Efficacy prediction of bacteriophage-antibiotic combinations against

Introduction: Phage-antibiotic combinations (PAC) may be effective in eradicating clinical, mostly biofilm-associated, infections. As the efficacy of PAC largely depends on the phage and antibiotic used, such combinations should be screened before their clinical application. Unfortunately, testing the efficacy of PAC on mature biofilms is laborious. This study aimed to assess whether the effects of PAC on biofilm-encased bacteria can be predicted by testing their effects on planktonic counterparts. Methods: Methicillin-sensitive Results: The results for planktonic bacteria showed antagonism between ISP and rifampicin or gentamicin, synergism between ISP and ciprofloxacin, clindamycin, or flucloxacillin, and lack of interaction between ISP and daptomycin. Similarly, ISP combined with rifampicin or gentamicin displayed antagonism on biofilm-encased MSSA, whereas ISP and ciprofloxacin, clindamycin, flucloxacillin, or high-dose daptomycin induced synergy. Notably, two to three consecutive daily exposures to PAC were necessary to reduce biofilm-encased MSSA maximally. Testing PAC on planktonic bacteria predicted antagonistic effects on biofilms (area under the curve (AUC) = 0.95), but did not predict synergistic effects (AUC = 0.30) after 3 days of exposure to the respective phage-antibiotic concentrations. Discussion: Together, PAC testing on planktonic bacteria provides a valuable first-line screening tool for clinicians treating biofilm-associated infections.