Prompt UTI Antibiotics Cut Mortality, Sepsis Risk in Older Adults

Janis C. Kelly

March 01, 2019

Patients older than 65 years who have urinary tract infections (UTIs) are at increased risk for sepsis and death within 60 days from UTI if not treated with immediate antibiotic therapy. Those older than 85 are at particularly high risk if antibiotics are deferred or are not prescribed, researchers Myriam Gharbi, PharmD, MPH, PhD, and colleagues report in an article published online February 27 in the BMJ.

"Our findings suggest that GPs [general practitioners] consider early prescription of antibiotics for this vulnerable group of older adults in view of their increased susceptibility to sepsis after UTI and despite a growing pressure to reduce inappropriate antibiotic use. Particular care is needed for the management of older men and those in deprived communities," write Gharbi, who is with the National Institute for Health Research (NIHR) Health Protection Research Unit, Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, United Kingdom, and colleagues.

The researchers analyzed data from the National Health Service (NHS) Clinical Practice Research Datalink on more than 150,000 patients aged 65 years or older who had presented to a GP with at least one case of suspected or confirmed lower UTI from November 2007 to June 2015. There were more than 300,000 UTIs among these patients. Most cases were suspected on the basis of clinical symptoms because, as Alastair D. Hay, MD, notes in a linked editorial, real-time microbiology analysis is largely unavailable in primary care in the United Kingdom.

Of those patients, 86.6% received an antibiotic prescription at the initial consultation, 6.2% received antibiotics after a delay of 7 days, and 7.2% were not given antibiotics.

Patients older than 85 were much less likely than those aged 65 to 74 to receive antibiotics immediately (20.6% vs 45.2%).

"Patients older than 85 years, living in a deprived area, with a high Charlson comorbidity index score, were mainly managed using either deferred antibiotics or a no antibiotics approach, whereas patients aged between 65 and 74 years were mainly prescribed immediate antibiotics. The female:male ratio was also much higher in the immediate antibiotics group compared with the other groups," they write.

They found that the risk of developing sepsis within 60 days was sevenfold higher for UTI patients who received no antibiotics than for those treated immediately and was sixfold higher for those whose antibiotic treatment was delayed. Specifically, the incidence of sepsis was 0.2% with immediate antibiotics, 2.2% with delayed antibiotics (P > .001 vs immediate antibiotics), and 2.9% with no antibiotics.

The number-needed-to-harm estimate for bloodstream infections showed that on average, there would be one additional case for every 37 patients in the no-antibiotic group and one additional case for every 51 patients in the deferred-antibiotic group than would have occurred had antibiotics been given immediately.

In addition, hospital admission rates were roughly double for the no-antibiotics group and the deferred-antibiotics group vs the immediate-treatment group (27.0% vs 26.8% vs 14.8%; P = .001). Hospital length of stay was also longer: 12.1 days vs 7.7 days vs 6.3 days.

All-cause mortality within 60 days of index UTI diagnosis was 2.18 times higher for the no-antibiotic group and 1.16 times higher for the deferred-antibiotic group vs the immediate-treatment group. These mortality rates were 5.4%, 2.8%, and 1.6%, respectively (P < .001).

The researchers also found a small but significant increase in 60-day survival for patients treated immediately with nitrofurantoin vs trimethoprim.

The authors comment that the presence of mild urinary symptoms may encourage clinicians to withhold antibiotics in the context of a working diagnosis of UTI but that this may put patients at risk for severe consequences. "Results from this large population-based cohort study suggest a significant increase in the risk of bloodstream infection and all-cause mortality and the rate of hospital admission associated with no antibiotics and deferred antibiotics compared with immediate antibiotics in older adults with a diagnosis of UTI in primary care. Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men aged >85 years) should be recommended to prevent serious complications."

The study was performed in the context of the NHS push to reduce unnecessary antibiotic prescribing among primary care physicians, who account for 80% of prescriptions in the United Kingdom. Hay, from the Center for Academic Primary Care, Bristol Medical School, explains that this initiative has helped reduce primary care antibiotic prescribing by 13% in the past 5 years without increasing serious complications, such as sepsis. However, he warns that studies also highlight the challenge of providing the right treatment to the right patient at the right time.

Hay notes that the increased risk for sepsis in the no-antibiotic or deferred-antibiotic group might not be a direct result of treatment, however. He explains that physicians may be more cautious in treating infections in vulnerable patients, that a deferred prescription might be a sign of diagnostic uncertainty, and that "a significant proportion of bloodstream infections" in older patients are not caused by UTIs.

In primary care, 10,000 patients are likely to present with about 1800 UTI episodes but only one or two bloodstream infections per year. Hay concludes, "What are the implications for practice? Prompt treatment should be offered to older patients, men (who are at higher risk than women), and those living in areas of greater socioeconomic deprivation who are at the highest risk of bloodstream infections. Further research is needed to establish whether treatment should be initiated with a broad or a narrow spectrum antibiotic and to identify those in whom delaying treatment (while awaiting investigation) is safe."

The study was supported by the NIHR Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London in partnership with Public Health England and by the NIHR Biomedical Research Center at Guy's and St Thomas' NHS Foundation Trust and King's College London. Lead author Myriam Gharbi, PharmD, MPH, PhD, has worked as an epidemiologist at GlaxoSmithKline in therapeutic areas not related to the submitted work. The other authors of the study and Hay report no relevant financial relationships.

BMJ. Published online February 27, 2019. Full text, Editorial

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