%0 Journal Article
%T Reduction of Beta-Lactam Antimicrobial Activity in <i>Staphylococcus aureus</i> Abscesses by Neutrophil Alteration of Penicillin-Binding Protein 2
%A David M. Bamberger
%A Matthew Goers
%A Tim Quinn
%A Betty Herndon
%J Advances in Infectious Diseases
%P 48-52
%@ 2164-2656
%D 2012
%I Scientific Research Publishing
%R 10.4236/aid.2012.22007
%X We previously demonstrated that brief nonkilling neutrophil exposure diminishes the binding affinity of <i>S. aureus</i> 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 <i>S. aureus</i>, cultured <i>in vitro</i> in sterile-filtered normal and neutrophil depleted abscess fluid, we sought to demonstrate an <i>in vivo</i> significance of the neutrophil effect upon the activity of antimicrobials that target PBP-2 by studying the same antimicrobials in an experimental <i>S. aureus</i> abscess. Rats were implanted with perforated tissue cages and infected with <i>S. aureus</i>; 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 ¦Ìg/kg/d cefotaxime or cephalexin for 7 days in other rats with 24 hour-old tissue-cage <i>S. aureus</i> abscesses. In time-kill studies, cefotaxime was highly active against stationary phase <i>S. aureus</i> in MHB and in neutropenic abscess fluid, but less active in the non-neutropenic abscess fluid (p &lt; 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 ¡À 1.7 log<sub>10</sub> kill, p = 0.029 vs. 0.81 ¡À 2.5, p = NS). These data suggest that neutrophil exposure, which diminishes <i>S. aureus</i> 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.
%K Neutrophils
%K Penicillin-Binding Proteins
%K &lt
%K i&gt
%K S. aureus&lt
%K /i&gt
%K Abscesses
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=19944