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vancomycin (Vancocin)

Tradename: Vancocin. Indications: - treatment of serious gram positive bacterial infections for which penicillins & cephalosporins are NOT effective* - treatment of gram positive bacterial infections in patients with serious allergies to penicillins & cephalosporins - gastrointestinal infection - C difficile colitis treatment that has failed proper metronidazole therapy - empiric treatment of febrile neutropenia [16] - empiric treatment for fever of unknown origin [16] - endocarditis - prophylaxis for endocarditis - prophylaxis for perioperative infection - procedures involving prosthetic devices/materials at institutions with a high rate of MRSA - myocarditis [16] - infectious arthritis, osteomyelitis [16] - anthrax, cutaneous anthrax [16] - brain abscess [16] * vancomycin inferior to penicillins & cephalosporins when antibiotic sensitivity not at issue [11] Dosage: 1) adults: a) 500 mg IV every 6 hours each dose over 1 hour, or b) 1 g IV every 12 hours 2) children & infants (> 1 month) 1) 40 mg/kg/day divided every 6 hours 2) 60 mg/kg/day divided every 6 hours (CNS Staphylococcus) 3) intrathecal a) adults: 20 mg/day b) children: 5-20 mg/day c) neonates: 5-10 mg/day 4) Clostridium difficile: b) 125 mg PO QID as effective as 250 mg QID [3,9] c) 6 days for resolution of diarrhea [9] 5) post-operative infections a) single dose prior to surgery b) may be repeated if surgery > 6 hours c) 2 dose max Tabs: 125 & 250 mg. Powder for oral solution: 10 g. Powder for injection: 500 mg, 1 g. Injectable vancomycin can be given orally [10] Dose adjustment in renal failure: creatinine clearance dose > 60 mL/min 1 g every 12 hours 40-59 mL/min 1.0-1.5 g every 24 hour 20-39 mL/min 1.0 g every 24 hours 10-19 mL/min 1 g every 36-48 hours < 9 mL/min 0.5-1.0 g with serial trough levels hemodialysis dose after dialysis, trough 15-20 ug/mL Monitor: Therapeutic drug monitoring: indicated - see vancomycin in serum/plasma Pharmacokinetics: 1) oral form is not absorbed 2) widely distributed 3) CSF penetration is poor 4) 80% is eliminated unchanged in the urine 5) 1/2life is 4-6 hours (200-250 hours ESRD) 6) dose adjustment with renal insufficiency 7) therapeutic range: a) peak: 20-40 ug/mL (not recommended) b) trough: 1] < 12 ug/mL; up to 15 ug/mL with serious infections 2] drawn just prior to 3rd or 4th dose 3] for creatinine clearance < 9 mL/min draw at 24, 48, 72 hour intervals Antimicrobial activity: Gram positive - Streptococcus - Streptococcus group A - Streptococcus group B - Streptococcus group C - Streptococcus group G - Streptococcus pneumonia - Enterococcus faecalis - Enterococcus faecium (+/-) - Staphylococcus aureus (MSSA) - Staphylococcus aureus (MRSA) - Staphylococcus epidermidis Gram negative - Neisseria gonorrhoeae (+/-) Anaerobes - Actinomyces - Clostridium difficile (+/-) - Clostridium species Adverse effects: 1) common (> 10%) a) bitter taste, nausea/vomiting (oral) b) "red man" syndrome (parenteral) - hypotension - flushing - erythematous rash on face & upper body - diminished by - increasing infusion time (up to 90 min) - diphenhydramine (Benadryl) 2) less common (1-10%) - fever/chills - eosinophilia - acute renal failure [7] - acute tubular necrosis* [15] 3) uncommon (< 1%) - ototoxicity, interstitial nephritis*, vasculitis, immune thrombocytopenia [12] - unlikely to develop within 5 days of hospital discharge [23] - drug-induced thrombocytopenia [20] 4) other - phlebitis - pruritus - neutropenia - DRESS [18] * more likely to cause acute tubular necrosis than acute interstitial nephritis [22] Drug interactions: - levels may be increased when given with aminoglycosides - increased nephrotoxicity when used in combination with piperacillin tazobactam (Zosyn) [19] Laboratory: 1) specimen: serum, plasma (EDTA, heparin) 2) methods: RIA, HPLC, MB, FPIA, FIA 3) see vancomycin in serum or plasma 4) vancomycin resistance gene Mechanism of action: 1) concentration independent 2) bactericidal 3) binds to bacterial cell walls causing blockage of glycopeptide polymerization at a different site than that of penicillins

