TB Flashcards
Mycobacteria species
rod shaped aerobic bacteria
Cell wall with:
peptidoglycan
mycolic acids
Fatty acids and waxes
responsible for slow growth, acid fastness, resistance to detergents and common antibiotics
do not stain very well
mycobacteria species that are pathogens
- Mycobacterium Tuberculosis
* pulmonary
* disseminated tuberculosis - Mycobacterium leprae
* leprosy (hansen’s disease)
mycobacterium bovis- tuberculosis like and rare
mycobacteria POTENTIALLY pathogenic
- Mycobacterium Avium complex (MAC)
* disseminated and pulmonary infections
* AIDS population
* reservoir in soil, water, birds, swine, cattle, environment
mycobacterium Kansasii- pulmonary like TB, grows slower
mycobacterium ulcerans- subcutaneous nodules and ulcers-> waterborne skin pathogen
Targets for MOA of Antimycobacterial agents
- ATP synthase
- NADH dehydrogenase
- Intracellular acidification
- Ribosome
- RNA polymerase
- DNA gyrase
- Folate metabolism
- Peptidoglycan
- ARabinoglactan
- Mycolic acids
Tuberculosis treatments
depends on if pt has active or latent tb infection
Latent:
* monotherapy
* no symptoms and cannot spread the disease
Active TB:
* minimum of two drug therapy
* can spread the disease
Latent TB infection drugs
- Isoniazid (INH)
- Rifapentine (RPT)
- Rifampin (RIF)
Isoniazid (INH)
GOOD IN PREGO AND PEDS
Bactericidal if actively growing-> otherwise inhibitory
MOA: inhibits cell wall biosynth by interfering with lipid and dna synthesis
Various resistance
Dosage: Injection of Oral
GI absorption
PREGO SAFE, PEDS SAFE, AND USED FOR LATENT OR ACTIVE TB
adverse effects: severe and fatal hepatitis within 3 months of treatment
* hepatitis- 1% liver metabolism
* sputum cultures monthly until 2 consecutive cultures
* rashes, SLE
* DECREASE DOSE IN CHRONIC ALCOHOLISM
* PERIPHERAL NEUROPATHY AT HIGHER DOSES= tx with pyridoxine (vit B6)
* at high risk: pregnancy, breastfeeding infants, HIV, chronic renal filure, DM
Rifampin
MOA: binds to RNA polymerase
Hepativ metabolism
POLYPHARMACY FOR ACTIVE TB TO PREVENT EMERGENCE OF RESISTANT STRAINS
Porphyrias
Adverse effects:
affect BG in Diabetes
Bloody dyscrasias
proteinuria
flu like illness
thrombocytopenia
RED ORANGE BODY FLUIDS- urine, breast milk, stool, tears, sweat
RARE- hypersensitivity reactions- hypotension, anaphylaxis, fever
cheaper than isoniazid
Rifampin drug interactions
is an enzyme inducer
Major interactions: methadone, protease inhibitors (HIV), steroids, oral contraceptives, warfarin, dogoxin, calcium channel blockers, ondansetron, simvastatin
Rifapentine
similar to rifampin
Hepatotoxicity
potential hypersensitivity
discoloration of body secretions
C. diff diarrhea - resistant to rifapentine
AVOID IN PT WITH PORPHYRIAS
Watch CBCS for white/red cell anomalies-
AVOID IN PREGO, TAKE WITH FOOD
Latent TB infxn tx regimen factors
- drug susceptibility results of the presumed source case
- Coexisting medical conditions-> Pregnancy status and HIV status
- Potential for drug-drug interactions
SIC
Schedule for tx of latent tb
- Isoniazid and Rifapentine
* 3 months
* NOT GOOD FOR PREGO OR HIV - Isoniazid and Rifampin
* 3 months
* not good for HIV
* Allowed for Pregnancy - Rifampin- first line
* 4 months
* not for HIV - Isoniazid
* 6 months
* ALLOWED IN PREGNANCY
* NEEDS EXACT DIRECT OBSERVATION TX - Isoniazid
* 9 months
* PREFERRED FOR PREGNANT WOMEN WITH PYRIDOXINE
* DIRECT OBSERVATION
DOT- direct observation tx
whenever possible to reduce tx failures and selection of drug resistance
meets with healthcare worker every day
Takes TB med while being watched
Discuss problems
Noncompliance rates are as high as 89% with TB therapy
