Anidulafungin compared with fluconazole therapy in critically ill patients (original) (raw)
Related papers
Low but Sufficient Anidulafungin Exposure in Critically Ill Patients
Antimicrobial Agents and Chemotherapy, 2013
ABSTRACTThe efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Patients in intensive care may be at risk for underexposure. In critically ill patients with an invasiveCandidainfection, the anidulafungin exposure and a possible correlation with disease severity or plasma protein levels were explored. Concentration-time curves were therefore obtained at steady state. Anidulafungin concentrations were measured with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The MIC values of theCandidaspecies were determined with the Etest. The target AUC/MIC ratio was based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) data. Twenty patients were included. The patients received a maintenance dose of 100 mg once daily after a loading dose of 200 mg on the first day. The mean (±standard deviation) AUC, maximum concentration of drug in plasma (Cmax), and minimum concentration of drug in plasma (Cmi...
Anidulafungin dosing in critically ill patients with continuous venovenous haemodiafiltration
The Journal of antimicrobial chemotherapy, 2014
Background: Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT.
Anidulafungin versus fluconazole: clinical focus on IDSA and ESCMID guidelines
Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive, 2014
Invasive infections by Candida spp. play a major role in the management of the critically ill patient. Rates of positive blood cultures for Candida species have risen fivefold in the past ten years, placing this pathogen between the fourth and the sixth-leading cause of nosocomial bloodstream infections in the United States and Europe. Candida albicans is still the cause of approximately 50% of invasive candidiasis, with heterogeneous epidemiology. The echinocandin class, along with voriconazole and liposomal amphotericin B, was recommended by 2009 IDSA guidelines with AI evidence for the treatment of candidaemia, reserving the use of fluconazole in selected situations. Conversely fluconazole was downgraded to CI recommendation (marginal use), with BI evidence for voriconazole and liposomal amphotericin B, maintaining AI (strong support) for echinocandins by 2012 ESCMID guidelines for the diagnosis and management of Candida disease in non-neutropenic adult patients. Our brief analys...
Antimicrobial Agents and Chemotherapy, 2017
Echinocandins, such as anidulafungin, are the first-line treatment for candidemia or invasive candidiasis in critically ill patients. There are conflicting data on the pharmacokinetic properties of anidulafungin in intensive care unit (ICU) patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included in the present study. Patients were considered evaluable if a pharmacokinetic curve for day 3 could be completed. Twentythree of 36 patients (7 female and 16 male) were evaluable. The median (range) age and body weight were 66 (28 to 88) years and 76 (50 to 115) kg, respectively. Pharmacokinetic sampling on day 3 (n ϭ 23) resulted in a median anidulafungin area under the concentration-time curve from 0 to 24 h (AUC 0-24) of 72.1 (interquartile range [IQR], 61.3 to 94.0) mg • h • liter Ϫ1 , a median daily trough concentration (C 24) of 2.2 (IQR, 1.9 to 2.9) mg/liter, a median maximum concentration of drug in serum (C max) of 5.3 (IQR, 4.1 to 6.0) mg/liter, a median volume of distribution (V) of 46.0 (IQR, 32.2 to 60.2) liters, and a median clearance (CL) of 1.4 (IQR, 1.1 to 1.6) liters • h Ϫ1. Pharmacokinetic sampling on day 7 (n ϭ 13) resulted in a median AUC 0-24 of 82.7 (IQR, 73.0 to 129.5) mg • h • liter Ϫ1 , a median minimum concentration of drug in serum (C min) of 2.8 (IQR, 2.2 to 4.2) mg/liter, a median C max of 5.9 (IQR, 4.6 to 8.0) mg/liter, a median V of 39.7 (IQR, 32.2 to 54.4) liters, and a median CL of 1.2 (IQR, 0.8 to 1.4) liters • h Ϫ1. The geometric mean ratio for the AUC day7 /AUC day3 term was 1.13 (90% confidence interval [CI], 1.03 to 1.25). The exposure in the ICU patient population was in accordance with previous reports on anidulafungin pharmacokinetics in ICU patients but was lower than that for healthy volunteers or other patient populations. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates. (This study has been registered at ClinicalTrials.gov under identifier NCT01438216.) KEYWORDS antifungal drugs, echinocandins, pharmacokinetics, intensive care unit, invasive fungal infections E chinocandins are deployed as primary treatment for patients with invasive candidiasis or candidemia. Anidulafungin is one of three available echinocandins currently on the market. Both the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) and Infectious Diseases Society of America (IDSA) guidelines have argued that with respect to therapeutic efficacy, all echinocandins are equally effective when it comes to treatment of invasive candidiasis or candidemia (1-3). Nevertheless, there are subtle differences in regard to pharmacokinetics (PK).
Limited-sampling strategies for anidulafungin in critically ill patients
Antimicrobial agents and chemotherapy, 2015
Efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Determination of the anidulafungin AUC along with MIC values can therefore be useful. Since obtaining a full concentration-time curve to determine an AUC is not always feasible or appropriate, limited-sampling strategies may be useful in adequately estimating exposure. The objective of this study was to develop a model to predict the individual anidulafungin exposure in critically ill patients using limited-sampling strategies. Pharmacokinetic data were derived from 20 critically ill patients with invasive candidiasis treated with anidulafungin. These data were used to develop a two-compartment model in MW\Pharm using an iterative 2-stage Bayesian procedure. Limited-sampling strategies were subsequently investigated using two methods, a Bayesian analysis and a linear regression analysis. The best possible strategies for these two methods were evaluated by a Bland-Altman analysis for c...
