title: The burden of bacteremia and invasive diseases in children aged less than five years with fever in Italy.
abstract: BACKGROUND
  Invasive diseases (ID) caused by Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis are a major public health problem worldwide. Comprehensive data on the burden of bacteremia and ID in Italy, including data based on molecular techniques, are needed.
  
  
  METHODS
  We conducted a prospective, multi-centre, hospital-based study (GSK study identifier: 111334) to assess the burden of bacteremia and ID among children less than five years old with a fever of 39 °C or greater. Study participation involved a single medical examination, collection of blood for polymerase chain reaction (PCR) and blood culture, and collection of an oropharyngeal swab for colonization analysis by PCR.
  
  
  RESULTS
  Between May 2008 and June 2009, 4536 patients were screened, 944 were selected and 920 were enrolled in the study. There were 225 clinical diagnoses of ID, 9.8 % (22) of which were bacteremic. A diagnosis of sepsis was made for 38 cases, 5.3 % (2) of which were bacteremic. Among the 629 non-ID diagnoses, 1.6 % (10) were bacteremic. Among the 34 bacteremic cases, the most common diagnoses were community-acquired pneumonia (15/34), pleural effusion (4/34) and meningitis (4/34). S. pneumoniae was the most frequently detected bacteria among bacteremic cases (29/34) followed by H. influenzae (3/34). Ninety percent (27/30) of bacteremic patients with oropharyngeal swab results were colonized with the studied bacterial pathogens compared to 46.1 % (402/872) of non-bacteremic cases (p < 0.001). PCV7 (7-valent pneumococcal conjugate vaccine) vaccination was reported for 55.9 % (19/34) of bacteremic cases. S. pneumoniae serotypes were non-vaccine serotypes in children who had been vaccinated. Mean duration of hospitalization was longer for bacteremic cases versus non-bacteremic cases (13.6 versus 5.8 days).
  
  
  CONCLUSIONS
  These results confirm that S. pneumoniae is one of the pathogens frequently responsible for invasive disease.
authors.affiliation: Division of Pediatric Immunology, Department of Health Sciences, University of Florence and Anna Meyer Children's University Hospital, Florence, Italy. Chiara.azzari@unifi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Azzari
authors.affiliation: Division of Pediatric Immunology, Department of Health Sciences, University of Florence and Anna Meyer Children's University Hospital, Florence, Italy. m.moriondo@meyer.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Moriondo
authors.affiliation: Istituto Giannina Gaslini, Ospedale Pediatrico IRCCS, Via Gerolamo Gaslini 5, 16148, Genoa, Italy. pasqualedipietro@ospedale-gaslini.ge.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Di Pietro
authors.affiliation: Azienda Ospedaliera Universitaria, Policlinico Consorziale di Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy. cesare.dibari@libero.it.
authors.forename: Cesare
authors.initials: C
authors.lastname: Di Bari
authors.affiliation: Anna Meyer Children's University Hospital, Florence, Italy. m.resti@meyer.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Resti
authors.affiliation: Anna Meyer Children's University Hospital, Florence, Italy. mannelli.francesco@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mannelli
authors.affiliation: Pediatric Highly Intensive Care Unit, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. susanna.esposito@unimi.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Paediatric Division, Bambino Gesù Children Hospital, v. Aurelia Km.30, 00100 Palidoro, Rome, Italy. guido.castelli@opbg.net.
authors.forename: Guido
authors.initials: G
authors.lastname: Castelli-Gattinara
authors.affiliation: Ospedale Santobono, Via Fiore Mario 6, 80129, Naples, Italy. antoniocampa2014@libero.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Campa
authors.affiliation: Ospedale Gaspare Salesi, via F. Corridoni, 60120, Ancona, Italy. debenedictis@ospedaliriunti.marche.it.
authors.forename: Fernando Maria
authors.initials: FM
authors.lastname: de Benedictis
authors.affiliation: Azienda Ospedaliera Maggiore della Carita', Corso Mazzini, n. 18, Novara, 28100, Italy. gianni.bona@maggioreosp.novara.it.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bona
authors.affiliation: CROS NT, SRL, Via Germania 2, 37136, Verona, Italy. lisa.comarella@crosnt.com.
authors.forename: Lisa
authors.initials: L
authors.lastname: Comarella
authors.affiliation: GSK Vaccines, Avenue Fleming 3, 1300, Wavre, Belgium. katsiaryna.x.holl@gsk.com.
authors.forename: Katsiaryna
authors.initials: K
authors.lastname: Holl
authors.affiliation: GSK Vaccines, Via A. Fleming 2, 37135, Verona, Italy. federico.e.marchetti@gsk.com.
authors.forename: Federico
authors.initials: F
authors.lastname: Marchetti
mesh_terms: D016470:Bacteremia / Q000150:complications / Q000191:economics* / Q000382:microbiology; D001419:Bacteria / Q000235:genetics* / Q000302:isolation & purification; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000191:economics* / Q000453:epidemiology / Q000382:microbiology; D017281:Cost of Illness; D004269:DNA, Bacterial / Q000032:analysis*; D005260:Female; D005334:Fever / Q000191:economics* / Q000453:epidemiology / Q000209:etiology; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007223:Infant; D007558:Italy / Q000453:epidemiology; D008297:Male; D016133:Polymerase Chain Reaction; D011446:Prospective Studies
chemical_list: D004269:DNA, Bacterial