Tuberculosis infection is caused by Mycobacterium tuberculosis.

X-ray

Content 12

 

 

 

Tuberculosis generally affects the lungs but can occur at many locations in the body [Treatment of Tuberculosis Guidelines4th ed.; 2009 (available at WHO/HTM/TB/2009.420)]. 

 

 

 

 


Treatment depends on whether a person has active or latent TB.

Latent

For people with latent TB, a doctor will recommend preventive therapy, which typically involves taking an antibiotic called isoniazid daily for 6–9 months.

Active

Isolation

Identified or suspected patients are isolated and treatment initiated.

Effective isolation is achieved by negative pressure rooms with high-level air exchanges. Isolation is discontinued only after either three negative AFB sputum smears or clinical improvement on multidrug therapy for at least 2 weeks, and in cases of multidrug resistant- (MDR-TB not until culture-negative.

Image result for image of hospital isolation TB

 

People with active TB need to take a combination of antibiotics for 6–12 months. First-line treatment options include isoniazid, rifampin, ethambutol, and pyrazinamide.

 

It is essential to complete the full course of treatment exactly as the doctor directs to keep the disease from recurring and to prevent the bacteria from becoming resistant to the drugs. Drug-resistant TB is much more difficult to treat and can be very dangerous if a person passes it on to other people.

Drug Treatment

Four major drugs are considered the first-line agents for the treatment of TB: 

isoniazid(INH), 

rifampin (RIF), 

pyrazinamide

Ethambutol.

These agents are bactericidal against M. tuberculosis; they rapidly reduce the number of viable organisms and render patients noninfectious. The sterilizing activity of these drugs contributes to their limiting disease relapse, as do their low rates of induction of drug resistance.

Optimum Treatment Regimen

The optimum treatment regimen as supported by the results of randomized clinical trials for virtually all forms of tuberculosis in both children and adults consists of a 2-month initial or bactericidal phase of INH, RIF, pyrazinamide, and ethambutol followed by 4-month continuation or sterilization phase with INH and RIF.

[This regimen can also be administered intermittently by direct observed therapy (DOT) given several times a week, which is the standard of therapy by improving completion rates of treatment and thereby limiting development of resistant strains. ]

 

Initial empiric therapy includes four drugs daily for 2 months:

  • Isoniazid orally (PO), intravenously (IV), or intramuscularly (IM) 5 mg/kg daily (maximum 300 mg/day),
    • 10–15 mg/kg daily in children (max 300); weekly adult dose 15 mg/kg (max 900 mg),
    • twice weekly adult dose 15 mg/kg (max 900), children 20–30 mg/kg (max 900).
  •  Isoniazid (INH) remains central to most antituberculous prophylactic and therapeutic regimens, despite its long-standing recognition as a hepatotoxin.

    In 10% of patients treated with INH, elevated serum aminotransferase levels develop during the first few weeks of therapy; however, these elevations in most cases are self-limited, mild (values for ALT <200 IU/L), and resolve despite continued drug use. This adaptive response allows continuation of the agent if symptoms and progressive enzyme elevations do not follow the initial elevations.

    Acute hepatocellular drug-induced liver injury secondary to INH is evident with a variable latency period up to 6 months and is more frequent in alcoholics and patients taking certain other medications, such as barbiturates, rifampin, and pyrazinamide. If the clinical threshold of encephalopathy is reached, severe hepatic injury is likely to be fatal or to require liver transplantation. Liver biopsy reveals morphologic changes similar to those of viral hepatitis or bridging hepatic necrosis. Substantial liver injury appears to be age-related, increasing substantially after age 35; the highest frequency is in patients over age 50. Even for patients >50 years of age monitored carefully during therapy, hepatotoxicity occurs in only ~2%, well below the risk estimate derived from earlier experiences.

    Many public health programs that require INH prophylaxis for a positive tuberculin skin test or Quantiferon test include monthly monitoring of aminotransferase levels, although this practice has been called into question. Even more effective in limiting serious outcomes may be encouraging patients to be alert for symptoms such as nausea, fatigue, or jaundice, because most fatalities occur in the setting of continued INH use despite clinically apparent illness.

