3/25/14  

1  

TB  Exposed:  Pharmacologic  Management  of  TB  

 April  11,  2014  

Diana  Fortune  RN  BSN  TB  Program  Manager  New  Mexico  Department  of  Health  

http://exposed.aeras.org/#_video2  

 

 

 

The  Global  Epidemic  

Is  TB  Elimination  a  Winnable  Battle?  

Roadmap  to  the  Future:      TB  Control  &  Elimination  

3/25/14  

2  

Tuberculosis:    The  SILENT  Global  Epidemic  

   

!  One person is newly infected with TB every second

!  One person dies every 10 seconds

!  6-10 people die every year of TB in New Mexico

!  1/3 of world population is infected with TB

!  1.4 million deaths each year

TB  Anywhere  is  TB  Everywhere  

“The  People  of  the  world  are  limbs  from  one  body,  sharing  one  essence;  When  a  single  limb  is  oppressed,  all  the  others  suffer  agony….”.  

 Sheikh  Sa’adi  of  Shiraz  

     

48 51 60 48 51 49 40

2.4 2.6

3.0

2.4 2.5 2.4

1.9

4.6 4.4

4.2

3.8 3.6

3.4

0

20

40

60

80

0

1

2

3

4

5

2006 2007 2008 2009 2010 2011 2012

# of

NM

Cas

es

TB

Rat

e pe

r 10

0,00

0 Po

pula

tion

Year

TB Rates, New Mexico vs. US, 2006 - 2012 # of NM Cases NM TB Rate US TB Rate

3/25/14  

3  

Looking  for  zebras’  again?  

Getting  over  the  horizon:  Making  the  Diagnosis  

A  person  with    Active  TB  Disease  

!  Have  replicating  TB  bacteria  in  his/her  body  

!  Feels  sick  and  experiences  symptoms    "   coughing  >  2  wks  "   weight  loss  "   fatigue,  night  sweats  

!  Potentially  infectious  &  may  spread  TB  bacteria  to  others  

!  Needs  treatment  to  cure  active  TB  disease  

How  is  TB  spread……?  

!  TB  is  spread  through  the  air  from  person  to  person        !  TB  bacteria  are  passed  through  the  air  when  a  

person  with  TB  disease  coughs,  laughs,  sings  or  sneezes..  

3/25/14  

4  

A  person  with    “Living”  with  TB  Infection    

!  Has  TB  bacteria  in  his/her  body    

!  Does  not  feel  sick  &    "   NOT  CONTAGIOUS  

!  May  become  infectious    if  the  bacteria  begin  replication    

!  Should  consider  treatment  for  TB  Infection  "   to  prevent  progression  to    active  TB  

disease  

Lurking  beneath  the  surface…..  

 TB  Infection  

Active  TB  Disease  

The  Continuum:    TB  Infection…………………TB  Disease  

TB Infection TB Disease Tubercle bacilli in the body

TST/IGRA reaction usually positive Chest x-ray usually normal Chest x-ray usually abnormal

Sputum smears and cultures NEGATIVE

Sputum smears and cultures POSITIVE

No symptoms Symptoms such as cough, fever, weight loss

Not infectious Presumed infectious before treatment

Take treatment to prevent progression to active disease

Needs treatment to cure active TB disease

A case of TB Infection A case of active TB Disease

3/25/14  

5  

Making  the  diagnosis:      Looking  for  zebras  again…  

!  Symptom  Screening  –  standardized  form  "  Risk  factors  

!  Foreign  birth/travel  to  TB  Endemic  countries  !  Contact  to  a  case  !  Immune  compromising  diseases  

!  CXR  –  red  flags  of  CXR  chart  !  Collect  sputum  x  3;    

"  may  collect  every  8  hours  "  at  least  one  specimen  early  AM  

!  Medical  exam  

Chest Radiograph

•  Abnormalities often seen in apical or posterior segments of upper lobe or superior segments of lower lobe

•  May have unusual appearance •  HIV-positive persons & diabetics

•  Cannot confirm diagnosis of TB

Arrow points to cavity in patient's right upper lobe.

Probably Not a TB Disease Suspect • negative

• no infiltrates • no active disease • no tuberculosis

• normal • clear

To Help Identify TB Disease Know the Red Flags in Chest X-ray Reports

Comments to Look For in CXR Reports:

❦ Pneumonic Process - frequently in the right upper lobe.

❦ Interstitial Infiltrates.

❦ Possibility of cavitary lesion.

