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.

Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices.

This retrospective multicenter study compared microorganisms documented by quantitative cultures from bronchoscopic samples in episodes of ventilator-associated pneumonia (VAP) from three different institutions in Barcelona (B), Montevideo (M), and Seville (S). The observations were compared with the findings reported by Trouillet and coworkers (AJRCCM 1998;157:531-539) in Paris (P). The objective was to evaluate whether a classification of etiologies of VAP in four groups, based on the number of ventilation days and previous antimicrobial use, might contribute to establishing generalized guidelines for empirical therapy. Significant variations in etiologies (p < 0.05) were found in all of the microorganisms isolated from VAP episodes across three treatment sites when compared with the reference site (P). In Group 1 (< 7 d and absence of antibiotics), Pseudomonas aeruginosa remained extremely infrequent (3 of 89, 3.3%) in the joint category, whereas the incidence of Acinetobacter baumannii was significantly higher, owing to M findings. On the other hand, one site (B) had a significantly lower incidence of multiresistant pathogens (Methicillin-resistant Staphylococcus aureus [MRSA] and nonfermenters other than P. aeruginosa), even in Group 2 (< 7 d and antibiotics), Group 3 (>/= 7 d and absence of antibiotics), and Group 4 (antibiotics and >/= 7 days). Similar findings were documented when episodes were grouped according to Groups 1 and 3 of the ATS guidelines. We conclude that causes of VAP varied markedly across four treatment sites, resulting in the need for large-scale variations in antimicrobial prescribing practices. Instead of following general recommendations, antimicrobial prescribing practices for VAP should be based on up-to-date information of the pattern of multiresistant isolates from each institution.

Midazolam and 2% propofol in long-term sedation of traumatized critically ill patients: efficacy and safety comparison.

OBJECTIVE: We proposed to compare the efficacy and safety of midazolam and propofol in its new preparation (2% propofol) when used for prolonged, deep sedation in traumatized, critically ill patients. We also retrospectively compared 2% propofol with its original preparation, 1% propofol, used in a previous study in a similar and contemporary set of patients. DESIGN: A prospective, randomized, unblinded trial (midazolam and 2% propofol) and a retrospective, contemporary trial (2% propofol and 1% propofol). SETTINGS: A trauma intensive care unit in a tertiary university hospital. PATIENTS: A total of 63 consecutive trauma patients, admitted within a period of 5 months and requiring mechanical ventilatory support for >48 hrs, 43 of whom (73%) suffered severe head trauma. We also retrospectively compared the 2% propofol group with a series of patients in whom 1% propofol was used. INTERVENTIONS: For the prospective trial, we randomized two groups--a midazolam group with continuous administration of midazolam at dosages 0.1-0.35 mg/kg/hr, and a 2% propofol group with continuous infusion at dosages 1.5-6 mg/kg/hr. Equal dosages of analgesics were administered. Similar management protocols were applied in the 1% propofol group, used in the retrospective analysis with 2% propofol. MEASUREMENTS AND MAIN RESULTS: Epidemiologic and efficacy variables were recorded. Hemodynamic and biochemical variables were also monitored on a regular basis. Neuromonitoring was also performed on those patients with head trauma. Sedation adequacy was similar and patient behavior after drug discontinuation was not different in either prospective group (midazolam and 2% propofol). Hemodynamic or neuromonitoring variables were also similar for both groups. Triglyceride levels were significantly higher in the 2% propofol group compared with the midazolam group. A higher number of therapeutic failures because of sedative inefficacy was seen in the 2% propofol group compared with the midazolam group, especially during the first sedation days. When comparing 2% propofol and 1% propofol, a significantly higher number of therapeutic failures because of hypertriglyceridemia were found in the 1% propofol group, as opposed to a major number of therapeutic failures because of inefficacy, found in the 2% propofol group. CONCLUSIONS: Propofol's new preparation is safe when used in severely traumatized patients. Its more concentrated formula improves the lipid overload problem seen with the prolonged use of the previous preparation. Nevertheless, a major number of therapeutic failures were detected with 2% propofol because of the need for dosage increase. This fact could be caused by a different disposition and tissue distribution pattern of both propofol preparations. New studies will be needed to confirm these results.