Phage Therapy for Limb-threatening Prosthetic Knee Klebsiella pneumoniae Infection: Case Report and In Vitro Characterization of Anti-biofilm Activity.

BACKGROUND: Prosthetic joint infection (PJI) is a potentially limb-threatening complication of total knee arthroplasty. Phage therapy is a promising strategy to manage such infections including those involving antibiotic-resistant microbes, and to target microbial biofilms. Experience with phage therapy for infections associated with retained hardware is limited. A 62-year-old diabetic man with a history of right total knee arthroplasty 11 years prior who had suffered multiple episodes of prosthetic knee infection despite numerous surgeries and prolonged courses of antibiotics, with progressive clinical worsening and development of severe allergies to antibiotics, had been offered limb amputation for persistent right prosthetic knee infection due to Klebsiella pneumoniae complex. Intravenous phage therapy was initiated as a limb-salvaging intervention. METHODS: The patient received 40 intravenous doses of a single phage (KpJH46Φ2) targeting his bacterial isolate, alongside continued minocycline (which he had been receiving when he developed increasing pain, swelling, and erythema prior to initiation of phage therapy). Serial cytokine and biomarker measurements were performed before, during, and after treatment. The in vitro anti-biofilm activity of KpJH46Φ2, minocycline and the combination thereof was evaluated against a preformed biofilm of the patient's isolate and determined by safranin staining. RESULTS: Phage therapy resulted in resolution of local symptoms and signs of infection and recovery of function. The patient did not experience treatment-related adverse effects and remained asymptomatic 34 weeks after completing treatment while still receiving minocycline. A trend in biofilm biomass reduction was noted 22 hours after exposure to KpJH46Φ2 (P = .063). The addition of phage was associated with a satisfactory outcome in this case of intractable biofilm-associated prosthetic knee infection. Pending further studies to assess its efficacy and safety, phage therapy holds promise for treatment of device-associated infections.

Biological challenges of phage therapy and proposed solutions: a literature review.

Introduction: In light of the emergence of antibiotic-resistant bacteria, phage (bacteriophage) therapy has been recognized as a potential alternative or addition to antibiotics in Western medicine for use in humans.Areas covered: This review assessed the scientific literature on phage therapy published between 1 January 2007 and 21 October 2019, with a focus on the successes and challenges of this prospective therapeutic.Expert opinion: Efficacy has been shown in animal models and experimental findings suggest promise for the safety of human phagotherapy. Significant challenges remain to be addressed prior to the standardization of phage therapy in the West, including the development of phage-resistant bacteria; the pharmacokinetic complexities of phage; and any potential human immune response incited by phagotherapy.

Implications of Bacteriophage- and Bacteriophage Component-Based Therapies for the Clinical Microbiology Laboratory.

Treatment of bacterial infections is increasingly challenged by resistance to currently available antibacterial agents. Not only are such agents less likely to be active today than they were in the past, but their very use has selected for and continues to select for further resistance. Additional strategies for the management of bacterial illnesses must be identified. In this review, bacteriophage-based therapies are presented as one promising approach. In anticipation of their potential expansion into clinical medicine, clinical microbiologists may wish to acquaint themselves with bacteriophages and their antibacterial components and, specifically, with methods for testing them. Here, we reviewed the literature spanning January 2007 to March 2019 on bacteriophage and phage-encoded protein therapies of relevance to clinical microbiology.

Antibacterial activity of reduced iron clay against pathogenic bacteria associated with wound infections.

Clay is a substance historically utilized by indigenous cultures for the treatment of superficial wound infections. This study evaluated the effects of a recently identified clay - OMT Blue Clay - against staphylococci, streptococci, Enterobacteriaceae and non-fermenting Gram-negative bacilli. The clay and its aqueous leachate were evaluated against the bacteria in biofilm and planktonic states. Time-kill studies were used to assess planktonic activity. Biofilms on medical-grade Teflon discs were treated with a hydrated clay suspension or leachate. For the planktonic studies, clay and leachate exhibited bactericidal activity against all strains tested, with the exception of leachate against Staphylococcus aureus IDRL-6169 and USA300. All strains treated with clay suspension and leachate resulted in statistically significant biofilm population reductions compared with controls, except S. aureus IDRL-6169 and USA300 (P ≤ 0.05). OMT Blue Clay and its aqueous leachate exhibited bactericidal activity against a range of human pathogens in the planktonic and biofilm states.