Successful portacath salvage using linezolid in children with acute leukemia

Successful Port-A-Cath Salvage Using Linezolid in Children With Acute Leukemia Rube´n B. Moreno, MD,1* Susana Rives, MD,1 Antonio Justicia, MD,1 Albert Catala`, MD,1 Anna Ruiz-Llobet, MD,1 Central venous catheter (CVC) removal is indicated when Simultaneous lock and systemic therapy with linezolid avoided the persistent catheter-related bloodstream infection (CRBSI) occurs.
removal of port-type-CVC in all cases. Treatment with linezolid was This is a retrospective study to analyze the use of linezolid as a salvage an alternative to catheter removal in these patients. Prospective therapy for CRBSIs due to coagulase-negative Staphylococci in studies are needed to confirm linezolid effectiveness as a salvage children diagnosed with acute leukemia. Seven treatment courses of treatment in CRBSI. Pediatr Blood Cancer 2013;60:E103–E105.
linezolid were administrated to six patients with port-type-CRBSI after non-effective intravenous vancomycin or teicoplanin treatment.
Key words: acute leukemia; catheter-related infections; children; linezolid 5 days before discarding them as negative. Isolated microorganismswere identified by the usual methods.
Central venous catheters (CVC) are an important source of The response to linezolid was defined as the absence of local catheter-related bloodstream infections (CRBSI), with high signs and symptoms of the previously demonstrated infection, and morbimortality and healthcare costs in patients with acute leukemia persistently negative serial blood cultures after the end of antibiotic (AL). The most frequent organisms responsible for CRBSI in therapy. Linezolid administration was stopped when one negative children with AL are coagulase-negative Staphylococci (CoNS), which have been associated with persistent and recurrentbacteremia despite the use of appropriate antibiotic regimens [1,2]. The Infectious Diseases Society of America’s Guidelinesrecommend the removal of long-term catheters in case of persistent Seven treatment courses with linezolid were administered to CRBSI. However, the use of systemic and lock-antibiotic therapy six patients, four patients diagnosed with acute lymphoblastic is allowed in case of uncomplicated CRBSI due to pathogens leukemia (ALL), and two with acute myeloid leukemia (AML).
other than S. aureus, P. aeruginosa, Bacillus species, Micrococcus Median age at diagnosis was 2.8 years (range: 1.9–6.6 years). In all species, Propionibacteria, fungi, or mycobacteria; and in children patients, a first-line treatment with intravenous glycopeptid had been administered prior to the use of linezolid, consisting of one Linezolid is a synthetic antibacterial agent active against a wide- course of intravenous vancomycin and six courses of intravenous range of Gram-positive aerobic bacteria and some Gram-positive teicoplanin, administered through the CVC without use of lock anaerobes, whose use in childhood has been described in therapy in any case. Patient characteristics at diagnosis, outcome, inmunocompetent children and pediatric cancer patients. However, and antibiogram information for each case is shown in Table I.
its efficacy and safety has not yet been clearly evidenced in children Of note, during the period study, four patients with AL having a with persistent CRBSI due to CoNS [4–7]. The aim of this study resistant CRBSI due to CoNS did not receive linezolid and had a was to analyze the clinical use of linezolid for CRBSIs caused by CVC replacement due to a complicated infection (pocket infection).
CoNS refractory to glycopeptide antibiotics in children diagnosed Linezolid treatment was administered both, systemic (p.o. at a dosage of 10 mg/kg t.i.d.) and catheter-lock (at a concentration of2 mg/ml every 72 hours) until a negative blood culture and recovery of neutrophil count was achieved. The mean duration of linezolidadministration was of 12.2 days (SD: 5.5 days).
From January 2008 to December 2011, a retrospective Microbiological eradication was achieved in all cases but one, observational study was conducted in children diagnosed with with a median time of 7 days (range: 3–11 days). CVCs were AL that received linezolid for persistent CRBSI due to CoNS.
preserved in all cases after therapy was discontinued with a median Persistent CRBSI was defined as the persistence of the infection time of follow up of 27 months (range from 10 to 30 months).
despite of an adequate first-line antibiotic to which the infecting Patient 1 developed a CVC pocket infection despite previous microbes were susceptible. Demographic information, clinicalcharacteristics, laboratory data, previous therapy, dosage, and days 1Department of Pediatric Hematology, Hospital Sant Joan de De´u, of linezolid treatment, as well as adverse events and outcome were Blood samples of at least 3 ml were processed with the BacT/ Conflict of interest: Nothing to declare.
