Activity of Isolated Staphylococcal Bacteriophage in Treatment of Experimentally Induced Chronic Osteomyelitis in Rabbits

Ibrahim, Orooba Mohammed Saeed; Sarhan, Sarhan Rashid; Salih, Serwa Ibrahim

doi:10.14737/journal.aavs/2016/4.11.593.603

Cited by 9 publications

(4 citation statements)

References 44 publications

(50 reference statements)

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“…A bacteriophage cocktail was used to successfully clear femoral infection with four intraperitoneal doses of phage (100 μL of ~2x10 12 pfu/mL) over the span of 48 hours[42]. Another study adopted a treatment regimen for tibial osteomyelitis consisting of a once daily 3x10 8 pfu/mL intramuscular bacteriophage injection for 14 days, which resolved the infection[43]. Recently, a case report was published describing the success of a weekly injection of bacteriophage over a seven-week period for human digital osteomyelitis[40].…”

Section: Discussionmentioning

confidence: 99%

CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection

et al. 2019

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Osteomyelitis, or bone infection, is often induced by antibiotic resistant Staphylococcus aureus strains of bacteria. Although debridement and long-term administration of antibiotics are the gold standard for osteomyelitis treatment, the increase in prevalence of antibiotic resistant bacterial strains limits the ability of clinicians to effectively treat infection. Bacteriophages (phages), viruses that in a lytic state can effectively kill bacteria, have gained recent attention for their high specificity, abundance in nature, and minimal risk of host toxicity. Previously, we have shown that CRISPR-Cas9 genomic editing techniques could be utilized to expand temperate bacteriophage host range and enhance bactericidal activity through modification of the tail fiber protein. In a dermal infection study, these CRISPR-Cas9 phages reduced bacterial load relative to unmodified phage. Thus we hypothesized this temperate bacteriophage, equipped with the CRISPR-Cas9 bactericidal machinery, would be effective at mitigating infection from a biofilm forming S. aureus strain in vitro and in vivo. In vitro, qualitative fluorescent imaging demonstrated superiority of phage to conventional vancomycin and fosfomycin antibiotics against S. aureus biofilm. Quantitative antibiofilm effects increased over time, at least partially, for all fosfomycin, phage, and fosfomycin-phage (dual) therapeutics delivered via alginate hydrogel. We developed an in vivo rat model of osteomyelitis and soft tissue infection that was reproducible and challenging and enabled longitudinal monitoring of infection progression. Using this model, phage (with and without fosfomycin) delivered via alginate hydrogel were successful in reducing soft tissue infection but not bone infection, based on bacteriological, histological, and scanning electron microscopy analyses. Notably, the efficacy of phage at mitigating soft tissue infection was equal to that of high dose fosfomycin. Future research may utilize this model as a platform for evaluation of therapeutic type and dose, and alternate delivery vehicles for osteomyelitis mitigation.

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Section: Discussionmentioning

confidence: 99%

CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection

et al. 2019

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“…It has also been documented that concentrations of antibiotics also have important ramification of synergistic or antagonistic activity with higher antibiotic concentrations tending to be more antagonistic compared to lower concentrations which tend to be more synergistic [ 43 ]. It is interesting that in vivo studies have shown more synergistic activity of antibiotics with bacteriophage therapy then antagonism [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Spatial and temporal interactions of antibiotics and bacteriophages in vivo likely account for this synergistic activity [ 43 ].…”

Section: Parameters That Impact Treatment Protocolsmentioning

confidence: 99%

“…Several preclinical animal studies support the use of bacteriophage therapy in clinical biofilm infections [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. These studies show that local administrations of bacteriophages to the site of biofilm infections result in biofilm reduction [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. In addition, these studies show that, without local administration of bacteriophage therapy, reduction in biofilms on hardware is not significantly reduced [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Bacteriophage Therapy for Clinical Biofilm Infections: Parameters That Influence Treatment Protocols and Current Treatment Approaches

Doub

2020

Antibiotics

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Biofilm infections are extremely difficult to treat, which is secondary to the inability of conventional antibiotics to eradicate biofilms. Consequently, current definitive treatment of biofilm infections requires complete removal of the infected hardware. This causes significant morbidity and mortality to patients and therefore novel therapeutics are needed to cure these infections without removal of the infected hardware. Bacteriophages have intrinsic properties that could be advantageous in the treatment of clinical biofilm infections, but limited knowledge is known about the proper use of bacteriophage therapy in vivo. Currently titers and duration of bacteriophage therapy are the main parameters that are evaluated when devising bacteriophage protocols. Herein, several other important parameters are discussed which if standardized could allow for more effective and reproducible treatment protocols to be formulated. In addition, these parameters are correlated with the current clinical approaches being evaluated in the treatment of clinical biofilm infections.

