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      Bacteriophages as Adjuvant to Antibiotics for the Treatment of Periprosthetic Joint Infection Caused by Multidrug-Resistant Pseudomonas aeruginosa

      Author(s): , , , ,
      Publication date Created:
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      Journal: Antimicrobial Agents and Chemotherapy
      Publisher: American Society for Microbiology

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          ABSTRACT

          We documented the adjunctive bacteriophage therapy to treat a chronic relapsing periprosthetic joint infection of the knee and chronic osteomyelitis of the femur caused by multidrug-resistant Pseudomonas aeruginosa. The combined antibiotic-phage treatment eradicated the infection, and no side effects to phages were observed.

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          A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy.

          A. Wright, C Hawkins, E Anggård … (2009)
          To evaluate the efficacy and safety of a therapeutic bacteriophage preparation (Biophage-PA) targeting antibiotic-resistant Pseudomonas aeruginosa in chronic otitis. Randomised, double-blind, placebo-controlled Phase I/II clinical trial approved by UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Central Office for Research Ethics Committees (COREC) ethical review process. A single specialist university hospital. 24 patients with chronic otitis with a duration of several years (2-58). Each patient had, at the time of entry to the trial, an ear infection because of an antibiotic-resistant P. aeruginosa strain sensitive to one or more of the six phages present in Biophage-PA. Participants were randomised in two groups of 12 treated with either a single dose of Biophage-PA or placebo and followed up at 7, 21 and 42 days after treatment by the same otologist. Ears were thoroughly cleaned on each occasion and clinical and microbiological indicators measured. Physician assessed erythema/inflammation, ulceration/granulation/polyps, discharge quantity, discharge type and odour using a Visual Analogue Scale (VAS). Patients reported discomfort, itchiness, wetness and smell also using a VAS. Bacterial levels of P. aeruginosa and phage counts from swabs were measured initially and at follow-up. At each visit patients were asked about side effects using a structured form. Digital otoscopic images were obtained on days 0 and 42 for illustrative purposes only. Relative to day 0, pooled patient- and physician-reported clinical indicators improved for the phage treated group relative to the placebo group. Variation from baseline levels was statistically significant for combined data from all clinic days only for the phage treated group. Variation from baseline levels was statistically significant for the majority of the patient assessed clinical indicators only for the phage treated group. P. aeruginosa counts were significantly lower only in the phage treated group. No treatment related adverse event was reported. The first controlled clinical trial of a therapeutic bacteriophage preparation showed efficacy and safety in chronic otitis because of chemo-resistant P. aeruginosa.
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            Bacteriophages as potential new therapeutics to replace or supplement antibiotics.

            Mzia Kutateladze, Revaz Adamia (2010)
            Over recent decades, a growing body of literature has validated the use of bacteriophages for therapy and prophylaxis in the war against drug-resistant bacteria. Today, much more is known about bacteriophages than in the 1930s when phage therapy first appeared and began to spread to many countries. With rapid dissemination of multi-drug-resistant bacterial pathogens, the interest in alternative remedies to antibiotics, including bacteriophage treatments, is gaining new ground. Based on recent experience and current results of bacteriophage applications against bacterial infections in countries where this alternative therapy is approved, many scientists and companies have come to believe that the use of phages for treating and preventing bacterial diseases will be successful. Copyright © 2010 Elsevier Ltd. All rights reserved.
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              Synergy and Order Effects of Antibiotics and Phages in Killing Pseudomonas aeruginosa Biofilms

              Waqas Chaudhry, Jeniffer Concepción-Acevedo, Taehyun Park … (2017)
              In contrast to planktonic cells, bacteria imbedded biofilms are notoriously refractory to treatment by antibiotics or bacteriophage (phage) used alone. Given that the mechanisms of killing differ profoundly between drugs and phages, an obvious question is whether killing is improved by combining antibiotic and phage therapy. However, this question has only recently begun to be explored. Here, in vitro biofilm populations of Pseudomonas aeruginosa PA14 were treated singly and with combinations of two phages and bactericidal antibiotics of five classes. By themselves, phages and drugs commonly had only modest effects in killing the bacteria. However some phage-drug combinations reduced bacterial densities to well below that of the best single treatment; in some cases, bacterial densities were reduced even below the level expected if both agents killed independently of each other (synergy). Furthermore, there was a profound order effect in some cases: treatment with phages before drugs achieved maximum killing. Combined treatment was particularly effective in killing in Pseudomonas biofilms grown on layers of cultured epithelial cells. Phages were also capable of limiting the extent to which minority populations of bacteria resistant to the treating antibiotic ascend. The potential of combined antibiotic and phage treatment of biofilm infections is discussed as a realistic way to evaluate and establish the use of bacteriophage for the treatment of humans.
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                Author and article information

                Journal
                Title: Antimicrobial Agents and Chemotherapy
                Abbreviated Title: Antimicrob Agents Chemother
                Publisher: American Society for Microbiology
                ISSN (Print): 0066-4804
                ISSN (Electronic): 1098-6596
                Publication date Created: December 20 2019
                Publication date (Electronic): December 20 2019
                Publication date (Print): September 16 2019
                Volume: 64
                Issue: 1
                Article
                DOI: 10.1128/AAC.00924-19
                PMC ID: 7187616
                PubMed ID: 31527029
                SO-VID: fdf971ac-f3f4-4636-ad4e-03d6d74582ae
                Copyright © © 2019
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