Ampicillin/sulbactam in elderly patients with community-acquired pneumonia.

Abstract

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, AUC0-8 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 MIC90 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/MIC90 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.

• Authors: J Majcher-Peszynska, M Loebermann, S Klammt, S Frimmel, R G Mundkowski, T Welte, E C Reisinger, B Drewelow, CAPNETZ Study Group
• Journal: Infection (Infection) Vol. 42 Issue 1 Pg. 79-87 (Feb 2014) ISSN: 1439-0973 [Electronic] Germany
• PMID: 23904004 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• sultamicillin
• Ampicillin
• Sulbactam

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Ampicillin (administration & dosage, pharmacokinetics, pharmacology)
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics, pharmacology)
• Community-Acquired Infections (drug therapy)
• Female
• Humans
• Injections, Intravenous
• Male
• Microbial Sensitivity Tests
• Plasma (chemistry)
• Pneumonia, Pneumococcal (drug therapy)
• Prospective Studies
• Streptococcus pneumoniae (drug effects)
• Sulbactam (administration & dosage, pharmacokinetics, pharmacology)
• Time Factors
• Treatment Outcome