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Abstract
Introduction
Despite aggressive medical and surgical management, the resolution of skin and skin structure infections is often difficult due to insufficient host response, reduced drug penetration, and a high prevalence of resistance organisms such as methicillin-resistant Staphylococcus aureus (MRSA). As a result of these factors, conventional management often consists of prolonged broad-spectrum systemic antimicrobials. An alternative therapy in development, ultrasonic drug dispersion (UDD), uses a subcutaneous injection followed by external trans-cutaneous ultrasound to deliver high tissue concentrations of cefazolin with limited systemic exposure. While it is postulated that these high concentrations may be suitable to treat more resistant organisms such as MRSA, the cefazolin minimum inhibitory concentration (MIC) distribution for this organism is currently unknown.
Materials and methods
We assessed the potency of cefazolin against a collection of 1,239 MRSA from 42 US hospitals using Clinical Laboratory Standard Institute-defined broth micro-dilution methodology.
Results
The cefazolin MIC inhibiting 50% of the isolates was 64 mg/L; 81% had MICs ≤128 and nearly all (99.9%) had MICs ≤512 mg/L.
Conclusion
The overwhelming majority of MRSA had cefazolin MICs that were considerably lower than achievable tissue concentrations (≥1,000 mg/L) using this novel drug delivery system. While the currently defined cefazolin MRSA phenotypic profile precludes the use of parenteral administration, techniques that deliver local exposures in excess of these inhibitory concentrations may provide a novel treatment strategy for skin and skin structure infections.
Acknowledgments
The authors thank Christina Sutherland and the staff of the Center for Anti-Infective Research and Development, Hartford Hospital, for conducting the in vitro susceptibility testing. Abstract of this paper has been presented: Nicolau DP, Silberg BN. Assessing the Potency of Cefazolin against Methicillin-Resistance Staphylococcus aureus (MRSA): Microbiologic Data Supporting Ultrasonic Drug Dispersion for the Management of Skin & Skin Structure Infections (SSSIs) (Abstract No. C-1071). 55th Interscience Conference on Antimicrobial Agents and Chemotherapy/International Congress of Chemotherapy and Infection, San Diego, CA, September 2015.
Author contributions
David P Nicolau and Barry N Silberg conceived and designed the experiments, reviewed the raw data and quality control procedures, analyzed the data, and wrote the paper.
Disclosure
Drs Nicolau and Silberg are shareholders in Sonesence, the developer of the UDD technique. The authors report no other conflicts of interest in this work.