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Early antibiotics for elderly with UTI linked to reduced sepsis risk

Prescribing antibiotics immediately for elderly patients with urinary tract infections is linked with a reduced risk of sepsis and death, compared with patients who receive antibiotics in the days following diagnosis, or none at all. These are the latest findings from researchers at Imperial College London and Public Health England.

The research team say the results provide further evidence to help GPs make clinical decisions about when to prescribe antibiotics immediately for a urinary tract infections (UTI) and when to defer treatment to see if symptoms improve on their own, to avoid overuse of antibiotics.

In the research, funded by the National Institute for Health Research, the team looked at records from 157,264 patients over the age of 65 across England who had been diagnosed by their GP with a suspected or confirmed UTI. Patients had been prescribed antibiotics immediately (87% of cases studied in the research), had antibiotics delayed by up to 7 days (6% of cases), or received no antibiotics at all (7% of cases).

Of the patients who received antibiotics immediately, 0.2% developed sepsis within the following 60 days. After taking into account available information about differences in age, gender, pre-existing illness and other personal characteristics, the results revealed that compared with patients who received antibiotics immediately, patients who had their antibiotic prescription delayed or received no antibiotics at all were up to eight times more likely to develop sepsis.

The research also revealed that 1.6% of patients who received antibiotics immediately died in the following 60 days. The risk of death over the same time period among patients who had their antibiotic prescription delayed showed a slight increase (16%), while patients who received no antibiotics had over double the risk.

The researchers estimated that, on average, for every 37 patients exposed to no antibiotics and for every 51 patients exposed to deferred antibiotics, one case of sespis would occur that would not have been seen with immediate antibiotics. They also found that the rate of hospital admissions roughly doubled (27%) in patients with either no or deferred antibiotic prescriptions, compared with those receiving immediate prescriptions (15%).

Older men, especially those aged over 85 years, and those living in more deprived areas were found to be most at risk.

The researchers stress this study only shows delayed antibiotics are associated with an increased risk of sepsis and death, rather than causing it directly. They add that patients may also have had other health conditions that the researchers weren't able to account for, which may have contributed to their increased risk of sepsis or death.

Lead author Dr Myriam Gharbi, from Imperial's School of Public Health, said: "Current national guidelines for GPs recommend they should ask patients about the severity of their symptoms, discuss possible self-care, such as drinking plenty of water to avoid dehydration and taking paracetamol or ibuprofen for pain relief, and consider a back-up antibiotic prescription to be used if symptoms worsen or have not improved after 48 hours. This is to avoid antibiotic overuse, as sometimes UTIs can get better without medication. However, our research suggests antibiotics should not be delayed in elderly patients."

UTIs are common in the elderly and may trigger symptoms such as pain when urinating, or needing to use the loo more often. UTIs are most commonly caused by E. coli bacteria, and if not treated the bacteria can trigger blood poisoning. However, doctors are increasingly concerned about the rise in antibiotic resistance. UTIs are the second most common diagnosis for which antibiotics are prescribed in the UK.

Therefore, to help clarify when antibiotics should be prescribed to the elderly with UTIs, the research team studied data from 157,264 patients aged 65 or above diagnosed with a UTI or suspected UTI, between 2007 and 2015. The data was from the Clinical Practice Research Datalink, which uses anonymised patient data from both GP practices linked to hospital data, allowing the same patients to be tracked between the two settings. The average age of the patients in the study was 77 years old.

Professor Paul Aylin, senior author of the research from the NIHR Health Protection Unit at Imperial, said: "Although antibiotic prescribing must be controlled to help combat the increasing problem of antibiotic resistance, our study suggests early use of antibiotics in elderly patients with UTIs is the safest approach."

Professor Alan Johnson from Public Health England who collaborated on the research said: "Antibiotic resistance is a major threat to public health that is being driven by the overuse of antibiotics. Current recommendations suggest healthcare professionals take a number of different factors into account when deciding whether to prescribe antibiotics immediately or consider deferring antibiotics for patients with a suspected urinary tract infection. This study highlights the importance of taking age into account when making clinical decisions about antibiotic prescribing in order to reduce the risk of complications. This work will help doctors target antibiotic use more effectively and improve patient wellbeing."

Objective: To evaluate the association between antibiotic treatment for urinary tract infection (UTI) and severe adverse outcomes in elderly patients in primary care.
Design: Retrospective population based cohort study.
Setting Clinical Practice Research Datalink (2007-15) primary care records linked to hospital episode statistics and death records in England.
Participants: 157 264 adults aged 65 years or older presenting to a general practitioner with at least one diagnosis of suspected or confirmed lower UTI from November 2007 to May 2015.
Main outcome measures: Bloodstream infection, hospital admission, and all cause mortality within 60 days after the index UTI diagnosis.
Results: Among 312 896 UTI episodes (157 264 unique patients), 7.2% (n=22 534) did not have a record of antibiotics being prescribed and 6.2% (n=19 292) showed a delay in antibiotic prescribing. 1539 episodes of bloodstream infection (0.5%) were recorded within 60 days after the initial UTI. The rate of bloodstream infection was significantly higher among those patients not prescribed an antibiotic (2.9%; n=647) and those recorded as revisiting the general practitioner within seven days of the initial consultation for an antibiotic prescription compared with those given a prescription for an antibiotic at the initial consultation (2.2% v 0.2%; P=0.001). After adjustment for covariates, patients were significantly more likely to experience a bloodstream infection in the deferred antibiotics group (adjusted odds ratio 7.12, 95% confidence interval 6.22 to 8.14) and no antibiotics group (8.08, 7.12 to 9.16) compared with the immediate antibiotics group. The number needed to harm (NNH) for occurrence of bloodstream infection was lower (greater risk) for the no antibiotics group (NNH=37) than for the deferred antibiotics group (NNH=51) compared with the immediate antibiotics group. The rate of hospital admissions was about double among cases with no antibiotics (27.0%) and deferred antibiotics (26.8%) compared with those prescribed immediate antibiotics (14.8%; P=0.001). The risk of all cause mortality was significantly higher with deferred antibiotics and no antibiotics than with immediate antibiotics at any time during the 60 days follow-up (adjusted hazard ratio 1.16, 95% confidence interval 1.06 to 1.27 and 2.18, 2.04 to 2.33, respectively). Men older than 85 years were particularly at risk for both bloodstream infection and 60 day all cause mortality.
Conclusions: In elderly patients with a diagnosis of UTI in primary care, no antibiotics and deferred antibiotics were associated with a significant increase in bloodstream infection and all cause mortality compared with immediate antibiotics. In the context of an increase of Escherichia coli bloodstream infections in England, early initiation of recommended first line antibiotics for UTI in the older population is advocated.

Myriam Gharbi, Joseph H Drysdale, Hannah Lishman, Rosalind Goudie, Mariam Molokhia, Alan P Johnson, Alison H Holmes, Paul Aylin

[link url=""]Imperial College London material[/link]
[link url=""]BMJ abstract[/link]
[link url=""]BMJ editorial[/link]

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