Exam 5 - TB PCT - Caulder

Mycobacterium tuberculosis is the cause of TB: → it is a _______(slow/fast) growing, gram _______ bacilli. → it is a ______ ______ bacteria, so the Ziehl-Neelsen or fluorochrome stain is used to identify it. → _______ is the most common infection site

-slow - positive bacilli -acid fast - lung

considerations for Rifabutin use?

-less potent against TB -less potent inducer *usually give to HIV patients* (but need to monitor DDIs since they are often on protease inhibitors- and can have a DDI that decreases Rifamycin levels)

principles of active TB treatment

-most effective therapy in shortest time -multiple drugs -never add a single drug to a failing regimen (always *add at least 2*) -ensure adherence

when could PPD result in a false-positive?

-non-TB mycobacteria -BCG vaccination

when will MDR-TB be suspected?

-prior TB therapy -areas w/ high prevalence of resistance -homeless, institutionalized, HIV, IVDA -positive cultures after 2-4 mo -failed tx -exposure to MDR-TB -*nonadherence*

What is the annual risk of developing TB with a normal immune system vs with HIV?

normal: - only 5% annual risk of developing *active* TB HIV/IC: - 10% risk each year **this is a 100 fold increase with HIV coinfection

explain the transmission of TB

spread by *droplet nuclei* --> expelled when person w/ *active TB* coughs, sneezes, sings, speaks

how long is the INTENSIVE phase of treatment?

~2 months/until the cultures come back and give us clues to tx length/necessity

SE of PZA

-hepatitis --> monitor LFTs -increased uric acid --> monitor for gout -GI intolerance -arthralgia -arthritis

SE of INH

-hepatitis --> monitor LFTs -peripheral neuropahty --> give Pyridoxine (vit B6)

goals for active TB therapy

-kill TB -prevent Multi-Drug Resistant-TB -prevent relapse

explain latent vs active TB

-latent: exposed, but not actively infected -active: infected/contagious

What is DOT?

(directly observed therapy) -to directly observe patients taking medication for adherence

pts are considered no longer infectious IF:

(meet all 3 criteria) 1) adequate therapy 2) significant clinical response to therapy 3) 3 consecutive negative sputum smears

who should be given a PPD?

(targeted TB test) -any patients at high risk for developing TB -close contact w/ patients that are infected -immigrants -healthcare workers -medically underserved/low-income -high risk racial/ethnic minority -children exposued to adults w/ high risk -HIV -IVDA

if CXR is positive- what to do next?

*3 sputum specimens + cultures* -looking for acid-fast bacilli -if + --> indicates active infection

initial tx of suspected ACTIVE TB depends on?

*empiric*- bc susceptibilities take 1-2 months since TB is so slow-growing --> then when susceptibilities are known you can de-escalate

initial treatment of latent TB

*monotherapy* w/ INH for 9 months OR Rifampin 600mg PO daily x 4 months

What organism is the cause of TB?

*mycobacterium tuberculosis*

Pros vs. cons: characteristics of the IGRA blood test (vs the PPD skin test)?

- 1 visit - blood draw - results NOT affected by BCG - results next day - objective

What is the induration size (size of PPD nodule after your injection is read) that indicates a positive TB screening for everyone? What is important to note about interpreting the induration size for special populations?

- 15mm - smaller induration sizes (10mm and 5mm) are sometimes seen as a positive indication for TB when the patient fits certain characteristics (she will give us whether the induration is deemed positive or negative, but this is just an important note about how sizing may differ in populations)

How long should you keep a patient with TB isolated?

- Determination of no TB - Patient is discharged - Patient is confirmed non-infectious (must meet all 3): 1) Patient is on effective therapy 2) Clinically improving 3) 3 negative acid-fast sputum smears on 3 different days w/ at least one taken during the morning

who is at high risk for reactivation of TB disease upon being infected?

- HIV positive - primary infection in past 2 years - immunocompromising conditions - <4 yrs old - Hx of undertreated TB

First phase of treatment: AKA the ______ phase What are the 1st line drugs to treat TB?

