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the pharmacokinetics of many medications change as we age , dictating the need for dosing strategies that adjust for these changes .
one such example is vancomycin . the half - life of vancomycin ranges from approximately 2 to 10 hours depending on age ( table 1 ) . focusing on patients aged 3 months to 4 years old compared to those older than 4 years
, there is an approximately twofold difference in their half - lives , which can lead to a huge difference in the dosing strategies of vancomycin . with these age - related differences in pharmacokinetics
, one would expect dosing strategies to be adjusted . however , dosing of vancomycin in the pediatric population , excluding neonates , is not age - specific ( i.e. , infants , children , and adolescents ) , failing to adjust for the variability in pharmacokinetics among pediatric age groups ( table 2 ) [ 1 , 2 ] .
previous studies have shown that higher doses and more frequent dosing strategies are needed to produce therapeutic concentrations .
glover and colleagues evaluated the dosing of vancomycin in 76 pediatric intensive care unit ( picu ) patients aged from 1 month to 18 years old .
vancomycin 20  mg / kg given every 8 hours was needed to obtain therapeutic concentrations . in another retrospective database review ,
benner and colleagues evaluated several vancomycin dosing schemes in 357 patients aged from 1 month to 18 years old .
vancomycin 10  mg / kg every 6 to 8  hours was compared to vancomycin 15 to 20  mg / kg every 6 to 8  hours . the latter dosing strategies were needed to produce more therapeutic levels .   at the moses h. cone
memorial hospital , the standard pediatric dosing protocol ordered by the physicians for vancomycin is 15  mg / kg every 8  hours .
the objective of this study is to assess the need for a revision to this initial vancomycin dosing strategy in three pediatric age groups . to our knowledge , there are not any other studies available that have evaluated vancomycin dosing strategies based on different pediatric age groups .
we hypothesize that patients falling into the infant and adolescent age groups would potentially still reach goal serum trough levels , while those in the child age group would need higher starting doses and/or more frequent dosing regimens .
this retrospective study reviewed data from patients admitted to the moses h. cone memorial hospital general pediatric unit and picu between 2006 and 2010 .
patients were included if the ages were from 1 month to 18 years old , received vancomycin 15  mg / kg every 8  hours , and had a respective trough concentration measured appropriately , defined as a serum level drawn approximately 30  minutes before the third or subsequent doses .
patients were excluded if they had poor renal function , defined as an increase in serum creatinine by 50 percent or more from their baseline or normal serum creatinine for their age .
electronic medical records were reviewed , and data collected include the initial vancomycin dose and respective serum trough concentration , timing of the trough concentration , patient demographics , and renal function .
the primary outcome was the percentage of patients achieving goal serum trough concentrations defined as 10 to 15  mcg / ml for cellulitis and 15 to 20  mcg / ml for bacteremia , pneumonia , meningitis , osteomyelitis , and endocarditis .  
secondary outcomes included the percentage of patients with subtherapeutic and supratherapeutic trough concentrations as well as the indication of vancomycin .
infants were defined as ages from 1 to 23 months old , children from 2 to 12 years old , and adolescents from 13 to 18 years old . demographics and the primary outcome were analyzed using descriptive statistics , while the secondary outcomes were analyzed by the fisher 's exact test .
the study was approved by the institutional review board of the moses cone health system .
of the 50 patients ' medical records reviewed , only 25 were included in the analysis due to exclusions .
eighteen patients had been started on vancomycin using different dosing strategies other than 15  mg / kg every 8  hours .
four patients were excluded due to inappropriate trough timing , in which the trough concentration was charted as being measured after the next dose of vancomycin .
other patients who were excluded consist of one patient being less than one month old , one had no weight documented , and three had documented acute renal failure , of which 2 were appropriately started on a different dosing regimen .  
the majority of patients were female and caucasian in the infant and child age groups , while all the patients in the adolescent group were male and evenly divided between caucasians and african americans ( table 3 ) .
