PEDIATRIC TUBERCULOSIS : TREATMENT AND MANAGEMENT

Treatment of Latent Tuberculosis Infection (TLTBI) is medication that is given to people who have latent TB infection to prevent them from developing TB disease. High-risk people should be evaluated for TLTBI if they have a positive skin test reaction, regardless of their age. Sometimes TLTBI is given to people who have a negative skin test result, such as high-risk contacts and children younger than 6 months old who have been exposed to active TB.

All patients being considered for TLTBI should receive a medical evaluation to:

  • Exclude the possibility of TB disease
  • Determine whether they have ever been treated for TB infection or disease
  • Identify any medical problems that may complicate therapy or require more careful monitoring

People who are suspected of having TB disease or who have been documented as adequately treated for latent TB infection or disease should not be given TLTBI.

The usual regimen for TLTBI is isoniazid given daily for 9 months for all patients. Patients should be clinically evaluated every month for signs of hepatitis and other adverse reactions to isoniazid. They should also be educated about the symptoms caused by adverse reactions to isoniazid and instructed to seek medical attention immediately if these symptoms occur. In addition, people at greatest risk for hepatitis should have liver function tests before starting isoniazid. Four months of rifampin is an acceptable alternative regimen for TLTBI.

TB disease must be treated for at least 6 months; in some cases, treatment lasts even longer. The initial regimen for treating TB disease should include four drugs: isoniazid, rifampin, pyrazinamide, and ethambutol. When the drug susceptibility results are available, clinicians may change the regimen accordingly. TB disease must be treated with at least two drugs to which the bacilli are susceptible. Using only one drug to treat TB disease can create a population of tubercle bacilli that is resistant to that drug. Drug resistance can also develop when patients do not take treatment as prescribed. Thus, to prevent relapse and drug resistance, clinicians must prescribe an adequate regimen and make sure that patients adhere to treatment. The best way to ensure that patients adhere to treatment is to use directly observed therapy (DOT).

There are several options for daily and intermittent treatment. For children with certain types of extrapulmonary TB, pregnant women, and people with drug-resistant TB, treatment may last longer or involve different regimens. Treatment of drug-resistant TB should always be done daily and under the supervision of a medical expert who is familiar with the treatment of drug-resistant TB.

All patients being treated for TB disease should be educated about the symptoms caused by adverse reactions to the drugs they are taking and instructed to seek medical attention immediately if they have symptoms of a serious side effect. Patients should be seen by a clinician at least monthly during treatment and evaluated for possible adverse reactions. In addition, before starting treatment, patients may have baseline tests to help clinicians detect any abnormalities that may complicate treatment.

Patients who are not receiving directly observed therapy should be carefully monitored for adherence to treatment. However, the only way to ensure adherence to treatment is to always directly observe therapy.

To determine whether a patient is responding to treatment, clinicians should do clinical evaluations and bacteriologic evaluations during treatment. Patients should be carefully reevaluated if their:

  • Symptoms do not improve during the first 2 months of treatment
  • Symptoms worsen after improving initially
  • Culture results have not become negative after 2 months of treatment
  • Culture results become positive after being negative

In some situations, clinicians may also use X-rays to monitor a patient’s response to treatment for pulmonary TB.

The treatment of TB can be complicated, especially in patients who fail to respond to treatment, who relapse, or who have drug-resistant TB or adverse reactions to medications. Clinicians who do not have experience with these situations should consult an expert. The New Jersey Medical School Global Tuberculosis Institute is qualified to assist clinicians in consultation to treat their difficult TB patients.

 

Medical Care

The ATS and CDC have provided standard guidelines for the treatment of tuberculosis. The ultimate goal of treatment is to achieve sterilization of the tuberculosis lesion in the shortest possible time. The general rule is strict adherence to tuberculosis treatment regimens for a sufficient period of time. To prevent the emergence of resistance, the regimens for the treatment of tuberculosis always should consist of multiple drugs.

Pulmonary tuberculosis

Current recommendations for the treatment of pulmonary tuberculosis include a 6-month course of isoniazid (INH) and rifampin, supplemented during the first 2 months with pyrazinamide. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) may need to be included in the initial regimen until the results of drug susceptibility studies are available. Drug susceptibility studies may not be required if the risk of drug resistance is not significant. Significant risk factors include residence in a community with greater than 4% primary resistance to INH, history of previous treatment with antituberculosis drugs, history of exposure to a drug-resistant case, and origin in a country with a high prevalence of drug resistance. The purpose of this recommendation is to decrease the development of multidrug-resistant (MDR) tuberculosis in areas in which primary INH resistance is increased.

