Attending Version
Management of Hospitalized Patients with Suspected Pulmonary Mycobacterium
Tuberculosis; created by Dr. Peggy Beeley
September 2006
Learning objectives:
1. Recognize patients who fit criteria for possible Pulmonary Tuberculosis.
2. Understand the basic immunology of initial TB infection and reason for various clinical presentations.
3. Understand the epidemiology of transmission and the importance of respiratory isolation and personal
protective gear.
4. Know the diagnostic testing required for confirmation of a Pulmonary Tuberculosis diagnosis.
Disclaimer: This exercise primarily focuses on prevention of transmission of Pulmonary MTB in the
hospital setting and management during evaluation of a patient suspected of having this disease. References
to MTB treatment will be limited as the complex subject requires much more time than allotted. All
patients strongly suspected of having TB should be referred to an Infectious Diseases Specialist and
Pulmonary Medicine Specialist with experience and knowledge of the diagnostic criteria and treatment
considerations for each individual case. Placing your patient in respiratory isolation and ordering AFB
smears and culture is an automatic Hospital Epidemiology consultation. The epidemiology staff members
follow the patient until exclusion criteria are met or until the patient is discharged.
Facts about TB and Transmission:
1.
2.
3.
4.
Epidemiology: In the years 1985-1992 the United States saw a resurgence of Pulmonary
MTB.
a. Prior to 1985 TB cases in the US had fallen in numbers each year.
b. After 1985 cases began to rise dramatically with peak of 10.5 per 100,000
population, then decline in 1992 to 5.2 per 100,000 population, the lowest in
recorded history.
c. The causes of increased number of cases in the late 1980s included in part: HIV
disease, international travel, rise in homelessness and relaxation of TB control
measures in hospitals and institutions.
Recognition of potential cases rests primarily upon astute clinical observation by
providers of infected persons seeking medical care.
a. Cardinal features to identify patients early during triage include:
i. Constitutional Symptoms
ii. Hemoptysis
iii. Chronic cough
iv. Weight loss of >10 lbs
b. These features have high sensitivity but low specificity in recognizing
Pulmonary TB cases.
c. Masking patient with two or more of these symptoms on arrival to the hospital,
before chest x-ray or other diagnostic procedures is important to reduce
exposure to other patients and HCWs.
High Risk groups include: HIV positive individuals, immigrants from high risk regions,
persons with known exposure, institutionalized patients, the homeless and persons with
abnormal immune systems, i.e. immunotherapy in Rheumatoid arthritis, Corticosteroid
treatment and ESRD.
Understanding MTB infection and the various presentations:
a. Infection occurs primarily by inhalation of infectious airborne droplet nuclei.
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b.
The initial focus is usually sub-pleural in the mid-lung zones (middle lobe,
upper lower lobe or lower upper lobe) where greater airflow favors delivery of
the bacteria. Generally this is a single focus but several foci may occur in one
fourth of cases.
c.
Immunity:
i. Although lung macrophages ingest the bacterium, during early
infection the growth is uninhibited by macrophages alone.
ii. Blood borne lymphocytes are attracted to the site and eventually lead to
antigen sensitivity and ultimate sequestration and granuloma formation
with lymphocytes, macrophages, Langhans giant cells, and fibroblasts
being key players. T cell activation orchestrates these cells and is
critical in containment.
iii. Lymphatic/hematologic spread occurs prior to development of adequate
tissue hypersensitivity to contain the growth of the bacilli.
1. Favored sites of deposition include the apices of the lungs,
lymph nodes, kidneys, vertebral bodies, and close to the
meninges.
2. Thus, post primary (or reactivation) MTB is more commonly
seen in these sites.
iv. Persons with normal immune systems develop hypersensitivy more
easily and thus, generally are able to sequester bacterial spread earlier
in infection.
1. Although sequestered within granulomas, bacilli remain viable
and can escape at any time, thus leading to replication and
active infection.
2. Treating asymptomatic persons with a positive skin test
prevents active disease from the re-emergence of MTB at a
later time.
Primary Pulmonary Tuberculosis may lead to:
i. A sub-acute pneumonia or slowly progressive pneumonia with cavitary
development or be asymptomatic leading to Latent TB infection
(LTBI).
ii. Persons with abnormal immune systems may have unusual
presentations of primary MTB.
