Pharmacokinetics of ceftazidime
The introduction of ceftazidime in patients with severe intra-abdominal infections by continuous intravenous administration is more preferable than its appointment in intermittent mode.
The results of a study by Dutch scientists have shown that administration of ceftazidime to patients with severe intra-abdominal infections (IAI) by continuous intravenous administration is more preferable than its appointment in intermittent mode. Constant administration of ceftazidime ensures that optimal levels of the drug are maintained in blood serum and peritoneal fluid for the duration of treatment.
Ceftazidime (like other β-lactams) exhibits time-dependent antimicrobial activity, maximum when the concentration of the drug at the site of infection is 4 to 5 times higher than the CPI of the pathogen. Therefore, to maintain optimal concentrations of ceftazidime, constant iv administration of the drug is proposed. Treatment of severe IAI consists of antibiotic therapy (ceftazidime is often prescribed) and surgical drainage of the abdominal cavity. Cardiovascular system disorders, metabolic disorders, liver damage and reduced kidney function that occur with severe IAI can affect the pharmacokinetics of drugs, but no studies of ceftazidime in peritoneal fluid have been done before.
The aim of this study was to study the pharmacokinetics of ceftazidime with constant iv administration compared to the intermittent regimen and to determine the concentration of the drug in the peritoneal fluid in patients with severe IAI.
The study included patients with severe IAI and creatinine clearance greater than 30 ml / min. In a pilot study, 6 patients received ceftazidime by continuous iv administration: 1 g iv, then 4.5 g as a continuous infusion over 24 hours. Another 12 patients participated in a prospective randomized comparative study: one group received ceftazidime as a continuous infusion (as indicated above), the second - 1.5 g of the drug as an intravenous bolus every 8 hours Samples to determine ceftazidime concentrations were obtained on the 2nd and 4th day of treatment.
The results of the study showed that with a continuous infusion of ceftazidime into the blood serum, antibiotic concentrations of more than 40 mg / l are created. In addition, the time during which the concentration of the antibiotic in serum and in peritoneal fluid is 4 times or more the MPC for most pathogens of severe IIA is more than 90% of the total duration of treatment. With an intermittent regimen, the last indicator in blood serum also represented more than 90% of the dosing interval, but only 44% in peritoneal fluid. With constant IV administration, the area under the pharmacokinetic curve (PFC) of the drug in the peritoneal fluid was 60% of the PFC in serum.
Thus, continuous infusions of ceftazidime in severe IAIs allow more predictable and optimal drug concentrations in serum and peritoneal fluid. Since ceftazidime PFC in peritoneal fluid does not exceed 60% of serum PFCs, in severe IAI caused by microorganisms with relatively high MIC values (e.g. Pseudomonas spp. ), An increase in the dose of the drug may be necessary to achieve clinical efficacy.