Antimycobacterial Drugs | Katzung & Trevor's Pharmacology: Examination & Board Review, 12e | AccessPharmacy

A 45-year-old homeless man presents to the emergency department with fever, weight loss, and a productive cough. Chest x-ray shows right apical infiltrate and TB is suspected. He is started on empiric INH, rifampin, and pyrazinamide. The primary reason for the use of drug combinations in the treatment of this patient’s TB is:

(A) Delay or prevent the emergence of resistance

(B) Ensure patient compliance with the drug regimen

(C) Increase antibacterial activity synergistically

(D) Provide prophylaxis against other bacterial infections

(E) Reduce the incidence of adverse effects

Although it is sometimes possible to achieve synergistic effects against mycobacteria with drug combinations, the primary reason for their use is to delay the emergence of resistance. The answer is A.

A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister’s preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/µL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acid-fast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture.

At this point, the most appropriate course of action is to

(A) Hospitalize the patient and start treatment with 4 antitubercular drugs

(B) Hospitalize the patient and start treatment with rifampin

(C) Prescribe isoniazid for prophylaxis and send the patient home to await culture results

(D) Provide no drugs and send the patient home to await culture results

(E) Treat the patient with isoniazid plus rifampin

Despite the fact that this patient does not appear to be acutely ill, she would in most cases be treated with 4 drugs that have activity against M tuberculosis. This is because organisms infecting patients from Southeast Asia are commonly INH-resistant, and coverage must be provided with 3 other antituberculosis drugs in addition to isoniazid. This patient should be hospitalized for several reasons, including potential difficulties with compliance regarding the drug regimen and the fact that young children are in the home where she is living. The answer is A.

A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister’s preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/µL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acid-fast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture.

Which drug regimen should be initiated in this patient when treatment is started?

(A) Amikacin, isoniazid, pyrazinamide, streptomycin

(B) Ciprofloxacin, cycloserine, isoniazid, PAS

(C) Ethambutol, isoniazid, pyrazinamide, rifampin

(D) Isoniazid, pyrazinamide, rifampin, streptomycin

(E) PAS, pyrazinamide, rifabutin, streptomycin

Sputum cultures will not be available for several weeks, and no information is available regarding drug susceptibility of the organism at this stage. For optimum coverage, the initial regimen should include INH, rifampin, pyrazinamide, and ethambutol. INH-resistant organisms are usually sensitive to both rifampin and pyrazinamide. Streptomycin is usually reserved for use in severe forms of tuberculosis or for infections known to be resistant to first-line drugs. Likewise, amikacin and ciprofloxacin are possible agents for treatment of multidrug-resistant strains of M tuberculosis. Cycloserine, PAS, and rifabutin are alternative second-line drugs that may be used in cases of failed response to more conventional agents. The answer is C.

A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister’s preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/µL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acid-fast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture.

Which statement concerning the possible use of isoniazid (INH) in this patient is false?

(A) Dyspnea, flushing, palpitations, and sweating may occur after ingestion of tyramine-containing foods

(B) In fast acetylators, lower maintenance doses are necessary

(C) Peripheral neuritis may occur during treatment

(D) The patient should take pyridoxine daily

(E) The risk of the patient developing hepatitis from INH is less than 2%

Fast acetylators may require higher doses of the drug than others. Peripheral neuropathy caused by INH is due to pyridoxine deficiency. It is more common in the diabetic, malnourished, or AIDS patient and can be prevented by a daily dose of 25–50 mg of pyridoxine. INH can inhibit monoamine oxidase type A and has caused tyramine reactions. Hepatotoxicity is age-dependent, with an incidence of 0.3% in patients aged 21–35 years and greater than 2% in patients older than 50 years. The answer is B.

A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister’s preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/µL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acid-fast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture.

On her release from the hospital, the patient is advised not to rely solely on oral contraceptives to prevent pregnancy because they may be less effective while she is being maintained on antimycobacterial drugs. The agent most likely to interfere with the action of oral contraceptives is

(A) Amikacin

(B) Ethambutol

(C) Isoniazid

(D) Pyrazinamide

(E) Rifampin

Rifampin induces the formation of several microsomal drug-metabolizing enzymes, including cytochrome P450 isoforms. This action increases the rate of elimination of a number of drugs, including anticoagulants, ketoconazole, methadone, and steroids that are present in oral contraceptives. The pharmacologic activity of these drugs can be reduced markedly in patients taking rifampin. The answer is E.

