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A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
Activity of cloxacillin against Cutibacterium acnes: MIC evaluation and utility of gradient test
Alkmini Angelopoulou1,2, Nicolai Riff Alexandersen1, Christian Salgaard Jensen1
1Department of Clinical Microbiology, Copenhagen Ø, DK, Denmark.
Background:
Cutibacterium acnes is a cause of implant-associated infections, often co-occurring with methicillin-susceptible Staphylococcus aureus (MSSA), especially in orthopedic settings. In Scandinavia, cloxacillin may be used as initial empiric intravenous treatment if MSSA implant-associated infection is suspected. Clinical breakpoints for C. acnes susceptibility to cloxacillin or other isoxazolyl-penicillins are lacking to guide therapy if C. acnes is subsequently cultured after empiric cloxacillin therapy has been initiated.
Objective:
We aimed to compare MIC distributions of C.acnes to benzylpenicillin and cloxacillin. Furthermore, we investigated if the gradient test is a reliable method for determining cloxacillin susceptibility in clinical C. acnes isolates in order to manage mixed infections in orthopedic settings.
Methods:
We evaluated the in vitro susceptibility of 39 clinical C. acnes isolates to benzylpenicillin and cloxacillin using gradient tests and validated cloxacillin MICs by agar dilution.
Results:
All isolates were susceptible to benzylpenicillin (MIC ≤0.064 mg/L) and cloxacillin (MIC ≤0.5 mg/L), with MIC50 values of 0.016 mg/L and 0.125 mg/L, respectively. The cloxacillin MIC distribution for C. acnes closely resembled that of S. aureus, suggesting that susceptibility to cloxacillin may be inferred from benzylpenicillin susceptibility. Gradient test results for cloxacillin showed high agreement with agar dilution (essential agreement 0.87), supporting its use as a practical alternative to agar dilution cloxacillin MIC determination if susceptibility testing is necessary.
Conclusion:
Our findings indicate that intravenous cloxacillin is an effective treatment of C. acnes infections, and that cloxacillin gradient testing is a convenient and reliable alternative for MIC determination for clinical laboratories.
Insights
Cloxacillin effectively treats Cutibacterium acnes infections, and gradient testing reliably determines its susceptibility. This aids managing implant-associated infections, especially in orthopedic settings.
Area of Science:
- Microbiology
- Infectious Diseases
- Clinical Pharmacology
Background:
- Cutibacterium acnes (C. acnes) is a common cause of implant-associated infections, frequently co-occurring with methicillin-susceptible Staphylococcus aureus (MSSA).
- Cloxacillin is often used empirically for suspected MSSA implant infections in Scandinavia.
- Lack of clinical breakpoints for C. acnes against cloxacillin complicates treatment decisions when C. acnes is identified post-initiation of empiric therapy.
Purpose of the Study:
- To compare the Minimum Inhibitory Concentration (MIC) distributions of C. acnes to benzylpenicillin and cloxacillin.
- To evaluate the reliability of the gradient test for determining cloxacillin susceptibility in clinical C. acnes isolates.
- To inform management strategies for mixed C. acnes and MSSA orthopedic implant infections.
Main Methods:
- In vitro susceptibility testing of 39 clinical C. acnes isolates.
- Evaluation of susceptibility to benzylpenicillin and cloxacillin using gradient tests.
- Validation of cloxacillin MICs determined by gradient testing through agar dilution.
Main Results:
- All C. acnes isolates were susceptible to both benzylpenicillin (MIC ≤0.064 mg/L) and cloxacillin (MIC ≤0.5 mg/L).
- The MIC distribution for cloxacillin in C. acnes resembled that of S. aureus, suggesting potential inference of susceptibility.
- Gradient testing demonstrated high agreement (0.87 essential agreement) with agar dilution for cloxacillin MIC determination.
Conclusions:
- Intravenous cloxacillin is indicated as an effective treatment for C. acnes infections.
- Cloxacillin gradient testing offers a practical and reliable alternative for MIC determination in clinical laboratories.
- These findings support the use of cloxacillin for C. acnes infections and gradient testing for susceptibility assessment.

