Author(s)

David M. Bamberger, Matthew Goers, Tim Quinn, Betty Herndon

Departments of Medicine and Basic Medical Science, School of Medicine, University of Missouri, Kansas City, USA.

We previously demonstrated that brief nonkilling neutrophil exposure diminishes the binding affinity of S. aureus penicillin-binding protein (PBP) 2. We sought to investigate further the role of the neutrophil in the alteration of antimicrobial activity and its interaction with PBP-2 by studying the activity of cefotaxime, which highly binds to PBP 2, and cephalexin, which minimally binds to PBP 2. Using S. aureus, cultured in vitro in sterile-filtered normal and neutrophil depleted abscess fluid, we sought to demonstrate an in vivo significance of the neutrophil effect upon the activity of antimicrobials that target PBP-2 by studying the same antimicrobials in an experimental S. aureus abscess. Rats were implanted with perforated tissue cages and infected with S. aureus; some rats were neutrophil depleted by mechlorethamine. Abscess fluids from normal and neutropenic abscesses were harvested, pooled, sterile-filtered and stored for the time-kill studies. Treatment studies were performed by administering either 300 μg/kg/d cefotaxime or cephalexin for 7 days in other rats with 24 hour-old tissue-cage S. aureus abscesses. In time-kill studies, cefotaxime was highly active against stationary phase S. aureus in MHB and in neutropenic abscess fluid, but less active in the non-neutropenic abscess fluid (p < 0.05 compared to neutropenic abscess fluid). Cephalexin was equally active in neutropenic and non-noneutropenic abscess fluids, and more active than cefotaxime in the abscess model after 7 days of therapy (2.1 ± 1.7 log₁₀ kill, p = 0.029 vs. 0.81 ± 2.5, p = NS). These data suggest that neutrophil exposure, which diminishes S. aureus PBP-2 binding affinity [or total quantity], also adversely affects the antimicrobial activity of cefotaxime, which binds to PBP-2, as compared to cephalexin. Altered PBP targets from neutrophil exposure may be a mechanism of antimicrobial resistance within abscesses.

Neutrophils; Penicillin-Binding Proteins; S. aureus; Abscesses

D. M. Bamberger, M. Goers, T. Quinn and B. Herndon, "Reduction of Beta-Lactam Antimicrobial Activity in Staphylococcus aureus Abscesses by Neutrophil Alteration of Penicillin-Binding Protein 2," Advances in Infectious Diseases, Vol. 2 No. 2, 2012, pp. 48-52. doi: 10.4236/aid.2012.22007.