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Abstract Background We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10–15 hours) from the initial and 21 hours (17–29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)–infected patients had significantly shorter STTPs (P < .001) and lower TTP ratios (P < .001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P = .002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3–5.6]; P = .01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings.

Abstract 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 to 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 = .244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (odds ratio [OR] = 2.12; 95% confidence interval [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. Conclusions 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.

ABSTRACT The use of ceftriaxone, a highly protein-bound drug, in the setting of hypoalbuminemia may result in suboptimal drug exposure. Patients with obesity also exhibit higher absolute drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone. This retrospective review included adult inpatients with weight >100 kg or body mass index >40 kg/m 2 who received ceftriaxone 2 g intravenously every 12 hours for at least 72 hours. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Secondary outcomes included clinical cure, microbiologic cure, length of stay, ICU length of stay, mortality, 30-day readmission, and adverse events. In all, 137 patients were included, 34 of whom had a serum albumin of ≤2.5 g/dL. In a propensity-score-weighted analysis, clinical success was significantly more common among those without hypoalbuminemia (91.2%) as compared to those with hypoalbuminemia (77.8%) ( P = 0.038). Death within 30 days (13.7% vs 0%, P < 0.001) and 30-day readmission (31.6% vs 12.0%, P = 0.008) were more common in the hypoalbuminemia group. In a univariate analysis, serum albumin and indication for ceftriaxone use were found to be predictors of clinical success. Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 g every 12 hours.

AbstractBackgroundThere are no established clinical breakpoints for antifungal agents against Cryptococcus species; however, epidemiological cut‐off values can help distinguish wild‐type (WT) isolates without any acquired resistance from non‐WT strains, which may harbour resistance mechanisms.Patients/MethodsWe describe the trends of antifungal MICs and percentages of WT C. neoformans species complex (CNSC) isolates processed in our reference laboratory from November 2011 to June 2021. There were only nine isolates in 2011, thus, we included them in the year 2012 for data analysis. Clinical data is also described when available.ResultsWe identified 632 CNSC, the majority collected from blood (n = 301), cerebrospinal fluid (n = 230), and respiratory (n = 71) sources. The overall percentage of WT isolates for amphotericin B (AMB), 5‐flucytosine, and fluconazole was 77%, 98%, and 91%, respectively. We noticed a statistically significant change in the percentage of AMB WT isolates over the years, with 98% of isolates being WT in 2012 compared to 79% in 2021 (p < .01). A similar change was not observed for other antifungal agents. Clinical data was available for 36 patients, primarily non‐HIV immunocompromised patients with disseminated cryptococcosis. There were no statistically significant differences in the clinical characteristics and outcomes between patients with WT (58.3%) versus non‐WT (41.7%) isolates, but we noticed higher mortality in patients infected with an AMB non‐WT CNSC isolate.ConclusionsWe observed an increase in the percentage of AMB non‐WT CNSC isolates in the past decade. The clinical implications of this finding warrant further evaluation in larger studies.

AbstractIntroductionGram‐negative bacillary bloodstream infection (GN‐BSI) is a frequent clinical challenge among immunocompromised hosts and is associated with a high mortality. The utility of follow‐up blood cultures (FUBCs) for GN‐BSI in this population, particularly in the setting of neutropenia, is poorly defined.MethodsWe conducted a single‐center, retrospective cohort study between the period of July 2018 and April 2022 to investigate the utility of FUBCs and delineate risk factors for positive cultures among neutropenic patients with monomicrobial GN‐BSI. Univariate logistic regression was performed to assess risk factors associated with positive FUBCs.ResultsOf 206 patients, 98% had FUBCs performed, and 9% were positive. Risk factors for positive FUBCs included multidrug‐resistant GN infection (OR 3.26; 95% confidence interval [CI] 1.22–8.72) and vascular catheter source (OR 4.82; CI 1.76–13.17). Among patients lacking these risk factors, the prevalence of positive FUBCs was low (2.8%) and the negative predictive value was 92%. Those with positive and negative FUBCs had similar rates of all‐cause mortality (16.7% vs. 16.6%; p = .942) and microbiologic relapse (11.1% vs. 6.0%; p = .401) within 90‐days of treatment completion. However, positive FUBCs were associated with prolonged hospitalization and longer duration of antimicrobial therapy.ConclusionPositive FUBCs were infrequent in neutropenic patients with GN‐BSI, and their occurrence did not significantly impact mortality or microbiologic relapse. Risk factors for positive FUBCs included multidrug resistant Gram‐negative infection and vascular catheter source. Prospective studies will be necessary to elucidate the benefits and risks of FUBCs when managing GN‐BSI in patients with underlying immune compromise. image

