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Research

PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship: a retrospective sentinel network cohort study

Simon de Lusignan, Mark Joy, Julian Sherlock, Manasa Tripathy, Oliver van Hecke, Kome Gbinigie, John Williams, Christopher Butler and FD Richard Hobbs
BJGP Open 2021; 5 (5): BJGPO.2021.0087. DOI: https://doi.org/10.3399/BJGPO.2021.0087
Simon de Lusignan
1 Professor of Primary Care & Clinical Informatics, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
MSc, MD(Res), FRCGP
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  • ORCID record for Simon de Lusignan
  • For correspondence: simon.delusignan{at}phc.ox.ac.uk
Mark Joy
2 Senior Researcher, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
MSc, PhD
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  • ORCID record for Mark Joy
Julian Sherlock
3 SQL Developer, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
BA
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  • ORCID record for Julian Sherlock
Manasa Tripathy
4 Research Officer/Practice Liaison Officer, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
BSc (Hons), MSc
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  • ORCID record for Manasa Tripathy
Oliver van Hecke
5 NIHR Academic Clinical Lecturer, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
MBChB (Pret), DMJ (Clin), MRCGP, FRACGP, DPhil
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Kome Gbinigie
6 GP and DPhil Student, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
MA(Cantab), MB BChir, MRCGP, DRCOG, DfSRH, PGCert(Health Research)
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John Williams
7 Senior Research Fellow, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
MBBChir, FRCGP, MSc
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Christopher Butler
8 Professor of Primary Care, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
BA, MBChB, DCH, CCH MD, FRCGP (Hon), FFPH, FMedSci
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FD Richard Hobbs
9 Head of Department, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
CBE, FMedSci, FRCGP, FRCP (London), FESC, FRCP (Edin), MA (Ox)
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  • For correspondence: richard.hobbs{at}phc.ox.ac.uk
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  • Figure 1.
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    Figure 1. Prescribing of azithromycin (Figure 1A) and doxycycline (Figure 1B) by month within the Research and Surveillance Centre. The 2020 prescription of both antibiotics (azithromycin = blue line, square markers; doxycycline = yellow line, square markers) was very similar in January and February to 2019 rates (azithromycin = green line, diamond markers; doxycycline = orange line; diamond markers). In March 2020, there was a peak of prescribing for both antibiotcs, coincident with the first wave of the COVID-19 pandemic. Thereafter azithromycin was prescribed in 2020 at or above the level in 2019, whereas doxycycline was prescribed less.

    Azith = azithromycin. Doxy = doxycycline. Px = prescribing.

  • Figure 2.
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    Figure 2. Comparison of monthly incidence of consultations for lower respiratory tract infections (Figure 2A), upper respiratory tract infections (Figure 2B), and influenza-like illness (Figure 2C), comparing 2020 with 2019 in the Research and Surveillance Centre dataset. There was a lower incidence of LRTI and URI in 2020 compared with 2019, with a small peak when pupils returned to school in September 2020. ILI peaked with the first wave of the COVID-19 pandemic, and also with the return to school.

    ILI = influenza-like illness. RTI = lower respiratory tract infections. URTI = upper respiratory tract infections.

  • Figure 3.
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    Figure 3. Monthly pattern of azithromycin (Figure 3A) and doxycycline (Figure 3B) prescription counts, for 2019 and 2020. OpenPrescribing data are only available up to October 2020.

    Azith = azithromycin. Doxy = doxycycline. RCGP RSC = Royal College of General Practitioners Research and Surveillance Centre.

Tables

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    Table 1. Comparison of rates of prescription of doxycycline and azithromycin in 2020 with 2019. In people aged ≥65 years there was a decrease in doxycycline use but an increase in azithromycin prescription. Lower respiratory tract infection and upper respiratory tract infection incidence fell across all age bands and both sexes. Influenza-like illness was much more similar between years.
    Age, years20192020
    FemaleMaleFemaleMale
    Antibiotic rates per 100000 patients (95% CI) Doxy.<1621.74(20.4 to 23.2)17.75(16.5 to 19.0)19.12(17.8 to 20.5)15.96(14.8 to 17.2)
    16–64385.28(382.1 to 388.5)231.99(229.6 to 234.4)380.15(377.8 to 383.3)222.57(220.2 to 224.9)
    ≥651136.15(1126.4 to 1145.9)1038.78(1028.6 to 1048.9)968.28(959.3 to 977.3)913.57(904.1 to 923.1)
    Azith.<1656.89(54.6 to 59.2)67.50(65.1 to 69.9)53.29(51.1 to 55.5)75.91(73.4 to 78.5)
    16–6470.02(68.7 to 71.4)39.39(38.4 to 40.4)70.69(69.4 to 72.1)40.77(39.8 to 41.8)
    ≥65305.17(300.1 to 310.3)288.43(283.1 to 293.9)339.13(333.8 to 344.5)307.59(302.1 to 313.2)
    Respiratory disease rates per 100000 patients (95% CI) LRTI <16229.25(224.67 to 233.82)292.18(287.1 to 297.2)68.43(65.9 to 70.9)90.9(88.1 to 93.8)
    16–64191.30(189.1 to 193.54)126.84(125.0 to 128.6)81.45(79.9 to 82.9)53.2(52.0 to 54.4)
    ≥65609.27(602.05 to 616.5)568.32(560.8 to 575.8)267.9(263.2 to 272.8)268.0(262.9 to 273.2)
    URTI <161320.33(1309.5 to 1331.3)1349.86(1339.1 to 1360.7)485.15(455.0 to 467.7)493.1(486.6 to 499.7)
    16–64485.65(482.1 to 489.2)229.3(226.9 to 231.8)265.73(254.9 to 260.1)117.38(115.7 to 119.1)
    ≥65285.17(280.3 to 290.1)208.6(204.1 to 213.2)148.01(144.5 to 151.6)104.61(101.4 to 107.9)
    ILI <1619.30(17.1 to 19.7)20.78(19.5 to 22.2)16.38(15.2 to 17.7)16.23(15.1 to 17.5)
    16–6432.57(30.8 to 32.6)22.15(21.4 to 22.9)37.68(36.7 to 38.7)21.86(21.1 to 22.6)
    ≥6525.40(28.2 to 31.7)22.18(20.7 to 23.7)29.41(27.9 to 31.0)24.38(22.9 to 25.9)
    • a95% confidence intervals. Azith = azithromycin. Doxy = doxycycline. ILI = influenza-like illness. LRTI = lower respiratory tract infections. URTI = upper respiratory tract infections.

