or orally (100% bioavailability).

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Jones & Bartlett Publishers, Sudbury MA.

. Tsiodras S, Gold HS, Sakoulas G, Eliopoulos GM, Wennersten C, Venkataraman L, Moellering RC, Ferraro MJ. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 2001; 358(9277):207-208.

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Several in vitro and in vivo studies have investigated combination therapy with oxazolidinones against a variety of resistant gram-positive pathogens. Sweeney et al examined the effects of linezolid in combination with 35 antimicrobial agents against various strains of gram positive bacteria using the checkerboard technique of detecting synergy. Against multidrug-resistant and –susceptible strains of S. aureus, S. pneumoniae, E. faecalis, and E. faecium greater than 90% of the antimicrobial combinations with linezolid showed indifference. However, against S. aureus linezolid plus amoxicillin and linezolid plus imipenem was synergistic against MRSA and methicillin-susceptible S. aureus (MSSA), respectively. Against vancomycin-susceptible E. faecalis linezolid plus teicoplanin was synergistic. In addition, linezolid plus imipenem or tetracycline demonstrated synergy against vancomycin-resistant E. faecium. In the case of penicillin-intermediate S. pneumoniae, linezolid also achieved synergy with erythromycin (). Time-kill experiments also have demonstrated synergistic combinations with linezolid. Grohs et al analyzed the effect of linezolid in combination with various antimicrobials against ten strains of S. aureus. Against MRSA and MSSA, no synergy was observed when linezolid was combined with fusidic acid, gentamicin, or rifampin at 4- and 8-fold the MIC. However, when linezolid was combined with vancomycin and ciprofloxacin slight antagonism was observed ().

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Congratulations to the winners of the 2016 Nobel Prize in Chemistry

Prescribing ZYVOX in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

including cases with concurrent bacteremia.

Linezolid is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.

caused by (methicillin-susceptible only) or .

Linezolid is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.

**In case of polymicrobial infection with gram-negative bacteria.

: Some individuals receiving ZYVOX may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Commonly used drugs such as phenylpropanolamine and pseudoephedrine have been specifically studied. Initial doses of adrenergic agents, such as dopamine or epinephrine, should be reduced and titrated to achieve the desired response.

Patients should be advised that:

: Co-administration of linezolid and serotonergic agents was not associated with serotonin syndrome in Phase 1, 2 or 3 studies. Spontaneous reports of serotonin syndrome associated with co-administration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported. Patients who are treated with ZYVOX and concomitant serotonergic agents should be closely observed as described in the Section.

There are no reported drug-laboratory test interactions.

Lifetime studies in animals have not been conducted to evaluate the carcinogenic potential of linezolid. Neither mutagenic nor clastogenic potential was found in a battery of tests including: assays for mutagenicity (Ames bacterial reversion and CHO cell mutation), an in vitro unscheduled DNA synthesis (UDS) assay, an in vitro chromosome aberration assay in human lymphocytes, and an in vivo mouse micronucleus assay.