Post Primary Pulmonary TB may occur months to years after primary infection.
i. 3-4% of infected persons develop active TB within the first year, 15%
lifetime risk.
ii. Post Primary Pulmonary infection usually presents as asymmetrical
pulmonary involvement.
iii. Caseation, cavity formation and fibrosis are common.
iv. Classically this presents as posterior apical disease due to poor
lymphatic flow and, perhaps, the relative hyperoxic environment and
aerobic nature of MTB.
v. Cavitary disease leads to unimpeded bacteria replication and is
considered more contagious than non-cavity disease due to drainage of
the cavity into the bronchi that is easily aerosolized by cough.
d.
e.
f.
Initial Evaluation:
i. Chest x-ray
ii. Sputums for AFB (stain and culture)
1. Early morning sputums from overnight pooling of bronchial
secretions are best.
2. CDC now gives alternative recommendations of 3 sputums in
48 hours with inclusion at least one early am sputum. This is
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iii.
iv.
v.
vi.
5.
felt to have significant yield without the extra-cost of
Respiratory Isolation days.
3. Nucleic Acid Amplification on sputum is also a way to
diagnose MTB early but does not replace the need for sputum
culture where the isolate can be tested for resistance patterns.
Placement of TST on the patient with documented reading at 48 hours.
Pulmonary Medicine and Infectious Disease Consultation if there is a
high suspicion of pulmonary TB.
Chest CT scan may provide additional information suggestive of the
diagnosis.
Bronchoscopy should be considered if sputums are of poor quality or if
the urgency of making a diagnosis demands it.
TB Control within the Hospitalized Setting
a. Patients with upper lobe pulmonary processes should be considered potentially
infected with TB until TB is excluded.
b. HIV positive patients with respiratory symptoms and/or abnormal chest x-rays
should always be placed in Respiratory isolation until TB is excluded.
c. Aerosolized droplet nuclei particles are the primary mode of transmission.
i. These particles remain airborne long after infected persons leave an
area.
ii. A cough or 5 minutes of talking or singing can produce 3000 – 5000
infectious particles. Sneezing can aerosolize many more particles.
iii. Laryngeal TB is the most infectious form of MTB.
iv. Fomite transmission is rare but can occur in some setting i.e. poorly
sterilized endoscopes.
d. Isolation techniques include:
i. Negative Pressure Respiratory Isolation Rooms are one of the most
important preventions of transmission in health care settings.
ii. High efficiency particulate air filtration (HEPA) to cleanse air of
infection droplet and reduce circulation to persons in close proximity
on a temporary basis (equipment used in temporary holding areas, i.e.
ER).
iii. N-95 masks with appropriate fit testing, soon to be a yearly ritual by all
HCWs.
iv. Training patients on appropriate respiratory hygiene, including cough
etiquette procedures is an important prevention of transmission.
v. Masking patients who are being transported within a health care facility
(recommendations include surgical mask or N-95 depending on
source).
vi. Infection does not generally occur outdoors, although patients would be
advised to remain at a distance from others even in this setting. (FYI
for your insistent smokers who threaten leaving AMA without a
permitted smoke break)
vii. Patients remain potentially infectious until on treatment for several
days to weeks (exact amount of time depends on organism load and
other factors).
1. Sputum smears for AFB collected after initiation of therapy
may continue to be positive for up to three weeks but not grow
in culture.
2. The safest approach is probably to continue isolation until
discharge.
3. If discharge is delayed, request Pulmonary or Infectious
Diseases Consultant input before stopping respiratory
isolation.
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6.
Tuberculin Skin Testing or TST, formerly known as PPD
a. TST is very important in the reduction of transmission of MTB by detecting
early infection in persons known to be exposed or at high risk of exposure.
b. Tuberculin positivity occurs 3-8 weeks after infection and indicates the
development of cellular immunity and tissue hypersensitivity
c. TST is recommended yearly for HCW and other high risk groups
i. If TST was done more than 1 year ago in newly hired HCWs, boosting
with a second TST is recommended to exclude remote infection in
which cellular immunity hypersensitivity to MTB has waned. This is
generally repeated within one to two weeks of initial TST.
ii. When MTB exposure occurs in the Health Care setting, TST should be
obtained immediately upon notification of the exposure and repeated in
8-12 weeks.
