Neonatal and Neurodevelopmental Outcomes Following Linezolid for Coagulase-negative Staphylococcal Infection

Abstract

Background: Coagulase-negative staphylococci (CoNS) frequently causes late-onset sepsis in preterm infants. Vancomycin is the first-line therapy, but the emergence of reduced vancomycin-susceptibility strains has resulted in linezolid use, of which long-term safety in preterm infants is unknown. Objective: Evaluate the association between linezolid exposure and neurodevelopmental impairment (NDI) or death at 18–21 months of corrected age, in preterm infants with CoNS sepsis. Methods: Multicentric retrospective cohort study comparing long-term outcomes of preterm infants exposed to linezolid versus other antistaphylococcal antimicrobials. We included infants ≤28 weeks’ gestational age (GA), with CoNS sepsis, admitted between January 2011 and June 2015 in 3 level-3 Canadian NICUs. Primary outcome was a composite of death or significant NDI (sNDI) at 18–21 months of corrected age. Secondary outcomes included NDI and individual components of the primary outcome. We assessed the relationship between linezolid exposure and outcomes using a multivariable logistic regression. Results: Of 274 infants included, 67 (24.4%) were exposed to linezolid. Median GA was 26 weeks and clinical characteristics were similar between groups. There was no difference in composite outcome of death or sNDI among the infants of both groups, but significantly more death by 18–21 months in the linezolid group (29.9% vs. 17.6%; P = 0.01). Conclusions: Linezolid exposure was not associated with composite outcome of death or sNDI at 18–21 months. The association between linezolid and death may be due to indication bias. Further studies are warranted.

Increasing use of linezolid in a tertiary NICU during a 10-year period: reasons and concerns for the future

“…Thanks to its wide bacterial spectrum, including Gram-positive bacteria and its excellent bioavailability, linezolid emerged in the early 2000s as a good alternative to vancomycin. In the speci c population of neonates, literature data dealing with linezolid pharmacology, safety, effectiveness and tolerance in neonates is exponential thus demonstrating its growing importance (6,8,9,13). In the study NICU, the rst use of this drug was reported in 2014 and then increased yearly, raising our concern and leading to this work.…”

Increasing use of linezolid in a tertiary NICU during a 10-year period: reasons and concerns for the future

“…Thanks to its wide bacterial spectrum, including Gram-positive bacteria and its excellent bioavailability, linezolid emerged in the early 2000s as a good alternative to vancomycin. In the specific population of neonates, literature data dealing with linezolid pharmacology, safety, effectiveness and tolerance in neonates is exponential thus demonstrating its growing importance [ 6 , 8 , 9 , 13 ]. In the study NICU, the first use of this drug was reported in 2014 and then increased yearly, raising our concern and leading to this work.…”

Antimicrobianos en neonatología. Parte I: Recomendaciones de dosificaciones basadas, en la más reciente evidencia en recién nacidos Comité Consultivo de Infecciones Neonatales, Sociedad Chilena de Infectología

“…Es un AM de origen sintético derivado de las oxazolidinonas. Su mecanismo de acción está dado por la inhibición de la síntesis proteica, al fijarse al sitio P (23s) de la subunidad ribosomal 50S e impedir que se forme el complejo ribosoma-fMet-tRNA 74 . Su espectro de actividad es exclusivo para bacterias grampositivas, incluyendo a Enterococccus y Staphylococcus resistentes a vancomicina.…”

“…En todos los casos, los valores regresan a la normalidad luego de suspender el fármaco [77][78][79] . También se han descrito neuropatías periféricas u ópticas en adultos y niños; generalmente ocurren después de una exposición prolongada a linezolid (≥ 28 días), aunque se reportó la producción de neuropatía óptica después de sólo 16 días de tratamiento en una mujer de 29 años 74 . La neurotoxicidad puede no desaparecer después de retirar el fármaco 74 .…”