Bacteriophages as an efficient therapy for antibiotic-resistant septicemia in man

Weber‐Dąbrowska, Beata; Mulczyk, M; Górski, Andrzej

doi:10.1016/s0041-1345(03)00525-6

Cited by 89 publications

(66 citation statements)

References 8 publications

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“…injection of phages did not evoke intense immune reactions. Our observation and those of others (16,(20)(21)(22) support the view that the immunologic elimination of phages in vivo may not be a serious issue for practical applications of phage therapy because before the occurrence of immunologic elimination in the body, the treating effect of phages has already been completed. Altogether, our current study reinforces the view that phage therapy can be used to treat drug-resistant bacterial infections.…”

Section: Discussionsupporting

confidence: 88%

Use of bacteriophage in the treatment of experimental animal bacteremia from imipenem-resistant Pseudomonas aeruginosa

Wang

Hu²,

Xu³

et al. 2006

Int J Mol Med

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Abstract. The emergence of antibiotic-resistant bacterial strains still remains a significant problem for antimicrobial chemotherapy in the clinic. Bacterial viruses (bacteriophages or phages) have been suggested to be used as alternative therapeutic agents for bacterial infections. However, the efficacy of phage therapy in treating drug-resistant infections in humans is uncertain. Therefore in the present study, we examined the effectiveness of phages in the treatment of imipenem-resistant Pseudomonas aeruginosa (IMPR-Pa) infection in an experimental mouse model. Twenty-nine strains of phage were isolated from our hospital sewage, and phage ØA392 was representatively used for all testing because it has lytic activity against a wide range of clinical isolates of IMPR-Pa. We found that intraperitoneal (i.p.) injections of one IMPR-Pa strain (3x10 7 CFU) caused bacteremia and all mice died within 24 h. A single i.p. inoculation of the phage strain (MOI ≥0.01) at up to 60 min after the bacterial challenge was sufficient to rescue 100% of the animals. This lifesaving effect coincided with the rapid appearance of ØA392 in the circulation (within 2 h after i.p. injection), which remained at substantially higher levels for up to 48 h until the bacteria were eradicated. However, the survival rates of the mice dropped to approximately 50% and 20% when the same dose of this purified phage preparation was administered at 180 min and 360 min, respectively, after IMPR-Pa infections. In addition, we demonstrated that the ability of this phage to rescue bacteremic animals was due to the functional capabilities of the phage and not to a nonspecific immune effect. The protection from death occurred only in animals inoculated with bacteria-specific virulent phage strains. When the heat-inactivated phages were used, the survival rate of the infected mice was dramatically reduced to 20% or lower. Moreover, the levels of the antibody against the phage were not significantly changed at the time when the bacteremic animals were protected by the active phages. Finally, our observations revealed that the inoculation of the mice with high-doses of ØA392 alone produced no adverse effects attributable to the phage. These data indicate that phages can save animals from pernicious P. aeruginosa infections and suggest that phage therapy may be potentially used as a stand-alone therapy for patients with IMPR-Pa infections.

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Section: Discussionsupporting

confidence: 88%

Use of bacteriophage in the treatment of experimental animal bacteremia from imipenem-resistant Pseudomonas aeruginosa

Wang

Hu²,

Xu³

et al. 2006

Int J Mol Med

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“…Similar results for phage T4 imply that this might be true of phage more generally. On the other hand, serum neutralization was rapid but incomplete, leaving 10 4 to 10 5 PFU/ml after 24 h of incubation, and phage could replicate in the presence of their pathogenic bacterial host and so compensate for phage losses (45). Whether different phages have various abilities to resist human serum inactivation remains to be evaluated; we suggest that future assessments of experimental phage therapy should include this evaluation.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Bacteriophage Therapy in Experimental Sepsis and Meningitis Caused by a Clone O25b:H4-ST131 Escherichia coli Strain Producing CTX-M-15

