Drug-resistant tuberculosis medical therapy

Jump to navigation Jump to search

Tuberculosis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Tuberculosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Children

HIV Coinfection

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Special Conditions
Drug-resistant

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Drug-resistant tuberculosis medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Drug-resistant tuberculosis medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Drug-resistant tuberculosis medical therapy

CDC on Drug-resistant tuberculosis medical therapy

Drug-resistant tuberculosis medical therapy in the news

Blogs on Drug-resistant tuberculosis medical therapy

Directions to Hospitals Treating Tuberculosis

Risk calculators and risk factors for Drug-resistant tuberculosis medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Drug-resistant tuberculosis is caused by M. tuberculosis organisms that are resistant to at least one first-line anti-TB drug. Multidrug-resistant TB (MDR TB) is resistant to more than one anti-TB drug and at least isoniazid (INH) and rifampin (RIF). Treatment should be started with an empirical treatment of at least 4 drugs based on expert advice as soon as drug-resistant TB disease is suspected.

Drugs Used in Drug-Resistant Tuberculosis

Groups Drugs
Group 1:
First-line oral drugs
Group 2:
Injectable drugs
Group 3: Fluoroquinolones
Group 4:
Oral bacteriostatic second-line drugs
Group 5:
Agents with unclear role in treatment of drug resistant-TB
Adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed.[1]

Multiple Drug-Resistant (MDR) Tuberculosis Adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed. [1]

  • MDR-TB is defined as resistance to isoniazid and rifampicin, with or without resistance to other first-line drugs.
  • Medical treatment for MDR-TB consists of at least 4 drugs that have shown effectiveness against MDR. Within these 4 drugs must be included at least one drug from each group.
  • Treatment duration will depend on the culture results. The duration of therapy should be > 18 months after culture is negative.
  • Chronic cases with severe pulmonary disease may require more than 24 months of therapy.
  • Empirical treatment should start immediately and the regimen should be modified according to the DST (Drug susceptibility testing) results.
  • Drugs in each group must be used, in order of preference, as shown below.[2]
  • The following treatment regimens show daily dosing for each drug.

▸ Click on the following categories to expand treatment regimens.

MDR Tuberculosis

  ▸  Adults

  ▸  Children

MDR-TB Adults
Standard Regimen
Group 1: First-line oral drugs

Pyrazinamide 20–30 mg/kg
OR
Ethambutol 15–25 mg/kg
OR
Rifabutin 5 mg/kg

PLUS
Group 2: Injectable drugs

Capreomycin 15 mg/kg
OR
Kanamycin 15 mg/kg
OR
Amikacin 7.5-10 mg/kg
OR
Streptomycin 12–18 mg/kg

PLUS
Group 3: Fluoroquinolones

Levofloxacin 500-1000 mg
OR
Moxifloxacin 400 mg
OR
Ofloxacin 400 mg

PLUS
Group 4:Oral bacteriostatic second-line drugs

Ethionamide 15-20 mg/kg
OR
Protionamide 15-20 mg/kg
OR
Cycloserine 10-15 mg/kg
OR
Terizidone 10-20 mg/kg
OR
Para-aminosalicylic acid 8-12 g/d divided q8-12h

Table adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed.[1]
MDR-TB Children
Standard Regimen
Group 1: First-line oral drugs

Pyrazinamide 20-30 mg/kg (Max: 600 mg)
OR
Ethambutol 15-20 mg/kg
OR
Rifabutin 5 mg/kg

PLUS
Group 2: Injectable drugs

Capreomycin 15-30 mg/kg (Max: 1000 mg)
OR
Kanamycin 15-30 mg/kg (Max: 1000 mg)
OR
Amikacin 15-22.5 mg/kg (Max: 1000 mg)
OR
Streptomycin 12-18 mg/kg

PLUS
Group 3: Fluoroquinolones

Levofloxacin 7.5-10 mg/kg
OR
Moxifloxacin 7.5-10 mg/kg
OR
Ofloxacin 15-20 mg/kg divided q12h (Max:800 mg)

PLUS
Group 4:Oral bacteriostatic second-line drugs

Ethionamide 15-20 mg/kg divided q12h (Max: 1000 mg)
OR
Protionamide 15-20 mg/kg divided q12h (Max: 1000 mg)
OR
Cycloserine 10-20 mg/kg (Max: 1000 mg)
OR
Terizidone 10-20 mg/kg (Max: 1000 mg)
OR
Para-aminosalicylic acid 150 mg/kg divided q8-12h(Max: 12 000 mg)

Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed.[1] and Guidance for national tuberculosis programmes on the management of tuberculosis in children [3]


Extensively Drug-Resistant (XDR) Tuberculosis Adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed. [1]

▸ Click on the following categories to expand treatment regimens.

