Impact of pH and cationic supplementation on in vitro postantibiotic effect

Abstract

Most studies on pharmacodynamic variables in vitro, including the postantibiotic effect (PAE), are performed at pH 7.4 in noncationic-supplemented media, a situation which may differ significantly from the true microenvironment in most infected foci. We studied the impact of five different pH levels (pH 5, 6, 7, 7.4, and 8) on the duration of the PAE, the MIC, and bactericidal activity. Acid pH was found to have in general a deleterious effect on the activity of aminoglycosides and ciprofloxacin against Escherichia coli and Pseudomonas aeruginosa, with the MIC being higher, the bactericidal rate being lower, and the PAE being shorter at pH 5 (and to a lesser extent at pH 6) than at more alkaline pH levels. Similar results were observed for imipenem against P. aeruginosa. The PAEs induced by ampicillin against E. coli and dicloxacillin against Staphylococcus aureus were not predictably dependent on the pH, whereas the PAEs induced by ciprofloxacin against S. aureus were longest at either end of the pH spectrum. The bactericidal activity of these agents was, however, pH dependent, being slower at acid pHs. The addition of 50 mg of Ca2+ and 20 mg of Mg2+ per liter of liquid medium at pH 7.4 did not affect the duration of the PAE. Since the pH in abscess cavities may be close to 5, these observations may be of importance for employment of the agents studied in closed or poorly drained infections.