Efficacy and safety of linezolid for the treatment of infections in children: a metaanalysis Maria Ioannidou, Fani ApostolidouKiouti, Anna-Bettina Haidich, Ioannis Niopas & Emmanuel Roilides European Journal of Pediatrics ISSN 0340-6199 Eur J Pediatr DOI 10.1007/s00431-014-2307-5
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Author's personal copy Eur J Pediatr DOI 10.1007/s00431-014-2307-5
ORIGINAL ARTICLE
Efficacy and safety of linezolid for the treatment of infections in children: a meta-analysis Maria Ioannidou & Fani Apostolidou-Kiouti & Anna-Bettina Haidich & Ioannis Niopas & Emmanuel Roilides
Received: 28 November 2013 / Revised: 13 March 2014 / Accepted: 24 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Linezolid is an oxazolidinone antibacterial agent, with activity against Gram-positive bacteria. This study aimed to evaluate the efficacy and safety of linezolid in children with infections caused by Gram-positive pathogens. A systematic search was conducted by two independent reviewers to identify published studies up to September 2013. The accumulated relevant literature was subsequently systematically reviewed, and a meta-analysis was conducted. Eligible studies were randomized controlled trials assessing the clinical efficacy and safety of linezolid in children versus other antimicrobial agents for infections caused by Gram-positive bacteria. The primary outcome was treatment success in patients who received at least one dose of study drug, had clinical evidence of disease, and had complete follow-up. Meta-analysis was conducted with random effects models because of heterogeneity across the trials. Two randomized controlled trials (RCTs),
involving 815 patients, were included. Linezolid was slightly more effective than control antibiotic agents, but the difference was not statistically significant [odds ratio (OR)=1.39, 95 % confidence interval (CI) 0.98–1.98]. Treatment with linezolid was not associated with more adverse effects in general (OR=0.61, 95 % CI 0.25–1.48). Eradication efficiency did not differ between linezolid and control regimens, but the sample size for these comparisons was small. Conclusion: The use of linezolid cannot be steadily supported from the results of the current meta-analysis. It appears to be slightly more effective than control antibiotic agents, but the difference was not significant, and the serious limitations present in this study restrict its use. Further studies providing evidence for clinical and microbiological efficacy of linezolid will support its use. Keywords Linezolid . Children . RCTs . Meta-analysis
Communicated by David Nadal M. Ioannidou : I. Niopas (*) Department of Pharmacognosy and Pharmacology, School of Pharmacy, Aristotle University, 54124 Thessaloniki, Greece e-mail:
[email protected] M. Ioannidou e-mail:
[email protected] F. Apostolidou-Kiouti : A.98th percentile for age), and increased respiratory rate (>2SD of normal for age). Fig. 1 Study selection
In addition to the inclusion signs and symptoms, other signs of septic shock (decreased peripheral perfusion or hypotension) and petechiae or purpura could also be used to meet inclusion for patients with catheter-related bacteremia. With regard to the definition of bacteremia of unknown origin, a clinical profile compatible with a diagnosis of bacteremia without an identified source was considered as equivalent to a diagnosis of bacteremia of unknown origin. In addition to the inclusion signs and symptoms, other signs of septic shock (decreased peripheral perfusion or hypotension) and petechiae or purpura could also be used to meet inclusion for patients with bacteremia of unknown origin. For a diagnosis of pneumonia, baseline chest radiograph needed to show new or progressive infiltrates, consolidation with or without effusion, and two of the following signs and symptoms: cough, new/worsened purulent sputum production, rales, pulmonary consolidation, or signs of respiratory distress (e.g., dyspnea, tachypnea, cyanosis, intercostal retractions, labored breathing, grunting, or nasal flaring). Patients with pneumonia could also have, as part of these two inclusion criteria, fever, hypothermia, leukocytosis, leukopenia or left shift of band neutrophils, increased pulse (>98th percentile for age), increased respiratory rate (>2SD of normal for age), requirement for mechanical ventilation, an increase in ventilator settings, altered mental status, lethargy, or irritability in infants
