Pharmacokinetic study of anidulafungin in ICU patients with intra-abdominal candidiasis.

Background: Only limited pharmacokinetic data are available for anidulafungin in ICU patients, especially in patients treated for severe intra-abdominal infection (IAI). Methods: This was a prospective multicentre observational study in ICU patients with suspected yeast IAI. All patients received an intravenous loading dose of 200 mg of anidulafungin, followed by 100 mg/day. Thirteen blood samples were drawn between day 1 and day 5 for pharmacokinetic analysis. Samples were analysed by an HPLC-tandem MS method. Demographics and SAPS2 and SOFA scores were recorded. Results: Fourteen patients with a median age (IQR) of 62 years (48-70) and with a mean BMI of 30.5 kg/m 2 were included from three centres; 57.1% were women. Their median (IQR) SAPS2 score was 54 (45-67) and their median (IQR) SOFA score was 8 (7-12). Six patients with community-acquired IAI and eight patients with nosocomial-acquired IAI were included. Twelve yeasts were isolated: six Candida albicans , two Candida glabrata , two Candida tropicalis , one Candida parapsilosis and one Candida krusei . Pharmacokinetic parameters were as follows [mean (% coefficient of variation)]: C max (mg/L) = 6.0 (29%); T max (h) = 1.6 (25.8%); C min (mg/L) = 3.2 (36.8%); AUC 0-24 (mg·h/L) = 88.9 (38.6%); t 1/2 (h) = 42.1 (68.2%); CL (L/h) = 1.2 (42.3%); and V (L) = 72.8 (87.8%). A two-compartment model best described the anidulafungin concentrations in the population pharmacokinetic study. Conclusions: The pharmacokinetic parameters of anidulafungin in critically ill ICU patients with complicated IAI are similar to those observed in the literature. However, an increased V and a longer t 1/2 were observed in this study. (EudraCT No. 2010-018695-25).

Place of diagnostic tools in the identification of Anaerobiospirillum succiniciproducens bacteraemia.

Anaerobiospirillum succiniciproducens is a rare but potentially lethal pathogen. We report a case of A. succiniciproducens bloodstream infection in a 55-year-old man hospitalized for pelvic trauma. The strain was identified by 16sRNA sequencing after several failures of identification by MALDI-TOF MS. The strain was susceptible to beta-lactam antibiotics and ciprofloxacin, but resistant to macrolides and clindamycin. Identification tools must be improved to enhance our knowledge on this rare pathogen and to define optimal therapy.

Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study.

BACKGROUND: Respiratory variation in pulse pressure (ΔPP) is commonly used to predict the fluid responsiveness of critically ill patients. However, some researchers have demonstrated that this measurement has several limitations. The present study was designed to evaluate the proportion of patients satisfying criteria for valid application of ΔPP at a given time-point. METHODS: A 1 day, prospective, observational, point-prevalence study was performed in 26 French intensive care units (ICUs). All patients hospitalized in the ICUs on the day of the study were included. The ΔPP validity criteria were recorded prospectively and defined as follows: (i) mechanical ventilation in the absence of spontaneous respiration; (ii) regular cardiac rhythm; (iii) tidal volume ≥8 ml kg(-1) of ideal body weight; (iv) a heart rate/respiratory rate ratio >3.6; (v) total respiratory system compliance ≥30 ml cm H2O(-1); and (vi) tricuspid annular peak systolic velocity ≥0.15 m s(-1). RESULTS: The study included 311 patients with a Simplified Acute Physiology Score II of 41 (39-43). Overall, only six (2%) patients satisfied all validity criteria. Of the 170 patients with an arterial line in place, only five (3%) satisfied the validity criteria. During the 24 h preceding the study time-point, fluid responsiveness was assessed for 79 patients. ΔPP had been used to assess fluid responsiveness in 15 of these cases (19%). CONCLUSIONS: A very low percentage of patients satisfied all criteria for valid use of ΔPP in the evaluation of fluid responsiveness. Physicians must consider limitations to the validity of ΔPP before using this variable.

Assessment of an uncalibrated pressure waveform device's ability to track cardiac output changes due to norepinephrine dose adjustments in patients with septic shock: a comparison with Doppler echocardiography.

OBJECTIVES: The FloTrac Vigileo (FTV) estimates cardiac output (CO) on the basis of an uncalibrated arterial pressure waveform. To assess the ability of the third-generation of FTV (v.3.02) to track changes in CO following norepinephrine dose adjustment in patients with septic shock, we performed a comparative study using Doppler echocardiography (DE). STUDY DESIGN: Prospective observational study. PATIENTS: We prospectively included 20 mechanically ventilated patients receiving norepinephrine and monitored with the FTV. Five minutes after each change in norepinephrine dose (decided by the attending physician), CO was measured simultaneously with the FTV (CO(FTV)) and DE (CO(DE)). The changes in CO were compared. ROC curves were built to assess the ability of FTV to detect significant changes in CO(DE) of at least 15%. RESULTS: Ninety pairs of CO variations measurements were made. The intertechnique correlation coefficient for changes in CO of at least 15% was r=0.59; P=0.0009. The AUC of a ROC curve built to test the FTV's ability to detect a CO(DE) increase of 15% or more was 0.783 (±0.083) (P=0.005). A CO(FTV) threshold value of 15% had a sensitivity of 54% (25-81) and a specificity of 87% (77-94). For a CO(DE) decrease of 15% or more, the ROC curve had an AUC of 0.616 (±0.075) (P=0.12) and a CO(FTV) threshold value of 13% yielded a sensitivity of 53% (27-79) and a specificity of 72% (60-82). CONCLUSIONS: The FTV was unable to accurately track changes in CO following norepinephrine dose adjustments in critically ill patients with septic shock.