49

CHAPTER
Tuberculosis

• Tuberculosis (TB) is a communicable infectious disease caused by Mycobacterium

tuberculosis. It can produce silent, latent infection, as well as progressive, active
dis- ease. Globally, 2 billion people are infected and roughly 2 million people die
from TB each year.
• M. tuberculosis is transmitted from person to person by coughing or sneezing.
Close contacts of TB patients are most likely to become infected.
• Human immunodeficiency virus (HIV) is the most important risk factor for active
TB, especially among people 25 to 44 years of age. An HIV-infected individual
with TB infection is over 100-fold more likely to develop active disease than an
HIV- seronegative patient.
• Approximately 90% of patients who experience primary disease have no further
clini- cal manifestations other than a positive skin test either alone or in
combination with radiographic evidence of stable granulomas. Tissue necrosis and
calcification of the originally infected site and regional lymph nodes may occur,
resulting in the forma- tion of a radiodense area referred to as a Ghon complex.
• Approximately 5% of patients (usually children, the elderly, or the immunocompro-
mised) experience progressive primary disease at the site of the primary infection
(usually the lower lobes) and frequently by dissemination, leading to meningitis and
often to involvement of the upper lobes of the lung as well.
• Approximately 10% of patients develop reactivation disease, which arises
subsequent to the hematogenous spread of the organism. In the United States, most
cases of TB are believed to result from reactivation.
• Occasionally, a massive inoculum of organisms may be introduced into the blood-
stream, causing widely disseminated disease and granuloma formation known as
miliary TB.

CLINICAL PRESENTATION AND DIAGNOSIS

• The classic presentation of pulmonary TB is nonspecific, indicative only of a slowly
evolving infectious process (Table 49–1). The onset of TB may be gradual.
Physical examination is nonspecific but suggestive of progressive pulmonary
• disease. Clinical features associated with extrapulmonary TB vary depending on the
organ system(s) involved but typically consist of slowly progressive decline of
organ func- tion with low-grade fever and other constitutional symptoms.
• Patients with HIV may have atypical presentation. HIV-positive patients are less
likely to have positive skin tests, cavitary lesions, or fever. They have a higher inci-
dence of extrapulmonary TB and are more likely to present with progressive
primary disease.
• TB in the elderly is easily confused with other respiratory diseases. It is far less
likely to present with positive skin tests, fevers, night sweats, sputum production, or
hemoptysis. TB in children may present as typical bacterial pneumonia and is called
progressive primary TB.
• The most widely used screening method for tuberculous infection is the tuberculin
skin test, which uses purified protein derivative (PPD). Populations most likely to
benefit from skin testing are listed in Table 49–2.
• The Mantoux method of PPD administration consists of the intracutaneous injection
of PPD containing five tuberculin units. The test is read 48 to 72 hours after
injection by measuring the diameter of the zone of induration.
• Some patients may exhibit a positive test 1 week after an initial negative test; this is
referred to as a booster effect.
• Confirmatory diagnosis of a clinical suspicion of TB must be made via chest radio-
graph and microbiologic examination of sputum or other infected material to rule
out active disease.

1
 Tuberculosis | CHAPTER 49

TABLE 49–1 Clinical Presentation of Tuberculosis

Signs and symptoms
Patients typically present with weight loss, fatigue, a productive cough, fever, and night
sweats
Frank hemoptysis
Physical examination
Dullness to chest percussion, rales, and increased vocal fremitus are observed frequently
on auscultation
Laboratory tests
Moderate elevations in the white blood cell count with a lymphocyte predominance
Diagnostic Considerations
Positive sputum smear
Fiber-optic bronchoscopy (if sputum tests are inconclusive and suspicion is high)
Chest radiograph
Patchy or nodular infiltrates in the apical area of the upper lobes or the superior
segment of the lower lobes
Cavitation that may show air–fluid levels as the infection progresses

