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A systematic review of phage therapy applied to bone and joint infections: an analysis of success rates, treatment modalities and safety.

ABSTRACT: Bone and joint infections are difficult to treat, and increasing antibiotic resistance has only made them more challenging. This has led to renewed interest in phage therapy (PT). The aim of this systematic review was to determine success rate, current treatment modalities and safety of PT in bone and joint infections.A systematic search of PubMed, EMBASE and Cochrane databases as well as the journal PHAGE for literature published between January 2000 and April 2021 was conducted according to PRISMA guidelines to identify all human studies assessing bacteriophages as therapy for bone and joint infections. All study designs and patient populations were eligible. The review's primary outcome was success rate.Twenty records describing a total of 51 patients and 52 treatment episodes were included. No randomized controlled studies were identified. The overall success rate was 71% (n = 37/52). Topical administration alone was the most frequent administration route (85%, n = 44/52). Antibiotics were administered concomitantly with PT in the majority of treatments (79%, n = 41/52), and surgery was performed for 87% (n = 45/52) of treatment episodes. Four minor adverse events related to PT were reported, representing 8% (n = 4/52) of treatment episodes.PT for bone and joint infections has not been evaluated in any randomized controlled clinical study, and current administration modalities are highly variable between case reports and case series. While publications included here show potential benefit and few adverse effects, clinical trials are warranted to assess the efficacy of PT for bone and joint infections and determine optimal treatment modalities. Cite this article: EFORT Open Rev 2021;6:1148-1156. DOI: 10.1302/2058-5241.6.210073.

SUBMITTER: Geneviere J

PROVIDER: S-EPMC8722473 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4-12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash (n = 1) and urgent surgery (n = 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4-12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.) IMPORTANCE Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections.

Project description:BackgroundBone marrow edema (BME) is a radiological term which can be found in many conditions with varied pathogenesis and histopathological images. It usually presents with pain in the affected joint and is diagnosed with MRI. Subchondroplasty (SCP) and core decompression (CD) are the surgical methods that are available to achieve pain relief and functional improvement. Both surgical methods have their own indications and are used depending on the patient's history. The aim of this literature review article is to discuss the surgical modalities for the management of bone marrow edema focusing on the knee joint. Such topic which analyzes both surgical methods for treatment of bone marrow edema of the knee joint has never been described in a review article before.Materials and methodsFor the purpose of our manuscript we thoroughly searched electronic databases such as Pubmed and Medline to acquire the appropriate material for our review paper. Only English articles were used in this review. In our study we included every article that had described the surgical management of BME of the knee by CD and SCP. In the discussion we included 18 studies (9 CD and 9 SCP) with a total number of patients equal to 397, while 206/397 had undergone surgical intervention (169 underwent SCP and 37 CD).ResultsFollow-up of 180 patients out of 206 were available for our review. A total number of 166 patients (92.2%) were successfully treated. Specifically, 29 (100%) patients were treated by CD and 137 (90.7%) by SCP. In a study, 10 patients who underwent SCP for BME secondary to advanced osteoarthritis (OA) yielded poor results. In other studies, pain persistency was observed in 2 patients, 1 patient had postoperative infection and another patient eventually underwent total knee arthroplasty (TKA). 70% prevention of TKA was achieved by SCP in a study of 66 patients with BME secondary to advanced OA. Thus, a total number of 166 patients were considered as clinical success and 14 patients as clinical failure.ConclusionsThe included studies that have been published referred to the surgical methods of CD or SCP for the management of BME of the knee but none of that summarizes all current studies on both methods. Those studies seem that CD is a surgical technique that is proposed to perform in patients without findings of OA that usually fail to respond to conservative treatment. On the other hand, the option of SCP technique is carried out in patients with varied stage of OA associated with subchondral BME. Both methods aim to reduce the pain and to improve function in the setting of subchondral BME. Nevertheless it is not clear in literature which method is the best according to the criteria of the use. This literature review shows a lack of standardized guidelines with respect to diagnosis and surgical treatment.

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A systematic review of phage therapy applied to bone and joint infections: an analysis of success rates, treatment modalities and safety.

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