Table 4.
Treatment outcomes of fluoroquinolone (FQ)-containing regimens for tuberculosis (TB) meningitis
| FQ | (mg) | Treatment regimenA | Study | Treatment outcome | Survival FQ/control | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| FQ (months) | Control (months) | Type | No.B | Patient | Primary endpoint | Endpoint monthsc | Endpoint FQB | Endpoint controlB | Hazard ratio (95% CI)B | P value | Refs. | ||
| L | 20/kg |
LR (8 weeks) + HRZE (3)D HR (6) |
HRZE (3) HR (6) |
Double-blind, placebo-controlled, RCT | 817 | Clinical diagnosis, no MDRE | Death | 0 | 28% | 28% | Death: 0.94 (0.73–1.22) |
0.66 | [20] |
| L | 10/kg (max. 500) |
HLZE (6) | HRZE (6) | Open-label, RCT | 120 | Clinical diagnosis | Death | 0 | 22%G | 38%G | Survival: 2.13 (1.04–4.34)F |
0.04 | [19] |
| M | 0 400 800 |
HRZE (2 weeks)H HRZM (2 weeks)H HRZM (2 weeks)H All arms > 2 weeks: HRZE (2 months–2 weeks) HR (4) |
– | Open-label, RCT, factorial design | + R450mg 12 10 9 + R600mg 10 9 10 |
Clinical diagnosis | DeathI | 0 | + R450mg 58% 60% 78% + R600mg 30% 22% 50% |
– | Death: 0.76 (0.30–1.94)J,K 1.27 (0.53–3.02)J,K |
0.55K | [21] |
E ethambutol, FQ fluoroquinolone, H isoniazid, L levofloxacin, MDR multi-drug resistance, M moxifloxacin, RCT randomized controlled trial, R rifampicin, Z pyrazinamide
ADaily regimen
B(Modified) intention-to-treat population
CMonths after the end of treatment
D+ 5 mg/kg/day rifampicin (total 15 mg/kg/day) in the first 8 weeks. Streptomycin was added for the first 3 months in treatment-experienced patients
EMDR proven by sputum culture or suspected
FAdjusted for covariates of survival such as stage of disease
GLevofloxaxin was withdrawn in 16 patients due to serious adverse events (SAEs). Death in the per-protocol analysis (patients with SAEs excluded): 25% (L) vs. 41% (R)
HSix arms: first randomization oral R450mg (standard) or intravenous R600mg (high-dose), second randomization M400mg, M800mg or E
ISecondary endpoint. No sample size calculation because of the exploratory nature of the study. Sample size was assumed to be sufficient to explore pharmacokinetics and safety of intensified regimens based on M and/or R
JAdjusted for R600mg, HIV status, and Glasgow coma scale at baseline
KM (400 mg, 800 mg) vs. E