TABLE 49–2 Criteria for Tuberculin Skin Test Positivity, by Risk Group
Reaction ≥5 mm of Reaction ≥15 mm
Induration Reaction ≥10 mm of Induration of Induration
HIV-positive persons Recent immigrants (ie, within the last Persons with no risk
Recent contacts of TB 5 years) from high-prevalence factors for TB
case patients countries Injection drug users
Fibrotic changes on chest Residents and employeesa of the
following radiograph consistent high-risk congregate settings:
prisons with prior TB and jails, nursing homes and other
long-term care facilities for the elderly,
hospitals and other healthcare facilities,
residential facilities for patients with
AIDS, and homeless shelters
Patients with organ Mycobacteriology laboratory personnel
transplants and other Persons with the following clinical
immunosuppressed conditions that place them at high
risk: patients (receiving silicosis, diabetes mellitus,
chronic renal the equivalent of failure, some
hematologic disorders prednisone for ≥1 (eg,
leukemias and lymphomas), other month)b
specific malignancies (eg, carcinoma of
the head or neck and lung), weight loss
≥10% of ideal body weight, gastrec-
tomy, and jejunoileal bypass
Children younger than 4 years or infants,
children, and adolescents exposed to
adults at high risk
AIDS, acquired immunodeficiency syndrome; HIV, human immunodeficiency virus; TB,
tuberculosis.
a
For persons who are otherwise at low risk and are tested at the start of employment, a
reaction ≥15 mm induration is considered positive.
b
Risk of TB in patients treated with corticosteroids increases with higher dose and longer duration.
Adapted from Centers for Disease Control and Prevention. Screening for tuberculosis and
tuberculosis infection in high-risk populations: Recommendations of the Advisory Council for
the Elimination of Tuberculosis. MMWR 1995;44(No. RR-11):19–34.
SECTION 8 | Infectious Diseases

• When active TB is suspected, attempts should be made to isolate M. tuberculo-

sis from the infected site. Daily sputum collection over three consecutive days is
recommended.
• Tests to measure release of interferon-γ in the patient’s blood in response to TB anti-
gens may provide quick and specific results for identifying M. tuberculosis.

TREATMENT
• Goals of Treatment: The goals are prompt resolution of signs and symptoms of
disease, achievement of a noninfectious state, thus ending isolation, adherence to
the treatment regimen by the patient, and cure as quickly as possible (generally with
at least 6 months of treatment)
• Drug treatment is the cornerstone of TB management. A minimum of two drugs,
and generally three or four drugs, must be used simultaneously. Directly observed
therapy (DOT) by a healthcare worker is a cost effective way to ensure completion
of treatment and is considered the standard of care.
• Drug treatment is continued for at least 6 months and up to 2 to 3 years for some
cases of multidrug-resistant TB (MDR-TB).
• Patients with active disease should be isolated to prevent spread of the disease.
• Public health departments are responsible for preventing the spread of TB, finding
where TB has already spread using contact investigation.
• Debilitated patients may require therapy for other medical conditions, including sub-
stance abuse and HIV infection, and some may need nutritional support.
• Surgery may be needed to remove destroyed lung tissue, space-occupying lesions,
and some extrapulmonary lesions.
PHARMACOLOGIC TREATMENT
Latent Infection
• As described in Table 49–3, chemoprophylaxis should be initiated in patients to
reduce the risk of progression to active disease.
• Isoniazid, 300 mg daily in adults, is the preferred treatment for latent TB in the
United States, generally given for 9 months.
• Rifampin, 600 mg daily for 4 months, can be used when isoniazid resistance is
sus- pected or when the patient cannot tolerate isoniazid. Rifabutin, 300 mg daily,
may be substituted for rifampin for patients at high risk of drug interactions.
• The CDC recommends the 12-week isoniazid/rifapentine regimen as an equal
alter- native to 9 months of daily isoniazid for treating latent tuberculosis infection
(LTBI) in otherwise healthy patients aged 12 years or older who have a predictive
factor for greater likelihood of TB developing, which included recent exposure to
conta- gious TB, conversion from negative to positive on an indirect test for
infection (ie, interferon-gamma release assays [IGRA] or tuberculin skin test), and
radiographic findings of healed pulmonary TB.
• Pregnant women, alcoholics, and patients with poor diets who are treated with iso -
niazid should receive pyridoxine, 10 to 50 mg daily, to reduce the incidence of
central nervous system (CNS) effects or peripheral neuropathies.
Treating Active Disease
• Table 49–4 lists options for treatment of culture-positive pulmonary TB caused
by drug-susceptible organisms. Doses of antituberculosis drugs are given in Table
49–5. Other sources should be consulted for treatment recommendations when TB
is concurrent with HIV infection. The standard TB treatment regimen is isoniazid,
rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and
rifampin for 4 months. Ethambutol can be stopped if susceptibility to isoniazid,
rifampin, and pyrazinamide is shown.
• Appropriate samples should be sent for culture and susceptibility testing prior to
initiating therapy for all patients with active TB. The data should guide the initial
drug selection for the new patient. If susceptibility data are not available, the drug
resistance pattern in the area where the patient likely acquired TB should be used.
 Tuberculosis | CHAPTER 49

