Tuberculosis Management Guidelines and Associated DENTAL

Management Guidelines

Tuberculosis: Assessment, Analysis, Management Guidelines and

Associated DENTAL Management Guidelines
TUBERCULOSIS EPIDEMIOLOGY
Mycobacterium tuberculosis (MTB) is an aerobic, acid-fast bacillus
that usually affects the lungs. There has been an increased incidence
of MTB secondary to HIV, homelessness, and emigration. Ninety
percent of the adult cases of tuberculosis (TB) are due to
reactivation of a dormant infection.
RISK FACTORS
Risk factors for TB are HIV; diabetes; prolonged steroid use;
alcoholism; immunosuppressive treatment; and being a prisoner,
nursing-home resident, or healthcare worker;
and close contact with infectious patients, underweight patients, and
persons from countries with a high TB prevalence.
TRANSMISSION
TB is spread from person to person through the air via coughed-
infected droplets.
Coughed-up, aerosolized particles stay around for a long time and
infect susceptible individuals.
SYMPTOMS AND SIGNS
Symptoms and signs frequently associated with TB are fever, chest
pain, chills, cough, weight loss, hemoptysis, night fever, night sweats,
and fatigue.
Table 36.1. Interpretation of a Positive TST PPD Reaction
Induration Size At-Risk Populations
5mm induration: A 5mm reaction is positive in:
! An immune-compromised patient
! A close contact of a patient with TB
10mm induration: A 10mm reaction is positive in:
! Recent migrant to the Unites States
! An IV drug user
! A patient less than 4 years old
15mm induration: A 15mm reaction is positive in:
! One with no known TB risk factors
DIAGNOSIS
The diagnosis of TB is made with:
1. The Tuberculin skin test (TST): The TST is done using purified
protein derivative (PPD) from Mycobacterium tuberculosis. The
PPD skin test is a delayed hypersensitivity reaction that shows
response in 48–72 hours. The response is indicated by
an induration or thickening at the site of the inoculum that is
measured to identify if the reaction is positive or negative (Table
36.1).
2. QuantiFERON TB Gold test (QFT-G): The QFT-G is a new test
for diagnosing latent M. tuberculosis infection. It is an in vitro
diagnostic test that measures a component of cell-mediated immune
reactivity to M. tuberculosis.
The test is based on the quantification of interferon-gamma (IFN-γ )
released from sensitized lymphocytes in whole blood incubated
overnight with purified protein derivative (PPD) obtained from M.
tuberculosis. The QFT-G can be used in place of the TST.
3. Sputum smear and culture: The bacteria, when cultured, can take
3–6 weeks to grow.
4. Chest x-ray: The chest x-ray can show hilar adenopathy, upper-
lobe infiltrates, pleural effusion (especially in young patients), and
calcifications. The chest x-ray is done if the PPD is positive. If the
chest x-ray is abnormal, the patient is evaluated for active TB.
WHEN TO INITIATE TB TREATMENT
Treatment for TB should be initiated with the presence of a positive
AFB smear or when there is a high clinical suspicion.
TYPES/FORMS OF TB
The three forms of TB are:
! Latent TB
! Active TB/Pulmonary TB
! Multidrug-Resistant (MDR) and Extensively Drug-Resistant
(XDR) TB
Latent TB
With latent TB the patient has a positive skin test; negative chest x-
ray; and no symptoms, signs, or physical findings of TB. The patient
is treated to prevent future reactivation to the active form of TB.
Active TB/Pulmonary TB
A patient is said to have active/pulmonary TB when the patient has
a positive skin test; the chest x-ray may be abnormal; the patient
experiences fever, cough, night sweats, hemopytosis, anorexia, and
weight loss; and the respiratory specimen smear test is positive.
