Razonable, Raymund R

AbstractThe contrasting outcomes of lymphocyte manipulation after solid organ transplantation are allograft rejection and infections, commonly with cytomegalovirus (CMV). Peripheral blood absolute lymphocyte count (ALC) may serve as a predictive marker for these outcomes. Using a retrospective review of clinical and laboratory dataset, we aimed to determine whether a range of ALC (termed “safe ALC corridor”) exists where CMV infection and rejection outcomes are minimal in a cohort of 381 kidney transplant recipients. In an extended Cox model using a time‐dependent covariate for peripheral blood ALC, a value below the cut‐off of 610 cells/uL was associated with the development of CMV infection both in the overall cohort (Hazard Ratio [HR] 2.25 (95% confidence internal [CI] 1.02‐4.96; P = .043) and the subgroup of high‐risk CMV D+/R‐ mismatch patients (HR 2.91 [95% CI 1.09‐7.77]; P = .033). In contrast, a time‐dependent Cox analysis did not show any significant association between ALC and rejection (per IQR decrease, HR 1.2 [95% CI: 0.76‐1.9]; P = .434). Accordingly, a “safe ALC corridor” could not be defined. In conclusion, a low peripheral blood ALC (ie, threshold of 610 cells/uL) can be used to stratify the risk of CMV disease after kidney transplantation.

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

AbstractBackgroundNo consensus exists regarding optimal strategy for antifungal prophylaxis following lung transplant.ObjectiveTo review data regarding antifungal prophylaxis on the development of fungal infections.Study selection/AppraisalWe searched MEDLINE, Embase, and Scopus for eligible articles through December 10, 2019. Observational or controlled trials published after January 1, 2001, that pertained to the prevention of fungal infections in adult lung recipients were reviewed independently by two reviewers for inclusion.MethodsOf 1702 articles screened, 24 were included. Data were pooled using random effects model to evaluate for the primary outcome of fungal infection. Studies were stratified by prophylactic strategy, medication, and duration (short term < 6 months and long term ≥ 6 months).ResultsWe found no difference in the odds of fungal infection with universal prophylaxis (49/101) compared to no prophylaxis (36/93) (OR 0.76, CI: 0.03‐17.98; I2 = 93%) and preemptive therapy (25/195) compared to universal prophylaxis (35/222) (OR 0.91, CI: 0.06‐13.80; I2 = 93%). The cumulative incidence of fungal infections within 12 months was not different with nebulized amphotericin (0.08, CI: 0.04‐0.13; I2 = 87%) compared to systemic triazoles (0.07, CI: 0.03‐0.11; I2 = 21%) (P = .65). Likewise, duration of prophylaxis did not impact the incidence of fungal infections (short term: 0.11, CI: 0.05‐0.17; I2 = 89%; long term: 0.06, CI: 0.03‐0.08; I2 = 51%; P = .39).ConclusionsWe have insufficient evidence to support or exclude a benefit of antifungal prophylaxis.

Abstract Background Mycobacterium tuberculosis disease may occur after treatment of latent TB infection (LTBI). Prompted by a case of reactivation TB disease in a solid organ transplant (SOT) recipient who received LTBI treatment, we reviewed the literature to examine outcomes, adverse effects, resistance, and treatment choices of tuberculosis after LTBI therapy. Methods MEDLINE and Web of Science from inception to 5/2019 were reviewed using key words “latent tuberculosis infection” and “SOT” or “transplantation.” The search yielded nine cases, 41 cohort studies and six randomized controlled trials (RCT). Results Cohort and RCT demonstrated significant reduction in TB disease among transplanted patients who received LTBI therapy; only 56/2651 (2.1%) SOT patients developed TB after LTBI therapy. Adverse drug reactions occurred in 149/1148 (12.9%) and 73/641 (11.4%) of cohort and RCT patients, respectively. Among liver recipients, 56/266 (21%) developed side effects, of which half (29/56, 51.8%) was INH‐related. There was no reported INH resistance. Conclusions Latent TB infection treatment is efficacious in SOT recipients at risk of TB disease. However, tuberculosis may still occur despite LTBI treatment. Hepatotoxicity associated with LTBI therapy is infrequent, although more commonly observed among liver recipients.

AbstractBackgroundLung transplant recipients are prone to invasive fungal infections prompting many transplant centers to use prolonged triazole antifungal prophylaxis. From a practical standpoint, it is unclear if lung transplant recipients are able to continue prolonged or lifelong prophylaxis without premature discontinuation from side effects, drug interactions, development of fungal disease, or medication cost. We examined the number of patients that are able to reach a prophylactic endpoint and understand the reasons for early termination.MethodsWe conducted a retrospective chart review of all lung and heart‐lung transplant patients at Mayo Clinic Rochester from May 1, 2002 to December 31, 2017. Type, duration, and reason for discontinuation of triazole prophylaxis were examined.ResultsDuring the study period, 193 patients underwent lung or heart‐lung transplantation. Itraconazole, voriconazole, and posaconazole were given to 180, 73, and 60 post‐transplant patients, respectively. Providers switched itraconazole to another prophylactic antifungal medication for reasons other than prophylactic completion in 61.8% (126 out of 204) of exposure episodes; this was similar with voriconazole (68.8%, 53 out of 77, P = 0.41). Posaconazole was actively discontinued significantly less often (18.3%, 11 out of 60, P < 0.05). The most common reasons for discontinuing itraconazole were malabsorption (15.5% of exposure episodes) and concern for breakthrough fungal infection (10.2%). In comparison, the most common reason for voriconazole discontinuation was side effect or intolerance (54.5% of VR exposure episodes vs 9.8% of IT exposure episodes, P < 0.05).ConclusionsItraconazole and posaconazole appeared to have fewer side effects prompting discontinuation than voriconazole, but itraconazole was discontinued more often because of malabsorption and clinical suspicion of fungal infections.