Extensive TB Resistance Must Be Wake-Up Call for Europe
12 November 2025
Experts have told Medscape News Europe that extensively drug-resistant tuberculosis (XDR-TB) is emerging as a serious threat in Europe, describing it as a “quietly growing monster” that could undermine efforts to eradicate the disease.
The stakes are high: without rapid diagnostics, rigorous stewardship, and equitable access to key medicines, Europe risks losing the most effective tools it has against DR-TB.
Across the region, resistance is rising, just as shorter World Health Organization (WHO)-recommended regimens are being rolled out. Gaps in drug susceptibility testing, delays and access issues around key drugs, and uneven adoption of guidance are colliding with migration and procurement hurdles.
New evidence from Moldova points to early signs of an XDR-TB epidemic in Eastern Europe. Preserving the effectiveness of bedaquiline and other Group A drugs, experts say, will require rapid scale-up of targeted next-generation sequencing, strict antibiotic stewardship, and sustained investment in new medicines.
A recent retrospective study in The Lancet found that 1.7% of 11,004 patients with multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) across 16 countries in the WHO European Region between 2017 and 2023 had XDR-TB. Among the 188 patients with XDR-TB, 48.4%, 34.0%, and 17.6% were resistant to bedaquiline, linezolid, or both, respectively. Only 40% were successfully treated.
“These results are extremely concerning, as a pooled 40% success rate is comparable to the rate of spontaneous cure for tuberculosis from the pre-antibiotic era,” the authors wrote.
Guidelines Meet Real-World Gaps
In 2022, recognizing the changing landscape of drug resistance, the WHO recommended a 6-month regimen containing bedaquiline, linezolid, pretomanid, and moxifloxacin for MDR/RR-TB. A year earlier, it also recognized a new definition of pre-XDR-TB, underscoring the seriousness of evolving resistance.
But implementation has lagged in parts of Europe. Professor Christoph Lange, MD, PhD, medical director of the Research Center Borstel, Leibniz Lung Center, scientist at the German Center for Infection Research, and corresponding author of The Lancet study, told Medscape News Europe that resistance in the region is being driven by several factors, including the continued provision of standard regimens without drug-susceptibility testing.
“Since 2022, WHO has advocated for shorter treatment regimens, but there are problems in some countries to roll out these regimens,” he said.
“Sometimes TB programs wish to use old medicines in stock before buying new ones and some national experts are skeptical towards newly advocated treatment regimens if they lack experience.”
He added that another major issue has been the delayed rollout of pretomanid, a key component of the new short-course regimen. “Due to difficulties in the supply chain from different stakeholders, availability for pretomanid has still been difficult in many countries of the WHO European Region…But even when newer regimens hit the ground, there can still be a lack of drug susceptibility testing,” he said.
“The same mistakes that were done in the 90s — giving the same regimen to a population where some of the bacteria are resistant to one or more of the drugs — are now repeated in some places despite the availability of tools for adequate drug susceptibility testing.”
Eastern Europe’s Warning
A nationwide study from Moldova — a country with one of the highest MDR/RR-TB rates globally — provides evidence of high levels of resistance among patients with treatment failure. Among 1034 patients on treatment for MDR/RR-TB, 55 experienced treatment failure; of these, 75% carried fluoroquinolone-resistant strains, 40% showed bedaquiline resistance, and 38% were resistant to linezolid.
“If these emerging resistant strains continue to spread within the community, we may be witnessing the beginning of a new XDR-TB epidemic in Eastern Europe. Such a scenario could bring us back to the period when treatment success rates for MDR-TB were as low as around 40%, effectively erasing much of the progress made over the past decade,” lead author and Associate Professor Dumitru Chesov, MD, PhD, from the Department of Pneumology & Allergology at the Nicolae Testemițanu State University of Medicine and Pharmacy in Chisinau, Moldova, told Medscape News Europe.
“Although Moldova currently has a well-developed system for diagnosing DR-TB, including both classical, culture-based, and modern PCR-based molecular tests, these methods still have limitations. Specifically, they cannot detect early resistance to critical Group A drugs such as bedaquiline and linezolid. The only reliable method for identifying resistance to these drugs at present is targeted next-generation sequencing, which remains not available in routine practice in most of the high-burden DR-TB countries.”
“Expanding access to such technologies is essential to improve early detection and treatment outcomes.”
He stressed that doctors across Europe must be aware that “migration, cross-border healthcare access, and delayed diagnosis can facilitate the regional spread of resistant strains.”
“Clinicians should maintain a high index of suspicion for resistance, especially in patients with prior TB treatment, poor clinical response, or links to high-burden regions,” he added.
Lange said resistance to bedaquiline was of particular concern, as it was the best yet available drug.
For patients in Moldova and other parts of the region affected by XDR-TB, he said, “Patients are most often left with an inadequate number of active drugs to achieve cure. These XDR-TB bacteria can be compared to biological weapons.”
“If we act immediately, it’s not too late. But someone needs to turn the switch on. One of the actions that should be immediately taken is a rollout of targeted next-generation sequencing to guide the design of individualized treatment regimens. Each patient affected by TB has the right to be treated with a sufficient number of active medicines. This must become a public health priority.”
Access and Cost Barriers
Lucica Ditiu, MD, MPH, executive director of the Stop TB Partnership, said both studies indicated “what several people have been worried about: the quietly growing monster.” “The findings in Moldova with resistance to bedaquiline are not big, but this can lead to us losing our best drugs for treating DR-TB. If we, by negligence, allow people to develop resistance to bedaquiline, we will have a bug that is spreading through air that will be extremely, extremely drug-resistant because the options to treat it are drastically reduced. The risks are numerous,” she told Medscape News Europe.
“This is a clear sign of the deterioration of the management of DR-TB. We need to ensure that when you start treatment, you start with the right drugs. You need the resistance profile. The entire management of the patient should be perfect, which is something we can only dream about right now.”
She said Eastern European countries were of most concern given their high number of MDR-TB cases but added that their systems to test, diagnose, and treat with newer drugs are better than those in other parts of the world — including some countries in Western Europe.
“Some parts of Western Europe surprisingly have less access to new drugs than in Eastern Europe and that’s because the EU has very stringent procurement and the cost of drugs are prohibitive,” Ditiu said. “The manufacturers who provide drugs to Eastern Europe give concessional prices that are not the same for the EU, so that’s why, for example, bedaquiline can cost up to 15 times more elsewhere. It’s a problem.”
Olha Konstantynovska, MD, PhD, associate professor in the Department of Infectious Diseases and Clinical Immunology at V.N. Karazin Kharkiv National University, Kharkiv, Ukraine, agreed, adding that many European countries were not prepared to meet the health needs of refugees from Ukraine, where TB is a major problem.
“In Ukraine, we’re working with new treatment regimens, but in many other European countries it’s not available. Many Ukrainian patients have no opportunity to continue their treatment abroad and have to return to Ukraine to do so. Any break in a treatment regimen is problematic.”
For now, Lange said the priorities, alongside a rapid rollout of targeted next-generation sequencing, are advancing the 20 novel medicines currently in development and building an antibiotic stewardship framework for DR-TB to prevent the emergence and selection of further resistance.
“We’re burning through the best medicine we’ve ever had to treat DR-TB. I wouldn’t be surprised if we looked in more detail in countries that have been using bedaquiline for a while that there’s more resistance. It’s not too late to dramatically slow this down.”
Lange, Chesov, Ditiu, and Konstantynovska reported no relevant financial relationships.
By Sophie Cousins
Source: Medscape
