Table 1.
Application of phage against drug-resistant Staphylococcus aureus infection in animals and humans.
| Bacterial strain | Infected object and type | Phage/Cocktail | Phage dose | Delivery vehicle | Route of administration | Antibiotic | Outcome | Reference |
|---|---|---|---|---|---|---|---|---|
| S. aureus CVCC 546(MRSA) | mice, mastitis | phage 4086–1 | 1 × 108 PFU/mL,100 µL | —— | mammary duct | ceftiofur sodium (5 mg/kg) | Compared to treatment with ceftiofur sodium,phage therapy was more effective in reducing the number of MRSA and inflammatory reaction | (Teng et al., 2022) |
| S. aureus ATCC 29740 (MSSA) | mice, mastitis | StaphLyse™ phage cocktail (SAML-4, SAML-12, SAML-150, SAML-229, SATA-8505) | 108PFU in 100 µL, two repeated doses at 8 h and 16 h after S. aureus infection | —— | intramammary or intravenously | amoxicillin (75 µg/mL, approximately 150 times MIC) | The bacterial load could be significantly reduced by using phage cocktail or amoxicillin alone | (Brouillette et al., 2023) |
| multidrug-resistant S. aureus SA63–2498 | mice, diabetic foot ulcer | AB-SA01 phage cocktail (J-Sa36, Sa83, and Sa87) | 70 µL AB-SA01, equivalent to 7.9 log10 PFU | —— | Topical wounds were coverd with AB-SA01 soaked Gauze patches and Opsite | vancomycin (150 mg/kg intraperitoneal twice daily for five consecutive days) | AB-SA01 treatment decreased the bacterial load with efficacy similar or superior to vancomycin treatment | (Kifelew et al., 2020) |
| S. aureus clinical isolate SA003 | mice, mastitis | phage ΦSA012 | 5 × 109 pfu/head for MOI of 100 or 5 × 107 pfu/head for MOI of 1 | —— | intraperitoneally (i.p.) or intravenously (i.v.) | —— | ΦSA012 treatment improved the survival rate of mice and the effect of intraperitoneal injection was better. | (Fujiki et al., 2022) |
| S. aureus ATCC 43300 (MRSA) | mice, diabetic skin wound infection | phage cocktail (MR-5 and MR-10) | 109 PFU/50 µL MR-5 and 109 PFU/50 µL MR-10 | liposome | Local administration | Two I/P doses of clarithromycin (10 mg/kg) given in 12 h intervals | Animals receiving liposomes entrapped cocktail of phages showed higher reduction in bacterial burden on all days as compared to free cocktail of phages and clarithromycin treated mice. Furthermore, entrapment of liposomes led to a significant increase in phage titer at the wound site | (Chhibber et al., 2018) |
| S. aureus JAR060131RifR (rifampicin resistance) | rabbit, fracture-related infection | phage ISP | 800 µL,109 PFU/mL | emulsion-based hydrogel | subcutaneous access tube injection | nafcillin subcutaneously (40 mg/kg four times per day) and rifampicin orally (40 mg/kg two times per day) for 7 days | No significant differences in bacterial load between treatment study groups, but no phage neutralization at euthanasia in the phage-loaded hydrogel group compared with that five out of eight animals receiving phage in saline developed neutralizing antibodies. | (Onsea et al., 2021) |
| S. aureus JE-2 (MRSA) | mice, lung infections | phage cocktail (phage K, phage 110, phage 134, phage 135 and phage 136) | 1 × 108 PFU/mouse | porous microparticles engineered from poly (lactic-co-glycolic acid (PLGA) | endotracheal delivery | —— | phage-loaded microparticles showed robust mitigation of MRSA in an acute lung infection mouse model and not any gross toxicity towards human lung epithelial cells | (Kalelkar et al., 2022) |
| S. aureus clinical isolate (MSSA) | patients, prosthetic knee infection | phage cocktail (PP1493, PP1815, and PP1957) | 1 mL of 1 × 1010 PFU/mL for each phage and final dilution 1 × 109 PFU/mL | —— | direct administration into the joint | Cefalexin or doxycycline as suppressive therapy | Beneficial with a clinically substantial improvement of the function for all patients | (Ferry et al., 2020) |
| S. aureus clinical isolate (MSSA) | patient, prosthetic knee infection | phage SaGR51ø1 | one-time dose of 10 mL of phage (2.89 × 1010 PFU/mL) and daily infusions every 12 h for 6 weeks | —— | intra-articular infusion | concomitant intravenously cefazolin (2 g every 8 h) for 6 weeks | negative bacterial culture and no adverse events related to bacteriophage therapy | (Ramirez-Sanchez et al., 2021) |
| S. aureus clinical isolate (MRSA) | patient, knee and hip prosthetic joint infection | phage SaWIQ0488ø1 | one-time dose of 10 mL of phage (1.2 × 109 PFU/mL) and daily infusions every 24 h for 3 days | —— | intra-articular or intravenous infusion | Daptomycin was used for three weeks | All intraoperative bacteriological cultures were negative and there has been no evidence of recurrence | (Schoeffel et al., 2022) |
| S. aureus clinical isolate (MRSA and MSSA) | patients, bacteraemia | AB-SA01 phage cocktail (J-Sa36, Sa83, and Sa87) | 109 PFU per 1 mL ampoule in 50–100 mL 0.9%Il twice daily for 14 days | —— | intravenously | flucloxacil-lin, cefazolin or vancomycin as antibiotic therapy supplemented by ciprofloxacin and/or rifampicin | No adverse reactions were reported, AB-SA01 intravenously administered was safe in severe drug-resistant S. aureus infections and it was possible that there was a synergistic effect between phages and antibiotics | (Petrovic Fabijan et al., 2020) |
| Staphylococcus spp, etc clinical isolate | patients, urinary tract infections | Pyophage cocktail | 20 mL in a double-blind manner twice daily for 7 days | —— | intravesical titration | either ceftriaxone (1 g once daily intravenously), amoxicillin and clavulanic acid (1 g twice daily orally), or ciprofloxacin (500 mg twice daily orally) | non-inferiority of bacteriophages in terms of efficacy compared with antibiotics, and high tolerability and safety. However, superiority of bacteriophages over placebo was not observed. | (Leitner et al., 2021) |
MSSA, Methicillin-sensitive Staphylococcus aureus; MRSA, Methicillin-resistant Staphylococcus aureus; PFU, Plaque-forming unit; MOI, Multiplicity of infection.