Multidrug Resistant (MDR) and Extensively Drug-Resistant (XDR)
TB
The four-drug standard regimen, or the first-line, anti-TB drugs,
when used correctly can successfully treat TB. When these drugs are
used incompletely, incorrectly, or not at all,
multidrug-resistant TB (MDR-TB) can develop. Drug-resistant TB
is a dangerous form of TB caused by the TB bacillus becoming
resistant to at least isoniazid and rifampicin, the two most powerful
anti-TB drugs. MDR-TB takes longer to treat with second-line
drugs and the care is often expensive. Extensively drug-resistant
tuberculosis (XDR-TB) develops when the second-line drugs are also
incompletely or inappropriately used, such that they become
ineffective. Treatment options for XDR-TB are even more
restrictive and expensive because the patient has severe resistance to
the first and second line of TB treatment.
Latent TB Treatment
New CDC guidelines for managing latent tuberculosis infection
(LTBI): Tuberculosis can be prevented by treating latent
Mycobacterium tuberculosis infection (LTBI). Studies
have shown that a new combination of isoniazid (INH) and
rifapentine (RPT) given once-per-week for 12 weeks, as directly
observed therapy (DOT) to otherwise healthy people ages 12 and
older who are at high risk for developing TB, is very effective in
preventing TB. The new INH-RPT DOT regimen is beneficial for
use in correctional institutions and homeless shelters.
Also, because the INH-RPT combination is given for a shorter
duration, patients are more likely to complete this regimen than the
nine months daily INH therapy without
DOT. It should be noted that previous regimens recommended for
treating LTBI are unchanged, and the rifampin-pyrazinamide (RIF-
PZA) regimen is not recommended any more.
Healthy individuals who are at high risk for developing TB include
anyone recently exposed to contagious TB; conversion from negative
to positive TB skin test or a chest xray showing prior TB disease;
and an otherwise healthy HIV patient not taking antiretrovirals if
TB preventive treatment is indicated.
It is not recommended for children under age 2; pregnant patients
or women planning to become pregnant; HIV-infected people taking
antiretrovirals; and patients that have been exposed to TB disease
that is resistant to isoniazide or rifapentine. The preferred regimen
for children aged 2–11 years is the nine months of daily INH. If the
patient is HIV-positive and has fibrotic lesions on the chest x-ray,
INH is given for nine months.
Active TB/Pulmonary TB Treatment Regimens
Initial Phase
The initial phase therapy consists of rifampin, isoniazide,
pyrazinamide, and ethambutol (RIPE) for two months.
Continuation Phase
The continuation phase therapy consists of four months
INH/rifampin daily or twice/week of INH/rifampin for seven
months. The multidrug approach is needed because of the high
incidence of resistance.
PRECAUTIONS
Transmission of TB can be curtailed by using the following
precautions: wash hands, sterilize instruments, disinfect surfaces,
minimize splash/aerosols, and use approved masks.
TREATMENT GUIDELINES: DETAILED DISCUSSION
The United States Public Health Service (USPHS) and the Infectious
Diseases Society of America (IDSA) develop treatment regimens.
Directly observed therapy (DOT) involves monitoring ingestion of
each antituberculosis dose to maximize the completion of treatment.
This is of particular benefit in the homeless, the drug-abusing
population, or individuals with a poor drug-compliance
history.
Each antituberculosis regimen has an initial phase of two months of
treatment followed by a continuation phase of four or seven months.
Isoniazide (INH), rifampin (RIF), ethambutol (EMB), and
pyrazinamide (PZA) are considered the first-line drugs in
the treatment of tuberculosis. The second-line drugs consist of
cycloserine, ethionamide, streptomycin, and capromycin.
All asymptomatic patients with positive TST/PPD skin reactions
(latent TB) should get preventive therapy with INH and pyridoxine
(vitamin B6) supplementation for six to nine months. As previously
stated in the latent TB treatment discussion, the CDC
now recommends a new combination of isoniazid (INH) and
rifapentine (RPT) given once-per-week for 12 weeks, as directly
observed therapy (DOT), to adults and children
above age 12.
BCG vaccine is given to all newborns in developing countries where
tuberculosis is endemic. It is given to attenuate an actual attack. A
PPD skin test with an induration of ≥15 mm in a vaccinated
individual warrants anti-TB treatment.
Without interruption, six months is the minimum duration of TB
treatment. When interruption occurs because of missed doses or
drug toxicity, the treatment should be completed in nine months.
In the initial phase of two months, the symptomatic patient (active
TB) is treated with all four drugs: isoniazide (INH), rifampin (RIF),
ethambutol (EMB), and pyrazinamide (PZA). Once the organism
shows susceptibility on testing, EMB is discontinued. The
initial phase may be given in one of three ways: daily for two
months, daily for two weeks followed by twice weekly for six weeks,
or thrice weekly for two months.
In the continuation phase there are three treatment options: daily,
twice weekly, or three times weekly, by DOT. The four-months
continuation phase is used for most patients.
INH and RIF are given for four months if the initial chest x-ray was
positive or the sputum smear was positive at two months. If the
initial cultures were negative and treatment with the four drugs was
initiated for two months (resulting in improvement of the symptoms
and signs or improvement of the chest x-ray at two months), INH
and RIF can be given for two additional months to complete
treatment as an alternate option.
If the initial chest x-ray was positive along with a positive smear at
two months, the patient is given an extended treatment for seven
months. Therefore, extended treatment is recommended for patients
with drug-susceptible tuberculosis who have cavitation
on the chest x-ray and positive sputum cultures, after completion of
two months of treatment.
The seven-month phase treatment is also used in those patients
where PZA could not be used for the initial treatment because of
liver problems or gout. INH, RIF, and PZA can cause hepatitis. If
hepatitis occurs, the drugs are stopped immediately for a short
period. The medications are restarted once the hepatitis resolves.
The physician routinely monitors liver, kidney, and platelet
functions during anti-TB treatment. The dental practitioner must
always evaluate these results prior to the start of
dental treatment. If the patient has preexisting hepatitis, INH is
avoided and the patient is given RIF, EMB, and PZA for six months.
In the presence of severe liver disease, only one hepatotoxic anti-TB
drug is used along with EMB. This patient is given RIF plus
EMB for 12 months. Gastrointestinal upsets are common in the first
few weeks of treatment and they resolve progressively. The drugs
can, however, be taken with food to minimize the gastrointestinal
side effects.
Two drug combinations are approved in the United States:
1. INH and RIF (Rifamate!R )
2. INH, RIF, and PZA (Rifater!R )
Isoniazide (INH) Side Effects
Hepatotoxicity
Hepatotoxicity with enzyme elevations occurs in 10–20% of the
patients. The hepatotoxicity is the worst in males around 40 years of
age.
Peripheral Neuropathy
The neuropathy is dose-related and is uncommon at conventional
doses. It is more common in the presence of conditions that
predispose to neuropathy – for example, diabetes, HIV, renal
failure, alcoholism, pregnancy, and breast-feeding. Pyridoxine
(vitamin B6) supplementation is given to prevent this neuropathy. It
typically causes circumoral tingling numbness and tingling
numbness in the hands and feet.
Rifampin (RIF) Side Effects
The following are RIF side effects:
! Body-fluid discoloration: Orange discoloration of bodily fluids
such as saliva, tears, sweat, and urine occurs.
! Cutaneous reactions: Pruritis with or without a rash can occur.
! Transient hepatotoxicity: Liver toxicity can occur and monitoring
of LFTs is a requirement with anti-TB treatment.
Ethambutol (EMB) Side Effects
The following are EMB side effects:
! Retrobulbar neuritis: Retrobulbar neuritis that occurs is
irreversible. It is doserelated and the risk is minimal with routine
dose.
! Peripheral neuritis: Peripheral neuritis with ethambutol and INH
are similar in presentation.
