ABSTRACT
Objectives: Heterogeneously resistant vancomycin-intermediate coagulase-negative staphylococci (hVICoNS) are emerging pathogens causing central-line-associated bloodstream infections (CLABSIs) in neonatal intensive care unit (NICU) patients. Given the burden of disease associated with CLABSI and the current lack of therapeutic guidelines, we aimed to compare the effectiveness of linezolid versus vancomycin used as the definitive antibiotic therapy for hVICoNS CLABSI. Methods: We performed a retrospective cohort study of infants with hVICoNS CLABSI from a single NICU between 2009 and 2014, treated with either linezolid or vancomycin as definitive antibiotic therapy. CLABSI duration, early and late recurrence and in-hospital mortality were compared using propensity score-adjusted proportional hazards and logistic regression models. Results: Of 89 infants with hVICoNS CLABSI, 33 (37.1%) treated with linezolid were compared with 56 (62.9%) treated with vancomycin. The median duration of CLABSI was 5 (range 1-12) versus 4 days (range 0-14) ( P = 0.11), early recurrences were 3.0% versus 7.1% ( P = 0.42), late recurrences 0% versus 14.3% ( P = 0.02) and mortality 27.3% versus 28.6% ( P = 0.90), when treated with linezolid versus vancomycin, respectively. When adjusting using a continuous propensity score, linezolid had an HR of 0.78 (95% CI 0.48-1.27) for CLABSI duration, an OR of 0.23 (95% CI 0.02-2.56) for early recurrence and an OR of 0.9 (95% CI 0.3-2.67) for mortality, relative to vancomycin. Conclusions: There was no statistically significant difference between linezolid and vancomycin when used as definitive treatment for hVICoNS CLABSI in NICU patients, in terms of CLABSI duration, recurrence or all-cause mortality.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Linezolid/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcus/drug effects , Vancomycin/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , Coagulase/deficiency , Cohort Studies , Female , Hospital Mortality , Humans , Infant , Infant, Newborn , Intensive Care Units, Neonatal , Linezolid/administration & dosage , Linezolid/blood , Male , Retrospective Studies , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcal Infections/mortality , Staphylococcus/classification , Staphylococcus/enzymology , Staphylococcus/isolation & purification , Treatment Outcome , Vancomycin/administration & dosage , Vancomycin/blood , Vancomycin/pharmacologyABSTRACT
Clindamycin is commonly prescribed to treat children with skin and skin-structure infections (including those caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)), yet little is known about its pharmacokinetics (PK) across pediatric age groups. A population PK analysis was performed in NONMEM using samples collected in an opportunistic study from children receiving i.v. clindamycin per standard of care. The final model was used to optimize pediatric dosing to match adult exposure proven effective against CA-MRSA. A total of 194 plasma PK samples collected from 125 children were included in the analysis. A one-compartment model described the data well. The final model included body weight and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (l/h) = 13.7 × (weight/70)(0.75) × (PMA(3.1)/(43.6(3.1) + PMA(3.1))); V (l) = 61.8 × (weight/70). Maturation reached 50% of adult CL values at ~44 weeks PMA. Our findings support age-based dosing.
