Appropriate antibiotic dosage levels in the treatment of severe sepsis and septic shock.

Antibiotic treatment of critically ill patients remains a significant challenge. Optimal antibacterial strategy should achieve therapeutic drug concentration in the blood as well as the infected site. Achieving therapeutic drug concentrations is particularly difficult when infections are caused by some pathogens, such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative rods, because of their low susceptibility to antimicrobials. In sepsis, pharmacokinetics (PKs) of antibiotics are profoundly altered and may result in inadequate drug concentrations, even when recommended regimens are used, which potentially contribute to increased mortality and spread of resistance. The wide inter-individual PK variability observed in septic patients strongly limits the a priori prediction of the optimal dose that should be administered. Higher than standard dosages are necessary for the drugs, such as β-lactams, aminoglycosides, and glycopeptides, that are commonly used as first-line therapy in these patients to maximize their antibacterial activity. However, the benefit of reaching adequate drug concentrations on clinical outcome needs to be further determined.