title: Lack of association between rifampicin plasma concentration and treatment-related side effects in osteoarticular infections.
abstract: The aim of this study was to assess the frequency of gastrointestinal side effects (GSE) and hepatotoxicity in patients treated with rifampicin for an osteoarticular infection and to determine if there is an association between rifampicin plasma concentrations and side effects. Rifampicin plasma concentrations were prospectively measured before (trough concentration, C(0)) and 2 +/- 0.5 h (peak concentration, C(2)) after drug intake. The presence of GSE, the alanine transferase (ALT) value, and concomitantly administered medications were recorded on the day rifampicin concentrations were measured. C(0) and C(2) were compared for differences regarding the presence or absence of side effects. Multivariate analysis was performed, with associated medications being taken into account. Seventy C(0) and 57 C(2) values were measured in 46 adults after a median treatment of 8 days (range, 1-179). Wide inter-individual variability was observed for C(0) and C(2). Thirteen (28%) patients reported GSE at least once. When GSE occurred, C(0) (median, 1 mg L(-1); range, 0.1-9.9 mg L(-1)) and C(2) (median, 10.3 mg L(-1); range, 1.8-40.3 mg L(-1)) were similar to C(0) (median, 0.6 mg L(-1); range, 0.1-10.3 mg L(-1)) and C(2) (median, 10.9 mg L(-1); range, 2.9-29.0 mg L(-1)) without GSE. The ALT value was more than normal in only three patients (6.5%) after rifampicin treatment began. The patients received no different associated medications whether or not GSE were present. Multivariate analysis showed no association between rifampicin plasma concentrations and GSE. GSE occur frequently in patients receiving rifampicin for osteoarticular infection but without an association with rifampicin plasma concentrations. Thus, therapeutic drug monitoring of rifampicin is irrelevant in the management of GSE.
authors.affiliation: CHRU de Tours, Service des Maladies Infectieuses, 2 boulevard Tonnellé, 37044 Tours Cedex, France.
authors.forename: France
authors.initials: F
authors.lastname: Roblot
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Besnier
authors.forename: Bruno
authors.initials: B
authors.lastname: Giraudeau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Simonnard
authors.forename: Annie-Pierre
authors.initials: AP
authors.lastname: Jonville-Bera
authors.forename: Patrick
authors.initials: P
authors.lastname: Coipeau
authors.forename: Patrick
authors.initials: P
authors.lastname: Choutet
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Autret-Leca
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Guellec
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D003967:Diarrhea / Q000139:chemically induced; D004064:Digestive System / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010019:Osteomyelitis / Q000188:drug therapy*; D010865:Pilot Projects; D011446:Prospective Studies; D012293:Rifampin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000900:Anti-Bacterial Agents; D012293:Rifampin