Andrej Spec

Impact of Infectious Diseases Consultation on Mortality of Cryptococcal Infection in Patients Without HIV

Background An infectious disease (ID) consultation is often obtained to treat patients with cryptococcosis due to the complex nature of the disease, but has never been demonstrated to impact outcomes. Methods We assembled a retrospective cohort of 147 consecutive cases of cryptococcosis in patients without HIV. Patients who were diagnosed less than 24 hours prior to death were excluded. Survival analysis was performed with Cox regression with survival censored past 90 days. Results The patients with an ID consult had a higher fungal burden but a lower 90-day mortality compared to patients without ID involvement (27% vs 45%, p<0.001), with an adjusted hazard ratio of not receiving an ID consult of 4.1 (95% CI: 2.2, 7.6). The ID consult group was more likely to receive an indicated lumbar puncture (86% vs 32%, p<0.001), and more likely to be treated with amphotericin B (AmB) (87% vs 24%, p<0.001) and flucytosine (5-FC) (57% vs 16%, p<0.001) when indicated. The duration of therapy with AmB (14 vs 11 days, p=0.05) and 5-FC (7.5 vs 1 days, p<0.001) was longer in the ID consult group. Conclusions Patients that received an ID consult were significantly less likely to die in the 90 days following diagnosis. Patients seen by ID physicians were more likely to be managed according to evidence based practice established by randomized controlled trials and published in IDSA guidelines. These data suggest that an ID consult should be an integral part of clinical care of patients with cryptococcosis.Background An infectious disease (ID) consultation is often obtained to treat patients with cryptococcosis due to the complex nature of the disease, but has never been demonstrated to impact outcomes. Methods We assembled a retrospective cohort of 147 consecutive cases of cryptococcosis in patients without HIV. Patients who were diagnosed less than 24 hours prior to death were excluded. Survival analysis was performed with Cox regression with survival censored past 90 days. Results The patients with an ID consult had a higher fungal burden but a lower 90-day mortality compared to patients without ID involvement (27% vs 45%, p<0.001), with an adjusted hazard ratio of not receiving an ID consult of 4.1 (95% CI: 2.2, 7.6). The ID consult group was more likely to receive an indicated lumbar puncture (86% vs 32%, p<0.001), and more likely to be treated with amphotericin B (AmB) (87% vs 24%, p<0.001) and flucytosine (5-FC) (57% vs 16%, p<0.001) when indicated. The duration of therapy with AmB (14 vs 11 days, p=0.05) and 5-FC (7.5 vs 1 days, p<0.001) was longer in the ID consult group. Conclusions Patients that received an ID consult were significantly less likely to die in the 90 days following diagnosis. Patients seen by ID physicians were more likely to be managed according to evidence based practice established by randomized controlled trials and published in IDSA guidelines. These data suggest that an ID consult should be an integral part of clinical care of patients with cryptococcosis.

Disseminated cryptococcosis with brain involvement in patients with chronic lymphoid malignancies on ibrutinib

Abstract We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.

End-Stage Liver Disease Is a Strong Predictor of Early Mortality in Cryptococcosis

End stage liver disease (ESLD) patients have a high mortality with cryptococcosis. In this retrospective cohort of 232 patients with cryptococcosis , 25 had ESLD. Their mortality was dramatically higher and more rapid, suggesting they are an important sub-population.

Comparative Epidemiology and Outcomes of Human Immunodeficiency virus (HIV), Non-HIV Non-transplant, and Solid Organ Transplant Associated Cryptococcosis: A Population-Based Study

In this population-based study in the contemporary era in the United States, the proportion of human immunodeficiency virus (HIV)-negative patients with cryptococcosis approaches that in HIV-infected patients. Cryptococcosis is associated with higher mortality rates in HIV-negative patients (including organ transplant recipients).

