Mycobacterium tuberculosis: Difference between revisions
From IDWiki
Mycobacterium tuberculosis
(→: added cxr findings) |
(→) |
||
(44 intermediate revisions by the same user not shown) | |||
Line 1: | Line 1: | ||
− | * ''Mycobacterium tuberculosis'' causes '''tuberculosis''' |
||
− | * Most commonly '''pulmonary TB''' but extrapulmonary tuberculosis is possible (including adenitis, gastrointestinal TB, pericarditis, meningitis) |
||
− | * Standard treatment for susceptible TB is '''RIPE x2mo then RI x4mo''' |
||
− | |||
== Background == |
== Background == |
||
+ | *''Mycobacterium tuberculosis'' causes '''tuberculosis''' |
||
− | === Microbiology === |
||
+ | *Most commonly '''pulmonary TB''' but extrapulmonary tuberculosis is possible (including adenitis, gastrointestinal TB, pericarditis, meningitis) |
||
− | * Fastidious [[Has Gram stain::acid-fast]] [[Has shape::bacillus]] |
||
+ | *Standard treatment for susceptible TB is '''RIPE x2mo then RI x4mo''' |
||
+ | |||
+ | ==Microbiology== |
||
+ | *Fastidious, aerobic [[Stain::acid-fast]] [[Shape::bacillus]] |
||
+ | *Cell wall has high lipid content |
||
+ | *Generation time is very long (15 to 20 hours) |
||
+ | *''M. tuberculosis'' is a complex that comprises seven species: |
||
+ | **''M. tuberculosis'' sensu stricto: most common causative organism worldwide |
||
+ | **''M. africanum'': 50% of cases in West africa |
||
+ | **''M. canetti'': rare cause in Eastern African |
||
+ | **''M. bovis'': disease in cattle but can infect humans |
||
+ | **''M. caprae'': disease in cattle |
||
+ | **''M. microti'': disease in rodents |
||
+ | **''M. pinnipdeii'': disease in seals, with rare human infection |
||
+ | |||
+ | ===Epidemiology=== |
||
+ | |||
+ | *Typically spread via airborne route |
||
+ | **Droplets are expelled during coughing, sneezing, or talking, and are suspended in the air |
||
+ | **They can remain for up to 30 minutes |
||
+ | **Killed by ultraviolet light |
||
+ | **Not transmitted via fomites |
||
+ | *About a third of the world is infected, mostly as latent tuberculosis |
||
+ | **This progresses to active tuberculosis at about 3 or 4% in the first year and 5% over the rest of their life |
||
+ | *Reinfection accounts for ~40% of active tuberculosis in endemic countries |
||
+ | *Highest rates in sub-Saharan Africa and south/southeast Asia |
||
+ | |||
+ | ===Risk Factors=== |
||
+ | |||
+ | *Source factors, such as sputum smear positivity, cough, cavitations |
||
+ | *Exposure duration, closeness of contact |
||
+ | *Factors in the exposed person, such as immune compromise, HIV status |
||
+ | |||
+ | ==Clinical Manifestations== |
||
+ | ===Classification=== |
||
+ | |||
+ | *Primary vs. reactivation vs. reinfection |
||
+ | *Latent vs. active |
||
+ | |||
+ | ===Primary Tuberculosis=== |
||
+ | |||
+ | *Primary tuberculosis is usually asymptomatic |
||
+ | *Possible presentations include mild URTI with cough and/or fever |
||
+ | *May be seen on CXR as infiltrate in mid-lung zones with hilar adenopathy |
||
+ | *Ghon complex, especially in children |
||
+ | *May progress in children and the immunocompromised patients |
||
+ | *Immunological phenomena |
||
+ | **Erythema nodosum |
||
+ | **Phlyctenular conjunctivitis |
||
+ | **Erythema induratum |
||
+ | |||
+ | ===Pulmonary Tuberculosis=== |
||
+ | |||
+ | *Most common presentation of active tuberculosis |
||
+ | *Refer to separate article on [[pulmonary tuberculosis]] |
||
+ | |||
+ | ===Extra-Pulmonary Tuberculosis=== |
||
+ | |||
+ | *Pleural tuberculosis is most common extrapulmonary site |
||
+ | *[[Scrofula]] (cervical lymph node infection) next-most common |
||
+ | *[[Tuberculous meningitis]] |
||
+ | *[[Tuberculous pericarditis]] |
||
+ | *Renal tuberculosis |
||
+ | *Abdominal tuberculosis |
||
+ | *Gastrointestinal tuberculosis |
||
+ | *[[Cutaneous tuberculosis]] |
||
+ | |||
+ | ===Latent Tuberculosis=== |
||
+ | |||
+ | *Refers to chronic latent infection contained within granulomas that may reactivate in the future |
||
+ | *Refer to [[Latent tuberculosis infection]] |
||
+ | |||
+ | ===Other=== |
||
+ | |||
+ | *[[Neonatal tuberculosis]] |
||
+ | |||
+ | ==Investigations== |
||
+ | |||
+ | *Radiography: chest x-ray with or without CT chest |
||
+ | **Primary TB: consolidation, lymphadenopathy, pleural effusion, Ghon complex |
||
+ | **Reactivation TB: patchy upper-lobe consolidation, cavitation, fibrosis, pleural disease |
||
+ | **Miliary TB: uniform 1-3 mm diameter diffuse nodules |
||
+ | |||
+ | ==Diagnosis== |
||
+ | |||
+ | *[[Latent tuberculosis infection#Diagnosis|Latent tuberculosis testing]] |
||
+ | **Tuberculin skin test (TST) |
||
+ | **Interferon-gamma release assay (IGRA) |
||
+ | *Serology or immunologic testing |
||
+ | **Urine lipoarabinomannan antigen |
||
+ | *Microbiology |
||
+ | **Samples can include routine or induced sputum (x3 q8h including 1 early AM) or bronchoscopy, or tissue sample |
||
+ | **Spontaneous sputum should include at least one morning sputum, ideally, but can be done all in a row at least one hour apart if needed |
||
+ | **Acid-fast bacillus culture of sputum x3 is about 70% sensitive, and PCR (ANTB) x1 is about 75% sensitive |
||
+ | *Molecular testing |
||
+ | **PCR, including GeneXpert |
||
+ | |||
+ | ==Management== |
||
+ | |||