     

  • Rifampin PO or IV, adult 10 mg/kg daily (maximum 600 mg/day, children 10–20 mg/kg per day (max 600).
  • Pyrazinamide orally 25 mg/kg per day (maximum 2 g/day), 15–30 mg/kg daily in children.
  • Ethambutol orally 15 mg/kg per day (maximum 1.6 g/day), 20 mg/kg per day in children.

  • Streptomycin 15 mg/kg per day may be an additional drug or substituted for ethambutol in some patients.

  • Regardless of initial regimen, continuation phase typically is 4 months with isoniazid and rifampin.

  • ++++++++++++++++++++++++++++++++++++++

The CDC-recommended number of doses to complete therapy is defined by completion of the recommended total number of doses, not necessarily the expected duration of therapy. If the specified number of doses cannot be administered in the expected timeframe, the initial phase can be extended to 3 months and doses for an 18-week continuation phase can be extended for 6 months If the longer timeframe is not feasible, consider as interrupted therapy. A 5-day/wk treatment with directly observed therapy (DOT) is considered equivalent to a 7-day/wk.

The WHO recommendations for dosing frequency in treatment of pulmonary TB in adults include DOT as the preferred initial management, and all patients receiving drugs <7 days a week must receive DOT. New patients with pulmonary TB may receive a daily intensive phase followed by 3 times weekly continuation phase if each dose is directly observed. New patients with pulmonary TB may receive 3 times weekly dosing throughout therapy, provided that every dose is directly observed therapy and the patient is not HIV-positive or living in an HIV-prevalent setting.

The standard regimen for new patients with TB is isoniazidrifampinpyrazinamide, and ethambutol orally daily for 2 months, followed by isoniazid and rifampin for 4 months. In countries with high levels of isoniazid resistance, in new patients, and where isoniazid drug susceptibility testing results are unavailable before the continuation phase begins, add ethambutol to 4-month isoniazidrifampin continuation phase (recommendation based on expert opinion not evidence).

The WHO recommendations for treatment of TB in children (note higher dose of pyrazinamide compared to CDC) are as follows:

  • Recommended doses of anti-TB medications:

    • Isoniazid: 10 mg/kg (range 10–15 mg/kg); maximum dose 300 mg/day

    • Rifampicin: 15 mg/kg (range 10–20 mg/kg); maximum dose 600 mg/day

    • Pyrazinamide: 35 mg/kg (30–40 mg/kg)

    • Ethambutol: 20 mg/kg (15–25 mg/kg)

A. Treatment of Active TB in Patients with HIV

Initiation of antiretroviral therapy (ART) during antituberculosis therapy is associated with not only increased survival but also an increase in the risk of immune reconstitution inflammatory syndrome (IRIS). This paradoxical response as the patient is responding to the antiretroviral treatment is attributed to the stronger immune response to TB and includes fever, worsening pulmonary infiltrates, and lymphadenopathy and rarely, death.

The United States Department of Health and Human Services (DHHS) recommendations for timing of ART in patients with HIV and Mycobacterium tuberculosis (TB) coinfection [DHHS Guidelines on Use of Antiretroviral Agents in Adolescents and Adults with HIV-1 Infection (available at AIDSinfo2013Feb12PDF)] are as follows:

  • Start TB treatment immediately in patients with HIV infection and active TB.

  • All patients with HIV infection and active TB should be given ART:

    • For patients with CD4 counts <50 cells/μL, start ART within 2 weeks of starting TB treatment to improve survival.

    • In patients with CD4 counts ≥50 cells/μL and no severe clinical disease, there is less evidence that early ART improves survival with treatment of active TB. ART can be delayed to 8–12 weeks to reduce the risk of IRIS.

    • In pregnant women, start ART as early as possible, for maternal health and prevention of mother-to-child transmission.

