Multi-drug-resistant tuberculosis medical therapy: Difference between revisions

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VisualWikitext

Revision as of 12:28, 25 September 2014

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Medical Therapy

Drugs Used in Drug-Resistant Tuberculosis


Groups	Drugs

Group 1: First-line oral drugs	Pyrazinamide Ethambutol Rifabutin
Group 2: Injectable drugs	Kanamycin Amikacin Capreomycin Streptomycin
Group 3: Fluoroquinolones	Levofloxacin Moxifloxacin Ofloxacin
Group 4: Oral bacteriostatic second-line drugs	Para-aminosalicylic acid Cycloserine Terizidone Ethionamide Protionamide
Group 5: Agents with unclear role in treatment of drug resistant-TB	Clofazimine Linezolid Amoxicillin/clavulanate Thioacetazone Imipenem/cilastatin High-dose isoniazid Clarithromycin
Adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed.^[1]

MDR Tuberculosis Regimen 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]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 "2013 WHO Treatment of Tuberculosis: Guidelines for National Programmes (4th Edition)".
↑ 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.
↑ "WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children, 2014" (PDF).

Template:WH Template:WS

[WHO_2013-1] 1.0 ^1.1 ^1.2 ^1.3 "2013 WHO Treatment of Tuberculosis: Guidelines for National Programmes (4th Edition)".

[CamineroSotgiu2010-2] 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.

[WHO_TB_Children-3] "WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children, 2014" (PDF).

[1]

[2]

[3]

