title: Ampicillin/sulbactam in elderly patients with community-acquired pneumonia.
abstract: OBJECTIVE
  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).
  
  
  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.affiliation: Center of Pharmacology and Toxicology, Institute of Clinical Pharmacology, University of Rostock, Schillingallee 70, 18057, Rostock, Germany, jolanta.majcher-peszynska@medizin.uni-rostock.de.
authors.forename: J
authors.initials: J
authors.lastname: Majcher-Peszynska
authors.forename: M
authors.initials: M
authors.lastname: Loebermann
authors.forename: S
authors.initials: S
authors.lastname: Klammt
authors.forename: S
authors.initials: S
authors.lastname: Frimmel
authors.forename: R G
authors.initials: RG
authors.lastname: Mundkowski
authors.forename: T
authors.initials: T
authors.lastname: Welte
authors.forename: E C
authors.initials: EC
authors.lastname: Reisinger
authors.forename: B
authors.initials: B
authors.lastname: Drewelow
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000667:Ampicillin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D017714:Community-Acquired Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D010949:Plasma / Q000737:chemistry; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D011446:Prospective Studies; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013407:Sulbactam / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; C035444:sultamicillin; D000667:Ampicillin; D013407:Sulbactam
references.citation: Clin Microbiol Infect. 2002 Mar;8(3):144-53
references.pmid: 12010169
references.citation: Antimicrob Agents Chemother. 1991 Oct;35(10):2098-101
references.pmid: 1759832
references.citation: Drugs Aging. 2003;20(4):289-302
references.pmid: 12641485
references.citation: Internist (Berl). 2009 Mar;50(3):331-9; quiz 340
references.pmid: 19156393
references.citation: Clin Pharmacokinet. 2005;44(7):767-8
references.pmid: 15966758
references.citation: Drugs. 2007;67(13):1829-49
references.pmid: 17722953
references.citation: Clin Infect Dis. 2004 Dec 1;39(11):1642-50
references.pmid: 15578365
references.citation: Arch Intern Med. 1999 Jul 26;159(14):1550-5
references.pmid: 10421277
references.citation: Drugs. 1987 Jun;33(6):577-609
references.pmid: 3038500
references.citation: Eur J Clin Pharmacol. 1997;53(2):111-5
references.pmid: 9403281
references.citation: Infection. 1994 Mar-Apr;22(2):149-51
references.pmid: 8070929
references.citation: Rev Infect Dis. 1986 Nov-Dec;8 Suppl 5:S528-34
references.pmid: 3026001
references.citation: Arch Intern Med. 2003 Feb 10;163(3):317-23
references.pmid: 12578512
references.citation: Rev Infect Dis. 1986 Nov-Dec;8 Suppl 5:S503-11
references.pmid: 3025997
references.citation: Clin Ther. 1991 Nov-Dec;13(6):714-26
references.pmid: 1790546
references.citation: Antimicrob Agents Chemother. 1998 Sep;42(9):2375-9
references.pmid: 9736566
references.citation: Antimicrob Agents Chemother. 1994 May;38(5):931-6
references.pmid: 8067772
references.citation: J Antimicrob Chemother. 2004 Nov;54(5):876-80
references.pmid: 15472003
references.citation: Int J Antimicrob Agents. 2008 Jul;32(1):10-28
references.pmid: 18539004
references.citation: Crit Care Med. 2009 Mar;37(3):840-51; quiz 859
references.pmid: 19237886
references.citation: Intern Med. 2006;45(17):995-9
references.pmid: 17015999
references.citation: Clin Infect Dis. 2001 Sep 15;33 Suppl 3:S233-7
references.pmid: 11524724
references.citation: Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72
references.pmid: 17278083
references.citation: Infection. 1989 Jul-Aug;17(4):272-4
references.pmid: 2767773
references.citation: Antimicrob Agents Chemother. 1990 Jun;34(6):958-62
references.pmid: 2393293
references.citation: Thorax. 2012 Jan;67(1):71-9
references.pmid: 20729232
references.citation: Antimicrob Agents Chemother. 1989 Sep;33(9):1470-6
references.pmid: 2817847
references.citation: Crit Care. 2009;13(3):214
references.pmid: 19519961
references.citation: Infection. 1990 Sep-Oct;18(5):307-9
references.pmid: 2276827
references.citation: Age Ageing. 2010 Jan;39(1):39-45
references.pmid: 19561160
references.citation: Infection. 2011 Dec;39(6):515-8
references.pmid: 21789524
references.citation: Infection. 1979;7 Suppl 5:S463-4
references.pmid: 511358
references.citation: Eur Respir J. 2005 Dec;26(6):1138-80
references.pmid: 16319346
references.citation: Pneumologie. 2010 Mar;64(3):149-54
references.pmid: 20180179
references.citation: J Chemother. 1997 May;9 Suppl 3:38-44
references.pmid: 9248979
references.citation: Ann Pharmacother. 2005 Jan;39(1):32-8
references.pmid: 15598967
references.citation: Expert Opin Drug Metab Toxicol. 2009 Sep;5(9):1099-112
references.pmid: 19621991
references.citation: Drugs Aging. 2008;25(7):585-610
references.pmid: 18582147
references.citation: J Antimicrob Chemother. 1989 Oct;24(4):573-80
references.pmid: 2613605
references.citation: J Antimicrob Chemother. 1983 May;11(5):435-45
references.pmid: 6307964
references.citation: Lancet. 1965 May 1;1(7392):929-33
references.pmid: 14275709