The Drug Monitor
Please read the Disclaimer
 

Antiinfectives

General Rx

Renal Rx

Transplant Rx

Pkinetics

Educational

KidneyWorks

Clinical Tools

 

Vancomycin

What is vancomycinAppropriate UsesInappropriate Uses
PK parametersDoseDosing interval
HD patientsPediatric patientsAdverse drug reactions
 References 

For the PDF Version click here

Due to the emergence of resistant organisms such as VRE, vancomycin is now a "restricted antibiotic".  Its use in most hospitals requires the approval of the Infectious Disease Unit.
Vancomycin is a relatively small glycoprotein (MWt @ 1,450) derived from Nocardia Orientalis (formerly known as Streptomyces Orientalis). Vancomycin is active against most G(+) bacteria including Streptococci, Corynebacteria, Clostridia, Listeria, and Bacillus species. It is bactericidal to most susceptible G(+) bacteria at levels 0.5 - 3 mg/L. Staphylococci including ß-lactamase producing and methicillin resistant species are killed at levels <10 mg/L. Resistant mutants are very rare, except for vancomycin resistant enterococcus (VRE). Vancomycin kills bacteria mainly by inhibiting bacterial cell wall synthesis. However, it also damages the bacterial cell membrane and interferes with bacterial RNA synthesis.   No significant post-antibiotic effect (PAE)(click here for definition) has been observed for vancomycin and any of the susceptible organisms. 
To treat systemic infections, vancomycin must be given intravenously. The intramuscular route is not used because of the possibility of tissue necrosis.
When given orally, vancomycin is not absorbed. Oral vancomycin is used only for the treatment of antibiotic-induced pseudomembranous colitis, which is caused by a toxin produced by Clostridium Difficile, a spore-forming, G(+) obligate anaerobic bacillus. 
"C dif " is treated with vancomycin (125 - 250 mg po qid x 10 - 14 days) or metronidazole (250 - 500 mg po tid x 14 days)

Appropriate Indications
For the Intravenous Use of Vancomycin
I. First-Line Therapy
  1. Proven methicillin-resistant (MR) Staph aureus (S.A.) or coagulase-negative Staph (cnS )
  2. Serious infections where cnS is highly suspected (e.g., central line, prosthesis, sternotomy, etc).
  3. Endocarditis caused by MR Staph [plus gentamicin and rifampin for prosthetic valve endocarditis caused by cnS ].
  4. Meningitis caused by flavobacteria or PCN-resistant pneumococcus (plus cefotaxime)
  5. CNS shunt infection caused by methicillin resistant Staph (+ rifampin)
  6. Infections caused by organisms susceptible only to vancomycin (e.g., Corynebacterium jeikium)
  7. Ampicillin-resistant enterococcal infections.
  8. Prophylaxis for major surgical procedures for implantation of prosthetic materials or devices at hospitals with a high rate of infections due to MR Staph. A single dose administered immediately before surgery is sufficient unless the procedure lasts more than 6 hours, in which case the dose should be repeated. Prophylaxis should be discontinued after a maximum of two doses.
II- In pts with true ß-lactam allergy
    as alternative therapy for the treatment of
  1. Endocarditis caused by diphtheroids, Staph A, cnS, Strep bovis or Strep viridans, or Enterococcus (+ gentamicin).
  2. Meningitis and CNS shunt infections caused by diphtheroids or G(+) cocci.
  3. Severe infections caused by G(+) cocci.
    For moderate and mild infections, co-trimoxazole (Bactrim®) or erythromycin may be used.

Inappropriate Use of Vancomycin
    Avoid using vancomycin for:
  1. Routine surgical prophylaxis other than in a patient with life-threatening allergy to ß-lactam antibiotics.
  2. Systemic or local prophylaxis for infection or colonization of indwelling central or peripheral intravascular catheters.
  3. Empiric therapy for febrile neutropenia unless there is strong evidence that the patient has an infection due to gram-positive microorganisms, and the prevalence of MRSA in the hospital is substantial.
  4. Treatment in response to a single blood culture positive for coagulase-negative staphylococci if other blood cultures drawn at the same time frame are negative, indicating likely contamination of the specimen.
  5. Continued empiric use for presumed infections in patients whose cultures are negative for ß-lactamase-resistant G(+) microorganisms.
  6. Selective decontamination of the gastrointestinal tract.
  7. Eradication of MRSA colonization
  8. Routine prophylaxis of very-low-birth-weight infants
  9. Routine prophylaxis for patients on continuous ambulatory peritoneal dialysis or hemodialysis.
  10. Treatment (chosen for dosing convenience) of infections due to ß-sensitive G(+) microorganisms.
  11. Use of vancomycin solution for topical application or irrigation
  12. Primary treatment of antibiotic-associated colitis (vancomycin should be used only when organism is resistant to metronidazole).

