Early lactic acidosis associated with linezolid therapy in paediatric patients
Introduction
Linezolid is an oxazolidinone class antibiotic that inhibits bacterial protein synthesis by binding to bacterial 23S ribosomal RNA of the 50S subunit [1], preventing the formation of a functional 70S initiation complex that is necessary for bacterial protein synthesis. Linezolid exhibits a broad spectrum of activity against Gram-positive bacteria, including meticillin-resistant staphylococci, vancomycin-resistant enterococci (VRE), penicillin-resistant Streptococcus pneumoniae and Nocardia spp. [2], [3]. Based on evidence from prospective studies, case reports and case series, the US Food and Drug Administration (FDA) has approved linezolid for use in infants and children of all ages [1], [4], [5], [6], [7]. The aim of this study was to analyse the safety of linezolid in a large cohort of children, with particular emphasis on the occurrence of lactic acidosis.
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Materials and methods
Patients aged ≤18 years who received ≥3 days of linezolid therapy between February 2007 and July 2012 at Ankara Hematology and Oncology Research Hospital (Ankara, Turkey) were included in the study. Data collected for each patient included: age; sex; diagnosis; day of therapy on which lactic acidaemia, and lactic acidosis if present, started; accompanying antimicrobial therapy if applicable; therapy modification if needed; outcome; and mortality. The normal range for serum lactate
Results
In total, 50 paediatric patients (20 female and 30 male) aged between 1 month and 17 years (median 3.5 years; mean 6.1 years) received ≥3 days of linezolid therapy; 22 were in the intensive care unit (ICU), of whom 20 were being mechanically ventilated. Indications for linezolid therapy are summarised in Table 1. Of the 50 patients, 31 (62%) had unresolved staphylococcal infections and the remainder had infections with VRE. In all patients, linezolid was administered at a dosage of 10 mg/kg
Discussion
Use of linezolid in children has been evaluated in several clinical studies and reviews [5], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Lactic acidosis is considered a rare adverse event that was first reported in 2003 by Apodaca and Rakita [17], who described the case of a 52-year-old woman developing lactic acidosis after 11 weeks of oral linezolid therapy. Since then, several additional cases have been published [18], [19], [20], [21], [22], [23], mostly in older patients [24].
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Lactic acidosis associated with standard dose linezolid in a kidney recipient with impaired renal function
2022, Brazilian Journal of Infectious DiseasesCitation Excerpt :In addition, comorbid conditions, such as hypoalbuminemia and decreased lean body mass, reduced LZD volume distribution, and p-glycoprotein-mediated drug-drug interaction with macrolides (azithromycin in this case), which may reduce LZD metabolism, could also worsen LZD toxicity, as shown in our patient.16-18 Apart from adult patients, the onset of LZD-induced lactic acidosis appears much earlier in pediatric cases, which makes detection more urgent.19 Accordingly, LZD should be optimized with TDM-guided dose adjustment in patients with renal dysfunction and coexisting comorbid conditions.20
Severe linezolid-induced lactic acidosis in a child with acute lymphoblastic leukemia: A case report
2020, Journal of Infection and ChemotherapyCitation Excerpt :Since then, other cases were reported predominantly among adult population. An estimated incidence of linezolid-induced lactic acidosis in children is 2–16% [3,4]. Its severity varies from asymptomatic hyperlactacidemia to fatal conditions [5–7] and mortality in adults is approximately 25% [8,9].
Staphylococcus capitis and NRCS-A clone: the story of an unrecognized pathogen in neonatal intensive care units
2019, Clinical Microbiology and InfectionCitation Excerpt :Linezolid thus appears as an interesting alternative. However it should be used cautiously because resistance to this drug has already been observed in S. capitis isolates from non-neonate patients [31] and because it exposes neonates to possible adverse effects [32]; in particular lactic acidosis during linezolid therapy has been reported as a frequent early side effect in children which should be carefully monitored [33]. S. capitis strains isolated from adult patients are classically poorly virulent.
Miscellaneous Antibacterial Drugs
2015, Side Effects of Drugs AnnualCitation Excerpt :A pediatric, prospective, cohort study was conducted in 50 children treated with linezolid to determine the incidence of lactic acidosis. Eight patients developed acidosis and eight developed lactic acidemia without acidosis [80c]. To further emphasize this association, four case reports were documented and described the development of lactic acidosis after linezolid administration.
Comparison of Incidence of Hyponatremia between Linezolid and Vancomycin by Propensity Score Matching Analysis
2023, Biological and Pharmaceutical Bulletin