General steps in designing the composition of a longer multidrug-resistant tuberculosis (MDR-TB) regimen#

1. Add one later-generation fluoroquinoloneALevofloxacin (Lfx)
Moxifloxacin (Mfx)
Gatifloxacin (Gfx)
2. Add one second-line injectable agentBAmikacin (Am)
Capreomycin (Cm)
Kanamycin (Km)
(Streptomycin) (S)+
3. Add two or more second-line agentsCEthionamide/prothionamide (Eto/Pto)
Cycloserine/terizidone (Cs/Trd)
Linezolid (Lzd)
Clofazimine (Cfz)
4. Add pyrazinamide and any other first-line agent (if they can help strengthen the regimen)D1Pyrazinamide (Z)
Ethambutol (E)
High-dose isoniazid (Hh)
5. Add bedaquiline or delamanidD2Bedaquiline (Bdq)§
Delamanid (Dlm)§
6. Add any of these agents (if the regimen cannot be composed otherwise)D3p-aminosalicylic acid (PAS)
Imipenem–cilastatin (Ipm-Cln)ƒ
Meropenem (Mpm)ƒ
Amoxicillin–clavulanate (Amx-Clv)ƒ
(Thioacetazone) (T)##
  • #: this stepwise approach guides the design of longer individualised regimens for patients who are not eligible for the World Health Organization-recommended shorter regimen (the composition of the shorter MDR-TB regimen is standardised) (see main text). The aim is to combine at least five effective agents in the intensive phase; more medicines may be included if they can safely increase the chances of cure. The choice of a medicine is based on the likelihood of its effectiveness, on reliable information on drug resistance and on the balance of expected benefits to risk. For instance, in case of nephrotoxicity or hearing loss, an injectable agent may be omitted and additional agents from Group C or D2 included. : medicines in Groups A and C are shown in decreasing order of preference for use (subject to other considerations). +: streptomycin may substitute other injectable agents when the other three cannot be used; resistance to streptomycin alone does not qualify for the definition of extensively drug-resistant TB [50]. §: bedaquiline or delamanid may be added to the longer regimen to replace another second-line agent or to strengthen it in accordance with the interim policies [20, 21, 27]. ƒ: carbapenems and clavulanate are used together; clavulanate is only available in formulations combined with amoxicillin. ##: HIV status must be tested and confirmed to be negative before thioacetazone is started.