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

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.

Two cases of overlap severe cutaneous adverse reactions to benznidazole treatment for asymptomatic Chagas disease in a nonendemic country.

Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk.

Acute kidney injury in critically burned patients resuscitated with a protocol that includes low doses of Hydroxyethyl Starch.

Acute kidney injury (AKI) is an important complication in burn patients. Recently, it has been recommended that hydroxyethyl starch (HES) be avoided in burn patients because it increases the incidence of AKI. Our purpose was to study incidence of AKI in critically ill burn patients resuscitated with Ringer's solution and supplements of HES. We conducted an observational study of 165 patients admitted to the critical care burn unit (with 30 ± 15% TBSA burned). The main outcome measures were incidence of AKI, contributions of colloids and crystalloids, various severity scores, comorbidities, complications and mortality. According to the RIFLE criteria, 10 (6.1%) patients presented with Risk, 11 (6.7%) presented with Injury and 11 (6.7%) presented with Failure. According to the AKIN criteria, 9.7% presented stage I, 3% stage II and 10.3% stage III. Replacement therapy (RRT) was performed in 15 patients (9.1%), but in 6 of them RRT was employed in the final stages of multi-organ failure. The incidence of AKI in severe burn patients is high according to the RIFLE or AKIN criteria and these patients experience more complications and higher mortality. Our study suggests that the use of HES in low doses in the burn resuscitation phase does not cause more AKI than resuscitation without HES, but further evaluation is required. Further studies should be conducted.

La souffrance rénale aiguë (SRA) est une complication sévère des patients brûlés. Il a récemment été recommandé d'éviter les HydroxyEthylAmidons (HEA) chez les patients brûlés en raison de l'augmentation de l'incidence des SRA. Le but de ce travail est d'évaluer l'incidence de la SRA chez des patients réanimés avec du Ringer Lactate et des HEA. Il s'agit d'une étude observationnelle conduite auprès de 165 patients admis en réanimation pour brûlés (surface 30 +/-15%). Les principaux paramètre recueillis étaient la SRA, les cristalloïdes et colloïdes utilisés, les scores de gravité, les comorbidités, les complications et la mortalité. Selon la classification de Rifle, 10 (6,1%) patients étaient dans le groupe à risque, 11 (6,7%) avaient une souffrance rénale et 11 (6,7%) une insuffisance rénale. Selon les critères AKIN, 9,7% des patients étaient au stade 1, 3% au stade 2 et 10,3% au stade 3. Une épuration extra-rénale a été nécessaire à 15 (9,1%) patients, 6 d'entre eux étant à un stade avancé de défaillance multiviscérale. Basée sur les scores Rifle comme AKIN, l'incidence de souffrance rénale est élevée chez les brûlés et ceux qui en souffrent ont une morbidité et une mortalité plus élevées. Toutefois, notre étude laisse à penser que les patients ayant reçu des HEA n'ont pas plus de souffrance rénale que ceux n'en ayant pas reçu, des études plus poussées restant nécessaires.