Fluconazole use in burns patients

Rayatt, Sukh; Wienbren, M; Clarke, J.A.

doi:10.1016/s0305-4179(99)00101-1

Cited by 5 publications

(6 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, it may be that the hypermetabolic phase (beyond 48 h after the burn injury), which can affect the intensity of physiological changes over different days, contributed to the altered and highly variable PKs (11). This lower level of exposure to micafungin observed in our patients has also been reported for other antifungals in burn patients (17,29,30). The PKs of caspofungin were assessed in two burn patients, and the exposure was similar to that observed in healthy volunteers in one patient, but it was 50% lower in the other (29).…”

Section: Discussionsupporting

confidence: 63%

Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection

Garcı́a-de-Lorenzo

Luque

Grau

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

g Severely burned patients have altered drug pharmacokinetics (PKs), but it is unclear how different they are from those in other critically ill patient groups. The aim of the present study was to compare the population pharmacokinetics of micafungin in the plasma and burn eschar of severely burned patients with those of micafungin in the plasma and peritoneal fluid of postsurgical critically ill patients with intra-abdominal infection. Fifteen burn patients were compared with 10 patients with intra-abdominal infection; all patients were treated with 100 to 150 mg/day of micafungin. Micafungin concentrations in serial blood, peritoneal fluid, and burn tissue samples were determined and were subjected to a population pharmacokinetic analysis. The probability of target attainment was calculated using area under the concentration-time curve from 0 to 24 h/MIC cutoffs of 285 for Candida parapsilosis and 3,000 for non-parapsilosis Candida spp. by Monte Carlo simulations. Twenty-five patients (18 males; median age, 50 years; age range, 38 to 67 years; median total body surface area burned, 50%; range of total body surface area burned, 35 to 65%) were included. A three-compartment model described the data, and only the rate constant for the drug distribution from the tissue fluid to the central compartment was statistically significantly different between the burn and intra-abdominal infection patients (0.47 ؎ 0.47 versus 0.15 ؎ 0.06 h ؊1 , respectively; P < 0.05). Most patients would achieve plasma PK/pharmacodynamic (PD) targets of 90% for non-parapsilosis Candida spp. and C. parapsilosis with MICs of 0.008 and 0.064 mg/liter, respectively, for doses of 100 mg daily and 150 mg daily. The PKs of micafungin were not significantly different between burn patients and intra-abdominal infection patients. After the first dose, micafungin at 100 mg/day achieved the PK/PD targets in plasma for MIC values of <0.008 mg/liter and <0.064 mg/liter for non-parapsilosis Candida spp. and Candida parapsilosis species, respectively.

show abstract

Section: Discussionsupporting

confidence: 63%

Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection

Garcı́a-de-Lorenzo

Luque

Grau

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…No control patients were included in this study, but the fluconazole pharmacokinetics in these burn patients were compared with those in published studies of healthy controls and patients with normal renal function; the authors noted a decreased t 1/2 , increased clearance, and increased V d of fluconazole in the burn patients. In a single case report, an 18-year-old woman with a 35% TBSA burn with skin and soft-tissue candidiasis who was treated with intravenous fluconazole had trough levels lower than those in published studies with healthy volunteers [30]. In five of six burn patients, intravenous fluconazole doses were increased 1.5 to 2 times the standard dosage of 400 mg daily to achieve a minimal effective concentration of 10 μg/mL (except in one patient, in whom this concentration was not reached) [31•].…”

Section: Fluconazolementioning

confidence: 59%

“…Similarly, none of the echinocandins are substrates or inhibitors of P-glycoprotein transporters [41]. The pharmacodynamic parameters that best describe antifungal activity are a concentration-dependent [25,30,31,36,[39][40][41] killing relative to the MIC and ratio of area under the concentration (AUC)-time curve to MIC for Candida and Aspergillus species [42,43]. Table 2 summarizes the pharmacokinetic parameters of the antifungal drugs commonly used for treatment of invasive fungal infections.…”

Section: Echinocandinsmentioning

confidence: 99%

Antifungal Pharmacokinetics and Dosing Considerations in Burn Patients

Walraven

Mercier

Lee

2011

Curr Fungal Infect Rep

View full text Add to dashboard Cite

Patients with burn injuries are at high risk of developing invasive fungal infections leading to increased morbidity and mortality. Burn patients undergo major physiologic changes, which produce significant alterations in the pharmacokinetics and pharmacodynamics of antimicrobial agents. These changes result from the breakdown of the body's natural barriers to infection and the systemic responses that subsequently ensue after burn injury, including systemic inflammatory responses, third spacing, and development of a hypermetabolic state. Severe burn injuries often lead to larger volumes of distribution and increased drug clearance. Limited data are available to guide the clinician in optimizing the dosing regimen of antifungals in patients with burn injuries. We present a review of antifungal pharmacokinetics and describe how these properties can be used to design rational therapeutic regimens tailored to the pharmacodynamic alterations characteristic of burn patients.

show abstract

“…Data obtained in the present study are in agreement with the results reported previously by Rayatt et al . based on changes in drug plasma levels as a consequence of kinetic changes in burn patients receiving the empirical dose (400 mg once daily) for the control of fungal infection 27. Controversially, Boucher et al .…”

Section: Discussionmentioning

confidence: 99%