causative microorganisms, comorbidities, and durations of symptoms were comparable between time intervals. Conclusions DAIR is a viable option in patients with early PJI presenting more than 4 weeks after index surgery, as long as DAIR is performed within at least 1 week after the onset of symptoms and modular components can be exchanged.