Impact of intravenous administration of voriconazole in critically ill patients with impaired renal function.

The administration of voriconazole by the intravenous (i.v.) route in patients with moderate or severe renal failure is limited because of potential toxic effects of the accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium. This study aimed to assess the impact of intravenous voriconazole administration on renal and liver function in critically ill patients with impaired renal function treated with this antifungal drug. The study population consisted of a retrospective cohort of patients admitted to medical-surgical intensive care units (ICUs) who were treated with i.v. voriconazole for more than 3 days. Patients with impaired renal function were those with serum creatinine concentration >1.5 mg/dL, creatinine clearance <50 mL/min, or under any extrarenal depuration procedure. Renal damage was defined as an increase of at least = 2 times initial serum creatinine level or starting of an extrarenal depuration procedure during voriconazole therapy. Liver damage was defined as an increase of = 4 times the initial serum concentration of liver enzymes, or = 2 times in patients with previous impaired liver function. A total of 69 patients was included in the study of which 26 (37.7%) had impaired renal function at the beginning of voriconazole treatment (serum creatinine >2.5 mg/dL in 10 patients). Mean (SD) duration of voriconazole treatment was 13.0 (9.5) days in patients with normal renal function and 11.2 (6.3) days in those with altered renal function. Renal damage during voriconazole therapy occurred in 13 (30.2%) patients with initial normal renal function and in 4 (15.4%) in patients with impaired renal function (P = 0.257). Liver damage during treatment with voriconazole was observed in 12 (27.9%) patients with normal initial renal function and in 3 (11.5%) patients with impaired renal function (P = 0.281). Renal failure developing during voriconazole treatment was associated with a significantly higher mortality rate (82.4% vs. 44.%, P = 0.01), except in the subgroup of patients with altered renal function before starting i.v. voriconazole (60% size=1>vs. 75%, P = 0.385). The use of i.v. voriconazole in ICU patients with pretreatment impaired renal function was not associated with renal or liver damage nor with an increase in ICU mortality.

Clinical use and tolerability of voriconazole in the treatment of fungal infections in critically ill patients.

The clinical use and tolerability of voriconazole in daily practice for the treatment of fungal infection in critically ill patients was assessed in an open-label, non-comparative, observational study. All patients admitted to medical-surgical Intensive Care Units (ICUs) of 21 hospitals in Spain between February 2003 and January 2004, who were treated with voriconazole because of known or suspected fungal infection, were included. A total of 130 patients received voriconazole (6.2 cases per ICU). Fungal infections were classified as proven in 50 patients (38.5%) and probable in 38 (29.2%). The etiology was established in 103 patients, with Candida albicans and Aspergillus fumigatus as the most common pathogens. In 98 (75.4%) patients, voriconazole was initially administered intravenously. Fifty-three patients (40.8%) were treated with other antifungal agents prior to the use of voriconazole. In 21 patients (16.2%), voriconazole was administered in combination with other antifungal drugs. Clinical responses were cure and improvement in 65 (50%) patients, failure in 26 (20%), and undetermined in 39 (30%). The crude ICU mortality was 49.2%. According to multivariate analysis, ICU mortality was significantly associated with pneumonia (OR = 3.30, 95% CI 1.07-10.18) and infection caused by Aspergillus spp. (OR = 3.70, 95% Cl 1.12-12.28), whereas eradication of the causative microorganisms was inversely associated (OR = 0.13, 95% CI 0.05-0.34). Adverse events were recorded in 65 patients, probably or possibly related to the study drug in 21. In conclusion, in critically ill patients admitted to the ICU, the use of voriconazole was affective in 50% of cases. The drug was well tolerated and discontinuation of voriconazole treatment due to adverse events was not necessary.

Evolution of closed urinary drainage systems use and associated factors in Spanish hospitals.

Although closed urinary drainage systems (CUDS) reduce the risk of catheter-associated urinary tract infection (CAUTI), open systems are still used in Spain. The object of this work was to describe the progress of CUDS use and factors associated with the drainage system type used in Spanish hospitals. The databases of the EPINE study (Study of Prevalence of Nosocomial Infections in Spain) from 1990 to 2000 were used. The EPINE study includes hospitalized patients of all ages in acute-care Spanish hospitals. Seventy-six thousand, seven hundred and eighty-eight catheterized patients were studied, and the whole database was used for the trend analysis of global hospital-acquired infection (HAI). The patient and the hospital were the two units of observation used in the analysis. Full implementation was defined as 90% CUDS use. A logistic regression model was applied to study factors influencing the use of CUDS and to determine prevalence trend. An odds ratio (OR) >1 indicates an incremental trend. The Pearson correlation coefficient between annual percentage of CUDS use and CAUTI prevalence was calculated. Variables for the year 2000 were compared using the Mann-Whitney U test between hospitals with and without full implementation. The prevalence of urinary catheterized patients in Spain increased from 12.4% in 1990 to 15.2% in 2000 (OR 1.019, 95% CI 1.016-1.021). The proportion of CUDS used increased from 50.6% in 1990 to 70% in 2000 (OR 1.1, 95% CI 1.095-1.104) and correlated with a significant decrease of UTIs (r = 0.65, P = 0.03). In 1990, 28.5% of hospitals had full implementation of CUDS and by 2000 this had risen to 40.3% (OR 1.093, 95% CI 1.06-1.127). Patients in medium (200-500 beds) and large (>500 beds) hospitals, as well as those with three of more diagnoses and two or more intrinsic risk factors had an increased probability of having a CUDS, whereas being hospitalized in areas other than intensive care, being male and less than 65 years old were associated with a lower probability of CUDS use. The median prevalence of catheterized patients in hospitals with full implementation, was significantly lower than in those without it (P = 0.049). Although CUDS use is increasing, there is still much work required to reach full implementation. Keeping CUDS for more severely ill patients may reflect a higher concern over the consequences of UTI in these patients. Nevertheless, it is necessary to change a practice that exposes patients to a known UTI risk factor and reach a consensus on indications for catheter insertion.

[Persistence of antibodies three years after vaccination with the 23-valent pneumococcal vaccine]. / Persistencia de anticuerpos a los 3 años de la inmunización antineumocócica 23-valente en pacientes con síndrome nefrótico.

OBJECTIVE: To study the persistence of antibodies after primary immunization with the 23-valent pneumococcal vaccine in children with nephrotic syndrome. METHODS: Sera from 14 of 26 children with nephrotic syndrome were obtained 3 years after vaccination. We used an ELISA method to measure IgG antibody levels to pneumococcal serotypes 14, 23F, 3 and 6B. Antibody levels before vaccination, 1 month and 3 years after vaccination were compared. RESULTS: Significant increases in specific antibody concentrations were observed 30 days after vaccination for all serotypes except serotype 3. Differences in response according to serotype were found. The highest serological response was observed for serotype 14 (78.5 % of the patients showed a good-to-moderate response). Three years after vaccination antibody levels were significantly decreased (27.3 % of children for serotype 14, 46.2 % for serotype 23F and 50 % for serotype 6B). CONCLUSIONS: The 23-valent pneumococcal vaccine is immunogenic in children aged more than 2 years with nephrotic syndrome. Response varied according to serotype. Persistence of vaccine-induced antibodies is short-term, with low antibody levels 3 years after immunization. The results of this study suggest that these patients require revaccination 3 years after the first dose.