Pharmacokinetic Parameters
Vd @ 0.7 L/kgProtein binding @ 55%
Elimination: > 90% renal Ke @ 0.00083 CLcr + 0.0044
Half-life @ 7 hrs (with normal CLcr) Vancomycin is not removed by standard HD or PD, but it is removed by CVVH

 

Dosing and Monitoring Guidelines
Initial dose @ 15 mg/kg  (actual body weight)
For adult patients, the dose should be rounded off to the nearest 250 mg increment (e.g., 500, 750, 1000, 1250, 1500, 2000, etc.)
The dose is diluted in D5W (max conc. = 5 mg/mL) and infused over at least 1 hr. The infusion rate must be reduced if the patient experiences "red man syndrome" See adverse reactions below
 

Dosing interval
The initial dosing interval is determined by the target vancomycin trough and the creatinine clearance (CLcr) which may be estimated by using either the Cockroft (for most pts) or the Sanaka equations (for elderly pts with muscle atrophy)
 
CLcr, mL/min³ 70 40 - 69 30 - 39 20 - 29 <20
Dosing interval, hrs12 24 48 72 see below
  • The dosing interval is adjusted to achieve and maintain a target trough level between 8 and 20 mg/L depending on the severity and location of the infection (the higher targets may be necessary for the treatment of CNS and bone infections). If necessary, the dosing interval may be as short as q6h. Continuous vancomycin infusion has been used successfully in special cases (see references below).
  • If the trough is < 8 mg/L, the dosing interval is shorten by one step (e.g., from 12 hr to 8 hr or from 24 hr to 12 hr, etc)
  • If the trough is >20 extend the dosing interval by one step.
  • "Peak" levels are usually kept at < 45 mg/L. However, monitoring vancomycin peaks has little or no clinical value and most centers have abandoned this practice.

Hemodialysis Patients
  • Hemodialyzed pts may be dosed at 15-20 mg/kg. A level is then taken 2-3 hrs after the next hemodialysis. Dosage will have to be individualized according to the level obtained and the severity of infection.
  • Because the commonly used assays (EMIT or FPIA) do not differentiate between vancomycin and its metabolites, the reported vancomycin level in HD patients may be falsely elevated (by 10 to 40% ). A trough level of 15 - 25 mg/L may be more appropriate in these patients.
  • Most patients will require dosing every other dialysis.
  • Peritoneal Dialysis
    • Give 15-20 mg/kg
    • Repeat dose once every ~ 7 days.
  • Oliguric / Anuric ARF Patients Who Are Not on Dialysis Yet:
    • Give 15-20 mg/kg. 
    • Draw a random levels every 2-3 days, and re-dose if level < 10 mg/L.
  • Oliguric / Anuric ARF Patients on continuous venovenous hemofiltration (CVVC):
    • Give a loading dose of 15 mg/kg   followed by 10 mg/kg q24h
    • Monitor trough level; should be maintained > 8 mg/L.

Pediatric Dosage
In pediatric pts, vancomycin must be used only to treat severe infections. Consult your Pediatric Pharmacist
    • Infants < one wk old: 30 mg/kg/day (q12 hrs)
    • Infants 1 - 4 wks: 30 - 42 mg/kg/day (q 8 hrs)
    • Infants more than one month and children
      the initial dosage is 10 mg/kg every 6 hrs.

Adverse Drug Reactions
The side effects of iv vancomycin include a histamine-mediated erythematous flushing of the face, neck and trunk, a reaction which occurs during the infusion, and may be associated with hypotension. Nephrotoxicity and ototoxicity may occur in < 1% of pts especially those receiving other "toxic' drugs like aminoglycosides. A relationship between vancomycin level and nephrotoxicity or ototoxicity has not been established. It is now widely believed that the ealier reports of nephrotoxicity may have been related to impurities in the product.
The other side effects (neutropenia, thrombocytopenia, and hypersensitivity) are very rare.

References
  1. Wilhelm MP, Estes L. Symposium on antimicrobial agents--Part XII. Vancomycin. Mayo Clin Proc. 1999;74(9):928-35
  2. Basic Clinical Pharmacokinetics Handbook by White and Garrison; '94
  3. Rational vancomycin use recommendations. Conn Med. '95; 59(2):87-90
  4. Why monitor peak vancomycin concentration. Lance '94; 344:8939-40.
  5. Comparison of conventional dosing versus continuous infusion vancomycin therapy ... Antimicrobial Agent & Chemotherapy '96; 40(3):696-700
  6. Continuous administration of vancomycin in patients with severe burns. Press Medicale '94; 23(34): 1554-58.
  7. Vancomycin Pharmacokinetics in .....Ther Drug Monitor. '94; 16(5): 513-518.
  8. Trough serum vancomycin levels predict the relapse of Gram(+) peritonitis in peritoneal dialysis patients. Am J Kidney Dis, '95; 25(4): 611-15.
  9. Methicillin-resistant Staphylococus aureus and vancomycin-resistant Enterococci: therapeutic realities and possibilities. Lancet '97; 349:1901-06
  10. Vancomycin-resistant Enterococci. Am J Med '97; 101: 284-293.
  11. Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR 1995;44(No. RR-12):1-13.
  12. Evans ME, Kortas KJ. Vancomycin use in a university medical center: comparison with Hospital Infection Control Practices Advisory Committeeguidelines. Infect Control Hosp Epidemiol 1996;17:356-359.
  13. Vancomycin and teicoplanin. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 4th ed. New York, NY: Churchill Livingstone; 1995:346-354).

 

theDrugMonitor | Nephrosite | Feedback

 

Copyrights ® 1997-2002 the Drug Monitor