Rifampicin potentiation of aminoglycoside activity against cystic fibrosis isolates of Pseudomonas aeruginosa.

Objectives: Rifampicin potentiates the activity of aminoglycosides (AGs) versus Pseudomonas aeruginosa by targeting the AmgRS two-component system. In this study we examine the impact of rifampicin on the AG susceptibility of cystic fibrosis (CF) lung isolates of P. aeruginosa and the contribution of AmgRS to AG resistance in these isolates.

Methods: amgR deletion derivatives of clinical isolates were constructed using standard gene replacement technology. Susceptibility to AGs ± rifampicin (at ½ MIC) was assessed using a serial 2-fold dilution assay.

Results: Rifampicin showed a variable ability to potentiate AG activity versus the CF isolates, enhancing AG susceptibility between 2- and 128-fold. Most strains showed potentiation for at least two AGs, with only a few strains showing no AG potentiation by rifampicin. Notably, loss of amgR increased AG susceptibility although rifampicin potentiation of AG activity was still observed in the ΔamgR derivatives.

Conclusions: AmgRS contributes to AG resistance in CF isolates of P. aeruginosa and rifampicin shows a variable ability to potentiate AG activity against these, highlighting the complexity of AG resistance in such isolates.