Invasive Fungal Infections Secondary to Traumatic Injury

Invasive fungal infection (IFI) is a rare but serious complication of traumatic injury. The purpose of this article is to review the epidemiology, natural history, mycology, risk factors, diagnosis, treatment, and outcomes associated with post-traumatic IFI in military and civilian populations. The epidemiology of post-traumatic IFI is poorly characterized, but incidence appears to be rising. Patients often suffer from severe injuries and require extensive medical interventions. Fungi belonging to the order Mucorales are responsible for most post-traumatic IFI in both civilian and military populations. Risk factors differ between these cohorts but include specific injury patterns and comorbidities. Diagnosis of post-traumatic IFI typically follows positive laboratory results in the appropriate clinical context. The gold standard of treatment is surgical debridement in addition to systemic antifungal therapy. Patients with post-traumatic IFI may be at greater risk of amputation, delays in wound healing, hospital complications, and death as compared to trauma patients who do not develop IFI. More research is needed to understand the factors surrounding the development and management of post-traumatic IFI to reduce the significant morbidity and mortality associated with this disease.

The Brief Case: Dyspnea in a Profoundly Immunocompromised Man

A 61-year-old male presented to a hospital in Missouri with several months of progressive shortness of breath and low-grade fevers. He had a past medical history of chronic obstructive pulmonary disease and diffuse large B-cell lymphoma, which was treated with a matched unrelated donor bone marrow

Creation and Assessment of a Clinical Predictive Calculator and Mortality Associated With Candida krusei Bloodstream Infections

Abstract Background Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis. Methods We conducted a retrospective analysis of hospitalized patients with Candida BSI at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and laboratory values. Multivariable logistic and Cox regression were used to identify risk factors associated with CK and mortality, respectively. Results We identified 1873 individual patients who developed Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted by hematologic malignancy, gastric malignancy, neutropenia, and the use of prophylactic azole antifungals, monoclonal antibodies, and β-lactam/β-lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence interval, 0.81–0.91). The crude mortality rates were 64.4% for CK BSI and 41.4% for non-CK BSI. Although CK was associated with higher mortality in univariable Cox regression, this relationship was no longer significant with the addition of the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic liver disease, and elevated creatinine. Conclusions Six patient comorbidities predicted the development of CK BSI with high accuracy. Although patients with CK BSI have higher crude mortality rates than patients with non-CK BSI, this difference is not significant when accounting for other patient characteristics.

Cryptococcal meningitis in AIDS

Cryptococcal meningitis remains a significant cause of morbidity and mortality amongst patients living with human immunodeficiency virus (HIV). The prevalence in the developed world has decreased as HIV is being diagnosed earlier, but is still significant, and the prevalence in resource-limited settings is exceedingly high. The presenting symptoms usually include a headache, fever, and, less often, cranial nerve abnormalities. Space-occupying lesions do occur, but are rare. Once diagnosed, patients should be treated with a combination of amphotericin and flucytosine, with step-down therapy to fluconazole for a minimum of a year, or until the CD4 count is above 100 cells/μL, whichever is longer. In the acute phase of treatment increased opening pressure is common, which should be managed aggressively with frequent lumbar punctures, or through neurosurgical interventions (lumbar drains, ventriculoperitoneal shunts) if those fail. Antiretrovirals should be delayed at least 2 weeks, but maybe as many as 10 weeks, after initiation of antifungal therapy in order to prevent clinical or subclinical immune reconstitution inflammatory syndrome (IRIS), which may lead to increased mortality. However, if IRIS does develop, there is no role for antiretroviral interruption, and the condition should be managed supportively by use of anti-inflammatories and aggressive management of elevated opening pressure, if present. Steroids should be administered for specific indications only (IRIS or cryptococcoma with cerebral edema and risk of herniation) as routine use of steroids increases mortality in cryptococcal meningitis.