Another treatment option is a 2-month regimen of INH, rifampin, and pyrazinamide daily, followed by 4 months of INH and rifampin twice a week. Effective treatment of hilar adenopathy when the organisms are fully susceptible is a 9-month regimen of INH and rifampin daily or a 1-month regimen of INH and rifampin once a day followed by 8 months of INH and rifampin twice a week.

Because poor adherence to these regimens is a common cause of treatment failure, directly observed therapy (DOT) is recommended for treatment of tuberculosis. DOT means a health care provider or other responsible person must watch the patient ingest the medications. Intermittent regimens should be monitored by DOT for the duration of therapy because poor compliance may result in inadequate drug delivery.

Another initiative recently launched by the WHO is the DOTS-plus strategy, which is based on finding appropriate treatment strategies for MDR tuberculosis and drug susceptibility testing, as well as judicious usage of second-line drugs.11,12  It also focuses on community involvement and a good recording and reporting system.

Extrapulmonary tuberculosis

Most cases of extrapulmonary tuberculosis, including cervical lymphadenopathy, can be treated with the same regimens used to treat pulmonary tuberculosis. Exceptions include bone and joint disease, miliary disease, and meningitis. For these severe forms of drug-susceptible disease, the recommendation is a regimen of 2 months of INH, rifampin, pyrazinamide, and streptomycin once a day, followed by 7-10 months of INH and rifampin once a day. The other recommended regimen is 2 months of INH, rifampin, pyrazinamide, and streptomycin, followed by 7-10 months of INH and rifampin twice a week. Streptomycin may be administered with initial therapy until drug susceptibility is known. Consider administering capreomycin or kanamycin instead of streptomycin in patients who may have acquired tuberculosis in areas in which resistance to streptomycin is common.

Tuberculosis in patients with HIV

Optimal therapy for tuberculosis in children with HIV infection has not been established. According to the current guidelines provided by the CDC, effective treatment of tuberculosis for patients infected with HIV should include DOT and consultation with a specialist. 

A regimen that uses rifabutin instead of rifampin has been advised when simultaneously treating HIV disease and tuberculosis. This situation may occur (1) when antiretroviral treatment is recommended for a newly diagnosed HIV infection in a patient with active tuberculosis or (2) when a patient with active tuberculosis has established HIV infection and continuation of antiretroviral therapy is recommended. This recommendation is based on the fact that the use of rifampin with protease inhibitors or nonnucleoside reverse transcriptase inhibitors is contraindicated.

The treatment regimen for tuberculosis should initially include at least 3 drugs and should be continued for at least 9 months. INH, rifampin, and pyrazinamide with or without ethambutol or streptomycin should be administered for the first 2 months. Treatment of disseminated disease or drug-resistant tuberculosis may require the addition of a fourth drug.

Multidrug resistant tuberculosisInfection caused by MDR organisms, defined as organisms resistant to at least INH and rifampin, has reached critical levels worldwide. The median prevalence of resistance to any of the 4 antituberculosis drugs in a recent update by the WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) has been shown to be 10.2% (range 0-57.1%).13,12

 

Two categories of drug resistance are recognized: primary and secondary. Primary resistance is defined as the occurrence of resistance to antituberculosis treatment in an individual who has no history of prior treatment. Secondary resistance involves the emergence of resistance during the course of ineffectual antituberculosis therapy.

In 2006, the WHO Global Task Force defined another category of MDR tuberculosis termed extensively drug-resistant (XDR) tuberculosis.3 This is defined as resistance to first-line drugs, including resistance to at least rifampicin and INH, in addition to resistance to any fluoroquinolone and at least one of following second-line antituberculosis drugs: capreomycin, kanamicin, and amikacin. This usually occurs as a result of mismanagement of MDR tuberculosis.

Risk factors for the development of primary drug resistance include patient contact with drug-resistant contagious tuberculosis, residence in areas with a high prevalence of drug-resistant M tuberculosis, birth outside the United States, ethnicity other than non-Hispanic white, young age, HIV infection, and the use of intravenous drugs. Secondary drug resistance reflects patient nonadherence to the regimen, inappropriate drug regimens, and/or interference with absorption of the drug.

