Vancomycin

What is AUIC?

**AUIC = AUC/MIC Correlates with vancomycin's ability to kill the bacteria

What is the MIC of "susceptible" MRSA?

0.5-2 g/ml MRSA with MIC > 1 may be clinically difficult to treat NOTE: These values only pertain to staph a.**

How is the distribution of vancomycin?

0.7L/kg = HIGH Vd

What is our trough goal for uncomplicated infections; easy to penetrate?

10-20 mg/L** FOR THE FOLLOWING: Cellulitis Uncomplicated UTI Bacteremia with coagulase negative Staphylococcus

What is our trough goal for serious infections, difficult to penetrate or MIC >1?

15-20 mg/L** FOR THE FOLLOWING: Pneumonia Osteomylitis Sepsis Other bacteremia

What is the range of vancomycin penetration in the lungs?

16-40%

What is the max single dose that most hospital set vancomycin at?

2 grams/single dose max

What is our trough goal for very difficult to penetrate sites or bordering resistance?

20 mg/L or higher** FOR THE FOLLOWING: Meningitis Endocarditis Non-urinary Staphylococcus aureus MIC > 2

AUC/MIC of what value is associated with vancomycin therapeutic success?

>400

What is significant regarding vancomycin's excretion?

Administered orally: Primarily feces Administered I.V.: Urine (~ 90% unchanged) Concentrations significantly affected by renal disease: will have to give at lower doses / less frequency for AKI etc.

What can PO vancomycin be used for?

C. diff

What is the purpose of using loading doses with vancomycin?

Consider 25-30 mg/kg loading dose to rapidly attain steady state, especially for those with serious infections (hypotensive) or severe pneumonia (poor renal functions) *May cap loading dose

How do we dose vancomycin?

Determined by ABW However, do not exceed 2 grams In these cases, use dosing weight** Starting dose for patients with normal renal function: 15mg/kg q12h

Which patients are most likely to benefit from vancomycin TDM?

Difficult to penetrate sites of infection -Pneumonia -Meningitis -Endocarditis -Osteomylitis Organisms with high MIC (> 1) Rapid elimination, at risk for accumulation, predisposed to ADRs

At what time should we draw troughs?

Ensure level drawn at steady state (usually before 4th dose) *3-4 half lives Trough should be < 1 hour of time for next dose due *Level may be higher if taken incorrectly

True or False; Vancomycin can easily diffuse into the CNS

False; Vancomycin doesn't penetrate CNS well even in inflammation settings (more porous membranes); must target higher troughs

How do we determine the frequency internal for vancomycin dosing?

Frequency is determined CrCl Trough goals: 10-20 Interval is usually between 1-2 half- lives Typically: q8-12 (normal renal function) Sometimes q6, q24h, q48h *Q24H - MILD *Q48H - SEVERE *Renal issues BE SURE TO ROUND dose to nearest 250 mg increment

Vancomycin can be used with which drug for synergy against S. aureus and Enterococcus sp.?

Gentamicin! Do not use genta alone for this, only in combination

What is the MOA of vancomycin + its spectrum?

Glycopeptide antibiotic with excellent gram positive activity and no gram negative activity** Bacteriocidal for gram positive organisms except Enterococcus (vancomycin is bacteriostatic @entero**)

When would we administer higher or more frequent doses of vancomycin?

Infections outside the blood and urine (lung, CNS, bone) *Higher trough goals in order to ensure vanco gets into these harder to penetrate sites MRSA with MIC > 1 Rapid renal elimination (augmented renal clearance) e.g., trauma, sepsis, burns

What is step 9 of the CDC step program to prevent bacterial resistance?

Know when to say "NO" to vanco - Treat infection, not contaminants or colonization - Fever in a patient with an IV catheter is not an indication for vancomycin; do NOT treat for fevers even if a line is involved as the line can be removed **Use vanco for ONLY for the treatment of systemic infections

Define MIC

Minimum (inhibitory) concentration we have to achieve at the site of action of vancomycin in order for vanco to work Higher MIC: needs higher concentration, more resistant Lower MIC: lower concentration; more susceptible

What is the trend between inflammation and penetration when it comes to vancomycin?

More inflammation = better penetration

True or false; We should always draw peaks

NO peaks; peaks do not correlate with toxicity

What is the half life of vancomycin?

Newborns: 6-10 hours Infants and Children >3 years: 2.2-4 hours Adults: 5-11 hours; significantly prolonged with renal impairment End-stage renal disease: 200-250 hours**

What is important to consider when dosing in dialysis?

Peritoneal dialysis -- minimally cleared **Give intraperitoneally or redose q 3-5 days Hemodialysis Can check levels checked 3-5 days post dose Can dose by level taken before or after hemodialysis; take a pre-dialysis level in order to decide whether or not to redose* Must allow for redistribution after HD wait 2 hours after HD to check blood concentration

How is the oral bioavailability of vancomycin?

Poor <5% Stays in the GI tract; good if the infection is local in the GI

When would we administer lower or less frequent doses of vancomycin?

Poor renal function Uncomplicated infections

What is significant regarding ototoxicity?

Rare; associated with peaks >80 mg/L but risk increases if used with aminoglycosides

What is significant regarding thrombocytopenia?

Rare; trough and cumulative-dose related

What are the most important adverse effects from vancomycin?

Red man syndrome Nephrotoxicity Otoxtoxicity Thrombocytopenia

How should we adjust doses?

Refer to slides! Try to adjust frequency not dose, when possible *shortening the frequency allows for additional accumulation of drug + will improve PD goal attainment

When should we draw levels?

Serious or difficult-to penetrate infections, especially if not improving Unstable or difficult-to-assess renal function Obesity (BMI > 40) Concomitant nephrotoxins (aminoglycosides, acyclovir, loop diuretics) Uncertain volume of distribution Prolonged course (> 3-5 days)

When should we NOT draw levels?

Short-term dosing (prophylactic dosing) Uncomplicated infections that are improving in patients with normal renal function (Cellulitis, UTIs )

What is significant regarding nephrotoxicity?

Significantly less since vanco is now more pure; only common if used with other nephro toxic drugs like aminoglycosides

Vancomycin use increased over the last decade due to increase incidence of C-MRSA; how can this be treated?

Susceptible to bactrim + tetracyclines NO need to use vanco

What is significant regarding red man syndrome?

Treat: decrease rate of vancomycin Non-allergic - direct histamine release: often occurs on face and neck, but can be entire body

What is our general goal for vancomycin troughs?

Troughs should always exceed *10 mg/L to avoid development of resistance Trough of <10 is associated with resistance @increased risk of VRE

What are the types of vancomycin resistance?

VISA (Vancomycin intermediate Staphlococcus aureus) is increasing VRE (Vancomycin Resistant Enterococcus) colonization and infection increasing *Use judiciously Do not use to treat colonization Ensure we achieve proper troughs

What is crucial to remember when it comes to vancomycin concentration time and MIC?

Vancomycin concentration time curve remains the same, independent of MIC** Change in MIC = changes AUIC AUIC = area between the MIC + concentration curve (AUC/MIC)

How is vancomycin's tissue penetration?

Very polar, poor penetration into most body tissues Roughly 30% penetration into soft tissue

How is vancomycin's protein binding?

~50% (45-70%) Multi-compartment distribution, but commonly thought of as 1 compartment