Wengenack, Nancy L.

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.

ABSTRACT Background Mycobacterium genavense is a rare opportunistic non-tuberculous mycobacterium primarily reported in advanced human immunodeficiency virus infection. Case Summary A 70-year-old woman with systemic lupus erythematosus developed progressive abdominal pain, weight loss, and mesenteric lymphadenitis repeatedly responsive to corticosteroids. Endoscopic biopsies revealed abundant acid-fast bacilli, and molecular testing confirmed the presence of M. genavense . Treatment with azithromycin, ethambutol, and rifabutin led to gradual recovery. Conclusion Steroid-responsive mesenteric inflammation in immunocompromised patients should prompt evaluation for infection, including mycobacteria and other culture-negative microorganisms using molecular diagnostics. This case report highlights the importance of plasma microbial cell-free DNA assays in the identification of fastidious organisms, like M. genavense , and, in some cases, serial testing may be useful to monitor treatment response.

Background: Candida auris is a globally emerging, multidrug-resistant fungal pathogen that causes serious, difficult-to-treat infections in hospitalized patients. C. auris cases in the United States have been linked to receipt of healthcare overseas. Outbreaks have also occurred in New York City, New Jersey, Illinois, Nevada, and California. We provide care to patients from all 50 states and 138 countries and are therefore, at risk for encountering C.auris within our facility. Methods: A case-finding tool was created by Infection Prevention and Control (IPAC) within the electronic medical record (EMR) to identify patients for screening. Inclusion criteria was centric to patients who were admitted in the previous 24 hours with a primary address in a foreign country or in areas of the United States with known C. auris transmission. Patients who are positive for Carbapenamase-producing organisms (CPO) are also included in screening criteria. In 2020, Clinical Microbiology validated a polymerase chain reaction (PCR) test in partnership with the State Health Department and IPAC. In January 2022, IPAC created a protocol that allows IPAC staff to order C. auris screening directly in the EMR utilizing the validated PCR test. The order is paired with communication from IPAC alerting the patient care team that C.auris screening is indicated. Instructions on test collection and information on C. auris are also included in messaging. The patient’s primary nurse then obtains verbal consent from the patient to collect a composite axilla–groin skin swab. Swabs are sent to Clinical Microbiology for testing, and results are reported directly into the EMR. Results: Since the introduction of the nursing protocol in January 2022, 2,660 patients have been identified for C. auris screening through November 2025. Of the 2,660 patients identified for testing, 1,111 patients had screening completed. Two patients tested positive for C. auris on screening. Both patients had prolonged travel to regions with known C. auris transmission. Conclusion: The EMR can be leveraged for early identification and screening of patients at risk of C.auris colonization. Case finding tools, combined with nursing protocols and communication strategies within the EMR can be effectively replicated and modified to respond to emerging infections.

Abstract Background Sputum color is a visual marker of airway inflammation and disease activity in bronchiectasis, ranging from clear or light gray (mucoid) to yellow-green (purulent), the latter largely reflecting neutrophil myeloperoxidase release. This study evaluated associations between sputum color and common clinical markers of disease activity to determine which parameters differed most between color categories. Methods Forty spontaneous sputum samples were analyzed from 80 consecutive adults with non-cystic fibrosis bronchiectasis (median age 70 years [IQR 12]; 74% female) enrolled between January 2024 and April 2025 in an observational study. Sputum color was graded using the Murray Sputum Color Chart and classified as mucoid (color #1) or purulent (colors #2-4). Clinical parameters, including blood cell counts, C-reactive protein (CRP), fractional exhaled nitric oxide (FeNO), and results of bacterial and acid-fast bacillus cultures (induced or bronchoscopic), were obtained from medical records if available within one month of enrollment. Categorical variables were analyzed using chi-square or Fisher’s exact tests and continuous variables with the Mann-Whitney U test. A secondary analysis compared patients who could versus could not produce spontaneous sputum. Results Of 40 samples, 20 (50%) were purulent. Blood neutrophil counts (median 4.5 vs. 3.9 x109/L), neutrophil-to-lymphocyte ratios (2.5 vs. 2.6), and eosinophil counts (1.7 vs. 1.7 x109/L) did not differ significantly between groups (n = 26). FeNO was normal in all 10 patients with available data and was not analyzed further. CRP was higher among patients with purulent sputum (4.6 vs. <3 mg/L; n = 20; p = 0.044). Bacterial growth was more frequent in purulent than mucoid samples (73% vs. 31%; n = 31; p = 0.032). Isolates in the purulent group included Klebsiella, Pseudomonas, Staphylococcus, and Streptococcus (n = 2 each), and single isolates of Acetobacter, Acinetobacter, Chryseobacterium, Delftia, Enterobacter, Escherichia, and Moraxella. In the mucoid group, Pseudomonas, Staphylococcus (n = 2 each), and Stenotrophomonas (n = 1) were identified. Mycobacterial growth did not differ significantly (20% vs. 12.5%; n = 31; p = 0.65). Patients unable to produce spontaneous sputum had a higher rate of mycobacterial isolation on induced/bronchoscopic samples (43% vs. 16%; n = 54; p = 0.027), though other parameters were similar. Over 90% of measurements were obtained within three days of enrollment, and freezing did not appear to alter sputum color. Conclusions Even within a small cohort, purulent sputum was associated with higher CRP and greater bacterial growth, supporting sputum color as a rapid, inexpensive marker of disease activity in bronchiectasis. Further research should clarify whether sputum color primarily reflects bacterial colonization, airway inflammation, or both. This abstract is funded by: None