+ | * Requires at least 2 effective drugs at all times, including at least 3 effective drugs during intensive phase |
||
+ | ** Consider rapid rifampin resistance testing (PCR) in all patients |
||
+ | * Most patients are started on RIPE |
||
+ | **In cases of increased risk for [[MDR-TB]], still use RIPE while awaiting rapid rifampin testing |
||
+ | **Typical duration is intensive therapy for 2 months (with at least 3 drugs), then narrowed to at least 2 drugs for the remainder of treatment |
||
+ | **Rifampin is the most effective agent, and any regimen that excludes rifampin must be extended to 12-18 months |
||
+ | * See also: |
||
+ | ** [[Pulmonary tuberculosis#Management|Management of pulmonary tuberculosis]] |
||
+ | ** [[Tuberculous meningitis#Management|Management of tuberculous meningitis]] |
||
+ | ** [[Drug-resistant tuberculosis#Management|Management of drug-resistant tuberculosis]] |
||
+ | |||
+ | ===Antibiotics=== |
||
+ | {| class="wikitable" |
||
+ | !Drug!!Dose!!Side effects |
||
+ | |- |
||
+ | ! colspan="3" |First-Line Medications |
||
+ | |- |
||
+ | |[[Is treated by::Rifampin]] |
||
+ | |10 mg/kg daily, no max |
||
+ | |Drug interactions, rash, hepatitis, flu-like illness, neutropenia, thrombocytopenia |
||
+ | |- |
||
+ | |[[Is treated by::Isoniazid]] |
||
+ | |5 mg/kg daily, max 300 mg daily, with pyridoxine 25 mg po daily |
||
+ | |Rash, hepatitis, neuropathy, CNS toxicity, anemia |
||
+ | |- |
||
+ | |[[Is treated by::Pyrazinamide]] |
||
+ | |25 mg/kg daily, max 2 g daily |
||
+ | |Hepatitis, rash, arthralgia, gout |
||
+ | |- |
||
+ | |[[Is treated by::Ethambutol]] |
||
+ | |15 mg/kg daily, max 1.6 g daily |
||
+ | |Optic/retrobulbar neuritis, rash |
||
+ | |- |
||
+ | ! colspan="3" |Second-Line Medications |
||
+ | |- |
||
+ | |[[Is treated by::Streptomycin]] |
||
+ | |15 mg/kg daily, max 1 g |
||
+ | | rowspan="2" |Auditory and vestibular toxicity, renal toxocity, avoid in pregnancy |
||
+ | |- |
||
+ | |[[Is treated by::Amikacin]], [[Is treated by::kanamycin]], or [[Is treated by::capreomycin]] |
||
+ | |15 mg/kg daily, man 1 g |
||
+ | |- |
||
+ | |[[Is treated by::Ethionamide]] |
||
+ | |250 mg BID to TID, max 1 g |
||
+ | |GI disturbance, hepatotoxicity, endocrine effects, neurotoxicity, avoid in pregnancy |
||
+ | |- |
||
+ | |[[Is treated by::Para-amino salicylic acid]] |
||
+ | |4 g BID or TID, max 10 g |
||
+ | |GI disturbance, hepatic dysfunction, hypothyroidism, avoid in aspirin allergy |
||
+ | |- |
||
+ | |[[Is treated by::Cycloserine]] |
||
+ | |250 mg BID to TID, max 1 g |
||
+ | |Avoid in epilepsy, psychiatric illness, and alcoholism |
||
+ | |- |
||
+ | |[[Is treated by::Levofloxacin]] |
||
+ | |500 to 1000 mg po daily |
||
+ | | rowspan="2" |GI disturbance, headache, anxiety, tremor, long QT, avoid in pregnancy and children |
||
+ | |- |
||
+ | |[[Is treated by::Moxifloxacin]] |
||
+ | |400 to 600 mg daily |
||
+ | |- |
||
+ | |[[Is treated by::Rifabutin]] |
||
+ | |300 mg daily |
||
+ | |Hepatotoxicity, uveitis, thrombocytopenia, neutropenia, drug interactions |
||
+ | |- |
||
+ | |[[Is treated by::Clofazimine]] |
||
+ | |100 to 300 mg daily |
||
+ | |Skin discolouration, conjunctiva, cornea, body fluid discolouration, GI intolerance, photosensitivity |
||
+ | |- |
||
+ | ! colspan="3" |Third-Line Medications |
||
+ | |- |
||
+ | |[[Is treated by::Linezolid]] |
||
+ | |600 mg po daily |
||
+ | | |
||
+ | |- |
||
+ | |[[Bedaquiline]] |
||
+ | |400 mg po daily for 2 weeks followed by 200 mg thrice weekly |
||
+ | |Arthralgias, dizziness, headache, hyperuriemia, insomnia, myalgia, nausea, prolonged ECG QT interval, pruritus, and vomiting |
||
+ | |- |
||
+ | |[[Pretomanid]] |
||
+ | | |
||
+ | | |
||
+ | |- |
||
+ | |[[Delamanid]] |
||
+ | | |
||
+ | | |
||
+ | |- |
||
+ | ! colspan="3" |Adjunctive Therapies |
||
+ | |- |
||
+ | |Corticosteroids for patients with [[tuberculous meningitis]] or [[tuberculous pericarditis]] |
||
+ | |[[Prednisone]] 40 to 80 mg po daily for 6 to 12 weeks |
||
+ | | |
||
+ | |} |
||
+ | |||
+ | ==== Doses by Weight ==== |
||
+ | {| class="wikitable" |
||
+ | ! rowspan="2" |Drug |
||
+ | ! rowspan="2" |Dose |
||
+ | ! rowspan="2" |Tabs |
||
+ | ! colspan="5" |Weight (kg) |
||
+ | |- |
||
+ | !30-35 |
||
+ | !36-45 |
||
+ | !46-55 |
||
+ | !56-70 |
||
+ | !>70 |
||
+ | |- |
||
+ | ! colspan="8" |First-Line Medications |
||
+ | |- |
||
+ | |[[rifampin]] |
||
+ | |10 mg/kg |
||
+ | |150 & 300 mg |
||
+ | |300 mg |
||
+ | | colspan="2" |450 mg |
||
+ | | colspan="2" |600 mg |
||
+ | |- |
||
+ | |[[isoniazid]] |
||
+ | |5 mg/kg |
||
+ | |100 & 300 mg |
||
+ | |150 mg |
||
+ | |200 mg |
||
+ | | colspan="3" |300 mg |
||
+ | |- |
||
+ | |[[pyrazinamide]] |
||
+ | |25 mg/kg |
||
+ | |500 mg |
||
+ | |750 mg |
||
+ | |1000 mg |
||
+ | |1250 mg |
||
+ | |1500 mg |
||
+ | |1750-2000 mg |
||
+ | |- |
||
+ | |[[ethambutol]] |
||
+ | |15 mg/kg |
||
+ | |100 & 400 mg |
||
+ | |600 mg |
||
+ | |800 mg |
||
+ | |1000 mg |
||
+ | | colspan="2" |1200 mg |
||
+ | |- |
||
+ | ! colspan="8" |Alternative Medications |
||
+ | |- |
||
+ | |[[rifabutin]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="5" |300 mg |
||
+ | |- |
||
+ | |[[levofloxacin]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="2" |750 mg |
||
+ | | colspan="3" |1000 mg |
||
+ | |- |
||
+ | |[[moxifloxacin]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="5" |400 mg |
||
