Pretomanid prescribing across NHS England went from an average of 9 patients per month in early 2024 to 45 in the same period of 2025—a fivefold increase that didn’t happen by accident.
This narrative review from pharmacists and clinicians at Imperial College and Leeds Teaching Hospitals traces how the UK navigated the practical barriers to adopting shorter all-oral multidrug-resistant (MDR-TB) regimens. The evidence base—Nix, ZeNix, TB-PRACTECAL, BEAT-TB, endTB—has made a compelling case for 6 to 9 month bedaquiline-based regimens, with favorable outcomes ranging from roughly 84% to 93% across trial populations. These regimens are generally better tolerated than older injectable-containing approaches, though toxicity—particularly linezolid-related—still requires careful monitoring.
The authors focus on implementation: how health systems deliver these regimens when drugs are unlicensed, expensive, and supply-constrained, and when eligibility remains limited to specific patient groups.
In the UK, implementation relied on three components: expert case-by-case oversight and high-cost drug approval through a national clinical advice service; formal commissioning policy establishing a funded access pathway; and open-access drug-specific monitoring guidance to support safe prescribing. Together, these enable the use of shorter regimens—now preferred in eligible patients—while ensuring access, safety monitoring, and equitable delivery, which remain essential despite reduced treatment duration. As the authors put it: “Targeted therapeutics, standardised eligibility, shorter durations and a move to more evidence-based oral therapy with improved outcomes are now the mainstay of MDR-TB management.”
That infrastructure extends beyond pharmacology. The authors highlight how shorter regimens reduce pill burden, adverse events, and time on directly or video-observed therapy—freeing clinical capacity and improving adherence. They also emphasize the role of social policy: TB treatment is free regardless of immigration status, and national programs explicitly support vulnerable populations (e.g., people experiencing homelessness), where reducing treatment duration lowers the risk of interruption.
Limitations remain. No systematic active drug safety monitoring scheme currently exists in the UK, trial populations were largely non-UK, and certain TB lineages present in some patients may carry higher minimum inhibitory concentrations for pretomanid, with uncertain implications for efficacy.
For clinicians and health systems still operating under longer MDR-TB frameworks, this paper offers a concrete example of how shorter regimens can be implemented in practice: defined approval pathways, centralized specialist oversight, coordinated procurement for high-cost or unlicensed drugs, and standardized monitoring guidance. The UK model may not be directly transferable, but it illustrates the level of system design required to make these regimens work safely and equitably.
Disclosures can be found in the published Perspective.
Source: BMJ Open Respiratory Research
