Table 1.
In vivo study of phage–antibiotic treatment in bacterial killing.
| Animal Model | Bacterial Species | Drugs Used | Phage | Highlights |
|---|---|---|---|---|
| Moth larvae (Galleria mellonella) [85] | Klebsiella pneumoniae | Mitomycin C, imipenem (1/4 × MIC, 1/2 × MIC) | vB_KpnM-VAC13 (107 or 109 PFU/mL) | Survival rate of larvae significantly increased to 50% and 75% when phage co-treated with mitomycin C and imipenem, respectively, in treating resistant strain and persisted strain, compared to either monotherapy, except for phage/imipenem on resistant strain. |
| Moth larvae (Galleria mellonella) [71] | Acinetobacter baumannii | Imipenem, meropenem (1/4 × MIC, 1/8 × MIC) | Ab105-2φ∆CI (108 PFU/mL) |
Combination therapy and meropenem alone had same survival rate; both survival rates were higher than phage monotreatment (p < 0.05); imipenem combined with phage showed high survival rate compared to monotherapy (p < 0.05). |
| Mouse: lung infection [25] | Pseudomonas aeruginosa | Ciprofloxacin (0.33 mg/mg) | PEV20 (106 PFU/mg) |
PEV20 combined with ciprofloxacin significantly decreased bacterial concentration by 5.9 log, where either monotherapy showed no obvious bacterial reduction. |
| Moth larvae (Galleria mellonella) [82] | Escherichia coli | Fosfomycin (200 mg/kg) | fWL-3 (107 PFU) |
Simultaneous treatment with phage and fosfomycin had higher survival rate than sequential treatment in both EC1 and ATCC 25922 strains. Phage and fosfomycin showed 75% of survival rate in ATCC 25922 strain. |
| Rat [86] | Pseudomonas aeruginosa | Ciprofloxacin (0.19 μg/mL) | Phage cocktail PP1131 Bolus injection (1 mL of 1010 PFU/mL in 1 min) Continuous infusion (0.1 mL/h of 1010 PFU/mL over 24 h) |
Phage/ciprofloxacin exerted highest synergistic effects with 6 log bacterial reduction and achieved 64% reduction in bacterial infection. No phage-resistant mutants in vivo. |
| Mouse: prosthetic joint infection [87] | Methicillin-resistant Staphylococcus aureus | Linezolid (5% w/w) | MR-4 (109 PFU/mL) | The combined treatment with phage and linezolid maximised the mice locomotor activity, reduced oedema at the affected limb, and significantly reduced the bacterial burden (~4.5 log) as compared with the untreated control. |
| Mouse: diabetic foot infection [88] | Methicillin-resistant Staphylococcus aureus | Linezolid (25 mg/kg) | MR-10 (108 PFU/mL) | The combination of phage and linezolid demonstrated a high antimicrobial effect in reducing the bacterial load (5 log) and lesion level. Healing was accelerated at Day 7 after the co-treatment compared to the untreated control (Day 12). |