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Background The dimorphic mycoses (DM) of the United States, Histoplasma, Coccidioides, and Blastomyces, commonly known as endemic mycoses of North America (in addition to Paracoccidioides), are increasingly being diagnosed outside their historical areas of endemicity. Despite this trend, the maps outlining their geographical distributions have not been updated in more than half a century using a large, nationwide database containing individual patient-level data. Methods Retrospective analysis of >45 million Medicare fee-for-service beneficiaries from 1 January 2007 through 31 December 2016. Diagnoses of histoplasmosis, coccidioidomycosis, and blastomycosis were defined by International Classification of Diseases 9th/10th edition codes. Primary outcome was the incidence of histoplasmosis, coccidioidomycosis, and blastomycosis for each US county. Clinically meaningful thresholds for incidence were defined as 100 cases per 100,000 person-years cases for histoplasmosis and coccidioidomycosis and 50 cases for blastomycosis. Results There were 79,749 histoplasmosis, 37,726 coccidioidomycosis, and 6,109 blastomycosis diagnoses in unique persons from 2007-2016 across 3,143 US counties. Considering all US states plus Washington DC, 94% (48/51) had at least one county above the clinically relevant threshold for histoplasmosis, 69% (35/51) for coccidioidomycosis, and 78% (40/51) for blastomycosis. Conclusion Persons with histoplasmosis, coccidioidomycosis, and blastomycosis are diagnosed in significant numbers outside their historical geographic distributions established more than 50 years ago. Clinicians should consider DM diagnoses based on compatible clinical syndromes with less emphasis placed on patient’s geographic exposure. Increased clinical suspicion leading to a subsequent increase in DM diagnostic testing would likely result in fewer missed diagnoses, fewer diagnostic delays, and improved patient outcomes.

Background IDSA guidelines on candidemia recommend fluconazole as first-line therapy when the risk of fluconazole-resistance (fluc-R) is low. There is no method to estimate risk of resistance resulting in extended use of echinocandins and prolonged hospitalization. This study aimed to develop a clinical predictive model to identify patients at low risk for fluc-R where initial use of fluconazole or early step-down would be appropriate. Methods We performed a retrospective analysis of all hospitalized adult patients with positive blood culture for Candida spp. from 2013 to 2019. We performed a multivariable logistic regression model to identify factors associated with fluc-R. Stepwise regression was performed on bootstrapped samples to test individual variable stability and estimate confidence intervals. We used receiver operator curves to assess performance across the probability spectrum. Results 539 adults with candidemia were identified. 13.4% (72/539) of Candida isolates were fluc-R. Increased risk of fluc-R was associated with older age, prior bacterial bloodstream infection (2.02 [1.13, 3.63]), myelodysplastic syndrome (3.09 [1.13, 8.44]) and receipt of azole therapy (5.42 [2.90, 10.1]) within 1 year prior to index blood culture, as well as history of bone marrow or stem cell transplant (2.81 [1.41, 5.63]). The model had good discrimination (optimism corrected c-statistic 0.771) and all the selected variables were stable. The prediction model had a negative predictive value of 95.7% for the selected sensitivity cut-off of 90.3%. Conclusions This model is a potential tool for identifying patients at low risk for fluc-R candidemia to receive fluconazole as initial therapy or early stepdown.

Background This study quantifies the mortality attributable to Candida bloodstream infections (BSI) in the modern era of echinocandins. Design We conducted a retrospective cohort study of adult patients admitted to Barnes Jewish Hospital, a 1,368-bed tertiary care academic hospital, in Saint Louis, Missouri from 1/2/2012-4/30/2019. We identified 626 adult patients with Candida BSI that were frequency-matched with 6,269 control patients that had similar Candida BSI risk-factors. The 90-day all-cause mortality attributable to Candida BSI was calculated using three methods—propensity score matching, matching by inverse weighting of propensity score, and stratified analysis by quintile. Results The 90-day crude mortality was 42.4% (269 patients) for Candida BSI cases and 17.1% (1,083 patients) for frequency-matched controls. Following propensity score-matching, the attributable risk difference for 90-day mortality was 28.4% with hazard ratio (HR) of 2.12 (95% CI, 1.98-2.25, p<0.001). In the stratified analysis, the risk for mortality at 90 days was highest in patients in the lowest risk quintile to develop Candida BSI (HR 3.13 (95% CI, 2.33-4.19). Patients in this lowest risk quintile accounted for 81(61%) of the 130 untreated patients with Candida BSI. Sixty nine percent of untreated patients (57/83) died versus 35% of (49/127) of treated patients (p<0.001). Conclusions Patients with Candida BSI continue to experience high mortality. Mortality attributable to Candida BSI was more pronounced in patients at lowest risk to develop Candida BSI. A higher proportion of these low-risk patients went untreated, experienced higher mortality, and should be the target of aggressive interventions to ensure timely, effective treatment.

Histoplasmosis is a common opportunistic infection in people with HIV (PWH); however, no study has looked at factors associated with the long-term mortality of histoplasmosis in PWH. We conducted a single-center retrospective study on the long-term mortality of PWH diagnosed with histoplasmosis between 2002 and 2017. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death < 90 days), late mortality (death ≥ 90 days), and long-term survivors. Patients diagnosed during or after 2008 were considered part of the modern antiretroviral therapy (ART) era. Insurance type (private vs. public) was a surrogate indicator of socioeconomic status. Out of 54 PWH infected with histoplasmosis, overall mortality was 37%; 14.8% early mortality and 22.2% late mortality. There was no statistically significant difference in survival based on the availability of modern ART (p = 0.60). Insurance status reached statistical significance with 38% of survivors having private insurance versus only 8% having private insurance in the late mortality group (p = 0.05). High mortality persists despite the advent of modern ART, implicating a contribution from social determinants of health, such as private insurance. Larger studies are needed to elucidate the role of these factors in the mortality of PWH.