none of the patients in the cohort had cystic fibrosis or any past medical histories that could have increased their volume of distribution .
most of the patients had their trough concentrations collected with the third or fourth doses of vancomycin and were on vancomycin for less than one week . in regards to the primary outcome , none of the patients achieved goal serum trough concentrations with vancomycin dosed at 15  mg / kg every 8  hours ( table 4 ) .
the majority of the trough concentrations were subtherapeutic , with only one infant having a supratherapeutic level ( table 5 ) .
the serum trough concentrations of the infants were more likely to fall between 5 to 10  mcg / ml ( 55.6% in the infant group compared to 41.7% in the child age group , p = 0.86 ) , while those in the child age group had more levels less than 5  mcg / ml ( 41.7% in the infant group compared to 58.3% in the child age group , p = 0.86 ) ( table 6 ) .
vancomycin is an antimicrobial indicated in patients suffering from infections with methicillin - resistant gram - positive pathogens .
it is usually used as the empiric therapy if the proportion of methicillin - resistant gram - positive pathogens is significant ( > 5% ) in the patient population , or if the patients are suspected to be suffering from serious infections ( e.g. , bacteremia ) , or if other antimicrobials like clindamycin can not effectively combat the infection believed to be caused by methicillin - resistant gram - positive pathogens . at our institution , vancomycin is only utilized when the latter two incidences occur .
our drug of choice for less serious infections with methicillin - resistant gram - positive pathogens is clindamycin , since such pathogens have a sensitivity of approximately 95% to clindamycin in our pediatric population .   many previous studies targeted vancomycin trough concentrations ranging from 5 to 15  mcg / ml , which is lower than the new recommendations by the american society of health system pharmacists , the infectious diseases society of america , and the society of infectious disease pharmacists . due to the rise in the mean inhibitory concentration ( mic )
, it is recommended that vancomycin trough concentrations should be maintained at least above 10  mcg / ml for less severe infection like cellulitis and between 15 and 20  mcg / ml for more complicated infections like bacteremia , pneumonia , meningitis , osteomyelitis , and endocarditis .
these recommendations are primarily for the adult population , but they can probably be extrapolated to pediatric patients .  
our institution 's standard physician vancomycin dosing protocol of 15 mg / kg every 8 hours did not achieve the new goal serum trough concentrations for any of the pediatric age groups .
only one patient had a level greater than 10  mcg / ml , and the level was found to be supratherapeutic .
again , this patient was also on other agents likely to cause nephrotoxicity including furosemide and gentamicin .
previous studies have shown that the risk of nephrotoxicity while on vancomycin increases with concomitant use of other nephrotoxic agents like gentamicin , as well as an extended duration of therapy , leading to high concentrations of vancomycin and potential kidney damage . in a study by glover and colleagues , vancomycin 20  mg / kg every 8  hours produced a mean trough concentration of 7.8  mcg / ml , whereas vancomycin 15 to 20  mg / kg every 6 to 8  hours produced levels from 8 to 12  mcg / ml in a study by benner et al . only the vancomycin dosing regimens with the frequency of every 6 hours was able to produce trough concentrations greater than 10  mcg / ml .
none of the dosing strategies in either trial were able to reach concentrations greater than 15  mcg / ml needed for more complicated infections per the new recommendations .
interestingly , the mean age for each study was 5 years old , falling into the shortest half - life group for vancomycin
.   in a newer study of 430 pediatric patients aged from 1 month to 18 years old , eiland and colleagues found that vancomycin dosing strategies of 70  mg / kg / day and 85  mg / kg / day were needed to produce target serum trough concentrations of 10  mcg / ml and 15  mcg / ml , respectively . using the standard pediatric dosing regimens of 40 to 60  mg / kg / day only reached therapeutic levels 49 percent of the time based on the new higher serum trough concentration recommendations .
the mean age of the patient population was 5.9 years , which also fell into the child age group .
in our study , those in the infant age group were more likely to have a trough level in the 5 to 10  mcg / ml range , while the patients in the child age group had more trough concentrations less than 5  mcg / ml .