    • In patients with documented multidrug-resistant and extensively drug-resistant TB, start ART within 2–4 weeks of confirmation of TB drug resistance and initiation of second-line TB therapy.

Recommended initial treatment is four drugs for 2 months, consisting of INH plus rifampicin (or rifampin) plus pyrazinamide plus ethambutolrifabutin is substituted for rifampin in patients taking protease inhibitors or maraviroc. The preferred continuation therapy is INH plus rifampicin for 4 months, given once daily or 2–3 times weekly (but not twice weekly if CD4 counts <100 cells/μL). Duration of therapy is 6 months, except 9 months for patients with cavitary lung disease, delayed response to therapy, or extrapulmonary TB. Extending treatment from 6 months to 12 months in HIV-positive patients with pulmonary TB may reduce relapse rates. Long-term isoniazid plus sulfadoxine-pyrimethamine may reduce recurrence and sick days after recovery from pulmonary TB in patients with HIV infection.

Trimethoprim-sulfamethoxazole (cotrimoxazole) reduces mortality in HIV-positive patients treated for pulmonary TB. Add corticosteroids when treating central nervous system (CNS) and pericardial disease. Adjunctive prednisolone therapy may reduce mortality in patients with tuberculous pericarditis. Recommended daily doses are dexamethasone 0.3–0.4 mg/kg tapered over 6–8 weeks or prednisone 1 mg/kg for 3 weeks and then tapered for 3–5 weeks.

The World Health Organization (WHO) proposes the following approach that is useful in limited resource environments for the diagnosis and treatment of TB in HIV prevalent settings. For ambulatory patients with cough for 2–3 weeks and no danger signs [ie, respiratory rate >30/minute, fever >39°C (102.2°F), pulse rate > 120/minute, inability to walk unaided], obtain an acid-fast bacilli (AFB) and an HIV test at the first visit. Treat patients who are HIV-positive or whose status remains unknown as follows:

  • If AFB-positive–treat for TB, cotrimoxazole, HIV assessment.

  • If AFB-negative–chest x-ray, sputum AFB and culture, clinical assessment (all at same time wherever possible to decrease visits and time to diagnosis).

    • If TB likely–treat for TB, cotrimoxazole, HIV assessment

    • If TB unlikely–HIV assessment and one of following: (1) treat for bacterial infection plus cotrimoxazole; (2) treat for Pneumocystis carinii pneumonia, especially if hypoxic; (3) if there is a response, advise to return if symptoms recur; (4) if there is no or only partial response, reassess for TB.

The WHO recommendations for dosing regimens in HIV-positive and HIV-negative children are as follows:

  • Four-drug regimen of isoniazidrifampinpyrazinamide, and ethambutol for 4 months followed by isoniazid and rifampin regimen for 4 months should be given in any of following cases:

    • Children with extensive pulmonary disease.

    • Children living in places with high isoniazid resistance or high HIV prevalence (≥ 1% in adult pregnant women or ≥ 5% in patients with TB) who have suspected/confirmed either

      • Pulmonary TB

      • Tuberculous peripheral lymphadenitis

  • Three-drug regimen (isoniazidrifampinpyrazinamide) for 2 months followed by a two-drug regimen of isoniazid and rifampin for 4 months can be given to children without HIV infection living in places with low HIV prevalence and isoniazid who have suspected/confirmed either

    • Pulmonary TB

    • TB peripheral lymphadenitis

  • Avoid intermittent (2 times weekly or 3 times weekly) dosing regimens in children with HIV infection or in any children living in high-HIV-prevalence areas with suspected/confirmed pulmonary TB or tuberculous peripheral lymphadenitis.

  • During continuation phase, consider 3 times weekly regimens for HIV-negative children in settings with well-established DOT.

  • Treat children with suspected or confirmed tuberculous meningitis or osteoarticular TB with standard four-drug regimen of isoniazidrifampinpyrazinamide, and ethambutol for 2 months, followed by standard two-drug regimen of isoniazid and rifampin for 10 months, for a total duration of treatment of 12 months.

