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Correlation between in vivo and in vitro efficacy of antimicrobial agents against foreign body infections
A F Widmer1, R Frei, Z Rajacic
1Department of Internal Medicine, University Hospital, Basel, Switzerland.
Abstract:
Implant-associated infections are often resistant to antibiotic therapy. Routine sensitivity tests fail to predict therapeutic success. Therefore experimental in vitro tests were sought that would better correlate with drug efficacy in device-related infections. The activity of six different antibiotics against methicillin-resistant Staphylococcus epidermidis was investigated. In vivo studies were performed with the guinea pig tissue-cage animal model; in vitro studies with minimum inhibiting and bactericidal concentrations, time-kill studies of growing and stationary-phase microorganisms, the killing of glass-adherent S. epidermidis. Drug efficacy on stationary and adherent microorganisms, but not minimum inhibiting concentrations, predicted the outcome of device-related infections. Rifampin cured 12 of 12 infections and was also the most efficient drug in any experimental in vitro test. Similarly, the failure of ciprofloxacin to eradicate foreign body infections correlated with its low efficacy on stationary-phase and adherent S. epidermidis.
Insights
Standard antibiotic sensitivity tests often fail for implant-associated infections. New in vitro tests focusing on stationary and adherent bacteria better predict treatment success for device-related infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Biomedical Engineering
Background:
- Implant-associated infections pose significant challenges due to antibiotic resistance.
- Conventional antibiotic sensitivity testing methods inadequately predict clinical outcomes for device-related infections.
Purpose of the Study:
- To evaluate novel in vitro experimental tests for predicting antibiotic efficacy in device-related infections.
- To compare the effectiveness of six antibiotics against methicillin-resistant Staphylococcus epidermidis (MRSA) in vitro and in vivo.
Main Methods:
- In vivo studies utilized the guinea pig tissue-cage animal model.
- In vitro studies included minimum inhibitory and bactericidal concentrations, time-kill assays on growing and stationary-phase bacteria, and assessment of killing efficacy against glass-adherent S. epidermidis.
Main Results:
- Antibiotic efficacy against stationary-phase and adherent microorganisms, not minimum inhibitory concentrations, correlated with therapeutic success in vivo.
- Rifampin demonstrated the highest efficacy in all in vitro tests and cured all 12 infections in the animal model.
- Ciprofloxacin's in vitro ineffectiveness against stationary and adherent S. epidermidis correlated with its failure to eradicate infections in vivo.
Conclusions:
- In vitro tests assessing antibiotic activity against stationary and adherent bacteria are superior predictors of treatment success for implant-associated infections compared to standard sensitivity tests.
- Rifampin shows significant promise for treating S. epidermidis device-related infections.
- The study highlights the limitations of traditional susceptibility testing for complex biofilm-related infections.