Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis.

Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.

Solid organ transplant recipients can be highly immune suppressed, and infection with Coccidioides (valley fever) after transplant can lead to severe infections in these patients. Our study showed that fluconazole was safe and effective for preventing Coccidioides in kidney transplant recipients.

Blood culture identification (BCID) performance in polymicrobial bacteremia.

The rapid multiplex PCR (rmPCR)-based FilmArray® blood culture identification (BCID) assay reduces time from positive blood culture to organism identification. Polymicrobial bacteremia (PMB) is a known area of reduced diagnostic fidelity for BCID and remains incompletely characterized. All cases of clinically confirmed PMB at a large academic single center from a 23-month period were evaluated in a retrospective cohort analysis. A total of 207 samples were identified and studied. Overall, 49.3% (N = 102) of polymicrobial cultures were incompletely identified by FilmArray® result. There were no significant between-group differences in comorbidity status, length of stay, mortality, or source between patients with PMB who had complete versus incomplete BCID identification. Our results suggest that rmPCR-based assays frequently miss organisms in PMB and should be interpreted accordingly.

Evolving Applications of Artificial Intelligence and Machine Learning in Infectious Diseases Testing.

BACKGROUND: Artificial intelligence (AI) and machine learning (ML) are poised to transform infectious disease testing. Uniquely, infectious disease testing is technologically diverse spaces in laboratory medicine, where multiple platforms and approaches may be required to support clinical decision-making. Despite advances in laboratory informatics, the vast array of infectious disease data is constrained by human analytical limitations. Machine learning can exploit multiple data streams, including but not limited to laboratory information and overcome human limitations to provide physicians with predictive and actionable results. As a quickly evolving area of computer science, laboratory professionals should become aware of AI/ML applications for infectious disease testing as more platforms are become commercially available. CONTENT: In this review we: (a) define both AI/ML, (b) provide an overview of common ML approaches used in laboratory medicine, (c) describe the current AI/ML landscape as it relates infectious disease testing, and (d) discuss the future evolution AI/ML for infectious disease testing in both laboratory and point-of-care applications. SUMMARY: The review provides an important educational overview of AI/ML technique in the context of infectious disease testing. This includes supervised ML approaches, which are frequently used in laboratory medicine applications including infectious diseases, such as COVID-19, sepsis, hepatitis, malaria, meningitis, Lyme disease, and tuberculosis. We also apply the concept of "data fusion" describing the future of laboratory testing where multiple data streams are integrated by AI/ML to provide actionable clinical knowledge.

Greater preexisting interferon γ responses to mycobacterial antigens and lower bacillary load during HIV-associated tuberculosis.

The role of preexisting interferon (IFN) γ responses in controlling bacillary burden in human immunodeficiency virus (HIV)-associated tuberculosis is not known. Among BCG-immunized HIV-infected adults who developed tuberculosis in a phase III trial of an investigational tuberculosis vaccine, greater baseline IFN-γ responses to early secretory antigenic target 6 and Mycobacterium tuberculosis whole-cell lysate were associated with reduced bacillary burden on sputum smear grade, days to culture positivity on agar, and sputum culture grade during subsequent tuberculosis. This association was most consistent among recipients of the investigational vaccine. When HIV-associated tuberculosis develops, greater preexisting IFN-γ responses to mycobacterial antigens are associated with reduced tuberculosis bacillary burden. ClinicalTrials.gov Identifier. NCT0052195.

Clostridium difficile infections in patients with severe burns.

With improved survival in burn patients, Clostridium difficile infection (CDI) remains a significant potential complication. The incidence of, risk factors for, and outcomes of CDI in severely burned patients are poorly studied and remain unclear. This study involves retrospective case control and cohort studies using electronic medical records from February 1, 2002 to January 31, 2009 at the US Department of Defense's only burn unit. Demographic, risk factor, and outcome data were collected for all C. difficile toxin positive patients in the burn, medical, and surgical intensive care units and the hospital's step down unit along with an additional analysis of a 2:1 matched control of C. difficile toxin negative to positive burn patients. In the burn intensive care unit (BICU) population there was an incidence of 7.9 cases per 10,000 patient days; less than the non-burn unit rate of 15.2 cases (p-value < 0.01). The BICU patients were young males with a median 42% total body surface area burns. There were higher frequencies of operations and prior aminoglycoside use, with longer unit stays and times until death or discharge. There was no difference in treatments, morbidity, or mortality. The comparison of patients with positive and negative C. difficile toxin among those in the BICU revealed few significant differences in risk factors or outcomes. Differences in risk factors between burn and non-burn patients were likely markers of the populations rather than independent risk factors for CDI in the burn population with overall lower rates likely reflective of younger, healthier patients in the BICU and more aggressive infection control practices.