Rising infections cause global shortage of antibiotics

A rise in bacterial infections after countries lifted pandemic restrictions has caused shortages of antibiotics such as penicillin and amoxicillin, underscoring the precarious state of global supply chains.

Of the 35 countries whose data are collected by the WHO, 80% experience acute shortages of penicillin-related antibiotics, said Lisa Hedman, leader of the WHO group on supply and access to medicines. The UK adopted “severe shortage protocols” last week, allowing pharmacists to prescribe alternative formulations of antibiotics following a rise in infections such as group A streptococcus.

During the pandemic, lower demand for antibiotics, combined with severe pressure on supply chains, led drugmakers to reduce production. But as many countries experience their first unfettered winter in two years, supply pressures and regulatory requirements are making it difficult for companies to grow and address shortages, health experts said.

The shortage also occurred because “countries did not anticipate that respiratory infections would hit us [com tanta força] in the first year without masks,” said Hedman.

Where has the shortage been reported?

Amoxicillin shortages have been reported in the United States and Canada, while 25 of the 27 member states of the European Union have reported low supplies of some antibiotics to the European Medicines Agency.

The impact on poorer or smaller countries is less well known, but they could be disproportionately affected, especially if their currencies have depreciated and they need to buy drugs on the open market, Hedman said.

While the volumes may be small compared to use in developed countries, they are far from irrelevant. Dusan Jasovsky, a pharmacist for the aid group Doctors Without Borders, said that about 5.7 million people die annually from lack of access to antimicrobials, which include antibiotics, antifungals and antivirals.

Fear of price increases acts as a “disincentive” to report shortages publicly and to the WHO, Hedman added.

Some American and European pharmacists have also reported shortages of common pain-relieving drugs such as acetaminophen, as a winter flu wave, respiratory syncytial virus (RSV) and cases of Covid-19 increase demand. Ilaria Passarani, secretary general of the European Union Pharmaceuticals Group, said drugs to treat infections such as tuberculosis and skin infections were also affected.

What is causing the deficit?

Shortages of drugs, from cancer drugs to anesthetics, were common at the height of Covid-19, highlighting pressure on supply chains. The war in Ukraine further disrupted the supply of antibiotic ingredients, while rising energy costs squeezed its manufacturers’ margins.

Adrian van den Hoven, director general of the generic drug manufacturers’ association Medicines for Europe, said that after two years of lockdowns, it would have been difficult for antibiotic makers to accurately predict the increase in demand this winter for treatments such as antibiotic solutions. liquids for children.

“You can predict a higher infectious season, but you can’t predict the very high rate in children,” he said.

MSF’s Jasovsky said the reduced stocks of antibiotics are “minor symptoms” of a broader “systemic challenge” that affects the entire chain, from wholesalers, final dose formulators and original manufacturers.

Most of the world’s active pharmaceutical ingredients today come from India and China rather than Europe, he said. And there is “little transparency” around these materials because production processes around the world are considered proprietary information visible only to regulatory bodies. This “makes it difficult to carry out a true risk assessment to determine areas of greatest vulnerability,” he said.

The antibiotic supply chain can take between four and six months from production to distribution. But Rajiv Shah, chief executive of UK-based wholesaler Sigma Pharmaceuticals, said additional regulatory checks meant it took longer for drugmakers to restart lines that were shut down when production was reduced during the pandemic.

Can shortages be fixed?

Sandoz, one of the biggest makers of generic antibiotics, said it has increased drug production by a double-digit percentage in 2022, hiring 140 new people since September. Next year, it intends to do the same, opening a factory in Austria.

But the Novartis-owned company is being pressured by rising costs, which are harder to pass on in European markets, which cap drug prices, adding that its Asian competitors have access to cheaper fuel sources for the process of use. energy intensive. Costs for other essential ingredients have also skyrocketed, such as sugar for fermentation — an important part of the manufacturing process.

“You can’t just throw a few extra cakes in the oven,” said the WHO’s Hedman. “When you make an antibiotic, you have to shut down and revalidate your equipment before you make another… [a escassez] can take months to fix.”

Passarani of the PGEU said solutions include forcing drug manufacturers seeking European authorization to market their drugs in all member states and creating a redistribution mechanism during a crisis.

Jasovsky, the MSF pharmacist, said that pooling mechanisms between countries, companies and multilateral organizations must be adopted, and that more must be done to diversify manufacturing capabilities and improve transparency, data sharing and forecasting.

Does scarcity increase the risk of antimicrobial resistance?

Doctors often prescribe “narrow-acting” antibiotics to prevent the emergence of drug-resistant superbugs — a growing phenomenon known as antimicrobial resistance. By targeting specific bacteria, the practice reduces the likelihood of infections becoming immune to antibiotics.

But the unavailability of some antibiotics means doctors and pharmacists are allowed to dispense other classes of antibiotics with a broader range of action, which are usually reserved for infections that are not cured by first-line antibiotics.

Lorenzo Moja, a scientist working on the WHO essential medicines list, said it was common for doctors to overprescribe antibiotics for mild infections in the colder months, so shortages were “leading to additional problems in terms of resistance”.

This risks what Moja calls prescribing “inertia,” in which some doctors find it difficult to revert back to prescribing specific antibiotics when shortages decrease, threatening the proliferation of more difficult-to-treat microbes.

Collaborated with Jamie Smyth, in New York

Translated by Luiz Roberto M. Gonçalves