The current guidelines endorsed by the CDC state that if a child is at risk of or has disease resistant to INH, at least 2 drugs to which the isolate is susceptible should be administered. Another important management principle is to never add a single drug to an already failing regimen. The resistance pattern, toxicities of the drugs, and patients’ responses to treatment determine duration and the regimen selected. The initial treatment regimen for patients with MDR tuberculosis should include 4 drugs. At least 2 bactericidal drugs (eg, INH, rifampin), pyrazinamide, and either streptomycin or another aminoglycoside (also bactericidal) or high-dose ethambutol (25 mg/kg/d) should also be incorporated into the regimen.

Six-month treatment regimens are not advocated for patients with strains resistant to INH or rifampin. Intermittent therapy with twice-a-week regimens is also not recommended. In isolated INH resistance, the 4-drug, 6-month regimen should be initially started for the treatment of pulmonary tuberculosis. INH should be discontinued when resistance is documented. Continue pyrazinamide for the entire 6-month course of treatment. In the 9-month regimen, INH should be discontinued upon the documentation of isolated INH resistance. If ethambutol was included in the initial regimen, continue treatment with rifampin and ethambutol for a minimum of 12 months. If ethambutol was not included, then repeating susceptibility tests is advocated, as are discontinuation of INH and the addition of 2 new drugs (eg, ethambutol and pyrazinamide).

Resistance to both INH and rifampin presents a complex problem that often necessitates consultation with a specialist. Continuing the initial drug regimen (with 2 drugs to which the organism is susceptible) until bacteriologic sputum conversion is documented is preferable; then administer at least 12 months of 2-drug therapy. The role of new agents such as quinolone derivatives and amikacin in MDR cases remains unclear.

Management of a neonate whose mother or other household contact has tuberculosis The AAP and CDC guidelines advocate avoidance of separation of the mother and infant if possible. Authorities have endorsed the following recommendations:

 

  • The mother has a positive TST result and no evidence of current disease: Because the positive TST result may be evidence of an unrecognized case of contagious tuberculosis within the household, careful screening and evaluation of the other members of the household should be performed. Perform a Mantoux test when the infant is aged 4-6 weeks and 3-4 months. Consider administration of INH (10 mg/kg/d) to the infant if the family cannot be promptly tested.
  • The mother is having current disease but is noncontagious at delivery: In this situation, separation of the mother and infant is not necessary, and the mother can breastfeed the infant. Evaluation of the infant includes chest radiography and Mantoux test at age 4-6 weeks; if negative, a repeat test is warranted at age 3-4 months and at age 6 months. INH should be administered even if the TST result and chest radiography do not suggest tuberculosis because sufficient cell-mediated immunity (CMI) to prevent progressive disease may not develop until age 6 months.
  • The mother has current disease and is contagious at delivery: In this situation, separation of the mother and infant is recommended until the mother is noncontagious. The rest of the management is the same as for category 2.
  • The mother has hematogenous spread: Congenital tuberculosis is possible in this scenario. Promptly perform a Mantoux test and chest radiography and immediately begin treatment for the infant. INH should be administered until the infant is aged 6 months, at which time evaluation of the infant with a TST should be repeated. If the TST result is positive, the infant should be treated with INH for a total of 9 months.

Monitoring for adverse effects

Adverse effects of INH (eg, hepatitis) are rare in children; therefore, routine determination of serum aminotransferase levels is not necessary. Consider monthly monitoring of hepatic function tests in the following patients: (1) those with severe or disseminated tuberculosis; (2) those with concurrent or recent hepatic disease; (3) those receiving high daily doses of INH (10 mg/kg/d) in combination with rifampin, pyrazinamide, or both; (4) women who are pregnant or within the first 6 weeks postpartum; (5) those with clinical evidence of hepatotoxic effects; and (6) those with hepatobiliary tract disease from other causes.

 

Surgical Care

Pulmonary resection in patients with tuberculosis may be required in drug-resistant cases because of the high likelihood of failure of the medication regimen. Surgical resection may also be required in patients with advanced disease with extensive caseation necrosis. Hemoptysis, although rare in children, may necessitate surgical intervention. Tubercular abscesses and bronchopleural fistulae also should be surgically removed.

Consultations

Infectious diseases consultation may be helpful.

