title: Meropenem Dosing Based on a Population Pharmacokinetic-Pharmacodynamic Model in Elderly Patients with Infection of the Lower Respiratory Tract.
abstract: Meropenem is used for the treatment of severe lower respiratory tract infections (LRTIs) caused by multidrug-resistant Gram-negative bacilli.
  
  
  
  We evaluated the clinical benefits of a strategy of meropenem dosing based on a population pharmacokinetics/pharmacodynamics (PK/PD) model in elderly patients with an LRTI.
  
  
  
  In this prospective single-center open-label randomized controlled trial, 79 elderly patients with an LRTI caused by Gram-negative bacilli were randomized to a study group (SG) or a control group (CG). The latter received meropenem according to a regimen decided by the attending physician. The SG received individualized meropenem therapy with a dosing strategy based on software developed from a meropenem population PK/PD model. The primary endpoint was clinical response to meropenem therapy. Secondary endpoints were the amount of antibiotics used and bacteriologic response.
  
  
  
  Klebsiella pneumoniae was the most common pathogen (32.9%), followed by Pseudomonas aeruginosa (30.4%) and Escherichia coli (17.7%). A total of 63 (79.7%) patients achieved clinical success. Prevalence of clinical success was significantly higher in the SG than in the CG (89.7 vs. 70.0%; p = 0.029). The daily dose of meropenem was significantly lower in the SG than in the CG (1.5 vs. 2.0 g; p = 0.017). A total of 52 (65.8%) patients experienced bacteriologic success, the median duration of meropenem therapy was 9 days, and the median total dose of meropenem was 18.0 g. There were no significant differences between the groups in these parameters.
  
  
  
  A strategy for meropenem dosing based on a population PK/PD model can improve clinical response and avoid overtreatment in elderly patients with an LRTI. ClinicalTrials.gov registration number NCT01944319.
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, No. 49 North Garden Road., Haidian District, Beijing, 100191, China.
authors.forename: Qing-Tao
authors.initials: QT
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, No. 49 North Garden Road., Haidian District, Beijing, 100191, China. puh3_hb@bjmu.edu.cn.
authors.forename: Bei
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, No. 49 North Garden Road., Haidian District, Beijing, 100191, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, No. 49 North Garden Road., Haidian District, Beijing, 100191, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, No. 49 North Garden Road., Haidian District, Beijing, 100191, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Sun
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D012137:Respiratory System / Q000187:drug effects; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem