Vancomycin in ICU

I am writing this today because someone is confused on prescribing vancomycin in critically ill patients. I hope this comment is useful, at least for my revision.

 

Vancomycin is a glycopeptide antibiotic, used for suspected or proven gram-positive infections.  Vancomycin's primary route of elimination is by renal excretion of unchanged drug. The rate of elimination is directly related to creatinine clearance.

 

The rate of killing depends primarily on time of concentration exceeding the organism's MIC (concentration dependent with time dependence). The ratio of area under the time concentration curve  during a 24 hour period to MIC(AUC0-24h/MIC ratio) is the best predictor of efficacy in this model.

Adverse effects:

1. Red man syndrome: is anaphylactoid reaction during or immediately following rapid infusion of large doses of vancomycin. Flushing usually involves face and neck, but can affect the whole body. It may be eliminated by avoiding massive doses and prolonging the infusion time e.g. no more than 500mg/hour or a maximum of 15 mg/min should prevent most infusion related reactions.

2. Nephrotoxicity: in monotherapy is not fully understood since early preparations were associated with nephrotoxicity. Only 20 cases reported in the medical literature in the years 1956-1984 despite the incessant use. Most of these cases were complicated by concomitant aminoglycoside therapy and pre-existing renal problems as well as investigator discrepancies in interpreting serum levels. Renal insufficiency due to vancomycin administered concomitantly with an aminoglycosides is well established. The incidence of acute renal failure in this setting may be as high as 20 to 30 percent.

3. Ototoxicity: has been described but it is the incidence is < 2%. Only approximately 40 cases of oto- and nephrotoxicity were reported in medical literature in the years 1956-1984.

Dosing

Vancomycin doses of 15 to 20 mg/kg should be administered q12h in patients with normal renal function, not to exceed 2g per dose. In settings where rapid clearance is anticipated, the intervals may be increased to q8h. For rapid achievement of target concentrations in seriously ill patients, a loading dose of 25 to 30 mg/kg may be administered. This may be appropriate for patients with critical illness in the setting of high anticipated Vd (e.g. burns, fluid overload).

 

Vancomycin dosing is based on actual BW (even in the setting of obesity), and doses are rounded to the nearest 250 mg. In general, the drug should b infused over 0.5 hours for each 500mg increment (e.g. 500mg over 0.5 hours, 1g over 1 hour etc). In the setting of the red man syndrome, the rate of infusion may be reduced to 500mg over 1 hour.

 

In recent RCT of continuous infusion regimens have not shown substantial improvement in patient outcomes compared with intermittent dosing.

 

In obesity, to avoid individual doses greater than 2g, the total daily dse can be divided into 3 administrations (q8h). In patients with renal insufficiency, doses in the range of 15-20mg/kg (based on target trough concentration) rounded to the nearest 250mg should be administered at frequencies based on estimations of creatinine clearance.

 

Serum concentration monitoring

Troughs versus peaks: Trough concentrations are useful as surrogate to AUC and are generally considered the most accurate and practical method to monitor vancomycin. Therefore, optimal dosing is guided by knowledge of both susceptibility and trough concentration.

There is little role for the routine monitoring of peak vancomycin concentrations, given the concentration independent pd properties and lack of data correlating peak concentrations with either efficacy or toxicity. IDSA 2005 guidelines for endocarditis endorsed target peak of 30-45 mcg/ml, the opinion was based on animal models and invitro susceptibility data rather than clinical evidence.

 

Target trough

At least 10 mcg/ml, may reduce emergence of isolates with elevated MIC. In the setting of invasive infections (e.g. bacteremia, endocarditis, osteomyelitis, prosthetic joint infections, HAP, infections of CNS) aim trough of 15-20 mcg/ml. Such concentrations generally achieve an AUC/MIC of > 400 for isolates with vancomycin MIC < 1. If MIC is > 2 mg/ml, alternate therapies should be considered.

 

Timing of levels: trough concentrations should be measured within 30 minutes prior to infusion of the fourth or fifth dose following the inital dose or dose adjustment. Trough concentration monitoring should be performed in patients receiving vancomycin therapy longer than 3 days. Once target concentrations are achieved, the trough should be monitored at least weekly for patients who receive longer therapy.

Serum creatinine concentration should be determined daily until stable,the weekly. More intensive monitoring may be considered if renal function unstable, if nephrotoxic drugs are administered concomitantly.

For patients on RRT via the newer, more permeable high flux membranes, repeat vancomycin is often required following each session. Many favour supplemental doses of at least 500 mg following each hemodialysis session.

Whenever practical, serum concentrations assessed immediately prior to hemodialysis may be used to guide subsequent dosing.