title: Molecular diagnosis of vascular access device-associated infection in children being treated for cancer or leukaemia.
abstract: Blood samples were collected for quantitative 16S rDNA analysis from the vascular access device (VAD) of patients presenting with fever at participating centres of the UK Children's Cancer and Leukaemia Group. In total, 260 of 301 episodes of fever were evaluable and were classified as probable, possible, unlikely or unclassifiable VAD-associated infection. The sensitivity of the 16S rDNA assay declined concomitantly with delays from time of presentation to sampling. The sensitivity with >0.125 pg of bacterial DNA/microL of whole blood was 80% for the 20 probable VAD-associated infections diagnosed with samples collected on the day of or day following presentation. The specificity rose with increasing amounts of bacterial DNA, from 93% with >0.125 pg, to 98% with 0.25-0.5 pg, and to 100% with >0.5 pg/microL blood. The positive predictive value (for probable or possible) was 88% (95% CI 70-98%) with 0.25 pg/microL, and 100% (95% CI 83-100%) with >0.5 pg/microL. All 18 (6.8%) episodes with >0.5 pg of bacterial DNA/microL blood were associated with positive blood cultures. Identifications derived from the DNA sequence were consistent with the blood culture identifications for 15 of the 17 episodes with a DNA sequence identification. The VAD was removed because of suspected infection in six (2.8%) of 216 episodes with <0.125 pg of bacterial DNA/microL, in one (5%) of 20 episodes with 0.125-0.25 pg/microL, in one (16.7%) of six episodes with 0.25-0.5 pg/microL, and in nine (50%) of 18 episodes with >0.5 pg/microL. A bacterial DNA concentration of >0.5 pg/microL in blood drawn through a central venous catheter at the time of fever presentation had a high positive predictive value for VAD-associated infection and predicted an increased risk of VAD removal because of suspected infection.
authors: Division of Infection, Barts and The London NHS Trust, London, UK. michael.millar@bartsandthelondon.nhs.uk
authors: M R
authors: MR
authors: Millar
authors: G
authors: G
authors: Johnson
authors: M
authors: M
authors: Wilks
authors: R
authors: R
authors: Skinner
authors: S
authors: S
authors: Stoneham
authors: B
authors: B
authors: Pizer
authors: S
authors: S
authors: Hemsworth
authors: A
authors: A
authors: Fogarty
authors: C
authors: C
authors: Steward
authors: R
authors: R
authors: Gilbert
authors: E M
authors: EM
authors: Hennessy
mesh_terms: D000293:Adolescent; D016470:Bacteremia / Q000175:diagnosis*; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification; D001769:Blood / Q000382:microbiology*; D002408:Catheters, Indwelling / Q000009:adverse effects* / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000150:complications*; D009369:Neoplasms / Q000150:complications*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D006113:United Kingdom
chemical_list: D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S