title: Rifabutin: where do we stand in 2016?
abstract: Rifabutin is a spiro-piperidyl-rifamycin structurally closely related to rifampicin that shares many of its properties. We attempted to address the reasons why this drug, which was recently recognized as a WHO Essential Medicine, still had a far narrower range of indications than rifampicin, 24 years after its launch. In this comprehensive review of the classic and more recent rifabutin experimental and clinical studies, the current state of knowledge about rifabutin is depicted, relying on specific pharmacokinetics, pharmacodynamics, antimicrobial properties, resistance data and side effects compared with rifampicin. There are consistent in vitro data and clinical studies showing that rifabutin has at least equivalent activity/efficacy and acceptable tolerance compared with rifampicin in TB and non-tuberculous mycobacterial diseases. Clinical studies have emphasized the clinical benefits of low rifabutin liver induction in patients with AIDS under PIs, in solid organ transplant patients under immunosuppressive drugs or in patients presenting intolerable side effects related to rifampicin. The contribution of rifabutin for rifampicin-resistant, but rifabutin-susceptible, Mycobacterium tuberculosis isolates according to the present breakpoints has been challenged and is now controversial. Compared with rifampicin, rifabutin's lower AUC is balanced by higher intracellular penetration and lower MIC for most pathogens. Clinical studies are lacking in non-mycobacterial infections.
authors.affiliation: APHP-Hôpital Necker-Enfants malades, Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, Paris, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Crabol
authors.affiliation: Service de Pneumologie, Hôpital Foch, Suresnes, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Catherinot
authors.affiliation: AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de Bactériologie-Hygiène, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France UPMC, INSERM, Centre d'Immunologie et des Maladies Infectieuses, E13, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veziris
authors.affiliation: AP-HP, Hôpital Européen Georges-Pompidou, Pharmacology Department, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Inserm U1129, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.affiliation: APHP-Hôpital Necker-Enfants malades, Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France IHU Imagine, Paris, France olivier.lortholary@aphp.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
mesh_terms: D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D008826:Microbial Sensitivity Tests; D009164:Mycobacterium Infections / Q000188:drug therapy; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D017828:Rifabutin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012293:Rifampin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000904:Antibiotics, Antitubercular; D017828:Rifabutin; D012293:Rifampin