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vancomycin is a glycopeptide antibiotic that used in the treatment of severe infections with pathogens such as staphylococcus and streptococcus spp .
following intravenous administration , vancomycin is poorly metabolized and is mainly excreted unchanged in urine .
total body clearance is thus dependent on the kidney , and is correlated with glomerular filtration rate and creatinine clearance .
accumulation of vancomycin may thus occur and may lead to toxic side effects if the dosage is not modified in accordance with the degree of renal failure .
furthermore , vancomycin has a low volume of distribution ( 0.6 l / kg ) , a low protein - bound fraction ( 50% ) and a low molecular weight ( 1449 da ) , suggesting that it can easily diffuse through dialysis membranes .
we synthesized results from studies on vancomycin dialyzability in different types of membranes and with different dialysis techniques ( intermittent and continuous ) .
the aim of the present review is not to detail the pharmacokinetics of vancomycin in dialysis patients but to establish guidelines for handling this drug in such patients .
the fundamental principle for the use of vancomycin in dialysis patients is that the drug should only be administered when the plasma concentration is too low to be effective .
we therefore indicate how and when plasma concentrations of vancomycin should be determined in dialysis patients .
finally , administration technique is not discussed here because the ideal technique is not clearly established .
the manufacturer of vancocin ( eli lilly and co. , indianapolis , in , usa ; reviewed april 2000 ) has reported that , in anephric patients , the average vancomycin elimination half - life is 7.5 days , whereas it is 46 hours in patients with normal renal function .
it has also been reported that total body clearance of vancomycin is correlated with creatinine clearance in patients with altered renal function .
although it is clear that renal clearance of vancomycin is decreased in patients with renal failure , it has also been suggested that nonrenal clearance of vancomycin , which usually accounts for approximately 30% ( 40 ml / min ) of total clearance in patients with normal renal function , is reduced to as low as 56 ml / min in patients with terminal renal insufficiency . while the mechanisms of this reduction are still unidentified , inhibition of vancomycin metabolism by uraemic toxins is suspected .
because both renal and nonrenal vancomycin clearances are reduced in patients with impaired renal function , accumulation of unchanged active drug in plasma is likely to occur .
for this reason , application of existing nomograms or equations for adjustment of vancomycin dosage in patients with renal impairment   should be accompanied by monitoring of plasma vancomycin levels .
these nomograms or equations were established on the basis of decline in renal clearance , and do not take into account the decline in nonrenal clearance .
therefore , their application in patients with compromised renal function may result in an insufficient reduction in dose and may lead to toxicity .
it has been suggested that a vancomycin plasma concentration of 80 g / ml would be a reliable level for the toxicity threshold .
however , it should be pointed out that the toxic serum level of vancomycin has not yet been precisely determined , and serum concentrations of vancomycin as high as 6070 g / ml may also be toxic in some patients , depending on the particular clinical situation or associated drugs .
furthermore , it has recently been shown that nephrotoxicity might be a marker of failure of vancomycin treatment .
the relationship between vancomycin - induced ototoxicity and plasma concentration of the drug ( peak or trough levels ) is still undergoing investigation .
however , vancomycin - induced nephrotoxicity has been clearly related to drug plasma concentrations . in a study involving 198 cancer patients administered vancomycin for treatment of gram - positive bacteraemia , kralovicova and coworkers  
trough vancomycin levels greater than 15 g / ml were associated with significantly more nephrotoxicity .
those investigators concluded that maintenance vancomycin doses should be administered according to the value of the trough level ( i.e. maintaining the trough level < 15 g / ml ) . in patients with terminal renal insufficiency undergoing haemodialysis , whether intermittent or continuous , and receiving vancomycin therapy , elimination of the drug during the procedure must be considered when establishing the dosing schedule .
the two major elements that can be concluded from analysis of these studies are as follows : vancomycin is not significantly dialyzable when haemodialysis is performed using a low flux membrane such as cuprophan ; and vancomycin is significantly dialyzable when haemodialysis is performed using a high flux membrane such as polysulfone , polyacrylonitrile and poly - methylmethacrylate .
an , acrylonitrile ; c , cuprophan ; ca , cellulose acetate ; cavh , continuous arteriovenous haemodialysis ; cavhdf , continuous arteriovenous haemodiafiltration ; cler , extrarenal clearance ; clhd , haemodialysis clearance ; ct , cellulose triacetate ; cvvh , continuous venovenous haemodialysis ; hd , haemodialysis ; nd , not determined ; pa , polyamide ; pan , polyacrylonitrile ; pmma , polymethylmethacrylate ; ps , polysulfone . studies of the pharmacokinetics of vancomycin in patients undergoing haemodialysis with high flux membranes demonstrated that there is a rebound in vancomycin plasma concentrations at the end of the session .
the plasma profile of vancomycin concentrations versus time indicates that concentrations decrease dramatically during the session and then increase when the session is stopped for 36 hours ( fig .
1 ) . this rebound may result from drug recirculation from plasma protein binding sites .
recirculation from peripheral compartments is less likely to occur because of the low vancomycin volume of distribution , indicating that the drug remains mainly in plasma .
this rebound may be clinically significant , and it must be taken into account when determining vancomycin trough levels .
subsequently , it is recommended that determination of vancomycin trough levels in patients undergoing chronic haemodialysis should be performed before the haemodialysis session ( table 2 ) .
vancomycin pharmacokinetic profile during chronic haemodialysis : evidence for a postsession rebound in plasma concentration .
however , quantification of vancomycin removal is difficult to estimate , and it is thus also recommended that plasma levels of the drug be monitored . when a continuous technique is used , there is no rebound in vancomycin plasma concentration .
total body clearance of vancomycin is almost constant , and determination of trough levels may be performed at any time while continuous haemodialysis is being performed ( table 2 ) . however , if dialysis is stopped and if vancomycin treatment must be continued , then the plasma concentration of vancomycin 46 hours after stopping haemodialysis should be determined before any readministration of the drug ( table 2 ) .
maintenance doses should be administered according to the plasma trough levels , as determined before the session when the patient is on chronic intermittent haemodialysis , at any time for continuous haemodialysis , and 6 hours after the end of haemodialysis when continuous therapy is stopped and vancomycin treatment is continued .
vancomycin therapy is widely used in patients with decreased renal function , and serum levels of this agent must be closely monitored in such patients in order to avoid toxicity and subtherapeutic levels , in particular because emergence of resistance to glycopeptide antibiotics has been noted .
following intravenous administration , vancomycin is poorly metabolized and is mainly excreted unchanged in urine . 
 total body clearance is thus dependent on the kidney , and is correlated with glomerular filtration rate and creatinine clearance . 
 accumulation of vancomycin in patients with renal insufficiency may therefore occur , and this may lead to toxic side effects if dosage is not modified according to the degree of renal failure . furthermore , vancomycin easily diffuses through dialysis membranes . 
 the aim of the present review is to establish guidelines for handling this drug in such patients . we indicate how and when plasma concentrations of vancomycin should be determined in dialysis patients .