Osmon, Douglas R.

Abstract 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.

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

Until recently, the laboratory diagnosis of central nervous system (CNS) infections with herpes simplex virus (HSV) has been limited by poor sensitivity and/or specificity. We assessed the diagnostic utility of PCR for detection of HSV in over 2,100 specimens referred to the Mayo Clinic from August 1993 to May 1996. DNA extracted from cerebrospinal fluid (CSF) samples with IsoQuick was amplified by PCR with oligonucleotide primers directed to the DNA polymerase gene of HSV, yielding a 290-bp amplicon. HSV DNA was detected in 150 (135 by gel electrophoresis, 15 by Southern blotting only) of 2,106 (7.1%) specimens. PCR-positive CNS disease occurred in patients ranging in age from 13 days to 89 years; 59% of the cases occurred in patients between the ages of 30 and 69, and 21 (14%) of the patients were infants. Genotype analysis was not routinely performed; however, amplification of a 335-bp product within the thymidine kinase gene of HSV revealed 13 positions within a span of 80 nucleotides that accurately identified the two serotypes of the virus according to 14 reference strains. We conclude that PCR detection of HSV DNA in CSF specimens should be considered an emerging "gold standard" for the laboratory diagnosis of CNS infections with this virus.

Abstract Introduction Patients with hematologic malignancies are at higher risk for infection due to the nature of their immunocompromised status, therapy-related complications, and numerous other factors. Multiple myeloma (MM) is the second most common hematologic malignancy after non-Hodgkin's lymphomas. Current literature on bone and joint infections (BJI) in MM is limited to case reports, and this study aims to identify the frequency and characteristics of BJI in MM. Methods We retrospectively reviewed 4607 patients within the MM database at Mayo Clinic from 1/1/2005 through 1/1/2015. A computerized search of the electronic medical record using diagnosis codes, pathology reports, and free text searches, followed by manual chart review, identified 39 unique patients with BJI as depicted in Figure 1. Results Of the 39 patients with BJI and a diagnosis of multiple myeloma, 28/39 (72%) were male, and median age was 70 years-old (range 39-86). 35/39 (90%) had IgG subtype MM, and 21/39 (54%) were in remission from MM while 4/39 (10%) were neutropenic at the time of BJI. 14/39 (36%) occurred after hematopoietic stem cell transplant, and the median duration from transplant to BJI was 45.0 months (range 1.0-88.7). 11/39 (28%) had chronic kidney disease on chart review, and 8/39 (21%) were on corticosteroids. 32/39 (82%) had prior exposure to chemotherapy, and median duration from most recent chemotherapy to BJI was 32 days (range 0-1559). Septic arthritis (9/39, 23%) and osteomyelitis (9/39, 23%) occurred most frequently followed by prosthetic joint infection (PJI) (8/39, 21%). Pathogens were primarily Gram positive organisms (20/39, 51%), and 7/20 (35%) had polymicrobial infections. All patients received culture-guided induction antimicrobial therapy. 27/39 (69%) underwent surgical intervention. Treatment and outcomes by infection can be seen in Figure 1. Of the 5 (13%) treatment failures (TF), 3 (60%) had PJI while 1 (20%) had osteomyelitis with necrotizing fasciitis, and 1 (20%) had septic arthritis. Median time from diagnosis of BJI to TF was 6.3 months (range 0.0-13.5), and none of the TF were neutropenic at the time of BJI. 26/39 (67%) were alive one year after BJI, and at latest chart review, 8/39 (21%) were alive, of whom 7 were treated successfully. Median overall survival from diagnosis of BJI was 34.3 months for all cases. Conclusions BJI are uncommon in MM, and pathogens are similar to patients without MM, though with polymicrobial infections occurring frequently. Treatment is successful in the majority of cases, but PJI appear to have higher TF rates. However, TF may not necessarily correlate with hematologic status or survival. Figure 1 Flowchart of the multiple myeloma study cohort, BJI, treatment, and outcomes MM = Multiple Myeloma; BJI = Bone and Joint Infection; PJI = Prosthetic Joint Infections; VO = Vertebral Osteomyelitis; I&D = Irrigation & Debridement; Abx = Antibiotic Therapy Alone; DAIR = Debridement and Implant Retention; TF = Treatment Failure; CHF = Congestive Heart Failure Figure 1. Flowchart of the multiple myeloma study cohort, BJI, treatment, and outcomes. / MM = Multiple Myeloma; BJI = Bone and Joint Infection; PJI = Prosthetic Joint Infections; VO = Vertebral Osteomyelitis; I&D = Irrigation & Debridement; Abx = Antibiotic Therapy Alone;. / DAIR = Debridement and Implant Retention; TF = Treatment Failure; CHF = Congestive Heart Failure Disclosures Kapoor: Amgen: Research Funding; Takeda: Research Funding; Celgene: Research Funding.

The in vitro activities of rifampin, rifabutin, rifapentine, and rifaximin were tested against 200 periprosthetic joint infection (PJI)-associated staphylococci. Seven rifampin-resistant isolates had MICs of ≥4 μg/ml. Three isolates had rifampin MICs of 0.25 to 1 μg/ml and harbored an Asp471Gly RpoB variant, suggesting that the CLSI rifampin-susceptible staphylococcal breakpoint of ≤1 μg/ml may be too high.

Patients with febrile neutropenia (FN) often are subject to antibiotic and diagnostic test overuse. We sought to improve appropriate use of antimicrobials and diagnostic tests for patients with FN. We used a blended quality approach with Lean Six Sigma tools and iterative improvement of a clinical decision aid to guide providers through empirical antimicrobial selection and diagnostic evaluation of patients with FN during a yearlong period. We evaluated the incidence of nonadherence to best practice before, during, and after rollout of a clinical decision aid in conjunction with an educational initiative. At baseline, 71% of patients with FN had at least one critical deviation from best practice. During the project, the percentage decreased to 27.3%; 4 months after the project was completed, the percentage was 33.3% ( P = .04). A clinical decision aid can improve adherence to best practices for the empirical management of FN.

Background: Povidone-iodine (PI) irrigation is often used prior to wound closure in total joint arthroplasty, but there are limited reports evaluating its efficacy in decreasing joint infections. The goal of this study was to compare the rate of any reoperation for infection (both superficial and deep) in primary total hip arthroplasty (THA) and primary total knee arthroplasty (TKA) among patients who did and did not receive PI irrigation prior to wound closure. Methods: Using our institution’s total joint registry, we identified 5,534 primary THA and 6,204 primary TKA procedures performed from 2013 to 2017. Cases were grouped on the basis of whether or not the wound was irrigated with 1 L of 0.25% PI prior to closure. PI irrigation was used in 1,322 (24%) of the THA cases and in 2,410 (39%) of the TKA cases. The rates of reoperation for infection at 3 months and 1 year were compared between the 2 groups. The same comparisons were then performed using propensity scores to account for differences in baseline characteristics. Results: The rate of reoperation for infection as assessed at 3 months following THA was similar between those who received dilute PI irrigation (0.9%) and who did not (0.7%) (p = 0.7). At 1 year, the rate of reoperation for infection was similar between those who received dilute PI irrigation (0.7%) and those who did not (0.9%) (p = 0.6). After using the propensity score, there was no difference between the groups in the risk of septic reoperations. For TKA, the rate of reoperation as assessed at 3 months was similar between those who received dilute PI irrigation (0.8%) and those who did not (0.3%) (p = 0.06). At 1 year, there was a greater rate of reoperations for infection among those who received dilute PI irrigation (1.2%) compared with those who did not (0.6%) (p = 0.03). However, there was no difference in the risk of septic reoperations between the groups after using the propensity score. Conclusions: Despite enthusiasm for and progressive adoption of the use of dilute PI irrigation at our institution, there was not a significant reduction in the risk of reoperation for infection as assessed at 3 months and 1 year following primary THA and TKA. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Aims There is little information regarding the risk of a patient developing prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) when the patient has previously experienced PJI of a TKA or total hip arthroplasty (THA) in another joint. The goal of this study was to compare the risk of PJI of primary TKA in this patient population against matched controls. Patients and Methods We retrospectively reviewed 95 patients (102 primary TKAs) treated between 2000 and 2014 with a history of PJI in another TKA or THA. A total of 50 patients (53%) were female. Mean age was 69 years (45 to 88) with a mean body mass index (BMI) of 36 kg/m 2 (22 to 59). In total, 27% of patients were on chronic antibiotic suppression. Mean follow-up was six years (2 to 16). We 1:3 matched these (for age, sex, BMI, and surgical year) to 306 primary TKAs performed in 306 patients with a THA or TKA of another joint without a subsequent PJI. Competing risk with death was used for statistical analysis. Multivariate analysis was followed to evaluate risk factors for PJI in the study cohort. Results The cumulative incidence of PJI in the study cohort (6.1%) was significantly higher than the matched cohort (2.6%) at ten years (hazard ratio (HR) 3.3; 95% confidence interval 1.18 to 8.97; p = 0.02). Host grade in the study group was not a significant risk factor for PJI. Patients on chronic suppression had a higher rate of PJI (HR 15; p = 0.002), with six of the seven patients developing PJI in the study group being on chronic suppression. The new infecting microorganism was the same as the previous in only two of seven patients. Conclusion In this matched cohort study, patients undergoing a clean primary TKA with a history of TKA or THA PJI in another joint had a three-fold higher risk of PJI compared with matched controls with ten-year cumulative incidence of 6.1%. The risk of PJI was 15-fold higher in patients on chronic antibiotic suppression; further investigation into reasons for this and mitigation strategies are recommended. Cite this article: Bone Joint J 2019;101-B(7 Supple C):91–97

Aims The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. Patients and Methods We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. Results Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. Conclusion PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9–15.