iii. HCWs with LTBI discovered through TST and without pulmonary
symptoms or an abnormal chest x-ray are safe to return to work but are
strongly encouraged to undergo LTBI treatment.
d. TST evaluation depends on the risk of the population being tested. Examples of
this include:
i. High risk: ≥5mm of induration (Example AIDS patients)
ii. Medium risk: ≥ 10 mm of induration (Example: HCW with exposure
risk)
iii. Low risk: ≥15 mm of induration (General US population)
iv. See CDC guidelines or Sanford’s for more detail.
e. False positives represent non-tuberculous mycobacterial infection:
i. This includes BCG or bacillus Calmettevaccine (M. bovis
strain used in high prevalence countries).
ii. Unless BCG was given very recently, TST of > 10mm is highly
suggestive of MTB infection.
f. False negatives TST
i. Occurs in at least 20% of persons with active TB.
ii. Other causes include: general illness, malnutrition, sarcoidosis,
intercurrent infections, reticuloendothelial disease, corticosteroid
therapy and immunocompromised individuals (i.e. AIDS)
iii. Remote MTB infections with loss of Tuberculin Reactivity
g. Prior BCG vaccination and prior positive TST is not a contraindication to TST
in evaluating for active TB disease.
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Question 1:
32 year old gay male from San Francisco presents to our ER soon after moving to Albuquerque. In
recent weeks he has developed night sweats, weight loss and complains that his smokers cough has
seemed more productive and more frequent than usual. He was healthy until recently and has no past
medical history except Childhood Asthma. He has not been to a doctor in years. He admits to having
anal receptive sex with many male partners, mostly at SF bathhouses. Although he is usually careful to
have partners use condoms, he admits that he sometimes has unprotected sex in “moments of passion”.
He has never been tested for HIV due to the fear of finding out he might be infected. As the admitting
Resident you are called to evaluate him for admission after a chest x-ray reveals left lower lobe
pneumonia.
Which of the following is true?
A. Respiratory isolation is not necessary since Pulmonary TB does not present as lower lobe disease
B. A sputum specimen for acid fast smear and culture and blood cultures should be obtained as soon as
possible. Community acquired Pneumonia treatment should be started while waiting for test results.
C. A negative TST excludes the diagnosis of pulmonary TB allowing Respiratory isolation to be
discontinued.
D. Three negative smears of sputum for AFB excludes the diagnosis of pulmonary TB in this patient.
E. HIV testing should be done and Community acquired pneumonia treatment and anti-TB medications
should be started immediately until the diagnosis of Pulmonary TB is excluded.
Correct answer is B.
This patient is likely to have HIV based on his risk profile. His constitutional symptoms are consistent with
untreated advanced HIV, TB or any number of other opportunistic infections or malignancies. A mask
should have been placed immediately on this patient when he arrived in triage because he meets ¾ criteria
for high risk of TB (constitutional symptoms, weight loss and chronic cough). Remember, the differential
diagnosis is broad and he could also have a sub-acute presentation of CAP. Waiting to initiate antibiotics
increases his risk for bacteremia or sepsis. He should be placed in respiratory isolation until the cause of his
pulmonary process is appropriately investigated and he has 3 negative smears for AFB. Answer A is
incorrect because HIV infected individuals may not have classic upper lobe reactivation TB. They are more
likely than immunocompetent individuals to have primary TB due to their suppressed cellular immunity.
Primary TB can occur anywhere in the respiratory system, often in the middle or lower lobes. Answer C is
incorrect because a negative TST never rules out Pulmonary MTB. Although most individuals with
pulmonary TB have a positive TST, persons with poor cellular immunity may have no reaction at all. In the
past anergy testing panels were placed with the PPD but this practice has been abandoned due to poor
reliability and inconsistent interpretation. Answer D is incorrect because: although negative AFB smears
predict decreased transmission and lower bacilli load they do not exclude TB. The literature describes
reports of AIDS patients with negative smears transmitting TB. Often culture growth is the first
confirmation of the diagnosis. Answer E is incorrect in that TB medications should not be empirically
started unless the patient is unstable and other empiric therapies (i.e. for CAP) are failing. Giving anti-TB
drugs empirically is likely to reduce the yield of cultures that are collected later. Obtaining the patient’s
MTB culture for drug resistance testing is very important and may significantly impact treatment outcome
in your patient. Obviously, HIV testing should be performed as soon as possible.
