Targeted versus universal antifungal prophylaxis among liver transplant recipients.

Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were 11 and 6 days, respectively (p < 0.0001). The incidence of invasive fungal infections (IFIs) in targeted and universal groups was 6.9% and 4.2% (p = 0.34). Overall, intra-abdominal candidiasis (73%) was the most common IFI. Posttransplant bile leaks (p = 0.001) and living donor transplants (p = 0.04) were independent risk factors for IFI. IFIs occurred in 6% of high-risk transplants who received prophylaxis and 4% of low-risk transplants who did not receive prophylaxis (p = 1.0). Mortality rates (100 days) were 10% (targeted) and 7% (universal) (p = 0.26); attributable mortality due to IFI was 10%. Compliance with prophylaxis recommendations was 97%. Prophylaxis was discontinued for toxicity in 2% of patients. Targeted antifungal prophylaxis in LT recipients was feasible and safe, effectively prevented IFIs and reduced the number of patients exposed to antifungals. Bile leaks and living donor transplants should be considered high-risk indications for prophylaxis.

Lactobacillus probiotic use in cardiothoracic transplant recipients: a link to invasive Lactobacillus infection?

Organisms contained in probiotics are generally regarded as non-pathogenic and safe to administer. However, increasing reports of probiotic-associated infection raise concern over the safety of these products. We report a case of Lactobacillus empyema in a human immunodeficiency virus-infected lung transplant recipient receiving a probiotic containing Lactobacillus rhamnosus GG. We compare the epidemiology of Lactobacillus infections in heart and lung transplant recipients at our institution before and after the introduction of this probiotic, and discuss the potential mechanism for Lactobacillus within the probiotic to cause infections and disseminate.

Bioavailability and population pharmacokinetics of voriconazole in lung transplant recipients.

This study was undertaken to characterize the pharmacokinetics and bioavailability of voriconazole in adult lung transplant patients during the early postoperative period, identify factors significantly associated with various pharmacokinetic parameters, and make recommendations for adequate dosing regimens. Thirteen lung transplant patients received two intravenous infusions (6 mg/kg, twice daily [b.i.d.]) immediately posttransplant followed by oral doses (200 mg, b.i.d.) for prophylaxis. Blood samples (9/interval) were collected during one intravenous and one oral dosing interval from each patient. Voriconazole plasma concentrations were measured by high-pressure liquid chromatography (HPLC). NONMEM was used to develop pharmacokinetic models, evaluate covariate relationships, and perform Monte Carlo simulations. There was a good correlation (R(2) = 0.98) between the area under the concentration-time curve specific for the dose evaluated (AUC(0-∞)) and trough concentrations. A two-compartment model adequately described the data. Population estimates of bioavailability, clearance, V(c), and V(p) were 45.9%, 3.45 liters/h, 54.7 liters, and 143 liters. Patients with cystic fibrosis (CF) exhibited a significantly lower bioavailability (23.7%, n = 3) than non-CF patients (63.3%, n = 10). Bioavailability increased with postoperative time and reached steady levels in about 1 week. V(p) increased with body weight. Bioavailability of voriconazole is substantially lower in lung transplant patients than non-transplant subjects but significantly increases with postoperative time. CF patients exhibit significantly lower bioavailability and exposure of voriconazole and therefore need higher doses. Intravenous administration of voriconazole during the first postoperative day followed by oral doses of 200 mg or 400 mg appeared to be the optimal dosing regimen. However, voriconazole levels should be monitored, and the dose should be individualized based on trough concentrations as a good measure of drug exposure.

Pseudomonas aeruginosa bacteremia over a 10-year period: multidrug resistance and outcomes in transplant recipients.

AIM: Transplant recipients are at risk for hospital-acquired infections (HAIs), including those caused by Pseudomonas aeruginosa. Of all HAIs, bloodstream infection (BSI) remains one of the most life-threatening. METHODS: Over a 10-year period, we studied 503 patients, including 149 transplant recipients, with pseudomonal BSI from the University of Pittsburgh Medical Center. Trends in antimicrobial susceptibility, risk factors for multidrug resistance (MDR), and outcomes were compared between transplant and non-transplant patients. RESULTS: Resistance to all antibiotic classes was significantly greater in pseudomonal blood culture isolates from transplant compared with non-transplant patients (P<0.001). Of isolates from transplant recipients (n=207), 43% were MDR, compared with 18% of isolates from non-transplant patients (n=391) (odds ratio [OR] 3.47; 95% confidence interval [CI] 2.34-5.14, P<0.001). Among all patients, independent risk factors for MDR P. aeruginosa BSI included previous transplantation (OR 2.38; 95% CI 1.51-3.76, P<0.001), hospital-acquired BSI (OR 2.41; 95% CI 1.39-4.18, P=0.002), and prior intensive care unit (ICU) admission (OR 2.04; 95% CI 1.15-3.63, P=0.015). Mortality among transplant recipients was 42%, compared with 32% in non-transplant patients (OR 1.55; 95% CI 0.87-2.76, P=0.108). For transplant recipients, onset of BSI in the ICU was the only independent predictor of mortality (OR 8.00; 95% CI 1.71-37.42, P=0.008). CONCLUSIONS: Transplant recipients are at greater risk of MDR P. aeruginosa BSI, with an appreciable mortality. Future management must concentrate on the implementation of effective preventative strategies.