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Case presentation
Tania Jain
Chief medical resident
Detroit Receiving Hospital
Idea of an M and M conference
• Learn (that’s why we are in a training
program ;)
• Improve the system (we owe it to the
hospital !)
Idea of an M and M conference
• Learn (that’s why we are in a training
program ;)
• Improve the system (we owe it to the
hospital !)
• Have fun
At admission
• 68 yo man with h/o CAD (s/p MI and PCI
in 2006)
• 2 weeks of generalized abdominal pain,
constipation (8 days) and weight loss (15-20
lbs)
• ROS – cough
Other histories….
• PMHx: CAD (patient reports he doesn't take
any medications, currently)
• PSHx: Cardiac stent 2006
• Family Hx: Mother - MI, Father - TB
• Social Hx: 1PPD x 20 years (quit 2006); 1
fifth/day (quit 2006); remote IV heroin (60's
and 70's)
• Allergies: NKDA
Physical exam
• HR 117
• Vital signs including RR and O2 Sat. were
normal range (12-18/ 96-100%)
• Respiratory: Positive egophony on left
lung.
• Gastrointestinal: Diffusely tender to
palpation without rebound/ guarding, no
masses
ER work-up
• Abdominal XR =
No obstruction/ air fluid level
Atelectasis with central bronchial obstruction
More about the cough ?
• Cough productive of thick, white phlegm.
• Dyspnea at rest as well as fatigue,
generalized weakness and inability to walk
• No fever, night sweats, hemoptysis
• Only exposure in distant past (father; died
many years ago)
CT Chest
• Multiple cavitary lesions
• Largest left lung apex 3.8 x 4.7 cm
with nodular thickened wall
• Smaller cavitary lesions in L lung
base
• R lung: smaller areas of ground-glass
opacities with areas of tree in bud
appearance.
Other labs
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•
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•
K 2.9
Liver enzymes 38/ 63/ 70
Blood cultures sent (negative)
AFB smear x3 ordered
TB QuantiFERON® ordered
HIV ordered
TB isolation precautions
Day 2
• With Pulmonary consulted, plan is to pursue
a bronchoscopy if AFB x3 negative
(concern infections vs malignancy)
By Day 5
• 3 x AFB sputum smear reported negative
* producing very little sputum
* one sample was induced sputum by RT
* One morning sample
Oh BTW….
• The morning of day 5 (which is the day
patient scheduled for bronchoscopy), TB
QuantiFERON® reported positive
What do you do now ?
? Discontinue isolation
? Bronchoscopy
? Nucleic acid amplification
? Treat active TB
? Treat latent TB
What actually happened ?
• AFB isolation discontinued
• Patient underwent bronchoscopy
A few hours post-bronchoscopy…
•
•
•
•
Tachypneic with RR 30s
Tachycardic to HR 150s
Hypoxic w/ SPO2 92 on 4L NC
Accessory muscle use. Crackles, most prominent
over left upper lung field. Decreased breath
sounds, more prominent on left side
• ABG 7.5 / 22 / 65 / 20 / 93, lact 3.4
• Transferred to MICU for new sepsis secondary to
HCAP ; Rx vancomycin and cefepime
Day 6 & 7
•
•
•
•
BAL smear : 4+ AFB
AFB isolation re-initiated
Started on RIPE
Blood and respiratory fungal
cultures negative
Back on floors
•
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•
•
Repeat 3 AFP sputum - negative
BAL sent for susceptibility testing
Continued RIPE and AFB isolation
Discharged after 2 weeks inpatient
RIPE; Detroit/ Michigan dept of
health informed; TB clinic follow
up
• Day 30, sputum cultures (from day 2, 3) are
reported positive for Mycobacterium
tuberculosis
Aim
• To understand the following about TB diagnosis and
prevention :
? CDC guidelines to prevent transmission
? Testing for TB diagnosis
? Role of bronchoscopy
? When in doubt
Typical TB patient
• Cough >= 3 weeks/ weight loss/ fever/
night sweats
• Chest xray
• Sputum Smear
• Sputum culture
• Sputum drug susceptibities
Our patient decision tree in
retrospect !
QuantiFERON®
positive
= means he
is infected
Latent
Active
“Latent” and Active TB
• Infected but not
symptomatic
• Not infectious
• skin test or blood test
result indicating TB
infection
• normal chest x-ray and a
negative sputum test
• Needs treatment for
latent TB
• Skin/ blood test positive
• Abnormal chest XR or
positive sputum
• Symptoms
• Treatment for TB
disease
QuantiFERON®
positive
= means he is
infected (latent or
active)
Latent : no
symptoms/ normal
chest xray/ sputum
negative
Active TB :
symptoms/ chest xr
findings/ sputum
smear +
Preventing transmission
• Who to isolate ?
“Anyone suspected to have TB disease OR
has known TB disease and has not had
enough treatment”
How to identify “infectious”
patient ?
