Linezolid Rifampicin

Infections limited to soft tissue will require between 7 and 10 days of intravenous therapy followed by an additional 14 days of oral therapy (total duration 2-4 weeks). If MRSA is isolated, intravenous vancomycin must not be switched to oral vancomycin which has negligible absorption from the gastrointestinal tract. Oral agents may be selected from rifampicin, tetracyclines, fusidic acid or trimethoprim depending on sensitivity data and a combination of two agents is recommended. Oral linezolid monotherapy is an effective alternative. 

Venlafaxine. An 85-year-old man taking venlafaxine 150 mg daily was prescribed ciprofloxacin, rifampicin and linezolid 600 mg twice daily for a hip prosthesis infection. After 20 days he was found to be confused and disorientated, and 4 days later he was also drowsy, and suffering myoclonic jerks. Linezolid and venlafaxine were stopped and the symptoms resolved over 2 days. However, another case report describes a 7-year-old boy treated with venlafaxine and methylphenidate who was prescribed linezolid for osteomyelitis. He was given all three drugs (doses not stated) for several days without any alterations in vital signs or evidence of the serotonin syndrome. ... 

Serum levels of intravenous linezolid are reduced by intravenous rifampicin. 

A 31-year-old woman was given intravenous rifampicin 300 mg every 8 hours and linezolid 600 mg every 12 hours for an MRSA infection. During rifampicin treatment her linezolid peak and trough levels were... 

In an earlier study, healthy subjects were given a single 600-mg dose of intravenous linezolid either alone or with a single 600-mg dose of intravenous rifampicin. This study also found that rifampicin reduced the serum levels of linezolid by 10%, 20% and 35% at 6,9 and 12 hours, respectively-... 

Linezolid is not metabolised by the cytochrome P450 enzyme system so the reduction in levels is unlikely to be due to increased metabolism associated with rifampicin enzyme induction. The reduction in linezolid serum levels may be attributable to the induction of P-glycoprotein by rifampicin, resulting in increased excretion of linezolid. ... 

The clinical significance of this interaction is unclear and the concurrent use of rifampicin and linezolid is not established. The available evidence suggests that, where possible, linezolid levels should be monitored if both drugs are given. If this is not possible it would seem prudent to monitor concurrent use closely to ensure that the antibacterial treatment is effective. 

Egle H, Trittler 1 Kummerer K, Lemmen SW. Linezolid and rifampicin drug interaction contrary to expectations CUn Pharmacol Ther (2005) 77,451 -3. 

Legout L, Valette M, Dezeque H, Nguyen S, Lemaire X, Loiez C, Caillaux M, Beltrand E, Dubreuil L, Yazdanpanah Y, Migaud H, Senneville E. Tolerability of prolonged linezolid therapy in bone and joint infection protective effect of rifampicin on the occurrence of anaemia J Antimicrob Chemother 2010 65(10) 2224-30. 

Rifampicin In eight healthy men intravenous rifampicin 600 mg reduced serum linezolid concentrations after a single intravenous dose of 600 mg after 6 hours, the concentration was 90% of expected, after 9 hours, it was 80%, and after 12 hours, it was 65% [166 ]. The authors suggested that this effect might be due to up-regulation of linezolid intestinal secretion. A similar reduction has been seen in a critically ill patient who was receiving linezolid and rifampicin [167 ]. 

The effect of rifampicin on the steady-state pharmacokinetics of linezolid has also been evaluated in an open, multiple-dose, crossover study in 16 healthy subjects [168 J. Rifampicin reduced the AUC of linezolid by 32% and the C ax by 21%, but the t ax and apparent volume of distribution were unaffected. The apparent oral clearance was increased and the half-life shortened. Parallel studies in human hepatocytes showed that rifampicin increased the metabolism of linezolid by about 50% compared with a 19- to 40-fold increase in testosterone metabolism. These increases were about 50% inhibited by ketoconazole. Modelling of these data using Simcyp suggested that rifampicin-induc-ible drug metabolizing enzymes play a very minor role in linezolid clearance. 

Comparative studies In a prospective comparison of a combination of rifampicin and linezolid with a combination of rifampicin and co-trimoxazole in the treatment of bone and joint infections in 56 adults, 36 had infected orthopedic devices and 20 had chronic osteomyelitis [80. Patients who discontinued antibiotic therapy within 4 weeks of starting treatment were considered to be cases of treatment failure and were excluded. The rates of adverse effects were similar in the two groups 43% versus 46% respectively, and led to... 

Nguyen S, Pasquet A, Legout L, Beltrand E, Dubreuil L, Migaud H, Yazdanpanah Y, Senneville E. Efficacy and tolerance of rifampicin-linezolid compared with rifampicin-cotrimoxazole combinations in prolonged oral therapy for bone and joint infections. Clin Microbiol Infect 2009 15(12) 1163-9. 

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