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Ceftazidime and amikacin alone and in combination against Pseudomonas aeruginosa and Enterobacteriaceae
Abstract:
The efficacy of ceftazidime alone and combined with amikacin was studied in a rabbit model simulating closed-space infections at locally neutropenic sites. Six strains of Pseudomonas aeruginosa, and six Enterobacteriaceae (two strains each of Klebsiella pneumoniae and Serratia marcescens and one strain each of Escherichia coli and Citrobacter freundii) in pooled rabbit serum were each inoculated into separate subcutaneous semipermeable chambers. Intramuscular antibiotic therapy was begun 4 hr later with ceftazidime (50 mg/kg) alone and combined with amikacin (15 mg/kg) for Enterobacteriaceae or ceftazidime (100 mg/kg) alone and combined with amikacin (15 mg/kg) for pseudomonads every 6 hr for 16 doses. Amikacin alone was ineffective for all 12 strains. Ceftazidime alone was successful (greater than or equal to 5.5 log10 colony forming units (CFU)/ml decrease from drug-free control) in eliminating five of six Enterobacteriaceae but was not successful against any of the pseudomonads. Ceftazidime plus amikacin was successful against the same five of six Enterobacteriaceae and five of six pseudomonads. The best in vitro tests for the prediction of in vivo outcome were high inoculum (greater than or equal to 7 log10 CFU/ml) susceptibility, checkerboard synergism testing, and conventional inoculum time-kill rates at concentrations of antimicrobials simulating extravascular levels obtained in vivo.
Insights
Ceftazidime combined with amikacin effectively treated Pseudomonas aeruginosa and Enterobacteriaceae infections in rabbits. In vitro tests accurately predicted these in vivo treatment outcomes.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Closed-space infections pose treatment challenges.
- Neutropenic sites can exacerbate infection severity.
- Assessing antibiotic efficacy in simulated infection models is crucial.
Purpose of the Study:
- To evaluate the efficacy of ceftazidime alone and in combination with amikacin.
- To investigate treatment outcomes in a rabbit model of closed-space infections.
- To identify predictive in vitro susceptibility tests for in vivo outcomes.
Main Methods:
- A rabbit model with subcutaneous semipermeable chambers was used.
- Inoculation with six strains of Pseudomonas aeruginosa and six Enterobacteriaceae.
- Intramuscular antibiotic therapy with ceftazidime and amikacin administered over 16 doses.
Main Results:
- Amikacin monotherapy was ineffective against all tested strains.
- Ceftazidime alone effectively treated five of six Enterobacteriaceae strains but not Pseudomonas.
- Ceftazidime plus amikacin successfully treated five of six Enterobacteriaceae and five of six Pseudomonas strains.
Conclusions:
- Ceftazidime combined with amikacin demonstrates significant efficacy against Pseudomonas aeruginosa and Enterobacteriaceae in a rabbit infection model.
- High-inoculum susceptibility, checkerboard synergism, and time-kill assays are valuable predictors of in vivo antibiotic response.
- This combination therapy offers a promising strategy for treating complex bacterial infections at neutropenic sites.