❦ Mass, lesion, often needing a CT Scan to further define.

❦ Pleural effusion (considered TB until proven otherwise).

❦ Parenchymal disease.

❦ Nodular densities consistent with old granulomatous disease.

❦ RUL densities.

❦ Nodular densities.

❦ Linear parenchymal changes.

❦ , Hilar or Perhilar adenopathy.

❦ Thickening/blunting of right costophrenic angle.

List created by: Mary V. Muench, RN, TB Program Coordinator and Carol Clark, RN, TB Program Nurse, Florida Department of Corrections-2003. This is not intended to be all-inclusive and as with any test must be considered with the clinical picture of the patient.

3/25/14  

6  

AFB  SMEAR  

!  Fluorescent  stain      !  Grading:  

"  4+  (Numerous)    "  3+  (Moderate)    "  2+  (Few)    "  1+  (Rare)    "  No  AFB/300  fields=No  

AFB  seen  (Negative  smear)          

Nucleic  Acid  Amplification  Test  (NAAT)    

!  Detects  TB  complex  nucleic  acid  

!  Smear  positive  or  smear  negative  specimens  "  Smear  POSTIVE:      >95%  sensitivity  "  Smear  NEGATIVE:    55-­‐75%  sensitivity  

!  All  NEW  sputum  smear  positive  samples  "  Recommend  lab  do  reflex  testing  

!  All  new  sputum  smear  Negative  samples    "  High  risk  populations  i.e.  (inmates,  homeless  shelters,  LTC)  

!  Does  NOT  distinguish  live  or  dead  bugs  

 Isolation  of  M.TB  Complex  

!  Liquid  media  (broth_  (MGIT)  and  solid  media  

!  Liquid  media    "  positive  within  7-­‐14  days    

!  Solid  media  "  Up  to  6  weeks  

!  Always  need  drug  susceptibilities    

3/25/14  

7  

Treatment  of  Active  Tuberculosis    Standard  Regimen  

*7 months for some patients

Isoniazid

Rifampin

PZA

Ethambutol

0 1 2 3 4 5 6

Months

Initial Phase" Continuation Phase*

Major  Goals  of  treatment  of  TB  Disease  

!  Cure  the  individual  patient  

!  Minimize  the  risk  of  death  &  disability  

!  Reduce  the  transmission  of  TB  to  others  

!  NOTE:      "  Responsibility  of  successful  treatment  is  assigned  to  the  health  care  provider  –  NOT  THE  PATIENT    

Current  Anti-­‐TB  Drugs  11  approved  by  FDA  

Bedaquiline  (Sirturo):    the  first  new  class  of  drugs  to  obtain  FDA  approval  for  TB  in  40  years  –  (for  use  in  MDR  only  cases)  

3/25/14  

8  

The  “FAB  Four”  +  one  groupie  !  INH,  Rifampin,  PZA  and  EMB  +  Vitamin  B6    

"  The  first-­‐line  anti-­‐TB  drugs    "  Core  of  standard  treatment  regimens  

 

Common  Side  Effects  

!  Gastrointestinal  (GI)  !  Dermatologic  reactions  !  Systemic  hypersensitive  reactions  !  Hematologic  abnormalities  !  Neurotoxicity  !  Ototoxicity  !  Ophthalmic  toxicity  !  Nephrotoxicity  !  Musculoskeletal  !  Endocrine  !  Drug/Drug  Interactions  

3/25/14  

9  

Baseline  &  Follow-­‐up  Laboratory  Monitoring  for  TBD  

!  Baseline:      "  Detect  underlying  problems  (may  require  modified  regimen)  "  Children:      

!  Baselines  only  (unless  other  medical  conditions)    "  Adult:  (standard  4  drug  regimen)  

!  Blood  work:  !  CBC  &  CMP  (usually  more  cost  effective  to  do  panel)  

"  Recommended:    Hepatic  enzymes,  bilirubin,  serum  creatinine  or  BUN,  Uric  acid  

!  Other  testing:    Visual  acuity  (snellen  chart)    &  color  vision  (ishihara)  (EMB)  

"  Adult:    (MDR  TB)  !  Monitoring  tailored  to  drug  regimen  !  Ensure  expert  consultation  i.e.  (Heartland)  

3/25/14  

10  

Baseline  monitoring  

Monitoring  During  Treatment  

Patient  Monitoring  During  Treatment    !  Clinical  evaluation  at  minimum  monthly  

 