TABLE 49–3 Recommended Drug Regimens for Treatment of Latent Tuberculosis

(TB) Infection in Adults
Interval and Ratinga (Evidence)b
Drug Duration Comments HIV− HIV+
Isoniazid Daily for 9 monthsc,d In HIV-infected patients, A (II) A (II)
isoniazid may be administered
concurrently with nucleoside
reverse transcriptase inhibitors,
protease inhibitors, or
nonnucleoside reverse
transcriptase inhibitors
Twice weekly for 9 Directly observed therapy must B (II) B
(II) monthsc,d be used with twice-weekly
dosing
Isoniazid Daily for 6 monthsd Not indicated for HIV-infected B (I) C (I)
persons, those with fibrotic
lesions on chest radiographs,
or children

Twice weekly for 6 Directly observed therapy must B (II) B

(III) monthsd be used with twice-weekly
dosing
Rifampin Daily for 4 months For persons who are contacts B (II) C (I)
of patients with isoniazid-
resistant, rifampin-susceptible
TB who cannot tolerate
pyrazinamide

HIV, human immunodeficiency virus; −, negative; +, positive.

a
Strength of recommendation: A, preferred; B, acceptable alternative; C, offer when A and B cannot
be given.
b
Quality of evidence: I, randomized clinical trial data; II, data from clinical trials that are not
randomized or were conducted in other populations; III, expert opinion.
c
Recommended regimen for children younger than 18 years.
d
Recommended regimens for pregnant women. Some experts would use rifampin and
pyrazinamide for 2 months as an alternative regimen in HIV-infected pregnant women, although
pyrazinamide should be avoided during the first trimester.
Adapted from Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment
of latent tuberculosis infection. MMWR 2000;49(RR-6):31.

• If the patient is being evaluated for the retreatment of TB, it is imperative to know
what drugs were used previously and for how long.
• Patients must complete 6 months or more of treatment. HIV-positive patients should
be treated for an additional 3 months and at least 6 months from the time that they
convert to smear and culture negativity. When isoniazid and rifampin cannot be
used, treatment duration becomes 2 years or more, regardless of immune status.
• Patients who are slow to respond, those who remain culture positive at 2 months of
treatment, those with cavitary lesions on chest radiograph, and HIV-positive
patients should be treated for 9 months and for at least 6 months from the time they
convert to smear and culture negativity.
DRUG RESISTANCE
• If the organism is drug resistant, the aim is to introduce two or more active agents
that the patient has not received previously. With MDR-TB, no standard regimen