Diet

Diet is as tolerated.

Activity

The advisability of bed rest varies with the type and severity of the disease. No limitation of activity is required in patients with tuberculosis infection or asymptomatic primary pulmonary tuberculosis. Severely ill patients with miliary tuberculosis and tubercular meningitis may require complete bed rest.

Medication

Antituberculous medications kill mycobacteria, thereby preventing further complications of early primary disease and progression of disease. However, disappearance of caseous or granulomatous lesions does not occur even with therapy.

Antitubercular drugs are classified as first-line and second-line drugs. First-line drugs have less toxicity with greater efficacy than second-line drugs. All first-line agents are bactericidal with the exception of ethambutol.

First-line agents include rifampin, isoniazid (INH), pyrazinamide, ethambutol, and streptomycin. Second-line agents are capreomycin, ciprofloxacin, cycloserine, ethionamide, kanamycin, ofloxacin, levofloxacin, and para-aminosalicylic acid.

INH and rifampin are effective against bacilli in necrotic foci and intracellular populations of mycobacteria. Streptomycin, aminoglycosides, and capreomycin have poor intracellular penetration. Multidrug-resistant (MDR) tuberculosis (TB) is defined as resistance to at least INH and rifampin. The emergence of drug-resistant strains has necessitated use of second-line agents.

Naturally drug-resistant organisms occur with a frequency of approximately 10-6; however, individual resistances may vary. The resistance to streptomycin is 10-5, to INH is 10-6, and to rifampin is 10-8. The chance that an organism is naturally resistant to both INH and rifampin is on the order of 10-14. Because populations of this size do not occur in patients, organisms naturally resistant to 2 drugs are essentially nonexistent. If only a single medication is administered to a patient with tuberculosis, the subpopulations susceptible to that medication are destroyed, but the other categories continue to multiply. Thus, the use of multiple agents in the treatment of tuberculosis is essential.

 

Antitubercular drugs

Antimycobacterial agents are a miscellaneous group of antibiotics whose spectrum of activity includes Mycobacterium species. They are used to treat tuberculosis, leprosy, and other mycobacterial infections.

 

Rifampin (Rifadin)

Bactericidal for M tuberculosis. Penetrates well into all body fluids including CSF. For use in combination with at least one other antituberculous drug. Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription. Cross-resistance may occur.

Adult

600 mg PO/IV qd

Pediatric

10-20 mg/kg PO/IV qd; not to exceed 600 mg/d

Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid or pyrazinamide may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in serum transaminases occur)

Documented hypersensitivit Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In adults and those at risk, obtain CBC counts and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occur; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur; orange discoloration of secretions or urine may occur; staining of contact lenses may occur

 

Isoniazid (Laniazid, Nydrazid)

Commonly referred to as INH. Best combination of effectiveness, low cost, and minor adverse effects. First-line drug unless known resistance or another contraindication is present. Therapeutic regimens of <6 mo demonstrate unacceptably high relapse rates. Coadministration of pyridoxine is recommended if peripheral neuropathies secondary to INH therapy develop. Prophylactic doses of 6-50 mg of pyridoxine daily are recommended in some populations.

Adult

5 mg/kg PO qd (usually 300 mg/d) and 10 mg/kg qd or divided bid in patients with disseminated disease; not to exceed 300 mg/d
DOT: 15 mg/kg twice PO weekly; not to exceed 900 mg/d

Pediatric

10-20 mg/kg PO qd; not to exceed 300 mg/d

Higher incidence of INH-related hepatitis can occur with alcohol ingestion on daily basis; aluminum salts may decrease INH serum levels (administer 1-2 h before taking aluminum salts); may increase anticoagulant effects with coadministration; may inhibit metabolic clearance of benzodiazepines; carbamazepine toxicity or INH hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver functions); coadministration with cycloserine may increase CNS adverse effects (eg, dizziness); acute behavioral and coordination changes may occur with coadministration of disulfiram; coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin

Documented hypersensitivity; previous INH-associated hepatic injury or other severe adverse reactions

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during INH therapy are recommended even when visual symptoms do not occur

 

Streptomycin

For treatment of susceptible mycobacterial infections. Use in combination with other antituberculous drugs (eg, INH, ethambutol, rifampin).