Pouillot

Chomton

Blois

et al. 2012

Antimicrob Agents Chemother

122

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bWe evaluated phage therapy in experimental infections due to S242, a fatal neonatal meningitis Escherichia coli strain belonging to the worldwide-distributed O25b:H4-ST131 clone that produces extended-spectrum beta-lactamase CTX-M-15. A lytic phage, EC200 PP , active against S242, was isolated from environmental water. After determining in vitro and ex vivo stabilities and pharmacokinetic properties of EC200 PP in rat pups, we assessed the therapeutic efficacy of a single dose of 10 8 PFU using models of sepsis and meningitis in which fatality was 100%. EC200 PP was partially neutralized by human serum. In contrast to the high concentration of phage in the spleen and the kidney, low titers in urine and the central nervous system were observed. Nevertheless, in the sepsis model, EC200 PP administered 7 h or 24 h postinfection resulted in 100% and 50% pup survival, respectively. In the meningitis model, EC200PP administered 1 h or 7 h postinfection rescued 100% of the animals. The most delayed treatments were associated with the selection of phage-resistant S242 mutants. However, a representative mutant was highly sensitive to killing serum activity and avirulent in an animal model. EC200PP is a potential therapeutic agent for sepsis and meningitis caused by the widespread E. coli O25:H4-ST131 multidrug-resistant clone.

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“…Studies from Eliava Institute and from Queen Astrid Military Hospital in Brussels showed the efficacy of phage therapy in curing bacterial infections, such as wound infections (Weber-Dabrowska et al 2003;Merabishvili et al 2009). The ongoing research aims at improving phage therapy to be effective in reducing the number of pathogenic bacteria accompanying the infection.…”

Section: Future Applicationsmentioning

confidence: 99%

Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

El‐Shibiny

El-Sahhar

2017

Can. J. Microbiol.

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Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.Key words: bacteriophages, antibiotics, biocontrol, infection, pathogenesis.Résumé : Les bactériophages ont été utilisés pour traiter des infections bactériennes chez l'animal et l'humain depuis leur découverte en 1915, à cause de leur capacité unique d'infecter leurs hôtes bactériens spécifiques, sans affecter les autres populations bactériennes. La recherche réalisée dans ce domaine au cours du vingtième siècle, principalement en Géorgie, dans une partie de l'URSS et en Pologne, a mené à l'établissement de protocoles thérapeutiques à partir de phages. Cependant, la découverte de la pénicilline et des antibiotiques sulfamidés au cours des années 1930 a retardé l'avancement de la thérapie par les phages. Le mauvais usage des antibiotiques depuis leur découverte a résulté en une augmentation du nombre de bactéries résistantes aux antibiotiques et une réduction de leur efficacité à contrôler d'importants pathogènes. Les bactériophages sont devenus un sujet d'intérêt comme alternative aux antibiotiques avec l'émergence de bactéries multirésistantes qui constituent une menace à la santé publique. Des études récentes ont indiqué que les bactériophages peuvent être utilisés indirectement pour détecter les bactéries pathogènes, ou directement, comme agents de contrôle biologique. De plus, ils peuvent être utilisés pour développer de nouvelles molécules à des fins d'applications cliniques, de production de vaccins, dans la conception de médicaments et dans le domaine de la nanomédecine, par l'exposition sur phage. [Traduit par la Rédaction]

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Bacteriophages as an efficient therapy for antibiotic-resistant septicemia in man

Cited by 89 publications

References 8 publications

Use of bacteriophage in the treatment of experimental animal bacteremia from imipenem-resistant Pseudomonas aeruginosa

Use of bacteriophage in the treatment of experimental animal bacteremia from imipenem-resistant Pseudomonas aeruginosa

Efficacy of Bacteriophage Therapy in Experimental Sepsis and Meningitis Caused by a Clone O25b:H4-ST131 Escherichia coli Strain Producing CTX-M-15

Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

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