Linezolid


Article Author:
Angela Azzouz


Article Editor:
Charles Preuss


Editors In Chief:
James Beauchamp
Mark Pellegrini
Nicole Hale-Crutch


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
3/17/2019 2:25:45 PM

Indications

Linezolid is a synthetic oxazolidinone antimicrobial drug. It is indicated for gram-positive infections and approved for the treatment of bacterial pneumonia, skin and skin structure infections and vancomycin-resistant enterococcal (VRE) infections, including infections complicated by bacteremia. Linezolid does not have approval for the treatment of gram-negative infections, catheter-related bloodstream infections, or catheter site infections. 

Linezolid’s primary place in therapy is as an alternative to vancomycin in inpatient settings. Vancomycin remains a standard treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. However, vancomycin-resistant isolates of Saureus have emerged, and there are increasing reports of vancomycin-resistant isolates worldwide. Alternative treatment agents merit consideration prior to using linezolid in outpatient settings as inappropriate use has led to an increase in linezolid-resistant VRE (vancomycin-resistant enterococci).[1]

Linezolid has activity against a broad range of antibiotic susceptible and resistant gram-positive bacteria, including activity against MRSA with intermediate resistance to glycopeptides like vancomycin.  

Linezolid is a recommended empirical therapy option for MRSA in hospitalized adult patients with complicated skin and soft tissue infection, for community-associated MRSA skin and soft tissue infection, and MRSA associated purulent and non-purulent cellulitis; linezolid is an alternative option for MRSA in hospitalized pediatric patients.

Non-FDA uses include anthrax, bone and joint infections, brain abscess, febrile neutropenia, infectious arthritis, meningitis, orthopedic device-related infection, osteomyelitis, sepsis, subdural empyema, and ventriculitis.

Linezolid has demonstrated activity against most strains of the following microorganisms: Enterococcus faecalis, Enterococcus faecium, Pasteurella multocida, Staphylococcus aureus (MRSA and MSSA, i.e., methicillin-sensitive), Staphylococcus epidermidisStaphylococcus haemolyticusStreptococcus agalactiae (group B streptococci), Streptococcus pneumonia, Streptococcus pyogenes (group A beta-hemolytic streptococci), and viridians group streptococci (S. mutans, S. salivarius, S. anginosus, S. mitis, S. sanguinis, and S. bovis)[2][2][3]

Mechanism of Action

Linezolid is the first available oxazolidinone to inhibit bacterial protein synthesis by interfering with translation. Linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit, which prevents the formation of a functional 70S initiation complex.[4] This activity essentially inhibits protein production and prevents bacteria from multiplying. 

Linezolid is bacteriocidal against the majority of streptococcal strains and bacteriostatic against staphylococci and enterococci; this makes linezolid a poor option for immunosuppressed patients.

Linezolid is also a reversible, non-selective monoamine oxidase (MAO) inhibitor.[5] Monoamine oxidase inhibition leads to an increased concentration of the neurotransmitters epinephrine, norepinephrine, dopamine and serotonin in the central nervous system and sympathetic nervous system. Inhibition may also lead to desensitization of alpha- and beta-adrenergic and serotonin receptors. In the GI tract and liver, inhibition of MAO can result in systemic absorption of large amounts of tyramine from the diet and potentially cause life-threatening hypertension. 

Administration

Linezolid is available in tablet, suspension, and injection. The dosage of IV and tablet formulations are interchangeable; there is no need to make dose adjustments. Renal dosing is not required. Invert gently to mix before administration; do not vigorously shake oral suspension. Administer without regard to meals; food delays the rate, but not the extent of oral absorption.

Administer linezolid intravenous infusion over 30 to 120 minutes. Do not mix or infuse with other medications.  When using the same IV line for sequential infusion, flush the line with D5W, NS, or LR before and after infusing linezolid. The yellow color of the injection may intensify with time without affecting potency.

Therapeutic doses vary by indication. The recommended dose is between 400 and 600 mg IV or orally every 12 hours for 10 to 28 days depending on the indication.

Absorption is rapid and extensive. Linezolid has excellent tissue penetration into the lungs and CNS and exhibits 100 percent oral bioavailability.[6]

Linezolid use may result in a suboptimal clinical response when treating organisms with a MIC (minimum inhibitory concentration) of 4 mcg/ml or greater and warrants a complete ID re-assessment and change in drug therapy.