- INTENSIVE → bc you don't have cultures yet 1) Isoniazid (INH) 2) Rifampin (RFM) 3) Pyrazinamide (PZA) 4) Ethambutol (EMB) (pt is started on all 4 if active TB) **NOTE TO REMEMBER: this is called the R.I.P.E. treatment!!

What is the reasoning for us caring/devoting so much time to TB?

- MILLIONS of people die of TB each year worldwide - over 1/4 of the world's population is infected with M. tuberculosis

What are the characteristics of an interferon gamma assay (IGRA) test?

- Measures the release of INF-γ in blood in response to the TB antigens - More specific than PPD - Quick and specific result w/in 24 h for identifying M. tuberculosis - Only designed to diagnose LATENT TB - Not to be used to confirm or reject a term-15diagnosis of active TB disease, but may provide supporting evidence - Cannot differentiate between active or latent TB

Due to the length of time it takes to get cultures back for mycobacterium tuberculosis, what is important to know?

- as we know, possible TB infections are treated incredibly seriously due to their likelihood to spread (respiratory precautions, isolation, etc) - even if the cultures haven't returned, we still need to get the patient isolated and on these precautions as soon as we expect TB, so we often treat TB aggressively for the first 2 months while awaiting cultures - treatment is then reassessed once the cultures finally return! (basically, if TB is expected, aggressive treatment starts immediately to prevent spread)

What is often noted in the patient assessment in patients with suspected latent, infectious TB?

- asymptomatic - previous successful treatment

________ is the vaccine for the prevention of TB. It is a _____ preparation of the BCG strain of Mycobacterium bovis

- bacillus of Calmette-Guerin) BCG vaccine - attenuated, live culture

what are the risk factors for TB infection?

- crowded, urban living space - birthplace outside of US or CA, FL, NY or TX - Ethnic Minority - HIV Coinfection

PRO TIP: ALWAYS check for _____ for anyone taking rifampin.

- drug-drug interactions - caulder says since there are 100+ DDIs w/ this drug, you can't memorize them all, so ALWAYS check

if CXR is negative- what to do next?

- evaluate for symptoms of TB? → likely latent TB! - evaluate over time bc symptoms may develop later in life

what drugs can cause peripheral neuropathy?

INH --> give Vit B6

What are the characteristics of a patient with Active TB infection?

- has a large amt of active TB bacteria in body - may spread TB bacteria to others - may feel sick & may have sx such as cough, fever, &/or weight loss - usually has a TB skin test or TB blood test reaction indicating TB infection - radiograph may be abnormal - sputum smears and cultures may be positive - needs tx for TB disease - may require respiratory isolation - IS a TB case

What are the characteristics of a patient with Latent TB infection (LTBI)?

- has a small amt of TB bacteria in body that are alive, but inactive - CANNOT spread TB bacteria to others - does NOT feel sick, but may become sick if the bacteria become active in his/her body - usually has a TB skin test or TB blood test reaction indicating TB infection - radiograph is typically normal - sputum smears and cultures are negative - should consider tx for LTBI to prevent TB disease - does NOT require respiratory isolation - not a TB case

The IGRA blood test is only designed to diagnose ____ TB. It is NOT used to confirm or reject a diagnosis of _____ TB, but may provide supporting evidence.

- latent - active

What should you NEVER do for the tx of active TB?

- never tx with a single regimen - never add a single agent to a failing regimen for active TB (this could cause resistance to each agent until there is nothing left to use)

SE of EMB

- ocular toxicity --> need baseline eye exam

What is often noted in the patient assessment in patients with suspected active, infectious TB?

