Yetmar, Zachary A.

Abstract Background Plasma microbial cell-free DNA (mcfDNA) sequencing, commercially available from Karius® (Redwood City, CA), has been increasingly utilized in diagnosing endovascular infections. The 2023 updated Duke criteria incorporated detection of pathogen via metagenomic sequencing in its microbiologic criteria. We analyzed the clinical impact of mcfDNA sequencing in the diagnosis and treatment of suspected infective endocarditis (IE) cases. Methods We performed retrospective review of patients with suspected IE who underwent Karius® test at Mayo Clinic, MN, between 2017 to 2023. Results We preformed preliminary analysis of 25 patients. Analysis of baseline characteristics (table 1) revealed that these patients had significant predisposing factors for IE. Before accounting for mcfDNA sequencing, 3 (12%) met criteria for definite IE, 10 (40%) met criteria for possible IE, and 12 (48%) were rejected per 2023 Duke criteria. After incorporating mcfDNA sequencing result, 1 patient who was classified as possible IE was escalated to definite IE. This patient had previous infection of implantable cardioverter-defibrillator (ICD) with Streptococcus dysgalactiae. ICD was removed. She had development of endophthalmitis and stroke, 1 week and 2 weeks after the completion of IV antibiotics, respectively, with echocardiogram showing new tricuspid valve vegetation. Routine work-up was negative despite that she was not on any systemic antibiotics at the time of blood culture collection. mcfDNA sequencing detected Streptococcus dysgalactiae, making definite diagnosis of IE, leading to the physician’s decision to extend the IV antibiotic treatment (treatment escalation). Overall, after mcfDNA sequencing result, treatment decision was not impacted in 14 (56%), ongoing treatment was escalated in 4 (16%), de-escalated in 5 (20%), and antimicrobials was newly initiated in 2 (8%) (figure 1). Positive mcfDNA sequencing result often led to treatment escalation or initiation; negative result often led to treatment de-escalation (figure 2). Conclusion In challenging cases of suspected IE, mcfDNA sequencing led to alteration of antimicrobial treatment in 44% of cases. Further data collection and final analysis will include larger number of patients. Disclosures All Authors: No reported disclosures

Abstract Background RSV is a common respiratory infection that causes significant morbidity in SOTR. However, risk factors for complications such as hypoxic respiratory failure, mechanical ventilation, and secondary infections have not been well described. Methods This retrospective, international, multicenter cohort study is actively recruiting SOTR hospitalized with RSV. Here, we analyzed data from Mayo Clinic (Rochester, Florida, Arizona), Miami Transplant Institute, Cleveland Clinic, and Royal Melbourne Hospital between 2016 and 2019. Secondary infection was defined as culture positive infection within 90 days of RSV diagnosis. Whenever appropriate, logistic and Cox regression analysis were conducted to identify risk factors. Survival functions were estimated using the Kaplan-Meier method.Figure 1:Forest plots of multivariable logistic regression models for risk factors for A) hypoxia, B) secondary infections, C) mechanical ventilation. Note: all variables included are the ones statistically significant on univariate analysis. Abbreviations: CI, confidence interval; OR, Odds ratio; LRTI: lower respiratory tract infection. Results 233 SOTRs (58.8% male; median, 61 years), including 77 (49.1%) kidney, 23 (9.9%) liver, 79 (33.9%) lung, and 38 (16.3%) heart transplants (Table). Hypoxic respiratory failure, mechanical ventilation, and secondary infection were seen in 98 (42.1%), 23 (9.9%), and 58 (24.9%) patients, respectively. After multivariate analysis, age >60 years, symptoms and imaging evidence of lower respiratory tract infection (LRTI) were associated with oxygen requirement (Figure 1A); similar results were observed in an analysis of the lung transplant cohort only. Risk factors on multivariate analysis for secondary infection include a history of rejection within six months and mechanical ventilation (Figure 1B). Risk factors for mechanical ventilation included age >60 years and LRTI on imaging (Figure 1C) after multivariate analysis. Seventeen (7.3%) patients died within 90 days of diagnosis. Cox univariate analysis identified age >60 years and LRTI on imaging, secondary infections, mechanical ventilation and hypoxia on admission were associated with higher mortality (Figure 2 and 3).Figure 2:Forest plot with Cox proportional hazards models. Note: only univariate results shown, multivariate not done due to low number of events. Conclusion This multicenter study of SOTR hospitalized with RSV identified older age ( >60 years old) as a risk factor for hypoxic respiratory failure, mechanical ventilation and death. Mechanical ventilation and a history if rejection within six months of RSV were associated with increased risk of secondary infections, identifying them as high-risk that needs close surveillance for this complication.Figure 3:Effects of A) Age older than 60 years old and B) mechanical ventilation on 90 day probability of survival after RSV infection Disclosures Michelle Yong, MBBS, FRACP, MPH, PhD, MSD: Grant/Research Support|MSD: Honoraria|Takeda: Advisor/Consultant Yoichiro Natori, MD, Eurofin/Viracor: Honoraria|Nobel Pharma: Advisor/Consultant