Adverse Effects

Most common side effects experienced while taking linezolid include decreased platelets, hemoglobin, and white blood cell counts, headache, nausea, diarrhea, elevated pancreatic enzymes, elevated LFT’s, and neuropathy.[7][8]

Warnings associated with linezolid include duration-related myelosuppression (thrombocytopenia, anemia, leukopenia), serotonin syndrome, hypoglycemia; caution in patients on insulin or hypoglycemic drugs, seizures, lactic acidosis, hypertension when used with adrenergic drugs, and irreversible peripheral and optic neuropathy when used for 28 days or greater; however, reports exist of these events (i.e., blurred vision) in patients receiving shorter courses of linezolid. Prolonged use may result in fungal or bacterial infection, including Clostridium difficile-associated diarrhea and pseudomembranous colitis; observations of C. difficile-associated diarrhea also may occur greater than two months of postantibiotic treatment.

Lactic acidosis may also occur with use; evaluate patients who develop recurrent nausea and vomiting, unexplained acidosis, or low bicarbonate concentrations.

Contraindications

  • Do not use within two weeks of MAO inhibitors, e.g., phenelzine.
  • Avoid tyramine-containing foods and serotonergic drugs; may precipitate hypertensive crisis. Examples of tyramine-containing foods include aged cheese, cured or smoked meats, draft beer, fava beans, and soy products. 
  • Use caution with serotonergic and adrenergic drugs, e.g., imipramine.

Monitoring

Monitoring parameters include heart rate, blood pressure, blood glucose, weekly CBC, and visual function. Blood pressure requires close monitoring in patients with untreated hyperthyroidism. Patients with disease-related concerns such as diabetes mellitus, hypertension, hyperthyroidism, pheochromocytoma, and carcinoid syndrome should also be monitored closely.

Toxicity

Toxicity is rare, and there is no antidote for linezolid. Symptomatic and supportive treatment is the recommendation for management of mild to severe toxicity.

For severe neutropenia, administer colony-stimulating factors such as filgrastim or sargramostim. Filgrastim 5 mcg/kg/day SQ or IV over 15 to 30 minutes, or sargramostim 250 mcg/meter (2)/day IV over 4 hours. Transfusion of platelets, packed red cells, or both may be necessary for patients with severe thrombocytopenia, anemia, or hemorrhage.

Transfusions are given as needed for severe thrombocytopenia, bleeding. For seizures, administer IV benzodiazepines; barbiturates or propofol may be an option if seizures persist or recur. Airway management may be necessary for patients with severe seizures. The primary treatment for serotonin syndrome is sedation with IV benzodiazepines, and cooling measures; cyproheptadine is an option for milder cases. Activated charcoal is a consideration in patients who are alert and airway protected with a recent overdose of linezolid tablets and co-ingested potentially dangerous medications, e.g., tricyclic antidepressants. 

Monitoring is necessary for vital signs and liver enzymes in symptomatic patients; additionally, monitor serial CBC (with differential) and platelet count. Reports exist of myelosuppression, including anemia, pancytopenia, leukopenia, and thrombocytopenia in patients receiving linezolid. Monitoring of serum electrolyte status is indicated for patients with significant diarrhea and/or vomiting — monitor for clinical evidence of serotonin syndrome.

Enhancing Healthcare Team Outcomes

The healthcare team, e.g.,  physicians, nurses and pharmacists need to work together to ensure that the patient correctly takes linezolid and that the patient monitors for adverse drug reactions. Educate the patient about signs of significant adverse drug reactions, e.g., wheezing, chest tightness, seizures, swelling of the face, lips, tongue, or throat and severe diarrhea, etc. Encourage the patient to consult the healthcare team for questions about linezolid treatment. To prevent empirical prescription of linezolid, most hospitals have a committee that includes a pharmacist and an infectious disease expert who must first permit the use of the drug.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Linezolid - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following antibiotics is NOT monitored by either peak or trough measurements of serum concentrations?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a contraindication for the antibiotic Zyvox?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is the brand name for the antibiotic linezolid?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 41-year-old woman presents with septicemia during recovering from surgery for two broken femurs because of a serious skiing accident. The provider empirically decides to treat the patient with linezolid. Which of the following is linezolid most clinically active against?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Linezolid - References

References

Perry CM,Jarvis B, Linezolid: a review of its use in the management of serious gram-positive infections. Drugs. 2001     [PubMed]
Hamel JC,Stapert D,Moerman JK,Ford CW, Linezolid, critical characteristics Infection. 2000 Jan     [PubMed]
Dresser LD,Rybak MJ, The pharmacologic and bacteriologic properties of oxazolidinones, a new class of synthetic antimicrobials. Pharmacotherapy. 1998 May-Jun     [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pharmacy-Technician (PTCB). The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pharmacy-Technician (PTCB), it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pharmacy-Technician (PTCB), you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pharmacy-Technician (PTCB). When it is time for the Pharmacy-Technician (PTCB) board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pharmacy-Technician (PTCB).