+ | |- |
||
+ | |[[ethionamide]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="2" |500 mg |
||
+ | | colspan="2" |750 mg |
||
+ | |1000 mg |
||
+ | |- |
||
+ | |[[prothionamide]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="2" |500 mg |
||
+ | | colspan="2" |750 mg |
||
+ | |1000 mg |
||
+ | |- |
||
+ | |[[cycloserine]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="3" |500 mg |
||
+ | | colspan="2" |750 mg |
||
+ | |- |
||
+ | |[[p-aminosalicylic acid]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="4" |4 g bid |
||
+ | |4 g bid to tid |
||
+ | |- |
||
+ | |[[bedaquiline]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="5" |400 mg daily for 2 weeks then 200 mg 3 times per week |
||
+ | |- |
||
+ | |[[clofazimine]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="5" |200-300 mg for 2 months then 100 mg |
||
+ | |- |
||
+ | |[[linezolid]] |
||
+ | | |
||
+ | | |
||
+ | | colspan="5" |600 mg daily |
||
+ | |} |
||
+ | |||
+ | === Duration === |
||
+ | {| class="wikitable" |
||
+ | !Syndrome |
||
+ | !Total Duration |
||
+ | !Notes |
||
+ | |- |
||
+ | ! colspan="3" |Pulmonary Tuberculosis |
||
+ | |- |
||
+ | |Standard |
||
+ | |6 months |
||
+ | | |
||
+ | |- |
||
+ | |Cavitary disease, with diabetes |
||
+ | |9 months |
||
+ | | |
||
+ | |- |
||
+ | |Elderly >75 years |
||
+ | |9 months |
||
+ | |without pyrazinamide |
||
+ | |- |
||
+ | |High risk of hepatitis |
||
+ | |9 months |
||
+ | |without pyrazinamide |
||
+ | |- |
||
+ | |High risk of recurrence |
||
+ | |9 months |
||
+ | |extensive disease, or baseline cavitary disease with smear or culture positive at 2 months |
||
+ | |- |
||
+ | |Pregnancy |
||
+ | |6-9 months |
||
+ | |with or without pyrazinamide |
||
+ | |- |
||
+ | |[[HIV]] (untreated) |
||
+ | |9 months |
||
+ | | |
||
+ | |- |
||
+ | |Severe liver disease, avoiding RIF |
||
+ | |12-18 months |
||
+ | |without rifampin, isoniazid, and pyrazinamide |
||
+ | |- |
||
+ | |Solid-organ transplant |
||
+ | |9 months |
||
+ | | |
||
+ | |- |
||
+ | |TNF-alpha inhibitors |
||
+ | |9 months |
||
+ | | |
||
+ | |- |
||
+ | ! colspan="3" |Extra-Pulmonary Tuberculosis |
||
+ | |- |
||
+ | |Bone and joint |
||
+ | |6-12 months |
||
+ | |high risk of relapse; duration depends on severity of disease |
||
+ | |- |
||
+ | |[[Tuberculous meningitis|CNS TB, meningitis]] |
||
+ | |9-12 months |
||
+ | |with steroids |
||
+ | |- |
||
+ | |CNS TB, tuberculoma or arachnoiditis |
||
+ | |9-12 months |
||
+ | |without steroids unless significant mass effect |
||
+ | |- |
||
+ | |Cutaneous |
||
+ | |6 months |
||
+ | | |
||
+ | |- |
||
+ | |Disseminated disease |
||
+ | |6 months |
||
+ | | |
||
+ | |- |
||
+ | |Disseminated disease, with diabetes |
||
+ | |9 months |
||
+ | | |
||
+ | |- |
||
+ | |Genitourinary |
||
+ | |6 months |
||
+ | | |
||
+ | |- |
||
+ | |[[Tuberculous adenitis|Lymphadenitis]] |
||
+ | |6 months |
||
+ | |surgery not necessary |
||
+ | |- |
||
+ | |Ocular |
||
+ | |6 months |
||
+ | | |
||
+ | |- |
||
+ | |[[Tuberculous pericarditis|Pericarditis]] |
||
+ | |6 months |
||
+ | |with steroids if HIV-negative, without steroids if untreated HIV, unclear use if treated HIV |
||
+ | |- |
||
+ | |[[Pleural tuberculosis|Pleural]] |
||
+ | |6 months |
||
+ | |drainage not necessary |
||
+ | |} |
||
+ | |||
+ | === Routine Monitoring === |
||
+ | |||
+ | ==== Clinical ==== |
||
+ | |||
+ | * Start of treatment: physical examination, weight, visual acuity, colour vision testing |
||
+ | * Follow-up: weight, repeat vision testing monthly while on EMB |
||
+ | * Assess adherence, adverse events, and response to therapy |
||
+ | |||
+ | ==== Radiology ==== |
||
+ | |||
+ | * Chest x-ray at diagnosis (if not already done as part of diagnostic process), at 2 months, and at end of therapy |
||
+ | |||
+ | ==== Laboratory ==== |
||
+ | |||
+ | * Start of treatment: CBC, ALT, bilirubin, creatinine, [[HIV]]/[[HBV]]/[[HCV]] serologies, [[HbA1c]] |
||
+ | * Follow-up: monthly CBC, creatinine, ALT, and bilirubin |
||
+ | |||
+ | ==== Microbiology ==== |
||
+ | |||
+ | * Sputum culture twice monthly (~q2wk) until smear negative |
||
+ | ** Repeat susceptibility testing if sputum culture is positive at 3 months |
||
+ | ** Sputum induction ''not'' required if unable to produce sputum and smear negative |
||
+ | * Nearing end of therapy, sputum culture 2 months and one month before planned end |
||
+ | ** If sputum remains culture positive at 2 months, repeat sputum cultures should be performed monthly until culture conversion is confirmed |
||
+ | |||
+ | ===Immune Reconstitution Inflammatory Syndrome (IRIS)=== |
||
+ | |||
+ | === Adverse Drug Reactions === |
||
+ | |||
+ | ==== Drug-Induced Liver Injury (DILI) ==== |
||
+ | *Most common complication leading to treatment interruption, with a mortality of 6-12% if drugs are not stopped |
||
+ | *[[Pyrazinamide]], followed by [[isoniazid]], then [[rifampin]], are the most common causes of liver injury[[CiteRef::yee2003in]][[CiteRef::saukkonen2006an]] |
||
+ | *Most patients can have the same TB drugs reintroduced without recurrence of DILI, though recurrence can be delayed |
||
+ | *Procedure |
||
+ | **Hold all medications if ALT >120 (3x ULN) and symptoms, if ALT >200 (5x ULN) even without symptoms, or bili >2x ULN |
||