The WHO recommendations for dosing frequency in HIV-positive patients are as follows:

  • TB patients with known positive HIV status and all TB patients living in HIV-prevalent settings should receive daily TB treatment at least during the intensive phase.

    • Optimal dosing frequency during continuation phase is also daily for these patients.

    • If a daily continuation phase is not possible for these patients, 3 times weekly dosing during the continuation phase is an acceptable alternative.

B. Treatment of Multidrug-Resistant Tuberculosis (MDR-TB)

1. CDC recommendations

Never add only one new drug to an ineffective regimen. When starting or changing treatment, use at least three previously unused drugs that have demonstrated in vitro susceptibility and include one injectable agent in the regimen (two simultaneous injectable agents not recommended). Use more than three agents if other previously unused drugs likely to be active are available. In patients with multidrug-resistant TB resistant to isoniazidrifampin, and other first-line agent regimens, consider regimens with four to six medications and institute hospital-based or home-based DOT for oral medications; intermittent therapy for injectable agents after 2–4 months of daily therapy is also an option.

Drug resistance patterns are as follows:

  • Rifampin resistance usually associated with cross-resistance to rifabutin and rifapentine; avoid rifabutin unless in vitro susceptibility is demonstrated.

  • No cross-resistance between streptomycin and other injectable agents amikacin, kanamycin, and capreomycin.

  • Cross-resistance between amikacin and kanamycin is universal.

  • If mono-resistance to pyrazinamide is demonstrated without resistance to other first-line drugs, evaluate for infection with Mycobacterium bovis.

For INH-resistant Mtuberculosis, use rifampinpyrazinamide, and ethambutol for 6 months and add a fluoroquinolone as a fourth agent in extensive disease.

For RIF-resistant M. tuberculosis, use isoniazidpyrazinamideethambutol either daily or 3 times weekly for 12 months. If extensive disease, consider adding a fluoroquinolone. If there is extensive disease, or to shorten duration of treatment, consider adding an injectable agent (streptomycin, amikacin, kanamycin, or capreomycin) during initial 2 months of therapy. Isoniazidpyrazinamide, and streptomycin for 9 months has demonstrated efficacy, although an injectable agent for 9 months may not be feasible.

For INH- and RIF-resistant M. tuberculosis, use fluoroquinolone, pyrazinamideethambutol and injectable streptomycin, amikacin, kanamycin, or capreomycin for 18–24 months. If there is extensive disease, consider adding one of following for 18–24 months: ethionamide, cycloserine, p-aminosalicylic acid, clarithromycin, amoxicillin/clavulanate, or linezolid. Resectional surgery may be appropriate.

For INH and RIF plus either ethambutol- or pyrazinamide-resistant M. tuberculosis, use fluoroquinolone (either ethambutol or pyrazinamide if susceptibility demonstrated on testing), and an injectable agent (streptomycin, amikacin, kanamycin, or capreomycin) for 24 months. If there is extensive disease, consider adding two of the following for 24 months: ethionamide, cycloserine, p-aminosalicylic acid, clarithromycin, amoxicillin/clavulanate, or linezolid. Surgery may be appropriate since drug treatment may be very difficult.

2. WHO principles of treatment

WHO (WHO 2007 PDF, National Guideline Clearinghouse 2010 March 1: 13595) recommends using at least four drugs known to be effective. It recommends againsst using drugs that may have cross-resistance or are not safe, and recommends including drugs from groups 1 to 5 in a hierarchical order based on potency:

  • Group 1: first-line oral agents–use any or all of the following drugs if clinical or laboratory suggest susceptibility:

  • Group 2: injectable agents– use one of the following in the drug regimen if laboratory susceptibility is documented or suspected:

  • Group 3: fluoroquinolones–use one of the following if laboratory susceptibility is documented or is deemed efficacious:

  • Group 4: oral bacteriostatic second-line agents–use two or three of the following to obtain a regimen of at least four drugs:

    • p-Aminosalicylic acid

    • Cycloserine

    • Terizidone

    • Ethionamide

    • Protionamide

  • Group 5: agents with unclear role in treatment of drug-resistant TB–use any two of the following in the drug regimen if unable to complete a four-drug regimen from selections in groups 1 to 4:

Children with proven or suspected multidrug-resistant pulmonary TB or tuberculous meningitis can be treated with a fluoroquinolone in the context of a well-functioning multidrug-resistant TB control program and within an appropriate multidrug-resistant TB regimen.

