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Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002–2017: Population-based cohort study and decision analytic model

Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002–2017: Population-based cohort study and decision analytic model
Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002–2017: Population-based cohort study and decision analytic model
Background
Efforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed.

Methods and findings
We conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57–82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0–4 years old, the NNT was 29,773 (95% UI 18,458–71,091) in boys and 27,014 (16,739–65,709) in girls; over 85 years old, NNT was 262 (236–293) in men and 385 (352–421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55–64 years, the NNT was 247 (156–459) in men and 343 (234–556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65–74 years, the NNT following RTI was 1,257 (1,112–1,434) in men and 2,278 (1,966–2,686) in women; the NNT following skin infection was 503 (398–646) in men and 784 (602–1,051) in women; following UTI, the NNT was 121 (102–145) in men and 284 (241–342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period.

Conclusions
These stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs.
1549-1277
1-17
Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Moore, Michael
1be81dad-7120-45f0-bbed-f3b0cc0cfe99
Gulliford, Martin C.
5c557aa2-db12-43a2-8778-eac74cf42138
Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Moore, Michael
1be81dad-7120-45f0-bbed-f3b0cc0cfe99
Gulliford, Martin C.
5c557aa2-db12-43a2-8778-eac74cf42138

Little, Paul, Moore, Michael and Gulliford, Martin C. (2020) Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002–2017: Population-based cohort study and decision analytic model. PLoS Medicine, 17 (7), 1-17, [e1003202]. (doi:10.1371/journal.pmed.1003202).

Record type: Article

Abstract

Background
Efforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed.

Methods and findings
We conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57–82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0–4 years old, the NNT was 29,773 (95% UI 18,458–71,091) in boys and 27,014 (16,739–65,709) in girls; over 85 years old, NNT was 262 (236–293) in men and 385 (352–421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55–64 years, the NNT was 247 (156–459) in men and 343 (234–556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65–74 years, the NNT following RTI was 1,257 (1,112–1,434) in men and 2,278 (1,966–2,686) in women; the NNT following skin infection was 503 (398–646) in men and 784 (602–1,051) in women; following UTI, the NNT was 121 (102–145) in men and 284 (241–342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period.

Conclusions
These stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs.

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PMEDICINE-D-20-01208_R3_23 June 2020 - Accepted Manuscript
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Accepted/In Press date: 25 June 2020
Published date: 23 July 2020

Identifiers

Local EPrints ID: 442986
URI: http://eprints.soton.ac.uk/id/eprint/442986
ISSN: 1549-1277
PURE UUID: 5dafe959-bb15-4e5c-ac1e-26f5ef454f39
ORCID for Michael Moore: ORCID iD orcid.org/0000-0002-5127-4509

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Date deposited: 05 Aug 2020 16:30
Last modified: 10 Jan 2022 02:49

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Contributors

Author: Paul Little
Author: Michael Moore ORCID iD
Author: Martin C. Gulliford

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