Surge in infections leads to global shortage of antibiotics

A surge in bacterial infections after countries lifted pandemic restrictions has led to shortages of antibiotic drugs such as penicillin and amoxicillin, highlighting the precarious state of global supply chains.

Of the 35 countries whose data is collected by the WHO, 80 percent have some form of shortage of amoxicillin-related antibiotics, said Lisa Hedman, WHO group lead for supply and access to medicines. The UK introduced “serious shortage protocols” last week allowing pharmacists to prescribe alternative formulations of antibiotics after a rise in infections such as Group A streptococcus.

During the pandemic, lower demand for antibiotics, combined with severe strain on supply chains, led drugmakers to draw down production. But as many countries experience their first winter with no restrictions in two years, supply pressures and regulatory requirements are making it difficult for companies to scale up and ease the shortages, said health experts.

The shortages have also occurred because “countries did not anticipate that respiratory infections were going to hit us [so hard] in the first year without masks”, Hedman said.

Where have shortages been reported?

Shortages of amoxicillin have been reported in the US and Canada, while in the EU 25 out of 27 member states have reported scarce supplies of some antibiotics to the European Medicines Agency.

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

Although the volumes may be small compared with use in developed countries, they are far from inconsequential. Dušan Jasovský, pharmacist at aid group Médecins Sans Frontières, said an estimated 5.7mn people die annually through a lack of access to antimicrobials, which include antibiotics, antifungal and antiviral medicines.

A phial of intravenous antibiotics: shortages have been reported in the US, Canada and Europe © Gado/Getty Images

The fear of pushing prices higher acts as a “disincentive” to report shortages publicly and to the WHO, added Hedman.

Some US and European pharmacists have also reported shortages of common pain relief medicines such as paracetamol, as a winter wave of flu, respiratory syncytial virus (RSV) and Covid-19 cases fuels demand. Ilaria Passarani, secretary-general of the Pharmaceutical Group of the European Union, said drugs to treat infections such as tuberculosis and skin infections have also been affected.

What’s causing the shortfall?

Shortages of drugs, ranging from cancer medicines to anesthetics, were common at the height of Covid-19, highlighting the pressure on supply chains. The Ukraine war has further disrupted the supply of antibiotic ingredients, while rising energy costs have reduced margins for antibiotic manufacturers.

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

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

MSF’s Jasovský said depleted stocks of antibiotics were “minor symptoms” of a wider “systemic challenge” affecting the whole chain from wholesalers, final dose formulators and original manufacturers.

Line chart of Number showing The UK has increased medicines that cannot be exported or hoarded

Most of the world’s active pharmaceutical ingredients now come from India and China rather than Europe, he said. And there is “little transparency” regarding these materials because production processes worldwide are regarded as proprietary information only visible to regulators. That “makes it difficult to perform 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, executive director of UK-based wholesaler Sigma Pharmaceuticals, said additional regulatory checks meant that it took longer for drugmakers to reboot lines that were mothballed when production was scaled back during the pandemic.

Can the shortages be fixed?

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

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

Line chart of Number of medicines whose procurement costs have risen for UK government showing An increase in drug price spikes suggests more shortages

“You can’t just throw a few extra cakes into 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 one. . .[shortages]can take months to correct.”

The PGEU’s Passarani said solutions include forcing drugmakers seeking European authorization to market their drugs in all member states and creating a redistribution mechanism during a crisis.

Jasovský, the MSF pharmacist, said pooling mechanisms between countries, companies and multilateral organizations should be introduced and more should be done to diversify manufacturing capacities and improve transparency, data sharing and forecasting.

Do shortages risk increasing antimicrobial resistance?

Doctors often prescribe “narrow-acting” antibiotics to avert the emergence of superbugs that resist treatment — a growing phenomenon known as antimicrobial resistance. By targeting specific bacteria, the practice lowers the likelihood of infections becoming resistant to antibiotics.

But the unavailability of some antibiotics means that doctors and pharmacists are being 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’s essential medicines list, said it was typical for doctors to overprescribe antibiotics for mild infections in colder months, so the shortages are “leading to additional problems in terms of resistance”.

This risks what Moja calls prescription “inertia”, where some doctors find it difficult to return to prescribing specific antibiotics once the shortages ease, which threatens the proliferation of more intractable bugs.

Additional reporting by Jamie Smyth in New York

Video: Antibiotic resistance: a matter of time

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