In populations with known or suspected high levels of isoniazid resistance, WHO recommends that new TB patients receive isoniazidrifampin, and ethambutol as therapy in continuation phase as an acceptable alternative to isoniazid and rifampin. Daily dosing during initial intensive phase may also prevent acquired drug resistance in patients with suspected isoniazid resistance.

C. Options for Drug Intolerance

The CDC recommendations for drug intolerance are as follows:

 


Treatment regimens for patients with culture-positive pulmonary tuberculosis caused by drug-susceptible organisms (CDC guidelines).

Initiation Phase Continuation Phase
Agents Dosage and Minimal Duration Agents Dosage and Minimal Duration Length of Therapy (Total Doses) Notes
Isoniazid (INH), rifampin (RIF), pyrazinamide, ethambutol Once daily for 8 weeks (56 doses) or 5 times per week for 8 weeks (40 doses DOT) Isoniazid and rifampin Once daily for 18 weeks (126 doses) or 5 times per week for 18 weeks (90 doses DOT) 26 weeks (130–182)

Preferred regimen.

Directly observed therapy (DOT) required for <7 times a week dosing.

Daily regimen is required if HIV- positive.

When susceptibility testing shows sensitivity to INH and RIF, then ethambutol may be discontinued.

If sputum is smear-positive at 2 months, repeat smear at 3 months.

Isoniazid and rifampin Twice weekly for 18 weeks (36 doses DOT) 26 weeks (76–92) Intermittent dosing not recommended for HIV- positive patients.
Isoniazid and rifampin Once weekly for 18 weeks (18 doses DOT) 26 weeks (58–74) Only for HIV-negative patients with no cavity on CXR and negatove sputum at 2 months.
Isoniazid and rifampin Daily for 31 weeks (217 doses, 155 DOT) 39 weeks (195–273) If cavity on CXR and sputum positive at 2 months, maintain continuation phase for 31 weeks.
Isoniazid and rifampin

Twice weekly for 31 weeks

(62 doses DOT)

39 weeks (102–118)
Isoniazid, rifampin, pyrazinamide, ethambutol Once daily for 2 weeks, then twice weekly for 6 weeks (26 doses DOT) or 5 times per week for 2 weeks, then twice weekly for 6 weeks (22 doses DOT) Isoniazid and rifampin Twice weekly for 18 weeks (36 doses DOT) 26 weeks (58–62) Intermittent dosing not recommended for HIV-positive patients
Isoniazid and rifapentine Once weekly for 18 weeks (18 doses DOT) 26 weeks (40–44) Only for HIV-negative patients with no cavity on CXR and negative sputum at 2 months.
Isoniazid, rifampin, pyrazinamide, ethambutol 3 times per week for 8 weeks (24 doses DOT) Isoniazid and rifampin 3 times per week for 18 weeks (54 doses DOT) 26 weeks (78)
Isoniazid, rifampin, ethambutol Once daily for 8 weeks (56 doses) or 5 times per week for 8 weeks (40 doses DOT) Isoniazid and rifampin Once daily for 31 weeks (217 doses) or 5 times per week for 31 weeks (155 doses DOT) 39 weeks (195–273) May withhold pyrazinamide if pregnant, severe liver disease, or gout with extended continuation phase.
Isoniazid and rifampin Twice weekly for 31 weeks (62 doses DOT) 39 weeks (102–118)

 

 

(3) to prevent acquisition of drug resistance during therapy.

The decision to initiate combination chemotherapy for tuberculosis is based on clinical, radiographic, laboratory, patient, and public health factors (Figure 1).

