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| |  Patients Outside Intensive Care Units Fare Better With Treatment for Serious Candida Infections: Presented at ECCMID By Chris Berrie HELSINKI, Finland -- May 20, 2009 -- Both micafungin and liposomal amphotericin B show lower success rates for treating serious Candida infections in patients in an intensive care unit (ICU) setting than for those outside an ICU, researchers noted here at the 19th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is the only explanatory variable associated with the treatment success of these agents and all-cause mortality, noted coinvestigator Bertrand Dupont, MD, Université Paris Descartes, Hôpital Necker-Enfants Malades, Centre d'Infectiologie Necker-Pasteur, Paris, France, presenting a post hoc analysis of efficacy data from a phase 3, noninferiority trial here on May 18. According to current antifungal treatment guidelines, initial management of moderately severe to severe invasive candidiasis should include an echinocandin. The original comparator trial, therefore, included the new echinocandin antifungal agent micafungin, which was demonstrated to be noninferior to caspofungin and liposomal amphotericin B, and better tolerated than liposomal amphotericin B. The main objective of Dr. Dupont's post hoc study was to investigate ICU versus non-ICU stay in patients receiving these drugs for Candida infections. "So we compared the overall results, the mycological results, and the survival at day 8 and day 30," Dr. Dupont stated. In the original trial, patients with serious Candida infections were randomised to either micafungin 100 mg/day (for patients weighing over 40 kg) or 2 mg/kg (for patients weighing 40 kg or less), or liposomal amphotericin B 3 mg/kg/day, stratified according to study centre and neutropenic status, but not ICU status. The modified intention-to-treat population for analysis (n = 494) was in patients 16 years or older with confirmed Candida infection at baseline and with at least 1 treatment dose received. The ICU patients (n = 263; mean age, 52.9 years; male, 62.6%) had at least 1 day in ICU from days -1 to 3. The remaining patients were grouped as non-ICU (n = 230; mean age, 53.4 years; male, 60.1%). The analysis endpoints were overall treatment success (complete/partial success in clinical/mycological responses), mycological response (eradication of baseline pathogen), and all-cause mortality at days 8 and 30. At baseline, the patient characteristics across the ICU and non-ICU groups were well matched, with primary diagnoses in 16.5% and 14.8% of patients, respectively, for invasive candidiasis and in 83.5% and 85.2% of patients, respectively for candidaemia. The mean hospital stay was 23.6 days in the ICU group and 22.5 days in the non-ICU group. The ICU group demonstrated greater mean APACHE II scores (18.1 vs 13.8) and more patients with a catheter (96.1% vs 71.8%), but fewer patients with neutropenia (4.3% vs 17.9%). For overall success according to treatment, although there was no difference for micafungin versus liposomal amphotericin B within the ICU group (62.5% vs 66.4%), there was significantly higher success for micafungin versus liposomal amphotericin B in the non-ICU patients (85.0% vs 72.1%; P = .0113). In the safety analysis, renal function was also significantly better with micafungin than with liposomal amphotericin B, irrespective of ICU stay, demonstrating a difference (liposomal amphotericin B - micafungin group) in mean peak change in estimated glomerular filtration rate of -17.7 mL/min/1.73 m2 (P = .0124) in the ICU group versus -18.2 mL/min/1.73 m2 (P < .001) in the non-ICU group. With treatment groups again combined as ICU versus non-ICU, significantly fewer ICU patients achieved overall treatment success (64.3% vs 78.3%; P = .0006). This was paralleled by a decreased mycological response (72.6% vs 81.7%) and increased all-cause mortality at days 8 (18.7% vs 7.6%) and 30 (36.5% vs 21.7%). In the final regression model, the only variable associated with all 4 outcomes continued to be patient APACHE II score (as continuous, high to low): overall treatment success: odds ratio (OR), 0.956 (95% confidence interval [CI], 0.929-0.983); mycological response: OR, 0.953 (95% CI, 0.925-0.982); and all-cause mortality at day 8: OR, 1.097 (95% CI, 1.055-1.142) and day 30: OR, 1.093 (95% CI, 1.057-1.131). "We have to take more care about APACHE II score, and to detail what are the real factors in the APACHE II score that have such an impact on outcome," Dr. Dupont concluded. Funding for this study was provided by Astellas Pharma Inc. [Presentation title: Micafungin Versus Liposomal Amphotericin B for the Treatment of Serious Candida Infections in Intensive Care Unit and Non-ICU Patients: Results of Post-Hoc Analyses. Abstract P1743]
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