Table 2.

Phages and antibiotics in recent clinic experiences

Disease	Phage	Antibiotic	Clinical outcome	References
76-year-old patient with a chronic P. aeruginosa infection of an aortic Dacron graft with associated aorto-cutaneous fistula	Single application 10 ml of the OMKO1 phage at a concentration of 107 PFU/ml for mediastinal fistula	Before phage therapy (PT) prolonged the course of antibiotics Along with PT 0.2 g/ml ceftazidime was administered for mediastinal fistula. Ceftazidime was continued at home	Approx. 4 weeks post-procedure, the patient developed significant bleeding from the mediastinal wound. Due to concerns that an aortic perforation may occur, the patient underwent exploratory surgery. The patient was cured without any recurrence of infection	Chan et al. [93]
42-year-old patient with a trauma-related left tibial infection with drug resistant A. baumannii and K. pneumoniae	Combination of phages: ϕAbKT21phi3 and ϕKpKT21phi1 1 ml of each phage 5 × 107 PFU/ml administered intravenously (iv) 3-times daily (tid) over 35 min for 5 days. Second course: 6 days 1 week later	Before PT prolonged course of antibiotics Simultaneously with PT administered iv meropenem (2 gr tid) and colistin 4.5 × 106 units/bid	Rapid tissue healing and positive culture eradication. The patient’s leg did not have to be amputated and he is undergoing rehabilitation	Nir-Paz et al. [94]
30-year-old patient with a fracture-related pandrug-resistant K. pneumoniae	Pre-adapted phage M1 (108 PFU/ml) used locally (in the surgical wound via a catheter) for 6 days	After unsuccessful antibiotic therapy simultaneously with PT administered meropenem and colistin followed by ceftazidime/avibactam	Finally, clinical and microbiological improvement was observed	Eskenazi et al. [95]
26-year-old cystic fibrosis (CF) patient awaiting lung transplantation with multidrug resistant (MDR) P. aeruginosa pneumonia, respiratory and renal failure	Combination of 4 lytic phages P. aeruginosa: AB-PA01 4 × 109 PFU/5 ml administered iv every 6 h for 8 weeks	Before PT prolonged course of antibiotics Simultaneously with PT systemic antibiotics: ciprofloxacin, piperacillin–tazobactam for 3 weeks. Later ciprofloxacin was discontinued and doripenem was added	Clinical resolution of infection, no recurrence of pneumonia and CF exacerbation within 100 days after PT. Successful bilateral lung transplantation 9 months later	Law et al. [96]
Three lung transplant recipients (LTR) with life-threatening MDR infections caused by P. aeruginosa (n = 2) and Burkholderia dolosa (n = 1). Two patients had P. aeruginosa pneumonia. A third patient had recurrent pneumonia B. dolosa infection following transplant	Case 1 received P. aeruginosa phage cocktail: AB-PA01 (109 PFU/ml) and two phage cocktails (107–109 PFU/ml) administered iv and nebulized Case 2 received P. aeruginosa phage cocktail AB-PA01 (109 PFU/ml) iv. Case 3 received single lytic phage BdPF16phi4281 (106–107 PFU/ml) iv PT was conducted for variable durations	Simultaneously with PT antibiotics Case 1: Post-transplant he had two episodes of MDR P. aeruginosa pneumonia Episode 1: systemic antibiotics (piperacillin–tazobactam and colistin Episode 2: Systemic antibiotics (piperacillin–tazobactam, tobramycin and inhaled colistin) Case 2: Post-transplant she had an MDR P. aeruginosa infection. Additionally Mycobacterium abscessus pulmonary infection treated with antibiotics Along with iv P. aeruginosa phage inhaled colistin. The isolate grown at day 60 and subsequent strains were successfully treated with piperacillin–tazobactam Case 3: At the time of lung transplant and after she received antibiotics. Then the phage was added to ceftazidime–avibactam and piperacillin–tazobactam. On week 10 of PT infusion meropenem, extended infusion ceftazidime–avibactam, minocycline, and inhaled tobramycin Her sepsis resolved, bloodstream infection cleared and her respiratory status improved. However, she developed progressive liver failure with concern for drug-induced toxicity, including from minocycline, dapsone, and posaconazole prophylaxis. She again developed pneumonia	Both patients with P. aeruginosa infection responded clinically and were discharged from the hospital off ventilator support. B. dolosa infection relapsed on PT and the patient expired	Aslam et al. [97]
52-year-old critically ill patient with MDR A. baumannii respiratory infection	A.baumannii phage AbW4878Ø1 iv. 1 × 109 PFU/ml twice daily and nebulized 0.1 × 109 PFU/ml twice daily along with antibiotics for a total 35 days	Before PT course of antibiotics. Along with PT broad-spectrum of antibiotics infusions	Successfully treated with antibiotics and intravenous and nebulized PT	Rao et al. [98]
63-year-old patient with a recurrent urinary tract infection caused by K. pneumoniae	K. pneumoniae phage cocktail after two rounds of PT causes appearance phage resistant mutants. Then combined use of phage and non-active antibiotics was used Phage cocktail III (5 × 108 PFU/ml for each phage) was administered by bladder-irrigation once a day for 5 days	K. pneumoniae was completely resistant to sulfamethoxazole–trimethoprim Antibiotics (800–160 mg) was used along with PT orally twice a day for 5 days	Synergistic effect was observed. Phage and higher dose of antibiotics inhibited the emergence of phage resistant mutant in vitro. The patient was successfully cured by this combination	Bao et al. [99]

CF: cystic fibrosis; iv: intravenously; LTR: lung transplant recipients; MDR: multidrug-resistant; PFU: plaque-forming unit; PT: phage therapy, tid: 3-times daily