Short-Term Outcomes of Phage-Antibiotic Combination Treatment in Adult Patients with Periprosthetic Hip Joint Infection

Abstract

Implant-associated infections are the most costly problem in modern orthopedics due to the continued increase in the occurrence of antibiotic-resistant bacterial strains that requires the development of new effective antimicrobials. A non-randomized, prospective, open-label, with historical control study on the use of combined phage/antibiotic therapy of periprosthetic joint infection (PJI) was carried out. Forty-five adult patients with deep PJI of the hip joint were involved in the study, with a 12-month follow-up after one-stage revision surgery. Patients from a prospective study group (SG, n = 23) were treated with specific phage preparation and etiotropic antibiotics, whereas patients from a retrospective comparator group (CG, n = 22) received antibiotics only. The rate of PJI relapses in the SG was eight times less than that in the CG: one case (4.5%) versus eight cases (36.4%), p = 0.021. The response rate to treatment was 95.5% (95% confidence interval (CI) = 0.7511–0.9976) in the SG and only 63.6% (95% CI = 0.4083–0.8198) in the CG. The odds ratio for PJI relapse in patients of the SG was 0.083 (95% CI = 0.009–0.742), which was almost 12 times lower than that in the CG. The obtained results support the efficacy of the combined phage-antibiotic treatment of PJI.

Automating Predictive Phage Therapy Pharmacology

“…These are all as found in situ while treating infections caused by what are typically somewhat uncharacterized bacterial strains and, in many cases, also in combination with antibiotics [ 41 , 57 , 86 , 87 , 88 , 89 ], which can have antagonistic impacts on phage infection abilities [ 41 , 51 , 85 , 90 ]. In particular for the latter, note that of 18 clinical phage therapy studies that I was able to obtain—published in 2023 or, at the time of writing, which are published but still online ahead of print—at least 16 indicate treatments using phages in combination with antibiotics [ 57 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. See also [ 109 ], where 79 of the 114 clinical phage treatments reported “were administered in combination with standard-of-care antibiotics”.…”

Bacteriophages as a potential substitute for antibiotics: A comprehensive review

“…24 In treating periprosthetic joint infection, a phage-antibiotic combination served a 95.5% response rate compared to conventional antibiotics. 25 Vibrio harveyi is the causative agent of vibriosis in shrimp hatcheries and can be treated using phage-antibiotic mediated methods, which gave better results than antibiotic treatments. 26 Phage's ability to undergo horizontal gene transfer will raise skepticism in the field of phage therapy.…”

“…Antibiotic failure in infection control is overcome with phage therapy 24 . In treating periprosthetic joint infection, a phage‐antibiotic combination served a 95.5% response rate compared to conventional antibiotics 25 . Vibrio harveyi is the causative agent of vibriosis in shrimp hatcheries and can be treated using phage‐antibiotic mediated methods, which gave better results than antibiotic treatments 26 .…”

A review and new perspective on oral bacteriophages: manifestations in the ecology of oral diseases

“…While writing this review, most clinical trials or case reports on phage therapy currently registered in the Cochrane Central Register of Controlled Trials (CENTRAL) are for pulmonary infection [ 44 ], cystic fibrosis [ 45 ], diarrheal [ 46 , 47 ], chronic wound infections [ 48 , 49 ], joint infections [ 50 , 51 ], metabolic syndrome [ 52 ]. Although an increasing number of diseases are also being included such as chronic rhinosinusitis and Alzheimer’s Disease [ 53 ], unfortunately none of the oral diseases is among them.…”