infectious diseases
Rifamycins
Rifabutin, Rifampin, and Rifapentine
Rifabutin,rifampin, andrifapentinehave similar pharmacokinetics, antimicrobial spectra, and adverse effects. Oral absorption is good, producing wide distribution in body tissues and fluids, including cerebrospinal fluid. Rifampinis concentrated in polymorphonuclear granulocytes and macrophages, facilitating clearance of bacteria from abscesses. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine. Rifampinis active against Most gram-positive and some gram-negative bacteria Tuberculosis (TB) species Resistance develops rapidly, sorifampinis rarely used alone.Rifampinis used with other antibiotics for First-line drugs for TB None is active against many nontuberculous mycobacteria, but rapidly growing Nontuberculous Mycobacterial Infections , such as Leprosy (with Staphylococcal Infections , including osteomyelitis, prosthetic valve endocarditis, and infections involving foreign bodies such as a prosthetic joint (with other antistaphylococcal antibiotics) Legionella Infections infections (older data suggest better outcomes for Pneumococcal meningitis when organisms are susceptible to can be used alone for prophylaxis of close contacts of patients with Diseases Caused by Meningococci or Rifabutinandrifampinare equally efficacious in regimens for tuberculosis in HIV-positive and HIV-negative patients. However, if patients are receiving antiretroviral therapy (ART),rifabutinis preferred because it is less likely to induce cytochrome P-450 metabolic enzymes that lower serum levels of protease inhibitors and non-nucleoside reverse transcriptase inhibitors. Rifampinis preferred overrifabutinforMycobacterium aviumcomplex (MAC) lung disease, unless patients are receiving ART; in such cases,rifabutinmay be substituted. However,rifabutinis preferred overrifampinfor disseminated MAC infections because of its superior activity in vitro and reduced drug interaction potential. Rifapentineis used to treat pulmonary and latent tuberculosis. Rifampinandrifabutinare contraindicated in patients who have had an allergic reaction to them. Some animal reproduction studies withrifabutinshowed adverse effects when drug levels were higher than those typically achieved in humans. No adequate and well-controlled studies have been done in pregnant or breastfeeding women. Safety during breastfeeding is unknown. Animal reproduction studies withrifampinorrifapentineshow some risk (ie, teratogenicity) at drug levels less than or equal to those typically achieved in humans. No adequate and well-controlled studies with either drug have been done in pregnant women. Because of potential tumorigenicity shown in animal studies, the manufacturer does not recommend use ofrifampinduring breastfeeding. However, the Centers for Disease Control and Prevention (CDC)does not consider rifampin a contraindication to breastfeeding; a decision to stop breastfeeding or to stop the drug should be made depending on the importance of the drug to the mother. Adverse effects of rifamycins include Hepatitis (most serious) Gastrointestinal disturbances Central nervous system effects Myelosuppression Hepatitis occurs much more often whenisoniazidorpyrazinamideis used concurrently withrifampin. During the first week of therapy,rifampinmay cause a transient rise in unconjugated serum bilirubin, which results from competition betweenrifampinand bilirubin for excretion and which is not in itself an indication for interrupting treatment. Central nervous system effects may include headache, drowsiness, ataxia, and confusion. Rash, fever, leukopenia, hemolytic anemia, thrombocytopenia, interstitial nephritis, acute tubular necrosis, renal insufficiency, and interstitial nephritis are generally considered to be hypersensitivity reactions and occur when therapy is intermittent or when treatment is resumed after interruption of a daily dosage regimen; they are reversed whenrifampinis stopped. Rifabutincan cause dose-dependent unilateral or bilateral uveitis. Less serious adverse effects are common; they include heartburn, nausea, vomiting, and diarrhea.Rifampin,rifabutin, andrifapentinecan cause temporary reddish orange discoloration of urine, saliva, sweat, sputum, and tears. Soft contact lenses may be permanently discolored. If patients have a liver disorder, liver tests should be done beforerifampintherapy is started and every 2 to 4 weeks during therapy, or an alternate drug should be used. Dose adjustments are unnecessary for renal insufficiency. Rifampininteracts with many drugs because it is a potent inducer of hepatic cytochrome P-450 (CYP450) microsomal enzymes.Rifampinaccelerates elimination and thereby may decrease the effectiveness of the following drugs: angiotensin-converting enzyme inhibitors,atovaquone, barbiturates, beta-blockers, calcium channel blockers,chloramphenicol,clarithromycin, oral and systemic hormone contraceptives, corticosteroids,cyclosporine,dapsone,digoxin,doxycycline,fluconazole,haloperidol,itraconazole,ketoconazole, the non-nucleoside reverse transcriptase inhibitorsdelavirdineandnevirapine, opioid analgesics,phenytoin, protease inhibitors,quinidine, sulfonylureas,tacrolimus,theophylline, thyroxine, tocainide, tricyclic antidepressants,voriconazole,warfarin, andzidovudine. To maintain optimum therapeutic effect of these drugs, clinicians may have to adjust the dosage whenrifampinis started or stopped. Conversely, protease inhibitors, as well as other drugs (eg, azoles, the macrolideclarithromycin, non-nucleoside reverse transcriptase inhibitors) inhibit CYP450 enzymes and increase levels of rifamycins and thus potentially increase the frequency of toxic reactions. For example, uveitis occurs more commonly whenrifabutinis used withclarithromycinor azoles. 