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Predicting in vivo efficacy of therapeutic bacteriophages used to treat pulmonary infections.

ABSTRACT: The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used to guide their choice among billions of available bacteriophages are still not clearly defined. We made use of a mouse lung infection model and a bioluminescent strain of Pseudomonas aeruginosa to compare the activities in vitro and in vivo of a set of nine different bacteriophages (PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5, CHA_P1, LBL3, LUZ19, and PhiKZ). For seven bacteriophages, a good correlation was found between in vitro and in vivo activity. While the remaining two bacteriophages were active in vitro, they were not sufficiently active in vivo under similar conditions to rescue infected animals. Based on the bioluminescence recorded at 2 and 8 h postinfection, we also define for the first time a reliable index to predict treatment efficacy. Our results showed that the bacteriophages isolated directly on the targeted host were the most efficient in vivo, supporting a personalized approach favoring an optimal treatment.

SUBMITTER: Henry M

PROVIDER: S-EPMC3837875 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Predicting in vivo efficacy of therapeutic bacteriophages used to treat pulmonary infections.

Henry Marine M Lavigne Rob R Debarbieux Laurent L

Antimicrobial agents and chemotherapy 20130916 12

The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used to guide their choice among billions of available bacteriophages are still not clearly defined. We made use of a mouse lung infection model and a bioluminescent strain of Pseudomona ...[more]

PMID: 24041900

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Project description:OBJECTIVE:This NMA compared the efficacy and safety between IV antibiotics that are used in the current standard of care for managing adult patients (?18 years of age) with ABSSSI. METHODS:Comparators were chosen on the basis that both direct and indirect comparisons between the interventions of interest could be performed. Outcomes of the analysis were selected on the basis that they are frequently measured and reported in trials involving ABSSSI patients, and only published randomised control trials of any size and duration and with any blinding status were eligible for inclusion in the analysis. The NMA was performed using both a fixed-effect and random-effect model. Efficacy-related endpoints were (1) clinical treatment success and (2) microbiological success at TOC visit. Safety-related endpoints were (1) number of discontinuations due to AEs/SAEs, (2) patients experiencing AEs, (3) patients experiencing SAEs and (4) all-cause mortality. RESULTS:Study interventions included daptomycin, dalbavancin, linezolid and tigecycline. Vancomycin was the comparator in all studies, except in two where it was linezolid and teicoplanin. The NMA showed that irrespective of patient subgroup, the likelihood of clinical and microbiological success with dalbavancin was statistically similar to the comparators studied. No statistically significant differences were observed between dalbavancin and any of the comparators in the discontinuation rate due to AEs/SAEs. In contrast, dalbavancin was associated with a significantly lower likelihood of experiencing an AE than linezolid, a significantly lower likelihood of experiencing a SAE than vancomycin and daptomycin, and a significantly lower risk of all-cause mortality than vancomycin, linezolid and tigecycline. CONCLUSION:Dalbavancin affords a promising, new alternative IV antimicrobial agent which is as effective as traditional therapies, but with the added benefit of enabling clinicians to treat patients with ABSSSI in different organisational settings. Notwithstanding, any introduction of an effective treatment with a differential mode of administration into healthcare systems must be followed by a change in clinical practice and patient management in order to fully achieve desirable economic outcomes.

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Predicting in vivo efficacy of therapeutic bacteriophages used to treat pulmonary infections.

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Predicting in vivo efficacy of therapeutic bacteriophages used to treat pulmonary infections.

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