479
 SE
CT
TABLE 49–4 Drug Regimens for Culture-Positive Pulmonary Tuberculosis Caused by Drug-Susceptible IO
48 Organisms Ratinga (Evidence)b N8
0
Initial Phase Continuation Phase |
Inf
HIV− HIV+ ect
Interval and Dosesc Interval and Dosesc,d Range of Total Doses
Regimen Drugs (Minimal Duration) (Minimal Duration) iou
(Minimal Duration) Regimen Drugs
s
Dis
1 Isoniazid, rifampin, Seven days per week 1a Isoniazid/rifampin Seven days per week for 182–130 (26 weeks) A (I) A (II) ea
pyrazinamide, for 56 doses (8 126 doses (18 weeks) se
ethambutol weeks) or or 5 days/week for 90
5 days/week for 40 doses (18 weeks)c
doses (8 weeks)c 1b Isoniazid/rifampin Twice weekly for 36 doses 92–76 (26 weeks) A (I) A (II)f
(18 weeks)
1cg Isoniazid/rifapentine Once weekly for 18 doses 74–58 (26 weeks) B (I) E (I)
(18 weeks)
2 Isoniazid, rifampin, 2a Isoniazid/rifampin Twice weekly for 36 doses 62–58 (26 weeks) A (II) B (II)f
pyrazinamide, Seven days per week (18 weeks)
ethambutol for 14 doses (2 2bg Isoniazid/rifapentine Once weekly for 18 doses 44–40 (26 weeks) B (I) E (I)
weeks), then twice (18 weeks)
weekly for 12 doses
(6 weeks) or
5 days/week for 10
doses (2 weeks)e
then twice weekly
for 12 doses (6
weeks)
 3 Isoniazid, rifampin, Three times weekly for 3a Isoniazid/rifampin Three times weekly for 54 78 (26 weeks) B (I) B (II)
pyrazinamide, 24 doses (8 weeks) doses (18 weeks)
ethambutol
4 Isoniazid, rifampin, Seven days per week for 4a Isoniazid/rifampin Seven days per week for 273–195 (39 weeks) C (I) C (II)
ethambutol 56 doses (8 weeks) or 217 doses (31 weeks)
5 days/week for 40 or 5 days/week for 155
doses (8 weeks)c doses (31 weeks)e
4b Isoniazid/rifampin Twice weekly for 62 doses 118–102 (39 C (I) C (II)
weeks)
(31 weeks)

HIV, human immunodeficiency virus.

