Anti-tubercular medications: rifampin, isoniazid, pyrazinamide, and ethambutol are FDA approved for the treatment of mycobacterium tuberculosis. The combination and duration on which medications to use for therapy rely on whether the patient has active or latent disease. A feared complication of tuberculosis therapy is multi-drug-resistant tuberculosis(MDR-TB). MDR-TB is distinguished from its resistance to first-line medications isoniazid and rifampin. Therapy for MDR-TB is steadily advancing, and suggestions are continually changing. Second-line drugs that are in common use for MDR-TB are kanamycin, capreomycin, and amikacin via injections. Fluoroquinolones such as levofloxacin, moxifloxacin, and gatifloxacin and are also amongst the common second-line agents used when drug resistance develops to the first-line agents. Drugs that have recently received FDA approval for the multi-drug resistance TB are pretomanid, used in sequence with bedaquiline, and linezolid. A more dangerous and uncommon type of MDR-TB is extensively multi-drug resistant tuberculosis(XDR-TB). This infection characteristically shows the resistance to first-line medications rifampin and isoniazid, one second-line aminoglycoside, and either of the fluoroquinolones.
Pyrazinamide's mechanism of action remains unknown and not fully understood. Pyrazinamide is converted to its active form pyrazinoic acid and exerts its effect by inhibiting trans-translation and possibly coenzyme A synthesis needed for the bacteria to survive.
Ethambutol inhibits the enzyme arabinosyltransferases and prevents the biosynthesis of the mycobacterial cell wall.
Aminoglycosides (Streptomycin, Kanamycin, Capreomycin, Amikacin)
Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin)
Fluoroquinolones exert their effects by inhibiting DNA gyrase and topoisomerase IV, further inhibiting DNA synthesis within the bacteria.
During active disease, there are two phases for treatment: the initiation phase and the continuation phase. The initiation phase consists of two months of rifampin, isoniazid, pyrazinamide, and ethambutol therapy. This regimen is administered orally daily for eight weeks for a total of 56 doses. Once completed, isoniazid and rifampin are continued for an additional four-month for the continuation phase. This regimen is administered orally daily for 18 weeks for a total of 126 doses. Patients that can not tolerate ethambutol, streptomycin can be substituted.
10 mg/kg /day
The maximum dose: 600mg
The maximum dose: 300mg
Dosages are adjusted according to weight
Dosages are adjusted according to weightSecond-line agents such as kanamycin, capreomycin, amikacin are administered as an injection, and fluoroquinolones such as moxifloxacin, gatifloxacin, and levofloxacin are administered orally. These agents are options when resistance to first-line medication develops.
The most typical and used treatment for latent tuberculosis is isoniazid therapy for a duration of nine months. This regimen is administered orally daily for nine months for a total of 270 doses. A three-month combination of isoniazid and rifampin or a fourth-month duration of rifampin monotherapy are also possibilities. Isoniazid monotherapy can have an effect of greater than 90% on the latent disease if taken upon completion of the full nine-month duration. Pyridoxine(Vitamin B6) use is advised alongside isoniazid therapy, as isoniazid use individually can cause peripheral neuropathy secondary to vitamin B6 deficiency.
The maximum dose: 300mg
10 to 25 mg/day
Anti-tubercular medications should be taken in the daytime one hour before consuming any meals.
Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin):
Liver function tests should be monitored routinely as rifampin, isoniazid, pyrazinamide, and ethambutol all may exert hepatotoxic effects. CBC also requires regular monitoring for patients taking rifampin, as it can cause thrombocytopenia and neutropenia. Rifampin also exerts its effects by inducing cytochrome P450(CYP450), which may cause unwanted drug interactions of medications that are metabolized by the CYP450 system and decrease there clinical efficacy. Isoniazid can cause pyridoxine deficiency that may lead to peripheral neuropathy in patients. The patient can supplement vitamin B6 to prevent this from happening. Pyrazinamide can increase uric acid levels and precipitate acute gout flare-ups in predisposed individuals. The recommendation is to monitor uric acid levels routinely for patients managed with pyrazinamide.
All first-line anti-tubercular medications, rifampin, isoniazid, pyrazinamide, and ethambutol can exert hepatotoxic effects. A continual rise in liver functions test should prompt discontinuation of treatment. Aminoglycoside induced nephrotoxicity is reversible when stopping the medication. Renal toxicity depends on the patient if any underlying renal disease is present, and on the dose of the medication being administered. Renal insufficiency is avoidable in most patients.
Rifampin, isoniazid, pyrazinamide, and ethambutol are first-line antitubercular medications, which are FDA-approved and indicated for the treatment of mycobacterium tuberculosis. The care for patients suffering from Tuberculosis prompts critical care from an interprofessional team of healthcare professionals as the preventable infectious disease can lead to medication resistance and mortality. These healthcare professionals include a primary care physician, an infectious disease specialist, a nurse, and a pharmacist. The primary care physicians and specialists should educate the patients about the consequences of noncompliance of therapy for the full duration, and how resistance to treatment can further develop into MDR-TB, and cause mortality. Primary care physicians should routinely monitor labs, as all four agents are hepatotoxic drugs. Counseling and careful monitoring should be conducted during pregnancy, as some second-line medications are teratogenic. Physicians should be up to date with the newly FDA approved MDR-TB, and their effects in the event drug resistance do develop. Interprofessional communication is key to building patient rapport and developing a therapeutic alliance, so the patients comply with therapy adequately to eradicate the bacteria and prevent further spread.
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