UK patients with MDR-TB have good outcomes but a quarter not receiving the recommended duration of therapy

Michael Carter
Published: 09 October 2013

Approximately 25% of people with multidrug-resistant tuberculosis (MDR-TB) in the UK are not completing the recommended course of treatment, data published in the 3 October edition of Eurosurveillance shows. Treatment was completed by 71% of patients in 24 months or more, which was below both the World Health Organization (WHO) and UK targets (75 and 85%, respectively).

“It is important to continue to monitor treatment outcomes of MDR-TB patients to improve treatment management policy,” write the authors.

Therapy with a fluoroquinolone or bacteriostatic drug was associated with better treatment outcomes.

MDR-TB is defined as resistance to the key first-line drugs isoniazid and rifampicin. It is a global health problem and represents a significant threat to efforts to control the spread of TB.

The annual number of confirmed cases of MDR-TB in the UK has increased in recent years from 28 cases in 2000 to 58 cases in 2009. During this time there were also eight confirmed cases of extensively drug-resistant TB (XDR-TB), infections involving resistance to important second-line drugs.

WHO guidelines issued in 2008 recommend that MDR-TB should be treated with a combination of ethambutol and pyrazinamide, an injectable agent, a fluoroquinolone, and if necessary, a bacteriostatic drug.  The treatment should last for at least 20 months and be administered by directly observed therapy (DOT).

There is no recent UK guidance for the management of MDR-TB. The NICE (National Institute of Health and Care Excellence) guidelines issued in 2011 did not cover MDR-TB, instead suggesting that doctors should consult clinicians with specialism in this area.

It is also currently unclear how many people with MDR-TB complete the recommended 24 months of therapy.

Investigators therefore used information gathered via enhanced surveillance to determine the number and proportion of MDR-TB patients diagnosed between 2004 and 2007 who completed the recommended course of therapy. They also examined the factors associated with a successful treatment outcome, loss to follow-up and death.

There were 204 culture-confirmed cases of MDR-TB during the period of analysis. Just over half the patients lived in London and were male. Most were aged between 15 and 44 years (83%) and were born outside the UK (85%). Only 30% had a previous TB diagnosis and less than a fifth had a social risk factor for TB (homelessness, injecting drug use or a history of imprisonment). Just over a quarter had a co-morbidity. The most common co-morbidity was HIV (16%).

Isolates showed resistance to a median of four drugs. A high proportion of people had resistance to one (42%) or two or more (24%) second-line drugs.

The median duration of treatment for people completing therapy was 19 months and increased from 18 to 23 months between 2003 and 2007.

The most commonly used drugs were pyrazinamide, moxifloxacin and ethambutol. A median of four effective drugs were used in the initial regimen, but approximately a fifth of patients were treated with fewer than four effective agents.

Just over half of patients (54%) changed at least one drug in their initial regimen at some point. The most common reasons were side-effects or intolerance.

Only 40% of all patients and 53% of individuals with known social risk factors were treated using DOT. The main reasons for not using this strategy were lack of indicators for poor adherence (40%), treatment as an inpatient (26%) or using a pillbox as an alternative (11%).

Overall, 71% of patients successfully completed therapy at month 24 or later.

“This completion rate met the EU target of 70% but was still below the WHO target of 75% and the UK Chief Medical Officer’s action plan goal of 85%,” comment the investigators.

Of the patients with unsuccessful outcomes, 7% stopped their treatment, 6% died with TB listed as the cause of death or a factor contributing to mortality, 8% were lost to follow-up, 3% completed treatment within twelve months and 1% completed treatment but then relapsed. One person died of a cause unrelated to TB and nine people left the UK, mainly to resource-poor countries.

Social and demographic factors associated with unsuccessful outcomes included being non-UK born (p = 0.026), poor treatment adherence (p = 0.019) and a co-morbidity (p = 0.001) such as HIV (p = 0.048).

After controlling for these factors, treatment with a fluoroquinolone (OR = 3.09; 95% CI, 1.21-7.88, p < 0.05) or bacteriostatic drug (OR = 4.23; 95% CI, 1.60-11.18, p < 0.05) were independently associated with successful treatment outcomes.

“Provided the future MDR-TB population remains similar to our study population, we recommend that a bacteriostatic drug should be considered an important part of all MDR-TB treatment regimens in the UK,” write the authors. They stress the importance of expert analysis of drug sensitivity tests and recommend that efforts should be made to ensure the continuity of care for patients transferring out of the UK.

Reference

Anderson LF et al. Treatment outcome of multi-drug resistant tuberculosis in the United Kingdom: retrospective-prospective cohort study from 2004 to 2007. Eurosurveillance, 18:40, 2013.