Pharmacokinetics of linezolid treatment using intravenous and oral administrations in extremely premature infants

Sicard, Mélanie; Launay, Élise; Caillon, Jocelyne; Jacqueline, Cédric; Legrand, Arnaud; Deslandes, Guillaume; Navas, Dominique; Rozé, Jean‐Christophe; Guen, C. Gras-Le

doi:10.1007/s00228-015-1813-3

Cited by 19 publications

(15 citation statements)

References 20 publications

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“…In a retrospective study, five preterm infants (GA 28 ± 3.5 weeks), treated for late-onset sepsis, who experienced renal failure, switched from iv vancomycin (30 mg/kg/day) to oral linezolid (30 mg/kg/day q8h). C max for all patients but one was above the measured MIC for the causative pathogen 33 …”

Section: Resultsmentioning

confidence: 72%

Oral antibiotics for neonatal infections: a systematic review and meta-analysis

Keij

Kornelisse

Hartwig

et al. 2019

Journal of Antimicrobial Chemotherapy

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BackgroundWorldwide many neonates suffer from bacterial infections. Adequate treatment is important but is associated with prolonged hospitalization for intravenous administration. In older children, oral switch therapy has been proven effective and safe for several indications and is now standard care.ObjectivesTo evaluate the currently available evidence on pharmacokinetics, safety and efficacy of oral antibiotics and oral switch therapy in neonates (0–28 days old).MethodsWe performed systematic searches in Medline, Embase.com, Cochrane, Google Scholar and Web of Science. Studies were eligible if they described the use of oral antibiotics in neonates (0–28 days old), including antibiotic switch studies and pharmacological studies.ResultsThirty-one studies met the inclusion criteria. Compared with parenteral administration, oral antibiotics generally reach their maximum concentration later and have a lower bioavailability, but in the majority of cases adequate serum levels for bacterial killing are reached. Furthermore, studies on efficacy of oral antibiotics showed equal relapse rates (OR 0.95; 95% CI 0.79–1.16; I2 0%) or mortality (OR 1.11; 95% CI 0.72–1.72; I2 0%). Moreover, a reduction in hospital stay was observed.ConclusionsOral antibiotics administered to neonates are absorbed and result in adequate serum levels, judged by MICs of relevant pathogens, over time. Efficacy studies are promising but robust evidence is lacking, most importantly because in many cases clinical efficacy and safety are not properly addressed. Early oral antibiotic switch therapy in neonates could be beneficial for both families and healthcare systems. There is a need for additional well-designed trials in different settings.

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Section: Resultsmentioning

confidence: 72%

Oral antibiotics for neonatal infections: a systematic review and meta-analysis

Keij

Kornelisse

Hartwig

et al. 2019

Journal of Antimicrobial Chemotherapy

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Matrat

Plaisant

Barreto

et al. 2020

Preprint

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Background: Linezolid has been increasingly used in tertiary NICUs. The objectives of this study were to explore the indications of these linezolid prescriptions, to analyze a possible misuse and to provide solutions to avoid such misuse.Methods: A monocentric retrospective cohort study included all neonates hospitalized in one tertiary NICU between January 1st, 2010 and December 31st, 2019 and who received at least one administration of linezolid. These data were confronted to epidemiological and antibiotic use data from the same NICU. Two independent pediatricians secondarily classified linezolid uses as adequate or not.Results: During the study period, 66 infections in 57 patients led to linezolid use. Most patients were pre-term and 21 patients (37%) died. Infections were mainly related to methicillin-resistant coagulase negative staphylococci and were frequently either pneumoniae (35%) or isolated bacteremia (48%), including 25 persistent bacteremia (64% of the 39 bacteremia). Need for a better tissue distribution or first-line treatment failure were the main reasons to initiate linezolid. Linezolid was administered for a median duration of 7 [3;10] days. No side effects were reported. Twenty-two (33%) of the 66 linezolid prescriptions were retrospectively classified as inadequate. Conclusions: A rapid increase in linezolid prescriptions has been observed in our tertiary NICU, from 2014 to 2019, with 33% inadequate uses. This worrisome trend should lead to search for therapeutic alternatives and to work on antibiotic stewardship to prevent the emergence of new antimicrobial bacterial resistance.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Matrat

Plaisant

Barreto

et al. 2020

Antimicrob Resist Infect Control

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Background Linezolid has been increasingly used in tertiary NICUs. The objectives of this study were to explore the indications of these linezolid prescriptions, to analyze a possible misuse and to provide solutions to avoid such misuse. Methods A monocentric retrospective cohort study included all neonates hospitalized in one tertiary NICU between January 1st, 2010 and December 31st, 2019 and who received at least one administration of linezolid. These data were confronted to epidemiological and antibiotic use data from the same NICU. Two independent pediatricians secondarily classified linezolid uses as adequate or not. Results During the study period, 66 infections in 57 patients led to linezolid use. Most patients were pre-term and 21 patients (37%) died. Infections were mainly related to methicillin-resistant coagulase negative staphylococci and were frequently either pneumoniae (35%) or isolated bacteremia (48%), including 25 persistent bacteremia (64% of the 39 bacteremia). Need for a better tissue distribution or first-line treatment failure were the main reasons to initiate linezolid. Linezolid was administered for a median duration of 7 [3;10] days. No side effects were reported. Twenty-two (33%) of the 66 linezolid prescriptions were retrospectively classified as inadequate. Conclusions A rapid increase in linezolid prescriptions has been observed in our tertiary NICU, from 2014 to 2019, with 33% inadequate uses. This worrisome trend should lead to search for therapeutic alternatives and to work on antibiotic stewardship to prevent the emergence of new antimicrobial bacterial resistance.

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Pharmacokinetics of linezolid treatment using intravenous and oral administrations in extremely premature infants

Cited by 19 publications

References 20 publications

Oral antibiotics for neonatal infections: a systematic review and meta-analysis

Oral antibiotics for neonatal infections: a systematic review and meta-analysis

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

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

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