Effect of hydrogen ion and protein concentrations on the activity of beta-lactam antibiotics

The susceptibility of 50 isolates of Staphylococcus aureus to seven beta-lactam antibiotics was measured under four conditions, involving two pH values and the presence or absence of serum protein. Multiple linear regression analysis was used to determine the effect of pH, protein, and antibiotic on the minimal inhibitory concentrations (MICs). Each of these factors as well as their interactions had significant effects on the MIC. The effects of pH and protein did not bear a predictable relationship to the extent of binding of antibiotic to serum proteins. All MICs were higher in the presence of protein at both pH values. For some antibiotics, the protein effect at pH 6.0 was larger than that at pH 7.4; for others the protein effect was smaller at pH 6.0. These data indicate that pH and protein effects must be determined individually for beta-lactam antibiotics.