Effect of pH on the in vitro susceptibility of planktonic and biofilm-grown Proteus mirabilis to the quinolone antimicrobials

Aims

To examine the effect of elevated pH, as reported during urinary catheter infections, on quinolone activity against the urease-producing pathogen Proteus mirabilis.

Methods and Results
Susceptibility of Pr. mirabilis to nalidixic acid, norfloxacin and ciprofloxacin was examined in media of pH 5 to pH 10 by determination of MICs, MBCs, minimum biofilm eradication concentrations (MBECs) and time-kill assays. Elevation of media pH from 5 to 9 caused a 10-fold decrease in bacteriostatic activity of nalidixic acid and was also associated with loss of the characteristic ‘paradoxical’ bactericidal activity. Alkaline pH, however, increased both bacteriostatic and bactericidal activities of the two fluoroquinolones tested against both planktonic and biofilm-associated Pr. mirabilis; MBC and MBEC values for ciprofloxacin decreased approx. 6000-fold and 10-fold, respectively, between pH 5 and pH 9. Rates of kill of all three agents were most rapid at pH 7, the optimal pH for bacterial replication.

Conclusions
pH has a pronounced effect on quinolone-mediated killing, which may be attributed to the dependence of cellular uptake on quinolone ionization state.
Significance and Impact of the Study

These results provide rationale for the use of these agents for Pr. mirabilis eradication in alkaline environments, including urinary catheter infections: the incidence, recurrence and recalcitrance of which pose a significant burden to healthcare providers.