Adult

1 g IM qd
2 times/wk dosing: 15 mg/kg/d IM; not to exceed 1 g/d
3 times/wk dosing: 25-30 mg/kg/d IM; not to exceed 1.5 g/d

Pediatric

2 times/wk dosing: 20-40 mg/kg/d IM; not to exceed 1 g/d
3 times/wk dosing: 25-30 mg/kg/d IM; not to exceed 1.5 g/d

Nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics

Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Narrow therapeutic index; not intended for long-term therapy; caution in patients with renal failure who are not on dialysis; caution with myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission

 

Pyrazinamide

Pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal against M tuberculosis, depending on concentration of drug attained at site of infection. Mechanism of action is unknown. Administer for initial 2 mo of a 6-mo or longer treatment regimen for patients who are drug-susceptible. Treat patients with drug-resistant cases with individualized regimens.

Adult

15-30 mg/kg PO qd; not to exceed 2 g/d
DOT: 50-70 mg/kg PO 2 times/wk, not to exceed 4 g/d; or 50-70 mg/kg 3 times/wk, not to exceed 3 g/d

Pediatric

Administer as in adults

Coadministration with rifampin may result in higher rate of hepatotoxicity (liver failure and death have occurred) than with either agent alone (discontinue if alterations in LFT results occur)

Documented hypersensitivity; severe hepatic damage; acute gout

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use only in combination with other effective antituberculous agents; inhibits renal excretion of urates; may result in hyperuricemia (usually asymptomatic); perform baseline serum uric acid determinations; discontinue if signs of hyperuricemia with acute gouty arthritis; perform baseline serum transaminases (closely monitor in liver disease); discontinue if signs of hepatocellular damage appear; caution in history of diabetes mellitus

 

Ethambutol (Myambutol)

Diffuses into actively growing mycobacterial cells, such as tubercle bacilli. Impairs cell metabolism by inhibiting synthesis of one or more metabolites, which in turn causes cell death. No cross-resistance demonstrated.
Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with second-line drugs that have not been previously administered.
Administer q24h until permanent bacteriologic conversion and maximal clinical improvement are observed. Absorption is not significantly altered by food.

Adult

No previous antituberculous therapy: 15 mg/kg (7 mg/lb) PO qd
Previous antituberculous therapy: 25 mg/kg (11 mg/lb) PO qd

Pediatric

<13 years: Not recommended
>13 years: Administer as in adults

Aluminum salts may delay and reduce absorption (give several hours before or after ethambutol dose)

Documented hypersensitivity; optic neuritis (unless clinically indicated)

Pregnancy

B – Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Reduce dose in impaired renal function; may have reversible visual adverse effects if promptly discontinued; monitor for visual acuity and color vision; avoid administration in children if unable to test vision

 

Cycloserine (Seromycin)

Inhibits cell wall synthesis in susceptible strains of gram-positive and gram-negative bacteria and in M tuberculosis. Structural analogue of D-alanine, which antagonizes role of D-alanine in bacterial cell wall synthesis and inhibits growth.

Adult

0.5-1 g PO qd in divided doses; monitor by blood levels
Alternatively, 250-500 mg PO bid for first 2 weeks; not to exceed 1 g/d
Reducing dose to 200-300 mg/d may prevent neurotoxic effects

Pediatric

10-20 mg/kg/d; not to exceed 0.75-1 g/d

Incompatible with alcohol consumption (may increase possibility and risk of epileptic episodes); INH in combination with cycloserine may result in increased cycloserine CNS adverse effects such as dizziness

Documented hypersensitivity; severe anxiety or psychosis; epilepsy; depression; severe renal insufficiency; alcoholism; patients with severe neurologic impairments should not receive this drug

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue or reduce dosage if allergic dermatitis or symptoms of CNS toxicity (eg, convulsions, headache, tremor, depression, confusion, psychosis, somnolence, hyperreflexia, vertigo, paresis, dysarthria) develop; risk of convulsions is increased in chronic alcoholism; administration has been associated with vitamin B-12 and folic acid deficiency, megaloblastic anemia, and sideroblastic anemia; monitor blood levels weekly in reduced renal function, in patients receiving more than 500 mg/d, and in those with symptoms of toxicity

 

Ethionamide (Trecator)

Bacteriostatic against M tuberculosis. Recommended when treatment with first-line drugs (INH, rifampin) has failed. Treats any form of active TB. However, should only be used with other effective antituberculous agents.

