Changes in resistance among coliform bacteraemia associated with a primary care antimicrobial stewardship intervention: a population-based interrupted time series study

Virginia Hernandez Santiago, Peter Davey, Dilip Nathwani, Charis Ann Marwick (Lead / Corresponding author), Bruce Guthrie

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Abstract

BACKGROUND: Primary care antimicrobial stewardship interventions can improve antimicrobial prescribing, but there is less evidence that they reduce rates of resistant infection. This study examined changes in broad-spectrum antimicrobial prescribing in the community and resistance in people admitted to hospital with community-associated coliform bacteraemia associated with a primary care stewardship intervention. METHODS AND FINDINGS: Segmented regression analysis of data on all patients registered with a general practitioner in the National Health Service (NHS) Tayside region in the east of Scotland, UK, from 1 January 2005 to 31 December 2015 was performed, examining associations between a primary care antimicrobial stewardship intervention in 2009 and primary care prescribing of fluoroquinolones, cephalosporins, and co-amoxiclav and resistance to the same three antimicrobials/classes among community-associated coliform bacteraemia. Prescribing outcomes were the rate per 1,000 population prescribed each antimicrobial/class per quarter. Resistance outcomes were proportion of community-associated (first 2 days of hospital admission) coliform (Escherichia coli, Proteus spp., or Klebsiella spp.) bacteraemia among adult (18+ years) patients resistant to each antimicrobial/class. 11.4% of 3,442,205 oral antimicrobial prescriptions dispensed in primary care over the study period were for targeted antimicrobials. There were large, statistically significant reductions in prescribing at 1 year postintervention that were larger by 3 years postintervention when the relative reduction was -68.8% (95% CI -76.3 to -62.1) and the absolute reduction -6.3 (-7.6 to -5.2) people exposed per 1,000 population per quarter for fluoroquinolones; relative -74.0% (-80.3 to -67.9) and absolute reduction -6.1 (-7.2 to -5.2) for cephalosporins; and relative -62.3% (-66.9 to -58.1) and absolute reduction -6.8 (-7.7 to -6.0) for co-amoxiclav, all compared to their prior trends. There were 2,143 eligible bacteraemia episodes involving 2,004 patients over the study period (mean age 73.7 [SD 14.8] years; 51.4% women). There was no increase in community-associated coliform bacteraemia admissions associated with reduced community broad-spectrum antimicrobial use. Resistance to targeted antimicrobials reduced by 3.5 years postintervention compared to prior trends, but this was not statistically significant for co-amoxiclav. Relative and absolute changes were -34.7% (95% CI -52.3 to -10.6) and -63.5 (-131.8 to -12.8) resistant bacteraemia per 1,000 bacteraemia per quarter for fluoroquinolones; -48.3% (-62.7 to -32.3) and -153.1 (-255.7 to -77.0) for cephalosporins; and -17.8% (-47.1 to 20.8) and -63.6 (-206.4 to 42.4) for co-amoxiclav, respectively. Overall, there was reversal of a previously rising rate of fluoroquinolone resistance and flattening of previously rising rates of cephalosporin and co-amoxiclav resistance. The limitations of this study include that associations are not definitive evidence of causation and that potential effects of underlying secular trends in the postintervention period and/or of other interventions occurring simultaneously cannot be definitively excluded. CONCLUSIONS: In this population-based study in Scotland, compared to prior trends, there were very large reductions in community broad-spectrum antimicrobial use associated with the stewardship intervention. In contrast, changes in resistance among coliform bacteraemia were more modest. Prevention of resistance through judicious use of new antimicrobials may be more effective than trying to reverse resistance that has become established.

