Safety and clinical efficacy of linezolid in children: a systematic review and meta-analysis

Abstract

Background We aimed to evaluate the tolerability and efficacy of linezolid in children for treating suspected and diagnosed Gram-positive bacterial infections. Methods A systematic literature search was conducted up to April 23, 2021, using linezolid and its synonyms as search terms. Two reviewers independently identified and extracted relevant randomized controlled trials and prospective cohort studies. The extracted studies were included in a single-rate meta-analysis of adverse events and clinical outcomes using random-effects models. Results A total of 1082 articles were identified, and nine studies involving 758 children were included in the meta-analysis. The overall proportion of adverse events was 8.91% [95% confidence interval (CI) = 1.64%–36.52%], with diarrhea (2.24%), vomiting (2.05%), and rash (1.72%) being the most common. The incidences of thrombocytopenia and anemia were 0.68% and 0.16%, respectively. Some specific adverse events, including rash and gastrointestinal events, were more frequent in the oral administration subgroup. In terms of efficacy, the overall proportion of clinical improvement was 88.80% (95% CI = 81.31%–93.52%). Children with a history of specific bacteriological diagnosis or concomitant antibiotic therapy had a 1.13-fold higher clinical improvement than children without such histories. The proportion of microbial eradication was 92.68% (95% CI = 84.66%–96.68%). The proportion of all-cause mortality was 0.16% (95% CI = 0.00%–7.75%). Conclusions Linezolid was well-tolerated in pediatric patients and was associated with a low frequency of adverse events, such as anemia, thrombocytopenia, and neutropenia. Moreover, linezolid was effective in children with diagnosed and suspected Gram-positive infections.

Evaluation of Pharmacokinetic Pharmacodynamic Target Attainment and Hematological Toxicity of Linezolid in Pediatric Patients

“…This nding aligns with previous literature highlighting linezolid's potential to induce thrombocytopenia in neonates and pediatric populations [32][33][34]47]. Despite the widespread use of linezolid in clinical practice, there is no consensus on the incidence of its hematological toxicity in pediatrics, and the rates vary markedly from country to country, possibly due to ethnic differences [31][32][33][34].…”

“…The bactericidal activity of linezolid is time-dependent, trough concentrations ranging from 2-7 mg/L and/or an estimated 24-hour area under the curve over minimum inhibitory concentration (AUC 24 /MIC) of 80-120 mg•h/L are suggested as the therapeutic target range for linezolid [24][25][26][27]. Myelosuppression is one of the most serious reported adverse drug reactions for linezolid, both in adults and pediatrics [28][29][30][31][32][33][34]. Studies in adult populations showed that high trough concentrations (> 7.5 mg/L) are associated with an increased risk of linezolid-related hematologic adverse effects [22,26,[35][36][37].…”

“…Most studies conducted to date concerning this issue have always focused on adults. Only a few studies have explored the incidence and risk factors associated with linezolid hematologic toxicities in pediatrics, with con icting results ranging from less than 1% up to 57% [31][32][33][34].…”

Compassionate use of contezolid in a toddler with severe community-acquired pneumonia induced by staphylococcus aureus: a case report and follow-up

“…More importantly, SA-induced CAP is associated with unfavorable clinical outcomes compared to the common pneumococcal CAP, involving a higher risk for sepsis and septic shock, need for ICU-level care and organ function support, and significant mortality, regardless of the presence of methicillin-resistance ( 13 , 14 ). However, the current practice of empirical antimicrobial agents for MRSA-induced lung infections remains suboptimal in consideration of potential adverse drug reactions (ADRs) associated with first-line anti-MRSA antimicrobial agents, leading clinicians have to carefully weigh the pros and cons of antibiotic choices ( 15 , 16 ). This predicament underscores the pressing need for the development of new antibiotics, leading to the emergence of contezolid.…”