+ | **If severe disease and patient needs to continue treatment, immediately start two second-line agents (e.g. a fluoroquinolone and an injectable) |
||
+ | **Once AST & ALT are less than twice the upper limit of normal, reintroduce the original drugs every 3 to 5 days, trending enzymes |
||
+ | **Only rechallenge with pyrazinamide if it was a mild case |
||
+ | |||
+ | ==== Dermatologic Reactions ==== |
||
+ | |||
+ | ===== Mild Reactions ===== |
||
+ | |||
+ | * Post-dose flushing or itching with or without rash |
||
+ | ** Mostly face or scalp, and may involve redness or watering of the eyes |
||
+ | ** Usually 2 to 3 hours after drug ingestion |
||
+ | ** Caused by [[rifampin]] and [[pyrazinamide]] |
||
+ | ** Can use an antihistamine if it is bothersome |
||
+ | * Flushing and/or itching with or without a rash, plus hot flashes, palpitations, headaches, or increased blood pressure |
||
+ | ** Immediately after ingestion of certain foods |
||
+ | ** Usually resolves within 2 hours |
||
+ | ** Caused by [[isoniazid]] plus tyramine-containing foods (cheese, red wine) or certain fish (tuna, skipjack) |
||
+ | ** Avoid the causative foods |
||
+ | |||
+ | ===== Moderate-to-Severe Reactions ===== |
||
+ | |||
+ | * Hives with or without fever |
||
+ | * Caused by [[isoniazid]] < [[rifampin]] < [[pyrazinamide]] < [[ethionamide]] < [[cycloserine]] < [[ethambutol]] < [[Para-aminosalicylic acid|PASA]] < [[streptomycin]] |
||
+ | * In children, viral infections may be confused for hives |
||
+ | |||
+ | ===== Management ===== |
||
+ | * Discontinue all drugs until the reaction resolves |
||
+ | * Can consider starting TB background regimen with [[levofloxacin]] 15-20 mg daily (max 1 g) plus [[linezolid]] 600 mg |
||
+ | ** Substitute [[amikacin]] 15 mg/kg daily if one of the above cannot be given |
||
+ | * Every 4 days, add a new drug back in the following order, with a lower challenge dose on the first day: |
||
+ | ** [[Isoniazid]] 50 mg challenge on day 1 followed by 300 mg on day 2 |
||
+ | ** [[Rifampin]] 75 mg challenge on day 1 followed by 300 mg on day 2 |
||
+ | ** [[Pyrazinamide]] 250 mg challenge on day 1 followed by 1 g on day 2 |
||
+ | ** [[Ethionamide]] 125 mg challenge on day 1 followed by 375 mg on day 2 |
||
+ | ** [[Cycloserine]] 125 mg challenge on day 1 followed by 250 mg on day 2 |
||
+ | ** [[Ethambutol]] 100 mg on day 1 followed by 500 mg on day 2 |
||
+ | ** [[Para-aminosalicylic acid|PASA]] 1 g on day 1 followed by 5 g on day 2 |
||
+ | ** [[Streptomycin]] 125 mg on day 1 followed by 500 mg on day 2 |
||
+ | * If the reaction was severe, use 10% of the day 1 dose (e.g. [[isoniazid]] 5 mg) |
||
− | === |
+ | ===Adherence to Treatment=== |
− | * Reinfection accounts for ~40% of active tuberculosis in endemic countries |
||
− | * Latent tuberculosis in ~30% of the global population |
||
+ | *Refer to [http://www.letstalktb.org/ Let's Talk TB] |
||
− | == Clinical Presentation == |
||
− | === Classification === |
||
− | * Primary vs. reactivation vs. reinfection |
||
− | * Latent vs. active |
||
− | === |
+ | === Special Populations === |
− | * Primary tuberculosis is usually asymptomatic |
||
− | * Possible presentations include mild URTI with cough and/or fever |
||
− | * May be seen on CXR as infiltrate in mid-lung zones with hilar adenopathy |
||
− | * Ghon complex, especially in children |
||
− | * May progress in children and the immunocompromised patients |
||
− | * Immunological phenomena |
||
− | ** Erythema nodosum |
||
− | ** Phlyctenular conjunctivitis |
||
− | ** Erythema induratum |
||
− | === |
+ | ==== Liver Disease ==== |
− | * Subacute or [[chronic cough]] (at least 2 to 3 weeks) eventually becoming productive and occasionally involving [[hemoptysis]] |
||
− | ** Should be suspected in any patient with '''cough and [[HIV]] infection''' |
||
− | * Constitutional symptoms, with fevers, night sweats, and unexplained weight loss |
||
− | * Usually from reactivation of [[latent tuberculosis infection]], and usually reactivates in lung apices |
||
− | * May transiently improve with partially-active antibiotics such as [[fluoroquinolones]] |
||
+ | * Most of the first-line medications (except [[ethambutol]]) can cause drug-induced hepatotoxicity and should be avoided |
||
− | === Extra-pulmonary tuberculosis === |
||
+ | **[[Rifampin]] may be considered in more extensive disease |
||
− | * Pleural tuberculosis is most common extrapulmonary site |
||
+ | *In general, a combination of [[fluoroquinolone]] plus [[ethambutol]] plus an injectable such as [[amikacin]] for the first 2 months, followed by [[fluoroquinolone]] and [[ethambutol]] alone to complete 18 months total |
||
− | * [[Scrofula]] (cervical lymph node infection) next-most common |
||
− | * [[Tuberculous meningitis]] |
||
− | * [[Tuberculous pericarditis]] |
||
− | * Renal tuberculosis |
||
− | * Abdominal tuberculosis |
||
− | * Gastrointestinal tuberculosis |
||
+ | ==Prevention== |
||
− | === Latent tuberculosis === |
||
− | * Refers to chronic latent infection contained within granulomas that may reactivate in the future |
||
− | * Refer to [[Latent tuberculosis infection]] |
||
+ | ===Vaccination=== |
||
− | == Investigations == |
||
− | * Radiography: chest x-ray with or without CT chest |
||
− | ** Primary TB: consolidation, lymphadenopathy, pleural effusion, Ghon complex |
||
− | ** Reactivation TB: patchy upper-lobe consolidation, cavitation, fibrosis, pleural disease |