Original languageEnglish
Article numbere1002825
Pages (from-to)1-19
Number of pages19
JournalPLoS Medicine
Volume16
Issue number6
DOIs
Publication statusPublished - 7 Jun 2019

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Bacteremia
Primary Health Care
Amoxicillin-Potassium Clavulanate Combination
Fluoroquinolones
Cephalosporins
Population
Scotland
Proteus
Klebsiella
Interrupted Time Series Analysis
National Health Programs
Causality
General Practitioners
Prescriptions
Regression Analysis
Escherichia coli
Infection

Keywords

  • family practice
  • primary care
  • antimicrobials
  • antimicrobial resistance
  • quality of healthcare
  • interrupted time series

Cite this

@article{57afea9b8f084650aa298e18fbe992a9,
title = "Changes in resistance among coliform bacteraemia associated with a primary care antimicrobial stewardship intervention: a population-based interrupted time series study",
abstract = "BACKGROUND: Primary care antimicrobial stewardship interventions can improve antimicrobial prescribing, but there is less evidence that they reduce rates of resistant infection. This study examined changes in broad-spectrum antimicrobial prescribing in the community and resistance in people admitted to hospital with community-associated coliform bacteraemia associated with a primary care stewardship intervention. METHODS AND FINDINGS: Segmented regression analysis of data on all patients registered with a general practitioner in the National Health Service (NHS) Tayside region in the east of Scotland, UK, from 1 January 2005 to 31 December 2015 was performed, examining associations between a primary care antimicrobial stewardship intervention in 2009 and primary care prescribing of fluoroquinolones, cephalosporins, and co-amoxiclav and resistance to the same three antimicrobials/classes among community-associated coliform bacteraemia. Prescribing outcomes were the rate per 1,000 population prescribed each antimicrobial/class per quarter. Resistance outcomes were proportion of community-associated (first 2 days of hospital admission) coliform (Escherichia coli, Proteus spp., or Klebsiella spp.) bacteraemia among adult (18+ years) patients resistant to each antimicrobial/class. 11.4{\%} of 3,442,205 oral antimicrobial prescriptions dispensed in primary care over the study period were for targeted antimicrobials. There were large, statistically significant reductions in prescribing at 1 year postintervention that were larger by 3 years postintervention when the relative reduction was -68.8{\%} (95{\%} CI -76.3 to -62.1) and the absolute reduction -6.3 (-7.6 to -5.2) people exposed per 1,000 population per quarter for fluoroquinolones; relative -74.0{\%} (-80.3 to -67.9) and absolute reduction -6.1 (-7.2 to -5.2) for cephalosporins; and relative -62.3{\%} (-66.9 to -58.1) and absolute reduction -6.8 (-7.7 to -6.0) for co-amoxiclav, all compared to their prior trends. There were 2,143 eligible bacteraemia episodes involving 2,004 patients over the study period (mean age 73.7 [SD 14.8] years; 51.4{\%} women). There was no increase in community-associated coliform bacteraemia admissions associated with reduced community broad-spectrum antimicrobial use. Resistance to targeted antimicrobials reduced by 3.5 years postintervention compared to prior trends, but this was not statistically significant for co-amoxiclav. Relative and absolute changes were -34.7{\%} (95{\%} CI -52.3 to -10.6) and -63.5 (-131.8 to -12.8) resistant bacteraemia per 1,000 bacteraemia per quarter for fluoroquinolones; -48.3{\%} (-62.7 to -32.3) and -153.1 (-255.7 to -77.0) for cephalosporins; and -17.8{\%} (-47.1 to 20.8) and -63.6 (-206.4 to 42.4) for co-amoxiclav, respectively. Overall, there was reversal of a previously rising rate of fluoroquinolone resistance and flattening of previously rising rates of cephalosporin and co-amoxiclav resistance. The limitations of this study include that associations are not definitive evidence of causation and that potential effects of underlying secular trends in the postintervention period and/or of other interventions occurring simultaneously cannot be definitively excluded. CONCLUSIONS: In this population-based study in Scotland, compared to prior trends, there were very large reductions in community broad-spectrum antimicrobial use associated with the stewardship intervention. In contrast, changes in resistance among coliform bacteraemia were more modest. Prevention of resistance through judicious use of new antimicrobials may be more effective than trying to reverse resistance that has become established.",
keywords = "family practice, primary care, antimicrobials, antimicrobial resistance, quality of healthcare, interrupted time series",
author = "{Hernandez Santiago}, Virginia and Peter Davey and Dilip Nathwani and Marwick, {Charis Ann} and Bruce Guthrie",
year = "2019",
month = "6",
day = "7",
doi = "10.1371/journal.pmed.1002825",
language = "English",
volume = "16",
pages = "1--19",
journal = "PLoS Medicine",
issn = "1549-1277",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Changes in resistance among coliform bacteraemia associated with a primary care antimicrobial stewardship intervention

