Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections.

The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists between trials and compassionate use in order to better develop future phage treatment and clinical applications. The multitude of observations reported over the years in the literature constitutes an invaluable experience, and we add to this by presenting a number of cases of patients treated compassionately with phages throughout the past decade with a focus on osteoarticular infections. Additionally, an abundance of scientific literature into phage-related areas is transforming our knowledge base, creating a greater understanding that should be applied for future clinical applications. Due to the increasing number of treatment failures anticipatedfrom the perspective of a possible post-antibiotic era, we believe that the introduction of bacteriophages into the therapeutic arsenal seems a scientifically sound and eminently practicable consideration today as a substitute or adjuvant to antibiotic therapy

HIV infection and severe malnutrition: a clinical and epidemiological study in Burkina Faso.

OBJECTIVE: To define a clinical profile indicative of HIV infection in a population of severely malnourished children in Burkina Faso. A total of 433 children (average age, 19 months) were recruited at the Sanou Souro National Hospital, Bobo Dioulasso, Burkina Faso. RESULTS: Sixty-three per cent presented with marasmus, 13% with kwashiorkor and 24% with both forms of malnutrition. The prevalence of HIV infection in children aged over 12 months was 13.8%, with a marked predominance of HIV-1 (95.8%). Mother-to-child transmission was proven in 77% of the cases; in 10% of the observed paediatric AIDS cases, transmission may have occurred through multi-injections with contaminated equipment. Marasmus was the form of malnutrition most frequently associated with HIV (P < 0.001); its severity was exacerbated by HIV infection. Adenopathy (P < 0.0001), oral candidiasis (P < 0.0006), skin disorders (P < 0.01) and hepatomegaly (P = 0.01) appeared to be significantly related to HIV infection. Discriminant analysis revealed that the presence of adenopathies was the strongest indicator symptom of HIV infection. Multivariate analysis revealed that a clinical profile of marasmus, adenopathies and oral candidiasis (specificity, 82%) was indicative of HIV infection in this population. The short-term clinical prognosis was poor and usually led to the death of the child when seropositive (P < 0.001). CONCLUSIONS: Among children exhibiting severe malnutrition, HIV-positive children are distinguished by a high horizontal transmission rate, a high specific clinical profile and a very poor prognosis

Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections.

The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists between trials and compassionate use in order to better develop future phage treatment and clinical applications. The multitude of observations reported over the years in the literature constitutes an invaluable experience, and we add to this by presenting a number of cases of patients treated compassionately with phages throughout the past decade with a focus on osteoarticular infections. Additionally, an abundance of scientific literature into phage-related areas is transforming our knowledge base, creating a greater understanding that should be applied for future clinical applications. Due to the increasing number of treatment failures anticipatedfrom the perspective of a possible post-antibiotic era, we believe that the introduction of bacteriophages into the therapeutic arsenal seems a scientifically sound and eminently practicable consideration today as a substitute or adjuvant to antibiotic therapy

The phage therapy paradigm: prêt-à-porter or sur-mesure?

The present opinion is the result of discussions on the future of phage therapy (personalized or large-scale uniform therapy?) during the first International Congress on Viruses of Microbes, held at the Institut Pasteur in Paris on June 21–25, 2010

Towards third generation matrix metalloproteinase inhibitors for cancer therapy

The failure of matrix metalloproteinase (MMP) inhibitor drug clinical trials in cancer was partly due to the inadvertent inhibition of MMP antitargets that counterbalanced the benefits of MMP target inhibition. We explore how MMP inhibitor drugs might be developed to achieve potent selectivity for validated MMP targets yet therapeutically spare MMP antitargets that are critical in host protection

Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to shamtreated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI

The Corinth Rift Laboratory, Greece (CRL): A Multidisciplinary Near Fault Observatory (NFO) on a Fast Rifting System

The western rift of Corinth (Greece) is one of the most active tectonic structures of the euro-mediterranean area. Its NS opening rate is 1.5 cm/yr ( strain rate of 10-6/yr) results into a high microseismicity level and a few destructive, M>6 earthquakes per century, activating a system of mostly north dipping normal faults. Since 2001, monitoring arrays of the European Corinth Rift Laboratory (CRL, www.crlab.eu) allowed to better track the mechanical processes at work, with short period and broad band seismometers, cGPS, borehole strainmeters, EM stations, …). The recent (300 kyr) tectonic history has been revealed by onland (uplifted fan deltas and terraces) and offshore geological studies (mapping, shallow seismic, coring), showing a fast evolution of the normal fault system. The microseismicity, dominated by swarms lasting from days to months, mostly clusters in a layer 1 to 3 km thick, between 6 and 9 km in depth, dipping towards north, on which most faults are rooting. The diffusion of the microseismicity suggests its triggering by pore pressure transients, with no or barely detected strain. Despite a large proportion of multiplets, true repeaters seem seldom, suggesting a minor contribution of creep in their triggering, although transient or steady creep is clearly detected on the shallow part of some majors faults. The microseismic layer may thus be an immature, downward growing detachment, and the dominant rifting mechanism might be a mode I, anelastic strain beneath the rift axis , for which a mechanical model is under development. Paleoseismological (trenching, paleoshorelines, turbidites), archeological and historical studies completed the catalogues of instrumental seismicity, motivating attempts of time dependent hazard assessment. The Near Fault Observatory of CRL is thus a multidisciplinary research infrastructure aiming at a better understanding and modeling of multiscale, coupled seismic/aseismic processes on fault systems.Grant for Researchers (CC) ID 188753

TRANSFER OF MULTIPLE ANTIBIOTIC-RESISTANCE BETWEEN SUBSPECIES OF BACTEROIDES-FRAGILIS

Resistance to clindamycin, erythromycin, streptogramins, and tetracycline was shown to be transferable from a clinical isolate of Bacteroides tragilis subspecies distasonis to a sensitive strain of B. tragilis subspecies [ragilis. Resistance to clindamycin, eryth-romycin, and streptogramins was transferable from a clinical isolate of B. tragilis subspecies [ragilis to the sensitive strain of B. tragilis subspecies [ragilis. Except for tetracycline, resistance to all of these antibiotics was spontaneously curable en bloc at a frequency of-10-2 • These results suggest that resistance to these antibiotics is determined by a plasmid. The resistance of the Bacteroides tragilis group to antibiotics may be extrachromosomally deter-mined as indicated by the enzymatic inactivation of IHactam antibiotics by these organisms and by the emergence of resistance to other antibiotics, particularly clindamycin, macrolides, and tetracy-cline [1-4). Plasmids have been demonstrated i

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