||
− | ** Miliary TB: uniform 1-3 mm diameter diffuse nodules |
||
− | * Microbiology: |
||
− | ** Samples can include routine or induced sputum (x3) or bronchoscopy, or tissue sample |
||
− | ** Spontaneous sputum should include at least one morning sputum, ideally, but can be done all in a row at least one hour apart if needed |
||
− | ** Acid-fast bacillus culture of sputum x3 is about 70% sensitive, and PCR (ANTB) x1 is about 75% sensitive |
||
+ | *BCG vaccine given at or shortly after birth in many countries |
||
− | == Management == |
||
− | * Standard HREZ x2mo then HR x4mo |
||
− | ** Isoniazid 5mg/kg/d, max 300mg daily |
||
− | ** Rifampin 10mg/kg/d |
||
− | ** Pyrazinamide 25mg/kg/d, max 2g daily |
||
− | ** Ethambutol 20mg/kg/d, max 1.2g daily |
||
− | ** Pyridoxine 25 mg po daily |
||
− | * Airborne precautions until: |
||
− | ** Treated for at least 2 weeks |
||
− | ** 3x negative sputum smears |
||
− | *** Collected at 8- to 24-hour intervals, including one early morning collection |
||
− | ** Improvement in symptoms |
||
+ | ===Infection Prevention and Control=== |
||
− | === Immune reconstitution inflammatory syndrome (IRIS) === |
||
+ | *All cases of suspected tuberculosis should be placed in airborne isolation until three sputum smears are negative for tuberculosis, unless it is still suspected and no other diagnosis is made |
||
− | === Drug-induced liver injury (DILI) === |
||
+ | **Sputum samples minimum of 1 hour apart, and at least one early morning sample |
||
− | * Most common complication leading to treatment interruption, with a mortality of 6-12% if drugs are not stopped |
||
+ | **Three induced sputa are preferable to one bronchoscopy |
||
− | * Rif > INH > PZA |
||
+ | **Can accept a single negative PCR test if patient is low probability |
||
− | * Most patients can have the same TB drugs reintroduced without recurrence of DILI, though recurrence can be delayed |
||
+ | **Can accept two negative PCR tests or 1 negative PCR and 2 negative smears if patient is high probability |
||
− | * Procedure |
||
+ | *For patients with smear-negative, culture-positive, drug-susceptible respiratory TB: |
||
− | ** Hold if ALT >120 and symptoms, if ALT >200 even without symptoms, or bili >2x ULN |
||
+ | **Continue airborne precautions until clinical evidence of improvement and a minimum of 2 weeks of effective therapy |
||
− | ** Switch to second-line meds |
||
+ | **Can be discharged home provided there is clinical improvement, drug-resistant TB is not suspected, and there is no contraindication for home isolation |
||
− | ** Reintroduce the original drugs once AST & ALT are <2x ULN |
||
+ | *For patient with smear-positive, culture-positive, drug-susceptible respiratory TB: |
||
− | ** Only rechallenge with pyrazinamide if it was a mild case |
||
+ | **Continue airborne precautions until clinical evidence of improvement and a minimum of 2 weeks of effective therapy |
||
+ | **Can be stopped at 4 weeks, or earlier if there are 3 negative smears |
||
+ | **Can be discharge home as above |
||
+ | *For patients with rifampin- or multidrug-resistant TB: |
||
+ | **Continue airborne precautions as above, but additionally require three negative sputum ''cultures'' to be negative before they are taken out of airborne isolation |
||
+ | ==Further Reading== |
||
− | === Adherence to Treatment === |
||
− | * Refer to [http://www.letstalktb.org/ Let's Talk TB] |
||
+ | *Canadian Tuberculosis Standards, 8th Edition. ''Can J Respiratory Crit Care Sleep Med''. 2022;6:sup1. |
||
− | == Further Reading == |
||
+ | **[https://doi.org/10.1080/24745332.2022.2033062 Chapter 1: Epidemiology of tuberculosis in Canada] |
||
− | * [https://www.canada.ca/en/public-health/services/infectious-diseases/canadian-tuberculosis-standards-7th-edition.htmlCanadian Tuberculosis Standards, 7th Edition (2014)] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2035540 Chapter 2: Transmission and pathogenesis of tuberculosis] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2035638 Chapter 3: Diagnosis of tuberculosis disease and drug-resistant tuberculosis] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2036503 Chapter 4: Diagnosis of tuberculosis infection] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2036504 Chapter 5: Treatment of tuberculosis disease] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2039498 Chapter 6: Tuberculosis preventive treatment in adults] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2036073 Chapter 7: Extra-pulmonary tuberculosis] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2039499 Chapter 8: Drug-resistant tuberculosis] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2043055 Chapter 9: Pediatric tuberculosis] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2039500 Chapter 10: Treatment of active tuberculosis in special populations] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2037909 Chapter 11: Tuberculosis contact investigation and outbreak management] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2041328 Chapter 12: An introductory guide to tuberculosis care to improve cultural competence for health care workers and public health professionals serving Indigenous Peoples of Canada] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2035544 Chapter 13: Tuberculosis surveillance and tuberculosis infection testing and treatment in migrants] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2043677 Chapter 14: Prevention and control of tuberculosis transmission in healthcare settings] |
