Table 1.
Summary of in vivo studies using phage therapy against A. baumannii.
| Infection Model | Bacteria | Phage Therapy | Antibiotic Combination | Outcome | References |
|---|---|---|---|---|---|
| Ex-vivo human lung epithelial A549 cells | 106 CFU of XDR strains | Φkm18p at MOIs of 0.01, 0.1 and 1 | No | Cell survival | [24] |
| HeLa cells | 107 CFU of AB1 strain in 100µL of DMEM | Abp (108 PFU in 100 µL) after 2 h | No | Survival of treated cells was similar to the positive control group at 24 h | [25] |
| Ex-vivo human heat-inactivated plasma blood and G. mellonella | Clinical strain | vB_AbaP_AGC01 | Phage alone and combined with gentamicin, ciprofloxacin and meropenem | Increased survival with antibiotic combination | [26] |
| G. mellonella | Ab177_GEIH-2000 | Ab105-2phiΔCI | Alone, imipenem or meropenem | Increased survival with antibiotic combination after 72 h | [27] |
| G. mellonella | Carbapenem-resistant strains | WCHABP1 and WCHABP12 | No | Survival increased from 20% to 75% in treated larvae | [28] |
| G. mellonella and murine model of bacteremia | 105 CFU of ESBL strains in larvae model and 6 × 107 CFU in murine model | vB_AbaM_3054 and vB_AbaM_3090 via IP in mice 2 h post-infection | No | 100% survival after 80 h post-infection in larvae model, and 100% survival in murine model after 7 d | [29] |
| G. mellonella and murine model of acute pneumoniae | Carbapenem-resistant strain | BΦ-R2096 at MOIs of 10 and 100 for larvae, and 0.1, 1 and 10 MOIs for mice | No | At 48 h, a MOI of 100 reached 50% of survival of larvae while a MOI of 10 obtained 10%. Only MOI of 1 exhibited 100% of survival in mice after 12 d | [30] |
| Rat wound model | 5 × 108 CFU/mL | vB-GEC_Ab-M-G7 | No | Efficacy was achieved. Treated rats reduced symptoms and bacterial load by 5 log | [31] |
| Full-thickness dorsal infected wound model | MDR AB5075 | Five-member cocktail | No | Neither increase of size nor necrosis was visualized in treated mice. Non-mature biofilm was present on treated mice | [32] |
| Wound model in uncontrolled diabetic rats | MDR strain | 48 h post-infection | No | Treated mice reduced inflammation and no bacteria was isolated at day 8 | [33] |
| Mouse model of sepsis | IP 106 CFU of AB900 and A9844 | ΦFG02 and ΦCO01 | No | Reduction of bacterial loads of treated mice with isolation of resistant strains sensitive to antibiotics | [34] |
| Mouse model of pneumonia | 108 CFU of MDR strain with IN infection | Cocktail of PBAB08 and PBAB25 injected from day −1 to day +7 (109 PFU) | No | 100-fold reduction in lungs was obtained in treated mice respect to the control group. In addition, inflammatory response was studied after IN, IP and oral routes and only IP phages increased 20% IgE compared to controls | [35] |
| Mouse model of sepsis | 5 × 107 CFU of panresistant ABZY9 | Immediate IP injection of Abp9 at MOI of 10 | No | 8 out of 12 treated mice survived | [36] |
| Mouse model of sepsis | 109 CFU/mL | IP inoculation of 109 PFU vB_AbaP_PD-6A3 1 h post-infection | No | A survival rate of 60% was obtained compared to 0% of control group | [37] |
| Mouse model of sepsis | 2 × 107 CFU of AB9 | 108 PFU of vB-AbaS-D0 and -D2 IP alone and combined | No | vB-AbaS-D2 and a mix of the 2 phages reached 90 and 100% of survival, respectively. vB-AbaS-D0 showed 50% of survival after 7 d | [38] |
| Mouse model of sepsis | AB3 | Cocktail | No | 100% of survival 6 weeks after infection | [39] |
| Mouse model of pneumonia | IN carbapenem-resistant strain | BΦ-C62 | No | 3 d post-treatment, no bacteria was found in lungs with a concomitant improvement of histological damage | [40] |
| Mouse model of sepsis | ESBL strain (2–3 × 108 CFU/mouse BALB/c and 6 × 108 CFU/mouse C57BL/6) | ϕkm18p at MOIs of 0.1, 1 and 10 after 10 min and 1 h from infection | No | 100% of survival in mice treated after 10 min and 56% of survival in BALB/C and 46% in C57BL/6 treated after 1 h | [41] |
| Mouse model of pneumonia in neutropenic mice | Carbapenem-resistant strain | SH-Ab15519 via IN 1 h post-infection at MOIs of 0.1, 1 and 10 and 2 h post-infection at 10 MOI | No | 90% of survival was obtained in all mice treated after 1 h. Mice treated 2 h post-infection showed 66.7% after 14 d | [42] |
| Mouse model of pneumonia in neutropenic mice | 2 × 108 CFU MDR strain via IN | IN vB_AbaM-IME-AB2 at MOI of 0.1, 1 and 10. A MOI of 10 was administered 1 h, 4 h and 24 post-infection | No | Only a MOI of 10 obtained 100% of survival, and only mice treated 1 h post-infection showed 100% of survival |
[43] |
Abbreviations: CFU, colony-forming units; ESBL, extended-spectrum beta-lactamase; IN, intranasal; IP, intraperitoneal; MDR, multidrug resistant; MOI, multiplicity of infection; PFU, plaque-forming units; XDR, extensively drug resistant.