Cumulative and temporal associations between antimicrobial prescribing and community-associated Clostridium difficile infection: population-based case control study using administrative data

Kimberley Kavanagh, Jiafeng Pan, Charis Marwick, Peter Davey, Camilla Wiuff, Scott Bryson, Chris Robertson, Marion Bennie

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background. Community-associated (CA) Clostridium difficile infection (CDI) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescription of antimicrobials in primary care and CA-CDI. CA-CDI is defined as cases without prior hospitalisation in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital.
Methods. Three National patient level datasets –covering CDI cases, community prescriptions and hospitalisations were linked by the NHS Scotland unique patient identifier, the community health index, CHI. All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression.
Results. 1446 unique cases of CA-CDI were linked with 7964 age, sex and location matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with excess of 28 defined daily doses (DDD) to any antimicrobial (19.9% of cases) had an odds ratio (OR)=4.4 (95% CI:3.4-5.6) compared to those unexposed. Individuals exposed to 29+ DDD of high risk antimicrobials (cephalosporins, clindamycin co-amoxiclav, or fluoroquinolones) had an OR=17.9 (95% CI:7.6-42.2). Elevated CA-CDI risk following high risk antimicrobial exposure was greatest in the first month (OR=12.5 (8.9-17.4)) but was still present 4-6 months later (OR=2.6 (1.7-3.9)). Cases exposed to 29+DDD had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long term prophylactic use.
Conclusions. This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials with an impact of exposure to high risk antimicrobials remaining 4-6 months later.
LanguageEnglish
JournalJournal of Antimicrobial Chemotherapy
Early online date20 Dec 2016
DOIs
Publication statusE-pub ahead of print - 20 Dec 2016

Fingerprint

Clostridium Infections
Clostridium difficile
Case-Control Studies
Population
Odds Ratio
Prescriptions
Scotland
Hospitalization
Amoxicillin-Potassium Clavulanate Combination
Population Control
Clindamycin
Fluoroquinolones
Cephalosporins
Primary Health Care
Public Health
Logistic Models

Keywords

  • Clostridium difficile
  • antimicrobials
  • community prescriptions
  • hospitalisations
  • dose-response
  • community associated
  • bacterial infections
  • temporal

Cite this

@article{33db656ea9a640539c0de511e1c69b3e,
title = "Cumulative and temporal associations between antimicrobial prescribing and community-associated Clostridium difficile infection: population-based case control study using administrative data",
abstract = "Background. Community-associated (CA) Clostridium difficile infection (CDI) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescription of antimicrobials in primary care and CA-CDI. CA-CDI is defined as cases without prior hospitalisation in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital.Methods. Three National patient level datasets –covering CDI cases, community prescriptions and hospitalisations were linked by the NHS Scotland unique patient identifier, the community health index, CHI. All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression.Results. 1446 unique cases of CA-CDI were linked with 7964 age, sex and location matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with excess of 28 defined daily doses (DDD) to any antimicrobial (19.9{\%} of cases) had an odds ratio (OR)=4.4 (95{\%} CI:3.4-5.6) compared to those unexposed. Individuals exposed to 29+ DDD of high risk antimicrobials (cephalosporins, clindamycin co-amoxiclav, or fluoroquinolones) had an OR=17.9 (95{\%} CI:7.6-42.2). Elevated CA-CDI risk following high risk antimicrobial exposure was greatest in the first month (OR=12.5 (8.9-17.4)) but was still present 4-6 months later (OR=2.6 (1.7-3.9)). Cases exposed to 29+DDD had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long term prophylactic use. Conclusions. This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials with an impact of exposure to high risk antimicrobials remaining 4-6 months later.",
keywords = "Clostridium difficile, antimicrobials, community prescriptions, hospitalisations, dose-response, community associated, bacterial infections, temporal",
author = "Kimberley Kavanagh and Jiafeng Pan and Charis Marwick and Peter Davey and Camilla Wiuff and Scott Bryson and Chris Robertson and Marion Bennie",
year = "2016",
month = "12",
day = "20",
doi = "10.1093/jac/dkw528",
language = "English",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",

}

TY - JOUR

T1 - Cumulative and temporal associations between antimicrobial prescribing and community-associated Clostridium difficile infection

T2 - Journal of Antimicrobial Chemotherapy

AU - Kavanagh, Kimberley

AU - Pan, Jiafeng

AU - Marwick, Charis

AU - Davey, Peter

AU - Wiuff, Camilla

AU - Bryson, Scott

AU - Robertson, Chris

AU - Bennie, Marion

PY - 2016/12/20

Y1 - 2016/12/20

N2 - Background. Community-associated (CA) Clostridium difficile infection (CDI) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescription of antimicrobials in primary care and CA-CDI. CA-CDI is defined as cases without prior hospitalisation in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital.Methods. Three National patient level datasets –covering CDI cases, community prescriptions and hospitalisations were linked by the NHS Scotland unique patient identifier, the community health index, CHI. All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression.Results. 1446 unique cases of CA-CDI were linked with 7964 age, sex and location matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with excess of 28 defined daily doses (DDD) to any antimicrobial (19.9% of cases) had an odds ratio (OR)=4.4 (95% CI:3.4-5.6) compared to those unexposed. Individuals exposed to 29+ DDD of high risk antimicrobials (cephalosporins, clindamycin co-amoxiclav, or fluoroquinolones) had an OR=17.9 (95% CI:7.6-42.2). Elevated CA-CDI risk following high risk antimicrobial exposure was greatest in the first month (OR=12.5 (8.9-17.4)) but was still present 4-6 months later (OR=2.6 (1.7-3.9)). Cases exposed to 29+DDD had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long term prophylactic use. Conclusions. This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials with an impact of exposure to high risk antimicrobials remaining 4-6 months later.

AB - Background. Community-associated (CA) Clostridium difficile infection (CDI) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescription of antimicrobials in primary care and CA-CDI. CA-CDI is defined as cases without prior hospitalisation in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital.Methods. Three National patient level datasets –covering CDI cases, community prescriptions and hospitalisations were linked by the NHS Scotland unique patient identifier, the community health index, CHI. All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression.Results. 1446 unique cases of CA-CDI were linked with 7964 age, sex and location matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with excess of 28 defined daily doses (DDD) to any antimicrobial (19.9% of cases) had an odds ratio (OR)=4.4 (95% CI:3.4-5.6) compared to those unexposed. Individuals exposed to 29+ DDD of high risk antimicrobials (cephalosporins, clindamycin co-amoxiclav, or fluoroquinolones) had an OR=17.9 (95% CI:7.6-42.2). Elevated CA-CDI risk following high risk antimicrobial exposure was greatest in the first month (OR=12.5 (8.9-17.4)) but was still present 4-6 months later (OR=2.6 (1.7-3.9)). Cases exposed to 29+DDD had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long term prophylactic use. Conclusions. This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials with an impact of exposure to high risk antimicrobials remaining 4-6 months later.

KW - Clostridium difficile

KW - antimicrobials

KW - community prescriptions

KW - hospitalisations

KW - dose-response

KW - community associated

KW - bacterial infections

KW - temporal

UR - https://jac.oxfordjournals.org/

U2 - 10.1093/jac/dkw528

DO - 10.1093/jac/dkw528

M3 - Article

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

ER -