!  Laboratory  evaluation  NOT  necessary  q  month  for  patients  on  first  line  medications  (per  CDC  guidelines)  "  UNLESS:    abnormalities  at  baseline  "  OR  exhibiting  s/s  of  adverse  reaction  "  Stable  abnormalities    i.e.  LFTs    

!  Repeat  frequently  initially  to  ensure  no  changes;  then  as  indicated  by  clinical  condition  

"  MDR  patient:    Labs  will  be  determined  by  the  patient  clinical  condition  and  medications  used  !  Always  get  expert  consultation  in  treating  MDR  patients  

3/25/14  

11  

Common  Side  Effects  &    Adverse  Reactions  

Gastrointestinal  (GI)  Upset  

!  Potential  Causes  of  GI  symptoms  "  Gastritis  "  Hepatitis  "  Biliary  Disease  "  Pancreatitis  "  Peptic  Ulcer  Disease  "  Inflammatory  bowel  disease  "  C.  Diff  "  Lactose  intolerance  "  Acute  renal  failure  "  GI  TB,  if  early  in  the  course  "  Pregnancy  

Gastrointestinal  (GI)  Upset    !  Nausea/vomiting/diarrhea  (NVD)  #  Common  within  first  few  weeks  of  treatment  #  NOTE:      

#  Ask  the  patient  which  medication  they  feel  is  causing  the  problem.      #  Their  opinions  must  be  addressed  and  respected  #  Even  if  no  changes  can  be  made  to  the  regimen  

 !  Initial  suggestion  

!  Change  time  of  medication:    give  closer  to  meal-­‐time  !  DOT    -­‐  may  be  difficult  to  do  

!  Have  patient  eat  small  snack  with  meds  !  If  persistent  –  take  all  meds  with  meals  

!  May  slow  absorption  BUT  get  better  absorption  with  meds  IN  the  patient…..!  

 

3/25/14  

12  

Gastrointestinal  (GI)  Upset  

!  Administer  antiemetic  or  antacids    "  Antacids  NOT  given  within  2  hours  of  fluoroquinolones  

!  Some  antiemetic  options:  !  Phenergan  !  Reglan  !  Zofran  

!  Encourage  hydration  "  Sports  drinks  –  electrolyte  replacement  

!  Check  glucose  content  i.e.  (especially  diabetic  patients)  !  If  odor  of  medication  problematic  

"  Put  drug  in  gelatin  capsule  

Dermatologic  &  Hypersensitivity  Reactions  

Maculopapular  RASH  and  pruritus  

!  All  TB  meds  (  all  meds??)  can  cause  a  rash  "  Management  depends  on  severity  &  type  of  rash  

!  Minor  Rash/Itching:  "  Limited  area  "  Transient  "  Anti-­‐histamines  may  be  given  (Benadryl  &  others)  "  Continue……………...  All  TB  medications!    

!  Consider  drawing  ALT/AST  (if  other  s/s  present)  

3/25/14  

13  

Evaluate  other  causes  for  Rash  

!  Scabies  &  insect  bites  

!  Contact  dermatitis  –  new  lotions,  creams  etc  

!  Other  medications  they  are  taking  

!  Other  dermatological  conditions  (psoriasis)  

!  Dry  Skin  (especially  diabetics!)  

!  Unusual  skin  lesions  may  be  associated  with  HIV  "  Did  the  patient  receive  an  HIV  test??  "  Does  the  patient  have  on  going  risk  factors  

!  additional  HIV  testing  may  be  needed  

Flushing  Reactions  

!  FLUSHING/ITCHING  WITHOUT  RASH      "  (Rifampin  and  PZA)  "  Involves  face  and  scalp  "  Resolves  within  2-­‐3  hours  after  meds  "  Make  take  antihistamines  "  Continue  meds    

!  Flushing  Reaction    "  (INH)  "  Tyramine-­‐containing  foods    

!  (cheese,  salami,  red  wine,  tuna)  !  Avoid  those  foods  while  on  INH  

Photo  toxicity  

!  PZA  the  culprit  "  Limit  sun  exposure  "  Use  sunscreens  "  May  continue  even  after  PZA  stopped  

3/25/14  

14  

RASH:    Hypersensitive  Reaction  

!  Petechial  Rash  –    "  Thrombocytopenia  –  esp.  with  Rifampin  

!  Do  platelet  count  !  What  was  the  baseline?  !  If  low  suspect  hypersensitive  reaction  to  Rifampin  !  Consult  with  Clinician  !  STOP  Rifampin  –  monitor  platelets  until  normal  !  Rifampin  should  not  be  restarted  

!  Additional  medication  will  need  to  be  added  "  Will  increase  treatment  length  w/o  Rifampin  "  May  need  expert  medical  consultation  

!   Heartland!  

