Spinal implant infections (SII) are serious complications following instrumented spinal fusion. Debridement with implant retention requires antibiotic therapy, yet the optimal duration remains unclear. We assessed whether longer antibiotic duration is associated with reduced risk of treatment failure. We conducted a multicenter retrospective cohort study of adult patients diagnosed with acute postoperative SII (≤90 days from index surgery) between January 1, 2017, and December 31, 2022. All patients underwent debridement with implant retention. Treatment failure was defined as unplanned reoperation, clinical recurrence, or infection-related death. A Cox proportional hazards model assessed whether being on antibiotics was protective, treating antibiotic use as a time-dependent covariate, adjusting for relevant clinical variables, and including death not attributable to infection as a competing event. A second Cox model evaluated whether shorter antibiotic duration was associated with increased risk of failure with landmark analysis at six weeks. There were 531 patients included in the study. Patient demographics are described in Table 1. During a median follow-up of 1,168 days (IQR 576-1,817), 151 patients experienced treatment failure. There was a non-significant trend toward decreased hazard of failure while on antibiotics (HR 0.70; 95% CI 0.46–1.05; p=0.087). Among 363 patients without early failure, 60 (16.5%) received ≤6 weeks of antibiotics and 303 (83.5%) received >6 weeks. Longer antibiotic duration was not associated with a differential risk of failure (HR 0.75, 95% CI 0.43–1.33; p=0.34). Continuing antibiotic therapy after debridement and implant retention may help reduce the risk of treatment failure in SII. However, it remains unclear whether extending antibiotic treatment beyond a certain duration continues to offer additional benefits. Prospective studies are needed to better define the optimal duration and approach to antibiotic therapy in these scenarios. Sandra B. Nelson, MD, UpToDate Wolters Kluwer Health: Author, Editor

BACKGROUND:Postoperative spinal implant infections (PSII) are a serious complication of instrumented spinal fusion. Although debridement with implant retention is standard for early infection, the optimal duration of antimicrobial therapy remains uncertain. METHODS:We conducted a multicenter retrospective cohort study across ten U.S. academic centers, including adults with early PSII (≤90 days after fusion surgery) from 2017 to 2021. We excluded patients who experienced treatment failure within 6 weeks of debridement. The primary outcome was treatment failure. Antibiotic therapy effect was analyzed as a time-varying exposure using adjusted Cox proportional hazards models. Secondary analyses included 12-week landmark and clone-censor-weighted models to compare durations ≤12 weeks versus >12 weeks. RESULTS:116 patients out of 499 (23.2%) experienced treatment failure during a median follow-up of 3.2 years. Among patients who remain failure-free six weeks from debridement, being on antibiotics was not associated with treatment failure (adjusted hazard ratio [aHR] 0.71, 95% confidence interval [CI] 0.48-1.07; p = 0.10). In a 12-week landmark analysis limited to 359 patients who were not on indefinite suppressive antibiotic therapy, treatment durations >12 weeks did not significantly reduce the risk of failure (aHR 1.01, 95% CI 0.62-1.64; p = 0.99). Results were consistent in the clone-censor-weight sensitivity analysis (aHR 0.85, 95% CI 0.62-1.16; p = 0.30). CONCLUSIONS:Prolonged antibiotic therapy was not associated with improved outcomes in early PSII managed with debridement and implant retention. These results support shorter, individualized antibiotic courses in patients with adequate surgical source control.

Abstract Background Best practice for patients on COpAT (Complex Outpatient Antimicrobial Therapy) includes close follow-up once discharged from the hospital. However, some patients discharged with COpAT do not receive monitoring for complications, increasing their risk for re-admission. There is limited analysis regarding patient-specific social determinants of health (SDOH) that may contribute to a reduced follow-up rate. We aimed to determine the percentage of patients discharged on long-term oral antibiotics who received recommended outpatient Infectious Disease (ID) support and potential barriers to follow-up for quality improvement.Table 1:Outcomes associated with social determinants of healthSelected social determinants of health associated with specified monitoring and outcomes. Bolded values are considered statistically significant. Methods In this single-center cohort, patients discharged between 1/1/2021 and 12/31/2022, on ≥ 2 weeks of oral antibiotics, age > 18 years, with inpatient ID consult, and with recommendations for follow-up in the University of Utah ID Clinic were examined. SDOH included distance from the medical center, age, race/ethnicity, employment status, substance use, homelessness, and history of bipolar disorder/psychoses. We assessed patient outcomes of treatment failure or lost to follow-up within 90 days post-discharge. We also evaluated the time to appointment, lab monitoring, and number of adverse drug events (ADEs) after discharge. Results One hundred ninety-seven patients met the inclusion criteria for the cohort. Median times to suggested lab monitoring and ID appointment were 13 and 21 days post-discharge respectively. 71% completed lab monitoring within 90 days of discharge. After 90 days, 19% of patients were lost to follow up and 20% had experienced treatment failure. Those younger than 55, unemployed, or experiencing substance use were more often lost to follow-up. Individuals with substance use or age < 55 had a longer time to lab monitoring. Patients with a history of substance use had fewer ADEs (Table 1). Conclusion SDOH that contribute to patient outcomes include a history of substance use and unemployment, suggesting an area of clinical quality improvement. Additionally, those younger than 55 were more often lost to follow-up. Further examination of follow-up protocol for these patients is important to improve patient outcomes. Disclosures Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support Laura Certain, MD, PhD, Zimmer Biomet: Advisor/Consultant