ABSTRACT Background Intravesical Bacillus Calmette–Guerin (BCG) is a live attenuated vaccine for tuberculosis. Intravesical BCG (iBCG) administration is a highly effective immunotherapy for non‐muscle invasive bladder cancer (NMIBC). Although live attenuated vaccines are generally contraindicated in solid organ transplant recipients (SOTR), iBCG has been utilized for NMIBC in SOTR. We describe the clinical manifestations, management, and outcomes of disseminated Mycobacterium bovis ‐BCG infection (Mb‐BCGi) following iBCG therapy in SOTR for NMIBC. Methods All adult patients (> 18 years of age) diagnosed with NMIBC who received iBCG across three tertiary referral and transplant centers between 2000 and 2025 were identified. The study cohort consisted of SOTR who had received iBCG for NMIBC and subsequently developed disseminated Mb‐BCGi. English language literature review was performed to identify additional cases. Results A total of 4207 patients received iBCG during the study period. Thirty (0.71%) were SOTR, of whom two (6.7%) developed disseminated Mb‐BCGi, including bloodstream infection and prostate abscesses. Literature review identified two additional disseminated Mb‐BCGi cases in SOTR with lungs, bloodstream, and native kidney involvement, and one fatality. All cases required extended antimycobacterial therapy. Median times from SOT to Mb‐BCGi and from iBCG to Mb‐BCGi were 104 and 8 months, respectively. Conclusion SOTR appear to be at a higher risk of disseminated Mb‐BCGi following iBCG. Administration of iBCG in SOTR with NMIBC warrants careful risk‐benefit assessment and subsequent close monitoring. image

Abstract Background Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) is standard therapy for high-risk nonmuscle-invasive bladder cancer. However, M bovis infections can occur and are not well understood. We aimed to characterize clinical phenotypes, diagnosis, management, and outcomes of culture-confirmed M bovis BCG infections following intravesical therapy for urothelial carcinoma. Methods A retrospective single-center review of adults with culture-confirmed M bovis infection after intravesical BCG (May 2009–July 2024) was conducted, abstracting clinical, microbiologic, treatment, and outcome data. Results Twenty-two White male patients (median age, 77 years) were included; 8 (36.4%) had localized genitourinary infection, 6 (27.3%) had dissemination limited to blood, and 8 (36.4%) had dissemination to other organs. Patients with bloodstream-only infection presented acutely (median 1.5 days after last BCG), whereas those with localized or organ-disseminated disease presented months to years after BCG, with the longest diagnostic delays in organ-disseminated infection. Despite all cases had culture-proven M bovis BCG infection, acid-fast smear, Mycobacterium tuberculosis complex polymerase chain reaction, and histopathology had limited sensitivity. All isolates were susceptible to rifampin, isoniazid, and ethambutol; all were resistant to pyrazinamide. Median treatment duration exceeded 9 months, 94.7% achieved cure, and attributable mortality was 5.0% (1 vascular graft infection). Conclusions M bovis BCG infections following intravesical therapy have favorable outcomes but are often associated with diagnostic delays and prolonged treatment. Early suspicion, comprehensive diagnostic evaluation, and timely surgical source control when indicated are critical. Management strategies should be tailored based on the extent of disease dissemination and individual host factors.