- presence of cough - failure to cover the mouth and nose when coughing - CXR +cavitation - AFB sputum smear is positive - positive culture for M. tuberculosis - respiratory tract disease with involvement of the larynx, lung, or pleura - lack of inappropriate antituberculosis treatment - undergoing cough-inducing or aerosol-generating procedures (e.g. bronchoscopy, sputum induction, & administration of aerosolized medications)

Rifamycin-based treatments are most effective for TB; but select agents based on susceptibility and HIV regimen. - Do not use rifampin with a __________ due to decreased serum concentrations of the PI and NNRTI. - Consider using _______ in these situations

- protease inhibitor and NNRTI - rifabutin or rifapentine

Based on specific patient characteristics and drug-drug interactions, during the RIPE treatment, _______ can be subbed out for other drugs from the same class.

- rifampin Class: rifamycins

What leads to a definitive diagnosis for Active TB?

- sputum culture (AFB) - PCR test - Tuberculin skin test (PPD) sputum culture (AFB) and PCR testing are both required for a definitive diagnosis

What are the clinical implication of mycobacterium tuberculosis identification in TB patients?

- susceptibility testing takes ~ 2 months - able to evade the immune system (so not always easy to detect)

What leads to a definitive diagnosis for latent TB?

- tuberculin skin test (PPD) - interferon-γ release assa (IGRA)

considerations for Rifapentine use?

- used in continuation phase of HIV-negative TB patients - after susceptibilities are completed

who should get interferon-gamma release assay?

- with a latent TB diagnosis - to act as Active TB diagnosis supporting evidence More specifically: >5 yo and: - likely to be infected w/ TB - low or immediate risk of disease progression - testing for latent TB indicated -*history of BCG vaccine* - unlikely to return to have their PPD read

Pros vs. Cons: characteristics of the PPD skin test (vs the IGRA blood test)?

-2 visits -injected into skin -results affected by BCG -results in 2-3 days -subjective - not always true reads (false positives and false negatives occur)

what drugs can cause hepatitis?

-Isoniazid -Pyrazinamide -Rifampin

What drugs are Rifamycins?

-Rifampin -Rifabutin -Rifapentine

when could PPD result in false-negative?

-anergy -recent TB infection -very young -live-virus vaccinations -overwhelming TB disease

ADE monitoring

-baseline monitoring (eye exam, LFTs) -DDI

efficacy monitoring

-check sputum AFB q month -repeat CXR -sx/s of infection

symptoms of TB

-fever/chills -*night sweats* -anorexia -*weight loss* -fatigue -hemoptysis

considerations for Rifampin use?

-first line (best studied option) -but potent CYP450 inducer (BCGRPh) - LOTS of Drug drug interactions!! - Causes orange-colored secretions and can discolor contact lenses!!

SE of RFM

-hepatitis --> monitor LFTs -discolors bodily fluids -P450 inducer --> monitor DDI

how to diagnose/identify TB organism

-sputum culture (2-8 wks)/acid fast -smear -rapid diagnostic tests -susceptibility tests

SE of Rifamycins

-thrombocytopenia -GI intolerance -DDI

What is done to address infection control in healthcare settings? (what are the 3 sections and what is done for them?)

1) Administrative: → a health care professional is assigned responsibility for the decrease in TB spread. This could be through programs, education, or even directly ensuring TB pt adheres to medication regimen 2) Environmental: → respiratory precautions like negative air pressure, proper ventilation, and patient isolation are employed. (doors remain closed, etc) 3) Respiratory: → contact precautions are employed until 3 sputum smears show negative results → PPE materials are used (N95 masks) **Note: these 3 aspects were represented in an upside down pyramid as seen in the photo

Goals of TB tx?

1) CURE the individual 2) minimize the risk of death and disability 3) reduce transmission of M. tuberculosis to other people

explain the progression of TB in person w/ normal immune system

1) inhale particle --> primary TB 2) can do PPD in 6-8 weeks bc that is how long it takes to show up 3) spontaneously heals --> latent TB (need annual CXR) 4) can be re-activated--> active TB

What are the phases of infection in TB?

1) primary infection 2) latent infection 3) reactivation 4) disseminated or miliary infection

two types of Multi Drug Resistant-TB?

