Six factors that increase the activity of antibiotics in vivo

The traditional study of antibiotic activity in vitro obviously cannot incorporate all host factors that may increase or decrease the activity, which may be bacteriostatic and/or bactericidal. Some specific host factors which canincrease the activity of antibiotics, thus producing host-antibiotic synergy, are: 1) biotransformation of the administered antibiotic to a more active molecule, 2) pH of the infected focus, 3) elevated temperature of the host, 4) effect of heat labile serum factors on bacteria exposed to antibiotics, 5) effect of local tissue factors on antibacterial activity, and 6) effect of phagocytic cell son bacteria exposed to antibiotics. A seventh host factor, which increases the practical antibiotic effect, but not its actual activity, is concentrating mechanisms which are most conspicuous in the kidney and the liver. Conversely, host factors which maydecrease the activity of antibiotics in vivo are: 1) biotransformation (metabolism) of the antibiotic to less active forms, 2) pH of the infected focus, 3) binding to albumin or other serum or tissue components, 4) antagonism by local tissue components other than pH (e. g., bile, cations, osmolarity), 5) anaerobic conditions (low Eh), 6) nutritional factors on bacterial metabolism, 7) foreign body effect, and 8) barriers to drug entry into precise locus where bacteria dwell (e. g. abscess cavity, cerebrospinal fluid, intracellular location). These barriers do not change the actual activity of antibiotics — only their practical effects, by excluding them and thus lowering their concentrations. The same is true of a ninth factor, physiological mechanisms which remove antibiotic from systemic compartments, as in secretion of antibiotic by liver and kidney.