Bactericidal In Vitro Activity of a Tissue-Achievable Concentration of Cefazolin against Methicillin-Resistant Staphylococcus aureus

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections and their recurrences. Although traditionally not considered for use against MRSA, cefazolin presents a possible option when administered using ultrasonic drug dispersion (UD2). This novel technique localizes delivery of drug into the subcutaneous tissue and achieves concentrations that exceed the minimum inhibitory concentrations (MICs) of most clinical MRSA isolates. The purpose of this study was to evaluate the impact of achievable cefazolin concentrations on the rate and extent of bactericidal activity using time-kill methodologies Materials and Methods: The cefazolin MICs of the four MRSA isolates selected for this in vitro time-kill study were 64, 128, 256, and 512 mg/L. Duplicates of drug-free control and cefazolin experiments were carried out using the average UD2-achievable cefazolin concentration (1,300 mg/L). Experiments were incubated at 37°C throughout each run. Samples were plated and incubated for 18 to 24 hours. The lower limit of detection of colony forming units per milliliter (CFU/mL) was 1.7 log10 CFU/mL. Cefazolin was considered bactericidal when it decreased bacterial density by ≥3 log10 CFU/mL from the initial inoculum after 24 hours of incubation. Results: Cefazolin produced mean 24-hour CFU changes of −4.39 to −4.89 log10 CFU/mL against MRSA isolates with MICs from 64 to 512 mg/L. Cefazolin demonstrated bactericidal activity against all studied MRSA isolates and no regrowth was observed at 24 hours. Conclusions: The mean cefazolin tissue concentration achieved by UD2 was bactericidal against four MRSA isolates. Further investigation is warranted to assess the utility of UD2-administered cefazolin against MRSA skin and soft tissue infections.