Meropenem Dosing Based on a Population Pharmacokinetic–Pharmacodynamic Model in Elderly Patients with Infection of the Lower Respiratory Tract

• DOI: 10.1007/s40266-016-0431-9
• Publication Date: 2017-01-17T12:22:18Z
• Authors: Qing-Tao Zhou; Bei He; Ning Shen; Ying Liang; Li-Na Sun
• Keywords: Male; 0301 basic medicine; Respiratory System; Meropenem; Middle Aged; Models, Biological; Anti-Bacterial Agents; 3. Good health; 03 medical and health sciences; Treatment Outcome; Drug Resistance, Multiple, Bacterial; Humans; Female; Thienamycins; Prospective Studies; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Aged

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.