Ziehl Neelsen and fluorochrome stain

Acid-fast for bacilli

Grow slowly when cultured 

BACTEC: takes 9-14 days and give a quantitative measure (MIC)

Rapid identification tests: use technique like PCR, high performance liquid chromatography(HLPC)

Genetic changes associated w/ resistance to particular drugs 

1) number of organism inhaled

2) virulence of the organism

3) host's immune response

Some macrophages carry replicating bacteria to the lymph nodes

Some bacteria travel to the bloodstream: from here they can travel and infect any area of the body 

Cell mediated immunity begins

Macrophages from granulomas to contain organism 

Replication begins to slow 

Most bacteria are now within the granulomas 

Tissue hypersensitivity occurs: this is characterized by a + TB skin test 

10%

1/2 occurs in the first 2 yrs of infection

1) Miliary TB: when a large amount of bacteria enter the bloodstream at once (rapidly progresses to death)

2) Extrapulmonary TB: when liquefied granulomas occur at locations other than the lungs (difficult to diagnose), most common locations  lymphatic and pleural locations 

Extensively drug resistant TB

Resistant to : rifampin, isoniazid, A FQ, one 2nd line injectable drug such as amikacin, capreomycin or kanamycin

Involves lower and middle lobes

Extrapulmonary TB in the lymph nodes, GI tract, genitourinary tract, bone marrow, and meninges is common. (rapidly fatal)

Mantoux test 

It uses tuberculin purified protein derivative (PPD), 5 unit inserted intercutaneously on the volar aspect of the forearm

Quick identification

Start specific TB therapy

Resolve signs and symptoms

REach non-infectious state

Adherence to drug regimen

Cure patient, Minimize transmission

RIPE:

Rifampin (RIF)or rifabutin or rifapentine

Isoniazid (INH)

Pyrazinamide (PZA)

Ethambutol (EMB)

Pyridoxine (B6) 10-50 mg 

Pts who are pregnant, alcoholics, or have a poor diet need to supplement with B6 

Inhibits metabolism of phenytoin, carbamazapine, primidone, warfarin 

Seprate dose from antacids for 2 hrs 

(take isoniazid on empty stomach)

Common SE: rash, fever, GI upset

Rare SE: Rash associated with flu-like syndrome, hemolytic anemia or acute renal failure 

May change urine and other secretions orange-red Hepatoxicity

Strong inducer of CYP3A4

Caution w/ protease inhibitors, oral contraceptives 

GI upset, arthralgias, elevations in serum uric acid concentrations (measurement not required)

- Hepatotoxicity (liver test shoud be done)

Occasional SE: Rash and photosensitivity

Retrobulbar neuritis, characterized by changes in visual acuity and inability to see the color green. Monitor monthly via Snellen wall chart and Ishihara red-green color discrimination card 

Rare SE: peripheral neuritis and rash

Rifater: 120 mg rifampin, 50 mg isoniazid, 300 mg pyrazinamide

Rifamate: 150 mg isoniazid, 300 mg rifampin

amikacin and kanamycin 

However, if resistant to amikacin likely resistant to kanamycin

when MDR-TB, take on empty stomack, can cause dose-related CNS toxicity 

Add pyridoxine 50-200 mg QD may help w/ tolerance 

May cause Goiter (more common when combined w/ p-aminosalicylic acid( (w or w/o hypothyroidism)

SE: gynecomastia, alopecia, acne, impotence, menorrhagia, photodermatitis, hypothyroidism. 

Empty granules will appear in the stool 

GI SE common 

Rare effects: hypersensitivity rx, hepatotoxicity, malabsorption syndrome, increased clotting time

may cause goiter 

audiogram, vestibular testing, romberg testing, and SCr done at baseline and every month while on therapy, also K+ and Mg2+

Can cause: nephrotoxicity and ototoxicity

Used for MDR-TB

SE: GI upset ans skin discoloration

Rarely may cause severe GI pain due to formation of crystals in the intestines

Levo, Cipro, and moxif (PO, IV)

used for MDR-TB 

Isoniazid 300 mg QD or 5-10 mg/kg (children) for 9 months (min 6 months)

Can be dosed 900 mg twice weekly if DOT (directly observed therapyused)

Rifampin 600 mg QD for 4 month can be used in case of resistance or person can't tolerate isoniazid 

Rifabutin can be substituted in pts at high risk for drug interactions

Isoniazid + rifampin + pyrazinamide + ethambutol (RIPE) for 2 months, Then isoniazid + rifampin for 4 more months

If TB susceptible to "RIP," E can be stopped early 

Treat for 9-12 months minimum 

Isoniazid, pyrazinamide, ethionamide, cycloserine (best CNS penetration)

Variable CNS penetration: rifampin, ethambutol, streptomycin.

Levo is preferred quinolone 

Soft tissue tx with RIPE

Site is pericarditis or CNS adjunct corticosteroids recommended 

Rifampin, isoniazid and ethambutol for 9 month 

B vitamins (B6, folic acid)

False, should not always use daily dose 

Tx for 9 months 

Streptomycin + levo +ethambutol

Tx minimum of 18 months 

typically switched to an isoniazid &/or rifampin when liver gets better 

Pyrazinamide and ethambutol require a frequency reduction 

Dosing interval must be increased w/ amikacin, kanamycin, streptomycin, capreomycin, ethambutol, cycloserine, and levofloxacin 

Rifampin has been associated w/ causing limb reduction and CNS lesions

Streptomycin may lead to hearing loss in child

Ethionamide can cause premature delivery and congenital deformities