1) primary: contracted from a known MDR-TB infected person 2) secondary: developed MDR-TB because of ineffective response to treatment or ineffective treatment

Tx of latent TB if high risk pt population?

12 weeks of once-weekly isoniazid and rifapentine by DOT

steps for TB diagnosis

1st: PPD or IGRA - Positive? Negative? 2nd: CXR - infiltrates present? 3rd: evaluate sputum culture - often ~2mo later, but is M. tuberculosis bacteria present in pt?

About how many total months will treatment take?

6 months (unless longer term treatment is needed)

duration of active TB treatment

6 months minimum - up to 2-3 years

TOPHAT: During my P4 rotations, I completed a medication reconciliation rotation at a large teaching institution. One morning, we had a new admission on my floor: PT: 81 YO AAF PMH: HIV+, GERD CC: Night sweats, productive cough, anxiety CXR: +cavitating nodules Page to floor pharmacist: MD needs med rec for HIV regimen. The team had a high suspicion for TB. Which of the following patient characteristics did NOT contribute to the differential? a. AAF b. HIV+ c. Productive cough d. Anxiety

Anxiety - being a minority race, having HIV, and having a productive cough are all indicating factors/risk factors for possible TB infection

what drugs can cause eye damage?

Ethambutol

T/F MAC is the cause of TB?

FALSE be sure to distinguish the fact that TB is caused by mycobacterium tuberculosis, NOT MAC (mycobacterium avium complex)

T/F a positive PPD skin test is a definitive diagnostic tool for TB

FALSE it is NOT a definitive diagnosis, but it is an indication for further inspection of the patient

T/F there is a vaccine available for TB that is for people actively infected with TB

FALSE the TB vaccine is indicated for the PREVENTION of TB in persons not previously infected with M. tuberculosis who are not at high risk for exposure

tx of active TB for initial phase

INH + RFM + PZA + EMB QD x 2 months (until susceptibilities come back) (RIPE)

What is important to note for active TB treatment and HIV?

No regimens prescribed for less than 3 days/week are used in HIV infected patients with a CD4+< 100

if cultures come back for latent TB and INH is resistant, what to use?

RFM

SN is a 93 kg 51 yo M, recently relocated from Vietnam. He presents to the ED with CC of hemoptysis. Also reports fever (103.2°F at home), subjective chills, chest pain, night sweats, fatigue, polyuria, polydipsia. PMH: s/p adenectomy 1987, T2DM dx 2015, HLD, HTN, TB dx 01/2019 (reports adhering to RIPE regimen from 01/19 to 03/?? in Vietnam), bound to wheelchair 2/2 MVA on 2/28/19. He was inpatient 3/1/19 - 3/10/19. SH: IVDU+, ETOH+ Home Meds: Lantus 35 U qPM (LF 2/2/19 #10mL), pitavastatin 4mg qHS (LF 12/19/19 #30), captopril 12.5mg TID (LF 12/19/19 #90) CXR: +cavitary nodules, diffuse scar tissue revealing partially treated TB Sputum Culture: pending PPD: 18mm induration Based on SN's presentation, his disease would most likely be described as: a) First Presentation of Primary Infection b) Latent Tuberculosis c) Secondary to BCG Vaccine d) Reactivation Disease

Reactivation Disease

Tx of latent TB is DDIs are a concern?

Rifabutin 300mg PO daily x 4 months

MI is in the continuation phase of treatment for active tuberculosis. She is still planning on getting married in May, but she doesn't want to wear her glasses during the ceremony. She would prefer to wear soft contact lenses. Which of her home medications might cause a problem with soft contact lenses? a) Rifampin b) Isoniazid c) Calcium Carbonate d) Singulair

Rifampin

T/F HIV doesn't increase the risk of contracting TB, but it actually increases the risk of progression of TB to the active phase.

TRUE! HIV coinfection is a major factor contributing to TB resurgence

what is another name for the PPD test?

TST

When using the RIPE treatment, what drug is needed PRN due to a side effect of isonizid?

