Effect of #antibiotic #stewardship on the #incidence of #infection and #colonisation with antibiotic-resistant #bacteria and #Clostridium difficile infection… (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis

David Baur, MD†, Beryl Primrose Gladstone, PhD†, Francesco Burkert, MD, Elena Carrara, MD, Federico Foschi, MD, Stefanie Döbele, MD, Prof Evelina Tacconelli, PhD

†Contributed equally

Published: 16 June 2017 / Article has an altmetric score of 1 / DOI: http://dx.doi.org/10.1016/S1473-3099(17)30325-0

© 2017 Elsevier Ltd. All rights reserved.

 

Summary

Background

Antibiotic stewardship programmes have been shown to reduce antibiotic use and hospital costs. We aimed to evaluate evidence of the effect of antibiotic stewardship on the incidence of infections and colonisation with antibiotic-resistant bacteria.

Methods

For this systematic review and meta-analysis, we searched PubMed, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Web of Science for studies published from Jan 1, 1960, to May 31, 2016, that analysed the effect of antibiotic stewardship programmes on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infections in hospital inpatients. Two authors independently assessed the eligibility of trials and extracted data. Studies involving long-term care facilities were excluded. The main outcomes were incidence ratios (IRs) of target infections and colonisation per 1000 patient-days before and after implementation of antibiotic stewardship. Meta-analyses were done with random-effect models and heterogeneity was calculated with the I2 method.

Findings

We included 32 studies in the meta-analysis, comprising 9 056 241 patient-days and 159 estimates of IRs. Antibiotic stewardship programmes reduced the incidence of infections and colonisation with multidrug-resistant Gram-negative bacteria (51% reduction; IR 0·49, 95% CI 0·35–0·68; p<0·0001), extended-spectrum β-lactamase-producing Gram-negative bacteria (48%; 0·52, 0·27–0·98; p=0·0428), and meticillin-resistant Staphylococcus aureus (37%; 0·63, 0·45–0·88; p=0·0065), as well as the incidence of C difficile infections (32%; 0·68, 0·53–0·88; p=0·0029). Antibiotic stewardship programmes were more effective when implemented with infection control measures (IR 0·69, 0·54–0·88; p=0·0030), especially hand-hygiene interventions (0·34, 0·21–0·54; p<0·0001), than when implemented alone. Antibiotic stewardship did not affect the IRs of vancomycin-resistant enterococci and quinolone-resistant and aminoglycoside-resistant Gram-negative bacteria. Significant heterogeneity between studies was detected, which was partly explained by the type of interventions and co-resistance patterns of the target bacteria.

Interpretation

Antibiotic stewardship programmes significantly reduce the incidence of infections and colonisation with antibiotic-resistant bacteria and C difficile infections in hospital inpatients. These results provide stakeholders and policy makers with evidence for implementation of antibiotic stewardship interventions to reduce the burden of infections from antibiotic-resistant bacteria.

Funding

German Center for Infection Research.

Keywords: Antibiotics; Drugs Resistance; Clostridium Difficile.

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#Transmissibility of #Clostridium difficile without contact #isolation: results from a prospective observational study with 451 patients (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

Transmissibility of Clostridium difficile without contact isolation: results from a prospective observational study with 451 patients

Andreas F. Widmer, MD1, Reno Frei, MD2, Stefan Erb, MD1, Anne Stranden, PhD1, Ed J. Kuijper, PhD3, Cornelis W. Knetsch, PhD3, and Sarah Tschudin-Sutter, MD1

Author Affiliations: 1  Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland; 2  Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland; 3 Section Experimental Microbiology, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands

Corresponding Author: Dr. Sarah Tschudin-Sutter, MD MSc Division of Infectious Diseases and Hospital Epidemiology University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland Tel.: +41 61 328 68 10, Fax: +41 61 265 38 54 E-Mail: Sarah.Tschudin@usb.ch

 

Abstract

Background

Contact precautions are recommended by health authorities in Europe and the US for patients with Clostridium difficile infection (CDI). Recently, the significance of nosocomial transmission has been challenged by screening on admission studies and whole-genome sequencing, providing evidence for an endogenous source of C. difficile. We discontinued contact precautions for CDI patients, except for patients infected with hypervirulent ribotypes or with stool incontinence, to determine the rate of transmission.

