Invasive fungal infections (IFIs) are one of the most feared complications associated with liver transplantation, with high rates of morbidity and mortality. We discuss the most common invasive fungal infections in the setting of liver transplant, including Candida, Aspergillus, and Cryptococcal infections, and some less frequent but devastating mold infections. Further, we evaluate the use of prophylaxis to prevent invasive fungal infection in this population as a promising mechanism to reduce risks to patients after liver transplant.
Background Blastomyces spp, the etiologic agents of blastomycosis, are endemic dimorphic fungi that require prolonged antifungal therapy, which can be complicated by adverse drug effects. Isavuconazonium sulphate (ISA) is a triazole with in vitro and in vivo activity against Blastomyces spp, but there is a paucity of clinical data supporting its use for treatment of blastomycosis. Methods This retrospective case series identified 14 patients with blastomycosis at least partially treated with ISA at the University of Wisconsin between 2015 and 2019. Treatment duration and outcomes were documented. In addition, 29 clinical isolates of Blastomyces spp between 2004 and 2017 were tested for minimum inhibitory concentrations against ISA and other antifungals. Results Fourteen patients were treated with a median of 255 days of ISA accounting for 68% of total therapy. Half (7 of 14) of the patients were immunocompromised, 11 of 14 (79%) were proven cases of blastomycosis, 7 of 14 (50%) had central nervous system (CNS) involvement, and 11 of 14 (79%) were cured. Antifungal susceptibility testing showed a consistently low minimum inhibitory concentration to ISA ≤ 0.015 mcg/mL. Conclusions This case series supports the efficacy and safety for ISA in the treatment of blastomycosis with or without CNS disseminated, especially when alternative triazoles cannot be used.
It is unknown whether patients with LTBI at high vs. low risk of developing active TB are currently adequately identified and treated in the US. In this study our objective was 1) To retrospectively apply the online calculator (tstin3d.com) to determine the probability of having LTBI and assign cumulative risk of progression. 2) Measure treatment outcomes in subjects with Low: 0-<10%, Intermediate: 10-<50% and High: 50–100% cumulative risk. We performed medical record review of tuberculin skin test and/or Interferon-γ release assay (IGRAs) positive patients with LTBI seen from 2010–2015. Of 125 subjects included, 51(41%), 46 (37%) and 28 (22%) subjects were in Low, Intermediate and High risk groups respectively. Tstin3d.com was useful in determining the probability of LTBI in tuberculin skin test positive US-born subjects. Overall treatment completion rate was 61% in 114 subjects with complete treatment information and similar completion rates were seen in the three groups (Low-60%, Intermediate-63% and High-57%). Provider assessment of important clinical risk factors was often incomplete. Logistic regression analysis showed no association of assessment of important risk factors with treatment completion. The major limitations of the calculator are the lack of an updated data on country-specific prevalence of TB disease as the global burden of TB continues to decrease as well as falsely high positive predictive values that due to “transiently” positive IGRA results in subjects from countries with low prevalence. Nonetheless, our findings suggest that tstin3d.com could be utilized in the US setting for improving providing awareness of risk stratification of patients with LTBI for short course treatment regimens based on risk.
Background HIV-infection leads to a higher risk of progression from asymptomatic, non-transmissible latent tuberculosis infection (LTBI) to active tuberculosis (TB). Specific comorbid medical risk factors increase this risk which can be decreased by successfully treating LTBI.Methods We compared risk of progression between HIV infected and uninfected adults seen at the Saint Louis University hospital from 2010 to 2015 using a validated online calculator (tstin3d.com). We also recorded information on prescribing practices and treatment completion rates in the two groups.ResultsOf 125 patients included, 10 had HIV, 10 AIDS, and 105 HIV-uninfected. The median annual TB-risk amongst the three groups was 8% (3–8%), 22% (21–25%), and 0.5% (0–6%) respectively. Smoking, recent TST/IGRA conversion, and diabetes were more prevalent among HIV/AIDS patients. Nine months of INH was most commonly prescribed for both HIV/AIDS (85%) and HIV-uninfected groups (45%). Of concern, were the equivalent rates of LTBI treatment non-completion seen between HIV/AIDS than HIV-uninfected patients (35% vs. 34%).Conclusion TSTin3D.com can facilitate increased provider awareness of TB activation risk factors and can quantitate risk of reactivation. We are currently implementing the calculator in the clinic to prospectively study how risk stratification can alter treatment choices for LTBI patients at highest risk for progression to TB.Disclosures All authors: No reported disclosures.
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