In addition, clinical judgment and the index of suspicion for tuberculosis are critical in making a decision to initiate treatment. For example, in patients (children and adults) who, based on these considerations, have a high likelihood of having tuberculosis or are seriously ill with a disorder suspicious for tuberculosis, empiric treatment with a 4-drug regimen (Tables 2 and 3) should be initiated promptly even before the results of acid-fast bacilli (AFB) smear microscopy, molecular tests, and mycobacterial culture are known. Sixty-five years of investigation, including many clinical trials, have consistently supported the necessity of treating with multiple drugs to achieve these treatment objectives, minimize drug toxicity, and maximize the likelihood of treatment completion [3, 4]. The success of drug treatment, however, depends upon many factors, and numerous studies have found an increased risk of relapse among patients with signs of more extensive disease (ie, cavitation or more extensive disease on chest radiograph) [5–9], and/or slower response to treatment (ie, delayed culture conversion at 2–3 months) [4, 6, 10, 11].1

 

Treatment of patients with tuberculosis is most successful within a comprehensive framework that addresses both clinical and social issues of relevance to the patient.

After initiation of therapy, the treating clinician must monitor its effects on the patient's presenting symptoms and signs, as well as evaluate for possible adverse specific anti-tubercular drugs effects. In this regard, noteworthy are the hepatotoxicity due to INH and RIF, hepatotoxicity and goutlike symptoms of pyrazinamide, optic neuritis due to ethambutol, and peripheral neuritis secondary to B6 (pyridoxine) deficiency related to INH. For this latter reason all patients receiving INH treatment should also receive 50 mg/d of Vitamin B6.

HIV-infected individuals

In HIV-infected individuals with active TB disease, anti-retroviral therapy may paradoxically worsen symptoms and signs via the immune reconstitution syndrome, in which fever, new pulmonary lesions, pleural effusions, and other manifestations of TB may become manifest. It is important to recognize this phenomenon in individuals who might otherwise be suspected of therapeutic failure of their TB antimicrobial regimen.

Multidrug-resistant tuberculosis is defined as M. tuberculosis resistant to isoniazid and rifampin. Extensively drug-resistant(XDR) tuberculosis is defined [MMWR 2006; 55(43):1176] as M. tuberculosis isolates resistant to isoniazid, rifampin, any fluroquinolone, and at least one of three injectable second-line drugs (amikacin, kanamycin, or capreomycin). Latent tuberculosis is exposure to M. tuberculosis without active disease. Primary tuberculosis infection is active disease due to M. tuberculosis. Secondary tuberculosis infection in patients previously sensitized to M. tuberculosis usually occurs as reactivation TB, but may occur with reinfection with a new strain of M. tuberculosis. Extrapulmonary tuberculosis refers to localized infection at a site other than the lungs, such as lymph nodes, pleura, kidney, genitalia, bones or joints, heart, nervous system (particularly meninges), any intraabdominal organ (particularly at terminal ileum and cecum), peritoneum, and pericardium.

 

 

 

World Wide

Nearly one-third of the world's population is infected with Tuberculosis (TB), nearly 9 million develop the disease, and it kills almost 2 million people per year.

According to the Centers for Disease Control and Prevention (CDC) in 2008, nearly one-third of the world's population is infected with Tuberculosis (TB), which kills almost 1.6 million people per year. TB is now the second most common cause of death from infectious disease in the world after human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). In the mid-1980s, a resurgence of outbreaks in the United States brought renewed attention to TB. An increase in high risk, immuno-suppressed individuals, particularly those infected with HIV, lead to an increase in TB cases. Drug-resistant strains of this deadly disease also contributed to the problem. However, through a broad range of Federal and community initiatives, TB rates have declined steadily. For 2010, a total of 11,182 tuberculosis (TB) cases were reported in the United States. The TB rate was 3.6 cases per 100,000 population, a decrease of 3.8% from the rate reported for 2009

United States

In the United States, approximately 13,000 new cases of TB are reported annually, and 650 persons die from TB each year.

