The objective of this study was to analyze the pharmacokinetics of cefepime, in six patients with acute renal failure related to septic shock, during continuous venovenous hemodiafiltration (CVVHD) (Hemospal AN 69S hemofilter; Hospal, Lyon, France). Six patients, mean age 65 +/- 4 years (range, 61 to 69), were included and each received 2 g of cefepime by intravenous infusion over a 30-min period every 12 h. Prefilter serum, dialysate outlet (DO), and ultrafiltrate samples were collected 0.47, 0.50, 0.57, 1, 3, 5, 7, and 12 h after the beginning of infusion. The time design of samples was optimized in accordance with the theory of D optimality. The cefepime concentrations were measured by high-performance liquid chromatography. The pharmacokinetics computation was carried out using P-PHARM software. Mean serum concentration peaks were 53 +/- 21.9 mg/liter (range, 13.0 to 68.9) one-half hour after the infusion. The mean elimination half-life was 8.11 +/- 2.22 h (range, 4.76 to 10.84). DO clearance was 66.57 +/- 30.14 ml/min (range, 38.66 to 119.87). The mean volume of distribution was 0.71 +/- 0.37 liters/kg of body weight. CVVHD was effective for cefepime elimination. In these subjects, the elimination half-life and DO clearance were almost constant. The results of this study suggested that a 2-g twice-daily infusion (usual dosage) was required for an effective concentration in this group of patients.

To assess the usefulness of the Gram stain in the early diagnosis of ventilator-associated pneumonia (VAP), we performed 146 protected specimen brushings (PSB) and bronchoalveolar lavages (BAL) in 118 patients suspected of having nosocomial pneumonia. Gram stain and counts of infected cells were performed in all samples from BAL fluid. A final diagnosis of pneumonia was established in 51 patients and there was no infection in 95 cases. A threshold of 2% of infected cells was used to distinguish between VAP and the group without VAP (sensitivity 86.3%, specificity 78.9%, positive predictive value 68.7% and negative predictive value 91.4%); there was good agreement with the final diagnosis (kappa statistic 0.616; concordance 81.5%). Regarding detection of bacteria using the Gram stain, we found a sensitivity of 90.2%, specificity 73.7%, positive predictive value 64.8% and negative predictive value 93.3%; there was moderate agreement with the final diagnosis (kappa statistic 0.586; concordance 79.4%). In the VAP group, we analysed the degree of qualitative agreement between Gram stain and PSB quantitative cultures: the correlation was complete in 51% (26 of 51 VAP), partial in 39.2% (20 of 51 VAP) and there was no correlation in 9.8% (five of 51 VAP). We conclude that the Gram stain is useful for rapid diagnosis of VAP but unreliable for early adaptation of empiric therapy.

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The objective of this study was to analyze the pharmacokinetics of isepamicin during continuous venovenous hemodiafiltration. Six patients received 15 mg of isepamicin per kg of body weight. The mean isepamicin concentration peak in serum was 62.88 ± 18.20 mg/liter 0.5 h after the infusion. The elimination half-life was 7.91 ± 0.83 h. The mean total body clearance was 1.75 ± 0.28 liters/h, and dialysate outlet (DO) clearance was 2.76 ± 0.59 liters/h. The mean volume of distribution was 19.83 ± 2.95 liters. The elimination half-life, DO clearance, and volume of distribution were almost constant. In this group of patients, the initial dosage of 15 mg/kg appeared to be adequate, but the dosage interval should be determined by monitoring residual isepamicin concentrations in plasma.