Fig. 8. Activity of preadapted phage M1, ceftazidime/avibactam, and combinations thereof against PDR K. pneumoniae isolate Kp36336 residing in mature biofilms.

Seven-day mature biofilms of K. pneumoniae isolate Kp36336 were exposed daily for 3 subsequent days to phages (7.7 × 108 PFU), moderate concentrations of ceftazidime/avibactam (just below and just above the MIC value of 2.0/0.5 μg/ml), and combinations thereof. After exposure for 1–3 days, bacteria in the biofilms were recovered by sonication (10 min at 40 kHz) in saline (or saline supplemented with 10 µM ammonium iron (II) sulphate hexahydrate to neutralize residual phage activity) and subsequently plated on Mueller Hinton agar for microbiological determination of bacterial counts. Results are presented as the median (horizontal bars) of biological replicates (n = 5), each dot representing the sum of bacterial counts from pools of 6 wells (technical replicates). The significance of the difference in bacterial counts between samples from biofilms exposed to antibiotic/phage combination and samples from biofilms exposed to the antibiotic alone was determined using a two-sided Mann Whitney U tests, *p < 0.05 (p = 0.0238), **p < 0.01 (p = 0.0079). Source data are provided as a Source Data file.