This seminal paper summarises the clinical outcomes of individual from 50 studies across 25 countries. This individual patient data meta-analysis included potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016.
Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died.
Compared with failure or relapse, treatment success was positively associated with the use of:
- linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18)
- levofloxacin (0·15, 0·13 to 0·18), moxifloxacin (0·11, 0·08 to 0·14)
- carbapenems (0·14, 0·06 to 0·21)
- bedaquiline (0·10, 0·05 to 0·14)
- clofazimine (0·06, 0·01 to 0·10)
There was a significant association between reduced mortality and use of
- linezolid (–0·20, –0·23 to –0·16)
- levofloxacin (–0·06, –0·09 to –0·04), moxifloxacin (–0·07, –0·10 to –0·04)
- bedaquiline (–0·14, –0·19 to –0·10)
For the drugs that are commonly used in the Indian scenario:
- Amikacin in people with susceptible strains was associated with greater success (adjusted risk difference 0·06, 95% CI 0·04 to 0·08) but no difference in death
- Kanamycin was associated with significantly lower success (–0·07, –0·08 to –0·05) but no difference in death (0·01, –0·01 to 0·02)
- Capreomycin use with lower success (–0·03, –0·06 to 0·00) and more deaths (0·04, 0·01 to 0·07)
- Use of ethambutol, ethionamide and protionamide, or para-aminosalicylic acid were associated with no benefit in patients with susceptible isolates, and worse outcomes in patients with resistant isolates
- Use of pyrazinamide was associated with lower mortality (adjusted risk difference −0·03, 95% CI −0·05 to −0·01) if isolates were susceptible, but significantly less success (−0·05, −0·08 to −0·03) and higher mortality (0·05, 0·02 to 0·07) if isolates were resistant
- Use of cycloserine was beneficial in patients with susceptible isolates contributing to treatment success and protection from death
This study is the basis of the recent WHO MDR-TB update. While this is the largest summary of clinical data we have, the following points merit special attention.
- The high baseline FQ resistance in many parts of India should be borne in mind
- Bedaquiline availability is an issue in India
- The paper did not look at toxicity data – prolonged use of linezolid requires close monitoring for bone marrow toxicity and neuropathy
- Probably, amikacin should be our aminoglycoside of choice for MDR TB