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tigecycline (Tygacil)

Tradename: Tygacil (expensive broad spectrum antibiotic) Indications: - bacterial infections due to susceptible organisms - complicated intra-abdominal infections - appendicitis - intra-abdominal abscess - bacterial peritonitis [9] - not MRSA - complicated skin infections, including MRSA - hospitalized patients with community-acquired pneumonia - refractory C-difficile colitis ? [4] Contraindications: - nosocomial pneumonia [7] * should be used only when other treatments are not available Dosage: 1) IV infusion over 30-60 minutes 2) 100 mg loading dose, then 3) 50 mg every 12 hours for 5-14 days Injection: 10 mg/mL Dosage adjustment with heptatic insufficiency - Child-Pugh class 3, decrease to 25 mg every 12 hours Antibiotic activity: Gram positive organisms - many, including MRSA (skin) Staphylococcus, Streptococcus, Enterococcus faecalis Gram-negative organisms - Citrobacter, Escherichia, Klebsiella, Enterobacter - Haemophilus influenza - Legionella pneumophila - Acinetobacter baumannii - NOT very effective against Pseudomonas Anaerobes - Bacteroides, Clostridium, Peptostreptococcus Adverse effects: 1) nausea/vomiting, diarrhea, abdominal pain 2) fever, headache, hypertension 3) thrombocythemia, anemia 4) hypoproteinemia 5) increase mortality when used to treat a) hospital-acquired pneumonia, especially ventilator associated pneumonia b) complicated skin infections c) complicated intra-abdominal infections d) diabetic foot infections [5,6] 6) increased risk of death when used for FDA-approved uses as well as for non-approved uses [8] * Black box warning for increased risk of death; use only when alternatives are not available [7] Drug interactions: 1) decreased effectiveness of oral contraceptives 2) monitor PT with warfarin [2] Interactions: 1) increased serum transaminases 2) increased serum lactate dehydrogenase Mechanism of action: 1) similar to tetracyclines, glycylcycline antibiotic 2) inhibits protein translation in bacteria by binding to the bacterial 30S ribosomal subunit 3) not affected by 2 major tetracycline resistance mechanisms a) ribosomal protection b) efflux

Interactions

drug interactions

General

glycylcycline

Properties

MISC-INFO: pregnancy-category D

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 12(7): 2005 New Drug: Tygacil (Tigecycline) Detail-Document#: 210711 (subscription needed) http://www.prescribersletter.com
  2. PDR Monthly Prescribing Guide, August 2005, pg 11
  3. Prescriber's Letter 16(7): 2009 Tigecycline (Tygacil) for Community-Acquired Pneumonia (CAP) Detail-Document#: 250521 (subscription needed) http://www.prescribersletter.com
  4. Herpers BL et al Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection. Clin Infect Dis 2009 Jun 15; 48:1732. PMID: 19435431
  5. FDA MedWatch Tygacil (tigecycline): Label Change - Increased Mortality Risk Posted 09/01/2010 http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm224626.htm
  6. Prasad P et al. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis 2012 Jun 15; 54:1699 PMID: 22467668 - Powers JH. Asking the right questions: Morbidity, mortality, and measuring what's important in unbiased evaluations of antimicrobials. Clin Infect Dis 2012 Jun 15; 54:1710. PMID: 22467671
  7. Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015
  8. FDA MedWatch. September 27, 2013 Tygacil (tigecycline): Drug Safety Communication - Increased Risk of Death. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm370170.htm
  9. Deprecated Reference
  10. Bai XR, Jiang DC, Yan SY. High-Dose Tigecycline in Elderly Patients with Pneumonia Due to Multidrug-Resistant Acinetobacter baumannii in Intensive Care Unit. Infect Drug Resist. 2020;13:1447-1454. PMID: 32547113 Free PMC article