Abstract Background The treatment of invasive fungal infections (IFI) is often complicated by drug-drug interactions, toxicities, and host comorbidities. Isavuconazole (ISA) has a favorable side effect profile and has FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data on its efficacy for other microbes and non-pulmonary infections. We report our experience of ISA in IFI treatment, with a particular focus on non-pulmonary sites and other microbial etiologies. Methods We identified patients who received ISA as part of IFI treatment from 1/1/2015–4/1/2020 at Mayo Clinic. We categorized them by organ involvement and by pathogens, and identified patterns of ISA use and clinical outcomes. Results A total of 131 patients were identified. Similar to the existing literature, the majority were pulmonary infections (60%), with 12% invasive sinus infection, 12% central nervous system (CNS) infection, and 7% fungemia. Aspergillus was the most common pathogen (39%), yeast comprised 19%, dimorphic fungi 15%, Mucormycosis 12%, phaeohyphomycosis 5%, and other molds 3%. ISA was used as secondary/salvage therapy in 89% of cases. The response rate varied by organ involvement and pathogen. ISA had complete/partial resolution or achieved stability in 57% of fungemia cases, 63% of invasive sinus infections, 64% of pulmonary infections, and 73% of CNS infections. Aspergillus species had a 67% response rate, with 72% response in yeast infections, 65% rate in dimorphic fungi, 53% for mucormycosis, and 86% in dematiaceous molds. Conclusion Although limited by a small sample size, the subgroup review based on organ site and microbial etiology did seem to show roughly similar results to approved uses. The CNS infections treated with ISA were particularly of interest, given the limited options available with reliable CNS penetration. The current available literature has little to say on the efficacy of ISA in these off-label uses, with the majority being similar case series. This report highlights the importance of prospective trials comparing ISA to other antifungals in a greater variety of indications to better identify when this better-tolerated agent can be safely used. Disclosures Courtney E. Harris, MD, Dynamed: Advisor/Consultant

Abstract Background Majocchi’s granuloma (MG) is an uncommon deep fungal folliculitis predominantly caused by dermatophytes. Available data regarding predisposing comorbidities/risk factors, clinical characteristics, offending microbiologic pathogens, diagnostics, pathologic findings, and treatment approaches has been inferred from historical cases. Given these limitations in the existing literature of MG, we sought to conduct a detailed review of our institutional experience with biopsy-confirmed cases of MG. Methods Following IRB approval, we retrospectively identified and analyzed a multicenter cohort of adult patients diagnosed with MG between September 1992 and September 2022 at Mayo Clinic campuses (Figure 1). Data extracted included demographics, comorbid conditions, presenting clinical characteristics, diagnostic, microbiologic, and biopsy characteristics, treatment details, and outcomes. Figure 1 Flow Diagram show exclusion of patients from the final cohort. Results A total of 147 patients with MG with the accompanying baseline characteristics met study criteria (Table 1). One-hundred and five patients were male with a median age of 55.6 years. Immunosuppressant and topical corticosteroid use were common prior to development of MG (Table 1). Dermatologic lesions and their sites of involvement did not differ based on the immune status of patients (Table 2). Trichophyton rubrum was the most common causative pathogen of MG, in addition to other dermatophytes and fungal organisms (Table 3a). Treatment duration for all prescribed agents was median 31.5 days. Oral terbinafine was the most frequently utilized agent and clinical resolution was achieved in 96.6% of cases (Table 3b). Baseline Characteristics of 147 Patients with Majocchi’s Granuloma Diagnostic, Microbiologic, and Biopsy Characteristics, Treatment Characteristics and Outcomes Conclusion While rare and clinically variable in presentation, the diagnosis of MG requires careful clinical examination and history-taking, histopathologic confirmation, and frequently fungal culture. Most cases of MG in our study responded well to a course of oral terbinafine at a median of 31.5 days of treatment. Disclosures All Authors: No reported disclosures

