Commonly used antibiotics may lead to heart problems

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Fluoroquinolone antibiotic use is linked with a higher than twofold risk of aortic and mitral regurgitation, risk being highest with current use followed by recent use., found a Canadian study.

Scientists have shown for the first time a link between two types of heart problems and one of the most commonly prescribed classes of antibiotics. In a study researchers at the University of British Columbia (UBC) in partnership with the Provincial Health Services Authority’s (PHSA) Therapeutic Evaluation Unit found that current users of fluoroquinolone antibiotics, such as Ciprofloxacin or Cipro, face a 2.4 times greater risk of developing aortic and mitral regurgitation, where the blood backflows into the heart, compared to patients who take amoxicillin, a different type of antibiotic. The greatest risk is within 30 days of use.

Recent studies have also linked the same class of antibiotics to other heart problems. Some physicians favour fluoroquinolones over other antibiotics for their broad spectrum of antibacterial activity and high oral absorption, which is as effective as intravenous, or IV, treatment.

“You can send patients home with a once-a-day pill,” said Mahyar Etminan, lead author and associate professor of ophthalmology and visual sciences in the faculty of medicine at UBC. “This class of antibiotics is very convenient, but for the majority of cases, especially community-related infections, they’re not really needed. The inappropriate prescribing may cause both antibiotic resistance as well as serious heart problems.”

The researchers hope their study helps inform the public and physicians that if patients present with cardiac issues, where no other cause has been discovered, fluoroquinolone antibiotics could potentially be a cause.

“One of the key objectives of the Therapeutic Evaluation Unit is to evaluate different drugs and health technologies to determine whether they enhance the quality of care delivered by our programs or improve patient outcomes,” said Dr Bruce Carleton, director of the unit and research investigator at BC Children’s Hospital, a programme of PHSA. “This study highlights the need to be thoughtful when prescribing antibiotics, which can sometimes cause harm. As a result of this work, we will continue working with the BC Antimicrobial Stewardship Committee to ensure the appropriate prescribing of this class of antibiotics to patients across British Columbia, and reduce inappropriate prescribing.”

For the study, scientists analysed data from the US Food and Drug Administration‘s adverse reporting system. They also analysed a massive private insurance health claims database in the US that captures demographics, drug identification, dose prescribed and treatment duration. Researchers identified 12,505 cases of valvular regurgitation with 125,020 case-control subjects in a random sample of more than 9m patients. They defined current fluoroquinolone exposure as an active prescription or 30 days prior to the adverse event, recent exposure as within days 31 to 60, and past exposure as within 61 to 365 days prior to an incident. Scientists compared fluoroquinolone use with amoxicillin and azithromycin.

The results showed that the risk of aortic and mitral regurgitation, blood backflow into the heart, is highest with current use, followed by recent use. They saw no increased risk aortic and mitral regurgitation with past use.

Etminan hopes that if other studies confirm these findings, regulatory agencies would add the risk of aortic and mitral regurgitation to their alerts as potential side effects and that the results would prompt physicians to use other classes of antibiotics as the first line of defence for uncomplicated infections.

This study was funded and conducted by the department of ophthalmology and the Therapeutic Evaluation Unit at the Provincial Health Services Authority.

Abstract
Background: Recent studies have linked fluoroquinolones (FQs) to cardiac adverse events, including aortic dissection and aneurysm. To date, whether FQs can increase the risk of aortic or mitral regurgitation has not been studied.
Objectives: This disproportionality analysis and case-control study examined whether FQs increase the risk of aortic and mitral regurgitation.
Methods: Data from the U.S. Food and Drug Administration’s adverse reporting system database was used to undertake a disproportionality analysis, and a random sample of 9,053,240 patients from the U.S. PharMetrics Plus database (IQVIA) was used for the matched nested case-control study. Current FQ exposure implied an active prescription at the index date or 30 days prior to the event date. Recent FQ exposure was defined as FQ use within days 31 to 60 and past within days 61 to 365 prior to the event date. Rate ratios (RRs) were compared to users of amoxicillin and azithromycin. Conditional logistic regression was used to compute RRs adjusting for confounders.
Results: The reported odds ratio for the disproportionality analysis was 1.45 (95% confidence interval [CI]: 1.20 to 1.77). A total of 12,505 cases and 125,020 control subjects were identified in the case-control study. The adjusted RRs for current users of FQ compared with amoxicillin and azithromycin users were 2.40 (95% CI: 1.82 to 3.16) and 1.75 (95% CI: 1.34 to 2.29), respectively. The adjusted RRs for recent and past FQ users when compared with amoxicillin were 1.47 (95% CI: 1.03 to 2.09) and 1.06 (95% CI: 0.91 to 1.21), respectively.
Conclusions: These results show that the risk of aortic and mitral regurgitation is highest with current use followed by recent use. No risk was observed with past use of FQs. Future studies are necessary to confirm or refute these associations.

Authors
Mahyar Etminan, Mohit Sodhi, Saeed Ganjizadeh-Zavareh, Bruce Carleton, Abbas Kezouh, James M Brophy

University of British Columbia material Journal of the American College of Cardiology abstract

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