Antituberculars, Antifungals, and Antivirals

This chapter covers antituberculars, antifungals, and antivirals. Although these drug categories differ from one another, they each contain drugs that inhibit or kill organisms that cause disease.


Tuberculosis (TB) is caused by the acid-fast bacillus Mycobacterium tuberculosis. The number of TB cases had declined until the mid-1980s, when the number of cases started to increase. The increase in cases of TB was attributed to multiple factors, such as human immunodeficiency virus (HIV), increased immigration, and the spread of multidrug-resistant TB (MDR TB). According to the U.S. Department of Health and Human Services (DHHS), tuberculosis is one of the world’s leading causes of death due to infectious diseases in persons older than 5 years of age. Each year, about 9 million people develop TB, and 2 million die because of it. With increased funding, prompt identification of persons with TB, appropriate initial treatment, and completion of treatments, the number of TB cases started declining again in the mid-1990s. However, MDR TB continues to be a serious health concern. Patients started on therapy for TB who do not finish the prescribed therapy can develop and spread resistant strains of M. tuberculosis.


TB is transmitted from one person to another by droplets dispersed in the air through coughing, sneezing, and speaking. TB microorganisms can be inhaled into the lungs, therefore persons in close contact with the infected patient are at highest risk of becoming infected. Others at high risk for contracting the disease include the immunocompromised (e.g., patients with HIV, diabetes, and renal failure and those taking certain medications, such as cortisol), people living or working in high-risk residential settings (e.g., nursing homes, shelters, correctional facilities), those who inject illegal drugs, and health care workers who serve high-risk patients.

Not everyone infected with TB will develop clinical manifestations, rather some will harbor the microorganisms and will have what is called latent tuberculosis infection; these persons are at risk of developing TB disease later, and only those with TB disease can infect others. Symptoms of TB disease include anorexia, cough with sputum production or blood, chest pain, fever, night sweats, weight loss, and positive acid-fast bacilli in the sputum. Isolating infectious persons and initiating treatment for TB disease as soon as possible is the best way to decrease transmission.

Nurses should be aware that persons coming to the United States from high-risk countries where TB disease is common may have been vaccinated with bacille Calmette-Guérin (BCG) as a child. This vaccine is seldom used in the United States. Previous vaccination with BCG may cause a positive reaction to skin testing; however, it does not affect interferon-gamma release assay (IGRA) blood testing.

Antitubercular Drugs

Antitubercular drugs (Table 27.1), which include antimycobacterials, treat persons with TB disease and those exposed to TB disease. Streptomycin was the first drug used in the treatment of TB disease in 1943. However, it was noted that patients began to deteriorate after 3 months of therapy due to drug resistance. In 1952, isoniazid (INH) began to see widespread use in the treatment of TB disease and was felt to be a “wonder drug.” To this day, INH remains the first-line treatment for TB disease. INH is a bactericidal drug that inhibits tubercle cell-wall synthesis and blocks pyridoxine (vitamin B6), which is used for intracellular enzyme production. When INH is prescribed, pyridoxine may also be prescribed to avoid vitamin B deficiency and to minimize peripheral neuropathy. INH is administered orally. Prototype Drug Chart 27.1 lists the data for INH.

TABLE 27.1

Antitubercular Drugs




A, Adult; C, child; d, day; ETOH, ethanol (alcohol); GI, gastrointestinal; h, hour; HIV, human immunodeficiency virus; IM, intramuscular; IV, intravenous; LFT, liver function test; max, maximum; min, minutes; PB, protein binding; PO, by mouth; t½, half-life; TB, tuberculosis; UK, unknown; wk, week; y, year; >, greater than; ≥, greater than or equal to; ≤, less than or equal to.

 Pregnancy categories have been revised. See for more information.