a
Ratings: A, preferred; B, acceptable alternative; C, offer when A and B cannot be given; E, should never be given.
b
Evidence ratings: I, randomized clinical trial; II, data from clinical trials that were not randomized or were conducted in other populations; III, expert opinion.
c
When directly observed therapy is used, drugs may be given 5 days per week and the necessary number of doses adjusted accordingly. Although there are no studies that
compare five with seven daily doses, extensive experience indicates this would be an effective practice.
d
Patients with cavitation on initial chest radiograph and positive cultures at completion of 2 months of therapy should receive a 7-month (31-weeks; either 217 doses [daily] or 62 doses
[twice weekly]) continuation phase.
e
Five-day-a-week administration is always given by directly observed therapy. Rating for 5-day-per-week regimens is A (III). Tu
f
Not recommended for HIV-infected patients with CD4+ cell counts less than 100 cells/μL [<100 × 106/L].
g
Options 1c and 2b should be used only in HIV-negative patients who have negative sputum smears at the time of completion of 2 months of therapy and who do not have ber
cavitation on initial chest radiograph. For patients started on this regimen and found to have a positive culture from the 2-month specimen, treatment should be extended an cul
extra 3 months. osi
From Centers for Disease Control and Prevention. Treatment of tuberculosis. MMWR 2003;52(RR-11). s
|
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TE
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1 49
48 TABLE 49–5 Dosesa of Antituberculosis Drugs for Adults and Childrenb SE
2 Doses CT
IO
Drug Preparation Adults/Children Daily 1 × per week 2 × per week 3 × per week N8
First-line drugs
|
Isoniazid Tablets (50 mg, 100 mg, 300 Adults (max) 5 mg/kg (300 mg) 15 mg/kg (900 mg) 15 mg/kg (900 mg) 15 mg/kg (900 Inf
mg) mg); elixir (50 mg/5 mL); Children (max) 10–15 mg/kg (300 mg) – 20–30
ect
mg/kg (300 mg) –
iou
aqueous solution (100 mg/
mL) for intravenous or s
intramuscular injection Dis
ea
Rifampin Capsule (150 mg, 300 mg); Adultsc (max) 10 mg/kg (600 mg) – 10 mg/kg (600 mg) 10 mg/kg (600 se
mg) powder may be suspended Children (max) 10–20 mg/kg (600 mg) – 10–20
mg/kg (600 mg) –
for oral administration;
aqueous solution for
intravenous injection
Rifabutin Capsule (150 mg) Adultsc (max) 5 mg/kg (300 mg) – 5 mg/kg (300 mg) 5 mg/kg (300 mg)
Children Appropriate dosing for Appropriate dosing for Appropriate dosing for Appropriate dosing for
children is unknown children is unknown children is unknown children is
unknown
Rifapentine Tablet (150 mg, film coated) Adults – 10 mg/kg (continua- – –
tion phase) (600 mg
usual adult dose)
Children The drug is not approved The drug is not The drug is not approved The drug is not
for use in children approved for use for use in children approved for use
in children in children
 Pyrazinamide Tablet (500 mg, scored) Adults 1000 mg (40–55 kg) – 2000 mg (40–55 kg) 1500 mg (40–55 kg)
1500 mg (56–75 kg) – 3000 mg (56–75 kg) 2500 mg (56–75 kg)
2000 mg (76–90 kg)j – 4000 mg (76–90 kg)j 3000 mg (76–90 kg)j
Children (max) 15–30 mg/kg (2 g) – 50 mg/kg (2 g) –
Ethambutol Tablet (100 mg, 400 mg) Adults 800 mg (40–55 kg) – 2000 mg (40–55 kg) 1200 mg (40–55 kg)
1200 mg (56–75 kg) – 2800 mg (56–75 kg) 2000 mg (56–75 kg)
1600 mg (76–90 kg)j – 4000 mg (76–90 kg)j 2400 mg (76–90 kg)j
Childrend (max) 15–20 mg/kg daily (1 – 50 mg/kg (2.5 g) –
g)
Second-line drugs
Cycloserine Capsule (250 mg) Adults (max) 10–15 mg/kg/day (1 g There are no data to There are no data to There are no data to
in 2 doses), usually support intermittent support intermittent support intermittent
500–750 mg/day in administration administration administration
2 doses – – –
Children (max) 10–15 mg/kg/day
(1 g/day)
Ethionamide Tablet (250 mg) Adultsf (max) 15–20 mg/kg/day There are no data to There are no data to There are no data to
(1 g/day), usually support intermittent support intermittent support intermittent Tu
500–750 mg/day in administration administration administration ber
a single daily dose or cul
two divided dosesf osi
Children (max) 15–20 mg/kg/day There are no data to There are no data to There are no data to s
(1 g/day) support intermittent support intermittent support intermittent
|
administration administration administration
CH
(continued) AP
TE
48 R
3 49
48 TABLE 49–5 Dosesa of Antituberculosis Drugs for Adults and Childrenb SE
4 Doses CT
IO
Drug Preparation Adults/Children Daily 1 × per week 2 × per week 3 × per week N8
Second-line drugs
|
Streptomycin Aqueous solution (1-g vials) Adults (max) g g g g
Inf
for intravenous or intra- Children (max) 20–40 mg/kg/day (1 g) – 20 –
ect
mg/kg muscular administration
iou
Amikacin/ Aqueous solution (500 mg Adults (max) g g g g s
kanamycin and 1 g vials) for Children (max) 15–30 mg/kg/day (1 g) – 15–30 – Dis
mg/kg intravenous or intramuscu- intravenous or ea
lar administration intramuscular as a se
single daily dose
Capreomycin Aqueous solution (1 g vials) Adults (max) g g 15–30 g
mg/kg for intravenous or intra- Children (max) 15–30 mg/kg/day (1 g) as – –
muscular administration a single daily dose
p-Amino-salicylic Granules (4 g packets) can be Adults 8–12 g/day in 2 or 3 There are no data to There are no data to There are no data to
acid (PAS) mixed with food; tablets doses support intermittent support intermittent support intermittent
(500 mg) are still available administration administration administration
in some countries, but
not in the United States;
a solution for intravenous
administration is available
in Europe
 Children (max) 200–300 mg/kg/day in There are no data to There are no data to There are no data to
2–4 divided doses support intermittent support intermittent support intermittent
(10 g) administration administration administration
Moxifloxacinh Tablets (400 mg); aqueous Adults 400 mg daily There are no data to There are no data to There are no data to
solution (400 mg/250 mL) support intermittent support intermittent support intermittent
for intravenous injection administration administration administration