XDR Tuberculosis

  ▸  Adults

  ▸  Children

XDR-TB Adults
Standard Regimen
Group 1: First-line oral drugs

Pyrazinamide 20–30 mg/kg
OR
Ethambutol 15–25 mg/kg
OR
Rifabutin 5 mg/kg

PLUS
Group 4:Oral bacteriostatic second-line drugs

Ethionamide 15-20 mg/kg
OR
Protionamide 15-20 mg/kg
OR
Cycloserine 10-15 mg/kg
OR
Terizidone 10-20 kg/mg
OR
Para-aminosalicylic acid 8-12 g/d divided q8-12h

PLUS
Group 5
Use at least 2 of the following:

Clofazimine 50 mg/d AND 300 mg once a month
OR
Amoxicillin/clavulanate 500 mg/125 mg q12h
OR
Linezolid 300-600 mg
OR
Imipenem 500mg q6h
OR
Clarithromycin 500-1000 mg q12h
OR
Thioacetazone 2.5 mg/kg
OR
Isoniazid (high-dose) 16–20 mg/kg

Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed.[1]
XDR-TB Children
Standard Regimen
Group 1: First-line oral drugs

Pyrazinamide 20-30 mg/kg (Max: 600 mg)
OR
Ethambutol 15 mg/kg
OR
Rifabutin 5 mg/kg

PLUS
Group 4:Oral bacteriostatic second-line drugs

Ethionamide 15-20 mg/kg (Max: 1000 mg)
OR
Protionamide 15-20 mg/kg (Max: 1000 mg)
OR
Cycloserine 10-20 mg/kg (Max: 1000 mg)
OR
Terizidone 10-20 mg/kg (Max: 1000 mg)
OR
Para-aminosalicylic acid 150 mg/kg/d divided q8-12h

PLUS
Group 5
Use at least 2 of the following:

Clofazimine 50 mg/d AND 300 mg once a month
OR
Amoxicillin/clavulanate
OR
Linezolid 300-600 mg
OR
Imipenem 500mg q6h
OR
Clarithromycin 500-1000 mg q12h
OR
Thioacetazone 2.5 mg/kg
OR
Isoniazid (high-dose) 16–20 mg/kg

Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed.[1] and WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children [3]

Extremely Drug-Resistant (XXDR) Tuberculosis

  • XXDR-TB or TDR-TB (totally drug resistant TB) is defined as resistance to all first-line (group 1) and second-line (groups 2-4) tuberculosis drugs.
  • Cases of XXDR-TB have been reported in Italy, India and Iran.[5][6][7]
  • There is no drug regimen for patients with extremely drug resistant TB that has shown successful response.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "2013 WHO Treatment of Tuberculosis: Guidelines for National Programmes (4th Edition)".
  2. Caminero, José A; Sotgiu, Giovanni; Zumla, Alimuddin; Migliori, Giovanni Battista (2010). "Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis". The Lancet Infectious Diseases. 10 (9): 621–629. doi:10.1016/S1473-3099(10)70139-0. ISSN 1473-3099.
  3. 3.0 3.1 "WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children, 2014" (PDF).
  4. Bonilla CA, Crossa A, Jave HO, Mitnick CD, Jamanca RB, Herrera C; et al. (2008). "Management of extensively drug-resistant tuberculosis in Peru: cure is possible". PLoS One. 3 (8): e2957. doi:10.1371/journal.pone.0002957. PMC 2495032. PMID 18698423.
  5. Udwadia, Z. F.; Amale, R. A.; Ajbani, K. K.; Rodrigues, C. (2011). "Totally Drug-Resistant Tuberculosis in India". Clinical Infectious Diseases. 54 (4): 579–581. doi:10.1093/cid/cir889. ISSN 1058-4838.
  6. G. B. Migliori, G. De Iaco, G. Besozzi, R. Centis & D. M. Cirillo (2007). "First tuberculosis cases in Italy resistant to all tested drugs". Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 12 (5): E070517. PMID 17868596. Unknown parameter |month= ignored (help)
  7. Velayati, Ali Akbar (2009). "Emergence of New Forms of Totally Drug-Resistant Tuberculosis Bacilli". CHEST Journal. 136 (2): 420. doi:10.1378/chest.08-2427. ISSN 0012-3692.