James J. Vaillant

Background: Phages are being assessed for treatment of periprosthetic joint infection (PJI). Staphylococci are the most common cause of PJI. Phages are traditionally considered to be strain-specific and restricted to specific species. We aimed to assess the in vitro activity of a collection of staphylococcal phages against a selection of clinical Staphylococcus isolates recovered from PJI over a 20-year period. Methods: The activity of 37 staphylococcal phages was evaluated against 204 staphylococcal isolates, including 102 Staphylococcus aureus, 81 Staphylococcus epidermidis , and 21 Staphylococcus lugdunensis , using a tetrazolium dye–based metabolic assay. Standardized inocula of bacteria and phage were incubated over 48 hours. Growth inhibition ≥8 hours was considered indicative of phage activity. Results: A total of 7,548 phage-isolate pairs were assessed. Overall, 31 of 37 phages had activity against at least 1 isolate. The most broadly active phage showed activity against 50 of 195 isolates (26%) tested. Twenty-three phages showed cross-species activity, with 11 phages active against all 3 Staphylococcus species, and 12 phages active against 2 species. Of all S. aureus isolates tested, 61% were susceptible to at least 1 phage, while 31% and 76% of S. epidermidis and S. lugdunensis isolates were susceptible to at least 1 phage, respectively. Conclusions: This is the largest library of phages evaluated against staphylococci from PJI. Results show that staphylococcal phages can have cross-species activity, suggesting that phage libraries may offer cross-species coverage of clinically encountered staphylococcal isolates from PJI. Level of Evidence: Level V . Mechanism-based reasoning. See Instructions for Authors for a complete description of levels of evidence.

Background: The underlying cause of fever of unknown origin (FUO) remains unidentified in up to 51% of cases despite systematic evaluation. Microbial cell-free DNA next-generation sequencing (mcfDNA-NGS) offers an agnostic, noninvasive approach to pathogen identification, but the utility and clinical impact of this assay in FUO remain unknown. Methods: This retrospective cohort study evaluated adult patients referred for FUO evaluation at a tertiary medical center between November 2019 and November 2023. Patients underwent both standard microbiologic testing (ST) and mcfDNA-NGS. Diagnostic impact was assessed in 4 domains: new diagnoses, earlier time to diagnosis, avoidance of invasive procedures, and non-hypothesis-driven diagnoses. Logistic regression was used to identify predictors of positive mcfDNA-NGS testing. Results: Among 176 patients, mcfDNA-NGS was positive in 44.3%, with 49% of these cases considered clinically significant. Infectious cause of FUO was identified in 39% of patients, noninfectious in 35%, and unknown in 26%. mcfDNA-NGS contributed to a positive diagnostic impact in 30% of cases, mainly by earlier diagnosis (16%) and potential for avoidance of invasive procedures (10%). Positive mcfDNA-NGS was significantly associated with higher Charlson comorbidity index score (odds ratio [OR], 1.22; P < .001) and white blood cell (WBC) count ≤4.5 × 109 cells/L (OR, 8.61; P < .001). Conversely, FUO without localization was associated with a decreased likelihood of positive mcfNDA testing (OR, 0.18; P < .001). Conclusions: mcfDNA-NGS effectively complements ST in diagnosing FUO, providing earlier detection and minimizing invasive testing. Clinical predictors such as high comorbidity and low WBC count may guide the optimal use of mcfDNA-NGS in FUO. Prospective evaluation of optimal timing and use of mcfDNA-NGS and cost-benefit analysis in FUO is needed.

Staphylococcus aureus bacteriuria (SABU) represents 0.2–4% of all positive urine cultures. While asymptomatic colonization or infection of the urinary tract is possible, hematogenous seeding from S. aureus bacteremia (SAB) represents a potentially life-threatening condition. The rate of concomitant SAB is estimated to be 6.9–17.2% among those with SABU, and these patients are at higher risk of in-hospital mortality, infective endocarditis, embolic events, and vertebral osteomyelitis. Detection of SABU represents an opportunity for early detection and intervention in SAB. We conducted a retrospective analysis of clinical and microbiological characteristics of adult patients with SABU as our pre-intervention baseline. We then implemented a comment with the urine culture result in the electronic medical record (EMR) advising providers about the possibility of concomitant bacteremia. We conducted an interim analysis of early post-intervention data. Figure 1: Study workflow depicting case recruitment and blood culture results. Figure 2: Example of intervention comment displayed with the urine culture result in the EMR. 250 adult patients developed SABU from January 1, 2021, to January 31, 2023. Of these, 87 (34.8%) had urinary tract symptoms, and 91 (36.4%) had a chronic indwelling urinary catheter. 74 (29.6%) patients had blood cultures collected within 7 days of positive urine culture. The presence of urinary symptoms or indwelling catheter was not associated with blood culture collection. Only 22 patients (8.8%) had SAB with SABU. One patient was diagnosed with SAB 20 days after detection of SABU with infective endocarditis and disseminated infection, representing a delay in diagnosis. Following implementation of the intervention, an additional 86 patients with SABU had the result comment displayed in the EMR. Blood cultures were collected in 19 (22.1%) patients, and 2 (2.3%) were positive for S. aureus. There were no significant differences in rates of blood culture collection or SAB after implementation of the EMR result comment. Our results show a similar rate of SABU associated SAB to that previously reported in the literature. Delayed diagnosis of SAB in SABU is uncommon but does occur rarely with significant morbidity. The addition of a result comment is a simple and cost-effective intervention; however, evaluation of its efficacy is presently limited by a short follow-up duration. All Authors: No reported disclosures