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awaiting culture results. Because the sensitivity of culture is 90%, negative
cultures do not guarantee the absence of TB.
D. Rapid detection methods, the Amplicor PCR and Amplified
Mycobacterium Tuberculosis Direct Test ([AMTD], Gen-Probe), can be
used in identification of M. tuberculosis in smear-positive sputum
specimens. These methods are more sensitive than acid-fast staining, but
are slightly less sensitive than culture, which remains the gold standard.
Rapid tests should not be used to confirm or exclude the diagnosis of TB
except in cases in which smears reveal acid-fast bacteria.
E. Diagnosis or treatment of TB can be accomplished in the outpatient
setting. Once a diagnosis of TB is made or appears likely, contact
investigation should be initiated (for confirmed cases) and exposure of
additional persons should be prevented.
Drug
First line drugs
Isoniazid
Rifampin
Ethambutol
Pyrazinamide
Second line drugs
Streptomycin
Ofloxacin
Ciprofloxacin
Amikacin
Capreomycin
Kanamycin
Ethionamide
Cycloserine
Clofazimine
Rifabutin
Para-aminosal
icylic acid (PAS)
Daily Dose
Route
300 mg
po or im
70 Mycobacterium Tuberculosis Infection
III. Treatment
A. Patients with HIV disease who have positive findings on AFB smears of
sputum or biopsy specimens, or whose cultures yield an acid-fast
organism, should be treated for M. tuberculosis pending final culture
results. If sputum smears do not reveal AFB, but active TB is suspected
in an HIV-infected patient, empiric therapy should be initiated pending
culture results. In some cases, Mycobacterium avium complex (MAC)
infection will be the final diagnosis.
Antituberculous Agents, Ranked in Order of Preference, Usual Daily
Dose, and Principle Toxicities
Toxicities
Hepatitis, neuritis
Hepatitis, drug interactions
Optic neuritis (at higher doses)
600 mg
15-25 mg/kg
25 mg/kg
15 mg/kg
400 mg bid
750 mg bid
15 mg/kg
15 mg/kg
po or iv
po
po
Hyperuricemia, hepatitis
im
Ototoxicity and vestibulotoxicity
with renal insufficiency
po
Gastrointestinal
po
Gastrointestinal
im
Same as streptomycin
im
Same as streptomycin
15 mg/kg
im
Same as streptomycin, but more
toxic
0.5 - 1.0 g
po
Gastrointestinal, hepatitis
0.5 - 1.0 g
po
Neuropsychiatric
200-300 mg
po
Dark skin
300 mg
po
Drug interactions, uveitis, rash
8-12 g
po
Gastrointestinal, rash
B. The recommended initial treatment regimen for patients with HIV infection
and TB consists of 2 months of daily isoniazid (INH), rifampin,
pyrazinamide, and ethambutol, followed by 4 to 7 months of daily or twice
weekly INH and rifampin.
Mycobacterium tuberculosis Infection 71
C. Interactions between rifamycins and protease Inhibitors.
1. Rifamycins (rifampin) are inducers of cytochrome P450 enzymes.
Because protease inhibitors are metabolized by this enzyme system,
the concentration of protease inhibitor is likely to be subtherapeutic
with concomitant administration of a rifamycin. Ritonavir and indinavir
also inhibit cytochrome P450 enzymes and decrease metabolism of
the rifamycins, which may accumulate to toxic levels.
2. The antiretroviral regimen should include indinavir (800 mg every 8
hours) as the protease inhibitor, and rifabutin (Mycobutin) (150 mg per
day) should be substituted for rifampin in a
9-month treatment
regimen.
IV.
Monitoring therapy
A. Response of pulmonary TB to therapy is monitored by following sputum
smear and culture results monthly until they become negative. Sputum
smears typically become negative after the first month. Cultures should
be negative after 2 to 3 months. Positive cultures persisting beyond the
third month suggest the possibility of noncompliance with medications,
drug resistance, or both. Sputum should also be cultured at 3, 6, and 12
months after therapy is completed to monitor for relapse.
B. Criteria for discontinuing isolation. Once effective chemotherapy has
been administered for at least 2 weeks, patients can resume work and
social contacts provided that three sputum smears are negative for AFB.
V. Screening and prevention
A. Tuberculin skin testing. All HIV-infected persons should be screened for
TB by tuberculin skin testing. When a reaction is $5 mm in a person who
does not have active TB, prophylaxis should be initiated with INH (300 mg
per day for 12 months).
B. Treatment of contacts
1. Patients with HIV disease and TB who have positive findings in sputum
or bronchoscopy specimens are infectious and their contacts should
be screened for TB and given prophylaxis when indicated. HIV-positive
contacts to individuals with active TB should receive INH, even if the
contact's PPD skin response is less than 5 mm because the contact
may be anergic. Active TB should be excluded before initiating
prophylaxis.
2. HIV-positive contacts to patients with multi-drug resistant TB should
receive prophylaxis with two drugs to which the organism from the
index patient is susceptible. A 12-month regimen of pyrazinamide 25
mg/kg plus ofloxacin 600 mg once daily is usually effective.
References: See page 94.
72 Cytomegalovirus Retinitis
Cytomegalovirus Retinitis
Cytomegalovirus (CMV) is a common opportunistic pathogen in individuals
infected with HIV, causing retinitis, colitis, and encephalitis. Cytomegalovirus
disease occurs in 20-40% of patients with AIDS. HIV-infected persons withCD4+
cell counts below 50/µL are at highest risk for CMV disease. Retinitis usually
begins unilaterally, but, untreated, progression to bilateral involvement is
common.
I. Clinical evaluation
A. Retinitis is the most common manifestation of CMV infection, accounting
for 75% to 85% of CMV disease. Typically, the disease appears as a
yellow to white area of retinal necrosis and edema, which follows a
vascular distribution and is sometimes hemorrhagic. An ophthalmologist
can establish the diagnosis with a dilated retinal examination.
B. Symptoms of CMV retinitis may include light flashes, floaters, loss of
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