a
Dose per weight is based on ideal body weight. Children weighing more than 40 kg should be dosed as adults.
b
For purposes of this document, adult dosing begins at age 15 years.
c
Dose may need to be adjusted when there is concomitant use of protease inhibitors or nonnucleoside reverse transcriptase inhibitors.
d
The drug can likely be used safely in older children but should be used with caution in children less than 5 years of age, in whom visual acuity cannot be monitored. In younger
children, ethambutol at the dose of 15 mg/kg per day can be used if there is suspected or proven resistance to isoniazid or rifampin.
e
It should be noted that although this is the dose recommended generally, most clinicians with experience using cycloserine indicate that it is unusual for patients to be able to
tolerate this amount. Serum concentration measurements are often useful in determining the optimal dose for a given patient.
f
The single daily dose can be given at bedtime or with the main meal.
g
Dose: 15 mg/kg per day (1 g) but 10 mg/kg in persons older than 59 years of age (750 mg). Usual dose: 750–1000 mg administered intramuscularly or intravenously, given as
a single dose 5–7 days/week and reduced to two or three times per week after the first 2–4 months or after culture conversion, depending on the efficacy of the other
drugs in the regimen.
h
The long-term (more than several weeks) use of moxifloxacin in children and adolescents has not been approved because of concerns about effects on bone and cartilage
growth. The optimal dose is not known. Tu
ber
Data from American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm
Rep 2003;52(RR-11):1–77. cul
osi
s
|
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TE
48 R
5 49
SECTION 8 | Infectious Diseases

can be proposed. It is critical to avoid monotherapy or adding only a single drug to

a failing regimen.
• Drug resistance should be suspected in the following situations:
✓Patients who have received prior therapy for TB
✓Patients from geographic areas with a high prevalence of resistance (South
Africa, Mexico, Southeast Asia, the Baltic countries, and the former Soviet
states)
✓Patients who are homeless, institutionalized, IV drug abusers, and/or infected
with HIV
✓Patients who still have acid-fast bacilli–positive sputum smears after 2 months of
therapy
✓Patients who still have positive cultures after 2 to 4 months of therapy
✓Patients who fail therapy or relapse after retreatment
✓Patients known to be exposed to MDR-TB cases
SPECIAL POPULATIONS
Tuberculous Meningitis and Extrapulmonary Disease
• In general, isoniazid, pyrazinamide, ethionamide, and cycloserine penetrate
the
cerebrospinal fluid readily. Patients with CNS TB are often treated for longer
periods (9–12 months). Extrapulmonary TB of the soft tissues can be treated with
conven- tional regimens. TB of the bone is typically treated for 9 months,
occasionally with surgical debridement.
Children
• TB in children may be treated with regimens similar to those used in adults, although
some physicians still prefer to extend treatment to 9 months. Pediatric doses of
drugs should be used.
Pregnant Women
• The usual treatment of pregnant women is isoniazid, rifampin, and ethambutol for
9 months.
• Women with TB should be cautioned against becoming pregnant, as the disease
poses a risk to the fetus as well as to the mother. Isoniazid or ethambutol is
relatively safe when used during pregnancy. Supplementation with B vitamins is
particularly important during pregnancy. Rifampin has been rarely associated with
birth defects, but those seen are occasionally severe, including limb reduction and
CNS lesions. Pyrazinamide has not been studied in a large number of pregnant
women, but anec- dotal information suggests that it may be safe. Ethionamide
may be associated with premature delivery, congenital deformities, and Down
syndrome when used during pregnancy, so it cannot be recommended in pregnancy.
Streptomycin has been asso- ciated with hearing impairment in the newborn,
including complete deafness and must be reserved for critical situations where
alternatives do not exist. Cycloserine is not recommended during pregnancy.
Fluoroquinolones should be avoided in preg- nancy and during nursing.
Renal Failure
• In nearly all patients, isoniazid and rifampin do not require dose modifications in
renal failure. Pyrazinamide and ethambutol typically require a reduction in dosing
frequency from daily to three times weekly (Table 49–6).