||
+ | **[https://doi.org/10.1080/24745332.2022.2035123 Chapter 15: Monitoring tuberculosis program performance] |
||
{{DISPLAYTITLE:''Mycobacterium tuberculosis''}} |
{{DISPLAYTITLE:''Mycobacterium tuberculosis''}} |
||
− | [[Category: |
+ | [[Category:Tuberculosis]] |
[[Category:Mycobacteria]] |
[[Category:Mycobacteria]] |
Latest revision as of 11:12, 13 June 2023
Background
- Mycobacterium tuberculosis causes tuberculosis
- Most commonly pulmonary TB but extrapulmonary tuberculosis is possible (including adenitis, gastrointestinal TB, pericarditis, meningitis)
- Standard treatment for susceptible TB is RIPE x2mo then RI x4mo
Microbiology
- Fastidious, aerobic acid-fast bacillus
- Cell wall has high lipid content
- Generation time is very long (15 to 20 hours)
- M. tuberculosis is a complex that comprises seven species:
- M. tuberculosis sensu stricto: most common causative organism worldwide
- M. africanum: 50% of cases in West africa
- M. canetti: rare cause in Eastern African
- M. bovis: disease in cattle but can infect humans
- M. caprae: disease in cattle
- M. microti: disease in rodents
- M. pinnipdeii: disease in seals, with rare human infection
Epidemiology
- Typically spread via airborne route
- Droplets are expelled during coughing, sneezing, or talking, and are suspended in the air
- They can remain for up to 30 minutes
- Killed by ultraviolet light
- Not transmitted via fomites
- About a third of the world is infected, mostly as latent tuberculosis
- This progresses to active tuberculosis at about 3 or 4% in the first year and 5% over the rest of their life
- Reinfection accounts for ~40% of active tuberculosis in endemic countries
- Highest rates in sub-Saharan Africa and south/southeast Asia
Risk Factors
- Source factors, such as sputum smear positivity, cough, cavitations
- Exposure duration, closeness of contact
- Factors in the exposed person, such as immune compromise, HIV status
Clinical Manifestations
Classification
- Primary vs. reactivation vs. reinfection
- Latent vs. active
Primary Tuberculosis
- Primary tuberculosis is usually asymptomatic
- Possible presentations include mild URTI with cough and/or fever
- May be seen on CXR as infiltrate in mid-lung zones with hilar adenopathy
- Ghon complex, especially in children
- May progress in children and the immunocompromised patients
- Immunological phenomena
- Erythema nodosum
- Phlyctenular conjunctivitis
- Erythema induratum
Pulmonary Tuberculosis
- Most common presentation of active tuberculosis
- Refer to separate article on pulmonary tuberculosis
Extra-Pulmonary Tuberculosis
- Pleural tuberculosis is most common extrapulmonary site
- Scrofula (cervical lymph node infection) next-most common
- Tuberculous meningitis
- Tuberculous pericarditis
- Renal tuberculosis
- Abdominal tuberculosis
- Gastrointestinal tuberculosis
- Cutaneous tuberculosis
Latent Tuberculosis
- Refers to chronic latent infection contained within granulomas that may reactivate in the future
- Refer to Latent tuberculosis infection
Other
Investigations
- Radiography: chest x-ray with or without CT chest
- Primary TB: consolidation, lymphadenopathy, pleural effusion, Ghon complex
- Reactivation TB: patchy upper-lobe consolidation, cavitation, fibrosis, pleural disease
- Miliary TB: uniform 1-3 mm diameter diffuse nodules
Diagnosis
- Latent tuberculosis testing
- Tuberculin skin test (TST)
- Interferon-gamma release assay (IGRA)
- Serology or immunologic testing
- Urine lipoarabinomannan antigen
- Microbiology
- Samples can include routine or induced sputum (x3 q8h including 1 early AM) or bronchoscopy, or tissue sample
- Spontaneous sputum should include at least one morning sputum, ideally, but can be done all in a row at least one hour apart if needed
- Acid-fast bacillus culture of sputum x3 is about 70% sensitive, and PCR (ANTB) x1 is about 75% sensitive
- Molecular testing
- PCR, including GeneXpert
Management
- Requires at least 2 effective drugs at all times, including at least 3 effective drugs during intensive phase
- Consider rapid rifampin resistance testing (PCR) in all patients
- Most patients are started on RIPE
- In cases of increased risk for MDR-TB, still use RIPE while awaiting rapid rifampin testing
- Typical duration is intensive therapy for 2 months (with at least 3 drugs), then narrowed to at least 2 drugs for the remainder of treatment
- Rifampin is the most effective agent, and any regimen that excludes rifampin must be extended to 12-18 months
- See also:
Antibiotics
Drug | Dose | Side effects |
---|---|---|
First-Line Medications | ||
Rifampin | 10 mg/kg daily, no max | Drug interactions, rash, hepatitis, flu-like illness, neutropenia, thrombocytopenia |
Isoniazid | 5 mg/kg daily, max 300 mg daily, with pyridoxine 25 mg po daily | Rash, hepatitis, neuropathy, CNS toxicity, anemia |
Pyrazinamide | 25 mg/kg daily, max 2 g daily | Hepatitis, rash, arthralgia, gout |
Ethambutol | 15 mg/kg daily, max 1.6 g daily | Optic/retrobulbar neuritis, rash |
Second-Line Medications | ||
Streptomycin | 15 mg/kg daily, max 1 g | Auditory and vestibular toxicity, renal toxocity, avoid in pregnancy |
