Pharmacokinetics and Pharmacodynamic Evaluation of Teicoplanin in Elderly Patients with Severe Methicillin-resistant Staphylococcus Aureus Infection

OBJECTIVE To investigate the pharmacokinetic differences and pharmacodynamic evaluation of teicoplanin in elderly patients with methicillin-resistant Staphylococcus aureus(MRSA) pulmonary infection. METHODS The 50 patients diagnosed with MRSA pulmonary infection from September 2018 to August 2019, the culture of lower respiratory tract sputum specimens before treatment indicated MRSA infection and sensitivity to teicoplanin. All patients were given intravenous teicoplanin, the first three doses of 400 mg, once every 12 h, and a maintenance dose of 400 mg once every 24 h. The maintenance dose regimen for patients with C_min ≤ 10 μg·mL^-1measured before the fifth dose after reaching steady state was changed to 600 mg qd. Teicoplanin 400 mg or 600 mg for injection was dissolved in 100 mL 0.9% sodium chloride injection, the administration time was 30 min, and the course of treatment is 14-21 d. The 2 mL of venous blood was collected at the specified time, the blood drug concentration was detected by HPLC, and the DAS 3.0 software was used for processing to obtain the pharmacokinetic parameters of each patient. After reaching steady state, the pharmacokinetic parameter of C_min>10μg·mL^-1measured before the fifth dose was set to A. For patients with C_min ≤ 10 μg·mL^-1, the maintenance dose was adjusted to 600 mg qd, and set the pharmacokinetic parameter of C_min>10 μg·mL^-1 as B before the fifth dose after adjusting the dose. Patients were divided into severe and non severe groups according to APACHE II score and SOFA score. Comparison of clinical treatment efficiency, bacterial clearance rate and adverse reactions between the two groups at C_min of 10-20 μg·mL^-1and 20-30 μg·mL^-1, AUC/MIC ≥ 345 and <345 combined with PK/PD principle. RESULTS The pharmacokinetics of teicoplanin was best described by two compartment model. The loading dose was the same, the pharmacokinetic parameters of group A with 400 mg maintenance dose and group B with 600 mg maintenance dose were as follows:C_max was(32.28±15.16)mg·L^-1vs (65.73±28.96)mg·L^-1, t_1/2 was(86.24±10.61)h vs (70.51±11.78)h, V_d was(2.73±1.32)L·kg^-1vs (2.58±1.02)L·kg^-1, CL was(0.11±0.05)L·h^-1·kg^-1vs (0.13±0.06)L·h^-1·kg^-1, AUC_(0-t)was(2 698.16±1 603.25)mg·h·L^-1vs (4 076.85±1 873.09)mg·h·L^-1, AUC_(0~∞) was(4 509.33±2 786.54)mg·h·L^-1vs (7 193.58±4 109.81)mg·h·L^-1, the difference was statistically significant (P<0.05). The clinical effective rates of patients with SOFA scores ≤ 5 and >5 were 65.71% and 53.33%, and the bacterial clearance rates were 65.79% and 47.37%. The clinical effective rates of APACHE II scores ≤ 15 and >15 were 63.64% and 58.82%, and the bacterial clearance rates were 63.16% and 52.63%. CONCLUSION The pharmacokinetics of teicoplanin in elderly patients with MRSA pulmonary infection is quite different. Combined with PK/PD principle, it can provide a scientific dosing plan for the individualized treatment.