Abstract Background Vancomycin resistant enterococcus (VRE) infective endocarditis (IE) is associated with poor outcomes. There are limited data to guide the antimicrobial choice and duration of therapy. Several in vitro and limited clinical studies demonstrate the synergistic effect of β-lactams with other agents, particularly daptomycin, in this setting. We sought to compare clinical outcomes in patients with VRE IE treated with adjunctive β-lactam therapy. Methods This was an IRB-approved, retrospective, single-center cohort study. The study included patients ≥18 years of age diagnosed with VRE IE via modified Duke criteria from 2011-2021. Data were collected by electronic medical record review. Descriptive statistics were obtained. The primary outcome was 90-day treatment failure compared between those receiving and not receiving adjunctive β-lactams. Treatment failure was defined as recurrence of bloodstream infection (BSI) or death within 90 days of diagnosis. Failure-free survival was analyzed by Kaplan-Meier curve with log-rank test. Results A total of 32 cases were identified. 12 received adjunctive β-lactams. Mean age was 67 years, and 71% were male. 13 (41%) had a prosthetic valve and 6 (19%) had a CIED (Table 1). A majority (78%) had E. faecium IE. Mean duration of bacteremia was 9 days (Table 2). About one-third had treatment failure with 7 deaths and 4 BSI recurrences. Adjunctive β-lactams included ampicillin (3), cefepime (1), ceftaroline (6) and ceftriaxone (2). There was no statistical difference in failure-free survival in patients treated with adjunctive β-lactam therapy (Figure 1). The results were similar when restricted only to those who received daptomycin with or without adjunctive β-lactam therapy.Table 1.Patient CharacteristicsTable 2.Disease characteristics Figure 1. Kaplan-Meier curve comparing failure-free survival between patients who were primary treated with adjunctive β-lactams versus non-adjunctive therapy. The p-value is calculated via the log-rank test. Conclusion VRE IE is associated with poor prognosis, including high rates of mortality and relapses. In our experience, adjunctive B-lactam use did not result in improved outcome. Limitations include small sample size, and heterogenous antibiotic use. More prospective randomized data are needed. Disclosures All Authors: No reported disclosures

Abstract Background 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. Methods 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 Figure 1: Study workflow depicting case recruitment and blood culture results. Figure 2: Intervention Flag Figure 2: Example of intervention comment displayed with the urine culture result in the EMR. Results 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. Conclusion 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. Disclosures All Authors: No reported disclosures

Abstract Background Due to extensive protein binding, use of ceftriaxone in the setting of hypoalbuminemia may result in suboptimal drug exposure via higher concentrations of unbound drug resulting in increased volume of distribution and increased drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone for a bacterial infection. Methods This retrospective review included adult inpatients with weight &gt; 100 kg or body mass index (BMI) &gt; 40 who received ceftriaxone 2 grams intravenously every 12 hours for at least 72 hours for one of the following indications: bloodstream infection, pneumonia, urinary tract infection, non-enterococcal endocarditis, skin and soft tissue infection, or bone and joint infection. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Clinical cure was defined as resolution of signs and symptoms compatible with active infection without need to change or extend antibiotic therapy due to inadequate effect of ceftriaxone. Microbiologic cure was defined as negative repeat sterile site cultures, if applicable. Secondary outcomes included length of stay, mortality, and 30-day readmission. Outcomes were analyzed with Mann-Whitney U tests, Pearson’s chi-squared tests, and Fisher’s exact tests (α level = 0.05). Results 137 patients were included, 34 of whom had a serum albumin ≤ 2.5 g/dL. Patients were predominantly white (94.2%) and male (69.3%) with a median BMI of 48.6 (Table 1). Clinical success, a composite of clinical and microbiologic cure, was achieved in 76.5% and 92.2% (p = 0.013) of those with and without hypoalbuminemia, respectively. Clinical cure was significantly more common among those without hypoalbuminemia (93.2%) as compared to those with hypoalbuminemia (76.5%) (p = 0.007). Death during hospitalization was more common (14.7% vs. 0%, p &lt; 0.001) and median length of stay was longer (14 vs. 9 days, p = 0.009) in the hypoalbuminemia group. No difference was seen in 30-day readmission (23.5% vs. 11.7%, p = 0.089). Conclusion Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 grams every 12 hours. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria