Ranganath, Nischal

Abstract Alternaria spp. are dematiaceous ascomycetes that can cause opportunistic infections in immunocompromised hosts. They are challenging to identify and treat. However, optimal antifungal therapy remains undefined. We retrospectively reviewed antifungal susceptibilities (AST) of all Alternaria spp. isolates from adults at a tertiary care center between 2011 and 2025. We evaluated culture sources, minimum inhibitory concentration (MIC) and minimal effective concentration (MEC) distributions, and MIC₅₀/MIC₉₀ and MEC50/MEC90 values. Clinical characteristics, treatment measures, and outcomes of patients with clinically significant Alternaria spp. infections were described. Forty-one patients had Alternaria spp. isolated, most commonly from skin (n = 13), bone/joint (n = 5), nail (n = 3), or cornea (n = 3). Posaconazole and itraconazole demonstrated low MICs (MIC₅₀/MIC₉₀: 0.06/0.5 and 0.25/0.5 µg/mL, respectively). Voriconazole and isavuconazole showed higher MIC₅₀/MIC₉₀ (1/2 and 2/4 µg/mL). Caspofungin (0.125/0.5 µg/mL) and amphotericin B (0.25/1 µg/mL) had low MICs and MECs.s. Alternaria spp. represented clinically significant infection in 27 cases (66%); 26% were solid organ transplant recipients and 15% had hematologic malignancies. Other risk factors included preceding trauma (22%) and autoimmune disease (15%). Posaconazole was the most frequently used empiric agent (6, 32%). Following AST results, 14 patients (52%) received oral antifungal therapy; posaconazole was used in all 14. In addition, 7 patients (26%) received combination therapy with IV amphotericin B. Adjunctive surgery occurred in 14 cases (52%). Five patients (19%) died before completing therapy; Alternaria infections occurred predominantly in immunocompromised hosts and were frequently managed with posaconazole and surgery. Interpretive criteria for Alternaria spp. are needed to guide empiric and definitive therapy.

In this retrospective cohort study at a quaternary referral hospital, 829 adult patients supported by extracorporeal membrane oxygenation (ECMO) between January 1, 2014, and October 31, 2024, were screened for ventilator-associated pneumonia (VAP). The incidence of VAP in ECMO-supported patients was 17.7 per 1,000 ECMO days (venoarterial [VA] ECMO, 22.1 per 1,000 ECMO days; venovenous [VV] ECMO, 13.8 per 1,000 ECMO days). Median time from ECMO cannulation to diagnosis of VAP was 4 (interquartile range [IQR], 3–8; range 1–84) days. Gram-negative bacteria comprised most respiratory pathogens. A significant increase in minimum ECMO sweep was noted from 2 days before to 1 day after VAP diagnosis (0.79 L/min increase, p = 0.004). Only 38 of 153 patients (24.8%) met National Healthcare Safety Network (NHSN) VAP definitions. After creating a modified VAP definition, which included an ECMO sweep increase of 0.5 L/min as evidence of worsening respiratory status, 78 (51.0%) met the modified definition. Those who met the modified VAP definition had worse in-hospital (60.3% vs. 28.0%, p < 0.001), 30 day (33.3% vs. 17.3%, p = 0.023), and 90 day (53.8% vs. 25.3%, p < 0.001) mortality compared with those who did not meet the modified VAP definition. The incorporation of ECMO parameters into diagnostic criteria may improve detection sensitivity, but further validation is necessary before implementation.

ABSTRACT Background Babesia microti , a parasite transmitted by the Ixodes scapularis tick, can cause infections ranging in presentation from asymptomatic to fulminant, life-threatening disease. Ocrelizumab, an anti-CD20 B-lymphocyte monoclonal antibody used to treat multiple sclerosis, increases the risk of severe or relapsing infections with tick-borne pathogens. In rare cases, babesiosis may trigger hemophagocytic lymphohistiocytosis (HLH). Case Summary We report a case of babesiosis manifesting in a subacute fashion with secondary HLH in a 51-year-old female on B cell-depleting therapy. She presented in December with generalized weakness and fever and was found to have pancytopenia, transaminitis, and hyperinflammatory markers consistent with HLH. A microbial cell-free DNA next-generation sequencing test detected Babesia microti , with subsequent confirmation by blood PCR and smear demonstrating <0.01% parasitemia. The patient improved following treatment with atovaquone and azithromycin, along with corticosteroids for HLH. Conclusion This case highlights the heterogeneity of babesiosis and its potential to present with minimal parasitemia, yet severe systemic inflammation in immunocompromised hosts. Additionally, this case underscores the importance of maintaining a broad differential in patients on B cell-depleting agents who present with new pancytopenia and systemic inflammatory symptoms. Early utilization of microbial cell-free DNA next-generation sequencing tests may aid in timely diagnosis and treatment.

Background: Candidemia is a serious complication after gastrointestinal (GI) perforation and/or ischemia, yet most evidence pools candidemia with intra-abdominal candidiasis (IAC). We sought candidemia-specific risk factors after GI perforation and/or ischemia and evaluated associated outcomes. Methods: We conducted a single-center, retrospective matched case–control study of adults undergoing emergency surgical procedure for GI perforation and/or ischemia and admitted to a surgical intensive care unit. Cases with candidemia during index admission were matched 4:1 to controls by age, Charlson Comorbidity Index, and surgical procedure year. Conditional logistic regression assessed pre-specified risk factors, and exploratory outcomes included mortality, length of stay, and days on invasive ventilation. Results: Twenty-four cases were matched to 99 controls. Factors identified to be independently associated with candidemia include the presence of IAC (adjusted OR [aOR]: 5.51, 95% CI: 1.61, 18.89; p = 0.007), upper GI injury (aOR: 4.28, 95% CI: 1.52–12.08; p = 0.006), and diffuse intra-abdominal contamination, compared with contained/none (aOR: 3.21, 95% CI: 1.06–9.74; p = 0.040). Among candidemia cases, species distribution was Candida albicans 41.7%, C. glabrata 33.3%, C. parapsilosis 12.5%, with single cases of C. tropicalis, C. krusei , and C. dubliniensis . Candidemia was associated with a longer hospital length of stay (+13.97 d; 95% CI: 0.90–27.04; p = 0.036), without significant differences in ICU stay, duration of invasive ventilation, or mortality. Conclusions: After GI perforation and/or ischemia, the risk of candidemia is highest in patients with upper GI injury and diffuse contamination, independent of IAC. These readily identifiable operative features may guide targeted surveillance and selective early antifungal strategies. Prospective validation is warranted.

Background: There are limited oral treatment options available for resistant Gram-negative bacterial (GNB) infections. Minocycline, a second-generation tetracycline antibiotic, offers good bioavailability and broad-spectrum coverage that may be an option for GNB infections. Methods: We conducted a retrospective review of minocycline susceptibility testing performed on GNB isolates at the Mayo Clinic reference lab between 2013 and 2022. Minocycline susceptibility was evaluated with a focus on difficult-to-treat organisms and relevant anatomic source. Organisms included resistant isolates of Escherichia coli and Klebsiella pneumoniae ; high-risk ampC-derepressors, including Citrobacter freundii, Enterobacter cloacae, and K. aerogenes; and clinically challenging non-Enterobacterales, Acinetobacter species, Achromobacter species, and Stenotrophomonas maltophilia . Results: Of 217,206 GNB isolates, 18,148 Enterobacterales (EB) and 8,190 non- Enterobacter isolates were tested for minocycline susceptibility. Of these, 80% of all EB and 92% of non-EB isolates were susceptible. Among E. coli isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 78%, 76%, 70%, and 70.9%, respectively. Among the K. pneumoniae isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 46%, 38%, 37%, and 39.3%, respectively. 85% of C. freundii , 81% of E. cloacae, and 85% of K. aerogenes isolates were susceptible to Minocycline. 83.5% of Achromobacter species isolates, 66% of Acinetobacter species isolates, and 99.1% of S. maltophilia isolates were susceptible. Conclusions: Our study reports the largest collection of minocycline susceptibility findings in GNB. Minocycline showed in vitro activity against many difficult-to-treat GNB isolates, including ceftriaxone- and multidrug-resistant E. coli and some K. pneumoniae isolates, common Amp-C-producing species, and non-fermenting GNB, including Stenotrophomonas , Acinetobacter , and Achromobacter .

