Kyle Brizendine

Predictors of Mortality and Differences in Clinical Features among Patients with Cryptococcosis According to Immune Status

Introduction Cryptococcosis is an invasive fungal infection causing substantial morbidity and mortality. Prognostic factors are largely derived from trials conducted prior to the modern era of antifungal and potent combination antiretroviral therapies, immunosuppression, and transplantation. Data describing the clinical features and predictors of mortality in a modern cohort are needed. Methods We conducted a retrospective cohort study of patients at our institution diagnosed with cryptococcosis from 1996 through 2010. Data included demographics, clinical features, diagnostics, treatment, and outcomes. Results We identified 302 individuals: 108 (36%) human immunodeficiency virus (HIV)-positive, 84 (28%) organ transplant recipients (OTRs), and 110 (36%) non-HIV, non-transplant (NHNT) patients including 39 with no identifiable immunodeficiency. Mean age was 49 years, 203 (67%) were male and 170 (56%) were white. All-cause mortality at 90 days was 21%. In multivariable logistic regression analyses, cryptococcemia (OR 5.09, 95% CI 2.54–10.22) and baseline opening pressure >25 cmH2O (OR 2.93, 95% CI 1.25–6.88) were associated with increased odds of mortality; HIV-positive patients (OR 0.46, 95% CI 0.19–1.16) and OTRs (OR 0.46, 95% CI 0.21–1.05) had lower odds of death compared to NHNT patients. Conclusions Predictors of mortality from cryptococcosis in the modern period include cryptococcemia, high intracranial pressure, and NHNT status while drug(s) used for induction and historical prognostic factors including organ failure syndromes and hematologic malignancy were not associated with mortality.

Carbapenem-Resistant Klebsiella pneumoniae Urinary Tract Infection following Solid Organ Transplantation

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging pathogen with a devastating impact on organ transplant recipients (OTRs). Data describing urinary tract infections (UTIs) due to CRKP, compared to extended-spectrum β-lactamase (ESBL)-producing and susceptible K. pneumoniae, are lacking. We conducted a retrospective cohort study comparing OTRs with a first episode of UTI due to CRKP, ESBL-producing K. pneumoniae, or susceptible K. pneumoniae. We identified 108 individuals; 22 (20%) had UTIs due to CRKP, 22 (20%) due to ESBL-producing K. pneumoniae, and 64 (60%) due to susceptible K. pneumoniae. Compared to susceptible K. pneumoniae (27%), patients with UTIs due to CRKP or ESBL-producing K. pneumoniae were more likely to have a ≥24-hour stay in the intensive care unit (ICU) before or after development of the UTI (64% and 77%, respectively; P < 0.001). Among 105/108 hospitalized patients (97%), the median lengths of stay prior to UTI with CRKP or ESBL-producing K. pneumoniae (7 and 8 days, respectively) were significantly longer than that for susceptible K. pneumoniae (1 day; P < 0.001). Clinical failure was observed for 8 patients (36%) with CRKP, 4 (18%) with ESBL-producing K. pneumoniae, and 9 (14%) with susceptible K. pneumoniae (P = 0.073). Microbiological failure was seen for 10 patients (45%) with CRKP, compared with 2 (9%) with ESBL-producing K. pneumoniae and 2 (3%) with susceptible K. pneumoniae (P < 0.001). In multivariable logistic regression analyses, CRKP was associated with greater odds of microbiological failure (versus ESBL-producing K. pneumoniae: odds ratio [OR], 9.36, 95% confidence interval [CI], 1.94 to 72.1; versus susceptible K. pneumoniae: OR, 31.4, 95% CI, 5.91 to 264). In conclusion, CRKP is associated with ICU admission, long length of stay, and microbiological failure among OTRs with UTIs. Greater numbers are needed to determine risk factors for infection and differences in meaningful endpoints associated with carbapenem resistance.

Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections.

Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.

Screening recipients of increased risk donor organs: A multicenter retrospective study

Organ Procurement & Transplantation Network policy requires post‐transplant screening of recipients of organs from donors at increased risk for transmission of HIV, hepatitis B virus, and hepatitis C virus. Available data suggest that follow‐up testing of recipients is not routinely conducted. Data on increased risk donors and recipients of their organs from 2008 to 2012 were retrospectively collected from 6 transplant centers after IRB approval. Descriptive statistics were performed. About 363 (60%) recipients were screened for transmission of HIV, HBV, and/or HCV at some time point; 257 (70.8%) within 90 days of transplant. The type of test used to screen for infection was variable with many recipients (25%‐43%) screened with serology alone. Our results reveal that post‐transplant screening for HIV, HBV, and HCV in recipients of increased risk donor organs did not universally occur and testing methods were variable.

A pharmacist-driven antimicrobial stewardship intervention targeting cytomegalovirus viremia in ambulatory solid organ transplant recipients

There is a growing need for robust antimicrobial stewardship interventions in both ambulatory and solid organ transplant (SOT) populations.

Fatal Fusarium infection manifesting as osteomyelitis following previous treatment with amphotericin B in a multi-visceral transplant: Case report and review of Fusarium infections in solid organ transplantation

Invasive fusariosis in solid organ transplant is uncommon and usually presents as localized infection with favorable outcomes compared to hematologic malignancies or bone marrow transplants. We report the first case of Fusarium osteomyelitis in a patient following multi‐visceral transplant and review Fusarium in organ transplant recipients and Fusarium bone and joint infections. Our case underscores the importance of early recognition and multidisciplinary approach to treatment and highlights potential failure to eradicate with amphotericin B monotherapy.

Real-World Use – Isavuconazole at a Large Academic Medical Center

Abstract Background Invasive fungal infections cause significant mortality and morbidity. Isavuconazole (ISV) is a new triazole approved for treatment of mucormycosis and aspergillosis. Data on its effectiveness outside clinical trials and in patients receiving prior triazole prophylaxis are lacking. Methods We conducted a retrospective cohort study on all patients at the Cleveland Clinic 6/1/2015–1/31/2017 who received ISV to determine 6-week response in a population with varying underlying diseases, and previous triazole prophylaxis or treatment. Descriptive statistics and univariate associations were calculated. Results Thirty-three patients were identified including organ transplant recipients (5), hematopoietic cell transplant recipients (7), and acute leukemia (18). Twenty-five had lung involvement while 13 had rhino-orbital-cerebral disease. In 13 cases, a fungal pathogen was identified: Mucorales (7) and Aspergillus (6). Fifteen received triazole prophylaxis prior to initiating ISV. Twenty-four received antifungal therapy immediately prior to switching to ISV: amphotericin B (1), fluconazole (1), voriconazole (16), posaconazole (4), and micafungin (2). Switching was often to broaden empiric coverage (18). Six-week response according to subgroups is presented in Figure 1 patients had therapeutic drug monitoring (TDM). Median level (IQR) was 6.75 (5.6–7.0) g/ml. Patients given ISV following triazole prophylaxis, those undergoing TDM, and those with an identified fungal pathogen had increased odds of complete or partial response, but this did not reach statistical significance (Figure 2). At 6 weeks mortality was 36%; complete or partial response observed in 45%. No ISV-related adverse effects reported. Conclusion To our knowledge, this is the first study to assess a real-world setting and a heterogeneous population with previous triazole prophylaxis or treatment. Our 6-week response (45%) compares favorably to published trials (35% Aspergillus; 11% Mucorales). Mortality in our study (36%) is similarly comparable to trial results (19% Aspergillus; 35% Mucorales). No major safety signal was observed. Larger cohorts are needed to describe additional real-world ISV use and determine associations with patient outcomes. Disclosures All authors No reported disclosures.