Austrian Clinical Practice with Anidulafungin in 2008: A Multicenter Survey
Journal of Chemotherapy, 2011
Anidulafungin had demonstrated favorable efficacy versus fluconazole in a randomized trial on invasive Candida infections. Since patient characteristics in the post-approval use of antifungals likely deviate from clinical trials, we surveyed the use of anidulafungin in clinical routine. We performed a retrospective survey of the post-approval use of anidulafungin in 9 Austrian clinical centers. Anidulafungin was used in 129 critically ill patients with severe comorbidities and multiple risk factors. Indications were suspected invasive fungal infections (IFI) (61%), proven candidemia (19%), and at risk for IFI (prophylaxis, 20%). Candida colonization in conjunction with other risk factors prompted treatment in many patients. Predominant pathogens were C. albicans, C. glabrata and C. krusei. Anidulafungin was mostly used for pre-emptive (69%) and first-line treatment (17%) of invasive candidiasis. Treatment response, i.e. complete response/stabilization as determined by investigators (89% in the overall population; 87% for documented candidemia) and survival rates (81% and 75%, respectively) were similar to previous trial data. No breakthrough IFI and few adverse events were reported. Overall, favorable clinical experiences were documented with anidulafungin in the clinical routine setting.
Empirical Fluconazole versus Placebo for Intensive Care Unit Patients
Annals of Internal Medicine, 2008
Background: Invasive infection with Candida species is an important cause of morbidity and mortality in intensive care unit (ICU) patients. Optimal preventive strategies have not been clearly defined. Objective: To see whether empirical fluconazole improves clinical outcomes more than placebo in adult ICU patients at high risk for invasive candidiasis. Design: Double-blind, placebo-controlled, randomized trial conducted from 1995 to 2000. Setting: 26 ICUs in the United States. Patients: 270 adult ICU patients with fever despite administration of broad-spectrum antibiotics. All had central venous catheters and an Acute Physiology and Chronic Health Evaluation II score greater than 16. Intervention: Patients were randomly assigned to either intravenous fluconazole, 800 mg daily, or placebo for 2 weeks and were followed for 4 weeks thereafter. Two hundred forty-nine participants were available for outcome assessment. Measurements: A composite primary outcome that defined success as all 4 of the following: resolution of fever; absence of invasive fungal infection; no discontinuation because of toxicity; and no need for a nonstudy, systemic antifungal medication (as assessed by a blinded oversight committee). Results: Only 44 of 122 (36%) fluconazole recipients and 48 of 127 (38%) placebo recipients had a successful outcome (relative risk, 0.95 [95% CI, 0.69 to 1.32; P ϭ 0.78]). The main reason for failure was lack of resolution of fever (51% for fluconazole and 57% for placebo). Documented invasive candidiasis occurred in 5% of fluconazole recipients and 9% of placebo recipients (relative risk, 0.57 [CI, 0.22 to 1.49]). Seven (5%) fluconazole recipients and 10 (7%) placebo recipients had adverse events resulting in discontinuation of the study drug. Discontinuation because of abnormal liver test results occurred in 3 (2%) fluconazole recipients and 5 (4%) placebo recipients. Limitations: Twenty-one randomly assigned patients were not included in the analysis because they either did not meet entry criteria or did not have postbaseline assessments. Fewer fungal infections than anticipated occurred in the control group. Confidence bounds were wide and did not exclude potentially important differences in outcomes between groups. Conclusion: In critically ill adults with risk factors for invasive candidiasis, empirical fluconazole did not clearly improve a composite outcome more than placebo.
International Journal of Antimicrobial Agents, 2012
Post hoc analysis of a non-comparative, prospective, multicentre, phase IIIb study was performed to compare efficacy and safety of anidulafungin in elderly (≥65 years) versus non-elderly (<65 years) Intensive Care Unit (ICU) patients with candidaemia/invasive candidiasis (C/IC). Adult ICU patients with confirmed C/IC meeting ≥1 of the following criteria were enrolled: post-abdominal surgery; solid tumour; renal/hepatic insufficiency; solid organ transplantation; neutropenia; age ≥65 years. Patients received anidulafungin (200 mg on Day 1, 100 mg/day thereafter) for ≥10 days followed by optional azole stepdown therapy for a total treatment duration of 14-56 days. The primary efficacy endpoint was global (clinical and microbiological) response at the end of all therapy (EOT). Primary efficacy analysis was performed in the modified intent-to-treat (mITT) population (n = 170), excluding unknown and missing responses. In total, 80 patients (47.1%) were aged ≥65 years and 90 (52.9%) were aged <65 years; the mean age difference between the two groups was 21.9 years. Global success at EOT in mITT patients was similar in elderly (68.1%) and non-elderly (70.7%) patients (P = 0.719). However, global success rates were significantly lower in elderly versus non-elderly patients at 2 and 6 weeks after EOT (P = 0.045 and P = 0.016, respectively). Ninety-day survival was significantly lower (P = 0.006) for elderly (42.8%) versus non-elderly patients (63.3%). The incidence and profile of adverse events were similar in elderly and non-elderly patients. Anidulafungin was effective and safe for treatment of C/IC in elderly ICU patients, despite higher baseline severity of illness scores.