@@ Line 4: / Line 4: @@
 ==Overview==
 ==Medical Therapy==
-{{see also|Tuberculosis treatment}}
+===Drugs Used in Drug-Resistant Tuberculosis===
-The treatment and prognosis of MDR-TB are much more akin to that for cancer than to that for infection.  It has a mortality rate of up to 80%, which depends on a number of factors, including
+{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px;" align=center
-#How many drugs the organism is resistant to (the fewer the better),
+|valign=top|
-#How many drugs the patient is given (patients treated with five or more drugs do better),
+|+
-#Whether an injectable drug is given or not (it should be given for the first three months at least),
+! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Groups}}
-#The expertise and experience of the physician responsible,
+! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Drugs}}
-#How co-operative the patient is with treatment (treatment is arduous and long, and requires persistence and determination on the part of the patient),
+|-
-#Whether the patient is HIV positive or not (HIV co-infection is associated with an increased mortality).
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Group 1: <br> First-line oral drugs
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* [[Pyrazinamide]]
+* [[Ethambutol]]
+* [[Rifabutin]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Group 2: <br> Injectable drugs
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*[[Kanamycin]]
+*[[Amikacin]]
+*[[Capreomycin]]
+*[[Streptomycin]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Group 3: Fluoroquinolones
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*[[Levofloxacin]]
+*[[Moxifloxacin]]
+*[[Ofloxacin]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Group 4: <br> Oral bacteriostatic second-line drugs
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*Para-[[aminosalicylic acid]]
+*[[Cycloserine]]
+*[[Terizidone]]
+*[[Ethionamide]]
+*[[Protionamide]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Group 5: <br> Agents with unclear role in treatment of drug resistant-TB
+| style="padding: 5px 5px; background: #F5F5F5;" |
+*[[Clofazimine]]
+*[[Linezolid]]
+*[[Amoxicillin]]/[[clavulanate]]
+*[[Thioacetazone]]
+*[[Imipenem]]/[[cilastatin]]
+*High-dose [[isoniazid]]
+*[[Clarithromycin]]
+|-
+| style="padding: 5px 5px; background: #F5F5F5;" colspan=2| <small>Adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed.<ref name="WHO 2013"> {{cite web|  url=http://www.who.int/tb/publications/tb_treatmentguidelines/en/| title=2013 WHO Treatment of Tuberculosis: Guidelines for National Programmes (4th Edition) }}</ref></small>
+|}
-Treatment courses are generally measured in months to years; it may require surgery, and despite that, the death rates remain still high despite optimal treatment.  That said, good outcomes are still possible.<!--
+==MDR Tuberculosis Regimen<small><small><small> Adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed. <ref name="WHO 2013"> {{cite web|  url=http://www.who.int/tb/publications/tb_treatmentguidelines/en/| title=2013 WHO Treatment of Tuberculosis: Guidelines for National Programmes (4th Edition) }}</ref></small></small></small>==
---><ref name="Mitnick2003">{{cite journal
- | author=Mitnick C ''et al.''
- | title=Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru
- | journal=N Eng J Med
- | volume=348
- | issue=2
- | year=2003
- | pages=119-128
-  | URL=http://content.nejm.org/cgi/content/abstract/348/2/119
- | id=PMID 12519922 }}</ref>
-The treatment of MDR-TB must be undertaken by a physician experienced in the treatment of MDR-TB. Mortality and morbidity in patients treated in non-specialist centres is significantly inferior to those patients treated in specialist centres.
+*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.<ref name="CamineroSotgiu2010">{{cite journal|last1=Caminero|first1=José A|last2=Sotgiu|first2=Giovanni|last3=Zumla|first3=Alimuddin|last4=Migliori|first4=Giovanni Battista|title=Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis|journal=The Lancet Infectious Diseases|volume=10|issue=9|year=2010|pages=621–629|issn=14733099|doi=10.1016/S1473-3099(10)70139-0}}</ref>
+*The following treatment regimens show daily dosing for each drug.
-Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. If treating a patient with suspected MDR-TB, the patient should be started on SHREZ ([[Streptomycin]]+[[INH|isonicotinyl Hydrazine]]+[[Rifampin]]+[[Ethambutol]]+[[pyrazinamide|pyraZinamide]])+[[moxifloxacin|MXF]]+[[cycloserine]] pending the result of laboratory sensitivity testing.