 Rifampin is the preferred agent from the class of rifamycins (rifabutin, rifampin, and rifapentine).


icon PROTOTYPE DRUG CHART 27.1Isoniazid


A, adult; Adol, adolescent; ALT, alanine aminotransferase; AST, aspartate aminotransferase; C, child; CDC, Centers for Disease Control and Prevention; CYP450, cytochrome P450; d, day; GI, gastrointestinal; h, hour; IM, intramuscular; INH, isoniazid; MAO, monoamine oxidase; MAOI, monoamine oxidase inhibitor; max, maximum; PB, protein binding; PO, by mouth; SNRI, serotonin norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; t½, half-life; TB, tuberculosis; UK, unknown; wk, week; y, year.

 Pregnancy categories have been revised. See for more information.


BOX 27.1Determining When to Treat Latent Tuberculosis Infection

People with a positive tuberculin skin test (TST) reaction of ≥5 mm if they are:

• HIV positive

• Recent contacts of someone with active tuberculosis (TB disease)

• Persons with fibrotic changes on chest radiography consistent with old TB

• Organ transplant recipients

• Persons who are immunosuppressed for other reasons (e.g., those taking the equivalent of >15 mg/day of prednisone for 1 month or longer, those taking tumor necrosis factor alpha [TNF-α] antagonists)

People with a positive TST reaction of ≥10 mm if they are:

• Recent immigrants (<5 years) from high-prevalence countries

• Injection drug users

• Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities)

• Mycobacteriology laboratory personnel

• Children under 4 years of age or children or adolescents exposed to adults in high-risk categories

Prophylactic antituberculars are drugs to prevent TB disease in individuals with latent TB infection. Prophylaxis is recommended for those who have a clinically significant result on tuberculin skin testing (≥5 mm for immunocompromised individuals or ≥10 mm for high-risk groups; Box 27.1) or a positive IGRA result. Patients who have converted from a negative to a positive TB skin test (TST) or from a negative to positive IGRA should be considered candidates for prophylactic therapy as well. Prototype Drug Chart 27.1 shows guidelines for latent TB infection treatment with INH.

Prophylactic therapy is contraindicated for persons with liver disease because INH is the primary antitubercular drug used, and it may cause INH-induced liver damage. Other antitubercular drugs may also cause liver damage if given in high doses over an extended period.

Single-drug therapy is ineffective in the treatment of TB disease due to drug resistance. Using a combination of antitubercular drugs has been shown to decrease bacterial resistance. Additionally, using combination therapy has decreased the duration of treatment from 2 years to 6 to 9 months. Different combinations of drugs can be used with INH, rifampin, ethambutol, and pyrazinamide.

Antitubercular drugs are divided into two categories: first-line drugs that form the core of treatment regimens and drugs used in the treatment of drug-resistant TB. First-line drugs—those drugs chosen first, such as INH, rifampin, pyrazinamide, and ethambutol—are considered more effective and less toxic than drugs used in the treatment of drug-resistant TB. Drugs used in the treatment of drug-resistant TB, in which M. tuberculosis is resistant to at least one first-line drug, or MDR TB, in which M. tuberculosis is resistant to INH and rifampin plus one other first-line drug, are used in combination with first-line drugs to treat drug-resistant M. tuberculosis. See Table 27.1 for drugs used in the treatment of drug-resistant TB.

Combination therapy against TB disease is more effective in eradicating infection than any single drug. The treatment regimen is divided into two phases: the initial phase lasts 2 months, and the continuation phase consists of the next 4 or 7 months. The total treatment plan can be up to 9 months or longer, depending on response to drug therapy. If drug resistance develops, other antibacterial drugs such as aminoglycosides (streptomycin, kanamycin, amikacin) or fluoroquinolones (levofloxacin, ciprofloxacin, or ofloxacin) may be given as part of combination therapy. Combination therapy for drug-resistant TB disease consists of a minimum of three drugs, but preferably four to five drugs, administered as part of directly observed therapy to ensure adherence. Drug therapy should be managed by an expert in the disease, and susceptibility testing to determine drug resistance should be performed before drug therapy; however, treatment with first-line therapy should not be delayed if TB disease is suspected. Aminoglycoside antibiotics should not be taken if kidney dysfunction is present. When antibacterial agents are used continuously or at high doses, serum drug levels should be closely monitored to avoid drug toxicity.