Alert (bioMe´rieux) automatic incubation system and inoculated ÃCorrespondence to: Dr. Rube´n Berrueco, Department of Pediatric into an aerobical pediatric bottle, BacT/Alert PF, with tryptic soy Hematology, Hospital Sant Joan de De´u, Passeig Sant Joan de De´u, 2, media supplemented with brain heart infusion, sodium polyane- 08950 Esplugues de Llobregat, Spain. E-mail: [email protected] tholesulfonate, and activated charcoal. Cultures were incubated for Received 7 November 2012; Accepted 6 February 2013 DOI 10.1002/pbc.24520Published online 15 June 2013 in Wiley Online Library(
TABLE I. Patient’s and Antibiogram Information for Each Episode treatment for CRBSI due to CoNS. Although linezolid improved were performed during antibiotic treatment. Plasma concentrations local signs of clinical infection, avoiding CVC removal, the of linezolid were not evaluated due to its demonstrated 100% addition of systemic vancomycin was necessary to achieve CoNS bioavailability after oral administration [7].
eradication. Patient 6 was treated twice, but we considered that the None of our patients showed impairment of their clinical second CRBSI episode was due to a new infection, as this occurred condition, although persistent CRBSI was observed in one case. In more than 3 months after the first one, with several negative cultures this patient, linezolid did not achieve CoNS eradication, but the in between. Moderate thrombocytopenia (30,000–50,000/ml) in one administration of vancomycin allowed CRBSI eradication and avoided CVC removal. CVC removal was spared in all cases.
Adverse events related to linezolid seem to be less frequent and significant compared to the cases reported in adult patients [4]. Inour series, only one patient with Down syndrome showed a CVC removal is recommended for the management of persistent moderate decrease of platelet levels.
CRBSI in adults and children. However, uncomplicated CRBSI due Linezolid has demonstrated its effectiveness for the treatment to non-aggressive pathogens in patients with limited access sites, or of infections caused by resistant Gram-positive pathogens in when removal is not possible or not convenient, can be treated with children [8], but the drug is more expensive than vancomycin. We alternative antibiotics [3]. Our data suggest that children with AL propose to balance linezolid costs against the costs of repeated and persistent CRBSI due to CoNS treated with simultaneous lock hospital admissions, CVC removal, and prolonged treatment with and systemic linezolid might avoid CVC removal.
other antibiotics in some cases, such as resistant CRBSI. As the Linezolid use in childhood has been scarcely described [5–8].
bioavailability of linezolid is excellent after oral administration, Successful use of both lock and systemic treatment with linezolid when possible, treatment might be completed in an outpatient had been previously described by Castagnola et al. [9] in a girl setting;[7] this would lead to a further decrease of healthcare costs.
affected with cystic fibrosis, short-bowel syndrome, and first-line The present study has the inherent limitations of a small series of antibiotic-resistant CRBSI due to CoNS. Nevertheless, to the best of patients, retrospective and non-comparative study in which the our knowledge, the use of lock therapy with linezolid in children attending physicians made decisions based on their experience. In with AL has not been described, although some authors have summary, our experience supports that linezolid can be an suggested its possible usefulness in this setting [10]. We describe a alternative to avoid CVC removal for selected patients with series of six pediatric patients with AL and an implantable port- resistant CRBSI, particularly inmunocompromised children under- CVC who received linezolid as a treatment for CRBSI due to CoNS going chemotherapy. Further studies with larger number of patients resistant to first-line glycopeptide antibiotics.
are needed in order to draw a definite conclusion.
As catheter removal in case of infection would involve surgery, which might delay chemotherapy administration, we decided toadministrate both lock and systemic linezolid in uncomplicated persistent CRBSI due to CoNS in order to avoid CVC removal.
1. Allen RC, Holdsworth MT, Johnson CA, et al. Risk determinants for catheter-associated blood stream Close clinical evaluations and additional control blood cultures infections in children and young adults with cancer. Pediatr Blood Cancer 2008;51:53–58.
Linezolid Use to Avoid Central Catheter Removal 2. Adler A, Yaniv I, Steinberg R, et al. Infectious complications of implantable ports and Hickman catheters 7. Sullivan J, Tobias JD. Preliminary experience with the use of oral linezolid in infants for the completion of in paediatric haematology–oncology patients. J Hosp Infect 2006;62:358–365.
antibiotic therapy in the outpatient setting after admission to the pediatric intensive care unit. Am J Ther 3. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin 8. Kaplan SL, Deville JG, Yogev R, et al. Linezolid versus vancomycin for treatment of resistant Gram- positive infections in children. Pediatr Infect Dis J 2003;22:677–686.
4. Dotis J, Iosifidis E, Ioannidou M, Roilides E. Use of linezolid in pediatrics: A critical review. Int J Infect 9. Castagnola E, Moroni C, Gandullia P, et al. Catheter lock and systemic infusion of linezolid for treatment of persistent Broviac catheter-related staphylococcal bacteremia. Antimicrob Agents Chemother 5. Garazzino S, Krzysztofiak A, Esposito S, et al. Use of linezolid in infants and children: A retrospective multicentre study of the Italian Society for Paediatric Infectious Diseases. J Antimicrob Chemother 10. Castagnola E, Bandettini R, Lorenzi I, Caviglia I, Macrina G, Tacchella A. Catheter-related bacteremia caused by methicillin-resistant coagulase negative staphylococci with elevated minimal inhibitory 6. Moschovi M, Trimis G, Tsotra M, et al. Efficacy and safety of linezolid in immunocompromised children concentration for vancomycin. Pediatr Infect Dis J 2010;29:1047–1048.
with cancer. Pediatr Int 2010;52:694–698.


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