Characteristics of neonates with

culture-proven bloodstream infection

who have low levels of C-reactive protein
( 10 mg/L)

Mei-Yin Lai, Ming-Horng Tsai, Chiang-Wen Lee, Ming-

Chou Chiang, Reyin Lien, Ren-Huei Fu,
Hsuan-Rong Huang, Shih-Ming Chu and Jen-Fu Hsu
BMC Infectious Diseases (2015) 15:320
Background

Blood stream infection: Antibiotic treatment

High incidence Early and appropriate
Morbidity dan mortality Clinical & laboratory
parameter spesificity ?
C-reactive protein
acute-phase protein of hepatic origin
increases following IL-6 secretion from
macrophages and T-cells
Inflamation rises to > 5 mg/L after 6 h and
peaks at 48 h
CRP Cut-off?
1,5-20 mg/L
Min. 2 CRP levels, 10 mg/L and 24 h interval
unlikely to be infected
Bacteremia + normal CRP

Aim:
Characterize outcomes in neonates with culture-
proven BSI and a CRP plasma level 10 mg/L.
Methods
Event: all episodes of culture-proven BSI
Place: NICU of Chang Gung Memorial Hospital
(CGMH)
Time: 1 July 2004 and 30 June 2012
Database
full-time nurse specialist
Data: clinical manifestations, laboratory results,
progression of septic conditions, concurrent
infectious focus, treatment, infectious
complications, and outcomes.
The severity of illness was evaluated at the most
severe period during the course of BSI using the
neonatal therapeutic intervention scoring system
(NTISS)
Inclusion criteria
LOS clinical sepsis with a positive blood
culture obtained after 3 days of life
NICU criteria < 3435 gestational weeks or
birth weight < 2 kg or > 5 kg or those with any
clinical signs of respiratory distress or
cardiovascular, gastrointestinal, or neurological
problems requiring surgical or intensive
treatment
 positive blood culture
Blood stream Infection
treated with antibiotic for 5 or more days or shorter period if
the patient died,

at least two clinical
presence symptoms
of clinical sepsisof sepsis:
and identification of
Fever or hypothermia,
pathogens (any mortality
bacteria isolated
hyper- or hypoglycemia,
Sepsis-attributable from
died within at
3 days
least one
after apnea
the or
onset of blood
tachypnea, culture,
sepsis and those who excluding
died of infectious
frequent desaturation with an increased requirement for
saprophytic
complications skin flora,
or clinically Corynebacterium
progressive spp.,
deterioration
ventilator support,
Propionibacterium
following the onset
bradycardia of BSI
and/or spp., Penicillium spp., or
cyanosis,
Diphtheroids spp. )
feeding intolerance,
abdominal distension,
seizure,
Microbiology assay system matrix-assisted laser
decreased activity,
skin mottling and hypotension
desorption ionization time-of-flight (MALDI-TOF)
system (Brukers flagship FLEX series).
CRP data
10instrument
an immunoturbidimetric
Low mg/L (Modular
P, Roche, Germany)
Exclusion: BSI without CRP data at onset
MoreIntermediate 11
than 1 CRP data 100 mg/L
closest to the time of
obtained blood culture
Normal CRP in lab 5 mg/L, lower limit >
0.5 mg/L, no upper
High limit
> 100 mg/L
Statistical analysis
Differences in categorical and continuous variables
2 test and one-way ANOVA
continuous variables with large standard deviations
nonparametric KruskalWallis H test
Multivariate analyses sex, gestational age,
underlying chronic co-morbidities, and bacterial
subgroups
OR with 95 % confidence intervals
SPSS version 15.00
 1010 episodes of BSI (LOS) ( n= 793 )

incomplete medical records (n = 8)

No CRP measurement at BSI onset
(n = 12),
or transfer to another hospital (n =
4)

986 episodes of BSI (LOS) ( n= 772 )

Intermediate CRP High CRP (n=176)

Low CRP (n=247)
(n=563)
Low CRP ( 10 mg/L)
Low CRP repeated CRP test in 72% patients
46.1 % CRP response > 10 mg/L
at a median of 2.8 days (range 17
days) after antibiotic treatment
Low CRP repeated CRP test Low CRP
32,3% CoNS (+)
Discussion
CRP pathogen related
Pseudomonas severe tissue damage &
inflammation
CoNS 25-35% low CRP
Gestational age / body weight related
immature immunology response
CRP level ~severity of sepsis
CRP unrecommended
inadequate assensitivity
a guide to rule out serious
infection/ delay antibiotic therapy
Discussion
Only 46% with low CRP developed an increase in
later CRP test
Limitations:
Antibiotic decrease
Lack of 2 positive blood CRP after
culture for 16 h
CoNS
CoNS
Retrospective, single center
Various timing of blood sampling for CRP and blood
culture
No control of high CRP without infection