+<SMALL><font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font></SMALL>
-A gene probe for ''[[rpoB]]'' is available in some countries and this serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe (''rpoB'') are known to be positive, then it is reasonable to omit RMP and to use SHEZ+[[moxifloxacin|MXF]]+[[cycloserine]]. The reason for maintaining the patient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs with rifampicin resistance).
+{|
+| valign=top |
-When sensitivities are known and the isolate is confirmed as resistant to both INH and RMP, five drugs should be chosen in the following order (based on known sensitivities):
+<div style="border-radius: 5px 5px 0 0; border: solid 1px #20538D; border-bottom: 0px; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #A1BCDD; text-align: center;">
-* an [[aminoglycoside]] (e.g., [[amikacin]], [[kanamycin]]) or polypeptide antibiotic (e.g., [[capreomycin]])
+<font color="#FFF">
-* [[pyrazinamide|PZA]]
+'''MDR Tuberculosis'''
-* [[ethambutol|EMB]]
+</font>
-* a [[fluoroquinolone]]s: [[moxifloxacin]] is preferred to [[ciprofloxacin]] or [[ofloxacin]];
+</div>
-* [[rifabutin]]
-* [[cycloserine]]
-* a [[thioamide]]: [[prothionamide]] or [[ethionamide]]
-* [[Aminosalicylic acid|PAS]]
-* a [[macrolide]]: e.g., [[clarithromycin]]
-* [[linezolid]]
-* high-dose [[isoniazid|INH]] (if low-level resistance)
-* [[interferon-γ]]
-* [[thioridazine]]
-Drugs are placed nearer the top of the list because they are more effective and less toxic; drugs are placed nearer the bottom of the list because they are less effective or more toxic, or more difficult to obtain.
+<div class="mw-customtoggle-table01" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #4479BA;">
+<font color="#FFF">
+&nbsp;&nbsp;▸&nbsp;&nbsp;'''Adults'''
+</font>
+</div>
-Resistance to one drug within a class generally means resistance to all drugs within that class, but a notable exception is rifabutin: rifampicin-resistance does not always mean rifabutin-resistance and the laboratory should be asked to test for it.  It is only possible to use one drug within each drug class.  If it is difficult finding five drugs to treat then the clinician can request that high level INH-resistance be looked for. If the strain has only low level INH-resistance (resistance at 1.0mg/l INH, but sensitive at 0.2mg/l INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four drug regimen, you must still choose another drug to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: if possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the treatment of tuberculosis if other fluoroquinolones are available.<ref>{{cite journal | author=Ziganshina LE, Vizel AA, Squire SB. | title=Fluoroquinolones for treating tuberculosis | journal=Cochrane Database Sys Rev | year=2005 | issue=3 | pages=CD004795 | doi=10.1002/14651858.CD004795.pub2 }}</ref>
+<div class="mw-customtoggle-table02" style="cursor: pointer; border-radius: 0 0 5px 5px; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #4479BA;">
+<font color="#FFF">
+&nbsp;&nbsp;▸&nbsp;&nbsp;'''Children'''
+</font>
+</div>
-There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results.  Directly observed therapy certainly helps to improve outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.<!--
+| valign=top |
---><ref name="Leimane2005">{{cite journal
+{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table01" style="background: #FFFFFF;"
- | author=Leimane V., ''et al.''
+| valign=top |
- | title=Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study
+{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
- | journal=Lancet
+! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|MDR-TB Adults}}
- | volume=365
+|-
- | issue=9456
+| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Standard Regimen'''''
- | year=2005
+|-
- | pages=318-26
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | '''<u>Group 1: First-line oral drugs</u>''' <br>
-  | URL=http://linkinghub.elsevier.com/retrieve/pii/S0140673605177861
+▸ ''' [[Pyrazinamide]] 20–30 mg/kg''' <br> OR <br> ▸ '''[[Ethambutol]] 15–25 mg/kg''' <br> OR <br> ▸ '''[[Rifabutin]] 5 mg/kg'''
- | id=PMID 15664227}}</ref>
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | '''<u>Group 2: Injectable drugs</u>''' <br>
+▸ '''[[Capreomycin]] 15 mg/kg'''<br> OR <br> ▸ '''[[Kanamycin]] 15 mg/kg'''<br> OR <br> ▸ '''[[Amikacin]] 7.5-10 mg/kg'''<br> OR <br> ▸ '''[[Streptomycin]] 12–18 mg/kg'''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | '''<u>Group 3: Fluoroquinolones</u>''' <br>
+▸ '''[[Levofloxacin]] 500-1000 mg'''<br> OR <br> ▸ '''[[Moxifloxacin]] 400 mg'''<br> OR <br> ▸ '''[[Ofloxacin]] 400 mg'''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | '''<u>Group 4:Oral bacteriostatic second-line drugs</u>''' <br>
