Drug-resistant tuberculosis treatment

Duration of (H)REZ. The analysis comparing (H)REZ treatment regimens for 6 months (6(H)REZ) and 
more than 6 months (>6(H)REZ) demonstrated that a 6(H)REZ regimen had a higher likelihood of 
treatment success than a >6(H)REZ regimen. Further analyses determined that there was no statistically 
significant difference in the treatment outcomes of patients receiving regimens of 6-month REZ (6REZ) 
and those receiving more than 6 months REZ (>6REZ). Since data were not included on intermittent 
dosing of the 6(H)REZ and >6(H)REZ regimens, no inferences could be drawn about the use of 
alternating versus daily regimens. The effect of length of pyrazinamide use in the (H)REZ regimen 
was assessed, to investigate whether the use of this medicine could be minimized to the shortest 
possible duration. The reduction in treatment with pyrazinamide to less than 3 months was associated 
with a worse treatment outcome, even with the addition of streptomycin (adjusted odds ratio [aOR]: 
0.4; 95% confidence limits [CL]: 0.2–0.7). In 118 patients on fluoroquinolone-containing regimens 
who received pyrazinamide for less than 4 months, the odds of treatment success were higher than 
in those who received a 6(H)REZ regimen, although the difference was not statistically
significant.
Duration of levofloxacin use. In a subsample of 241 patients on an (H)REZ plus fluoroquinolone 
regimen, the median duration of fluoroquinolone use was 6.1 months (interquartile range [IQR]: 
3.5; 8.4), and for REZ it was 9 months (IQR: 7; 11). Hence, in the observational studies that informed 
the IPD, it seems that treatment length was based on the completion of 6 months of treatment with 
a
fluoroquinolone.
Acquisition of drug resistance. The analysis suggested that amplification of resistance to rifampicin 
was lower in patients receiving the 6(H)REZ regimen (0.6%) than in those receiving >6(H)REZ (4.3%). 
This observation could be due to the effect of selection and allocation of patients into specific 
regimens; for instance, the number of patients with extensive disease was slightly larger in those 
receiving >6(H)REZ. However, overall, the number of observations for each comparison was small 
and the effect was not statistically significant (aOR: 0.2; 95% CL: 0.02–1.70).
Adverse events. Data on adverse events were not evaluated owing to a of lack of standardization 
(dissimilar reporting). The GDG also considered two reports containing data from patients from 
the United States of America (USA) in whom a detailed assessment of adverse events suggested 
a risk of excess hepatotoxicity with the 6(H)REZ combination (18). Drug-induced hepatotoxicity is 
not uncommon with anti-TB drugs. It has also been reported in individuals receiving rifampicin and 
pyrazinamide for 2 months for the treatment of latent TB infection (LTBI) – in such individuals, a 
much higher occurrence of hepatotoxicity has been observed than in those receiving only isoniazid 
preventive therapy (19). It is not known whether the risk of hepatotoxicity differs between 6REZ 
and
6HREZ.