Amikacin, kanamycin, or capreomycin | 15 mg/kg daily, man 1 g | |
Ethionamide | 250 mg BID to TID, max 1 g | GI disturbance, hepatotoxicity, endocrine effects, neurotoxicity, avoid in pregnancy |
Para-amino salicylic acid | 4 g BID or TID, max 10 g | GI disturbance, hepatic dysfunction, hypothyroidism, avoid in aspirin allergy |
Cycloserine | 250 mg BID to TID, max 1 g | Avoid in epilepsy, psychiatric illness, and alcoholism |
Levofloxacin | 500 to 1000 mg po daily | GI disturbance, headache, anxiety, tremor, long QT, avoid in pregnancy and children |
Moxifloxacin | 400 to 600 mg daily | |
Rifabutin | 300 mg daily | Hepatotoxicity, uveitis, thrombocytopenia, neutropenia, drug interactions |
Clofazimine | 100 to 300 mg daily | Skin discolouration, conjunctiva, cornea, body fluid discolouration, GI intolerance, photosensitivity |
Third-Line Medications | ||
Linezolid | 600 mg po daily | |
Bedaquiline | 400 mg po daily for 2 weeks followed by 200 mg thrice weekly | Arthralgias, dizziness, headache, hyperuriemia, insomnia, myalgia, nausea, prolonged ECG QT interval, pruritus, and vomiting |
Pretomanid | ||
Delamanid | ||
Adjunctive Therapies | ||
Corticosteroids for patients with tuberculous meningitis or tuberculous pericarditis | Prednisone 40 to 80 mg po daily for 6 to 12 weeks |
Doses by Weight
Drug | Dose | Tabs | Weight (kg) | ||||
---|---|---|---|---|---|---|---|
30-35 | 36-45 | 46-55 | 56-70 | >70 | |||
First-Line Medications | |||||||
rifampin | 10 mg/kg | 150 & 300 mg | 300 mg | 450 mg | 600 mg | ||
isoniazid | 5 mg/kg | 100 & 300 mg | 150 mg | 200 mg | 300 mg | ||
pyrazinamide | 25 mg/kg | 500 mg | 750 mg | 1000 mg | 1250 mg | 1500 mg | 1750-2000 mg |
ethambutol | 15 mg/kg | 100 & 400 mg | 600 mg | 800 mg | 1000 mg | 1200 mg | |
Alternative Medications | |||||||
rifabutin | 300 mg | ||||||
levofloxacin | 750 mg | 1000 mg | |||||
moxifloxacin | 400 mg | ||||||
ethionamide | 500 mg | 750 mg | 1000 mg | ||||
prothionamide | 500 mg | 750 mg | 1000 mg | ||||
cycloserine | 500 mg | 750 mg | |||||
p-aminosalicylic acid | 4 g bid | 4 g bid to tid | |||||
bedaquiline | 400 mg daily for 2 weeks then 200 mg 3 times per week | ||||||
clofazimine | 200-300 mg for 2 months then 100 mg | ||||||
linezolid | 600 mg daily |
Duration
Syndrome | Total Duration | Notes |
---|---|---|
Pulmonary Tuberculosis | ||
Standard | 6 months | |
Cavitary disease, with diabetes | 9 months | |
Elderly >75 years | 9 months | without pyrazinamide |
High risk of hepatitis | 9 months | without pyrazinamide |
High risk of recurrence | 9 months | extensive disease, or baseline cavitary disease with smear or culture positive at 2 months |
Pregnancy | 6-9 months | with or without pyrazinamide |
HIV (untreated) | 9 months | |
Severe liver disease, avoiding RIF | 12-18 months | without rifampin, isoniazid, and pyrazinamide |
Solid-organ transplant | 9 months | |
TNF-alpha inhibitors | 9 months | |
Extra-Pulmonary Tuberculosis | ||
Bone and joint | 6-12 months | high risk of relapse; duration depends on severity of disease |
CNS TB, meningitis | 9-12 months | with steroids |
CNS TB, tuberculoma or arachnoiditis | 9-12 months | without steroids unless significant mass effect |
Cutaneous | 6 months | |
Disseminated disease | 6 months | |
Disseminated disease, with diabetes | 9 months | |
Genitourinary | 6 months | |
Lymphadenitis | 6 months | surgery not necessary |
Ocular | 6 months | |
Pericarditis | 6 months | with steroids if HIV-negative, without steroids if untreated HIV, unclear use if treated HIV |
Pleural | 6 months | drainage not necessary |
Routine Monitoring
Clinical
- Start of treatment: physical examination, weight, visual acuity, colour vision testing
- Follow-up: weight, repeat vision testing monthly while on EMB
- Assess adherence, adverse events, and response to therapy
Radiology
- Chest x-ray at diagnosis (if not already done as part of diagnostic process), at 2 months, and at end of therapy
Laboratory
- Start of treatment: CBC, ALT, bilirubin, creatinine, HIV/HBV/HCV serologies, HbA1c
- Follow-up: monthly CBC, creatinine, ALT, and bilirubin
Microbiology
- Sputum culture twice monthly (~q2wk) until smear negative
- Repeat susceptibility testing if sputum culture is positive at 3 months
- Sputum induction not required if unable to produce sputum and smear negative
- Nearing end of therapy, sputum culture 2 months and one month before planned end
- If sputum remains culture positive at 2 months, repeat sputum cultures should be performed monthly until culture conversion is confirmed
Immune Reconstitution Inflammatory Syndrome (IRIS)
Adverse Drug Reactions
Drug-Induced Liver Injury (DILI)
- Most common complication leading to treatment interruption, with a mortality of 6-12% if drugs are not stopped
- Pyrazinamide, followed by isoniazid, then rifampin, are the most common causes of liver injury12
- Most patients can have the same TB drugs reintroduced without recurrence of DILI, though recurrence can be delayed
- Procedure
- Hold all medications if ALT >120 (3x ULN) and symptoms, if ALT >200 (5x ULN) even without symptoms, or bili >2x ULN
- If severe disease and patient needs to continue treatment, immediately start two second-line agents (e.g. a fluoroquinolone and an injectable)
- Once AST & ALT are less than twice the upper limit of normal, reintroduce the original drugs every 3 to 5 days, trending enzymes
