Is there a pharmacodynamic need for the use of continuous versus intermittent infusion with ceftazidime against Pseudomonas aeruginosa? An in vitro pharmacodynamic model.
OBJECTIVE
In order to explore the pharmacodynamic need for continuous versus intermittent (three times a day) administration of ceftazidime in critically ill patients, a pharmacokinetic computerized device was used to simulate concentrations of ceftazidime in human serum after 6 g/day.


METHODS
Efficacy was measured as the capability of simulated concentrations over time to reduce initial inoculum against four strains of Pseudomonas aeruginosa. MICs of the strains matched NCCLS breakpoints: one susceptible strain (MIC = 8 mg/L), two intermediate strains (MIC = 16 mg/L) and one resistant strain (MIC = 32 mg/L). C(max) was 119.97+/-2.53 mg/L for intermittent bolus and C(ss) (steady-state concentration) was 40.38+/-0.16 mg/L for continuous infusion. AUC(0-24) was similar for both regimens (approximately 950 mg x h/L). Inhibitory quotients were three times higher for the intermittent administration whereas t > MIC was higher for continuous infusion (100%) versus intermittent administration (99.8%, 69% and 47.6% for the susceptible, intermediate and resistant strains, respectively).


RESULTS
Against the susceptible and intermediate strains, no differences were found between both regimens with > or = 3 log10 reduction from 8 to 24 h. Against the resistant strain, only the continuous infusion achieved this bactericidal activity in the same time period, minimizing the differences between resistant and susceptible strains. Significantly higher initial inoculum reduction at 32 h was obtained for the continuous versus the intermittent administration (83.35% versus 38.40%, respectively).


CONCLUSIONS
These results stress the importance of optimizing t >MIC, even at peri-MIC concentrations, of ceftazidime against resistant strains. Local prevalence of resistance justifies, on a pharmacodynamic basis, electing for continuous infusion versus intermittent administration.
Alou
Luis
L
Microbiology Department, School of Medicine, Universidad Complutense, Madrid, Spain.
Aguilar
Lorenzo
L
Sevillano
David
D
Giménez
María-José
MJ
Echeverría
Olatz
O
Gómez-Lus
María-Luisa
ML
Prieto
José
J
D002442:Ceftazidime / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D008954:Models, Biological; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology
D002442:Ceftazidime