Abstract

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. 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. 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.

Highlights

  • The threat of antimicrobial drug resistance (AMR) is attracting the concern of national governments and international organisations [1]

  • Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following urinary tract infection (UTI)

  • These results show that risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following urinary tract infections

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Summary

Introduction

The threat of antimicrobial drug resistance (AMR) is attracting the concern of national governments and international organisations [1]. Antibiotic-resistant infections are increasing and are more often identified in primary care as well as hospital settings. Respiratory tract infections (RTIs) represent the most common reason for antibiotic treatment [2], with general practitioners prescribing antibiotics at about half of the consultations for ‘selflimiting’ RTIs, including common colds, acute cough and bronchitis, sore throat, otitis media, and rhinosinusitis [3], with little change over the last 2 decades [4,5]. The UK government has developed a 5-year antimicrobial resistance strategy that identifies reducing unnecessary antibiotic prescribing and improving antibiotic selection as key elements of antimicrobial stewardship [8,9]. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed

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