Drug-resistant tuberculosis: how it is diagnosed and treated in the UK

The NHS describes tuberculosis (TB) as an infection that usually affects the lungs and can be treated with antibiotics, but can be serious if not treated. Standard treatment, according to the NHS, is to take antibiotics, usually for at least 6 months. In drug-resistant TB, the bacteria are no longer killed by one or more of those standard medicines.

NICE's guideline on tuberculosis separates resistance into groups. Multidrug-resistant TB is covered in its own set of recommendations, and the guideline also covers drug-resistant TB that is resistant to a single drug, and extensively drug-resistant TB. Resistance to rifampicin, one of the key TB medicines, is the marker NICE uses to trigger a multidrug-resistant pathway.

Drug resistance is important because it changes the treatment plan, the length of treatment, how closely a person is monitored and the infection control measures used in hospital.

NHS inform explains that it is important to take TB antibiotics correctly and until the course is completed, even if you feel better. If treatment is stopped early or a dose is skipped, the TB infection may become resistant to the antibiotics and the infection could return. The NHS gives the same message: if treatment is stopped early, TB could come back.

NICE lists risk factors for multidrug resistance that prompt rapid testing: a history of previous TB drug treatment, particularly if there was known to be poor adherence to that treatment, contact with a known case of multidrug-resistant TB, and birth or residence in a country where the World Health Organization reports that a high proportion (5% or more) of new TB cases are multidrug-resistant. These describe circumstances in which testing is offered, not a judgement about the person.

Symptoms of drug-resistant TB are the same as those of ordinary TB. The NHS says symptoms usually come on gradually and common symptoms include a cough that lasts more than 3 weeks, which may bring up mucus or mucus with blood in it, feeling tired all the time, a high temperature or night sweats, loss of appetite, losing weight without trying and feeling generally unwell.

The NHS advises seeing a GP if you have had a cough for more than 3 weeks, feel tired for no reason, have a high temperature or night sweats that do not go away or keep losing weight, or have spent a lot of time with someone who has TB and symptoms. It advises asking for an urgent GP appointment or getting help from NHS 111 if you are coughing up blood. It says to call 999 or go to A&E for a stiff neck and severe headache, pain on looking at bright lights, a seizure, a change in behaviour such as sudden confusion, or weakness or loss of movement in part of the body, because these could be signs that TB has spread to the brain.

The NHS lists tests for TB including chest imaging, samples of mucus you cough up and, when needed, a biopsy. NICE explains what happens next when drug resistance is suspected. For people with clinically suspected TB, a TB specialist should request rapid nucleic acid amplification tests for rifampicin resistance on primary specimens if a risk assessment identifies any of the risk factors above.

If the rapid test is positive for rifampicin resistance, NICE says to continue infection control measures until pulmonary or laryngeal disease has been excluded, manage treatment with a multidisciplinary team experienced in multidrug-resistant TB, offer a regimen involving at least 6 drugs to which the mycobacterium is likely to be sensitive, and test for resistance to second-line drugs. If the rapid test is positive but rifampicin resistance is not detected, NICE says to treat as drug-susceptible TB with the standard regimen.

When the definitive laboratory susceptibility results are available, NICE says treatment should be modified as needed.

NICE sets out regimens for TB resistant to a single drug. For example, for isoniazid resistance it suggests rifampicin, pyrazinamide and ethambutol for the first 2 months, then rifampicin and ethambutol for 7 months, up to 10 months for extensive disease. For resistance to rifampicin, NICE says to treat as multidrug-resistant TB. These details are for clinicians and are summarised here only to show that the choice of drugs and the duration depend on which drug the bacteria resist.

For multidrug-resistant TB, NICE says to consider more intensive clinical follow-up, including directly observed therapy throughout treatment because of the complexity of treatment and risk of adverse events. It also says care should be discussed with clinicians who specialise in this, the person's views should be sought, and shared care considered. Surgery may be considered in potentially resectable multidrug-resistant disease if optimal medical therapy under direct observation has not worked or is likely to fail because of extensively drug-resistant TB.

NICE adds that, for drug-resistant TB with central nervous system involvement, a TB specialist with experience in drug-resistant TB should be involved in decisions about the regimen and duration.

Longer treatment brings practical challenges: more tablets, more side effects and more appointments. NHS inform says that after taking the medicine for 2 weeks most people with ordinary TB are no longer infectious and feel better. For drug-resistant disease, your specialist team is the right source of advice on when it is safe to return to work, school and normal social contact. NICE notes that treatment for TB is free for everyone, irrespective of eligibility for other NHS care.

NICE recommends that people with TB are supported to complete treatment, and that local services provide help including directly observed therapy where needed. If you are struggling to take your medicines, tell your specialist team early, because stopping or skipping doses is exactly what can worsen resistance.