Vancomycin concentrations

In clinical practice, serum concentration monitoring is routinely performed on patients receiving aminoglycosides. Despite the lack of supporting evidence for its usefulness or need, serum vancomycin concentration monitoring is also widespread. Flucytosine serum concentration monitoring has been shown to reduce toxicity when doses are adjusted to maintain peak concentrations below 100 mcg/mL. 

Yeung MY, Smyth IP. Concurrent frusemide-theophylline dosing reduces serum vancomycin concentrations in preterm infants. Aust J Hosp Pharm 1999 29 269-72. 

A 14-month-old girl with chronic renal insufficiency due to renal dysplasia was empirically treated with ceftazidime and vancomycin for fever. Her calculated creatinine clearance was 10 ml/minute/1.73 m. She erroneously received vancomycin 1.5 g in 3 doses 6 hours apart. Her serum creatinine concentration increased and her vancomycin concentrations remained markedly high (338 mg/1 5 hours after the third dose). The half-Ufe of vancomycin was 145 hours. Hearing loss developed. Continued charcoal hemoperfusion and hemodialysis were used to treat the disorder. Thrombocytopenia was noted as significant consequence of hemoperfusion. The patient did not fully recover her previous renal function and became dialysis dependent. The audiogram normalized by 6 months. 

Of 69 neonates (including 8 with peak vancomycin concentrations over 40 pg/ml) with culture-proven S. aureus or coagulase-negative staphylococcal septicemia who received vancomycin for more than 3 days, 6 had a doubling of serum creatinine concentration during vancomycin treatment, and all were in the group with peak serum vancomycin concentrations under 40 pg/ml (58). 

Hemodialysis with high-efficiency dialysis membranes resulted in a removal of plasma vancomycin of about 60% (calculated half-life 2 hours) in two children with initial plasma vancomycin concentrations of 238 gg/ml and 182 gg/ml (114). 

Fluorescence polarization immunoassay determination of serum vancomycin concentrations can result in falsely high vancomycin concentrations in excess of 30-80% in patients with renal dysfunction. This is due to the formation of a non-toxic, non-microbiologically active pseudometabolite, the vancomycin crystalline degradation product (132). A report on a 48-year-old man underlies the significance of resulting underdosing and eventually suboptimal clinical response (133). 

A 17-year-old anuric woman with end-stage renal insufficiency received a massive overdose of vancomycin (40 mg/kg/day for 8 days) and was treated three times with high-flux hemodiafUtration with a polysulfone membrane (134). The vancomycin concentration fell from 101 to 17 mg/1 at the end of the procedure. There were no adverse effects of either vancomycin or hemodiafUtration. 

Cantu TG, Yamanaka-Yuen NA, Lietman PS. Serum vancomycin concentrations reappraisal of their clinical value. Clin Infect Dis 1994 18(4) 533 3. 

Thomas MP, Steele RW. Monitoring serum vancomycin concentrations in children is it necessary Pediatr Infect Dis J 1998 17(4) 351-3. 

Kim JS, Perkins RJ, Briceland LL, Tobin EH. Clinical significance of falsely elevated vancomycin concentrations in end-stage renal disease. Ann Pharmacother 1999 33(1) 116-18. 

De Gatta, del M.F. Calvo, V. Hernandez, J.M. Caballero, 48. D. San Miguel, J.F. Dominguez-Gil, A. Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies. Clin. Pharmacol. Ther. 1996, 60 (3), 332-340. 

Trough only" measurement of steady-state vancomycin concentrations is becoming a mainstream method to monitor therapy. The exact range for this value is uncertain. Some clinicians recommend 5 to 10 mcg/mL, whereas others suggest 5 to IS mcgfmL. Many clinicians continue to measure both steady-state peak and trough vancomycin concentrations. 

Vancomycin requires multicompartment models to completely describe its serum-concentration-versus-time curves. However, if peak serum concentrations are obtained after the distribution phase is completed (usually V2 to 1 hour after a 1-hour intravenous infusion), a one-compartment model can be used for patient dosage calculations. Also, since vancomycin has a relatively long half-life compared with the infusion time, only a small amount of drug is eliminated during infusion, and it is usually not necessary to use more complex intravenous infusion equations. Thus simple intravenous bolus equations can be used to calculate vancomycin doses for most patients. Although a recent review paper questioned the clinical usefulness of measuring vancomycin concentrations on a routine basis, research articles" " have shown potential benefits in obtaining vancomycin concentrations... 

When trough-only monitoring of vancomycin concentrations is chosen by a chnician, a simple variant of hnear pharmacokinetics can... 

No demonstrated benefit of vancomycin empirical therapy vs. addition of vancomycin if needed later increased risk of selection for vancomycin-resistant enterococci risk of toxicities excessive cost need for therapeutic monitoring of vancomycin concentrations Marginal gram-positive activity fluoroquinolones not recommended as monotherapy resistance may develop rapidly... 

Ferencz JR, Assia El, Diamantstein L, Rubinstein E. Vancomycin concentration in the vitreous after intravenous and intravitreal administration for postoperative endophthalmitis. Arch Ophthalmol 1999 117 1023-1027. 

Morishige, H. Shuto, H. leiri, L Otsubo, K. Oishi, R. Instability of standard calibrators may be involved in overestimating vancomycin concentrations determined by fluorescence polarization immunoassay. Ther.Drug Monit., 1996,18, 80—85... 

S. aureus arul coagulase-negative staphylococci may express reduced or intermediate susceptibility to vancomycin or high-level resistance. Intermediate resistance is associated with (and may be preceded by) a heterogeneous phenotype in which a small proportion of cells within the population ( 1 in 10 ) will grow in the presence of vancomycin concentrations above 4 pg/mL. 

These calculations show that this dosage regimen will provide peak, trough and average plasma vancomycin concentrations within the therapeutic range of the drug. 

Figure 14.1 is a graph, on rectilinear co-ordinates, of plasma vancomycin concentration for this regimen. In this figure we see the fairly rapid attainment (after approximately 36 h) of steady-state conditions, where successive peak dmg concentrations (Cpk)ss are equal to each other and... 

Figure 14.3 Effect of choice of time of "peak" vancomycin concentration on estimate of trough level. Cp- plasma drug concentration.

Calculate a multiple intermittent infusion rate, Q, that will deliver a "peak" steady- state plasma vancomycin concentration of 30mgL , ... 

What is a more accurate estimate of the trough plasma vancomycin concentration in this patient ... 

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