Many drug-drug interactions and side effects occur with antituberculars. To increase adherence to drug therapy, direct observation therapy (DOT) is recommended.

Side Effects and Adverse Reactions

Side effects and adverse reactions to antituberculars differ according to the drug prescribed. For INH, peripheral neuropathy can be a problem, especially for those who are malnourished, have diabetes mellitus, or are alcoholics. This condition can be prevented if pyridoxine (vitamin B6) is administered. Hepatotoxicity (liver toxicity) is an adverse reaction to many antituberculars. Patients with moderate to severe liver dysfunction should not take these drugs. Patients with liver disease should have hepatic transaminases monitored closely. Patients may also develop headaches, blood dyscrasias, paresthesias, gastrointestinal (GI) distress (e.g., nausea, vomiting, diarrhea, dyspepsia), and ocular toxicity. An ophthalmic exam before and during treatment is warranted. INH may cause hyperglycemia, hyperkalemia, hypophosphatemia, and hypocalcemia. Rifampin turns body fluids orange, and soft contact lenses may be permanently discolored. It may also cause thrombocytopenia and GI intolerance. The patient taking ethambutol may develop dizziness, confusion, hallucinations, and joint pain. Streptomycin may lead to many adverse effects such as ototoxicity, optic nerve toxicity, encephalopathy, angioedema, central nervous system (CNS) and respiratory depression, nephrotoxicity, and hepatotoxicity.


icon Patient Safety

Do not confuse…

Rifampin with other antituberculars such as rifabutin and rifapentine.

Special Populations

Pregnancy and Tuberculosis

The benefits of treating a pregnant woman with TB disease outweigh the risks of treatment. Women with untreated TB disease are at risk for passing the disease to their fetus and delivering an infant with low birthweight. The drugs used in initial treatment of TB disease do cross the placenta but do not appear to harm the fetus.

Treatment of latent TB infection in the pregnant woman includes INH daily or twice weekly for 9 months with pyridoxine supplementation. Three-month combination therapy of INH with rifapentinem, referred to as 3HP, is not recommended for pregnant women or those planning to become pregnant within 3 months.

The pregnant woman with TB disease should be treated with INH, rifampin, and ethambutol daily for 2 months followed by INH and rifampin daily or twice weekly for 7 months for a total of 9 months. Streptomycin should not be used due to potential harmful effects on the fetus. Pyrazinamide is also not recommended due to unknown effects on the fetus.

Tuberculosis and HIV Coinfection

HIV is a risk factor for the development of TB, and TB disease is one of the leading causes of death for people living with HIV. Left untreated, latent TB infection can quickly develop into TB disease. The recommended treatment for an adult with latent TB infection and HIV is INH daily for 9 months.

Adults with HIV and TB disease should be treated for 6 months with INH, rifabutin, pyrazinamide, and ethambutol during the initial phase. The 4-month continuation phase should consist of INH and rifabutin.

A pregnant woman with HIV and TB disease should be treated the same as a nonpregnant woman but with concern for the fetus when choosing drug therapy.

Pediatric Tuberculosis

Children are more likely than adults to be sickened more quickly by TB. Because of this, children with latent TB infection should be treated to prevent development of TB disease. The recommended treatment is INH for 9 months. Treatment of TB disease should be managed by a pediatric TB expert in conjunction with drug susceptibility studies. It is very important for the nurse to make sure parents understand that if a child stops taking the drugs before therapy is finished, the child can become sick again. Additionally, nurses should stress to parents that if drugs are not taken correctly, the bacteria may become drug resistant. Drug-resistant TB is harder and more expensive to treat.


icon Nursing Process: Patient-Centered Collaborative Care

Antitubercular Drugs


• Determine any past instances of TB in the patient’s health history—including the last purified protein derivative (PPD) tuberculin test and the reaction or the serum IGRA result, the last chest radiograph and result, and the last ophthalmic exam—along with any allergies.

