241. A Pilot Study Evaluating Urine to Plasma Ratios of Inflammatory Cytokines to Allow for Discrimination of Urinary Tract as the Source of Serious Bacterial Infections in Young Febrile Infants
Session: Poster Abstract Session: Diagnostics: Miscellaneous
Thursday, October 8, 2015
Room: Poster Hall
Posters
  • ID Week 2015 Arrieta1.pdf (198.6 kB)
  • Background:

    Bacteremia is common among young febrile infants < 3 months (5% - 12%) and could be associated with complications or death.  Urinary tract infection (UTI) is the most common serious bacterial infection (SBI) in febrile infants. In this age group UTI is frequently complicated by bacteremia (12% - 20%). Recent data suggest that UTI, even when complicated by bacteremia, has better outcome than other SBI. A means to discriminate bacteremic UTI (B-UTI) from primary bacteremia (PB) would be helpful in the evaluation of these patients. We evaluated inflammatory cytokines [tumor necrosis factor (TNF) α, interleukin (IL)-1 β, and IL-6] levels in plasma and urine to discriminate B-UTI from other SBIs.

    Methods:

    After obtaining consent we scavenged urine and plasma specimens from infants < 3 months old evaluated in the emergency department for fever, and divided them in 4 diagnosis based cohorts [Controls (no UTI or PB), UTI, PB, and B-UTI]. We measured cytokine levels (TNFα, IL-β, and IL-6 ) using A2 multiplex ELISA (QuantaScientifics) in plasma and urine and described the urine/plasma (U/P) ratio of each cytokine for each cohort.

    Results:

    Plasma inflammatory cytokines were elevated in all infectious syndromes compared to controls; levels were consistently and noticeably higher in plasma compared to urine only in subjects with PB (Table 1). Inflammatory cytokines U/P ratios discriminate UTI as the source of SBI.U/P ratios of IL-1β and IL-6 were > 1 when UTI was present; highest on B-UTI suggesting  severe local renal inflammation. Specifically, IL-1β and IL-6 ratios were < 1 in PB subjects (Fig 1-3).

    Table 1 Mean cytokine levels

    Plasma

    Urine

    Control

    B-UTI

    PB

    UTI

    Control

    B-UTI

    PB

    UTI

    TNFα

    41.1

    51.9

    115.4

    63.7

    62.4

    18.7

    4.1

    81.9

    IL-1β

    26.7

    32.1

    96.1

    63.9

    18.1

    4379.1

    23.7

    509.8

    IL-6

    108.2

    326.33

    2058.6

    693.1

    12.3

    743.7

    245.4

    901.8

    Conclusion:

    Inflammatory cytokines are elevated in plasma during systemic infection as previously described. Urinary inflammatory cytokines are only elevated in UTI syndromes, reflecting local inflammatory process rather than filtration from plasma. The U/P ratio of these cytokines (IL-1β and IL-6) can be used to discriminate SBI from urinary tract origin allowing for less invasive evaluation and more cost effective treatment of febrile infants.

    Antonio Arrieta, MD, FIDSA1, Stephanie Osborne, BS, RN2, Siobhan Poling, MD3, David Michalik, DO4, Janet Hoang, BS5, Shirley Williams, PhD5, Robert Matson, PhD6 and Diane Nugent, MD5, (1)Pediatrics, University of California Irvine, Orange, CA, (2)Research Institute, CHOC Children's, Orange, CA, (3)UC Irvine SOM, Orange, CA, (4)Miller Children's Hospital of Long Beach, Long Beach, CA, (5)CHOC Children's, Orange, CA, (6)QuantiScientifics, Irvine, CA

    Disclosures:

    A. Arrieta, None

    S. Osborne, None

    S. Poling, None

    D. Michalik, None

    J. Hoang, None

    S. Williams, None

    R. Matson, quantiscientific: Shareholder , Provided equipment

    D. Nugent, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.