- Only rechallenge with pyrazinamide if it was a mild case
Dermatologic Reactions
Mild Reactions
- Post-dose flushing or itching with or without rash
- Mostly face or scalp, and may involve redness or watering of the eyes
- Usually 2 to 3 hours after drug ingestion
- Caused by rifampin and pyrazinamide
- Can use an antihistamine if it is bothersome
- Flushing and/or itching with or without a rash, plus hot flashes, palpitations, headaches, or increased blood pressure
- Immediately after ingestion of certain foods
- Usually resolves within 2 hours
- Caused by isoniazid plus tyramine-containing foods (cheese, red wine) or certain fish (tuna, skipjack)
- Avoid the causative foods
Moderate-to-Severe Reactions
- Hives with or without fever
- Caused by isoniazid < rifampin < pyrazinamide < ethionamide < cycloserine < ethambutol < PASA < streptomycin
- In children, viral infections may be confused for hives
Management
- Discontinue all drugs until the reaction resolves
- Can consider starting TB background regimen with levofloxacin 15-20 mg daily (max 1 g) plus linezolid 600 mg
- Substitute amikacin 15 mg/kg daily if one of the above cannot be given
- Every 4 days, add a new drug back in the following order, with a lower challenge dose on the first day:
- Isoniazid 50 mg challenge on day 1 followed by 300 mg on day 2
- Rifampin 75 mg challenge on day 1 followed by 300 mg on day 2
- Pyrazinamide 250 mg challenge on day 1 followed by 1 g on day 2
- Ethionamide 125 mg challenge on day 1 followed by 375 mg on day 2
- Cycloserine 125 mg challenge on day 1 followed by 250 mg on day 2
- Ethambutol 100 mg on day 1 followed by 500 mg on day 2
- PASA 1 g on day 1 followed by 5 g on day 2
- Streptomycin 125 mg on day 1 followed by 500 mg on day 2
- If the reaction was severe, use 10% of the day 1 dose (e.g. isoniazid 5 mg)
Adherence to Treatment
- Refer to Let's Talk TB
Special Populations
Liver Disease
- Most of the first-line medications (except ethambutol) can cause drug-induced hepatotoxicity and should be avoided
- Rifampin may be considered in more extensive disease
- In general, a combination of fluoroquinolone plus ethambutol plus an injectable such as amikacin for the first 2 months, followed by fluoroquinolone and ethambutol alone to complete 18 months total
Prevention
Vaccination
- BCG vaccine given at or shortly after birth in many countries
Infection Prevention and Control
- All cases of suspected tuberculosis should be placed in airborne isolation until three sputum smears are negative for tuberculosis, unless it is still suspected and no other diagnosis is made
- Sputum samples minimum of 1 hour apart, and at least one early morning sample
- Three induced sputa are preferable to one bronchoscopy
- Can accept a single negative PCR test if patient is low probability
- Can accept two negative PCR tests or 1 negative PCR and 2 negative smears if patient is high probability
- For patients with smear-negative, culture-positive, drug-susceptible respiratory TB:
- Continue airborne precautions until clinical evidence of improvement and a minimum of 2 weeks of effective therapy
- Can be discharged home provided there is clinical improvement, drug-resistant TB is not suspected, and there is no contraindication for home isolation
- For patient with smear-positive, culture-positive, drug-susceptible respiratory TB:
- Continue airborne precautions until clinical evidence of improvement and a minimum of 2 weeks of effective therapy
- Can be stopped at 4 weeks, or earlier if there are 3 negative smears
- Can be discharge home as above
- For patients with rifampin- or multidrug-resistant TB:
- Continue airborne precautions as above, but additionally require three negative sputum cultures to be negative before they are taken out of airborne isolation
Further Reading
- Canadian Tuberculosis Standards, 8th Edition. Can J Respiratory Crit Care Sleep Med. 2022;6:sup1.
- Chapter 1: Epidemiology of tuberculosis in Canada
- Chapter 2: Transmission and pathogenesis of tuberculosis
- Chapter 3: Diagnosis of tuberculosis disease and drug-resistant tuberculosis
- Chapter 4: Diagnosis of tuberculosis infection
- Chapter 5: Treatment of tuberculosis disease
- Chapter 6: Tuberculosis preventive treatment in adults
- Chapter 7: Extra-pulmonary tuberculosis
- Chapter 8: Drug-resistant tuberculosis
- Chapter 9: Pediatric tuberculosis
- Chapter 10: Treatment of active tuberculosis in special populations
- Chapter 11: Tuberculosis contact investigation and outbreak management
- Chapter 12: An introductory guide to tuberculosis care to improve cultural competence for health care workers and public health professionals serving Indigenous Peoples of Canada
- Chapter 13: Tuberculosis surveillance and tuberculosis infection testing and treatment in migrants
- Chapter 14: Prevention and control of tuberculosis transmission in healthcare settings
- Chapter 15: Monitoring tuberculosis program performance
References
- ^ Daphne Yee, Chantal Valiquette, Marthe Pelletier, Isabelle Parisien, Isabelle Rocher, Dick Menzies. Incidence of Serious Side Effects from First-Line Antituberculosis Drugs among Patients Treated for Active Tuberculosis. American Journal of Respiratory and Critical Care Medicine. 2003;167(11):1472-1477. doi:10.1164/rccm.200206-626oc.