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Question 2
The hospital epidemiologist calls you and tells you that a patient you cared for 2 weeks ago has confirmed
MTB from sputum culture.
You immediately review her medical record and begin to recall the details of the case. Ms. N is an 80 year
old Vietnamese female who has recently come to the United States to visit her daughter for a month. Her
daughter brought her to the hospital on the second day of her visit because Ms. N had dramatically lost
weight since her daughter last saw her. The daughter also noticed a persistent cough. Upon reviewing the
chart and seeing the patient you have a strong suspicion of TB. The ER Attending had the same suspicion
and immediately had placed her in respiratory isolation (private room with HEPA filtration). Her chest XRay revealed a right middle lobe infiltrate but no cavitations. She was dehydrated with mild tachycardia
and a small supplemental oxygen requirement. She was placed on CAP therapy (Levofloxacin and
Cefotaxime) and 3 early morning sputum smears/cultures for acid fast bacilli and blood cultures were
obtained. A TST was placed and was negative at 48 hours. By hospital day 4 the acid fast smears were
reported out as negative and blood cultures remained negative. Isolation was discontinued. She appeared to
be clinically improving with less cough and her vitals had returned to normal. Chest X-Ray showed
minimal or no improvement but was attributed to delay of radiographic improvement which is often seen in
CAP. The patient reported feeling better and requested discharge under her daughters care. She was treated
with outpatient Levofloxacin and had a scheduled follow-up in MFU.
You, as a UNM employee, had a required TST placed 10 months ago that was negative.
Which of the following is true?
A. You immediately get a TST and Chest X-Ray. If both are normal, no follow-up is required.
B. You wait and have TST placed in 3 months
C. You immediately have TST placed, start Isoniazid/pyridoxine therapy and request counseling for
occupationally acquired PTSD
D. None of the above
:
The most appropriate answer is D.
Answer A is incorrect because a Chest X-ray is not necessary unless you have a positive TST or have
symptoms consistent with Pulmonary TB. If your immune system is normal, your likelihood of having
active pulmonary TB is virtually near zero from this recent exposure. Follow-up TST for HCWs exposed to
MTB is required at 8-12 weeks after exposure (usually 3 months) as most TST conversion will occur within
this time period. Answer B is incorrect because a “baseline” TST is needed to assure documentation of
your current TST status. It should not be positive if the exposure was less than 3 weeks ago. The
importance of knowing your baseline skin testing is vital to determine if this occupational exposure has led
to TST conversion and LTBI. Although you may feel worried about your exposure to this patient, you
should be reassured that you followed standard respiratory isolation procedures during your initial
interview and physical exam (probably the longest exposure period). In addition, the patient was not likely
to be highly contagious due to her negative AFB smears. Negative smears essentially equal very low
number of aerosolized bacilli. The two days your patient was out of isolation was enough to lead to contact
investigation but was unlikely to lead to your acquiring infection. Isoniazid prophylaxis with a negative
baseline TST is only indicated if you have HIV infection or other profound cellular immunity impairment.
If this applies to you, Answer C may indeed be true.
Case discussion:
Why would the patient seem to be improving? Hydration and improved nutrition might have resulted in
some symptom relief. Pulmonary TB infection may have waxing and waning symptoms. In addition,
Levofloxacin has activity against TB. This is not a first line therapy and should be reserved for patients
intolerant of other anti-tuberculin therapy or patients with a multi-drug resistant strain. Multi-drug therapy
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is always needed in the treatment of MTB so she should be placed on appropriate first line agents as soon
as possible. Resistance testing of her cultured MTB will also guide her future treatment. The Department of
Health should be notified immediately to do community contact investigation, particularly for her daughter
and contacts during travel. DOH would likely be the best providers to initiate her treatment and follow-up
since she is Vietnamese and has no other financial means for health care. Interestingly, a temporary VISA
for a visit with relatives in the US does not require TB screening by interview or TST.
References:
American Thoracic Society/Centers for Disease Control and Prevention/Infectious Disease Society of
America: Controlling Tuberculosis in the United States
Am J Respir Crit Care Med Vol 172, pp 1169-127, 2005
MMWR: Guidelines for Preventing the transmission of Mycobacterium tuberculosis in Health-Care
Settings, 2005
Mandell’s Principles and Practice of Infectious Diseases, Sixth edition
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