Methods

From 01/2004 to 12/2013, contacts of each index case with CDI were screened for toxigenic C. difficile by culturing rectal swabs. Transmission was defined as possible if toxigenic C. difficile was detected in contacts, as probable if the identical PCR-ribotype was identified in index-contact pairs, and as confirmed if next-generation sequencing (NGS) revealed clonality of strains.

Results

451 contacts were exposed to 279 index patients nursed in two-to-four-bed-rooms. Toxigenic C. difficile was detected in 6.0% (27/451) after a median contact time of five days. Identical ribotypes were identified in six index-contact pairs, accounting for probable transmission in 1.3% (6/451). NGS was performed for 4/6 pairs with identical strains, and confirmed transmission in two contact patients.

Conclusions

The rate of transmission of toxigenic, predominantly non-hypervirulent C. difficile was low and no outbreaks were recorded over a 10-year period after discontinuing contact precautions for patients with CDI who were not severely incontinent and who used dedicated toilets.

As contact precautions may lead to lower levels of care, their implementation needs to balanced against the risk of nosocomial transmission.

Key words: C. difficile – transmission – contact precautions – screening acute-care hospital

Received July 22, 2016.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Keywords: Clostridium Difficile; Nosocomial Outbreaks.

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Lack of #adherence to #SHEA-IDSA #treatment #guidelines for #Clostridium difficile #infection is associated with increased #mortality (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Lack of adherence to SHEA-IDSA treatment guidelines for Clostridium difficile infection is associated with increased mortality

I. Patel†, M. Wungjiranirun*,†, T. Theethira, J. Villafuerte-Galvez, N. Castillo, M. Akbari, C. D. Alonso, D. A. Leffler and C. P. Kelly

Author Affiliations: Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA

*Corresponding author. E-mail: manida9@gmail.com

† These authors contributed equally to this research work and manuscript.

Received May 13, 2016. Revision requested June 8, 2016. Revision received September 1, 2016. Accepted September 8, 2016.

 

Abstract

Objectives

The objective of this study was to determine our institution’s compliance with 2010 Society for Healthcare Epidemiology of America and IDSA Clostridium difficile infection (CDI) treatment guidelines and their respective outcomes.

Methods

We collected clinical parameters, laboratory values, antibiotic therapy and clinical outcomes from the electronic medical records for all patients hospitalized at our institution with a diagnosis of CDI from December 2012 to November 2013. We specifically evaluated whether SHEA-IDSA treatment guidelines were followed and evaluated the associations between guideline adherence and severe outcomes including mortality.

Results

We identified 230 patients with CDI meeting inclusion criteria during the study period. Of these, 124 (54%) were appropriately treated, 46 (20%) were under-treated and 60 (26%) were over-treated. All-cause 90 day mortality was 17.4% overall; 43.5% in the under-treated group versus 12.9% in those appropriately treated (P < 0.0001) and 10.9% in those appropriately treated plus over-treated (P < 0.0001). Similarly, 90 day mortality attributed to CDI was 21.7% in those under-treated versus 8.9% in those appropriately treated (P = 0.03) and 8.2% in those either appropriately treated or over-treated (P = 0.015). Severe-complicated CDI occurred in 46 patients. In this subgroup, there was a non-significant trend towards increased mortality in under-treated patients (56.7%) compared with appropriately treated patients (37.5%, P = 0.35). Under-treatment was also associated with a higher rate of CDI-related ICU transfer (17.4% versus 4.8% in those appropriately treated, P = 0.023).

Conclusions

Adherence to CDI treatment guidelines is associated with improved outcomes especially in those with severe disease. Increased emphasis on provision of appropriate, guideline-based CDI treatment appears warranted.

© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Keywords: Clostridium Difficile.

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Effect of a #national 4C #antibiotic #stewardship #intervention on the clinical and molecular #epidemiology of #Clostridium difficile infections in a region of #Scotland: a non-linear time-series analysis (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Articles

Effect of a national 4C antibiotic stewardship intervention on the clinical and molecular epidemiology of Clostridium difficile infections in a region of Scotland: a non-linear time-series analysis

Dr Timothy Lawes, MSc, José-María Lopez-Lozano, PhD, Cesar A Nebot, MSc, Gillian Macartney, MSc, Rashmi Subbarao-Sharma, MSc, Karen D Wares, MSc, Carolyn Sinclair, MSc, Ian M Gould, MBChB

Published: 04 November 2016 / DOI: http://dx.doi.org/10.1016/S1473-3099(16)30397-8

© 2016 Elsevier Ltd. All rights reserved.