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    Table 2. Model reporting the incident rate ratio (IRR) comparing prescribing of azithromycin in 2020 with 2019. Taking the variables in the model into account there was a 22% increase, with people aged ≥65 years, female sex, the most deprived, northern regions and people with lower respiratory tract infections and upper respiratory tract infections all being associated with a higher rate of prescribing.
    Azithromycin prescribing ratescomparing 2020 with 2019IRRLowerUpperP
    95% CI95% CI
    Year 2020 (reference level: 2019)1.221.191.26<0.0001
    Age band (reference level: 0–15)
     16–640.710.680.73<0.0001
     ≥ 65 4.774.584.98<0.0001
     Sex (reference level: F)0.910.880.93<0.0001
    IMD quintile (reference level: Q1, most deprived)
     Q20.900.860.94<0.0001
     Q30.870.830.90<0.0001
     Q40.750.720.78<0.0001
     Q5 (least deprived)0.670.640.70<0.0001
    NHS region (reference: London)
     The Midlands and East 1.081.031.12<0.0001
     North East and Yorkshire1.471.401.54<0.0001
     North West1.131.081.18<0.0001
     South East0.940.890.98<0.0001
     South West0.720.690.76<0.0001
    Respiratory disease
     LRTI count1.00511.00431.0058<0.0001
     URTI count1.00301.00261.0035<0.0001
     ILI count1.00170.99821.00530.3400
    • ILI = influenza-like illness. IMD = Index of Multiple Deprivation. LRTI = lower respiratory tract infections. URTI = upper respiratory tract infections.

    • View popup
    Table 3. Azithromycin prescribing in cases of COVID-19. For each unit rise in COVID-19 cases there has been a 3% rise in azithromycin prescriptions. Aged ≥65 years, female sex, being more deprived, northern regions, lower respiratory tract infections or influenza-like-illness infections are all associated with a higher rate of prescribing.
    Azithromycin prescribing rateIRRLowerUpperP
    95% CI95% CI
    COVID-19 confirmed count1.031.021.03<0.0001
    Age band (reference level: 0–15)    
     16–640.250.200.31<0.0001
     ≥6510.958.6713.83<0.0001
     Sex (reference level: F)0.540.450.65<0.0001
    IMD quintile (reference level: Q1 most deprived)
     Q20.540.410.72<0.0001
     Q30.410.310.55<0.0001
     Q40.540.410.72<0.0001
     Q5 (least deprived)0.660.500.880.0048
    NHS region (reference: London)
     The Midlands and East5.734.287.69<0.0001
     North East and Yorkshire12.889.1818.07<0.0001
     North West10.317.3414.49<0.0001
     South East2.822.013.96<0.0001
     South West1.411.011.980.0453
    Respiratory disease
     LRTI count1.941.921.97<0.0001
     URTI count0.890.880.90<0.0001
     ILI count1.601.541.68<0.0001
    • ILI = influenza-like-illness. IMD = Index of Multiple Deprivation. LRTI = lower respiratory tract infections. URTI = upper respiratory tract infections.

Supplementary Data

  • BJGPO.2021.0087_Supp.pdf -

    Supplementary material is not copyedited or typeset, and is published as supplied by the author(s). The author(s) retain(s) responsibility for its accuracy.

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PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship: a retrospective sentinel network cohort study
Simon de Lusignan, Mark Joy, Julian Sherlock, Manasa Tripathy, Oliver van Hecke, Kome Gbinigie, John Williams, Christopher Butler, FD Richard Hobbs
BJGP Open 2021; 5 (5): BJGPO.2021.0087. DOI: 10.3399/BJGPO.2021.0087

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PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship: a retrospective sentinel network cohort study
Simon de Lusignan, Mark Joy, Julian Sherlock, Manasa Tripathy, Oliver van Hecke, Kome Gbinigie, John Williams, Christopher Butler, FD Richard Hobbs
BJGP Open 2021; 5 (5): BJGPO.2021.0087. DOI: 10.3399/BJGPO.2021.0087
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Keywords

  • primary health care
  • COVID-19
  • clinical trial
  • pandemics
  • medical records systems, computerized
  • antimicrobial stewardship

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