The use of rifampicin for the treatment of infectious diseases in children
Rifampicin was first isolated in 1957. The drug has a wide range of activities and has already been used in various infections in children. The emergence of resistance in bacteria has limited its use. Today, rifampicin is considered a component of combined antimicrobial regimens for resistant infections and as a drug for prevention after exposure to invasive bacterial infections.
Rifampicin inhibits the activity of DNA-dependent RNA polymerase in sensitive bacterial strains, disrupting protein synthesis. The drug has shown in vivo and in vitro activity against Micobacterium tuberculosis and Neisseria meningitidis, as well as in vitro activity against M.leprae, Haemophilus influenzae, coagulase positive and coagulase negative staphylococci, Streptococcus pneumoniae , species Peptostreptococcus, Chlamydia trachomatis and C.psittaci. Resistance to rifampicin often develops as a result of single-step mutations in DNA-dependent RNA polymerase.
The US Food and Drug Administration (FDA) has currently approved 2 indications for the use of rifampicin: the treatment of tuberculosis and the eradication of Neisseria meningitidis in asymptomatic carriers. In case of tuberculosis, rifampicin in combination with ethambutol or isoniazid is prescribed at a dose of 10-20 mg / kg / day for 2 to 6 months, depending on the location and severity of the infection. Rifampicin is also recommended for the combined treatment of non-tuberculous mycobacterial infections in children. In the treatment of the oligobacillary form of M.leprae infection, rifampicin is prescribed in combination with dapsone. Treatment usually lasts 1 year using the same doses as for tuberculosis.
Due to the high risk of developing resistance, rifampicin monotherapy is not recommended. Rifampicin can be used in combination with other antibiotics for the treatment of streptococcal and staphylococcal infections (usually in combination with vancomycin) or type Haemophilus influenzae type b infection.
The combination of doxycycline and rifampicin is recommended for the treatment of brucellosis; doses of 15-20 mg / kg / day (but not more than 900 mg / day) are used in 1-2 doses. Rifampicin may supplement azithromycin treatment for legionellosis in immunocompromised patients or patients who do not respond to azithromycin monotherapy. Rifampicin is effective in treating cat scratch disease (a disease caused by Bartonella henselae) and in combination with other antibiotics for refractory cases of meningitis caused by Naegleria fowleri and Acanthamoeba.
In some cases, rifampicin has been used as monotherapy. 2 cases of the use of rifampicin as monotherapy at a dose of 10 mg / kg twice a day in children with granulocytic ehrlichiosis have been described. Rifampicin was preferred to doxycycline, the drug of choice, due to the lack of risk of staining of teeth.
Rifampicin is used prophylactically after contact with a patient with an invasive infection caused by Haemophilus influenzae type b or a meningococcal infection. Rifampicin is also recommended for the eradication of Neisseria meningitidis nasopharynx and group A β-hemolytic streptococcus in carriers. It has been used to eliminate porting to the nasopharynx of group B streptococcus in infants with repeated invasive infections, although monotherapy has been unsuccessful recently.
After oral administration, rifampicin is well absorbed. The maximum concentration in serum is generally reached within the next 1 to 4 hours. For adults, the maximum concentration is 4 to 32 μg / ml, in children, the level is 3.5 to 15 μg / ml lower.. Food reduces the bioavailability of rifampicin by approximately 30%. The drug is well distributed throughout the body, the volume of distribution at an equilibrium concentration is about 0.64 l / kg. Binding to plasma proteins - 80%. Rifampicin is metabolized in the liver to form an active metabolite. The half-life in adults is 2 to 5 hours after the first dose, reduced to 2 to 3 hours with the following doses. In a study of 12 children aged 3 months to 12 years, the elimination half-life ranged from 1.04 to 3.81 hours. The unchanged drug and its metabolite are excreted from the body through bile and urine. Dose adjustment is necessary in patients with hepatic impairment. Kidney failure does not require a dose reduction.
The most common side effects of rifampicin are headache, drowsiness, fatigue, dizziness, hyperemia and itching of the skin (with or without a rash), anorexia, nausea, vomiting , diarrhea, increased levels of liver transaminases and bilirubin, muscle weakness. Rare but serious side effects are transient leukopenia, anemia, thrombocytopenia, hepatitis, hypersensitivity reactions, porphyria, interstitial nephritis and acute tubular necrosis. The drug reduces the concentration of hormones of the adrenal glands and thyroid gland, disrupts the metabolism of vitamin D. Treatment with high intermittent dose (more than 25 mg / kg per week) causes flu-like syndrome, including fever, chills, headache, dizziness, bone pain in 50% of patients.
Patients and their loved ones should be warned that the drug causes tear fluid, sputum, sweat, and red-orange colored urine stains. Rifampicin can cause irreversible stains on contact lenses. A suspension of rifampicin in contact with clothing stains clothing and plastic items.
Rifampicin is an inducer of microsomal enzymes in the cytochrome P-450 system (CYP3A4). Co-administration of rifampicin lowers the concentration in the blood plasma of many drugs:
Co-administration with aminosalicylic acid or azole antifungals may reduce the serum rifampicin concentration to a sub-therapeutic level. Concomitant administration of protease inhibitors may be accompanied by a decrease in the rate of rifampicin metabolism, resulting in an increase in serum concentration. Whenever possible, the combinations of drugs listed should be avoided.
The use of halothane in patients taking rifampicin has a hepatotoxic effect and may lead to the development of hepatic encephalopathy. With the simultaneous use of isoniazid and rifampicin, the risk of hepatotoxicity also increases. A pronounced interaction can be observed in children under 2 years of age. Careful monitoring of liver function is recommended.
In the treatment of tuberculosis in children, a number of treatment regimens have been used. One of the effective regimens recently described consisted of a daily intake of 2 weeks followed by 2 times per week for 6 months with a combination of rifampicin at a dose of 10-20 mg / kg, isoniazid and pyrazinamide for the 6 first weeks. This treatment regimen allows you to directly control compliance. Improvement in this therapy was observed in 173 patients, complete resolution of the disease in 37% of children.
For other infections, rifampicin can be administered iv or orally at a dose of 10-20 mg / kg / day in 1-2 doses after 12 hours.The maximum recommended dose for most infections in adults is 600 mg / day, although in severe infections the dose may be increased to 900 mg / day.
Prevention after contact with a patient with an invasive infection caused by Haemophilus influenzae type b consists of prescribing rifampicin at a dose of 20 mg / kg once a day for 4 days. For patients less than a month old. a dose of 10 mg / kg / day may be prescribed. For prophylactic purposes and for the eradication of meningococcal and streptococcal carriage in children under one month of age. a dose of 5 mg / kg / day is administered orally every 12 hours for 2 days. In children 1 month. and above, a dose of 10 mg / kg (but not more than 600 mg) is applied every 12 hours for 2 days. The drug is taken on an empty stomach (1 hour before or 2 hours after eating), washed with a full glass of water. For patients who cannot take the drug inside, it is administered iv at the same dose. The drug is not administered subcutaneously and intramuscularly.