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“…It is crucial for researchers, therefore, to employ pharmacologically rigorous follow up should they observe disappointing phage therapy performance. In particular, though not necessarily easily determined, Bull et al, 2012;Ibrahim et al, 2016;Chhibber et al, 2017) 15 4 (7) 0 Intraperitoneal (i.p.) 16 (Matsuda et al, 2005;Vinodkumar et al, 2005;Wang et al, 2006a;Wang et al, 2006b;Capparelli et al, 2006;McVay et al, 2007;Chhibber et al, 2008;Nishikawa et al, 2008;Uchiyama et al, 2008;Vinodkumar et al, 2008;Kumari et al, 2009a;Kumari et al, 2009b;Zimecki et al, 2009;Carmody et al, 2010;Kumari et al, 2010;Sunagar et al, 2010;Zimecki et al, 2010;Hung et al, 2011;Tothova et al, 2011;Jun et al, 2014;Shivshetty et al, 2014;Takemura-Uchiyama et al, 2014;Pincus et al, 2015;Singla et al, 2015;Chai et al, 2016;Guang-Han et al, 2016;Regeimbal et al, 2016;Chadha et al, 2017;Cheng et al, 2017;Green et al, 2017;Yin et al, 2017;Can et al, 2018;Gelman et al, 2018;Jasim et al, 2018;…”

Section: Pharmacology Of Antibacterial Virusesmentioning

confidence: 99%

Phage Therapy: The Pharmacology of Antibacterial Viruses

Danis-Wlodarczyk¹,

Dąbrowska²,

Abedon³

2020

Bacterial Viruses: Exploitation for Biocontrol and Therapeutics

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Pharmacology can be differentiated into two key aspects, pharmacodynamics and pharmacokinetics. Pharmacodynamics describes a drug's impact on the body while pharmacokinetics describes the body's impact on a drug. Another way of understanding these terms is that pharmacodynamics is a description of both the positive and negative consequences of drugs attaining certain concentrations in the body while pharmacokinetics is concerned with our ability to reach and then sustain those concentrations. Unlike the drugs for which these concepts were developed, including antibiotics, the bacteriophages (or 'phages') that we consider here are not chemotherapeutics but instead are the viruses of bacteria. Here we review the pharmacology of these viruses, particularly as they can be employed to combat bacterial infections (phage therapy). Overall, an improved pharmacological understanding of phage therapy should allow for more informed development of phages as antibacterial 'drugs', allow for more rational post hoc debugging of phage therapy experiments, and encourage improved design of phage therapy protocols. Contrasting with antibiotics, however, phages as viruses impact individual bacterial cells as single virions rather than as swarms of molecules, and while they are killing bacteria, 49 bacteriophages also can amplify phage numbers, in situ. Explorations of phage therapy pharmacology consequently can often be informed as well by basic principles of the ecological interactions between phages and bacteria as by study of the pharmacology of drugs. Bacteriophages in phage therapy thus can display somewhat unique as well as more traditional pharmacological aspects. Abd El-Aziz, A.M., Elgaml, A., and Ali, Y.M. (2019). Bacteriophage therapy increases complement-mediated lysis of bacteria and enhances bacterial clearance after acute lung infection with multidrug-resistant Pseudomonas aeruginosa.

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Activity of Isolated Staphylococcal Bacteriophage in Treatment of Experimentally Induced Chronic Osteomyelitis in Rabbits

Cited by 9 publications

References 44 publications

CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection

CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection

Bacteriophage Therapy for Clinical Biofilm Infections: Parameters That Influence Treatment Protocols and Current Treatment Approaches

Phage Therapy: The Pharmacology of Antibacterial Viruses

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