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Diagnosis of Bacteremia in Febrile Neutropenic Episodes in Children With Cancer: Microbiologic and Molecular Approach

Santolaya, María E. MD*†; Farfán, Mauricio J. PhD‡; De La Maza, Verónica RN§; Cociña, Manuela MD§; Santelices, Felipe MD§; Alvarez, Ana M. MD†¶; Avilés, Carmen L. MD†∥; Becker, Ana MD†**; O'Ryan, Miguel MD††; Román, Paulina‡‡; Salgado, Carmen MD†§§; Silva, Pamela MD†∥; Topelberg, Santiago MD†¶¶; Tordecilla, Juan MD†¶¶; Varas, Mónica MD†¶; Villarroel, Milena MD*†; Viviani, Tamara MD†**; Zubieta, Marcela MD†§§; Torres, Juan P. PhD*

Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0b013e31822a37d7
Original Studies
Abstract

Background: Bacterial isolation using conventional microbiologic techniques rarely surpasses 25% in children with clinical and laboratory findings indicative of an invasive bacterial infection. The aim of this study was to determine the role of real-time polymerase chain reaction (RT-PCR) from whole blood samples compared with automated blood cultures (BC) in detection of relevant microorganisms causing bacteremia in episodes of high-risk febrile neutropenia (HRFN) in children with cancer.

Methods: Children presenting with HRFN at 6 hospitals in Santiago, Chile, were invited to participate. Blood samples were obtained at admission for BC, and at admission and 24 hours for RT-PCR targeting DNA of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa causing bacteremia in children with HRFN.

Results: A total of 177 HRFN episodes were evaluated from May 2009 to August 2010, of which 29 (16.3%) had positive BC, 9 (5%) positive for 1 of the 3 selected bacterial species: 5 for E. coli, 3 for S. aureus, and 1 for P. aeruginosa. RT-PCR detected 39 bacteria in 36 episodes (20%): 14 E. coli, 20 S. aureus, and 5 P. aeruginosa. The sensitivity, specificity, and positive and negative predictive values of RT-PCR compared with BC were 56%, 80%, 13%, and 97%. The final clinical diagnosis was compatible with an invasive bacterial infection in 30/36 (83%) RT-PCR-positive episodes.

Conclusions: In our series, RT-PCR significantly improved detection of the most relevant bacteria associated with HRFN episodes. Large number of patients and close clinical monitoring, in addition to improved RT-PCR techniques will be required to fully recommend RT-PCR-based diagnosis for the routine workup of children with cancer, fever, and neutropenia.

Author Information

From the *Department of Pediatrics, Hospital L. Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile; †Infectious Diseases Committee, National Children's Program for Antineoplastic Drugs (PINDA), Santiago, Chile; ‡Center for Molecular Studies, Hospital L. Calvo Mackenna, Department of Pediatrics, Faculty of Medicine, Universidad de Chile, Santiago, Chile; §Clinical Research Unit, Hospital L. Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile; ¶Department of Pediatrics, Hospital San Juan de Dios, Faculty of Medicine, Universidad de Chile, Santiago, Chile; ∥Department of Pediatrics, Hospital San Borja Arriarán, Faculty of Medicine, Universidad de Chile, Santiago, Chile; **Department of Pediatrics, Hospital Sótero del Río, Santiago, Chile; ††Program of Microbiology and Mycology, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile; ‡‡Pregraduate School, Faculty of Medicine, Universidad de Chile, Santiago, Chile; §§Department of Pediatrics, Hospital E. González Cortés, Faculty of Medicine, Universidad de Chile, Santiago, Chile; and ¶¶Department of Pediatrics, Hospital Roberto del Río, Faculty of Medicine, Universidad de Chile, Santiago, Chile.

Accepted for publication June 20, 2011.

Supported by Proyecto FONDECYT, Grant 1090194, Grant 11080113.

The authors have no conflicts of interest or funding to disclose.

Address for correspondence: María Elena Santolaya, MD, Atalaya 11152, Las Condes, Santiago. E-mail: msantola@med.uchile.cl.

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© 2011 by Lippincott Williams & Wilkins, Inc.