RASH:    Hypersensitive  Reaction  

!  Generalized  Erythematous  Rash:  "  Assoc  with  fever  OR  mucous  membrane  involvement  

"  STOP  TB  medications                      

!  Drug  (Re)challenge  "  If  no  anaphylaxis  or  airway  compromise  "  May  consider  drug  re-­‐challenge  "  See  “Drug  Resistant  TB”    Curry  National  TB  Center  p.

153    http://www.currytbcenter.ucsf.edu/drtb/drtb_ch7.cfm  

Hepatotoxicity  !  ANY  GI  complaint  could  represent  liver  toxicity    !  Liver  toxicity  could  be  3  of  4  first  line  TB  meds  

!  INH,  Rifampin,  PZA  

!  Bilirubin  &  alkaline  phosphatase  increases  "  Typically  with  Rifampin    

3/25/14  

15  

Hepatitis/Liver  toxicity    

!  Patient  Symptoms  "  Fatigue  "  Abdominal  pain  "  Fever  for  3  or  more  days  "  N/V  "  Flu-­‐like  symptoms  "  Lack  of  appetite  "  Dark  urine  "  Yellowing  of  skin/eyes  

Hepatotoxicity  

!  If  s/s  of  liver  toxicity  "  HOLD  ALL  TB  MEDS  UNTIL  LAB  RESULTS  KNOWN!  

!  If  normal  LFTS  –  may  continue  TB  medications  

!  ALT(SGPT)  more  specific  for  liver  injury      !  AST(SGOT)  indicate  abnormalities  

"  Muscle,  heart  or  kidney  

!  If  ALT>AST  consistent  with  liver  inflammation  

!  If  AST>  ALT  consider  alcohol  related  elevation  

Hepatotoxicity  

!  LFTs  less  than  3x  upper  limit  of  normal    "  Without  symptoms  –  continue  TB  meds  "  With  Symptoms  –  hold  meds  

!  LFTs  5x  upper  limit  of  normal  "  HOLD  meds  with/without  symptoms  

!  Bilirubin  increased  <2x  normal  "  With  no  explanation  "  Hold  TB  meds  

3/25/14  

16  

Hepatotoxicity  

!  Monitor  LFTS  weekly  

!  Reintroduce  meds    after  LFTs  return  to  “normal”  "  Reintroduce  meds  one  at  a  time  &  monitor  "  Assess  for  clinical  symptoms    

!  Monitor  LFTs  at  least  monthly  rest  of  treatment    

Neurotoxicity  

!  Peripheral  Neuropathy  "  More  likely:  Diabetic,  alcoholic,  HIV  infection,  pregnancy,  poor  nutrition,  hypothyroidism  

"  Tingling,  prickling  &  burning  balls  of  feet  or  tips  of  toes  

"  Sensory  loss  can  occur;  ankle  reflexes  lost;  unsteady  painful  gait    

"  Can  progress  to  the  fingers  and  hands  "  INH  likely  causative  agent  (  of  first  line  drugs)  

Neurotoxicity  

!  Administer  Vitamin  B6  (pyridoxine)  50mg  daily  

!  Increased  symptoms  can  increase  "  100  –  150mg  daily  

!  Note:    B6  in  doses  greater  than  200mg  can  CAUSE  neuropathy  

3/25/14  

17  

Central  Nervous  System  (CNS)  Toxicity  

!  Variety  of  mild  effects  can  occur  "  Drowsiness,  headaches,  concentration,  irritability,  

mood  changes,  insomnia  "  Caution  patients  to  expect  but  generally  abates  after  

initial  weeks  of  therapy  "  Do  NOT  discontinue  meds  

!  Coping  Suggestions  "  Change  timing  of  medications  if  able    "  Use  analgesics  –  not  Tylenol  "  Limit  caffeine  intake  "  Exercise  may  help  

Depression  !  Situational  depression  

"  Isolation  "  Diagnosed  with  communicable  disease  

!  Coping  Mechanism  "  Support  from  friends/family  "  Support  from  Health  care  provider  "  If  significant:    may  need  to  see  counselor  

!  INH  has  been  associated  with  depression  

Ototoxicity  

!  No  first  line  drugs  have  this  effect  "  Streptomycin  is  2nd  line  drug    