+▸ '''[[Ethionamide]] 15-20 mg/kg'''<br> OR <br> ▸ '''[[Protionamide]] 15-20 mg/kg''' <br> OR <br> ▸ '''[[Cycloserine]] 10-15 mg/kg'''<br> OR <br> ▸ '''[[Terizidone]] 10-20 mg/kg '''<br> OR <br>▸ '''[[Aminosalicylic acid|Para-aminosalicylic acid]] 8-12 g/d divided q8-12h'''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left |<small>Table adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed.<ref name="WHO 2013"> {{cite web|  url=http://www.who.int/tb/publications/tb_treatmentguidelines/en/| title=2013 WHO Treatment of Tuberculosis: Guidelines for National Programmes (4th Edition) }}</ref></small>
+|}
+|}
+{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table02" style="background: #FFFFFF;"
+| valign=top |
+{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
+! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|MDR-TB Children}}
+|-
+| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Standard Regimen'''''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | '''<u>Group 1: First-line oral drugs</u>''' <br>
+▸ ''' [[Pyrazinamide]] 20-30 mg/kg (Max: 600 mg)''' <br> OR <br> ▸ '''[[Ethambutol]] 15-20 mg/kg''' <br> OR <br> ▸ '''[[Rifabutin]] 5 mg/kg'''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | '''<u>Group 2: Injectable drugs</u>''' <br>
+▸ '''[[Capreomycin]] 15-30 mg/kg (Max: 1000 mg)'''<br> OR <br> ▸ '''[[Kanamycin]] 15-30 mg/kg (Max: 1000 mg)'''<br> OR <br> ▸ '''[[Amikacin]] 15-22.5 mg/kg (Max: 1000 mg)'''<br> OR <br> ▸ '''[[Streptomycin]] 12-18 mg/kg'''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | '''<u>Group 3: Fluoroquinolones</u>''' <br>
+▸ '''[[Levofloxacin]] 7.5-10 mg/kg'''<br> OR <br> ▸ '''[[Moxifloxacin]] 7.5-10 mg/kg'''<br> OR <br> ▸ '''[[Ofloxacin]] 15-20 mg/kg divided q12h (Max:800 mg)'''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
+|-
+| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | '''<u>Group 4:Oral bacteriostatic second-line drugs</u>''' <br>
+▸ '''[[Ethionamide]] 15-20 mg/kg divided q12h (Max: 1000 mg)'''<br> OR <br> ▸ '''[[Protionamide]] 15-20 mg/kg divided q12h (Max: 1000 mg)''' <br> OR <br> ▸ '''[[Cycloserine]] 10-20 mg/kg (Max: 1000 mg)'''<br> OR <br> ▸ '''[[Terizidone]] 10-20 mg/kg (Max: 1000 mg)'''<br> OR <br> ▸ '''[[Aminosalicylic acid|Para-aminosalicylic acid]] 150 mg/kg divided q8-12h(Max: 12 000 mg)'''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left |<small>Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed.<ref name="WHO 2013"> {{cite web|  url=http://www.who.int/tb/publications/tb_treatmentguidelines/en/| title=2013 WHO Treatment of Tuberculosis: Guidelines for National Programmes (4th Edition) }}</ref> and Guidance for national tuberculosis programmes on the management of tuberculosis in children <ref name="WHO TB Children"> {{cite web |url=http://apps.who.int/iris/bitstream/10665/112360/1/9789241548748_eng.pdf| title=WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children, 2014}} </ref></small>
+|}
+|}
+|}
-Response to treatment must be obtained by repeated sputum cultures (monthly if possible). Treatment for MDR-TB must be given for a minimum of 18 months and cannot be stopped until the patient has been culture-negative for a minimum of nine months. It is not unusual for patients with MDR-TB to be on treatment for two years or more.
-Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients with MDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason). Some physicians will insist that these patients are isolated until their sputum is smear negative, or even culture negative (which may take many months, or even years). Keeping these patients in hospital for weeks (or months) on end may be a practical or physical impossibility and the final decision depends on the clinical judgement of the physician treating that patient. The attending physician should make full use of therapeutic drug monitoring (particularly of the aminoglycosides) both to monitor compliance and to avoid toxic effects.
-Some supplements may be useful as adjuncts in the treatment of tuberculosis, but the for the purposes of counting drugs for MDR-TB, they count as zero (if you already have four drugs in the regimen, it may be beneficial to add arginine or vitamin D or both, but you still need another drug to make five).
-* [[arginine]]<ref>{{cite journal | journal=Eur Respir J | year=2003 | volume=21 | pages=483&ndash;88 | title=Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis | author=Schön T, Elias D, Moges F, ''et al.'' | url=http://erj.ersjournals.com/cgi/content/abstract/21/3/483 }}</ref> (peanuts are a good source)
