Safety of bacteriophage therapy in severe Staphylococcus aureus infection

Fabijan, Aleksandra Petrović; Lin, Ruby C.Y.; Ho, Josephine; Maddocks, Susan; Zakour, Nouri L. Ben; Iredell, Jonathan R.; Team, Westmead Bacteriophage Therapy

doi:10.1038/s41564-019-0634-z

Cited by 274 publications

(188 citation statements)

References 20 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…2a). Increased phage dosing in the second week was associated with further bacterial lysis but the dynamics of bacterial and phage DNAemia (to ~ 10 5 genome equivalents/mL), similar to previous observations 3,4 are most consistent overall with a classic "predator-prey" relationship ( Fig. 2a), with predators (phage) thriving while prey (bacterial hosts) are plentiful but declining as prey populations are consumed.…”

Section: Main Textsupporting

confidence: 86%

“…Bacteriophages (phages), rst used as antibacterial agents more than a century ago 1 , offer new hope for highly resistant infections 2,3 but clinicians remain uncertain about optimal dosing and treatment duration. Here we describe phage, bacterial and host responses to intravenous (IV) phage therapy for a chronic osteoarticular infection complicating K-wire insertion for traumatic fracture-dislocation in a 7year-old girl.…”

Section: Main Textmentioning

confidence: 99%

“…Standard curves were generated by spiking tenfold serial dilutions of log-phase P. aeruginosa and PASA16 into whole human blood (P. aeruginosa, 1.3-1.3 × 10 6 colony forming units [CFU]/mL) or serum (phage, 1 × 10 1-7 PFU/mL). Viable phage was recovered from serum onto a lawn of an aztreonam-and colistin-resistant strain of P. aeruginosa (JIP697; EOP ~ 100%), also as previously described 3 . All experiments were performed in duplicate.…”

Section: Main Textmentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic monitoring of the host-bacterium-phage interaction in a child

Khatami

Lin

Petrovic-Fabijan

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Successful phage therapy for extensive chronic osteoarticular infection in a child resulted in an initial flush of bacterial contents into the bloodstream with an inflammatory response marked by fever, local pain and upregulation of genes associated with autophagy and innate immunity. Monitoring of phage and bacterial kinetics and the human host response allowed early dose adjustment and indicated a strong therapeutic effect within two weeks.

show abstract

Section: Main Textsupporting

confidence: 86%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic monitoring of the host-bacterium-phage interaction in a child

Khatami

Lin

Petrovic-Fabijan

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Of the remaining two articles, Doub and colleagues suggested that their patient's pre-existing liver pathology explained their observation of non-life threatening reversible transaminitis in response to intravenous phage used at a titre of 2.7 × 10 9 plaque forming units (PFU)/mL [32]. This would be consistent with the absence of transaminitis among other patients treated with intravenous phage of a similar titre [27,36,56,57]. This suggests that liver function should be closely monitored in patients with pre-existing liver pathology receiving intravenous phage, but that the risk of adverse effects from intravenous phage remains low.…”

Section: Discussionmentioning

confidence: 78%

The Safety and Efficacy of Phage Therapy for Bone and Joint Infections: A Systematic Review

2020

View full text Add to dashboard Cite

Bacterial resistance to antibiotics has catalysed interest in alternative antimicrobial strategies. Bacteriophages (phages) are viruses of bacteria with a long history of successful therapeutic use. Phage therapy is a promising antibacterial strategy for infections with a biofilm component, including recalcitrant bone and joint infections, which have significant social, financial and human impacts. Here, we report a systematic review of the safety and efficacy of phage therapy for the treatment of bone and joint infections. Three electronic databases were systematically searched for articles that reported primary data about human phage therapy for bone and joint infections. Two authors independently assessed study eligibility and performed data extraction. Seventeen reports were eligible for inclusion in this review, representing the treatment of 277 patients. A cautionary, crude, efficacy estimate revealed that 93.1% (n = 258/277) achieved clinical resolution, 3.3% (n = 9/277) had improvement and 3.6% (n = 10/277) showed no improvement. Seven of the nine reports that directly commented on the safety of phage therapy did not express safety concerns. The adverse effects reported in the remaining two were not severe and were linked to the presence of contaminating endotoxins and pre-existing liver pathology in a patient treated with high-titre intravenous phage therapy. Three other reports, from 1940–1987, offered general comments on the safety of phage therapy and documented adverse effects consistent with endotoxin co-administration concomitant with the use of raw phage lysates. Together, the reports identified by this review suggest that appropriately purified phages represent a safe and highly efficacious treatment option for complex and intractable bone and joint infections.

show abstract

“…They are abundantly present in the natural microflora of the human body (De Paepe et al, 2014; Manrique et al, 2016). A recent non-comparative clinical trial showed that the intravenous delivery of anti-staphylococcal phages in patients with severe infection did not pose any challenges to tolerability and safety (Petrovic Fabijan et al, 2020). Moreover, phages remain infective and lyse antibiotic-resistant bacteria (Kortright et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Antimycobacterial potential of Mycobacteriophage under disease-mimicking conditions

Kalapala

Sharma

Agarwal

2020

Preprint

View full text Add to dashboard Cite

Antibiotic resistance continues to be a major global health risk with an increase in multi-drug resistant infections seen across nearly all bacterial diseases. This global burden is further pronounced by the misuse of antibiotics and the availability of only a handful of antibiotics in the development pipeline. Amongst the drug-resistant infections, mycobacterial infections such as Tuberculosis (TB) and Non-Tuberculosis infections have seen a significant increase in the incidence of multi-drug resistant and extensively drug-resistant infections. With this increase in drug-resistant Mycobacteria, mycobacteriophage therapy offers a promising alternative. However, a comprehensive study on the infection dynamics of mycobacteriophage against their host bacteria and the evolution of bacteriophage (phage) resistance in the bacteria remains elusive. We aim to study the infection dynamics of a mixture of phage against Mycobacteria under various pathophysiological conditions such as low pH, low growth rate and hypoxia. We show that mycobacteriophages are effective against M. smegmatis under various conditions and that the mixture of phages prevents the 2 evolution of resistance for long durations. Mycobacteriophages are effective against antibiotic-resistant strains of Mycobacterium and show synergy with antibiotics. Finally, we also show that mycobacteriophages are infective and efficient against M. tuberculosis and prevent its growth for several weeks. These findings have important implications for developing phage therapy against Mycobacterium.

show abstract

Safety of bacteriophage therapy in severe Staphylococcus aureus infection

Cited by 274 publications

References 20 publications

Therapeutic monitoring of the host-bacterium-phage interaction in a child

Therapeutic monitoring of the host-bacterium-phage interaction in a child

The Safety and Efficacy of Phage Therapy for Bone and Joint Infections: A Systematic Review

Antimycobacterial potential of Mycobacteriophage under disease-mimicking conditions

Contact Info

Product

Resources

About