title: Efficacy and safety of biapenem against lower respiratory tract infections in elderly Chinese patients and optimal dosing regimen based on pharmacokinetic/pharmacodynamic analysis.
abstract: The present study evaluated the efficacy and safety of biapenem in elderly Chinese patients with lower respiratory tract infections (LRTIs) and proposed optimal dosage regimen on the basis of pharmacokinetic/pharmacodynamic (PK/PD) analysis. The clinical efficacy, bacterial eradication and comprehensive therapeutic effect rates of biapenem were 70.3 (78/111), 68.5 (37/54) and 61.1% (33/54), respectively. Drug-related adverse reactions were seen in 12.6% of patients (14/111). The total protein level, Acute Physiology and Chronic Health Evaluation (APACHE) II score, %fT>MIC, fAUC24/MIC and fCmax/MIC values of patients had significant impacts (P < 0.05) on clinical and bacteriological efficacy. However, logistic regression analysis showed that only %fT>MIC independently influenced comprehensive therapeutic effect (P < 0.01, odds ratio = 1.064). The cut-off value for predicting comprehensive therapeutic effect using %fT>MIC was 75.0%; the sensitivity and specificity were 87.9 and 85.7%, respectively. Monte Carlo simulations revealed that the usual dosage regimen (300 mg every 12 hours, 0.5 hour infusion) was considered to be insufficient to obtain satisfactory therapeutic outcomes against low susceptible pathogens for elderly Chinese patients with LRTIs (CLcr = 70 ml/min).
authors.affiliation: a Center of Drug Metabolism and Pharmacokinetics , China Pharmaceutical University , Nanjing , China.|b Department of Pharmacy , Gongli Hospital of Pudong New Area in Shanghai , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: c Institute of Antibiotics , Huashan Hospital, Fudan University , Shanghai , China.
authors.forename: Yuan-Cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: d Department of Respiratory , Gongli Hospital of Pudong New Area in Shanghai , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: d Department of Respiratory , Gongli Hospital of Pudong New Area in Shanghai , China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: a Center of Drug Metabolism and Pharmacokinetics , China Pharmaceutical University , Nanjing , China.
authors.forename: Ye-Bin
authors.initials: YB
authors.lastname: Sun
authors.affiliation: e Eshelman School of Pharmacy , University of North Carolina at Chapel Hill , NC , USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: b Department of Pharmacy , Gongli Hospital of Pudong New Area in Shanghai , China.
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: b Department of Pharmacy , Gongli Hospital of Pudong New Area in Shanghai , China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Li
authors.affiliation: a Center of Drug Metabolism and Pharmacokinetics , China Pharmaceutical University , Nanjing , China.
authors.forename: Xi-Jing
authors.initials: XJ
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D044466:Asian People; D005260:Female; D006801:Humans; D008297:Male; D009010:Monte Carlo Method; D012372:ROC Curve; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D013845:Thienamycins / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000890:Anti-Infective Agents; D013845:Thienamycins; C065257:biapenem
keywords: Biapenem; Efficacy and safety; Elderly Chinese patients; PK/PD analysis