ABSTRACT Background Solid organ transplant (SOT) recipients are at risk for Pneumocystis jirovecii pneumonia (PCP), yet how their clinical phenotype and outcomes compare with other immunocompromised patients without HIV remains poorly defined. Methods We conducted a multicenter retrospective cohort study of adults with proven or probable PCP from 2017 to 2025, including 95 SOT recipients and 588 non‐SOT, non‐HIV immunocompromised patients. The primary outcome was 90‐day mortality, secondary outcomes included new renal failure requiring dialysis, and 30‐day mortality. Outcomes were analyzed using inverse probability weighting (IPW) with winsorization to adjust for baseline differences. Results In unadjusted analysis, SOT recipients had lower 90‐day mortality (hazard ratio [HR]: 0.62, 95% CI 0.39–0.97, p = 0.037). After IPW with winsorization of extreme weights, SOT status remained associated with lower 90‐day mortality (HR: 0.32, 95% CI 0.13–0.76, p = 0.009), and 30‐day mortality (HR: 0.35, 95% CI: 0.14–0.92, p = 0.034). SOT recipients had higher odds of renal failure requiring dialysis in unadjusted analysis (OR: 3.49, 95% CI 1.94–6.14, p < 0.001), which persisted after IPW adjustment (OR: 1.62, 95% CI: 1.04–2.51, p = 0.032). Conclusions Despite higher rates of renal failure requiring dialysis, SOT recipients with PCP experienced significantly improved short‐ and intermediate‐term survival compared with other non‐HIV immunocompromised patients, underscoring the need for further investigation into transplant‐associated contributors to PCP outcomes.

ABSTRACT Bloodstream infections (BSIs) caused by opportunistic yeasts, namely those of the genus Candida , demonstrate strikingly high mortality rates and require early therapeutic intervention to optimize patient outcomes. Advancements in microbiological diagnosis of BSIs have introduced rapid molecular methods, including multiplex PCR panels, to detect common organisms directly from blood culture media. The BIOFIRE FilmArray Blood Culture Identification 2 (BCID2) assay is one such method and detects seven of the most common yeast species responsible for fungemia, enabling timelier therapeutic optimization by clinicians. Here, we evaluated the clinical performance of BCID2 for yeast identification from positive blood cultures between 2021 and 2025 at a tertiary medical center, compared to the reference standard method, which couples subculturing and diagnostic mass spectrometry. A total of 252 individual yeast identification events were confirmed using the reference method during our study period, 33 (13%) of which represent organisms that lack BCID2 PCR-based targets and 219 (87%) represent organisms targeted by this assay. Of the 219 identifications compatible with the BCID2 panel targets, 209 (95%) were correctly identified. Discordance between BCID2 and the reference method commonly stemmed from the inability of BCID2 to target all yeasts encountered clinically in blood culture, as well as its reduced accuracy in cultures where >1 yeast is present. Overall, these data suggest that the BCID2 assay is a rapid and accurate method to identify the most common organisms causing yeast BSI from blood culture; however, subculture-based reference techniques are important complementary tools in the clinical microbiology laboratory. IMPORTANCE Invasive fungal diseases, including bloodstream infections (BSIs) caused by yeasts, are increasing in prevalence alongside the growing global population of immunocompromised individuals. Prompt and targeted treatment is necessary for effective management of yeast BSI, and microbiological diagnostics play an important role in tailoring patient treatment. Rapid molecular assays that simultaneously detect multiple pathogens associated with a specific syndrome are attractive strategies to expedite pathogen identification. This includes the BIOFIRE FilmArray Blood Culture Identification 2 (BCID2) assay, which detects 33 organisms including 7 yeasts commonly associated with fungemia, directly from blood culture media. Its performance has been well established for the detection of bacteria and bacterial resistance markers from blood cultures. Here, we provide a yeast-specific snapshot into the microbiological performance of BCID2, highlighting its accuracy as well as limitations in detecting medically important yeasts compared to standard culture-based identification from a four-year specimen cohort collected in a tertiary care hospital.