Continuous versus intermittent intravenous administration of antibiotics: a meta-analysis of randomised controlled trials.

Intermittent intravenous administration of antibiotics is the first-line approach in the management of severe infections worldwide. However, the potential benefits of alternate modes of administration of antibiotics, including continuous intravenous infusion, deserve further evaluation. We did a meta-analysis of randomised controlled trials comparing continuous intravenous infusion with intermittent intravenous administration of the same antibiotic regimen. Nine randomised controlled trials studying beta-lactams, aminoglycosides, and vancomycin were included. Clinical failure was lower, although without statistical significance, in patients receiving continuous infusion of antibiotics (pooled OR 0.73, 95% CI 0.53-1.01); the difference was statistically significant in a subset of randomised controlled trials that used the same total daily antibiotic dose for both intervention arms (0.70, 0.50-0.98, fixed and random effects models). Regarding mortality and nephrotoxicity, no differences were found (mortality 0.89, 0.48-1.64; nephrotoxicity 0.91, 0.56-1.47). In conclusion, the data suggest that the administration of the same total antibiotic dose by continuous intravenous infusion may be more efficient, with regard to clinical effectiveness, compared with the intermittent mode. In an era of gradually increasing resistance among most pathogens, the potential advantages of continuous intravenous administration of antibiotics on several clinical outcomes should be further investigated.

Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis.

Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of multidrug-resistant gram-negative bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to multidrug-resistant gram-negative bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 +/- 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against gram-negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to multidrug-resistant gram-negative bacteria appears to be safe and effective.