Macrolides are one of the most frequently prescribed antibiotic families for a variety of reasons, some of which (e.g., non-tuberculous mycobacterial infections and Helicobacter pylori infections) need months of therapy. While earlier studies have shown that macrolide usage may cause ototoxicity (hearing loss and tinnitus), the results have been inconsistent. As a result, prescribers seldom address these side effects when advising and monitoring patients on macrolides. Now, a new study confirms the link.

The study

In the Rotterdam Study, Vanoverschelde et al. conducted cross-sectional and longitudinal assessments of macrolide-related ototoxicity in 4286 and 636 individuals, respectively (begun in 1989 to examine the consequences of ageing). Blood pressure, diabetes, renal function, and the use of known ototoxic medicines were all included in the models, and macrolide exposure was classified by defined daily dose (DDD; median, 12) and duration.

Antibiotics classified as macrolides include erythromycin, roxithromycin, azithromycin, and clarithromycin. Tinnitus was linked to macrolides in a dose-dependent manner. Azithromycin and clarithromycin were the most often utilised antibiotics. Macrolide usage was linked to a 25% increase in the likelihood of tinnitus (P=0.006). Those who received >14 DDD, intermediate- and long-acting macrolides, and those who had daily rather than occasional tinnitus were at higher risk. There was no significant link between macrolide usage and hearing threshold or hearing loss in general, but the link between higher hearing thresholds and recent macrolide use was marginally significant (P=0.053).

Results

Long-term use of macrolide antibiotics is linked with long-term tinnitus (and potentially reversible hearing loss) via multifactorial processes. If extended macrolide treatment is anticipated, patients with a history of these side effects (e.g., older age, preexisting tinnitus or hearing loss, use of concurrent ototoxic medicines) should be advised to monitor for these symptoms. Future research should examine the effect of formal audiometry in macrolide users who have been taking the medication for an extended period of time.

The current status of the medicine in India

Due to chronic respiratory illnesses, India accounts for 32% of worldwide disability-adjusted life years. This has resulted in a high incidence of disease-related death. Antibiotics are often used to treat respiratory diseases. Macrolides are one of the best therapeutic choices for respiratory, urogenital, cutaneous, and other bacterial infections due to their good tissue penetration, extended tissue persistence, and benign side effect profile.

According to research company IQVIA, India sold 12 crore strips of the medication last year, which equates to about 60 crore pills (an average of 5 tablets a strip). The usage increased significantly in 2020 as a result of its claimed promise in the treatment of COVID.

Chronic respiratory illnesses are becoming more common in India, with COPD and asthma being the most prevalent. The kind and severity of the respiratory illness dictate the course of therapy. Antibiotics taken orally, such as macrolides, are extensively utilised as antibacterial agents and for their immunomodulatory properties.

Azithromycin and other macrolides are indicated for a variety of diseases, including COPD, asthma, and bronchiectasis. Prolonged azithromycin usage in individuals with chronic respiratory illnesses has also been associated with cardiovascular and otological toxicity, as well as the development of resistant bacteria.

Antibiotics of the macrolide class have been shown to increase the frequency of gastrointestinal side effects such as nausea, vomiting, abdominal discomfort, and diarrhoea. However, there is no indication that macrolides create an increased risk of heart problems, liver problems, or blood infections.

While macrolides are commonly used as first-line treatment for respiratory infections, there is worry that their prolonged usage may contribute to antimicrobial resistance. Additionally, frequent usage of macrolides such as azithromycin has been shown to have a substantial impact on the rates of antimicrobial resistance in a variety of microbiological agents.

While azithromycin is recommended, patients should have a thorough examination for cardiovascular risk factors and unusual microorganisms in the sputum. While data from RCTs and retrospective studies are available, there is an urgent need for trial data on azithromycin in the Indian population in order to provide better advice on the drug regimen and its usage in a variety of diseases.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.