Interactions

drug interactions

Related

antibiotic prophylaxis for bacterial endocarditis vancomycin in serum/plasma vancomycin resistant enterococcus (VRS)

General

antibacterial glycopeptide

Properties

MOTIF: glycosylation site MISC-INFO: elimination route KIDNEY 1/2life 4.7-7.8 HOURS therapeutic-range 20-40 UG/ML 5-10 UG/ML toxic-range >80 UG/ML protein-binding 55% elimination by hemodialysis - peritoneal dialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

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  6. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  7. Bamgbola O. Review of vancomycin-induced renal toxicity: an update. Ther Adv Endocrinol Metab. 2016 Jun;7(3):136-47. Review. PMID: 27293542 Free PMC Article
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  10. Prescriber's Letter 13(10): 2006 Alternative or 'Off-label' Routes of Drug Administration Detail-Document#: 221012 (subscription needed) http://www.prescribersletter.com
  11. Stryjewski ME et al Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin- susceptible Staphylococcus aureus bacteremia. Clin Infect Dis. 2007 Jan 15;44(2):190-6. Epub 2006 Dec 8. PMID: 17173215
  12. Von Drygalski A, Curtis BR, Bougie DW, McFarland JG, Ahl S, Limbu I, Baker KR, Aster RH. Vancomycin-induced immune thrombocytopenia. N Engl J Med. 2007 Mar 1;356(9):904-10. PMID: 17329697 - Warkentin TE. Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis. N Engl J Med. 2007 Mar 1;356(9):891-3. No abstract available. PMID: 17329695
  13. Prescriber's Letter 16(2): 2008 Vancomycin Dosing and Monitoring in Adults Detail-Document#: 250215 (subscription needed) http://www.prescribersletter.com
  14. Kullar R et al. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: Support for consensus guidelines suggested targets. Clin Infect Dis 2011 Apr 15; 52:975 PMID: 21460309 - Patel N et al. Vancomycin: We can't get there from here. Clin Infect Dis 2011 Apr 15; 52:969. PMID: 21460308
  15. Shah-Khan F, Scheetz MH, Ghossein C. Biopsy-Proven Acute Tubular Necrosis due to Vancomycin Toxicity. Int J Nephrol. 2011;2011:436856 PMID: 21716699 - Belen C, Budhiraja P, Bracamonte E, Popovtzer M. Biopsy-proven acute tubular necrosis associated with vancomycin in an adult patient. Ren Fail. 2012;34(4):502-5 PMID: 22329801
  16. Deprecated Reference
  17. van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013 Feb;57(2):734-44. Review. PMID: 23165462 Free PMC Article
  18. Blumenthal KG et al. Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics. J Allergy Clin Immunol 2015 Nov; 136:1288. PMID: 25981739
  19. Rutter WC et al. Acute kidney injury in patients treated with vancomycin and piperacillin-tazobactam: A retrospective cohort analysis. J Hosp Med 2017 Feb; 12:77 PMID: 28182801 http://www.journalofhospitalmedicine.com/jhospmed/article/130044/hospital-medicine/acute-kidney-injury-patients-treated-vancomycin-and - Luther MK, Timbrook TT, Caffrey AR et al Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis. Crit Care Med. 2018 Jan;46(1):12-20. Review. PMID: 29088001
  20. NEJM Knowledge+ Question of the Week. Jan 12, 2021 https://knowledgeplus.nejm.org/question-of-week/1082/
  21. Alvarez-Arango S, Ogunwole M, Sequist TD et al Vancomycin Infusion Reaction - Moving beyond "Red Man Syndrome". N Engl J Med. 2021. April 3. PMID: 33830710 https://www.nejm.org/doi/full/10.1056/NEJMp2031891
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