Vancomycin Dosing and Monitoring PDF

DOSING AND MONITORING OF DRUG 0 LEVELS OF VANCOMYCIN 0 Objectives • • • • To learn Pharmacokinetics of Vancomycin. To know Therapeutic and Toxic Plasma concentrations. To understand its BIOAVAILABILITY(F), volume of distribution, half life, clearance and time of sampling. To learn about its sid...

DOSING AND MONITORING OF DRUG 0 LEVELS OF VANCOMYCIN 0 Objectives • • • • To learn Pharmacokinetics of Vancomycin. To know Therapeutic and Toxic Plasma concentrations. To understand its BIOAVAILABILITY(F), volume of distribution, half life, clearance and time of sampling. To learn about its side effects. 0 VANCOMYCIN Introduction ●Antibiotic with gram-positive spectrum of activity. ● Effective in treatment of Nafcillin or Methicillin resistant Staphylococcus aureus ( NRSA or MRSA). Loading… ● Alternative to penicillin in patients having history of serious penicillin allergy. ● Bactericidal for most gram positive organisms, except against enterococci. ● Synergistic with Gentamicin against most strains 0 of S.aureus and enterococci. ● Not an effective agent for gram-negative bacteria. ● Resurgence because of increased prevalence of Nafcillin - resistant Staphylococcus. ● Used to treat gastrointestinal overgrowths of gram positive bacteria. 0 •● Poorly absorbed orally •●Systemic infections- i.v. route or intraperitoneally for those patients receiving continuous ambulatory peritoneal dialysis. •Doses: Loading… ● Normal renal function: 1g ( 10 to 15 mg/kg) administered intravenously over 60 minutes every 12 hours. In elderly and patients with diminished renal function doses adjusted 0 ● Not given I/M : Painful and causes local irritation and histamine reaction. Therapeutic and Toxic Plasma concentrations Ideal regimen: ●That results in peak plasma concs. that are less than 40 to 50 mg/L and trough concs. in range of 5 to 15 mg/L ● Peak concs greater than 50 mg/L associated with ototoxicity. 0 ●Exhibits conc.- independent killing Specific peak plasma concs have not been correlated with efficacy. MIC for sensitive bacteria< 5 mg/L Limited postantibiotic effect of 0.5 to 3 hours Patients requiring monitoring: Pediatric patients- have high clearances and short half lives Their trough concs are frequently well below 5mg/L 0 Patients with poor renal functionGreater risk of toxicity Side effects : Phlebitis, histamine reaction(flushing, tachycardia, hypotension) Should be infused slowly over 60 min to minimize histamine response. 0 • • • • Single agent : low incidence of nephrotoxicity Combination with aminoglycosides Incidence as high as 30 % Reason not clear 0 BIOAVAILABILITY(F): ● Poorly absorbed after oral administration(<5 %) ● Parenteral or intraperitoneal admin necessary for systemic infections ●Limited oral availability used advantageously to treat enterocolitis. ● Oral vancomycin and metronidazole used to treat Clostridium difficile produced pseudomembranous colitis, clinical condition precipitated by use of broad spectrum antibiotics. -------------------------------------------------------------------------------- 0 Volume of distribution(v): ● 0.5- 1.0 L/kg ( 0.7 L/kg ) . Need No ● Age and gender influence distribution V(L) in adults ( older than 18 years of age) = Loading… 0.17( age in years)+0.22( TBW in kg) + 15 Two or three compartment model best describes distribution. impo In clinical practice, one compartment model to distribution GClarge de Green frequently used. 0 au CLEARANCE (Cl) ● Eliminated primarily by the renal route. ● 5% dose is metabolized. ● Clearance approximates that of creatinine clearance. Cl cr for males (ml/min)=(140-Age)(Weight)/(72)scrss) Cl crfor females (ml/min)=(0.85)× (140-(Age)(Weight) (72)scrss) Vancomycin Cl ~ Cl cr 0 • In patients with hemo or peritoneal dialysis vancomycin loss should be replaced with intermittent i.v. injections.on frequent basis. • Or instill directly into the peritoneal space. 0 Half life ● 5 to 10 hours ● In patients with end stage renal disease half life may approach 7 days. ● Patients with normal renal function Receive drug every 8 to 12 hours End stage renal disease Receive dose once a week 0 • • • • • • TIME TO SAMPLE Wide fluctuation suggests monitoring of both peak and trough concn. Steady state trough concs appear to be adequate in most cases. General rule: Dosed with an interval of approx.one half life. For very overweight or underweight patients monitoring both peak and trough concs is advisable, particularly for seriously – ill patients. 0 • Follows multicompartment model • Difficult to avoid distribution phase when obtaining peak plasma concs. • If peak levels are to be measured, samples should be obtained at least 1 or possibly 2 imp hours after the end of infusion period. 0 Conclusion • • • • • Effective in treatment of Nafcillin or Methicillin - resistant Staphylococcus aureus ( NRSA or MRSA Poorly absorbed orally Not given I/M : Painful and causes local irritation and histamine reaction Half life 5 to 10 hours Steady state trough concs appear to be adequate in most cases. 0 Learning outcomes • At the end of the chapter the students will be able to : • Understand the use of antibiotics in MRSA cases. • Learn the Pharmacokinetic parameters of Vancomycin and know when to sample the drug based on its bioavailability, clearance etc. 0