ABSTRACT Background Multiple outpatient therapies have been developed for COVID‐19 in high‐risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population. Methods We performed a retrospective cohort study using de‐identified administrative claims data from OptumLabs Data Warehouse. Patients were included if they were age ≥ 18 years, diagnosed with COVID‐19 between January 2022 and December 2023, and underwent SOT prior to COVID‐19. The primary outcome was 30‐day hospitalization. Stabilized inverse probability of treatment weighting was used to account for potential confounding variables. Results 4192 SOT recipients with COVID‐19 were identified. 1403 received an outpatient COVID‐19 therapy, including anti‐spike monoclonal antibodies ( N = 748, 53.3%), molnupiravir ( N = 327, 23.3%), ritonavir‐boosted nirmatrelvir ( N = 217, 15.5%), or remdesivir ( N = 141, 10.0%). In weighted analysis compared to no treatment, anti‐spike monoclonal antibodies (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.28–0.55; p < 0.001), molnupiravir (HR 0.56, 95% CI 0.36–0.89; p = 0.013), and nirmatrelvir (HR 0.47, 95% CI 0.25–0.89; p = 0.020) were associated with reduced hospitalization risk, while remdesivir (HR 1.00, 95% CI 0.50–1.98; p = 0.992) was not. Hospitalization rates were similar between the treatment agents, apart from remdesivir showing a higher risk compared to anti‐spike monoclonal antibodies. Conclusions Outpatient COVID‐19 therapies were largely associated with improved outcomes among SOT recipients. These treatment agents showed similar rates of 30‐day hospitalization, except for remdesivir. The choice of outpatient COVID‐19 therapy in SOT recipients should primarily account for patients’ individual circumstances and drug‐drug interactions rather than differential therapeutic efficacy. image

Abstract Nocardiosis is an uncommon yet potentially devastating infection. Nocardia tends to affect individuals with chronic lung disease or immunocompromising conditions, 2 groups increasing in number. Incidence of nocardiosis is likely to increase as well, and it is vital to have an approach to this complex disease. Here, we aim to review the presentation, diagnosis, and management of Nocardia in the modern era. We will also highlight areas of uncertainty in our understanding of nocardiosis and propose a general approach to nocardiosis therapy, accounting for response and tolerance of Nocardia treatment.

Abstract Background Nocardia tends to cause infection in immunocompromised patients or those with chronic pulmonary disease. Nocardia is known to recur, prompting the practice of secondary prophylaxis in patients perceived at high risk. However, few data exist regarding the epidemiology of recurrent nocardiosis or the effectiveness of secondary prophylaxis. Methods We performed a multicenter, retrospective cohort study of adults diagnosed with nocardiosis from November 2011 to April 2022, including patients who completed primary treatment and had at least 30 days of posttreatment follow-up. Propensity score matching was used to analyze the effect of secondary prophylaxis on Nocardia recurrence. Results Fifteen of 303 (5.0%) patients developed recurrent nocardiosis after primary treatment. Most recurrences were diagnosed either within 60 days (N = 6/15, 40.0%) or between 2 to 3 years (N = 4/15, 26.7%). Patients with primary disseminated infection tended to recur within 1 year, whereas later recurrences were often nondisseminated pulmonary infection. Seventy-eight (25.7%) patients were prescribed secondary prophylaxis, mostly trimethoprim-sulfamethoxazole (N = 67/78). After propensity-matching, secondary prophylaxis was not associated with reduced risk of recurrence (hazard ratio, 0.96; 95% confidence interval, .24–3.83), including in multiple subgroups. Eight (53.3%) patients with recurrent nocardiosis required hospitalization and no patients died from recurrent infection. Conclusions Recurrent nocardiosis tends to occur either within months because of the same Nocardia species or after several years with a new species. Although we did not find evidence for the effectiveness of secondary prophylaxis, the confidence intervals were wide. However, outcomes of recurrent nocardiosis are generally favorable and may not justify long-term antibiotic prophylaxis for this indication alone.