the adolescent group 's trough concentrations were evenly divided between troughs less than 5  mcg / ml and 5 to 10  mcg / ml . however , due to the small sample size of adolescents , no conclusions can be drawn though one would expect based on the hypothesized adolescent half - life that their trough concentrations would be similar to those of the infant group . we expect that if our patient population had been larger , we might have been able to see more of a trend with each age group .
unfortunately , the sample size was small due to half of the patients being excluded .
originally , we had set out to collect and analyze more patient data , but due to the fact that all the patients ' serum trough concentrations were subtherapeutic , data collection was stopped early .
other limitations to the study include its retrospective nature and the fact that it was conducted at a single center .
nonetheless , it is very important to provide a vancomycin dosing regimen to patients that will lead to therapeutic concentration in a timely manner , since methicillin - resistant gram - positive pathogens , especially staphylococcus aureus , have become more virulent in recent years . as a matter of fact ,
a study by welsh and colleagues confirmed a high rate of vancomycin treatment failures ( 50% ) in pediatric patients with methicillin - resistant staphylococcus aureus ( mrsa ) bacteremia .
this failure might have been due to either subtherapeutic vancomycin trough concentrations or the development of vancomycin - resistant mrsa .
the latter is of a grave concern , since there are limited data on the use of other more powerful antimicrobials treating methicillin - resistant or vancomycin - resistant gram - positive pathogens in the pediatric population .
numerous reports and studies exist that describe the safe and effective use of linezolid in the pediatric population [ 1012 ] ; however , there is not any comparative study between these two agents ( i.e. , vancomycin and linezolid ) in pediatric patients with mrsa infections .
if this study is to be conducted , the higher vancomycin dosing strategies need to be considered in the design in order to reach therapeutic concentration .
the traditional dosing schemes of vancomycin , including our standard physician protocol of 15  mg / kg every 8  hours , most likely do not produce therapeutic trough concentrations in otherwise healthy patients with normal renal function .
our next step at the moses h. cone memorial hospital is to start dosing vancomycin at 20  mg / kg every 8  hours for patients in the infant and adolescent age groups , and vancomycin 15  mg / kg every 6  hours for patients in the child age group .
however , for our pediatric patients with clinically significant comorbidities ( e.g. , congenital heart disease , nephrotic syndrome , and renal dysfunction ) , we will continue dosing vancomycin at 15  mg / kg every 8  hours .
we then hope to evaluate these two dosing strategies in the future , as these doses and/or frequencies may need to be pushed even higher , especially for patients in the child age group due to their short half - life .
large randomized controlled trials are needed to determine the most appropriate dosing regimens of vancomycin in the pediatric population , and the differences in pharmacokinetics must be recognized in order to develop the best dosing for each patient .
background . 
 the pharmacokinetics of many medications change as we age , thus most would assume dosing strategies would adjust for these changes . 
 the objective of this study is to evaluate the initial vancomycin dosing in three pediatric age groups based on measured serum trough concentrations . methodology . 
 this retrospective database review included patients aged from 1 month to 18  years old admitted to the moses h. cone memorial hospital . 
 patients had to have received vancomycin dosed at 15  mg / kg every 8  hours with an appropriately measured trough concentration . 
 the primary outcome was to determine the percentage of patients in 3 pediatric age groups achieving therapeutic trough concentrations with the initial vancomycin dosing regimen . 
 results . 
 twenty - five patients were included in the study . 
 none of the patients had therapeutic trough concentrations after receiving vancomycin 15  mg / kg every 8  hours . 
 only one patient had a supratherapeutic level , while all of the other patients had levels less than 10  mcg / ml . conclusions . 
 vancomycin 15  mg / kg every 8  hours did not provide therapeutic serum trough concentrations for any pediatric age groups . 
 higher doses and/or more frequent dosing regimens need to be evaluated for each age group to determine the most appropriate strategies for producing therapeutic trough concentrations .