An update on multidrug-resistant tuberculosis

Mirae Park; Giovanni Satta; Onn Min Kon

doi:10.7861/clinmedicine.19-2-135

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Table 1.

World Health Organization guidelines for drug-resistant tuberculosis, 2016 update^a

Group	Medicine		Abbreviation
A. Fluroquinolones^b	Levofloxacin Moxifloxacin Gatifloxacin		Lfx Mfx Gfx
B. Second-line injectable agents	Amikacin Capreomycin Kanamycin (Streptomycin)^c		Am Cm Km (S)
C. Other core second-line agents^b	Ethianomide / Prothionamide Cycloserine / Terizidone Linezolid Clofazimine		Eto / Pro Cs / Trd Lzd Cfz
D. Add-on agents (not part of the core MDR-TB regimen)	D1	Pyrazinamide Ethambutol High-dose isoniazid	Z E H
	D2	Bedaquiline Delamanid	Bdq Dlm
	D3	p-aminosalicylic acid Imipenem-cilastatin^d Meropenem^d Amoxicillin-clavulanate^d (Thioacetazone)^e	PAS Ipm Mpm AMx-Clv (T)

Reprinted with permission from World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. Geneva: WHO, 2016:23.²²

MDR-TB = multidrug-resistant tuberculosis.
↵^aThis regrouping was intended to guide the design of longer regimens; the composition of the recommended shorter MDR-TB regimen is standardised.
↵^bMedicines in Groups A and C are shown by decreasing order of usual preference for use (subject to other considerations).
↵^cRefer to the source text for the conditions under which streptomycin may substitute other injectable agents. Resistance to streptomycin alone does not qualify for the definition of extensively drug-resistant tuberculosis.
↵^dCarbapenems and clavulanate are meant to be used together; clavulanate is only available in formulations combined with amoxicillin.
↵^eHIV status must be confirmed to be negative before thioacetazone is started.

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Table 2.

Proposed 2018 grouping of medicines recommended for use in longer multidrug-resistant tuberculosis regimens

Group	Medicine	Abbreviation
Group A: Includes all three medications (unless they cannot be used)	Levofloxacin or moxifloxacin Bedaquiline^a ^,^d Linezolid^b	Lfx or Mfx Bdq Lzd
Group B: Add both medicines (unless they cannot be used)	Clofazimine Cycloserine or terizidone	Cfz Cs or Trd
Group C: Add to complete the regimen and when medicines from Group A and B cannot be used	Ethambutol Delamanid^c ^,^d Pyrazinamide^e Imipenem-cilastatin or Meropenem^f Amikacin (or streptomycin)^g Ethionamide or prothionamide P-aminosalicylic acid	E Dlm Z Ipm-Cln or Mpm Am or S Eto or Pto PAS

↵^aEvidence on the safety and effectiveness of Bdq beyond 6 months was insufficient for review; extended Bdq use in individual patients will need to follow ‘off-label’ use best practices.
↵^bOptional duration of use of Lzd is not established. Use for at least 6 months was shown to be highly effective, although toxicity may limit its use.
↵^cThe position of Dlm will be re-assessed once individual patient data from trial 213 has been reviewed; these data were not available for the evidence assessment in July outlined above. Evidence on the safety and effectiveness of Dlm beyond 6 months was insufficient for review; extended use of Dlm in individual patients will need to follow ‘off-label’ use best practices.
↵^dEvidence on concurrent use of Bdq and Dlm was insufficient for review.
↵^eZ is only counted as an effective agent when DST results confirm susceptibility.
↵^fAmoxicillin-clavulanic acid is administered with every dose of Imp-Cln or Mpm but is not counted as a separate agent and should not be used as a separate agent.
↵^gAm and S are only to be considered if DST results confirm susceptibility and high-quality audiology monitoring for hearing loss can be ensured. S is to be considered only if Am cannot be used and if DST results confirm susceptibility (S resistance is not detectable with second-line molecular line probe assays and phenotypic DST is required).
Reprinted with permission from World Health Organization. Rapid Communication: Key changes to treatment of multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). Geneva: WHO, 2018:3–4.³⁰