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ObjectiveTo characterize the pharmacokinetics (PK) of vancomycin in patients in the initial phase of septic shock.MethodsTwelve patients with septic shock received an intravenous infusion of vancomycin 30 mg/kg over 2 h. The vancomycin PK study was conducted during the first 12 h of the regimen. Serum vancomycin concentration–time data were analyzed using the standard model-independent analysis and the compartment model.ResultsFor the noncompartment analysis the mean values ± standard deviation (SD) of the estimated clearance and volume of distribution of vancomycin at steady state were 6.05±1.06 L/h and 78.73±21.78 L, respectively. For the compartmental analysis, the majority of vancomycin concentration–time profiles were best described by a two-compartment PK model. Thus, the two-compartmental first-order elimination model was used for the analysis. The mean ± SD of the total clearance (3.70±1.25 L/h) of vancomycin was higher than that obtained from patients without septic shock. In contrast, the volume of the central compartment (8.34±4.36 L) and volume of peripheral compartment (30.99±7.84 L) did not increase when compared with patients without septic shock.ConclusionThe total clearance of vancomycin was increased in septic shock patients. However, the volume of the central compartment and peripheral compartment did not increase. Consequently, a loading dose of vancomycin should be considered in all patients with septic shock.

Background Antibiotic-loaded bone cement, or antibiotic-impregnated polymethylmethacrylate (PMMA), were developed to prevent and treat bone and joint infections. Gentamicin is an antibiotic that is commonly used in combination with PMMA; however, gentamicin powder is hard to obtain in many countries. This study aimed to evaluate the elution characteristics of gentamicin-impregnated PMMA made with lyophilized liquid gentamicin, compared with PMMA; which is made from commercial gentamicin powder. Methods The experimental sample was divided into 2 groups: the gentamicin power group (PG-PMMA) and the lyophilized liquid gentamicin group (LG-PMMA). Ten cement spacers were prepared in each group. These were produced by mixing gentamicin powder, or lyophilized liquid gentamicin, with a powder polymer before adding the liquid monomer (2 g of gentamicin and 40 g of PMMA). The volume and surface area of the antibiotic-impregnated cement spacers were 50 cm3 and 110 cm2, respectively. Each spacer was immersed in phosphate-buffered saline, which was changed daily under sterile conditions. The solutions were collected to measure the level of gentamicin using the enzyme multiplied immunoassay technique (EMIT), at days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28, 35 and 42. Results The collections from both groups had high concentrations of gentamicin on day 1 (113.63 ± 23.42 mg/dL in LG-PMMA and 61.7 ±8.37 mg/dL in PG-PMMA), but experienced a continuous decrease over time. The PMMA spacers from both groups could release gentamicin for up to 6 weeks (3.28 ± 1.17 mg/dL in LG-PMMA and 1.21 ± 0.28 mg/dL in PG-PMMA). However, there were significantly higher levels of gentamicin concentrations in the LG-PMMA group compared to the PG-PMMA group at all time points (P< 0.05). Conclusion Gentamicin-impregnated PMMA made with lyophilized liquid gentamicin had approximately a two times higher rate of antibiotic elution in preliminary in vitro studies, as compared with PMMA made with premixed gentamicin powder.