Erratum: In vitro activity of isavuconazole against fluconazole-resistant isolates of Histoplasma capsulatum

No clinical trials for histoplasmosis have been performed with the newer azoles, leaving itraconazole as the azole of choice. In vitro studies suggest that Histoplasma capsulatum from patients that relapse on fluconazole has higher minimum inhibitory concentrations (MICs) to fluconazole and voriconazole but not itraconazole and posaconazole. The newest azole, isavuconazole, shares structural similarity to voriconazole, but to date nobody has explored emergence of resistance. In vitro susceptibilities to isavucoanzole and fluconazole were performed on previously obtained isolates from the patients who relapsed on fluconazole therapy. Susceptibilities were determined by NCCLS method M27A developed for yeasts, as modified for H. capsulatum. The change in the MIC from the primary to the relapse isolate was tested using Wilcoxon Rank-Sum for paired data. Among the primary isolates, the median MICs were 1.0 (range 0.25 to 4.0) μg/ml for fluconazole and ≤0.007 (range ≤0.007 to 0.015) μg/ml for isavuconazole. In the group of relapsed isolates, the median MICs rose to 8.0 (range 0.25 to 64.0) μg/ml for fluconazole and remained unchanged at ≤0.007 (range ≤0.007 to 0.015) μg/ml for isavuconazole (P < .001). Only one isolate exhibited a nonsignificant increase in MIC to isavuconazole. Histoplasma isolates from patients who relapsed on fluconazole did not have an elevation in MICs to isavuconazole. This differs from the results previously seen with voriconazole and suggests that despite a closer structural similarity to voriconazole than itraconazole and posaconazole, isavuconazole has a higher barrier to resistance and may be effective as therapy for histoplasmosis.

Risk Factors and Mortality Associated with Candida krusei Bloodstream Infections

Abstract Background Candida krusei (CK) candidemia is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. We analyzed factors associated with C. krusei candidemia and its outcomes. Methods A retrospective analysis of hospitalized patients with candidemia was conducted at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and labs. Univariable logistic and Cox regression were used to identify potential risk factors associated with CK and mortality, respectively. Multivariable analyses were then constructed parsimoniously from these variables. Results Of 1,873 candidemia events, 59 were due to CK. In multivariable analysis, CK candidemia was predicted by hematologic malignancy (OR 8.9, 95% CI [4.1, 19.7]), stomach cancer (OR 14.6, 95% CI [2.9, 72.5]), absolute neutrophil count (OR 2.4, 95% CI [1.2, 4.8]), and the use of prophylactic azole antifungals (OR 2.2, 95% CI [1.1, 4.3]), monoclonal antibodies (OR 5.7, 95% CI [2.0, 15.8]), and penicillin β-lactamase inhibitors (OR 2.5, 95% CI [1.3, 4.8]). The C-statistic was 0.86 (95% CI [0.81, 0.91]). The crude mortality rates were 86.4% for CK candidemia and 63.6% for non-CK candidemia. Although CK was associated with higher mortality in univariable Cox regression (Figure 1, HR 1.8, 95% CI [1.3, 2.4]), this relationship was no longer significant (HR 1.2, 95% CI [0.8, 1.7]) with the addition of the following confounders: hematologic malignancy (HR 0.9, 95% CI [0.7, 1.1]), absolute neutrophil count (HR 1.7, 95% CI [1.4, 2.2]), stomach cancer (HR 1.0, 95% CI [0.5, 1.9]), coagulopathy (HR 1.0, 95% CI [0.9, 1.2], and prophylactic corticosteroids (HR 1.4, 95% CI [1.2, 1.7] (Figure 2). Conclusion A similar set of patient characteristics is associated with both CK infection and increased mortality, suggesting that patients with CK candidemia are at higher risk of mortality due to underlying illness rather than organism-specific mechanisms.Figure 1. Univariable 90-day survival analysis stratified by CK (red) versus non-CK (blue) candidemia.Figure 2. Multivariable 90-day survival analysis stratified by CK (red) vs non-CK (blue) candidemia. Disclosures W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant Gilead: Scientific Advisor, Consulting fee Astellas: Grant Investigator, Research grant A. Spec, Astellas Pharma US, Inc.: Grant Investigator, Research grant