Figures
- FIGURE 1
New anti-tuberculous drugs currently in development. Data from [104].
Tables
- TABLE 1
Current medications in use for TB treatment and their notable side-effects
Drug Notable side-effects Rifampicin (RIF) Hepatotoxicity, nausea, dyspepsia, abdominal pain, rash, CYP450 interactions Isoniazid (INH) Hepatotoxicity, peripheral neuropathy#, optic neuritis, CYP450 interactions Pyrazinamide (PZA) GI disturbance, hepatotoxicity, gout Ethambutol (EMB) Optic neuropathy Levofloxacin (LFX)/Moxifloxacin (MFX) QT prolongation, tendonitis, hypoglycaemia, psychiatric disturbance Bedaquiline (BDQ) QT prolongation, CYP450 interactions Linezolid (LZD) Myelosuppression, dysglycaemia, peripheral neuropathy#, optic neuropathy Clofazimine (CFZ) Hepatotoxicity, GI disturbance, neurological disturbance, QT prolongation, altered skin pigmentation Cycloserine (CYS) Psychiatric disturbance, peripheral neuropathy Delamanid (DLM) QT prolongation, CYP450 interactions Aminoglycosides (AMK,CAP, STR) Nephrotoxicity, ototoxicity Ethionamide (ETH)/Prothionamide (Pro) Psychiatric disturbance, peripheral neuropathy, hepatotoxicity, hypothyroidism, dysglycaemia p-Aminosalicylic acid (PAS) Hepatotoxicity, dysglycaemia, hypothyroidism Amoxicillin–Clavulanate¶ with Meropenem or Imipenem–Cilastatin Diarrhoea, candidiasis #: given with pyridoxine prophylaxis to ameliorate risk; ¶: beta-lactams must be given with Clavulanate for success in TB treatment; however, the only available preparations include Amoxicillin. Information from [50].
- TABLE 2
Current ATS/CDC/ERS/IDSA consolidated guidelines on treating drug-resistant TB
RR-TB As per MDR-TB INH-resistant TB RIF+PZA+ETM+FLQ for 6 months (can discontinue PZA after 2 months; FLQ only required in patients with extensive disease, i.e. cavitary or bilateral infiltrates) MDR-TB First line Levofloxacin or Moxifloxacin with all 4 of: Bedaquiline + Linezolid + Clofazimine# + Cycloserine# Second line Consider Delamanid¶2 or Pyrazinamide¶3 or Ethambutol¶1 or Amikacin or Streptomycin¶5 Third line Consider ETH¶6 or Prothionamide or Imipenem-Cilastatin/Clavulante or Meropenem/Clavulanate¶4 or p-Aminosalicylic Acid¶7 or High Dose Isoniazid ATS: American Thoracic Society; CDC: US Centers For Disease Control And Prevention; ERS: European Respiratory Society; IDSA: Infectious Diseases Society of America. #: in contrast, the WHO suggests only one of these drugs are required, comprising a 4-drug regimen (see text for full details); ¶: superscript numbers refer to the order in which the WHO suggests drugs be incorporated into regimes. Information from [50].
- TABLE 3
New drug regimens under evaluation
Trial Drugs Purpose Status Trial ID# ReDEFINe RIF (HD) Assess high-dose RIF on treatment outcomes and duration in TB meningitis Phase II NCT02169882 TB-PRACTECAL BDQ, Pa, LZD, MFX, CFZ Assess 6 months of regimen for MDR-TB Phase III (data Analysis) NCT02589782 Stream stage 2 CFZ, ETM, MFX, PZA, INH, Kan, Pro, BDQ, LFX Varying combinations at differing durations for RR-TB and MDR-TB Phase III NCT02409290 SimpliciTB BDQ, Pa, MFX, PZA 4 months for DS-TB
6 months for MDR-TBPhase III NCT03338621 Truncate-TB BDQ, RFP, LZD, MFX 2 months for DS TB Phase III NCT03474198 TBTC study 31 RFP, INH, ETM, PZA, MFX Evaluate 4 months treatment for DS-TB Phase III NCT02410772 endTB BDQ, DLM, LZD, MFX, PZA, LFX, CFZ 47 weeks treatment with combinations of 5 drugs for MDR-TB Phase III NCT02754765 RIFASHORT RIF (HD) Evaluate 4 months of RIF (HD) Phase III NCT02581527 NEXT trial LZD, BDQ, PZA, ETH or INH (HD) Evaluate efficacy of ETH or INH (HD) with 6–9 months treatment for MDR-TB Phase III (data Analysis) NCT02454205 ZeNix Pa, LZD, BDQ, Pl Evaluate 26 weeks treatment Phase III NCT03086486 DELIBERATE BDQ, DLM Evaluate safety in MDR-TB Phase III NCT02583048 BEAT TB BDQ, DLM, LZD, LFX, CFZ Evaluate safety and efficacy of 6 months treatment for RR-TB Phase III NCT04062201 HD: high dose; RIF: rifampicin; INH: isoniazid; RFP: rifapentine; ETM: ethambutol; PZA: pyrazinamide; MFX: moxifloxacin; LFX: levofloxacin; LZD: linezolid; ETH: ethionamide; BDQ: bedaquiline; DLM: delamanid; Pa: pretomanid; CFZ: clofazamine; Kan: kanamycin; Pro: prothionamide; Pl: Placebo. #: ClinicalTrials.gov identifier. Information from [1, 104].