Objective:Despite many reports of similar effectiveness between oral and intravenous antibiotics for bone and joint infections, prescribing practice has been slow to change in the United States. We sought to determine if implementing an intravenous-to-oral treatment guideline could increase prescribing of oral antibiotic regimens at our center. Design:Retrospective, quasi-experimental study. Setting:Single US academic medical center. Patients:Patients with bone or joint infections managed by Infectious Disease providers from September 2020 to December 2022. Intervention:An intravenous-to-oral treatment guideline for patients with bone and joint infections. Methods:The prescribing rates of fully oral antibiotic regimens before and after implementation of the guideline were compared. Additionally, variables independently associated with oral antibiotic prescribing were identified by logistic regression. Results:There were 450 patients included: 213 before and 237 after implementation of the guideline. Oral antibiotic prescribing significantly increased following implementation of the treatment guideline to 59% from 33% of patients (difference 25.8%, 95% CI [16.7%, 34.4%]. In multivariable analysis, the post-intervention phase was associated with a significantly greater likelihood of oral antibiotic prescribing (aOR 2.89 [1.90, 4.45]). Other variables independently associated with oral antibiotic prescribing included male sex (aOR 1.88 [1.20, 2.98]), prosthetic joint infection (aOR 0.29 [0.17, 0.47]), and infection with Enterobacterales (aOR 2.86 [1.45, 5.92]), methicillin-sensitive Staphylococcus aureus [aOR 0.41 [0.26, 0.65]), or coagulase-negative staphylococci (aOR 0.34 [0.18, 0.62]). Conclusions:Implementation of a treatment guideline resulted in a significant increase in oral antibiotic prescribing. Antimicrobial stewardship programs should implement similar interventions to improve outpatient antibiotic utilization.

Background: Prior studies have indicated that administration of prolonged courses of oral antibiotics after Stage 2 reimplantation surgery for periprosthetic joint infection (PJI) results in a lower rate of recurrent PJI. However, there is concern that this antibiotic usage results in an increased risk of antibiotic resistance in any subsequent PJI that does occur.Methods: We retrospectively reviewed patients who underwent Stage 2 reimplantation surgery for PJI within the national Veterans Affairs hospital system of the United States. We compared those who received at least 2 weeks of oral antibiotics after Stage 2 reimplantation to those who did not. The primary outcome was the proportion of organisms resistant to four classes of antibiotics (tetracyclines, fluoroquinolones, oral beta-lactams, and sulfonamides) in recurrent PJI. Secondary outcomes included recurrent PJI and death.Results: Of the 605 patients who underwent Stage 2 reimplantation for PJI, 154 patients received at least 14 d of antibiotics after surgery and 451 patients did not. Bacteria causing recurrent PJI in patients who received prolonged antibiotics were more likely to be resistant to tetracyclines and trimethoprim-sulfamethoxazole but not oral beta-lactams or fluoroquinolones. There was no difference in risk of recurrent PJI or death between the two groups.Conclusions: Prolonged oral antibiotic treatment after Stage 2 reimplantation increases the risk of antibiotic resistance to some antibiotics in subsequent PJI. We recommend further research to identify the best choice of antibiotic and duration after Stage 2 reimplantation, to maximize benefits while minimizing risks.

