Older patients have a higher risk of UTIs than younger patients, largely due to immunosenescence, but they are also more prone to the harms of antibiotic treatment, including adverse events, drug–drug interactions, and C. difficile infection, explains Bradley J. Langford, PharmD. “Assessing both the risks and benefits of antibiotics is particularly important in this population,” he adds. “UTIs are one of the most common infections leading to hospitalization. A common treatment strategy for recurrent UTI is the use of long-term antibiotic prophylaxis. However, despite antibiotic prophylaxis being associated with a reduced risk of recurrent UTI, this benefit is less certain in older adults and can pose certain health risks.”

For a paper published in Clinical Infectious Diseases, Dr. Langford and colleagues aimed to quantify the benefits and risks of antibiotic prophylaxis among older adults. They conducted a matched cohort study using linked administrative data on 3,190 adults aged 66 and older with a positive urine culture who received antibiotic prophylaxis; this group was compared with a similar group of 30,542 adults with a positive urine culture who did not receive prophylaxis.

Prophylaxis Linked With 1.3-Fold Increased Hospitalization Risk

Participants were followed for 1 year to determine hospitalization and emergency department (ED) visit rates for UTI, sepsis, or bloodstream infection, explains Nick Daneman, MD, MSc, senior author of the paper. The study team also looked for antibiotic-associated harms to assess whether patients experienced a drug-related adverse event or had a follow-up urine culture with an antibiotic-resistant organism.

The researchers were surprised to discover that antibiotic prophylaxis was associated with a 1.3-fold increase, not decrease, in the risk of hospitalizations or ED visits for infection. What they expected to be benefits were actually harms. The findings indicate that 4.7% of UTI prophylaxis patients and 3.6% of controls required an ED visit or hospitalization for UTI, sepsis, or bloodstream infection. “Since this was an observational study, there is always the possibility that this finding is due to underlying differences between the prophylaxis and non-prophylaxis patients,” Dr. Langford notes. “Because we matched UTI prophylaxis patients quite closely to controls, however, a more intriguing explanation may relate to the detrimental impact that antibiotics have on protective flora. It is possible that because antibiotic prophylaxis disrupts local gastrointestinal and vaginal flora, it may predispose patients to colonization with more pathogenic and/or more resistant strains of organisms.”

Risks of UTI Prophylaxis Underestimated in Elderly

“UTI prophylaxis recipients were at greater risk of several antibiotic-related harms, including antimicrobial resistance, adverse events, C. difficile, and candidiasis,” Dr. Daneman says. Antibiotic-associated harm occurred in 7.6% of patients receiving prophylaxis and 7.1% of non-prophylaxis controls. Notable harms included the risk of C. difficile infection and general medication adverse events, both of which were elevated in UTI prophylaxis recipients when compared with controls (Table).

Dr. Daneman believes that clinicians may have overestimated the benefits and underestimated the risks of UTI prophylaxis in older adults. “We hope that this study encourages clinicians to be more cognizant of potential harms of UTI antibiotic prophylaxis when deciding on treatment options,” he says, adding that findings of increased risk of antimicrobial resistance are also particularly important to highlight. “As shown in our study and in previous studies evaluating UTI prophylaxis, prolonged antibiotic use can create an environment conducive to antimicrobial-resistant organisms, which can make subsequent symptomatic episodes more difficult to treat and can lead to worse patient outcomes.”

Looking ahead, Dr. Langford and colleagues express the need for a large, randomized, controlled trial of older adults with symptomatic UTI that compares prophylaxis to no prophylaxis. “Given that our findings indicate increased risk of harm, it is important that such studies have an adequate sample size and duration of follow-up to assess infectious complications, as well as harms attributable to antibiotics, such as antimicrobial resistance,” he concludes.