Vitamin B6 - bc of peripheral neuropathy

Which agent in the single tablet HIV regimen Symtuza® should not be taken with rifampin? a) Darunavir 800 mg b) Cobicistat 150 mg c) Emtricitabine 200 mg d) TAF 10 mg

a) Darunavir 800 mg

SN is a 93 kg 51 yo M, recently relocated from Vietnam. He presents to the ED with CC of hemoptysis. Also reports fever (103.2°F at home), subjective chills, chest pain, night sweats, fatigue, polyuria, polydipsia. PMH: s/p adenectomy 1987, T2DM dx 2015, HLD, HTN, TB dx 01/2019 (reports adhering to RIPE regimen from 01/19 to 03/?? in Vietnam), bound to wheelchair 2/2 MVA on 2/28/19. He was inpatient 3/1/19 - 3/10/19. SH: IVDU+, ETOH+ Home Meds: Lantus 35 U qPM (LF 2/2/19 #10mL), pitavastatin 4mg qHS (LF 12/19/19 #30), captopril 12.5mg TID (LF 12/19/19 #90) CXR: +cavitary nodules, diffuse scar tissue revealing partially treated TB Sputum Culture: pending PPD: 18mm induration What is the most appropriate next step for the management of SN? Select all that apply. a) Obtain sputum culture BCID (PCR) and susceptibilities b) Consider ID specialist consult c) Order stat CXR d) Respiratory precautions: ensure that SN is placed in a negative pressure room with HEPA filtered air and that PPE are available to all HCPs e) Recommend consolidating RIPE regimen to ethambutol monotherapy

a) Obtain sputum culture BCID (PCR) and susceptibilities b) Consider ID specialist consult d) Respiratory precautions: ensure that SN is placed in a negative pressure room with HEPA filtered air and that PPE are available to all HCPs

SN is a 93 kg 51 yo M, recently relocated from Vietnam. He presents to the ED with CC of hemoptysis. Also reports fever (103.2°F at home), subjective chills, chest pain, night sweats, fatigue, polyuria, polydipsia. PMH: s/p adenectomy 1987, T2DM dx 2015, HLD, HTN, TB dx 01/2019 (reports adhering to RIPE regimen from 01/19 to 03/?? in Vietnam), bound to wheelchair 2/2 MVA on 2/28/19. He was inpatient 3/1/19 - 3/10/19. SH: IVDU+, ETOH+ Home Meds: Lantus 35 U qPM (LF 2/2/19 #10mL), pitavastatin 4mg qHS (LF 12/19/19 #30), captopril 12.5mg TID (LF 12/19/19 #90) CXR: +cavitary nodules, diffuse scar tissue revealing partially treated TB Sputum Culture: pending PPD: 18mm induration With the information available at this time, which of SN's patient characteristics would make him a good candidate for DOT? Select all that apply. a) Previous treatment for TB b) Substance abuse c) Physical disability d) T2DM

a) Previous treatment for TB b) Substance abuse c) Physical disability

SN's cultures resulted today. Sensitive: Ethambutol, Pyrazinamide, Levofloxacin, Rifabutin Resistant: Rifampin, Isoniazid What do you recommend to your team? a) Re-initiate previous RIPE regimen under DOT and extend for 9 months b) Initiate rifabutin + levofloxacin + ethambutol + pyrazinamide under DOT c) Initiate rifabutin + isoniazid + pyrazinamide + ethambutol under DOT d) Initiate IV levofloxacin monotherapy under DOT

b) Initiate rifabutin + levofloxacin + ethambutol + pyrazinamide under DOT

tx choice for active TB for continuation phase? (after cultures have returned)

