of rifampicin and pyrazinamide had previously been recommended but is no longer recommended due to high rates of hepatotoxicity. Rifampicin should be taken on an empty stomach with a glass of water. It is generally taken either at least one hour before meals or two hours after meals. Rifampicin is also used to treat nontuberculous mycobacterial infections including leprosy (Hansen's disease) and Mycobacterium kansasii. With multidrug therapy used as the standard treatment of Hansen's disease, rifampicin is always used in combination with dapsone and clofazimine to avoid causing drug resistance. It is also used in the treatment of Mycobacterium ulcerans infections as associated with Buruli ulcer, usually in combination with clarithromycin or other antibiotics. Other bacteria and protozoans In 2008, tentative evidence showed rifampicin may be useful in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in combination with other antibiotics, including in difficult-to-treat infections such as osteomyelitis and prosthetic joint infections. As of 2012, if rifampicin combination therapy was useful for pyogenic vertebral osteomyelitis was unclear. A meta-analysis concluded that adding adjunctive rifampicin to a β-lactam or vancomycin may improve outcomes in staphylococcus aureus bacteremia. However, a more recent trial found no benefit from adjunctive rifampicin. It is also used as preventive treatment against Neisseria meningitidis (meningococcal) infections. Rifampicin is also recommended as an alternative treatment for infections by the tick-borne pathogens Borrelia burgdorferi and Anaplasma phagocytophilum when treatment with doxycycline is contraindicated, such as in pregnant women or in patients with a history of allergy to tetracycline antibiotics. It is also sometimes used to treat infections by Listeria species, Neisseria gonorrhoeae, Haemophilus influenzae, and Legionella pneumophila. For these nonstandard indications, antimicrobial susceptibility testing should be done (if possible) before starting rifampicin therapy. The Enterobacteriaceae, Acinetobacter species, and Pseudomonas species are intrinsically resistant to rifampicin. It has been used with amphotericin B in largely unsuccessful attempts to treat primary amoebic meningoencephalitis caused by Naegleria fowleri. Rifampicin can be used as monotherapy for a few days as prophylaxis against meningitis, but resistance develops quickly during long-term treatment of active infections, so the drug is always used against active infections in combination with other antibiotics. Rifampicin is relatively ineffective against spirochetes, which has led to its use as a selective agent capable of isolating them in materials being cultured in laboratories. Viruses Rifampicin has some effectiveness against vaccinia virus. Pathogen susceptibility The minimum inhibitory concentrations of rifampicin for several medically significant pathogens