Combination of phage and antibiotic treatment on the ascent of antibiotic resistance.

<p>Treatment of <i>P</i>. <i>aeruginosa</i> PA14 biofilm populations grown for 48 hours either fully resistant to the treating drug (CipR, GenR) or containing an initial mix of susceptible and drug-resistant bacteria (designated as—Mix). Abbreviations are given by the first 3 letters of the treating drug name followed by the status of the initial population (mixed or fully drug resistant). A prefix N- indicates inclusion of both phages with the drug. <b>A-</b> Viable cell density after 48 hours of treatment with ciprofloxacin (Cip) and ciprofloxacin with phage mixture (NCip) <b>B-</b> Viable cell density after 48 hours of treatment with gentamicin (Gen) and gentamicin with phage mixture (NGen) <b>C-</b> Titers of phage in (A). <b>D-</b> Titers of phage in (B). The horizontal line in (C) and (D) is the initial density of phage. For ciprofloxacin, the differences in total cell density were not statistically significant between Cip-Mix and Cip-CipR nor between NCip-Mix and NCip-CipR. The difference in the drug resistant fraction between Con-Mix and NCip-Mix is highly significant (P << 10⁻⁴). For gentamicin, the differences in total cell density were not statistically significant between NGen-Mix and NGen-GenR but were statistically significant between Gen-Mix and Gen-GenR (P < 10⁻⁴); however the magnitude of difference in this latter case is not large. The difference in the drug resistant fraction between Con-Mix and NGen-Mix is highly significant (P < 10⁻⁴). Raw data of these experiments can be found in (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168615#pone.0168615.s003" target="_blank">S3 Excel File</a>).