 

Summary

Background

Whereas many antibiotics increase risk of Clostridium difficile infection through dysbiosis, epidemic C difficile ribotypes characterised by multidrug resistance might depend on antibiotic selection pressures arising from population use of specific drugs. We examined the effect of a national antibiotic stewardship intervention limiting the use of 4C antibiotics (fluoroquinolones, clindamycin, co-amoxiclav, and cephalosporins) and other infection prevention and control strategies on the clinical and molecular epidemiology of C difficile infections in northeast Scotland.

Methods

We did a non-linear time-series analysis and quasi-experimental study to explore ecological determinants of clinical burdens from C difficile infections and ribotype distributions in a health board serving 11% of the Scottish population. Study populations were adults (aged ≥16 years) registered with primary carer providers in the community (mean 455 508 inhabitants) or admitted to tertiary level, district general, or geriatric hospitals (mean 33 049 total admissions per month). A mixed persuasive-restrictive 4C antibiotic stewardship intervention was initiated in all populations on May 1, 2009. Other population-specific interventions considered included limiting indications for macrolide prescriptions, introduction of alcohol-based hand sanitiser, a national hand-hygiene campaign, national auditing and inspections of hospital environment cleanliness, and reminders to reduce inappropriate use of proton-pump inhibitors. The total effect of interventions was defined as the difference between observations and projected scenarios without intervention. Primary outcomes were prevalence density of C difficile infection per 1000 occupied bed-days in hospitals or per 100 000 inhabitant-days in the community.

Findings

Between Jan 1, 1997, and Dec 31, 2012, we identified 4885 cases of hospital-onset C difficile infection among 1 289 929 admissions to study hospitals, and a further 1625 cases of community-onset C difficile infection among 455 508 adults registered in primary care. Use of 4C antibiotics was reduced by 50% in both hospitals (mean reduction 193 defined daily doses per 1000 occupied bed-days, 95% CI 45–328, p=0·008) and the community (1·85 defined daily doses per 1000 inhabitant-days, 95% CI 0·23–3·48, p=0·025) during antibiotic stewardship. Falling 4C use predicted rapid declines in multidrug-resistant ribotypes R001 and R027. Hospital-onset C difficile infection prevalence densities were associated with fluoroquinolone, third-generation cephalosporin, macrolides, and carbapenem use, exceeding hospital population specific total use thresholds. Community-onset C difficile infection prevalence density was predicted by recent hospital C difficile infection rates, introduction of mandatory surveillance in individuals older than 65 years, and primary-case use of fluoroquinolones and clindamycin exceeding total use thresholds. Compared with predictions without intervention, C difficile infection prevalence density fell by 68% (mean reduction 1·01 per 1000 occupied bed-days, 0·27–1·76, p=0·008) in hospitals and 45% (0·083, 0·045–0·121 cases per 100 000 inhabitant-days, p<0·0001) in the community, during antibiotic stewardship. We identified no significant effects from other interventions.

Interpretation

Limiting population use of 4C antibiotics reduced selective pressures favouring multidrug-resistant epidemic ribotypes and was associated with substantial declines in total C difficile infections in northeast Scotland. Efforts to control C difficile through antibiotic stewardship should account for ribotype distributions and non-linear effects.

Funding

NHS Grampian Microbiology Endowment Fund.

Keywords: UK; Scotland; Antibiotics; Drugs Resistance; Clostridium difficile.

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More than 50% of #Clostridium difficile Isolates from #Pet #Dogs in #Flagstaff, #USA, Carry #Toxigenic Genotypes (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE

More than 50% of Clostridium difficile Isolates from Pet Dogs in Flagstaff, USA, Carry Toxigenic Genotypes

Nathan E. Stone, Lindsay C. Sidak-Loftis, Jason W. Sahl, Adam J. Vazquez, Kristin B. Wiggins, John D. Gillece, Nathan D. Hicks, James M. Schupp, Joseph D. Busch, Paul Keim, David M. Wagner

Published: October 10, 2016 / http://dx.doi.org/10.1371/journal.pone.0164504

 