ABSTRACT Introduction Cytomegalovirus (CMV) causes substantial morbidity after solid organ transplantation. Valganciclovir (VGCV) remains a first‐line prophylactic agent, but it has significant myelosuppressive effect. Letermovir is approved for CMV prophylaxis in high‐risk kidney transplant recipients, but data on its use outside of that population are limited. We describe characteristics and outcomes of letermovir prophylaxis in non‐kidney transplant recipients. Methods We performed a retrospective, multi‐center study of all adult non‐kidney solid organ transplant recipients (SOTr) who received letermovir (March 2018–June 2024) for CMV prophylaxis. Outcomes included breakthrough and post‐prophylaxis delayed‐onset CMV infections, adverse events, and survival. Results A total of 64 patients were included in the final analysis. Of those, letermovir was used for primary prophylaxis in 56.2% of patients, while the remainder received it for secondary prophylaxis. The main rationale behind selecting letermovir was myelosuppression related to VGCV. During the median follow‐up of 361 days (IQR, 190–536), 40.6% remained on letermovir (median, 387 days); 25.0% completed prophylaxis (median, 116 days); and 34.3% discontinued prematurely (median, 49 days), mainly for cost barriers or adverse effects. Breakthrough infections occurred in 9 patients (14.1%), but only three (4.7%) were clinically significant. After stopping letermovir, 39.5% (15/38 among those who discontinued letermovir) developed post‐prophylaxis delayed‐onset CMV infection. Overall survival was 81.2%; there was one death attributed to CMV. Conclusion In this cohort of non‐kidney solid organ recipients, letermovir was well tolerated with low rates of clinically significant breakthrough infections. Early discontinuation was commonly cost‐driven. Post‐prophylaxis delayed‐onset CMV infections remain common. Large‐scale registry studies are needed to provide evidence for use of letermovir in non‐kidney transplant recipients.

Abstract Background Candidemia can occur as a consequence of gastrointestinal (GI) injury. The mortality of candidemia is high, ranging 30-60%, even with treatment with antifungal agents. In this retrospective matched case-control study, we aimed to elucidate the medical and surgical risk factors of developing candidemia in patients who received emergency surgery for GI ischemia and/or perforation, and compare clinical outcomes in these patients with or without candidemia. Methods All patients ≥ 18 years of age who had emergency GI surgery at Mayo Clinic Rochester, MN, for the indication of GI ischemia and/or perforation between 01/01/2018 to 07/31/2024 were included. Cases were defined as patients who developed candidemia during index admission and had no alternative sources of candidemia. Controls and cases were matched 4:1 on age (± 5 years), Charlson Comorbidity Index (± 3), and year of surgery (± 2 years). The relationships between risk factors of interest and case/control were assessed using conditional logistic regression. Results Among medical risk factors, any shock requiring vasopressor (OR = 3.44, 95% CI 1.00, 11.97) or respiratory failure (OR = 8.20, 95% CI 1.04, 64.53) during hospitalization were associated with increased risk of candidemia. Among surgical risk factors, perforation in the upper GI tract was strongly associated with development of candidemia (OR = 16.99, 95% CI 2.11, 136.95) and perforation in the lower GI tract were less likely to lead to candidemia (OR = 0.06, 95% CI 0.01, 0.44). The patients who had diffuse intraabdominal contamination were more likely to develop candidemia compared to those who had no contamination or contained contamination (OR = 3.87, 95% CI 1.33, 11.25). The patients with candidemia showed signal towards higher in-hospital and 30-day mortality, and had significantly longer stay in the hospital. Conclusion Candidemia was more frequently identified in patients with shock, respiratory failure, upper GI perforation, and intra-abdominal contamination, and contributed to significant morbidity and mortality. Further analysis will include building a multivariate logistic regression model to implement prospective trial for early initiation of antifungal therapy for high-risk population. Disclosures All Authors: No reported disclosures

Abstract Background Catheter related bloodstream infections (CRBSI) are associated with increased resource use, treatment costs, and mortality among patients with cancer. Coagulase-negative staphylococci (CoNS) are the most common cause of central venous catheter (CVC) infection in this population. While CVC removal remains the gold standard, CRBSI with CoNS is sometimes managed with CVC salvage, despite incomplete safety and efficacy data in patients with hematological malignancy.Table 1.Baseline Demographic and Clinical DataTable 2.Baseline Characteristics by Treatment Strategy Methods A retrospective review was conducted of adult patients at Mayo Clinic Rochester from 2013 to 2024 diagnosed with hematological malignancy and CRBSI with CoNS. Patients were included in a “CVC removed” group if the line was removed within 5 days of bacteremia onset, and all others were included in a “CVC retained” group. Electronic medical records were evaluated for relevant clinical comorbidities, risk factors, and management. The primary outcomes of interest were 90-day mortality and relapse. To control for baseline differences between groups, we employed a propensity weighted analysis based on inverse probability of treatment weighting using the propensity score.Weighted cumulative event rates for Relapse and Mortality Results A total of 140 cases were included, of whom 95 (67.9%) had undergone BMT and 111 (80.4%) were neutropenic at time of CRBSI. The predominant CoNS identified was Staphylococcus epidermidis (88.6%). 79 (56.4%) patients had the CVC retained and 61 (43.6%) underwent CVC removal. Those in whom the CVC was retained were more likely to be BMT recipients (p=0.007). However, line removal was more common with PICC lines (p&lt; 0.001) and in those hospitalized for management of line-associated bacteremia (p=0.022). Within 90 days, there were 10 patients (cumulative incidence 8.2%) who had microbiological relapse (2 [4.3%] in the CVC removed group and 8 [11.1%] in the CVC retained group). Propensity weighted analysis demonstrated significantly higher rate of microbiologic relapse with CVC retention (p=0.043) but no difference in mortality (p=0.128), as shown by weighted cumulative event rate curves in Figure 1. Conclusion Despite the finding of increased risk of relapse associated with CVC retention, there was no significant difference in mortality between CVC removal and retention among individuals with CoNS CRBSI and hematological malignancy. Disclosures All Authors: No reported disclosures

