The selection of antibiotic- and bacteriophage-resistant Pseudomonas aeruginosa is prevented by their combination

Objectives Bacteria developing resistance compromise the efficacy of antibiotics or bacteriophages (phages). We tested the association of these two antibacterials to circumvent resistance. Methods With the Hollow Fiber Infection Model (HFIM), we mimicked the concentration profile of ciprofloxacin in the lungs of patients treated orally for Pseudomonas aeruginosa infections and independently, mimicked a single inhaled administration of phages (one or two phages). Results Each treatment selects for antibiotic-or phage-resistant clones in less than 30 h. By contrast, no bacteria were recovered from the HFIM at 72 h when ciprofloxacin was started 4 h post-phage administration, even when increasing the initial bacterial concentration by a 1000 fold. Conclusion The combination of phages with antibiotics used according to clinical regimens prevents the growth of resistant clones, providing opportunities to downscale the use of multiple antibiotics.