We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and stratified according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 x 400 mg of intravenous ciprofloxacin for 4 days, together with a mixture of topical gentamicin and polymyxin applied to the nostrils, mouth, and stomach throughout their ICU stay or to receive intravenous and topical placebo. When receiving prophylaxis, significantly fewer patients acquired infections (p = 0.001, risk ratio [RR], 0.477; 95% confidence interval [CI], 0.367-0.620), especially pneumonias (6 versus 29, p = 0.007), other lower respiratory tract infections (39 versus 70, p = 0.007), bloodstream infections (14 versus 36, p = 0.007), or urinary tract infections (36 versus 60, p = 0.042). Also, significantly fewer patients acquired severe organ dysfunctions (63 versus 96 patients, p = 0.0051; RR, 0.636; 95% CI, 0.463-0.874), especially renal dysfunctions (17 versus 38; p = 0.018). Within 5 days after admission, 24 patients died in each group, whereas 28 patients receiving prophylaxis and 51 receiving placebo died in the ICU thereafter (p = 0.0589; RR, 0.640; 95% CI, 0.402-1.017). The overall ICU mortality was not statistically different (52 versus 75 fatalities), but the mortality was significantly reduced for 237 patients of the midrange stratum with APACHE-II scores of 20-29 on admission (20 versus 38 fatalities, p = 0.0147; RR, 0.508; 95% CI, 0.295-0.875); there was still a favorable trend after 1 year (51 versus 60 fatalities; p = 0.0844; RR, 0.720; 95% CI, 0.496-1.046). Surveillance cultures from tracheobronchial, oropharyngeal, and gastric secretions and from rectal swabs did not show any evidence for the selection of resistant microorganisms in the patients receiving prophylaxis.

In patients with score-defined severe sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce mortality.

No abstract

Background: In patients with acute renal failure, the pharmacokinetics of meropenem depend on the operational characteristics of the renal replacement therapy. Dosage recommendations are based on the correlation of plasma levels with pharmacodynamic requirements. Methods: Eight critically ill patients with acute renal failure were treated by continuous veno-venous hemofiltration with a filtrate flow of 1,600 ml/h and received 500 mg of meropenem every 12 h. Plasma and hemofiltrate concentrations of meropenem at steady state were determined by HPLC. Results: Peak levels in plasma amounted to 39.5 ± 10.5 mg/l (mean ± SD) and trough levels were 2.4 ± 1.5 mg/l. The minimal inhibitory concentration (MIC) for susceptible bacteria (4 mg/l) was covered for 40% of the dosing interval or longer in all patients. The MIC for intermediately susceptible organisms (8 mg/l) was covered for 33% in 6 of the 8 patients. The elimination half-life was prolonged to 3.63 ± 0.77 h. The sieving coefficient of meropenem was 0.91 ± 0.10 and the recovery in hemofiltrate amounted to 30.9 ± 11.5% of the dose. Conclusions: A dosage of 500 mg twice daily provides appropriate serum levels for the treatment of infections caused by susceptible bacteria. A higher dosage is adequate for infections by intermediately susceptible bacteria or for renal replacement therapies with markedly higher filtrate flow rates.

Patients undergoing cardiac surgery (involving cardiopulmonary bypass) who develop severe SIRS derive no improvement in short-term morbidity or 28-day mortality from ivIgG.

No abstract

Plasma lipolytic activity and hydrolysis of intravenous fat were studied in six healthy subjects during infusion of a long-chain triglyceride (LCT) fat emulsion (Intralipid 20%) or of a medium-chain triglyceride (MCT)/LCT emulsion (Lipofundin MCT 20%). The fat emulsions were infused continuously at a rate of 0.17 g triglyceride kg-1 body weight (BW)h-1 for 6 h in random order at 7-day intervals. A continuous infusion of glucose (0.18 g kg-1 BW h-1) was administered for a period of 7 h and was started 1 h before the lipid infusion. Infusions of both types of fat increased plasma triglyceride (TG), free fatty acid (FFA) and lipoprotein lipase (LPL) levels and steady-state values were present during the 3rd to 5th h of infusion. MCT/LCT infusion resulted in higher plasma levels at steady-state of TG (3.63 +/- 0.45 [SEM] vs 2.73 +/- 0.45 mmol l-1; P less than 0.05), FFA (1.05 +/- 0.08 vs 0.54 +/- 0.04 mmol l-1; P less than 0.01) and LPL (4.6 +/- 0.6 vs 2.6 +/- 0.5 mU ml-1; P less than 0.05) in comparison with LCT administration. There was a positive correlation between plasma LPL activity and TG concentration (r = 0.77; P less than 0.001) when data for the two infusions were combined. Although the same amount of fat was infused on a weight basis, the molar infusion rate was 40% higher with MCT/LCT than with LCT infusion, due to differences in molecular weights (634 vs 885 Da).(ABSTRACT TRUNCATED AT 250 WORDS)

In a multicenter observational study of 163 medical and surgical patients with a total of 173 episodes of sepsis or septic shock (Elebute sepsis score: 19.0 +/- 0.5), the effects of supplemental i.v. immunoglobulin (i.v. IG) treatment (unmodified polyvalent IgG pH 4.25, n = 123; for Pseudomonas sepsis, n = 50, Pseudomonas IgG) on multiple organ failure (MOF) were investigated by means of APACHE II score changes (pretreatment: 23.7 +/- 0.6). In 44% of the cases ("responders"), a prompt improvement in APACHE II score (defined as decrease greater than or equal to 4) was evident from day 0 to day 4 after onset of therapy, thus being in close time relationship to the i.v. IG administration. This improvement, associated with a better prognosis (mortality 24% vs. 55%), was found in all subgroups, most importantly the following: polyvalent IgG vs. Pseudomonas IgG treatment; medical vs. surgical patients; moderate vs. severe MOF; and gram-positive vs. gram-negative septicemia. In a small-sized second comparative nonrandomized control group (n = 27, antibiotic treatment alone) of septic patients (Elebute: 14.7 +/- 1.0) with similar MOF severity (APACHE II: 23.6 +/- 1.4), the response rate (30%) was, though not statistically significant, lower by one-third. The optimal baseline score ranges for patient inclusion into future placebo-controlled randomized i.v. IG trials were found to be 20-35 for the APACHE II score and 12-27 for the Elebute score.