 

TB in HIV Pa

TB is the leading cause of mortality among persons infected with HIV. [More...] Respiratory protection from tuberculosis is now covered under OSHA's Respiratory Standard 29 CFR 1910.134.

 

 

Content 4

Content 3

Content 11

 

All of the following statements regarding antituberculosis therapeutic agents are true EXCEPT:

Complete Quiz and View Results
You will be able to view all answers at the end of your quiz.

The correct answer is C. You answered C.

The answer is C.  Pyrazinamide (PZA) is first-line treatment for M tuberculosis. Addition of PZA for 2 months to isoniazid and rifampin allows the total duration of treatment to be shortened from 9 months to 6 months. PZA has no utility in the treatment of nontuberculous mycobacteria. Ethambutol has no serious drug interactions, but patients must be closely monitored for optic neuritis, which may manifest with decreased visual acuity, central scotoma, or difficulty seeing green (or red). All patients initiating therapy with ethambutol should have a visual and ophthalmologic examination at baseline. In the United States overall, isoniazid resistance remains uncommon. Primary isoniazid resistance is more common in patients with tuberculosis born outside the United States. Rifampin is a potent inducer of the cytochrome P450 system and has numerous drug interactions. The CDC has guidelines for managing antituberculosis drug interactions including rifampin (www.cdc.gov/tb/). Rifabutin is a less potent inducer of hepatic cytochromes. Rifabutin is recommended for HIV-infected patients who are on antiretroviral therapy with protease inhibitors or nonnucleoside reverse transcriptase inhibitors (particularly nevirapine) in place of rifampin.

 

A 31-year-old healthcare worker is found to have a newly positive tuberculin skin test 6 weeks after an exposure to a patient with active pulmonary tuberculosis. He is asymptomatic and has a normal chest radiograph. Which of the following statements regarding initiation of isoniazid (INH) prophylactic therapy is true?

Next Question
You will be able to view all answers at the end of your quiz.

The correct answer is E. You answered C.

The answer is E.  Isoniazid (INH) remains central to most antituberculous prophylactic and therapeutic regimens, despite its long-standing recognition as a hepatotoxin.

In 10% of patients treated with INH, elevated serum aminotransferase levels develop during the first few weeks of therapy; however, these elevations in most cases are self-limited, mild (values for ALT <200 IU/L), and resolve despite continued drug use. This adaptive response allows continuation of the agent if symptoms and progressive enzyme elevations do not follow the initial elevations. Acute hepatocellular drug-induced liver injury secondary to INH is evident with a variable latency period up to 6 months and is more frequent in alcoholics and patients taking certain other medications, such as barbiturates, rifampin, and pyrazinamide. If the clinical threshold of encephalopathy is reached, severe hepatic injury is likely to be fatal or to require liver transplantation. Liver biopsy reveals morphologic changes similar to those of viral hepatitis or bridging hepatic necrosis. Substantial liver injury appears to be age-related, increasing substantially after age 35; the highest frequency is in patients over age 50. Even for patients >50 years of age monitored carefully during therapy, hepatotoxicity occurs in only ~2%, well below the risk estimate derived from earlier experiences. Many public health programs that require INH prophylaxis for a positive tuberculin skin test or Quantiferon test include monthly monitoring of aminotransferase levels, although this practice has been called into question. Even more effective in limiting serious outcomes may be encouraging patients to be alert for symptoms such as nausea, fatigue, or jaundice, because most fatalities occur in the setting of continued INH use despite clinically apparent illness.

 

A 23-year-old man who takes anti-mycobacterial therapy for pulmonary tuberculosis presents to the clinic because of recent visual disturbance and pain with movement of his left eye. On examination, there is tenderness to the pressure of the left eye and a blind spot at the center of vision. Fundus examination reveals pale optic disc.

What is the most likely etiology of this patient’s visual symptoms?

A-As a complication of tuberculosis

B-A side effect of isoniazid

C-A side effect of rifampin

D-A side effect of ethambutol

E-A side effect of pyrazinamide

Answer



 

 

 

USMLE Reviewer (By Subscription)