!  Aminoglycosides  and  capreomycin  "  Cause  vestibular  &  auditory  toxicity  

!  Drug-­‐  Resistant  TB:    A  Survival  Guide  for  Clinicians;  2nd  Edition;  Curry  International  TB  Center  "  http://www.currytbcenter.ucsf.edu/drtb/  

3/25/14  

18  

Ophthalmic  Toxicity  

!  Ethambutol  (EMB)  –  most  common  causal  drug  

!  Baseline  "  Visual  acuity  –  Snellen  Chart  "  Color  discrimination  –  Ishihara  

!  Conduct  Monthly  while  on  EMB  

Musculoskeletal    Adverse  Effects  

!  Aches  &  Pains  !  Variety  of  TB  meds  can  cause  

"  INH,  PZA,  Rifabutin,  fluroquinolones  "  Do  Not  Stop  meds  "  NSAIDS  can  be  helpful  

3/25/14  

19  

Sources:  

!  CDC  Core  Curriculum  on  TB:    What  the  Clinician  Should  Know;  5th  edition  "  http://www.cdc.gov/tb/education/corecurr/index.htm  

!  TB  Nursing:    A  Comprehensive  Guide  to  Patient  Care;  2nd  Edition  "  http://www.tbcontrollers.org/resources/tb-­‐nursing-­‐

manual/#.UaVINJxnerg  !  Drug-­‐  Resistant  TB:    A  Survival  Guide  for  Clinicians;  

2nd  Edition;  Curry  International  TB  Center  "  http://www.currytbcenter.ucsf.edu/drtb/  

!  TB  Drug  Information  Guide  2nd  Edition;    Curry  International  TB  Center  "  http://www.currytbcenter.ucsf.edu/products/

product_details.cfm?productID=WPT-­‐17A  

Prevention:      

reducing  Future  Cases  by  treating  

TB  Infection  

Treatment  of  TB  Infection  !  Since  the  1960s;  6-­‐9  months  of  INH  main  treatment  for  TB  infection  

!  Key  Component  of  TB  Elimination  strategy    "  Prevented  4,000  –  11,000  TBD  in  2002  

!  Liver  toxicity  is  an  adverse  reaction  to  INH  !  Carefully  monitor  TB  infection  patients  each  month  for  s/s  of  liver  toxicity  "  Patient  should  be  educated  to  STOP  INH  for  any  s/s  of  liver  toxicity  

 

3/25/14  

20  

Diagnosing  TB  Infection  (TBI)  

!  Two  types  of  TB  Testing  available  "  TB  Skin  Test  

!  CURRENT  SHORTAGES  OF  TUBERSOL/APLISOL    

"  Blood  Test    !  Immune  gamma  release  assay  (IGRAs)  !  QFT  !  T-­‐Spot  

 

Treatment  of  TB  Infection    

!  Once  active  TB  has  been  ruled  out  

!  Consider  treatment  for  TB  Infection  

Treatment  of  TB  Infection        

!  Isoniazid  (INH)  "  300mg  x    daily  9    months  (270  doses)  

!  Isoniazid    "   900mg  twice  weekly  for  9  months  (52  -­‐  76  doses)  "  DOT  must  be  used  

!  INH  &  Rifapentine  "  INH  900mg  &  Rifapentine  900mg                                                

once  weekly  !  12  weeks  DOT  must  be  used    

3/25/14  

21  

Treatment  of  TB  Infection  -­‐  Adults  

!  Rifampin    "  600mg  daily  for  4  months  (120  doses)  "  INH-­‐resistant  ,  rifampin-­‐susceptible  source  case  "  INH  intolerant  

 

!  Rifampin/PZA    "   NO  longer  recommended  "  Significant  hepatotoxicity    "  Deaths  occurred  even  in  persons  closely  monitored  

 

Why  do  we  treat  TB  Infection?  

!  Prevent  TB  Deaths  "  NM  Mortality  greater  than  Nationally  "  Study  17%  vs.  4%  

!  Navajo  and  Hispanics  born  in  Mexico  

!  Prevent  Morbidity  "  Especially  in  children  

!  Cost  Effective  "  Cheaper  to  treat  TB  Infection  than  TB  disease  

!  Terms  of  dollars  &  human  suffering  

 

 New  Mexico  &  the  World  Need:      An  effective  TB  vaccine  

 Better  diagnostic  tools    Safer  medications  

3/25/14  

22  

THINK