Efficacy and safety of linezolid in immunocompromised children with cancer

Moschovi, Maria; Trimis, Georgios; Tsotra, Maria; Chatzi, Fotini; Karamolegou, Kalliopi; Santou, Antina; Tourkantoni, Natalia; Chrousos, George P.

doi:10.1111/j.1442-200x.2010.03097.x

Cited by 15 publications

(17 citation statements)

References 31 publications

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“…However, this is not assumed to be the case for the toddler, based on the above-described work with caspofungin, and associated predictions are included for comparative purposes. General recommendations for pediatric dosing of linezolid are 10 mg/kg every 8 to 12 h for 14 to 28 days (13,18). It can be seen that the present theory and calculations shown in Table 2 (for both dose and interval) are in good agreement with these dosing recommendations.…”

Section: Figsupporting

confidence: 77%

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Scaling Adult Doses of Antifungal and Antibacterial Agents to Children

Dawson¹

2012

Antimicrob Agents Chemother

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My general pharmacokinetic scaling theory is discussed for the important matter of determining pediatric dosing for existing and new therapeutic drugs when optimal, or near-optimal, dosing for adults is known. The basis for the scaling is the requirement of a time-scaled likeness of the free-drug concentration time histories of children and adults. Broad categories of single and periodic dosing are considered. The former involves the scaling of dosage, and the latter involves both the dosage and schedule. The validity of the scaling relations is demonstrated by using measurements from previously reported clinical trials with adults and children (with ages generally 1 year or older) for the relatively new antifungal agent caspofungin and for the relatively new antibacterial agent linezolid. Standard pharmacodynamic effectiveness criteria are shown to be satisfied for the scaled dosage and schedule for children to the same extent that they are for the referenced adult. Consideration of scaling from adults to children is discussed for the case of new agents where no pediatric data are available and needed parameters are determined from in vitro measurements and preclinical animal data. A connection is also made between the allometric representation of clearance data and the dosing formulas. Limitations of the scaling results for infants because of growth and maturational matters are discussed. The general conclusion from this work is that the scaling theory does indeed have application to pediatric dosing for children, for both confirmation and refinement of present practice and guidance in pediatric treatment with new therapeutic agents.

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Section: Figsupporting

confidence: 77%

“…The latter equations are like equations 6 and 7 for single dosing except that, now, the left-hand side refers to the dose per interval, with the latter being defined by equation 18. The recognition that the scaling of the dose should be accompanied by the scaling of the time interval between dosing was discussed previously by Mordenti (17).…”

Section: Figmentioning

confidence: 99%

Scaling Adult Doses of Antifungal and Antibacterial Agents to Children

Dawson¹

2012

Antimicrob Agents Chemother

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“…Linezolid use in childhood has been scarcely described . Successful use of both lock and systemic treatment with linezolid had been previously described by Castagnola et al in a girl affected with cystic fibrosis, short‐bowel syndrome, and first‐line antibiotic‐resistant CRBSI due to CoNS.…”

Section: Discussionmentioning

confidence: 99%

“…Linezolid is a synthetic antibacterial agent active against a wide‐range of Gram‐positive aerobic bacteria and some Gram‐positive anaerobes, whose use in childhood has been described in inmunocompetent children and pediatric cancer patients. However, its efficacy and safety has not yet been clearly evidenced in children with persistent CRBSI due to CoNS . The aim of this study was to analyze the clinical use of linezolid for CRBSIs caused by CoNS refractory to glycopeptide antibiotics in children diagnosed with AL.…”

Section: Introductionmentioning

confidence: 99%

Successful port-a-cath salvage using linezolid in children with acute leukemia

Moreno

Rives

Justicia

et al. 2013

Pediatr Blood Cancer

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Central venous catheter (CVC) removal is indicated when persistent catheter-related bloodstream infection (CRBSI) occurs. This is a retrospective study to analyze the use of linezolid as a salvage therapy for CRBSIs due to coagulase-negative Staphylococci in children diagnosed with acute leukemia. Seven treatment courses of linezolid were administrated to six patients with port-type-CRBSI after non-effective intravenous vancomycin or teicoplanin treatment. Simultaneous lock and systemic therapy with linezolid avoided the removal of port-type-CVC in all cases. Treatment with linezolid was an alternative to catheter removal in these patients. Prospective studies are needed to confirm linezolid effectiveness as a salvage treatment in CRBSI.

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“…A potential concern with linezolid is the occurrence of medication-induced bone marrow suppression; this could be potentially worrisome in the already immunocompromised host. A series of 17 pediatric cancer patients from Athens, Greece sought to evaluate the safety and efficacy of linezolid for Gram-positive infections in this population 102. All patients achieved microbiologic cure in this small series; 23.5% experienced adverse events; however, chemotherapy induced myelosuppression did not appear to be exacerbated by linezolid.…”

Section: Specific Antimicrobial Therapy For Drug Resistant S Aureus mentioning

confidence: 99%

Staphylococcus aureus – antimicrobial resistance and the immunocompromised child

McNeil¹

2014

IDR

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Children with immunocompromising conditions represent a unique group for the acquisition of antimicrobial resistant infections due to their frequent encounters with the health care system, need for empiric antimicrobials, and immune dysfunction. These infections are further complicated in that there is a relative paucity of literature on the clinical features and management of Staphylococcus aureus infections in immunocompromised children. The available literature on the clinical features, antimicrobial susceptibility, and management of S. aureus infections in immunocompromised children is reviewed. S. aureus infections in children with human immunodeficiency virus (HIV) are associated with higher HIV viral loads and a greater degree of CD4 T-cell suppression. In addition, staphylococcal infections in children with HIV often exhibit a multidrug resistant phenotype. Children with cancer have a high rate of S. aureus bacteremia and associated complications. Increased tolerance to antiseptics among staphylococcal isolates from pediatric oncology patients is an emerging area of research. The incidence of S. aureus infections among pediatric solid organ transplant recipients varies considerably by the organ transplanted; in general however, staphylococci figure prominently among infections in the early posttransplant period. Staphylococcal infections are also prominent pathogens among children with a number of immunodeficiencies, notably chronic granulomatous disease. Significant gaps in knowledge exist regarding the epidemiology and management of S. aureus infection in these vulnerable children.

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Efficacy and safety of linezolid in immunocompromised children with cancer

Abstract: Linezolid may be another effective and safe therapy to treat infections from resistant Gram-positive bacteria in immunocompromised children, even in young ages.

Cited by 15 publications

References 31 publications

Scaling Adult Doses of Antifungal and Antibacterial Agents to Children

Scaling Adult Doses of Antifungal and Antibacterial Agents to Children

Successful port-a-cath salvage using linezolid in children with acute leukemia

Staphylococcus aureus – antimicrobial resistance and the immunocompromised child

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Efficacy and safety of linezolid in immunocompromised children with cancer

Abstract: Linezolid may be another effective and safe therapy to treat infections from resistant Gram-positive bacteria in immunocompromised children, even in young ages.

Cited by 15 publications

References 31 publications

Scaling Adult Doses of Antifungal and Antibacterial Agents to Children

Scaling Adult Doses of Antifungal and Antibacterial Agents to Children

Successful port-a-cath salvage using linezolid in children with acute leukemia

Staphylococcus aureus &ndash; antimicrobial resistance and the immunocompromised child

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Product

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Staphylococcus aureus – antimicrobial resistance and the immunocompromised child