Abstract

Nosocomial acquisition of Clostridium difficile is well documented, yet recent studies have highlighted the importance of community acquired infections and identified community associated reservoirs for this pathogen. Multiple studies have implicated companion pets and farm animals as possible sources of community acquired C. difficile infections in humans. To explore the potential role of pet dogs in human C. difficile infections we systematically collected canine fecal samples (n = 197) in Flagstaff, AZ. Additionally, nineteen fecal samples were collected at a local veterinary clinic from diarrheic dogs. We used these combined samples to investigate important questions regarding C. difficile colonization in pet canines: 1) What is the prevalence and diversity of C. difficile in this companion pet population, and 2) Do C. difficile isolates collected from canines genetically overlap with isolates that cause disease in humans? We used a two-step sequence typing approach, including multilocus sequence typing to determine the overall genetic diversity of C. difficile present in Flagstaff canines, and whole-genome sequencing to assess the fine-scale diversity patterns within identical multilocus sequence types from isolates obtained within and among multiple canine hosts. We detected C. difficile in 17% of the canine fecal samples with 10% containing toxigenic strains that are known to cause human disease. Sequencing analyses revealed similar genotypes in dogs and humans. These findings suggest that companion pets are a potential source of community acquired C. difficile infections in humans.

_____

Citation: Stone NE, Sidak-Loftis LC, Sahl JW, Vazquez AJ, Wiggins KB, Gillece JD, et al. (2016) More than 50% of Clostridium difficile Isolates from Pet Dogs in Flagstaff, USA, Carry Toxigenic Genotypes. PLoS ONE 11(10): e0164504. doi:10.1371/journal.pone.0164504

Editor: Hsin-Chih Lai, Chang Gung University, TAIWAN

Received: July 26, 2016; Accepted: September 26, 2016; Published: October 10, 2016

Copyright: © 2016 Stone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All whole genome sequencing reads generated during this study have been deposited in NCBI BioProject database under accession #PRJNA309189. The associated SRA numbers for these 54 isolates are sequentially assigned beginning with #SRR3115454 and ending with #SRR3115507. Multilocus sequence types for one representative of the 44 unique isolates discovered during this study have been deposited in the isolate database of http://www.pubmlst.org/cdifficile.

Funding: This project was funded by the Northern Arizona University Technology & Research Initiative Fund (TRIF) and the Flinn Foundation, https://nau.edu/research/funding/technology-research-initiative-fund/, http://www.flinn.org/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Clostridium Difficile; Dogs; Human; USA; Arizona.

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#Antibodies to #Toxin B Are Protective Against #Clostridium difficile Infection Recurrence (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

Antibodies to Toxin B Are Protective Against Clostridium difficile Infection Recurrence

Swati B. Gupta1, Vinay Mehta2, Erik R. Dubberke3, Xuemei Zhao4, Mary Beth Dorr5, Dalya Guris5, Deborah Molrine6,7, Mark Leney7,8, Mark Miller9, Marilyne Dupin10, and T. Christopher Mast2

Author Affiliations: 1Public Health and Scientific Affairs  – 2Pharmacoepidemiology, Merck & Co, Inc, Kenilworth, New Jersey  – 3Division of Infectious Diseases, Washington University School of Medicine, St Louis, Missouri  – 4Translational Molecular Biomarkers  – 5Clinical Research, Merck & Co, Inc, Kenilworth, New Jersey  – 6Department of Pediatrics, University of Massachusetts Medical School, Worcester
7MassBiologics, Boston  – 8Department of Medicine, University of Massachusetts Medical School, Worcester  – 9Office of Medical and Scientific Affairs  – 10Medical Diagnostics Discovery Department, bioMérieux, Marcy L’Etoile, France

Correspondence: S. B. Gupta, Merck & Co, Inc., 770 Sumneytown Pike, West Point, PA 19486 (swati.gupta5@merck.com).

 

Abstract

Background. 

Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti–toxin A and anti–toxin B antibody levels.

Methods. 

Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays.

Results. 

A predictor of recurrence was age ≥65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI.

Conclusions. 

Our findings demonstrate the importance of clinical as well as immunological risk factors in rCDI and provide more robust evidence for the protective effects of antibody to toxin B in the prevention of rCDI.

Clinical Trials Registration. NCT00350298.

Key words: epidemiology – risk factors – antibodies – toxin A – serology

10.1093/cid/ciw366 Received February 15, 2016.

Accepted May 7, 2016.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Keywords: Research; Abstracts; Clostridium Difficile.