Abstract Background In 2019, the US performed 290,000 breast reconstructions with an estimated infection rate of 3-35%. Tissue expander infections detract from desired aesthetic effects, delay adjuvant treatments, increase morbidity and mortality, and have high recurrence rates (20-40%). Little is known about risk factors for recurrent tissue expander infections, particularly the impacts of different treatment modalities. Methods We conducted a single-center retrospective cohort study of adult women post-mastectomy who developed microbiologically-proven tissue expander infection between the period of 2017 – 2024. Outcomes including 12-month infection recurrence and risk factors for recurrence were compared between surgical versus nonoperative groups, as well as between three surgical strategies (i.e., one-stage, two-stage, explantation). Unadjusted and adjusted logistic regression models were used to assess the associations between the treatment modalities and the outcomes. Univariate models assessed the relationship between the covariates of interest and infection recurrence. Results 107 patients were included, with the majority treated with combination of antibiotics and surgical therapy (Table 1). There was no significant difference in outcomes when the operative versus antibiotics alone cohorts were compared (Table 2). The odds of infection recurrence and rehospitalization in patients who underwent two-staged exchange or explantation were significantly lower when compared with the one-staged group (Table 3). Univariate modeling found severity and radiation therapy to be numerically more common in the group experiencing recurrence, with a trend towards statistical significance (Table 4). Conclusion Our study demonstrates reduced risk of recurrent tissue expander infection with two-staged exchange or explantation, compared to one-staged exchange. Though limited by small sample size, the strengths of our study include our presentation of the real-world variability of these syndromes and their management, adjustment for infection severity and other potential confounders; and the focus on microbiologically-defined infections. Disclosures All Authors: No reported disclosures

Abstract Background Hematopoietic stem cell transplant (HSCT) recipients are susceptible to infections with respiratory viruses resulting in higher morbidity and mortality. Parainfluenza virus (PIV) infection in the setting of leukopenia is associated with higher risk of lower respiratory tract infection and mortality. Intravenous immunoglobulin (IVIG) has been used as adjunctive treatment in viral respiratory infections, although data guiding its use is limited.Table 1:Patient CharacteristicsTable 2:Clinical Outcomes Methods We conducted a retrospective cohort study of adult HSCT recipients diagnosed with PIV infection at our institution from January 2014 to September 2024. Diagnosis of PIV infection was made via BioFire® Respiratory Panel multiplex polymerase chain reaction (PCR) or viral culture from nasopharyngeal or bronchoalveolar lavage. Data on clinical characteristics and outcomes were collected and reviewed.Table 3:Clinical Outcomes for Patients with IgG &lt;767 mg/dL Results A total of 110 HSCT recipients were diagnosed with PIV infection by PCR or viral culture within the study period. Patient characteristics and clinical outcomes are summarized in Tables 1 and 2. PIV type 3 was the most common, followed by PIV type 4 and type 1. Eighteen patients (16.36%) had co-infections with another virus. A total of 16 patients received IVIG at time of PIV infection. The mean cumulative IVIG dose was 28.75 grams. Patients who received IVIG were more likely to have been hospitalized due to symptoms related to the viral infection (p=0.03) and had a lower immunoglobulin G level (p&lt; 0.001). Overall, there was no significant difference in rates of mechanical ventilation (12.5% vs 7.45%, p=0.616), development of secondary fungal or bacterial infection (12.5% vs 12.7%, p=1), or 90-day mortality (18.75% vs 6.38%, p=0.123) among patients treated with or without IVIG, respectively. Similarly, in a subset analysis of patients with IgG level &lt; 767 mg/dL, there were no significant difference in outcomes for patients treated with or without IVIG (Table 3). Conclusion There were no significant differences in clinical outcomes, including rates of mechanical ventilation, secondary infections, or 90-day mortality, between HSCT patients who received IVIG and those who did not for PIV infection. Larger studies are needed to gain insight into efficacy of IVIG as adjunctive treatment in PIV infections in this population. Disclosures All Authors: No reported disclosures