8.1 Introduction


A combination of several antibacterial drugs is necessary for treating the disease and avoiding the emergence of resistance. Treatment regimens define the specific drug combinations used and the intended length of treatment.

Anti-TB drugs are classified into 5 groups based on efficacy, experience of use and drug class. Not all drugs in the same group have the same efficacy, mechanisms of action, adverse effect profile or safety. Each drug has a specific action on one or more bacillary populations but none on dormant bacilli1 .

Treatment regimens are expressed in a standardised and abbreviated manner.

8.1.1 Standard code for TB treatment regimens

Anti-TB drugs

Table 8.1 - Drug groups and abbreviations (adapted from the WHO1)

Group name

Anti-TB drug

Abbreviation

GROUP 1
First-line oral agents

Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
Rifabutin

H
R
Z
E
Rfb

GROUP 2
Injectable agents

Streptomycin
Amikacin
Kanamycin
Capreomycin

S
Amk
Km
Cm

GROUP 3
Fluoroquinolones (FQs)

Moxifloxacin
Levofloxacin
Ofloxacin

Mfx
Lfx
Ofx

GROUP 4
Oral bacteriostatic second-line anti-TB drugs

Ethionamide
Prothionamide
Cycloserine
Para-aminosalicylic acid

Eto
Pto
Cs
PAS

GROUP 5
Drugs with limited data on efficacy and/or long-term safety in the treatment of DR-TB

Bedaquiline
Linezolid
Clofazimine
Amoxicillin/clavulanic acid
Isoniazid high dose
Thioacetazone
Imipenem/cilastatin
Meropenem

Bdq
Lzd
Cfz
Amx/Clv
High dose H
Thz
Ipm/Cln
Mpm

Notes:
– The traditional “first-line anti-TB drugs”: H, R, Z, E and streptomycin (S) are now referred to as Group 1 drugs, with the exception of S, which is included in Group 2. Groups 2 (except S) to 5 are usually reserved for drug-resistant (DR) TB and are referred as “second-line anti-TB drugs”.
– In these guidelines, clarithromycin (Clr) is not included in the Group 5 drugs until further data on its efficacy is available.

Treatment regimens

TB regimens are abbreviated according to the following system:
– Drugs are listed using their abbreviations.
– Treatment is divided into two phases, initial (or intensive) phase and continuation phase. These two phases are divided by a slash.
– The number before each phase represents the duration of that phase in months.
– A number in subscript (e.g. 3) after a letter means that intermittent dosing is used (H3R3 means isoniazid and rifampicin are given 3 times weekly).
– No number in subscript means that medications must be taken every day.
– When drugs are placed in brackets, it means that fixed-dose combinations (FDC) are used.
– When drugs are not placed in brackets, individual drugs are used.
– Second line drugs are separated by a hyphen.

Examples:
– 2 (HRZE)/4 (HR): the patient receives a FDC containing four drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) daily for two months, then a FDC containing two drugs (isoniazid, rifampicin) daily for four months.
– 8 Km-Lfx-Eto-Cs-Z/14 Lfx-Eto-Cs-Z: the patient receives a combination of five individual drugs daily for eight months, then a combination of four individual drugs daily for fourteen months. The injectable drug is mentioned first, the fluoroquinolone second, Group 1 drug(s) are mentioned last.

8.1.2 Treatment approaches

Standardized treatment or regimen:
All patients in a defined group receive the same regimen. Different groups might receive a different regimen.
For example:
– All patients with a strain susceptible to first-line drugs receive the same standard treatment for 6 months, or for 12 months, depending on the site involved.
– Patients who failed to respond to the first-line drugs may start an empiric standardized regimen for multiresistant TB (MDR-TB), based on drug resistance data of first- and second-line anti-TB drugs from representative patient populations, until the full drug susceptibility testing (DST) returns and the patient’s regimen is individualized.

Individualized treatment or regimen:
Each regimen is designed based on the patient’s previous history of TB treatment and individual DST results.

DR-TB programmes often use a combination of the standardized and individualized approaches. However, in situations where DST is unavailable or limited to only one or two first-line drugs, programmes will most commonly use a purely standardized approach.



Footnotes
Ref Notes
1 An active TB lesion contains distinct M. tuberculosis populations: actively multiplying bacilli in open cavities (responsible for transmission); slowly multiplying bacilli in acidic inflammatory tissue; sporadically multiplying bacilli in tissues and dormant bacilli in solid lesions.