title: Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.
abstract: OBJECTIVE
  To determine efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection.
  
  
  METHODS
  Prospective, multicentre, randomized study in children presenting with FN at five hospitals in Santiago, Chile, evaluated at admission for diagnosis of bacterial and viral pathogens including PCR-microarray for 17 respiratory viruses. Children positive for a respiratory virus, negative for a bacterial pathogen and with a favourable evolution after 48 h of antimicrobial therapy were randomized to either maintain or withhold antimicrobials. Primary endpoint was percentage of episodes with uneventful resolution. Secondary endpoints were days of fever/hospitalization, bacterial infection, sepsis, admission to paediatric intensive care unit (PICU) and death.
  
  
  RESULTS
  A total of 319 of 951 children with FN episodes recruited between July 2012 and December 2015 had a respiratory virus as a unique identified microorganism, of which 176 were randomized, 92 to maintain antimicrobials and 84 to withdraw. Median duration of antimicrobial use was 7 days (range 7-9 days) versus 3 days (range 3-4 days), with similar frequency of uneventful resolution (89/92 (97%) and 80/84 (95%), respectively, not significant; OR 1.48; 95% CI 0.32-6.83, p 0.61), and similar number of days of fever (2 versus 1), days of hospitalization (6 versus 6) and bacterial infections throughout the episode (2%-1%), with one case of sepsis requiring admission to PICU in the group that maintained antimicrobials, without any deaths.
  
  
  CONCLUSIONS
  The reduction of antimicrobials in children with FN and respiratory viral infections, based on clinical and microbiological/molecular diagnostic criteria, should favour the adoption of evidence-based management strategies in this population.
authors.affiliation: Department of Paediatrics, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: M E
authors.initials: ME
authors.lastname: Santolaya
authors.affiliation: Department of Paediatrics, Hospital San Juan de Dios, Faculty of Medicine, Universidad de Chile, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: A M
authors.initials: AM
authors.lastname: Alvarez
authors.affiliation: Department of Paediatrics, Hospital Dr Roberto del Río, Faculty of Medicine, Universidad de Chile, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Acuña
authors.affiliation: Department of Paediatrics, Hospital San Borja Arriarán, Faculty of Medicine, Universidad de Chile, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: C L
authors.initials: CL
authors.lastname: Avilés
authors.affiliation: Department of Paediatrics, Hospital Dr Exequiel González Cortés, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Salgado
authors.affiliation: Department of Paediatrics, Hospital Dr Roberto del Río, Faculty of Medicine, Universidad de Chile, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Tordecilla
authors.affiliation: Department of Paediatrics, Hospital San Juan de Dios, Faculty of Medicine, Universidad de Chile, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Varas
authors.affiliation: Department of Paediatrics, Hospital San Juan de Dios, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Venegas
authors.affiliation: Department of Paediatrics, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Villarroel
authors.affiliation: Department of Paediatrics, Hospital Dr Exequiel González Cortés, Santiago, Chile; Committee of Infectious Diseases, National Child Programme of Antineoplastic Drugs Network, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Zubieta
authors.affiliation: Department of Paediatrics, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Toso
authors.affiliation: Department of Paediatrics, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Bataszew
authors.affiliation: Department of Paediatrics, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: M J
authors.initials: MJ
authors.lastname: Farfán
authors.affiliation: Department of Paediatrics, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: V
authors.initials: V
authors.lastname: de la Maza
authors.affiliation: Centre for Molecular Studies, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Vergara
authors.affiliation: Department of Paediatrics, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Valenzuela
authors.affiliation: Department of Paediatrics, Hospital Dr Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile. Electronic address: jptorres@clc.cl.
authors.forename: J P
authors.initials: JP
authors.lastname: Torres
mesh_terms: D000293:Adolescent; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002677:Chile; D064147:Febrile Neutropenia / Q000188:drug therapy*; D006761:Hospitals; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009369:Neoplasms / Q000150:complications; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D016896:Treatment Outcome; D014777:Virus Diseases / Q000188:drug therapy*; D028761:Withholding Treatment
chemical_list: D000890:Anti-Infective Agents
keywords: Antimicrobials; Cancer; Children; Febrile neutropenia; Respiratory viral infection