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(wileyonlinelibrary.com).
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 .
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 . 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 , but the drug is more expensive than vancomycin. We
alternative antibiotics . 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.  in a girl
setting; 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 . 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.
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