In the United States, rates of Mycobacterium tuberculosis infection have been declining for decades. Osteoarticular tuberculosis of the ankle is rarely observed. We present the case of a 65-year-old man who immigrated to the United States from India 24 years before the onset of symptoms. The patient initially reported atraumatic swelling and pain of the left ankle and foot and was treated for venous insufficiency. Later, the patient was referred to a nonsurgical orthopaedic clinic for additional workup and was found to have elevated inflammatory markers. MRI showed septic arthritis and osteomyelitis of the talus, distal tibia, and calcaneus. Joint aspiration revealed elevated white blood cell counts with predominately PMNs. The patient was then referred to an orthopaedic foot and ankle surgeon and underwent extensive irrigation and débridement. The patient was discharged on empiric antibiotics. Culture results from the original joint aspirate returned 14 days after surgery as positive for acid-fast bacillus, later identified as M tuberculosis by sequencing. Empiric antibiotics were discontinued, and the patient was started on appropriate antituberculotic therapy. This case report illustrates the challenge in the diagnosis of skeletal tuberculosis and the importance of including this condition on the differential for patients with atypical foot and ankle presentations.

The optimal treatment of prosthetic joint infection (PJI) remains uncertain. Patients undergoing debridement, antibiotics, and implant retention (DAIR) receive extended antimicrobial treatment, and some experts leave patients at perceived highest risk of relapse on suppressive antibiotic therapy (SAT). In this narrative review, we synthesize the literature concerning the role of SAT to prevent treatment failure following DAIR, attempting to answer 3 key questions: (1) What factors identify patients at highest risk for treatment failure after DAIR (ie, patients with the greatest potential to benefit from SAT), (2) Does SAT reduce the rate of treatment failure after DAIR, and (3) What are the rates of treatment failure and adverse events necessitating treatment discontinuation in patients receiving SAT? We conclude by proposing risk-benefit stratification criteria to guide use of SAT after DAIR for PJI, informed by the limited available literature. Limited data suggest suppressive antibiotic therapy (SAT) may reduce treatment failure following debridement and implant retention (DAIR) for prosthetic joint infection. We propose a structured approach to selecting patients for SAT following DAIR incorporating known DAIR treatment failure risk factors.

Purpose: We describe a case of severe scleritis possibly caused by Bacillus coagulans. Observations: Conventional laboratory evaluation was inconclusive. The associated organism was identified with metagenomic RNA deep sequencing (MDS). The infection resolved with trimethoprim-sulfamethoxazole treatment. Conclusions: This case demonstrates the utility of unbiased, high-throughput sequencing for infectious scleritis.

BackgroundVancomycin and tobramycin have traditionally been used in antibiotic spacers. In 2020, our institution replaced tobramycin with ceftazidime. We hypothesized that the use of ceftazidime/vancomycin (CV) in antibiotic spacers would not lead to an increase in treatment failure compared to tobramycin/vancomycin (TV).MethodsFrom 2014 to 2022, we identified 243 patients who underwent a stage I revision for periprosthetic joint infection (PJI). The primary outcome was a recurrent infection requiring antibiotic spacer exchange. We were adequately powered to detect a 10% difference in recurrent infection. Patients who had a prior failed stage I or two-stage revision for infection, acute kidney injury (AKI) prior to surgery, or end-stage renal disease were excluded. Given no other changes to our spacer constructs, we estimated cost differences attributable to the antibiotic change. Chi-square and t-tests were used to compare the two groups. Multivariable logistic regressions were utilized for the outcomes.ResultsThe combination of TV was used in 127 patients; CV was used in 116 patients. Within one year of stage I, 9.8% of the TV group had a recurrence of infection versus 7.8% of the CV group (P = 0.60). By final follow-up, results were similar (12.6 versus 8.6%, respectively, P = 0.32). Adjusting for potential risk factors did not alter the results. Cost savings for ceftazidime versus tobramycin are estimated to be $68,550 per one hundred patients treated.ConclusionReplacing tobramycin with ceftazidime in antibiotic spacers yielded similar PJI eradication success at a lower cost. While larger studies are warranted to confirm these efficacy and cost-saving results, our data justifies the continued investigation and use of ceftazidime as an alternative to tobramycin in antibiotic spacers.