Preferred tx for latent tb
Short course Rifamycin based 3-4 months regimens
Effective, safe, higher completion rates, than isoniazid monotherapy
Active TB
core drugs
- Rifampin RIF
- Isoniazid INH
- Pyrazinamide PZA
- Ethambutol EMB
Ethambutol (EMB)
Cell wall drug but bacteriostatic
absorbed orally well
reduced dose in renal failure
AE: optic neuritis, RED/GREEN discrimination, visual acuity
Pyrazinamide PZA
MOA: taken up by macrophages and penetrates lysosomes
Phase 1 hepatic, then renal clearance
AE: HYperuricemia, liver, GI, rash, monitor uric acids and LFTs
MOA: inhibit fatty acid synthetase enzyme of M. tuberculosis
MOR: NOT USED AS A MONOTHERAPY
USUALLY TX BY ID
SHOULD NOT BE USED IN PREGNANCY AS EFFECTS ON FETUS UNKNOWN
Active TB regimens
Intensive phase 2 months:
* INH, RIF, PZA, EMB (RIPE)
Continuation phase 4-7 months:
* INH, RIF
4 round regimen
Additional TB drugs- Streptomycin
Aminoglycoside- for more severe disease
AE: nephro/ototoxic, get audios, BUN
CONTRAINDICATED IN PREGNANCY
Drugs sometimes used
Capreomycin
* MOA: cyclic polypeptide antimicrobial
* AE: ototoxicity, nephrotoxicity
* NOT FOR PEDS/PREGNANCY
Cycloserine
* MOA: inhibits bacterial cell wall synthesis by ocmpeteing with aminod acid to be incorporated into cell wall
* USED FOR MULTIDRUG RESISTANCE TB
* AE: CNS effects- seizures, psychosis, depression, confusion
* pyridoxine to prevent cns
* vitamin b12 and folic acid supplementation
Additional drugs sometimes used
Ethionamide
* inhibits mycolic acid synthesis
* AE: diabetes, hepatotoxicity, thyroid dysfunction
Para-aminosalicylic acid (aminosalicylate)
* MOA: structurally related to PABA
* AE: Pericarditis, vasculitis, rashes, GI
* CI: ASA ALLERGY
Drug resistance to TB
remained stable over the last 20 years
most common is isoniazid
Multidrug resistance: isoniazid and rifampin
MDR-TB and XDR TB
MDR= resistant to isoniazid and rifampin
XDR= resistant to INH and RIF AND at least 3 of second line anti-TB drugs
Non tb mycobacterial tx
Atypical mycobacterial infections:
* Mac= mycobacterium avium complex
* pt with AIDS, fever, weightloss
* usually in severely immunocomp- HIV
SXS:
* sweating
* fatigue
* diarrhea
* sob
* right upper quadrant abdominal pain
Pulmonary pathogen
associated w/: osteo myelitis, tenosynovitis, synovitis
Mycobacterium avium infection
pulmonary and disseminated agents
Tx with 2 or more drugs
can sub Azithromycin or clarithromycin
atleast for 12 months
1. Rifabutin
2. Rifampin
3. Azithromycin
4. Clarithromycin
5. Ethambutol
Mycobacterium Kansasii tx
like TB
SX: hemoptysis, chest pain, cavitary lung disease
Effectively tx: Isoniazid, Rifampin, Ethambutol
Alt meds: fluroquinolones, clarithromycin, aminoglycosides
tx for 1 yr post neg
resistant to pyrazinamide
easily cured
Mycobacterium Kansasii tx
like TB
SX: hemoptysis, chest pain, cavitary lung disease
Effectively tx: Isoniazid, Rifampin, Ethambutol
Alt meds: fluroquinolones, clarithromycin, aminoglycosides
tx for 1 yr post neg
resistant to pyrazinamide
easily cured
M. Leprae
Leprosy
armadillos naturally infected
Requires sustained exposure in childhood
Endemic= Africa, Asia, Brazil
TX: Dapsone and Rifampin -> paucibacillary form
TX: Clofazimine plus rifampin and dapsone-> multibacillary form
Mycobacterium Marinum
swimming pool granuloma
Found: NON CHLORINATED WATER
RF: Aquaria and swimming pools
Superficial cutaneous infection: minocycline, clarithromycin, doxycycline, trimethoprim-sulfamethozazol (monotherapy)
Severe inf: combo of rifampicin and ethambutol
Spontateous remission- in untreated infection adn immunocompetent
opportunistic infection
ALL OF THIS IS RED ON SLIDE