Efficacy of amikacin and ceftazidime in experimental aortic valve endocarditis due to Pseudomonas aeruginosa

A. S. Bayer, D. Norman, K. S. Kim

Research output: Contribution to journalArticlepeer-review

Abstract

The in vivo efficacies of amikacin, ceftazidime, and their combination were evaluated in experimental aortic valve endocarditis due to Pseudomonas aeruginosa. Eighty catheterized rabbits were infected with a P. aeruginosa strain susceptible to both amikacin and ceftazidime and then received no therapy (controls), amikacin (15 mg/kg per day), ceftazidime (100 mg/kg per day), or amikacin-ceftazidime. Amikacin-ceftazidime significantly lowered vegetation titers of P. aeruginosa at day 7 of therapy versus other regimens (P < 0.0005). However, by day 14 of therapy, vegetation titers in animals receiving amikacin or ceftazidime regimens or both were not different from those of untreated controls; this was associated with in vivo development of amikacin resistance in most infected vegetations (79%), a phenomenon not seen at day 7 of therapy. Amikacin resistance was unstable in vivo, being undetectable in vegetations examined 5 days after treatment with amikacin had been completed. In contrast, ceftazidime resistance (first noted at day 7 of therapy in 12% of vegetations) persisted after termination of treatment with this agent. These in vivo observations on loss of amikacin resistance and persistence of ceftazidime resistance were mirrored during in vitro passage studies of amikacin- or ceftadizime-resistant P. aeruginosa strains isolated from cardiac vegetations. Amikacin resistance was no longer detectable by passage 5 in antibiotic-free media; however, ceftazidime resistance was stable despite 15 such passages. In vivo development of aminoglycoside-β-lactam resistances was associated with poor bacteriologic efficacy in this model.

Original languageEnglish (US)
Pages (from-to)781-785
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume28
Issue number6
DOIs
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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