based on the cultures, the susceptibilities and the pt characteristics

A MD in your ID clinic wants to initiate RIPE therapy for TB on a new pt, QR. QR is therapy naïve and sputum cultures are pan-sensitive. He asks for your thoughts on the following regimen for this 80 kg male: Home Meds: 1. APAP 500mg BID PRN HA 2. Omeprazole 20mg QAM for GERD 3. Warfarin 7.5 mg T/TH, 5 mg M/W/F/Sa/Su for mechanical heart valve 4. Atorvastatin 40mg QHS for HLD 5. Lisinopril 40mg QAM for HTN Plan to Initiate: 1. Rifampin 600mg PO daily x 2 mo. 2. Isoniazid 300mg PO daily x 2 mo. 3. Pyrazinamide 1600mg PO daily x 2 mo. 4. Ethambutol 1600mg PO daily x 2 mo. What is your recommendation? a) Continue as written. b) Change rifampin dose to 800mg PO daily and continue the rest as written. c) Substitute rifampin with rifabutin d) The infection will self-resolve.

c) Substitute rifampin with rifabutin

What are OTHER diagnostic tests for TB diagnosis?

chest xray bacteriological examination of clinical specimens: → AFB smear → direct detection of M. tuberculosis in clinical specimen using nucleic acid amplification → specimen culturing and identification - drug susceptibility testing

continuation phase: if multi-drug resistant

consider second line agents -para-aminosalicylic acid -cycloserine -kanamycin -amikacin etc

continuation phase: treatment if INH and RFM resistant?

continue: PZA and EMB for rest of duration

continuation phase: treatment if INH is resistant?

continue: RFM, PZA and EMB for rest of duration

does CXR confirm diagnosis of TB?

does not confirm --> just a step in diagnosis

T/F TB is not a curable disease?

false TB remains one of the largest public health concerns and millions of deaths occur from this curable disease

False positive PPD results may occur in patients who ________

have received the BCG vaccine

what is tuberculosis?

highly contagious respiratory infx caused by mycobacterium tuberculosis

what is the reservoir of TB

humans

When is the BCG vaccine contraindicated?

immunocompromised populations or previous TB

What is important to note about the sputum culture?

it is important to get the sputum culture ASAP(preferably before meds), but growth can take weeks AND since the mycobacterium tuberculosis has a waxy coating, the smears may appear negative at first because of bad stains → then, you might get a positive culture later on (so don't be surprise by a false negative)

during the developmental stages of TB, bacteria multiply _______

logarithmically

how to interpret PPD?

look to see if spot is raised/elevated (AKA the induration size) --> indurations of a certain size indicate a reaction

What happens if the sputum cultures come back positive at the end of the continuation phase?

may need to add 4-7 months to extend to a total of 9 months of more of treatment

what is interferon-gamma release assay?

new TB test that only requires one visit and results are quick

How is the BCG vaccine administered? (route)

percutaneously (NOT IM)

Where in the body are active TB infections located?

primarily the lungs (80-84% of infections) Extrapulmonary TB: - CNS - lymph nodes - bones and joints → almost anywhere on the body and may require special treatments

what persons are at increased risk for progression of TB from a latent infection to active?

read picture*

Upon receiving a positive result for a TB diagnostic test, what is required?

report positives within 24 hours to the health department

How does HIV coinfection with TB contribute to the progression of a TB infection?

synergy of the diseases leads to a worse presentation of each disease

What is the primary infection stage of TB?

→ a patient actively infected with TB breathes out a droplet into the air (can remain in air 2-40 hours) → droplet enters new pts lungs (primary infection occurs) This infection can be inhibited by the host response or it can develop into active TB

What pathophysiological process is occuring during the primary infection phase of TB that leads to a latent and possibly, active TB infections?

→ w/in 2-8 wks, macrophages surround and ingest the bacteria. they form a barrier shell called a granuloma that tries to contain/control the infection (this is when the TB infection is latent) - if macrophages inhibit/kill the bacteria, the the infx is aborted → in they're not killed, then the macrophage ultimately ruptures and releases the bacteria into the hosts' body (active TB) → these bacteria are then "eaten" by other macrophages and this cycle of bursting and "eating" recurs until the body mounts an appropriate response (or doesn't)