Tooth Discoloration After Treatment with Linezolid

Kelly L. Matson, Pharm.D., Susan E. Miller, Pharm.D.


Pharmacotherapy. 2003;23(5) 

In This Article

Abstract and Introduction

With the increasing frequency of methicillin-resistant Staphylococcus aureus in immunocompromised hosts, clinicians are increasingly prescribing the oral treatment option of linezolid. Linezolid is the first of a new class of antibiotics, the oxazolidinones. The drug is generally well tolerated. However, mild-to-moderate adverse effects have been reported, such as gastrointestinal effects (most frequent), myelosuppression, skin eruptions, elevated liver enzymes, and tongue discoloration. As with any new drug on the commercial market, not all adverse effects are elucidated during preclinical trials. An immunocompromised 11-year-old girl with cellulitis of the toe experienced tooth discoloration after receiving a 28-day course of linezolid. The discoloration was present on the enamel of her lower anterior teeth and was superficial and reversible with dental cleaning.

Over the past 15 years, the number of methicillin-resistant Staphylococcus aureus (MRSA) isolates has increased. In the United States, the frequency of MRSA among hospitalized patients in intensive care units in 1999 was 43% higher than during the period from 1994-1998. Currently, the frequency of MRSA infection among intensive care patients exceeds 50%.[1] In U.S. hospitals, the pathogen was isolated in patients with pneumonia (49.8% of patients) and bloodstream (26.9%), wound (29.0%), and urinary tract (48.0%) infections.[2] In addition, MRSA has spread from the hospital setting to noninstitutional environments; reports of community-acquired MRSA have increased throughout the 1990s, with four deaths occurring in Minnesota and North Dakota.[3,4,5,6,7,8,9]

With the rising occurrence of MRSA, empiric therapy with vancomycin has increased notably. However, the recent emergence of S. aureus strains with reduced susceptibility to vancomycin in the United States and Japan and the isolation of clinical strains of vancomycin-resistant S. aureus in 2002 are alarming.[10,11,12,13,14,15] Specifically, antimicrobial resistance has occurred in patients with skin and soft tissue infections such as cellulitis. Methicillin-resistant S. aureus is the causative organism identified in up to 22% of skin infections.[11] Thus, new antimicrobial agents with enhanced activity against these increasingly resistant pathogens are needed.

Linezolid is the first in a structurally distinctive class of antibiotics, the oxazolidinones. The agents in this class have a novel mechanism of action in that they inhibit bacterial protein synthesis by binding the 50S ribosomal subunit near the interface with the 30S subunit, thereby blocking formation of the 70S initiation complex.[16] Despite rising rates of resistant gram-positive organisms, linezolid has demonstrated activity by overcoming altered penicillin-binding sites of these types of organisms, such as MRSA.[11,12,17] Linezolid was approved in April 2000 for treatment in adults with nosocomial pneumonia, infections due to vancomycin-resistant Enterococcus faecium, complicated and uncomplicated skin and skin structure infections, and community-acquired pneumonia.[18]

Due to its unique mechanism of action, linezolid lacks cross-resistance to other antimicrobial agents. Its bioavailability after oral administration approaches 100%, which allows for ease of conversion from intravenous to oral therapy. In addition, linezolid is generally well tolerated.[11,18,19] However, in adult patients, mild self-limiting adverse effects have been noted, such as diarrhea (8.3% of patients), headache (6.5%), nausea (6.2%), and vomiting (3.7%).[18,20]

In children, recent data indicate that the most frequently reported adverse effects are gastrointestinal (diarrhea, vomiting, and loose stools).[21] Serious treatment-related adverse effects, each occurring in fewer than 1% of pediatric patients, were bronchiolitis, convulsions, neutropenia, and pneumothorax. Additional data from a pediatric pharmacokinetic study indicated that intravenous linezolid was well tolerated.[19] Mild adverse effects reported in six patients consisted of redness or burning at the catheter site (two patients), rash (three patients), and raised papillae on the tongue (one patient).[19]