• Cough > 3 weeks
• Cavitation on chest xray
• Positive AFB sputum smear
• Lung/ laryngeal involvement
• Failure to cover mouth/ nose
• Cough-inducing/ aerosol generating prcedures
* Extrapulmonary TB is not infectious unless
open abscess or lesion
When to discontinue
isolation in a TB “suspect”
• Likelihood of TB
AND
Another possible diagnosis
OR
AFB smears negative x 3
Excerpts from CDC :
• Hospitalized patients for whom suspicion of
TB remains after 3 negative AFB sputum
smear should not be released from airborne
precautions until they are on standard
multidrug antituberculosis treatment and
are clinically improving.
Fun fact
• In one study, 17% of transmission occurred
from person with negative AFB smear
results.
Behr MA etal. Transmission of mycobacterium tuberculosis from patients smearnegative for acid-fast bacilli. Lancet 1999;353:444-9
When to discontinue
isolation in a TB
“disease”
• Effective therapy for 2 weeks
• Clinical improvement
• AFB smears negative x 3
How about discharge home ?
• Specific plan for follow up
• Standard multidrug TB Rx and DOT
• No infants/ children < 4 yrs or
immunosuppressed
• Immunocompetent members have been
exposed
Diagnostic procedures for TB
QuantiFERON® TB Gold
• Cell mediated immune
response
• IFN gamma
• ELISA based
• Positive in both latent and
active disease
Tuberculin skin test
• PPD, 48-72 hrs
• Beyond 72 hours ?
*repeat
*If ≥15 mm up to 7 days  +
Measure the induration; not redness
 OK to do in HIV, BCG exposure,
pregnancy
Interpreting the TST
Size of induration:
>5 mm
highest risk, HIV,
known exposure
>10 mm
other risk factors
>15 mm
no known risk factors
Chest radiography
• Active disease: upper lobe infiltration/
cavity/ effusion
• Healed: nodules, fibrotic scars, calcified
granulomas or basal pleural effusion
• Normal in latent TB
• HIV: infiltrate in any lung zone, mediastinal
or hilar LAD, normal
Sputum samples
• 3 samples, 8 – 24 hours apart, atleast 1
morning
• Type:
Spontaneous expectoration
Induced sputum
Gastric aspirate (esp children)
Bronchoscopy sample
• Stained smear - Auramine rhodamine/
Ziehl-Neelsen or Kinyoun stained smear
under flourescence microscopy
• Culture – definitive identification, drug
susceptibilities
Nucleic acid amplification
• 70% sensitivity in smear negative
• Utilize a lot of amount of specimen, which
could be used for culture/ drug
susceptibilities
• Should not replace culture and drugsusceptibility testing in suspected TB.
Role of bronchoscopy
• Those with negative induced-sputum results
still suspected with TB are then referred for
bronchoscopy
• 30 suspected cases:
Induced sputum smear/culture 60 days
BAL culture + 3/30 (10%)
BAL smear + none
BAL NAA + none
Diagnostic utility
• Drug susceptibilities
• Identification of alternative diagnosis:
granulomatous/ malignancy
Lower yield
• Operator expertise
• Lidocaine – antibacterial and antifungal
properties
101 Smear negative patients
• BAL culture:
Sensitivity 73%
NPV 91%
• Induced sputum:
Sensitivity 87%
NPV 96%
Low cost
Well tolerated
Excerpt from
* If possible, bronchoscopy should be
avoided in patients with a clinical syndrome
consistent with pulmonary or laryngeal TB
disease because bronchoscopy substantially
increases risk for transmission either
through an airborne route or a contaminated
broncoscope, including in persons with
negative AFB sputum smear results.
Excerpt from
• If the underlying cause of radiographic
abnormality remains unknown, additional
evaluation with bronchoscopy might be
indicated; however, in case where TB
disease remains a diagnostic possibility,
initiation of a standard TB regimen for a
period before bronchoscopy might reduce
the risk for transmission.
Excerpt from
• If bronchoscopy is performed, because it
is a cough-inducing procedure, additional
sputum samples for AFB smear and
culture should be collected after the
procedure to increase the diagnostic yield.
HIV Testing
 Who to test for HIV ?
Every patient with latent or active TB
 Why ?
Progression from latent to active TB.
Rapid progression/ fatal.
Rapid expansion of outbreaks.
 What test ?
Rapid HIV/ Standard labs assays
Hot off the press from MMWR..
DMC does not have this test
available !
• Automated nucleic acid amplification test
that can simultaneously identify M.
tuberculosis and rifampin resistance within
2 hours.
• 98 percent of patients with smear-positive
tuberculosis and 72 percent of patients with
smear-negative/culture-positive tuberculosis
This recent newsletter says…
• To aid in decision of whether continued airborne
isolation is warranted for pts with suspected
pulmonary TB.
• Per the data presented at Conference on Retroviruses
and Opportunistic Infections in Seattle in Feb 2015,
negative Xpert MTB/RIF assay results form either one
or two sputum samples are highly predictive of results
of two or three negative AFB sputum smears.
• Single negative Xpert assay NPV 99.7% (99.6% in
USA and 100% outside)
• Two serial negative NPV 100%
Take home !
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High suspicion
“Intraweb” / DMC resources
Take you own history
It’s ok to seek help when in doubt
Acknowledgments
Dr D. Kissner
Dr R. Roxas
Dr S. Dhar
CDC