Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study.

This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Nine hundred lung transplant recipients were included. Median follow-up time from transplantation to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC. EU PAS registration number: EUPAS5269.

Delay of adequate empiric antibiotic therapy is associated with increased mortality among solid-organ transplant patients.

Empiric antibiotic therapy is often prescribed prior to the availability of bacterial culture results. In some cases, the organism isolated may not be susceptible to initial empiric therapy (inadequate empiric therapy or IET). In solid-organ transplant recipients, the overall incidence and clinical importance of IET is unknown. We performed a retrospective cohort study of patients admitted from 2002 to 2004. Multiple logistic regression analyses were conducted to determine associations between potential determinants and mortality. IET was administered in 169/312 (54%) patients, with a hospital mortality rate that was significantly greater than those receiving adequate therapy (24.9% vs. 7.0%; relative risk [RR] 3.55; 95% confidence interval [CI], 1.85-6.83; p < 0.001). Regression analysis demonstrated that an increasing duration of IET (adjusted odds ratio [OR] at 24 h: 1.33; 95% CI: 1.15-1.53; p < 0.001), ICU-associated infections (adjusted OR: 6.27; 95% CI: 2.79-14.09; p < 0.001), prior antibiotic use (adjusted OR: 3.56; 95% CI: 1.51-8.41; p = 0.004) and increasing APACHE-II scores (adjusted OR: 1.26; 95% CI: 1.16-1.34; p < 0.001) were independently correlated with hospital mortality. IET is common and appears to be associated with an increased hospital mortality rate in the solid-organ transplant population.