Short case

Lateefah T. AlShammari
18 YO Saudi man
Medically free
Smoker
1-week Hx of
productive cough
Associated with night
sweats and weight
loss
 • Cancer
• Bronchogenic carcinoma (SCC)
• Cavitary pulmonary metastises
• Autoimmune Granuloma
• Granulomatosis with polyangiitis

DDX of cavity • RA – rheumatoid nodules etc.

• Vascular
lesions in • Bland/septic emboli
• Infection
CXR • Pulmonary abscess
• Pulmonary TB
• Trauma
• Pneumatocele
• Youth
• Congenital pulmonary airway malformation
• Pulmonary sequestration
• Bronchogenic cyst
 Pulmonary TB

Management and monitoring

 • Rapid killing of multiplying bacilli
(“bactericidal effect”)
Goals of anti-TB • Achievement of relapse-free cure
(“sterilizing effect”)
therapy • To prevent acquisition of drug resistance
during therapy.
 • Patient factors, such as age, comorbid conditions, immunologic
competence, nutritional status, alcohol abuse;

Factors • Radiographic features, such as extent of disease, presence and size

of cavities;
Influence the • Microbiologic factors, such as baseline colony count, culture
positivity at 2 or 3 months;
Outcome of • Genetic factors, including individual genetic features of drug
absorption and metabolism, individual vulnerability to toxicities,
Tuberculosis immunologic characteristics;
• Programmatic factors, including adherence support interventions
Treatment (enhancers, enablers, monitoring, supervision/DOT), dosing
frequency;
• Pharmacokinetic factors, such as absorption, metabolism, protein
binding, drug clearance, total drug quantities administered;
• Bacillary factors, such as drug tolerance, strain susceptibilities to
drugs in the regimen; and
• Regimen factors, such as number of active drugs, bactericidal and
sterilizing potency, synergy or antagonism, and duration of therapy in
relation to drugs employed.
1st line of therapy regimens
2nd line options
 Drug Mechanism of action Common side effects
Rifampicin inhibits bacterial RNA potent liver enzyme
polymerase inducer
hepatitis, orange secretions
flu-like symptoms

Isoniazid inhibits mycolic acid peripheral neuropathy:

synthesis prevent with pyridoxine
(Vitamin B6)
hepatitis, agranulocytosis
liver enzyme inhibitor

Side effects Pyrazinamide pyrazinamidase into

pyrazinoic acid which in
hyperuricemia causing
gout
turn inhibits fatty acid arthralgia, myalgia
synthase (FAS) hepatitis

Ethambutol inhibits the enzyme optic neuritis: check visual

arabinosyl transferase acuity before and during
treatment
dose needs adjusting in
patients with renal
impairment
 • All patients should be monitored to assess their response
to therapy.

• Regular monitoring of patients also facilitates Rx

Monitoring completion and allows the identification of adverse drug
reactions.
• All TB patients should be followed clinically for at least
two years following cessation of planned therapy.
 • LFTs should be checked within 2 weeks after the initiation
of treatment, then monthly if any abnormalities were
detected.

• Sputum should be re-examined after two months of

therapy to document smear and culture.

• Monthly evaluation of pt’s weight, to adjust the dose if

Monitoring there is any change.

• CXR should be performed after two months and at the end

of therapy.
 • Ethambutol The need for routine periodic visual acuity
testing during therapy is controversial.

Monitoring •Pyrazinamide Serum uric acid measurements may be

obtained in individuals who have a history of gout
 • Drug induced hepatotoxicity is defined as
Hepatotoxicit AST/ALT >= 3x ULN with the presence of symptoms.
y Or
AST/ALT >5x ULN in the absence of symptoms.
 • STOP immediately all antituberculosis drugs.

• Consult with an expert who is familiar with the

Hepatotoxicit management of hepatotoxicity.

y • Perform serologic testing for Hepatitis A, B, and C on

patients who are high risk for hepatitis.

• Rule out other causes.

• Consider initiation of “liver friendly” drugs.

 • Continue checking LFT. If LFT <2x ULN, rechallenge first
Rechallenge with Rifampin and EMB.

Anti TB • If LFT does not increase after 1 week, then INH should
drugs be added to the regimen.

• Pyrazinamide can be added next (1 week after INH) if

LFT does not increase.

Important point: if at any time of rechallenged period, symptoms recur or

AST and ALT increases, the last drug added should be stopped.