T2 - a population-based interrupted time series study

AU - Hernandez Santiago, Virginia

AU - Davey, Peter

AU - Nathwani, Dilip

AU - Marwick, Charis Ann

AU - Guthrie, Bruce

PY - 2019/6/7

Y1 - 2019/6/7

N2 - BACKGROUND: Primary care antimicrobial stewardship interventions can improve antimicrobial prescribing, but there is less evidence that they reduce rates of resistant infection. This study examined changes in broad-spectrum antimicrobial prescribing in the community and resistance in people admitted to hospital with community-associated coliform bacteraemia associated with a primary care stewardship intervention. METHODS AND FINDINGS: Segmented regression analysis of data on all patients registered with a general practitioner in the National Health Service (NHS) Tayside region in the east of Scotland, UK, from 1 January 2005 to 31 December 2015 was performed, examining associations between a primary care antimicrobial stewardship intervention in 2009 and primary care prescribing of fluoroquinolones, cephalosporins, and co-amoxiclav and resistance to the same three antimicrobials/classes among community-associated coliform bacteraemia. Prescribing outcomes were the rate per 1,000 population prescribed each antimicrobial/class per quarter. Resistance outcomes were proportion of community-associated (first 2 days of hospital admission) coliform (Escherichia coli, Proteus spp., or Klebsiella spp.) bacteraemia among adult (18+ years) patients resistant to each antimicrobial/class. 11.4% of 3,442,205 oral antimicrobial prescriptions dispensed in primary care over the study period were for targeted antimicrobials. There were large, statistically significant reductions in prescribing at 1 year postintervention that were larger by 3 years postintervention when the relative reduction was -68.8% (95% CI -76.3 to -62.1) and the absolute reduction -6.3 (-7.6 to -5.2) people exposed per 1,000 population per quarter for fluoroquinolones; relative -74.0% (-80.3 to -67.9) and absolute reduction -6.1 (-7.2 to -5.2) for cephalosporins; and relative -62.3% (-66.9 to -58.1) and absolute reduction -6.8 (-7.7 to -6.0) for co-amoxiclav, all compared to their prior trends. There were 2,143 eligible bacteraemia episodes involving 2,004 patients over the study period (mean age 73.7 [SD 14.8] years; 51.4% women). There was no increase in community-associated coliform bacteraemia admissions associated with reduced community broad-spectrum antimicrobial use. Resistance to targeted antimicrobials reduced by 3.5 years postintervention compared to prior trends, but this was not statistically significant for co-amoxiclav. Relative and absolute changes were -34.7% (95% CI -52.3 to -10.6) and -63.5 (-131.8 to -12.8) resistant bacteraemia per 1,000 bacteraemia per quarter for fluoroquinolones; -48.3% (-62.7 to -32.3) and -153.1 (-255.7 to -77.0) for cephalosporins; and -17.8% (-47.1 to 20.8) and -63.6 (-206.4 to 42.4) for co-amoxiclav, respectively. Overall, there was reversal of a previously rising rate of fluoroquinolone resistance and flattening of previously rising rates of cephalosporin and co-amoxiclav resistance. The limitations of this study include that associations are not definitive evidence of causation and that potential effects of underlying secular trends in the postintervention period and/or of other interventions occurring simultaneously cannot be definitively excluded. CONCLUSIONS: In this population-based study in Scotland, compared to prior trends, there were very large reductions in community broad-spectrum antimicrobial use associated with the stewardship intervention. In contrast, changes in resistance among coliform bacteraemia were more modest. Prevention of resistance through judicious use of new antimicrobials may be more effective than trying to reverse resistance that has become established.