• Obtain a general medical history from the patient. Most antitubercular drugs are contraindicated if the patient has severe hepatic disease.

• Check laboratory results for liver function studies, bilirubin, blood urea nitrogen (BUN), and serum creatinine. These baseline values can be compared with future laboratory test results.

• Evaluate the patient for signs and symptoms of paresthesia (tingling, numbness, or burning).

• Assess for hearing changes if the antitubercular drug regimen includes streptomycin. Drug-induced ototoxicity is the major irreversible toxicity of aminoglycosides.

Nursing Diagnoses

• Nonadherence, Risk for

• Infection, Risk for

• Knowledge, Deficient related to unfamiliarity with medications


• The patient’s sputum test for acid-fast bacilli will be negative 2 to 3 months after the prescribed antitubercular therapy.

Nursing Interventions

• If INH is ordered, administer the drug 1 hour before or 2 hours after meals because food decreases the absorption rate. Other antitubercular drugs are given without regard to meals.

• Give pyridoxine (vitamin B6) as prescribed with INH to prevent peripheral neuropathy.

• Monitor serum liver enzyme levels. Elevated levels may indicate liver toxicity.

• Collect sputum specimens for acid-fast bacilli early in the morning. Usually three consecutive morning sputum specimens are sent to the laboratory.

• Encourage eye examinations for patients taking INH and ethambutol because these antitubercular drugs may cause visual disturbances.

• Emphasize the importance of complying with the drug regimen.

Patient Teaching

• Tell patients who take INH to take the drug 1 hour before meals or 2 hours after meals for better absorption.

icon Direct patients to take antitubercular drugs as prescribed. Ineffective treatment and development of drug resistance might occur if drugs are taken intermittently or discontinued when symptoms are decreased or when the patient is feeling better. Adherence to the drug regimen is essential to prevent the spread of drug-resistant M. tuberculosis.

• Instruct patients not to take antacids while taking antitubercular drugs because they decrease drug absorption. Patients should also avoid alcohol because it increases the risk of hepatotoxicity.

• Advise patients to keep medical appointments and to participate in sputum testing, which is important in evaluating the effectiveness of drug regimens.

• Warn patients contemplating pregnancy to first check with their health care provider about taking the antitubercular drugs ethambutol and rifampin.

• Guide patients to report any numbness, tingling, or burning of hands and feet. Peripheral neuropathy is a common side effect of INH. Vitamin B6 prevents peripheral neuropathy.

• Encourage patients to avoid direct sunlight to decrease the risk of photosensitivity. Patients should use a sunscreen with a minimum sun protection factor (SPF) of 30 and ultraviolet A and B (UVA/UVB) protection while in the sun.

• Inform patients taking rifampin that urine, feces, saliva, sputum, sweat, and tears may turn a harmless red-orange color. Soft contact lenses may be permanently stained.

• Alert patients receiving ethambutol to take daily single doses to avoid visual problems. Divided doses of ethambutol may cause visual disturbances.

• Increase access to health care. Community involvement and culturally sensitive patient education are important. Explain to patients who have active TB that family members should get a TB skin test and may receive a prophylactic drug for 6 months to 1 year. Emphasize the importance of family members seeking medical care.

• Provide a written sheet for drug and treatment regimens in the language the patient speaks or reads most easily. Explain the importance of good hygiene (e.g., discarding tissues that contain sputum, separating dishes, using a dishwasher to clean dishes if possible).

• Understand the significance of community if multiple individuals in the same community are treated for latent TB infection. Make all attempts to place community members on a treatment plan to increase compliance through social support.

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Apr 8, 2017 | Posted by in PHARMACY | Comments Off on Antituberculars, Antifungals, and Antivirals

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