Successful Treatment of Antibiotic-resistant, Poly-microbial Bone Infection With Bacteriophages and Antibiotics Combination

Nir-Paz, Ran; Gelman, Daniel; Khouri, Ayman; Sisson, Brittany M.; Fackler, Joseph; Alkalay-Oren, Sivan; Khalifa, Leron; Rimon, Amit; Yerushalmy, Ortal; Bader, Reem; Amit, Sharon; Coppenhagen-Glazer, Shunit; Henry, Matthew; Quiñónes, Javier; Malagón, Francisco; Biswas, Biswajit; Moses, Allon E.; Merril, Greg; Schooley, Robert T.; Brownstein, Michael J.; Weil, Yoram A.; Hazan, Ronen

doi:10.1093/cid/ciz222

Cited by 189 publications

(135 citation statements)

References 11 publications

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“…Other recent clinical experience that exhibited positive outcomes with phage‐antibiotic combinations were described in another cystic fibrosis case, lung transplant patients, polymicrobial osteomyelitis, and others …”

Section: Review Of Positive Interactions Between Phage‐antibiotic Commentioning

confidence: 79%

Bacteriophage Therapeutics: A Primer for Clinicians on Phage‐Antibiotic Combinations

et al. 2020

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Multidrug-resistant organisms have caused a marked depletion of effective antimicrobials, and the narrow pipeline of antibiotics has demanded the need to find novel therapeutic alternatives including nonantibiotic agents. Bacteriophages (phages) are viruses that use the bacterial machinery to infect, replicate, and kill bacterial cells. Although a marked decline in their use was driven by the discovery of antibiotics, the era of antibiotic resistance has led to a resurgence of phage therapy into clinical practice. The term phage-antibiotic synergy (PAS) was coined just over a decade ago and described that sublethal concentrations of antibiotics could stimulate phage production by bacterial cells. Recent literature has described PAS and other encouraging interactions with various phage and antibiotic combinations against a variety of bacterial strains. The primary objective of this review is to discuss the positive interactions between phage and antibiotic combinations, with an emphasis on PAS, reductions in bacterial growth or minimum inhibitory concentrations, enhanced biofilm eradication, and alterations in the emergence of bacterial resistance. A peer-reviewed literature search was conducted (1890-2019) using the PubMed, Medline, and Google Scholar databases. Although more investigation is certainly needed, the combination of bacteriophages with antibiotics is a promising strategy to target organisms with limited or no therapeutic options. This approach may also foster the ability to lower the antibiotic dose and may reduce the potential for antibiotic resistance emergence during therapy.

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Section: Review Of Positive Interactions Between Phage‐antibiotic Commentioning

confidence: 79%

Bacteriophage Therapeutics: A Primer for Clinicians on Phage‐Antibiotic Combinations

et al. 2020

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“…36 The superiority of phage and antibiotic combination treatment to monotherapy of either has been reported, commonly with rifampin, implying a potential synergistic effect. 35,[37][38][39][40] In vivo, phage has also shown significant clearance of soft tissue infections. 41,42 In one abscess study, 10 9 PFU of bacteriophage M Sa eradicated infection in 97% of mice, when treated immediately after inoculation of 10 8 CFU of S. aureus intravenously.…”

Section: Bacteriophagesmentioning

confidence: 99%

Therapeutics and delivery vehicles for local treatment of osteomyelitis

Cobb

McCabe

Priddy

2020

Journal Orthopaedic Research

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Osteomyelitis, or the infection of the bone, presents a major complication in orthopedics and may lead to prolonged hospital visits, implant failure, and in more extreme cases, amputation of affected limbs. Typical treatment for this disease involves surgical debridement followed by long‐term, systemic antibiotic administration, which contributes to the development of antibiotic‐resistant bacteria and has limited ability to eradicate challenging biofilm‐forming pathogens including Staphylococcus aureus—the most common cause of osteomyelitis. Local delivery of high doses of antibiotics via traditional bone cement can reduce systemic side effects of an antibiotic. Nonetheless, growing concerns over burst release (then subtherapeutic dose) of antibiotics, along with microbial colonization of the nondegradable cement biomaterial, further exacerbate antibiotic resistance and highlight the need to engineer alternative antimicrobial therapeutics and local delivery vehicles with increased efficacy against, in particular, biofilm‐forming, antibiotic‐resistant bacteria. Furthermore, limited guidance exists regarding both standardized formulation protocols and validated assays to predict efficacy of a therapeutic against multiple strains of bacteria. Ideally, antimicrobial strategies would be highly specific while exhibiting a broad spectrum of bactericidal activity. With a focus on S. aureus infection, this review addresses the efficacy of novel therapeutics and local delivery vehicles, as alternatives to the traditional antibiotic regimens. The aim of this review is to discuss these components with regards to long bone osteomyelitis and to encourage positive directions for future research efforts.

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“…A recent systematic review has concluded that phage therapy is effective and safe based on the limited publications to date, but more data are needed as challenges in manufacturing and the regulatory process remain. 147,148 Ultimately, all of these therapies need to overcome several obstacles not limited to optimal dosing and delivery and high-quality human trials of safety and comparative effectiveness before they can be incorporated into routine care limiting their current role in clinical practice.…”

Section: Inhaled Antibioticsmentioning

confidence: 99%

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

Strich

Kadri

2019

Semin Respir Crit Care Med

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Antibiotic resistance among gram-negative pathogens is a world-wide problem that poses a constant threat to patients in the intensive care unit and a therapeutic challenge for the intensivist. Furthermore, the substantial economic burden and increased mortality associated with infections due to highly resistant gram-negative pathogens exacerbate these challenges. Understanding the mechanisms, epidemiology, and risk factors for these infections is paramount to the successful control of outbreaks and for guiding therapy which often entails use of antibiotics with suboptimal efficacy and/or toxicity profiles. In this review we will discuss the global epidemiology, burden, risk factors, and treatment of highly resistant gram-negative infections as they apply to the intensive care population.

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Successful Treatment of Antibiotic-resistant, Poly-microbial Bone Infection With Bacteriophages and Antibiotics Combination

Cited by 189 publications

References 11 publications

Bacteriophage Therapeutics: A Primer for Clinicians on Phage‐Antibiotic Combinations

Bacteriophage Therapeutics: A Primer for Clinicians on Phage‐Antibiotic Combinations

Therapeutics and delivery vehicles for local treatment of osteomyelitis

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

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