AB - BACKGROUND: Primary care antimicrobial stewardship interventions can improve antimicrobial prescribing, but there is less evidence that they reduce rates of resistant infection. This study examined changes in broad-spectrum antimicrobial prescribing in the community and resistance in people admitted to hospital with community-associated coliform bacteraemia associated with a primary care stewardship intervention. METHODS AND FINDINGS: Segmented regression analysis of data on all patients registered with a general practitioner in the National Health Service (NHS) Tayside region in the east of Scotland, UK, from 1 January 2005 to 31 December 2015 was performed, examining associations between a primary care antimicrobial stewardship intervention in 2009 and primary care prescribing of fluoroquinolones, cephalosporins, and co-amoxiclav and resistance to the same three antimicrobials/classes among community-associated coliform bacteraemia. Prescribing outcomes were the rate per 1,000 population prescribed each antimicrobial/class per quarter. Resistance outcomes were proportion of community-associated (first 2 days of hospital admission) coliform (Escherichia coli, Proteus spp., or Klebsiella spp.) bacteraemia among adult (18+ years) patients resistant to each antimicrobial/class. 11.4% of 3,442,205 oral antimicrobial prescriptions dispensed in primary care over the study period were for targeted antimicrobials. There were large, statistically significant reductions in prescribing at 1 year postintervention that were larger by 3 years postintervention when the relative reduction was -68.8% (95% CI -76.3 to -62.1) and the absolute reduction -6.3 (-7.6 to -5.2) people exposed per 1,000 population per quarter for fluoroquinolones; relative -74.0% (-80.3 to -67.9) and absolute reduction -6.1 (-7.2 to -5.2) for cephalosporins; and relative -62.3% (-66.9 to -58.1) and absolute reduction -6.8 (-7.7 to -6.0) for co-amoxiclav, all compared to their prior trends. There were 2,143 eligible bacteraemia episodes involving 2,004 patients over the study period (mean age 73.7 [SD 14.8] years; 51.4% women). There was no increase in community-associated coliform bacteraemia admissions associated with reduced community broad-spectrum antimicrobial use. Resistance to targeted antimicrobials reduced by 3.5 years postintervention compared to prior trends, but this was not statistically significant for co-amoxiclav. Relative and absolute changes were -34.7% (95% CI -52.3 to -10.6) and -63.5 (-131.8 to -12.8) resistant bacteraemia per 1,000 bacteraemia per quarter for fluoroquinolones; -48.3% (-62.7 to -32.3) and -153.1 (-255.7 to -77.0) for cephalosporins; and -17.8% (-47.1 to 20.8) and -63.6 (-206.4 to 42.4) for co-amoxiclav, respectively. Overall, there was reversal of a previously rising rate of fluoroquinolone resistance and flattening of previously rising rates of cephalosporin and co-amoxiclav resistance. The limitations of this study include that associations are not definitive evidence of causation and that potential effects of underlying secular trends in the postintervention period and/or of other interventions occurring simultaneously cannot be definitively excluded. CONCLUSIONS: In this population-based study in Scotland, compared to prior trends, there were very large reductions in community broad-spectrum antimicrobial use associated with the stewardship intervention. In contrast, changes in resistance among coliform bacteraemia were more modest. Prevention of resistance through judicious use of new antimicrobials may be more effective than trying to reverse resistance that has become established.

KW - family practice

KW - primary care

KW - antimicrobials

KW - antimicrobial resistance

KW - quality of healthcare

KW - interrupted time series

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U2 - 10.1371/journal.pmed.1002825

DO - 10.1371/journal.pmed.1002825

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VL - 16

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JO - PLoS Medicine

JF - PLoS Medicine

SN - 1549-1277

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