Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae

Abstract

A 30-year-old bombing victim with a fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term (>700 days) antibiotic therapy is treated with a pre-adapted bacteriophage along with meropenem and colistin, followed by ceftazidime/avibactam. This salvage therapy results in objective clinical, microbiological and radiological improvement of the patient’s wounds and overall condition. In support, the bacteriophage and antibiotic combination is highly effective against the patient’s K. pneumoniae strain in vitro, in 7-day mature biofilms and in suspensions.

Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far

“…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 × 10 6 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 (10 8 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 × 10 9 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.…”

“…A successful combination of phages and antibiotics has also been used in orthopedic infections in humans [ 94 , 95 ]. A 42-year-old patient with a trauma-related left tibial infection with drug-resistant A. baumannii and K. pneumoniae treated with a combination of the phages A. baumannii and K. pneumoniae administered intravenously for 5 days and 1 week later for 6 days with meropenem and colistin iv simultaneously had a good clinical outcome with rapid tissue healing and positive culture eradication [ 94 ].…”

“…A 42-year-old patient with a trauma-related left tibial infection with drug-resistant A. baumannii and K. pneumoniae treated with a combination of the phages A. baumannii and K. pneumoniae administered intravenously for 5 days and 1 week later for 6 days with meropenem and colistin iv simultaneously had a good clinical outcome with rapid tissue healing and positive culture eradication [ 94 ]. Recently, a clinical case of a 30-year-old patient with a fracture-related pandrug-resistant K. pneumoniae was treated with phages and antibiotics [ 95 ]. Testing of a day-702 K. pneumoniae before PT indicated non-susceptibility to all antibiotics in all antimicrobial categories.…”

“…Clinical improvement was observed after combined treatment in this clinical case. Considering the clinical data and the in vitro phage–antibiotic synergy data, there is evidence that a combination of the phage M1 and the antibiotics meropenem and ceftazidime/avibactam finally caused clinical improvement in this patient [ 95 ].…”

Phage Paride hijacks bacterial stress responses to kill dormant, antibiotic-tolerant cells

“…However, a lack of reliability and technical difficulties caused rapid disappearance of phage therapy in the West once antibiotic drugs became available 3,4 . This trend has reversed in recent years when phages, owing to advances in medicine and biotechnology, have been increasingly used as attractive treatment options for multidrug-resistant bacterial infections 3,4,[17][18][19] . Given the bleak prospects of the antibiotic resistance crisis with around five million deaths linked to resistant bacterial infections in 2019 5 , this trend is likely going to continue.…”