A patient with AIDS and a CD4 cell count of 100/µL has persistent fever and weight loss associated with invasive pulmonary disease due to M avium complex (MAC). Optimal management of this patient is to

(A) Choose an antibiotic based on drug susceptibility of the cultured organism

(B) Initiate a two-drug regimen of INH and pyrazinamide

(C) Prescribe rifabutin because it prevents the development of MAC bacteremia

(D) Start treatment with the combination of azithromycin, ethambutol, and rifabutin

(E) Treat with trimethoprim-sulfamethoxazole

Combinations of antibiotics are essential for suppression of disease caused by M avium complex in the AIDS patient, and treatment should be started before culture results are available. Although rifabutin is prophylactic against MAC bacteremia when it is used as sole therapy in active disease, resistant strains of the organism emerge rapidly. MAC is much less susceptible than M tuberculosis to conventional antimycobacterial drugs. Currently, the optimum regimen consists of azithromycin (or clarithromycin) with ethambutol and rifabutin. The answer is D.

A 10-year-old boy has uncomplicated pulmonary tuberculosis. After initial hospitalization, he is now being treated at home with isoniazid, rifampin, and ethambutol. Which statement about this case is accurate?

(A) A baseline test of auditory function test is essential before drug treatment is initiated

(B) His mother, who takes care of him, does not need INH prophylaxis

(C) His 3-year-old sibling should receive INH prophylaxis

(D) Polyarthralgia is a potential adverse effect of the drugs the boy is taking

(E) The potential nephrotoxicity of the prescribed drugs warrants periodic assessment of renal function

A baseline test of ocular (not auditory) function may be useful before starting ethambutol. None of the drugs prescribed is associated with nephrotoxicity. Polyarthralgia is a common adverse effect of pyrazinamide that was not prescribed in this case. Periodic tests of liver function may be advisable in younger patients who are treated with INH plus rifampin, especially if higher doses of these drugs are used. Prophylaxis with INH is advisable for all household members and very close contacts of patients with active tuberculosis, especially young children. The answer is C.

Which statement about antitubercular drugs is accurate?

(A) Antimycobacterial actions of streptomycin involve inhibition of arabinosyltransferases

(B) Cross-resistance of M tuberculosis to isoniazid and pyrazinamide is common

(C) Ocular toxicity of ethambutol is prevented by thiamine

(D) Pyrazinamide treatment should be discontinued immediately if hyperuricemia occurs

(E) Resistance to ethambutol involves mutations in the emb gene

Arabinosyltransferase is inhibited by ethambutol (not streptomycin) and resistance involves alterations in the emb gene. Ocular adverse effects of ethambutol are dose-dependent and usually reversible when the drug is discontinued. Thiamine is not protective. There is minimal cross-resistance between pyrazinamide and other antimycobacterial drugs. Pyrazinamide uniformly causes hyperuricemia, but this is not a reason to halt therapy even though the drug may provoke gouty arthritis in susceptible persons. The answer is E.

Once-weekly administration of which of the following antibiotics has prophylactic activity against bacteremia caused by M avium complex in AIDS patients?

(A) Acedapsone

(B) Azithromycin

(C) Clarithromycin

(D) Kanamycin

(E) Rifabutin

Because of its long elimination half-life (3–4 d), weekly administration of azithromycin has proved to be equivalent to daily administration of clarithromycin when used for prophylaxis against M avium complex in AIDS patients. Acedapsone is a repository form of dapsone used in leprosy. The answer is B.

Risk factors for multidrug-resistant tuberculosis include

(A) A history of treatment of tuberculosis without rifampin

(B) Recent immigration from Asia and living in an area of over 4% isoniazid resistance

(C) Recent immigration from Latin America

(D) Residence in regions where isoniazid resistance is known to exceed 4%

(E) All of the above

Multidrug-resistant tuberculosis (MDR-TB) is defined as resistance to 2 or more drugs. All the risk factors are relevant. In the case of resistance to both INH and rifampin, initial regimens still include both drugs, plus ethambutol, pyrazinamide, streptomycin (or other aminoglycoside), and a fluoroquinolone. Continuation therapy should include at least 3 drugs shown to be active in vitro against the infecting strain. The appropriate duration of therapy has not been established. The answer is E.

Chapter 47: Antimycobacterial Drugs

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Chapter 47: Antimycobacterial Drugs

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