Objective: To compare outcomes between patients discharged on intravenous (IV) versus oral (PO) antibiotics for the treatment of orthopedic infections, after creation of an IV-to-PO guideline, at a single academic medical center in the United States.Methods: This was a retrospective, propensity score matched, cohort study of adult patients hospitalized for orthopedic infections from September 30, 2020, to April 30, 2022. Patients discharged on PO antibiotics were matched to patients discharged on IV antibiotics. The primary outcome was one-year treatment failure following discharge. Secondary outcomes were incidence of 60-day treatment failure, adverse drug events (ADE), readmissions, infectious disease clinic "no-show" rates, and emergency department (ED) encounters.Results: Ninety PO-treated patients were matched to 90 IV-treated patients. Baseline characteristics were similar in the two groups after matching. There was no significant difference in the proportions of patients on PO versus IV antibiotics experiencing treatment failure at one year (26% vs 31%, P = .47). There were no significant differences for any secondary outcomes: treatment failure within 60 days (13% vs 14%, P = 1.00), ADE (13% vs 11%, P = .82), unplanned readmission (17% vs 21%, P = .57), or ED encounters (9% vs 18%, P = .54). Survival analyses identified no significant differences in time-to-event between PO and IV treatment for any of the outcomes assessed.Conclusions: There were no appreciable differences in outcomes between patients discharged on PO compared to IV regimens. Antimicrobial stewardship interventions to increase prescribing of PO antibiotics for the treatment of orthopedic infections should be encouraged.

Background. The optimal duration and choice of antibiotic for fracture-related infection (FRI) is not well defined. This study aimed to determine whether antibiotic duration (<= 6 vs >6 weeks) is associated with infection- and surgery-free survival. The secondary aim was to ascertain risk factors associated with surgery- and infection-free survival. Methods. We performed a multicenter retrospective study of patients diagnosed with FRI between 2013 and 2022. The association between antibiotic duration and surgery- and infection-free survival was assessed by Cox proportional hazard models. Models were weighted by the inverse of the propensity score, calculated with a priori variables of hardware removal; infection due to Staphylococcus aureus, Staphylococcus lugdunensis, Pseudomonas or Candida species; and flap coverage. Multivariable Cox proportional hazard models were run with additional covariates including initial pathogen, need for flap, and hardware removal. Results. Of 96 patients, 54 (56.3%) received <= 6 weeks of antibiotics and 42 (43.7%) received >6 weeks. There was no association between longer antibiotic duration and surgery-free survival (hazard ratio [HR], 0.95; 95% CI, .65-1.38; P = .78) or infection-free survival (HR, 0.77; 95% CI, .30-1.96; P = .58). Negative culture was associated with increased hazard of reoperation or death (HR, 3.52; 95% CI, 1.99-6.20; P < .001) and reinfection or death (HR, 3.71; 95% CI, 1.24-11.09; P < .001). Need for flap coverage had an increased hazard of reoperation or death (HR, 3.24; 95% CI, 1.61-6.54; P = .001). Conclusions. The ideal duration of antibiotics to treat FRI is unclear. In this multicenter study, there was no association between antibiotic treatment duration and surgery- or infection-free survival.

Abstract Background Oral (PO) regimens have been utilized more frequently for orthopedic infections in place of intravenous (IV) regimens at our center following publication of the OVIVA trial. Given limited published experience of this approach at US medical centers, we reviewed safety and effectiveness outcomes at ours. Methods This was a retrospective, propensity-score matched, cohort study of adult patients hospitalized for orthopedic infections from 9/30/2020 to 4/30/2022. Patients discharged on PO antibiotics were matched to patients discharged on IV antibiotics, using a 1:1 nearest neighbor approach without replacement. Variables expected to be associated with treatment selection and/or outcome were included in the propensity score (Table 1). Primary outcomes were early (60-day) and late (1-year) treatment failure following discharge. Secondary outcomes were incidence of adverse drug events (ADE), readmissions, and ED encounters within 60 days of discharge. Outcomes were assessed through chart review.Table 1:Baseline Characteristics Results Six hundred sixty-four patients were screened and 401 met criteria for inclusion. Of these, 123 PO-treated patients were matched to 123 IV-treated patients. Baseline characteristics were similar in the two groups after matching, although there were differences in microbiological indication, and patients discharged on PO regimens were treated for shorter durations and were more likely to be discharged home (Table 1). There was no significant difference in the proportions of patients on PO vs IV antibiotics experiencing treatment failure at 60 days (14% vs 9%, P = 0.23), treatment failure at 1 year (21% vs 20%, P = 0.75), ADE within 60 days (6% vs 11%, P = 0.16), 60-day readmission (26% vs 33%, P = 0.26), or 60-day ED encounter (11% vs 10%, P = 0.83). Survival analyses identified no significant differences in time-to-event between PO and IV treatment for any of the outcomes assessed (Figure 1).Figure 1:Kaplan-Meier Survival Plots Conclusion There was no appreciable difference in outcomes between patients discharged on PO compared to IV regimens. Quality-improvement interventions to increase prescribing of PO antibiotics for the treatment of orthopedic infections should be encouraged. Disclosures Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support