Adult

0.5-1 g/d PO divided qid; concomitant administration of 25 mg pyridoxine recommended

Pediatric

15-20 mg/kg/d PO divided tid/qid; not to exceed 1 g/d; concomitant administration of pyridoxine recommended

None reported

Documented hypersensitivity; severe hepatic damage

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Make determinations of serum transaminases prior to therapy and q2-4wk thereafter; perform in vitro susceptibility tests of recent cultures of M tuberculosis from patient with ethionamide and usual first-line antituberculous drugs; management of diabetes mellitus may be more difficult, and hepatitis may occur more frequently

 

Para-aminosalicylic acid (Sodium P.A.S.)

Bacteriostatic agent useful against M tuberculosis. Inhibits onset of bacterial resistance to streptomycin and INH. Administer aminosalicylate sodium with other antituberculous drugs.

Adult

12 g/d PO divided bid/tid

Pediatric

150 mg/kg/d PO divided tid/qid; not to exceed 12 g/d

Oral absorption of digoxin may be reduced, causing reduction in serum levels when administered concurrently; increase in digoxin dosing may be necessary; deficiency in vitamin B-12 (oral) may be induced due to PAS interference of its GI absorption; parenteral vitamin B-12 supplementation may be required

Documented hypersensitivity

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in gastric ulcer and history of CHF; avoid situations in which excess sodium is potentially harmful

 

Capreomycin (Capastat)

Obtained from Streptomyces capreolus for coadministration with other antituberculous agents in pulmonary infections caused by capreomycin-susceptible strains of M tuberculosis. For use only when first-line agents (eg, INH, rifampin) have been ineffective or cannot be used because of toxicity or presence of resistant tubercle bacilli.

Adult

1 g IM qd for 60-120 d, followed by 1 g IM bid/tid; not to exceed 20 mg/kg/d

Pediatric

Not established; limited data suggest 15 mg/kg/d IM; not to exceed 1 g/d

Coadministration with aminoglycosides may increase risk of respiratory paralysis and renal dysfunction; with nondepolarizing neuromuscular blocking agents, has synergistic effects on myoneural function

Documented hypersensitivity

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Assess vestibular auditory function prior to therapy and regularly while treating; monitor renal function throughout treatment (reduce dose in renal impairment); monitor serum potassium levels

 

Levofloxacin (Levaquin)

For treatment of TB in combination with rifampin and other anti-TB agents.

Adult

0.5-1 g PO qd or divided bid

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Documented hypersensitivity

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

 

Ciprofloxacin (Cipro)

For treatment of TB in combination with rifampin and other anti-TB agents. Fluoroquinolones have not been approved for use in patients <18 y. Use in pediatric population necessitates assessment of risk versus benefit.

Adult

750 mg PO bid

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Documented hypersensitivity

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

 

Ofloxacin (Floxin)

For treatment of TB in combination with rifampin and other anti-TB agents. Fluoroquinolones have not been approved for use in patients <18 y. Use in pediatric population necessitates assessment of risk versus benefit.

Adult

400-800 mg/d PO divided bid

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase ofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Documented hypersensitivity

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

 

Kanamycin (Kantrex)

Aminoglycoside antibiotic produced by Streptomyces kanamyceticus. May be used as second-line agent in treatment of TB.

Adult

15-30 mg/kg/d IM

Pediatric

Administer as in adults

Nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics

Documented hypersensitivity

Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May lead to auditory and vestibular toxicity, renal toxicity, and neuromuscular blockade; increased risk exists for patients with present or past history of renal impairment, for those receiving concomitant or sequential treatment with other ototoxic or nephrotoxic drugs or rapid-acting diuretic agents given IV (eg, ethacrynic acid, furosemide, mannitol), and for patients treated for longer periods and/or with higher doses than recommended; monitor renal function by measuring serum creatinine concentration or calculating endogenous CrCl rate; measure peak and trough serum concentrations intermittently during treatment to monitor toxicity

 

Rifabutin (Mycobutin)

Ansamycin antibiotic derived from rifamycin S. Inhibits DNA-dependent RNA polymerase, preventing chain initiation, in susceptible strains of Escherichia coli and Bacillus subtilis but not in mammalian cells. If GI upset occurs, administer dose bid with food.

 

 

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CLINICAL PEDIATRIC ONLINE 

Yudhasmara Foundation 

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646 

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

 

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO 

 

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

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