Background. Surgical-site infections (SSIs) are common in liver transplant recipients. The optimal SSI antimicrobial prophylaxis agent and duration are not established. We aimed to explore risk factors for SSIs after transplant, with a particular interest in the impact of perioperative antibiotic regimen on the development of SSIs. Methods. Retrospective study of adults undergoing liver transplant across 3 transplant programs between January 1, 2020, and June 01, 2021. Results. Of 557 patients included in the study, 32 (5.7%) were infected or colonized with a multidrug-resistant organism (MDRO) within 1 y before liver transplant. Narrow-spectrum SSI prophylaxis with ceftriaxone or cefazolin alone was administered in 488 of 577 patients (87.6%); the remaining 69 patients (12.4%) received broad-spectrum prophylaxis with vancomycin and aztreonam (n = 40), piperacillin–tazobactam (n = 11), carbapenems (n = 8), ceftriaxone and another antibiotic (n = 7), and others. Patients with pretransplant MDRO were more likely to receive broad-spectrum coverage than those without pretransplant MDROs (28.1% versus 11.4%, P = 0.005). SSIs were identified in 40 patients (7.2%); 25 (62.5%) were organ–space infections, 3 (7.5%) were deep incisional infections, and 12 (30.0%) were superficial incisional infections. The median time from liver transplant to SSIs was 14 d (interquartile range, 10–20.2). MDROs were identified in 12 SSIs (30%). Multivariable analysis revealed no significant association between antimicrobial spectrum and risk of SSIs (P = 0.5), whereas surgical leak (P<0.001) and reoperation (P = 0.017) were independently associated with increased risk of SSIs. SSIs were not significantly associated with composite risk of death or liver allograft failure. Conclusions. The spectrum of antimicrobial prophylaxis did not impact the development of SSIs in liver transplant recipients.

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 There is scarce data surrounding the epidemiology of invasive fungal infections (IFI) after pancreas transplantation (PT). Our centers’ PT protocols recommend universal fluconazole prophylaxis for at least 1 month, which is extended to 1 year for recipients who live in Coccidioides endemic areas. The purpose of our study was to evaluate the epidemiology of IFIs after PT while on our antifungal prophylaxis protocol. Methods A retrospective cohort study was performed among adult patients who underwent PT at Mayo Clinic sites in Arizona, Florida, or Minnesota between January 1, 2010 and December 31, 2020. IFI was defined based on EORTC/MSGERC criteria. The primary aim was to describe epidemiology and timing of IFI after PT, particularly in the context of the universal antifungal prophylaxis protocol. Results Among 482 pancreas transplant recipients, 35 developed IFIs (7.3%). All patients received antifungal prophylaxis per protocol for a median duration of 33 days (Figure 1). Median duration from time of transplant to IFI was 16 (IQR 10.5-28.2) days for Candida IFIs versus 529 (IQR 192.5-1195.0) days for non-Candida IFI. 20 IFIs (57.1%) were secondary to Candida species with 45% of these cases caused by either C. glabrata or C. krusei (Figure 2). 90% were on antifungal prophylaxis (85% fluconazole) at time of diagnosis of invasive candidiasis. All the Candida IFIs were intra-abdominal infections. Amongst the 15 non-Candida IFIs (42.9%), 9 were secondary to endemic mycoses and 4 were secondary to invasive molds. Conclusion Our study shows a high incidence of IFIs secondary to Candida, with few patients diagnosed with non-Candida IFIs (Figure 3). Non-Candida IFIs, mostly secondary to endemic mycoses, occurred more than a year after transplant. Patients are at highest risk for Candida IFIs within the first 30 days after PT, likely secondary to organ space surgical site infections, despite receipt of antifungal prophylaxis. Breakthrough invasive candidiasis occurred in 90% of cases. Though our study lacked a comparator group without prophylaxis, these data question the effectiveness of fluconazole prophylaxis after PT. Disclosures All Authors: No reported disclosures