EVALUATION OF THERAPEUTIC OUTCOMES AND PATIENT MONITORIG

• The most serious problem with TB therapy is nonadherence to the prescribed regi-
men. The most effective way to ensure adherence is with directly observed therapy.
• Patients who are who are AFB smear positive should have sputum samples sent for
acid-fast bacilli stains every 1 to 2 weeks until two consecutive smears are negative.
Once on maintenance therapy, patients should have sputum cultures performed
monthly until negative, which generally occurs over 2 to 3 months. If sputum

486
 Tuberculosis | CHAPTER 49

cultures continue to be positive after 2 months, drug susceptibility testing should be

repeated, and serum drug concentrations should be checked.

487
 TABLE 49–6 Dosing Recommendations for Adult Patients with Reduced Renal
Function and for Adult Patients Receiving Hemodialysis
Recommended Dose and Frequency
for Patients with Creatinine Clearance
Change in <30 mL/min or for Patients Receiving
Drug Frequency? Hemodialysis
Isoniazid No change 300 mg once daily, or 900 mg 3 times
weekly
Rifampin No change 600 mg once daily, or 600 mg 3 times
weekly
Pyrazinamide Yes 25–35 mg/kg per dose 3 times weekly
(not daily)
Ethambutol Yes 15–25 mg/kg per dose 3 times weekly
(not daily)
Levofloxacin Yes 750–1000 mg per dose 3 times
weekly (not daily)
Cycloserine Yes 250 mg once daily, or 500 mg/dose 3
times weeklya
Ethionamide No change 250–500 mg per dose daily
p-Aminosalicylic acid No change 4 g per dose twice daily
Streptomycin Yes 12–15 mg/kg per dose 2 or 3 times
weekly (not daily)
Capreomycin Yes 12–15 mg/kg per dose 2 or 3 times
weekly (not daily)
Kanamycin Yes 12–15 mg/kg per dose 2 or 3 times
weekly (not daily)
Amikacin Yes 12–15 mg/kg per dose 2 or 3 times
weekly (not daily)

Note: Standard doses are given unless there is intolerance.

The medications should be given after hemodialysis on the day of hemodialysis.
Monitoring of serum drug concentrations should be considered to ensure adequate drug
absorption,
without excessive accumulation, and to assist in avoiding toxicity. Data currently are not avail-
able for patients receiving peritoneal dialysis. Until data become available, begin with doses
recommended for patients receiving hemodialysis and verify adequacy of dosing using serum
concentration monitoring.
a
The appropriateness of 250 mg daily doses has not been established. There should be
careful monitoring for evidence of neurotoxicity.
Adapted from American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases
Society of America. Treatment of tuberculosis. MMWR Recomm Rep 2003;52(RR-11):1–77.