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Potential of #lactoferrin to prevent #antibiotic-induced #Clostridium difficile #infection (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection [      ]

C. H. Chilton 1, G. S. Crowther 1, K. Śpiewak 2, M. Brindell 2, G. Singh 3, M. H. Wilcox 1 and T. M. Monaghan 3,*

Author Affiliations: 1Leeds Institute for Molecular Medicine, University of Leeds, Leeds, UK 2Department of Inorganic Chemistry, Jagiellonian University, Krakow, Poland 3NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK

*Corresponding author. Tel: +44-(0)115-9249924; Fax: +44-(0)115-9709955; E-mail: tanya.monaghan@nottingham.ac.uk

Received August 8, 2015. Revision requested September 27, 2015. Revision received October 20, 2015. Accepted November 24, 2015.

 

Abstract

Objectives

Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe3+ saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe3+ saturated) bovine holo-lactoferrin (holo-bLf) in a human in vitro gut model that simulates CDI.

Methods

Two parallel triple-stage chemostat gut models were inoculated with pooled human faeces and spiked with C. difficile spores (strain 027 210, PCR ribotype 027). Holo- or apo-bLf was instilled (5 mg/mL, once daily) for 35 days. After 7 days, clindamycin was instilled (33.9 mg/L, four times daily) to induce simulated CDI. Indigenous microflora populations, C. difficile total counts and spores, cytotoxin titres, short chain fatty acid concentrations, biometal concentrations, lactoferrin concentration and iron content of lactoferrin were monitored daily.

Results

In the apo-bLf model, germination of C. difficile spores occurred 6 days post instillation of clindamycin, followed by rapid vegetative cell proliferation and detectable toxin production. By contrast, in the holo-bLf model, only a modest vegetative cell population was observed until 16 days post antibiotic administration. Notably, no toxin was detected in this model. In separate batch culture experiments, holo-bLf prevented C. difficile vegetative cell growth and toxin production, whereas apo-bLf and iron alone did not.

Conclusions

Holo-bLf, but not apo-bLf, delayed C. difficile growth and prevented toxin production in a human gut model of CDI. This inhibitory effect may be iron independent. These observations suggest that bLf in its iron-saturated state could be used as a novel preventative or treatment strategy for CDI.

© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: Research; Abstracts; Clostridium difficile; Lactoferrin.

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Better together: #bacteriophage combinations significantly reduce #Clostridium difficile #growth in vitro and proliferation in vivo (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Better together: bacteriophage combinations significantly reduce Clostridium difficile growth in vitro and proliferation in vivo [      ]

Janet Y. Nale a, Janice Spencer b, Katherine R. Hargreaves a, Anthony M. Buckley b, Przemysław Trzepiński a,  Gillian R. Douce b# and Martha R. J. Clokie a#

Author Affiliations: aDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester, England, UK. bInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graham Davies Building, University Place, University of Glasgow, Scotland, UK

 

ABSTRACT

Microbiome dysbiosis caused by antibiotic treatment has been associated with both the susceptibility and relapsing of Clostridium difficile infection (CDI). Bacteriophage (phage) therapy offers target specificity and dose amplification in situ, but few studies have focused on their use in CDI treatment. This mainly reflects the lack of strictly virulent phages that target this pathogen. Whilst it is widely accepted that temperate phages are unsuitable for therapeutic purposes due to their transduction potential, analysis of seven C. difficile phages confirmed that this impact could be curtailed by the application of multiple phage types. Here, host range analysis of six myoviruses and one siphovirus was conducted on 80 strains representing 21 major epidemic and clinically severe ribotypes. The phages had complementary coverage; lysing 18 and 62 of the ribotypes and strains tested respectively. Single-phage treatments of ribotypes 076, 014/020 and 027 strains showed an initial reduction in bacterial load followed by emergence of phage-resistant colonies. However, these colonies remained susceptible to phage infection with an unrelated phage. In contrast, specific phage combinations caused complete lysis of C. difficile in vitro and prevented the appearance of resistant/lysogenic clones. Using a hamster model, oral delivery of optimized phage combinations resulted in reduced C. difficile colonization 36 h post-infection. Interestingly, free phages were recovered from the bowel at this time. In a challenge model of the disease, phage treatment delayed the onset of symptoms by 33 h compared to untreated animals. These data demonstrate the therapeutic potential of phage combinations to treat CDI.

 

FOOTNOTES

#Address correspondence to: M. R. J. Clokie, mrjc1@le.ac.uk and G. R. Douce. Gillian.Douce@glasgow.ac.uk

Copyright © 2015 Nale et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 International license.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Clostridium Difficile; Bacteriophages.

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