A Pharmacokinetic and Pharmacodynamic Study on Intravenous Cefazedone Sodium in Patients with Community-acquired Pneumonia.

Background: As a time-dependent antibiotic, the time of cefazedone concentration exceeds the minimum inhibitory concentration (MIC) is the key pharmacokinetic-pharmacodynamic (PK-PD) variable associated with the killing of pathogens. The purpose of the study was to evaluate the clinical regimen rationality of intravenous cefazedone sodium in the treatment of community-acquired pneumonia (CAP) by PK/PD study.

Methods: Ten patients with mild to moderate CAP were enrolled to receive intravenous cefazedone sodium (2 g q12 h) for 7-14 days. Blood samples were collected in any day during day 5-7. Sputum specimens were collected before treatment for bacteria isolated, and susceptibility to cefazedone determined. PK-PD analysis was performed using the noncompartmental analysis of Phoenix WinNolin software (version 6.1, Pharsight Corporation, CA, USA). The maximal time above MIC (ƒT > MIC) was calculated, and its correlation with clinical efficacy was analyzed.

Results: All 10 patients completed the study and 8 of them were cured. Six strains were isolated from patients before treatment (one for each patient) and all susceptible to cefazedone. Five patients of six in culture positive group were cured. All pathogens were cleared at the end of therapy. The MICs were between 0.25 and 1 mg/L. The main PK parameters were C max 175.22 ± 36.28 mg/L; T½ 1.52 ± 0.23 h; AUC (0-∞) 280.51 ± 68.17 mg·L -1·h -1 ; CL 7.37 ± 1.84 L/h; Vd 16.06 ± 4.42 L. The average ƒT > MIC was 55.45 ± 8.12%.

Conclusions: Intravenous injection of cefazodone sodium with 2 g q12 h dosage regimen is used in the treatment of CAP caused by sensitive bacteria, either ƒT > MIC or clinical efficacy shows that such dosing regimen is reasonable.