-* [[Vitamin D]]<ref>{{cite journal | journal=Infect Immunity | year=1998 | pages=5314&ndash;21 | volume=66 | issue=11 | author=Rockett KA, Brookes R, Udalova I, ''et al.'' | title=1,25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of ''Mycobacterium tuberculosis'' in a human macrophage-like cell line  | url=http://iai.asm.org/cgi/content/abstract/66/11/5314 }}</ref>
-The drugs listed below have been used in desperation and it is uncertain whether they are effective at all.  They are used when it is not possible to find five drugs from the list above.
-* [[imipenem]]<ref>{{cite journal | journal=Antimicrob Agents Chemother | year=2005 | volume=49 | issue=7 | pages=2816&ndash;21 | title=Imipenem for treatment of tuberculosis in mice and humans | author=Chambers HF, Turner J, Schecter GF, Kawamura M, Hopewell PC. | id=PMID 15980354 }}</ref>
-* [[co-amoxiclav]]<ref>{{cite journal | journal=Clin Infect Dis | year=1998 | volume=26 | issue=4 | pages=874&ndash;7 | title=Activity of amoxicillin/clavulanate in patients with tuberculosis | author=Chambers HF, Kocagoz T, Sipit T, Turner J, Hopewell PC. | id=PMID 9564467 }}</ref><ref>{{cite journal | journal=Scand J Infect Dis | year=2001 | volume=33 | issue=6 | pages=466&ndash;9 | title=Early bactericidal activity of amoxicillin in combination with clavulanic acid in patients with sputum smear-positive pulmonary tuberculosis | author=Donald PR, Sirgel FA, Venter A, ''et al.'' | id=PMID 11450868 }}</ref>
-* [[clofazimine]]<ref>{{cite journal | journal=Am J Respir Crit Care Med | volume=151 | issue=4 | year=1995 | pages=1083&ndash;86 | title=Chemotherapeutic activity of clofazimine and its analogues against Mycobacterium tuberculosis. In vitro, intracellular, and ''in vivo'' studies. | author=Jagannath C, Reddy MV,  Kailasam S, O'Sullivan JF, Gangadharam PR. | url=http://ajrccm.atsjournals.org/cgi/content/abstract/151/4/1083 }}</ref><ref>{{cite journal | journal=Antimicrob Agents Chemother | year=1999 | pages=1638&ndash;43 | volume=43 | issue=7 | title=Effective treatment of acute and chronic murine tuberculosis with liposome-encapsulated clofazimine | author=Adams LM, Sinha I, Franzblau SG, ''et al.'' | url=http://aac.asm.org/cgi/reprint/43/7/1638.pdf }}</ref><ref>{{cite journal | journal=Antimicrob Agents Chemother | year=2004 | pages=3133&ndash;35 | volume=48 | issue=8 | title=Lack of activity of orally administered clofazimine against intracellular ''Mycobacterium tuberculosis'' in whole-blood culture | url=http://aac.asm.org/cgi/reprint/48/8/3133.pdf }}</ref>
-* [[prochlorperazine]]<ref>{{cite journal | journal=Antibiotic Med Clin Ther. | year=1958 | volume=5 | issue=5 | pages=305&ndash;9 | title=Prochlorperazine (compazine) as an aid in the treatment of pulmonary tuberculosis | author=Shubin H, Sherson J, Pennes E, Glaskin A, Sokmensuer A.
-| id=PMID 13521769 }}</ref>
-* [[metronidazole]]<ref>{{cite journal | journal=Antimicrob Agents Chemother | year=1994 | volume=38 | issue=9 | pages=2054&ndash;58 | title=Metronidazole is bactericidal to dormant cells of ''Mycobacterium tuberculosis'' | author=Wayne LG, Sramek HA | url=http://aac.asm.org/cgi/content/abstract/38/9/2054 }}</ref>
-The follow drugs are experimental compounds that are not commercially available, but which may be obtained from the manufacturer as part of a clinical trial or on a compassionate basis.  Their efficacy and safety are unknown:
-* [[PA-824]]<ref name="Stover2000">{{cite journal | journal=Nature | year=2000 | volume=405| issue=6789 | pages=962&ndash;6 | title=A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis | author=Stover CK, Warrener P, VanDevanter DR, ''et al.'' | id=PMID 10879539}}</ref> (manufactured by [[PathoGenesis Corporation]], Seattle, Washington)
-* [[R207910]]<ref name="Andries2005">{{cite journal | title=A diarylquinoline drug active on the ATP-synthase of ''Mycobacterium tuberculosis'' | author=Andries K, Verhasselt P, Guillemont J, ''et al.'' | journal=Science | year=2005 | volume=307 | issue=5707 | pages=223&ndash;27 | DOI=10.1126/science.1106753 }}</ref> ([[Koen Andries]] et al., under development by [[Johnson & Johnson]])
 ==References==
 {{reflist|2}}

Multi-drug-resistant tuberculosis medical therapy: Difference between revisions

Revision as of 12:28, 25 September 2014

Overview

Medical Therapy

Drugs Used in Drug-Resistant Tuberculosis

MDR Tuberculosis Regimen Adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed. [1]

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MDR Tuberculosis Regimen Adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed. ^[1]