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

• 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

• 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 !

“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

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 smear-negative 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

>5 mmhighest risk, HIV, known exposure

>10 mm

other risk factors

>15 mm

no known risk factors

Interpreting the TST

Size of induration:

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 drug-

susceptibility 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

Lower yield

• Operator expertise

• Lidocaine – antibacterial and antifungal properties

Diagnostic utility

• Drug susceptibilities

• Identification of alternative diagnosis: granulomatous/ malignancy

101 Smear negative patients

• BAL culture:

Sensitivity 73%

NPV 91%

• Induced sputum:Sensitivity 87%NPV 96%

Low costWell 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.

• 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.

Excerpt from

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 !

• High suspicion

• “Intraweb” / DMC resources

• Take you own history

• It’s ok to seek help when in doubt

Acknowledgments

Dr D. KissnerDr R. RoxasDr S. Dhar

CDC