BiosecurityFragile supply chain causing antibiotic shortages, resistance threat

Published 1 June 2018

A white paper released yesterday argues that a fragile global supply chain that’s dependent on a small number of antibiotics manufacturers, along with a financially unstable economic model, are responsible for shortages of antibiotics on a global and national level. Because of these shortages, some patients in need of antibiotics are being treated with lower-quality medications that don’t cure their infections and increase the risk of resistance.

A new report is warning about an emerging crisis in the global antibiotic supply chain that’s causing antibiotic shortages and contributing to antimicrobial resistance (AMR).

In a white paper released yesterday, the Dutch nonprofit Access to Medicine Foundation argues that a fragile global supply chain that’s dependent on a small number of antibiotics manufacturers, along with a financially unstable economic model, are responsible for shortages of antibiotics on a global and national level. Because of these shortages, some patients in need of antibiotics are being treated with lower-quality medications that don’t cure their infections and increase the risk of resistance.

“Less effective or more toxic treatment alternatives can contribute to AMR because every time we use an antibiotic, we give bacteria the chance to adapt and develop resistance,” the authors write. “To reduce the threat of AMR, doctors must ensure that the right antibiotic is used against the right organism.”

The shortages highlighted in the report include the commonly prescribed benzathine penicillin G (BPG), which is the first-line therapy for syphilis and rheumatic heart disease. In 2015, BPG was unavailable in 39 out of 114 countries. The shortage coincided with a syphilis outbreak in Brazil that has led to a doubling of the babies born with congenital syphilis.

Meanwhile, a global shortage of the combination antibiotic piperacillin-tazobactam, which is used for a variety of infections and is on the World Health Organization’s essential medicines list, has forced clinicians to reserve the drug for more serious infections and increase their reliance on other antibiotics. In some cases, this has resulted in increasing use of powerful last-resorts drugs like meropenem. In other cases, the piperacillin-tazobacatm shortage has meant switching to antibiotics that can increase the risk of Clostridium difficile infections.
Supply chain can’t meet rising demand
CIDRAP notes that the shortages come at a time of rising antibiotic use. According to a recent study from the Center for Disease Dynamics, Economics & Policy, global antibiotic use grew by 65 percent from 2000 through 2015, driven largely by rising living standards in low- and middle-income countries. At the same time, however, because the market for antibiotics is less lucrative than it is for other drugs, there are fewer companies producing and developing antibiotics.

With fewer pharmaceutical companies in the antibiotic market, there are only a handful of manufacturing facilities, mainly in India and China, that are producing the active pharmaceutical ingredient (API) for antibiotics. This not only makes it hard for companies to respond to surges in demand for antibiotics, it also means that problems at a single manufacturing facility can cause worldwide shortages. The shortage of piperacillin-tazobactam, for example, was caused by an explosion at a Chinese manufacturing facility in 2016. The factory was the only facility producing the API needed for the drug.

The report warns that if pharmaceutical companies continue to leave the antibiotic market, there will be fewer API manufacturers, weakening the supply chain even further.

To address the issue in the short-term, the authors of the report argue that pharmaceutical companies must take steps to strengthen their supply chains. Citing examples of steps some vaccine makers have taken to address shortages, they say that supply chains can be bolstered by focusing on demand planning, which involves forecasting future demand for antibiotics using consumption data and epidemiological patterns and sharing that information with healthcare workers, government health ministries, and public health organizations. This can help ensure that the right quantities of antibiotics are being produced.

They also encourage pharmaceutical companies to use multiple manufacturers and procurement sources and improve stock management to ensure an uninterrupted supply of antibiotics, and to strengthen the distribution chain so that patients are getting the right drugs at the right time.

But in the long run, the report cautions, to get more companies commit to producing antibiotics and maintain a sufficient supply of affordable antibiotics, steps to improve the market for antibiotics are needed. These could include market entry rewards or other economic incentives to encourage new antibiotic development. “Without a competitive market, there will not only be more frequent shortages and quality issues, but the last few companies left in the market will have greater power to dictate prices,” the authors write.

This effort, they say, will require collaboration between the pharmaceutical companies, regulators, governments, public health officials, and other stakeholders.