Pharmacy Facts

Pediatrics Edition

June 2016
Vancomycin for Methicillin Resistant Coagulase Negative Staphylococcus (CONS) Infections
What does the evidence say?
Bloodstream infections are a frequent complication of indwelling central  Risk of CONS nosocomial infection identified in patients admitted greater than 14 days but less
venous infections (CRBSI) in children-Castagnola et al than 21 days (Wisplinghoff)
CONS represent a regular part of the microbiota of the skin & mucus  CONS remains the predominant microorganism identified from CVC-BSI in NICUs & PICUs in Canada
membranes1 (Nosocomial Surveilance network)
S. epidermidis is the most frequently staphylococcus species
 A retrospective review of nosocomial infection in pediatric patients found 83.4% of CONS
recovered1
infections were in the PICU (16.6% general wards). 96% of patients were nonneutropenic
S. epidermidis group comprises typical “medium”-pathogenic
 majority of patients (93% NICU, 88% PICU in 2011) are alive at 30 days after onset of CVC-BSI (92%
staphylococci, necessitating a decision, each time they are detected in
clinical specimens, on whether they represent true infection or only NICU, 91% PICU in 2006) –(Nosocomial Surveilance Network)
colonization/contamination1  In vivo testing reported ~10% reduction in Staph Epi (MIC 0.12-2 mg /L) colony forming counts
“CONS are the most common cause of catheter-related infection. Most exhibit at 8 hours for a concentration of vancomycin 1 mg/L (Harland et al.)
methicillin resistance, and this should be considered when choosing empirical 
therapy for catheter-related infection2
AHS CONS susceptibility rates reported 70% resistance to
Cloxacillin/Cefazolin & 100 % susceptibility to vancomycin3

How does vancomycin erradicate CONS?
Vancomycin interferes with cell wall synthesis in susceptible
bacteria by binding to the terminal aminoacyl D-alanyl–D-alanines sequence. It is still unclear
which serum concentration-time profile in relation to minimal inhibitory concentration (MIC)
leads to the optimal efficacy for vancomycin. Time that the concentration in serum exceeds the
MIC is the parameter most important for the efficacy of this drug, hence dosing schedules that
maintain the vancomycin concentration above the MIC for most of the dosing interval. There is
no concentration-dependent killing of vancomycin against the strains of S. epidermidis.
However, vancomycin displays a very short Post-antibiotic effect and a long postantibiotic sub-
MIC effect (PA SME). A 99.9% reduction in viable bacterial density in an 18–24-h period is
the generally accepted definition of bactericidal5.
Bottom line:
No randomized trials have evaluated the treatment of CONS CRBSI. (IDSA
treatment Guidelines)
Vancomycin is 1st line therapy for CONS CRBSI (IDSA Treatment Guidelines)
There is no established specific vancomycin target exposure for CONS
CRBSI(Blanchard)
CONS with MIC 2-4 mg/L, 20 mg/kg IV Q12H of vancomcyin may result in treatment
failure. Castagnola et al
Recent studies suggest minimum serum vancomycin trough concentrations should
always be 7- 10 mg/L to avoid development of resistance (Blanchard)

References:
1. Becker, K., Heilmann, C., & Peters, G. (2014). Coagulase-negative staphylococci. Clinical microbiology reviews, 27(4), 870-926.
2. Mermel, L. A., Allon, M., Bouza, E., Craven, D. E., Flynn, P., O'Grady, N. P., ... & Warren, D. K. (2009). Clinical practice guidelines for the diagnosis

Questions? Just ask one of us! Team pharmacist pagers: and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clinical infectious
diseases, 49(1), 1-45
PICU – 01842, Red – 06962, Green – 13560, Complex Care – 07759 3. AHS Antibiogram