Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m2/day for neonates?

Abstract

Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m(2)/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m(2)/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m(2)/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p<0.001). A dose of 27mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.

An Overview of Antibiotic Therapy for Early- and Late-Onset Neonatal Sepsis: Current Strategies and Future Prospects

“…The common first antibiotic combination used for empiric Gram-positive coverage, the main cause of LOS, is a glycopeptide antibiotic, often Vancomycin, plus an aminoglycoside (e.g., Gentamycin or Amikacin) or an antibiotic with optimal penetration of the cerebrospinal fluid if meningitis is suspected (e.g., Cefotaxime) [ 32 , 65 , 66 , 68 , 74 ]. However, due to increased Vancomycin resistance, narrow empirical first-line therapy with a β-lactam antibiotic (most commonly Ampicillin, Flucloxacillin, Nafcillin or Oxacillin), combined with an aminoglycoside could be initiated in infants who are non-colonized with methicillin-resistant Staphylococcus aureus (MRSA) to offer anti-staphylococcal coverage and reduce Vancomycin use in neonatal intensive care units [ 66 , 67 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. In high-income countries, most identified pathogens are susceptible to the empirical antibiotic regimens of β-lactam antibiotic and aminoglycoside, while in LMICs, most of the pathogens isolated from LOS may not be covered by these empirical antibiotics due to the dissemination of resistant bacterial strains, including extended-spectrum beta-lactamase- producing bacteria (ESBL) and MRSA [ 78 , 80 ].…”

Empirical use of vancomycin in neonates. Risks greater than benefits

“…La misma tendencia a dosis del rango mencionado aun considerando si se encuentra en estado crítico, no crítico, e infusión continua si lo consideran necesario (48,49) . Las concentraciones séricas adecuadas se relacionan mejor con la dosis calculada por mg/kg/día que con mg/m2/día (50) .…”