Rising public health concerns on antibiotic overuse in India: The Lancet

Antibiotic resistance is a global health concern, making curing many infections expensive and impossible. The unwise use of antibiotics is driving antibiotic resistance in India. A study published in the Lancet mentions that broad-spectrum antibiotics like Azithromycin and Fixed-dose-combination (FDC), discouraged by WHO, are used excessively in India.

The data also shows a rising number of non-NLEM formulations and unapproved formulations. This is attributed to the unrestricted selling of over-the-counter (OTC) antibiotics and fixed-dose combinations (FDC). The overlapping regulatory powers between national and state-level agencies complicate drug availability, sale, and consumption. Indian states can provide market approval without Central Drugs Standard Control Organization (CDSCPO) approval, while the capacity of State Regulatory Drug Authorities (SDRA) is confined.

The study says that this public health concern requires urgent implementation of policy and regulatory reform. The Lancet Study is the first pioneer study based on such data from India.

The cross-sectional dataset was collected from January 1 till December 31. This included 9000 stockists from PharmaTrac to get details of 5000 pharmaceutical manufacturers and Tata 1 mg to get unavailable information from PharmaTrac. The study included AWaRe classification (Access, Watch, Reserve) and Defined Daily Dose (DDD) in calculating per capita private-sector consumption of systemic antibiotics. Four categories involved in the study were AWaRe groups, FDC vs. single formulations (product type), approved vs. unapproved (central regulatory status), and listed vs. not listed in NLEM (National List of Essential Medicines). R software was used to clean and analyze the data.

The study data and conclusive points are:

• The study included the JOI group of the WHO Anatomical Therapeutic Chemical (ATC) Classification system to classify systemic antibiotics and DDD of parenteral formulations. Topicals, ear, eye drops, gel, pessaries, and suppositories were excluded from the study.

• Worldwide antibiotic consumption increased by 36 % between 2000 and 2010, with 23 % of the retail sales volume from India due to poorly enforced regulations, the literature mentions.

• In 2019, 5071 million total DDDs were consumed. The consumption of 12 antibiotic molecules was high resulting in 75 % of the total consumption. Watch contributed 54.9 % DDD and Access contributed 27%. Azithromycin was the most consumed Watch antibiotic constituting 22.4 % of Watch antibiotics.

48.7 % of combinations were discouraged by the WHO.

• 77.1 % of the systemic antibiotics were sold in 2019, with eighty-five identified antibiotic molecules. Watch antibiotics constituted 72.7 % of unapproved products.

• The most consumed antibiotic was Azithromycin, 12.6 % with 640 million DDDs, followed by cefixime. The dosage was 500 mg for Azithromycin (7.6 %) and 200 mg for cefixime (6.5 %).

• 200 mg tablet of cefpodoxime, including 8.3 % of 215 million DDD was second most consumed after Cefixime-ofloxacin 200/200 mg tablet, outside the NLEM category.

• Reserve antibiotics are used as a last resort and reserved for treating extensive drug-resistant bacteria. The most consumed reserved antibiotic in 2019 was linezolid, with 41 million DDDs constituting 66.7 % of Reserve antibiotics.

• The most discouraged FDC used was cefixime-ofloxacin, constituting 42.4 % with 310 million DDDs.

• A market analysis of 2007-2012 shows that CDSCO did not approve a substantial proportion of antibiotics. The study data mentioned that 2408 million of total DDDs were accountable to 47.1 % of unapproved formulations. In this category, Cephalosporins (38.1%), Macrolides (31.7 %), and Penicillin (10.3%) were among the top three unapproved formulations.

• 60.9 % of single formulations were unapproved.

• 91.2 % of macrolides and 61.3 % of cephalosporins were in the category of those sold products, which the central agency did not approve.

• The study has evidenced the urgent need to strengthen policy measures and whack new efforts to reach the target of appropriate antibiotic use globally.

The main focus of the study says that Azithromycin was the most inappropriately used, so what is this related to? Is this due to inappropriate prescription or dispensing?

The data presented requires strict implementation and programs to dig deep into the present and upcoming major health crises. A study shows India has sold the highest number of non-US-FDA-approved antibiotics and incompatible combinations.

This study has broadened the aspect of research data. The four factors listed in the study are essential to identifying the extensive use of antibiotics in India.

The study's limitations include using adult dosage to calculate DDDs, data set to cover only the private sector and not the public, the data collection from the stockiest level limit the information on community and hospital use, and the appropriateness of the prescription at the patient group cannot be determined.

References:

2. Koya S, Ganesh S, Selvaraj S, Wirtz V, Galea S, Rockers P. Consumption of systemic antibiotics in India in 2019. The Lancet Regional Health - Southeast Asia. 2022;4:100025. doi:10.1016/j.lansea.2022.100025