Antibiotic administration in Gram-negative bacilli infections.

The optimization of antibiotic administration is essential to maximalize th erapeutic effectiveness and limit the selection of resistant bacteria. For the cephalosporins, the interval of time during which the free concentratio ns of antibiotic are higher than the minimum inhibitory concentration (MIC) is the pharmacokinetic/pharmacodynamic parameter best correlated with the antibacterial activity. Thus, the continuous infusion seems to be the most suitable mode of drug administration, particularly for the treatment of Gra m-negative bacilli infections. Indeed, this mode of drug administration all ows the maintenance of adequate tissue concentrations during all the nycteh omeral period, limit the risk of potential neurological toxicity and would reduce the cost of the processing by the reduction in the dosage that it ma y authorize. Nevertheless, the use of high dosages remains necessary to lim it the selection of resistant mutants, particularly for bacteria to which t he MIC are close to the breaking values. The rotation of antibiotics used i s another concept of drug administration that, theoretically, should make i t possible to limit the selection of mutant. Conclusive studies have been p ublished with aminoglycosides, various beta -lactam agents and ciprofloxaci n, but various issues remain unresolved, such as which antibiotics should b e cycled, what is the optimal duration of cycle periods, what is the prefer red order of agents to be cycled, etc. The cure of severe Gram-negative bac illi infections being multifactorial, complementary studies relating to bro ad collectives of patients are essential to validate these new concepts of drug administration and to propose them for the daily practice. (C) 2001 Ed itions scientifiques et medicales Elsevier SAS.