• Patients should have blood urea nitrogen, serum creatinine, aspartate transaminase
or alanine transaminase, and a complete blood count determined at baseline and
peri- odically, depending on the presence of other factors that may increase the
likelihood of toxicity (advanced age, alcohol abuse, and possibly pregnancy).
Hepatotoxicity should be suspected in patients whose transaminases exceed five
times the upper limit of normal or whose total bilirubin exceeds 3 mg/dL (51.3
 µmol/L). At this point, the offending agent(s) should be discontinued and
alternatives selected.
See Table 49–7 for drug monitoring recommendations.
 TABLE 49–7 Antituberculosis Drug Monitoring Table
Drug Adverse Effects Monitoring
Isoniazid Asymptomatic elevation of amino- LFT monthly in patients who
transferases, clinical hepatitis, fatal have preexisting liver disease
hepatitis, peripheral neurotoxicity, or who develop abnormal liver
CNS effects, lupus-like syndrome, function that does not require
hypersensitivity, monoamine discontinuation of drug; dosage
poisoning, diarrhea adjustments may be necessary
in patients receiving anticonvul-
sants or warfarin
Rifampin Cutaneous reactions, GI reactions Liver enzymes and interacting
(nausea, anorexia, abdominal pain), drugs as needed (e.g., warfarin)
flu-like syndrome, hepatotoxicity,
severe immunologic reactions,
orange discoloration of bodily fluids
(sputum, urine, sweat, tears), drug
interactions due to induction of
hepatic microsomal enzymes
Rifabutin Hematologic toxicity, uveitis, GI symp- Drug interactions are less
toms, polyarthralgias, hepatotoxicity, problematic than rifampin
pseudojaundice (skin discoloration
with normal bilirubin), rash, flu-like
syndrome, orange discoloration of
bodily fluids (sputum, urine,
sweat,
tears)
Rifapentine Similar to those associated with Drug interactions are being
rifampin investigated and are likely
similar to rifampin
Pyrazinamide Hepatotoxicity, GI symptoms (nausea, Serum uric acid can serve as
a vomiting), nongouty polyarthralgia, surrogate marker for
adherence; asymptomatic hyperuricemia, acute LFTs in patients
with underlying gouty arthritis, transient liver disease
morbilliform rash, dermatitis
Ethambutol Retrobulbar neuritis, peripheral Baseline visual acuity testing and
neuritis, cutaneous reactions testing of color discrimination;
monthly testing of visual
acuity and color discrimination
in patients taking >15–20
mg/ kg, having renal
insufficiency, or receiving the
drug for >2 months
Streptomycin Ototoxicity, neurotoxicity, Baseline audiogram, vestibular
nephrotoxicity testing, Romberg’s testing, and SCr
Monthly assessments of renal
function and auditory or
vestibular symptoms
Amikacin/ Ototoxicity, nephrotoxicity Baseline audiogram, vestibular
kanamycin testing, Romberg’s testing, and
SCr; monthly assessments of
renal function and auditory or
vestibular symptoms
 TABLE 49–7 Antituberculosis Drug Monitoring Table (Continued)
Drug Adverse Effects Monitoring
Capreomycin Nephrotoxicity, ototoxicity Baseline audiogram, vestibular
testing, Romberg’s testing, and
SCr
Monthly assessments of renal
function and auditory or
vestibular symptoms
Baseline and monthly serum
K+ and Mg2+
p-Aminosalicylic Hepatotoxicity, GI distress, Baseline LFTs and TSH
acid malabsorption syndrome, TSH every 3 months
hypothyroidism, coagulopathy
Moxifloxacin GI disturbance, neurologic effects, No specific monitoring
cutaneous reactions recommended

LFT, liver function test; TSH, thyroid-stimulating hormone.

Adapted from American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases
Society of America. Treatment of tuberculosis. MMWR Recomm Rep 2003;52(RR-11):1–77.

See Chapter 90, Tuberculosis, authored by Rocsanna Namdar, Michael Lauzardo, and
Charles A. Peloquin, for a more detailed discussion of this topic.