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. Author summary Why was this study done? Sepsis is a severe reaction to an infection that may lead to life threatening damage to organ systems. Sepsis is an increasingly recognised concern for health professionals and patients in primary care. Inappropriate and unnecessary antibiotic prescribing is a widespread problem in primary care that may be contributing to antimicrobial resistance. This study aimed to estimate the probability of a patient developing sepsis after an infection consultation in primary care if antibiotics are or are not prescribed. What did the researchers do and find? We analysed the electronic health records of all registered patients at 706 general practices, with 66.2 million person-years of follow-up from 2002 to 2017 and 35,244 first episodes of sepsis. We found that 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. Frailty was associated with greater risk of sepsis and lower NNT. At all ages, the probability of sepsis was greatest for urinary tract infection, followed by skin infection, followed by respiratory tract infection. What do these findings mean? 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. Antibiotic use may be more safely reduced in groups with lower probability of sepsis. We caution that our results represent averages over diverse localities and years of study, and lack of random allocation to antibiotic therapy might have caused bias.