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Amoxicillin (Amx) Fails to Prevent Penicillin-Resistant Streptococcus mitis Experimental Endocarditis (EE) Using a Human-Like Pharmacokinetic Model.

MIRO JM, MARCO F, GARCIA DE LA MARIA C, DEL RIO A, GAVALDA J, ALMELA M, ARMERO Y, DIAZ ME, SOY D, MORENO A, PAHISSA A, GATELL JM, JIMENEZ DE ANTA MT; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 49.

Idibaps-Hosp. Clin., Barcelona, Spain

BACKGROUND: The prevalence of resistance to b-lactam antibiotics among the viridans group streptococci (VGS) is increasing during the last decade worldwide. In order to evaluate if Amx, Amx plus gentamicin (Gen) or ceftriaxone (Cro) were effective for preventing EE caused by a highly penicillin-resistant S. mitis strain, we conducted an experimental study using a human-like pharmacokinetic model.METHODS: A clinical isolate of S. mitis was used. Amx, Gen and Cro MIC/MBC were 8/16, 4/8, 4/4 mg/L respectively. Twenty-four hours after the catheter induced aortic valve vegetations, 105 cfu/mL of S. mitis were injected by iv route. One hour before the animals were treated with a single i.v. dose of either Amx, Amx + Gen or Cro given with a computer-controlled infusion pump system which simulates the human serum kinetics of either Amx (2 gr iv), Gen (80 mg iv) or Cro (1 gr iv). Control and treated rabbits were sacrificed 24 h and 48 h after the i.v. challenge respectively. Valve vegetations were qualitatively cultured.RESULTS: Peak and trough antibiotic serum levels were: 100 and 1.4 mg/L for Amx, 9.3 and 1 mg/L for Gen and 150 and 8 mg/L for Cro. Antibiotic serum levels above the MIC were maintained during 2 h, 1.5 h and 22 h respectively. Endocarditis developed in all (20/20, 100%) untreated animals, in 19 out of 22 rabbits (86%) receiving Amx, in 2 out of 19 rabbits (10%) treated with Amx plus Gen and in none of the animals receiving Cro (0/19, 0%). Amx plus Gen or Cro were more effective than Amx alone (p<0.001).CONCLUSIONS: The current Amx regimen was ineffective for preventing penicillin-resistant S. mitis EE. If penicillin resistance is increasing among VGS the role of Amx as standard prophylactic regimen for the prevention of VGS endocarditis in humans should be reconsidered.KEYWORDS: Endocarditis; Prophylaxis; Viridans streptococci

Publication Types:
  • Meeting Abstracts
Keywords:
  • Amoxicillin
  • Animals
  • Anti-Bacterial Agents
  • Ceftriaxone
  • Endocarditis
  • Gentamicins
  • Humans
  • Microbial Sensitivity Tests
  • Penicillin Resistance
  • Penicillins
  • Rabbits
  • Streptococcus mitis
  • Viridans Streptococci
  • pharmacokinetics
Other ID:
  • GWAIDS0010037
UI: 102247535

From Meeting Abstracts




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