The rapid increase and inadequate use of linezolid prescriptions at a neonatal intensive care unit (NICU) raises concern about potential misuse, according to study research published in Antimicrobial Resistance and Infection Control.

Neonatal survival has increased with the advances in neonatal care, although neonatal exposure to risk for nosocomial infections has also increased as a result of long-term invasive procedures and devices. As a result of the high frequency of nosocomial sepsis in NICUs and the lack of specificity of septic signs in neonates, wide antibiotic indications are rapidly de-escalated if a diagnosis is refuted. For nosocomial infections, vancomycin is usually prescribed as a first-line antibiotic for coverage of methicillin-resistant coagulase-negative staphylococci, Staphylococcus aureus, and Enterococcus.

An increase in linezolid use in neonates has been reported during the last decade and may be related to either the emergence of vancomycin-resistant bacteria or an inadequate use of linezolid, the investigators wrote. This monocentric, retrospective cohort study explored the use of linezolid in a tertiary NICU setting from January 2010 through December 2019 in Lyon, France.

The study included 66 prescriptions in 57 neonates that led to at least 1 administration of linezolid. Linezolid use, other antibiotic use, and epidemiologic data were analyzed; 2 independent pediatricians secondarily classified each linezolid order as adequate or inadequate. Adequate linezolid use included use for a Gram-positive infection with resistance to other antibiotics, persistent bacteremia despite vancomycin therapy with appropriate serum level and removal of central venous line, or contraindication to vancomycin.


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Study results show a rapid increase in number of linezolid prescriptions from 2014 to 2019. Of the 57 patients included, 54 (95%) were pre-term with a median gestational age of 26 gestational weeks (interquartile range [IQR], 25-27) and a median birth weight of 717 grams (IQR, 590-880). In the study, 21 patients died during NICU hospitalization; 12 of these patients had deaths related to the infectious episode that led to linezolid use. From 2010 to 2013, no linezolid was prescribed. From 2014 to 2019, there were a total of 66 linezolid prescriptions (3, 10, 7, 13, 12, and 21 prescriptions from 2014 to 2019, respectively). Of these 66 prescriptions, 22 (33%) were retrospectively classified as inadequate (0%, 30%, 28%, 23%, 42%, and 43%, respectively).

The first line treatment was vancomycin in 51 (77%) patients and linezolid in 12 (18%) patients. The primary reasons to initiate linezolid were need for better tissue distribution or first-line treatment failure. Infections leading to linezolid use were mostly related to methicillin-resistant coagulase-negative staphylococci and presented as either pneumoniae (35%) or isolated bacteremia (48%). The most common infection strains that led to linezolid use were Staphylococcus epidermis (n=23 [35%]), Staphylococcus capitis (n=11 [17%]), and polymicrobial (n=11 [17%]). The median delay before linezolid use was 3 days (IQR, 2-6) and the median duration of linezolid treatment was 7 days (IQR, 3-10).

Study limitations included difficulty in classifying adequate and inadequate linezolid use due to lack of standardization in medical records. The study was monocentric, making it difficult to generalize findings to all NICU settings.

Overall, the study authors concluded that the “worrisome trend” of increasing use of linezolid in the NICU “should lead to search for therapeutic alternatives and to work on antibiotic stewardship to prevent the emergence of new antimicrobial bacterial resistance.”

Reference

Matrat L, Plaisant F, Barreto C, Claris O, Butin M. Increasing use of linezolid in a tertiary NICU during a 10-year period: reasons and concerns for the future. Antimicrob Resist Infect Control. 2020. doi:10.1186/s13756-020-00818-2.