Pyrazinamide (PZA) Side Effects
PZA is associated with the following:
! Hepatotoxicity
! Gastrointestinal side effects: nausea and vomiting
! Non-gouty polyarthritis
DDIs Among Anti-TB Medications and AAAs Used in Dentistry
The following are DDIs among anti-TB medications and anesthetics,
analgesics, and antibiotics:
! Antibiotics: The concentrations of clarithromycin, erythromycin,
and doxycycline are decreased (thus becoming ineffective) by RIF
because of the effect on the P4503A4 enzyme system. Rifampin is a
CYP3A4 inducer drug.
! Azole antifungals: Rifampin appears to increase the metabolism of
the azole antifungal. Fluconozole, however, can be used with
increased doses.
! Methadone: Methadone levels are also negatively affected by the
anti-TB medications.
SUGGESTED DENTAL GUIDELINES FOR TUBERCULOSIS
The following are dental guidelines for TB:
1. The nonsymptomatic TST/PPD skin test–positive patient does not
transmit the disease. This patient needs preventative anti-TB
treatment to prevent any future reactivation with decreased
immunity or when exposed to a symptomatic coughing patient or
“open” case of tuberculosis. This patient can have routine dental
treatment without any delay because the patient is not infective.
2. The noncoughing symptomatic patient: Within 2–4 weeks of the
initial phase of anti-TB treatment, the bacterial count is negligible in
the sputum in most of the non-coughing symptomatic cases. The
patient can be treated in the dental setting subsequent to this time
period, after obtaining clearance from the patient’s
physician.
3. The symptomatic coughing patient: The symptomatic coughing
patient must complete the first two months of the initial phase
treatment, start the continuation phase treatment, obtain a
clearance from the physician, and then be scheduled
for routine dentistry. Avoid the use of a high-speed hand-piece in
the first month of dentistry in such patients, to avoid aerosolization
of droplets into the environment.
4. Always consult and confirm with the patient’s MD regarding the
type of drug therapy recommended for your patient and the status
of the disease.
5. Evaluate the liver function tests (LFTs), serum creatinine,
complete blood count (CBC) with platelets, and WBC differential
before initiating dental treatment.
6. Always use strict universal precautions when treating all patients
and not just the TB patient.
7. Avoid all drugs metabolized by the liver to minimize added
hepatotoxicity.
8. TB and local anesthetics: Use no more than two carpules of local
anesthetics.
9. TB and analgesics: Avoid aspirin, NSAIDS, extra-strength
acetaminophen (Tylenol), meperidine (Demerol), and propoxyphene
(Darvon). Use regularstrength Tylenol or Tylenol #1–3 or Vicodin
or Percocet for 2–3 days only.
10. TB and antibiotics: Avoid macrolides, ampicillin, tetracycline
HCL, and metronidazole. Use penicillins, cephalosporins, and
clindamycin when needed. Clindamycin can be used without dose
alteration in the presence of a normal liver or hepatitis. Decrease the
total daily dose by 50% in the presence of cirrhosis.
11. Mycobacterium avium intracellulare (MAI) and/or
Mycobacterium kansassi (MK) occurs only in the HIV patient due
to a dramatic reduction in immunity. The T4 cell
count is usually <200 cells/mm3 when MK occurs. MAI is frequently
seen with a T4 count of 50cells/mm3. Anti-TB management protocol
for MAI and MK is the same as with MTB, as previously stated.
12. Aerosols pose a threat because of their ability to remain airborne
and because they are small enough to reach the lower respiratory
tract. Droplet nuclei, however, have been associated with
transmission of Mycobacterium tuberculosis (TB). Patients
who are known to have an active infection should not receive routine
dental care in the dental office, because a higher level of respiratory
protection is required during patient care. In treating the patient
with active TB, among other precautions, the staff must participate
in a respiratory protection program, receive annual training,
and wear fit-tested N95 respirators because standard, surgical face
masks do not protect against TB transmission.