Ceftazidime in combination with avibactam is a last-line antibiotic, to be used as a targeted therapy for certain carbapenem-resistant Gram-negative infections and not to be used as an empirical therapy. But the antibiotic recently lost its exclusivity and became a generic drug in India. And scientists from ICMR are foreseeing certain potential adverse implications of introducing generic versions of ceftazidime/avibactam into the Indian market.
It is known that whenever prices of life saving medications declined, it is able to reach the poor class population and benefit the patients. But when this happens in case of antibiotics, it may lead to excessive prescriptions and the risk of developing resistance.
In India, the utility of ceftazidime/avibactam as standalone is restricted to infections caused by susceptible OXA-48-like-producing Klebsiella pneumoniae or Escherichia coli as KPC- producers are rare. In other Low- and middle-income countries (LMICs), wherever KPCs are prevalent, ceftazidime/avibactam would find greater utility.
Ceftazidime/avibactam was initially registered with the U.S. FDA in 2015 and after 3 years it was approved in India. As of now, ceftazidime/avibactam is mostly available in the pharmacies of tertiary-care hospitals. After a span of 5 years, the antibiotic recently lost its exclusivity and became a generic drug in India.
Many pharmaceutical companies are set to introduce generic versions of ceftazidime/avibactam in India. When generic players aggressively market the drug, they will make it freely available even in pharmacies catering to primary- and secondary-care hospitals. Due to multiple sellers in the market, the cost of the drug is expected to fall. It is very likely that ceftazidime/avibactam will be available at a much cheaper cost in the near future compared to the innovator product.
The ICMR study which was published in Lancet Regional Health - Southeast Asia in May 2023, stated that in the past there have been reports elsewhere of the detection of acquired resistance to ceftazidime/avibactam among isolates which were initially susceptible to this drug. The existing widespread prevalence of MBL-producing isolates in India, they will be further enhanced by the indiscriminate use of ceftazidime/avibactam. The various resistance mechanisms found in the ceftazidime/avibactam-resistant isolates.
As per ICMR scientists, to limit the rampant use of valuable generic drugs, the government should control the supply chain of such antibiotics. There have been previous examples of this approach in India. For example, when the antivirals oseltamivir phosphate and zanamivir which are used to treat infections with influenza viruses were launched in India, manufacturing and distribution could not occur without approval from the drugs controller. Initially, these drugs were supplied directly to hospitals without any retail sales.
Recently, delamanid and bedaquiline have been approved under the revised national tuberculosis control programme for conditional access. 15 In order to prevent the overuse of these drugs which are indicated for treating multi-drug resistant tuberculosis(MDR-TB),the RNTCP manages the use of delamanid and bedaquiline through the programmatic management of drug resistant tuberculosis (PMDT) framework in alignment with the world health orga- nisation (WHO) consolidated guideline on drug- resistant tuberculosis treatment
Authors also suggested that, it is now time for all stakeholders concerned about the upcoming availability of generic version of ceftazidime/avibactam to actively educate the medical community on the need to only prescribe ceftazidime/ avibactam for the infections caused by confirmed OXA- 48-like-producing-Enterobacterales. Currently, recommendations to safeguard the use of new high-end antibiotics, when they are introduced into the Indian market, have not been implemented.
