Innovations for the treatment of a complex bone and joint infection due to XDR Pseudomonas aeruginosa including local application of a selected cocktail of bacteriophages

Ferry, Tristan; Boucher, F.; Fèvre, Cindy; Perpoint, Thomas; Château, J.; Petitjean, Charlotte; Josse, Jérôme; Chidiac, Christian; L’Hostis, Guillaume; Leboucher, Gilles; Laurent, François; Bone, Lyon

doi:10.1093/jac/dky263

Cited by 77 publications

(49 citation statements)

References 7 publications

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“…The results with the bacteriophage cocktail used were encouraging and showed good capacity of the phages in reducing bacterial load and biofilm formation. This could be a useful strategy for local treatment of deep infections, such as bone and joint infections caused by XDR P. aeruginosa (335). Another study was based on the isolation of different P. aeruginosa phages from hospital sewage samples, specifically SL1, SL2, and SL4 (336).…”

Section: Bacteriophagesmentioning

confidence: 99%

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

et al. 2019

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SUMMARYIn recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR)Pseudomonas aeruginosahas become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options.In vitroandin vivotreatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDRP. aeruginosainfections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other “old” antimicrobials, such as certain β-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDRP. aeruginosastrains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDRP. aeruginosa, especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.

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Section: Bacteriophagesmentioning

confidence: 99%

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

et al. 2019

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“…• Not yet tested to treat UTIs Bacteriophages (Dufour et al, 2016;Sybesma et al, 2016;Leitner et al, 2017;Ferry et al, 2018;Ujmajuridze et al, 2018;Jault et al, 2019;Kuipers et al, 2019) • Direct bacteria killing • Interesting animal models and human case reports.…”

Section: Chinese Medicalmentioning

confidence: 99%

“…Bacteriophage therapy is currently applied in different areas of medical research. Indeed, it has been recognized as an alternative treatment in localized infections such as otitis, infected burns and osteoarticular infections (Ferry et al, 2018;Jault et al, 2019). However, its use in UTI is scarce.…”

Section: Bacteriophagesmentioning

confidence: 99%

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

et al. 2020

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Urinary tract infections (UTIs) mainly caused by Uropathogenic Escherichia coli (UPEC), are common bacterial infections. Many individuals suffer from chronically recurring UTIs, sometimes requiring long-term prophylactic antibiotic regimens. The global emergence of multi-drug resistant uropathogens in the last decade underlines the need for alternative non-antibiotic therapeutic and preventative strategies against UTIs. The research on non-antibiotic therapeutic options in UTIs has focused on the following phases of the pathogenesis: colonization, adherence of pathogens to uroepithelial cell receptors and invasion. In this review, we discuss vaccines, small compounds, nutraceuticals, immunomodulating agents, probiotics and bacteriophages, highlighting the challenges each of these approaches face. Most of these treatments show interesting but only preliminary results. Lactobacillus-containing products and cranberry products in conjunction with propolis have shown the most robust results to date and appear to be the most promising new alternative to currently used antibiotics. Larger efficacy clinical trials as well as studies on the interplay between non-antibiotic therapies, uropathogens and the host immune system are warranted.

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“…Recently, 3 studies using animal models have highlighted the potential of bacteriophages in combination with antibiotics to prevent and treat S. aureus BJIs (13)(14)(15). In addition, with the approval of the French National Agency for Medicines and Health Products Safety (Agence nationale de sécurité du médicament et des produits de santé [ANSM], Paris, France), bacteriophages have also been used successfully in humans as a salvage therapy for severe periprosthetic joint infections (16,17). This efficacy is supported by very few in vitro studies that have demonstrated the particular activity of bacteriophages against biofilm (18)(19)(20).…”

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confidence: 99%

Evaluation of the Activity of a Combination of Three Bacteriophages Alone or in Association with Antibiotics on Staphylococcus aureus Embedded in Biofilm or Internalized in Osteoblasts

Kolenda

Josse

Medina

et al. 2020

Antimicrob Agents Chemother

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Staphylococcus aureus is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm and to be internalized and persist inside osteoblasts. Recently, bacteriophage therapy has emerged as a promising option to improve treatment of such infections, but data on its activity against the specific bacterial lifestyles presented above remain scarce. We evaluated the activity of a combination of three bacteriophages, recently used for compassionate treatment in France, against S. aureus HG001 in a model of staphylococcal biofilm and a model of osteoblasts infection, alone or in association with vancomycin or rifampin. The activity of bacteriophages against biofilm-embedded S. aureus was dose dependent. In addition, synergistic effects were observed when bacteriophages were combined with antibiotics used at the lowest concentrations. Phage penetration into osteoblasts was observed only when the cells were infected, suggesting a S. aureus-dependent Trojan horse mechanism for internalization. The intracellular bacterial count of bacteria in infected osteoblasts treated with bacteriophages as well as with vancomycin was significantly higher than in cells treated with lysostaphin, used as a control condition, owing to the absence of intracellular activity and the rapid killing of bacteria released after the death of infected cells. These results suggest that bacteriophages are both inactive in the intracellular compartment after being internalized in infected osteoblasts and present a delayed killing effect on bacteria released after cell lysis into the extracellular compartment, which avoids preventing them from infecting other osteoblasts. The combination of bacteriophages tested was highly active against S. aureus embedded in biofilm but showed no activity against intracellular bacteria in the cell model used.

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Innovations for the treatment of a complex bone and joint infection due to XDR Pseudomonas aeruginosa including local application of a selected cocktail of bacteriophages

Cited by 77 publications

References 7 publications

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

Evaluation of the Activity of a Combination of Three Bacteriophages Alone or in Association with Antibiotics on Staphylococcus aureus Embedded in Biofilm or Internalized in Osteoblasts

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