Ampicillin/sulbactam in elderly patients with community-acquired pneumonia

Purpose Age-related physiological changes affect body systems, altering pharmacokinetics, which may potentiate or alter the effects of drugs. The aim of this study was to assess the influence of age on the steady-state pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sul...

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Bibliographic Details
Published in:Infection 2014-02, Vol.42 (1), p.79-87
Main Authors: Majcher-Peszynska, J., Loebermann, M., Klammt, S., Frimmel, S., Mundkowski, R. G., Welte, T., Reisinger, E. C., Drewelow, B.
Format: Article
Language:English
Subjects:
Age Factors
Aged
Aged, 80 and over
Ampicillin - administration & dosage
Ampicillin - pharmacokinetics
Ampicillin - pharmacology
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - pharmacokinetics
Anti-Bacterial Agents - pharmacology
Clinical and Epidemiological Study
Community-Acquired Infections - drug therapy
Family Medicine
Female
General Practice
Humans
Infectious Diseases
Injections, Intravenous
Internal Medicine
Male
Medicine
Medicine & Public Health
Microbial Sensitivity Tests
Plasma - chemistry
Pneumonia, Pneumococcal - drug therapy
Prospective Studies
Streptococcus pneumoniae - drug effects
Sulbactam - administration & dosage
Sulbactam - pharmacokinetics
Sulbactam - pharmacology
Time Factors
Treatment Outcome
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Summary:Purpose Age-related physiological changes affect body systems, altering pharmacokinetics, which may potentiate or alter the effects of drugs. The aim of this study was to assess the influence of age on the steady-state pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sulbactam in the population of elderly patients (age ≥65 years) with community-acquired pneumonia (CAP). Patients and methods The pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sulbactam were determined at steady state in a total of 13 elderly patients with CAP following the administration of multiple intravenous doses of 2 g ampicillin + 1 g sulbactam (Unacid ® , Pfizer), each over 15 min thrice a day. Results A reduced C max , AUC 0–8 h and total clearance, a prolonged half-life, and an increased steady-state volume of distribution were observed for ampicillin. The mean estimated free C min of 1.8 mg/L for ampicillin was higher than that predicted to be effective against Streptococcus pneumoniae . Based on an MIC 90 of 1 mg/L for Streptococcus pneumoniae , the calculated T  > MIC and T  > 4 × MIC for ampicillin was 75–100 % (median 100 %) and 12.5–100 % (median 50 %), respectively. A T  > 4 × MIC of at least 50 % was achieved in 7 of 13 elderly patients with CAP. Conclusions Age and, probably, pneumonia did affect the pharmacokinetics of ampicillin and sulbactam. Despite the reduced C max , adequate free C min /MIC 90 ratios due to impaired renal function were observed in elderly patients with CAP. In elderly patients without renal impairment and/or in severe infection with less susceptible pathogens, more frequent dosing of ampicillin 2 g/sulbactam 1 g can be necessary to avoid the risk of underdosing in CAP.
ISSN:0300-8126
1439-0973
DOI:10.1007/s15010-013-0518-8