Background Antibiotic-loaded bone cement (ALBC) is commonly used in the treatment of periprosthetic joint infections (PJIs) to increase the local concentration of antibiotic at the site of infection. Use of ALBC has been associated with rare instances of acute kidney injury (AKI) despite low systemic absorption of the nephrotoxic antibiotics; however, the incidence of AKI is unknown. The purpose of this study was to determine the incidence of and risk factors for AKI associated with ALBC. Methods This single-site, retrospective cohort study compared 162 PJI patients who underwent Stage 1 revision to a spacer with ALBC to 115 PJI patients who underwent debridement, antibiotics, and implant retention (DAIR) without the use of ALBC. Both groups received similar systemic antibiotics postoperatively. Descriptive statistics and multivariable logistic regressions were used to analyze risk factors for AKI. Results There was no statistically significant difference in the rate of AKI: 29 patients (17.9%) in the ALBC group and 17 (14.7%) in DAIR group developed AKI (odds ratio 1.43; 95% CI 0.70 to 2.93). There was a trend toward increased severity of AKI in the ALBC group. Chronic kidney disease, systemic vancomycin, and diuretic use were independent factors associated with the risk of AKI. Conclusion An AKI occurred in 17% of PJI patients receiving either a spacer with ALBC or a DAIR. The use of ALBC was not associated with a significant increased risk of AKI. However, the use of systemic vancomycin and diuretic use were independent predictors of AKI in this patient population.

Background:Cutibacterium acnes is a common commensal of human skin but may also present as an opportunistic pathogen in prosthetic joint and wound infections. Unfortunately, few complete genomes of C. acnes are publicly available, and even fewer are of isolates associated with infection. Here we report the isolation, characterization, and complete genomes of 2 C. acnes isolates from a surgical site infection of an elbow.Methods:We used standard microbiological methods for phenotypic characterization and performed whole genome sequencing on 2 C. acnes isolates using a combination of short-read and long-read sequencing.Results:Antibiotic susceptibility testing showed beta-lactamase negative and low minimal inhibitory concentrations to all antibiotics tested, with the exception of metronidazole. We assembled complete genomes of the 2 isolates, which are approximately 2.5 megabases in length. The isolates belong to the single-locus sequence type (SLST) H1 and the multi-locus sequence type (MLST) IB. Both isolates have similar composition of known virulence genes, and we found no evidence of plasmids but did find phage-associated genes. Notably, the 2 genomes are 99.97% identical but contain a large genomic inversion encompassing approximately half of the genome.Conclusions:This is the first characterization of this large-scale genomic inversion in nearly identical isolates from the same wound. This report adds to the limited numbers of publicly available infection-associated complete genomes of C. acnes.

Abstract Background The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial concluded that oral antibiotic therapy was noninferior to intravenous antibiotic therapy for complex orthopedic infections. Similar studies have confirmed the OVIVA trials findings. However, there is limited information regarding the impact of Social Determinants of Health (SDOH) on decisions regarding IV vs. PO treatment and treatment outcomes of bone and joint infections. This study aimed to determine how SDOH affect IV vs. PO treatment choices and overall treatment outcomes for patients with bone and joint infections. Methods In this single-center cohort, patients discharged between 4/1/2018 and 4/1/2022 were examined. Inclusion criteria were patients who had bone and joint infections, inpatient Infectious Disease (ID) consult, discharged on IV vancomycin, age >18 years, and scheduled follow up in the University of Utah Infectious Disease Clinic. SDOH assessed included primary language, race/ethnicity, insurance, history of intravenous drug use (IVDU), and history of homelessness. The primary outcome was the number of patients switched from IV to PO antibiotics two weeks after discharge. Secondary outcomes included total duration of antibiotics, duration of follow up with ID, and rate of treatment failure. Results Two hundred seventy-seven patients met inclusion criteria for the cohort. There was no difference with respect to history of homelessness, primary language, history of IVDU, race, ethnicity, or insurance status in patients who were switched to PO antibiotics within two weeks of discharge compared to patients maintained on IV antibiotics. With respect to secondary outcomes, individuals on Medicaid were more likely to experience treatment failure (Table 1B). Conclusion For patients with bone and joint infections, SDOH were not associated with a switch from IV to PO antibiotics. However, patients on Medicaid experienced higher rates of treatment failure despite no difference in antibiotic route. The examined SDOH and transition to PO regimens were infrequently observed among study participants which created difficulty with drawing further conclusions. Further examination of these SDOH is important to understand their impact on treatment failure and improve patient care. Disclosures Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support