,

Serious bacterial
infection in children:
A new evidence
Dr. Manar Ahmed
PHC-NGHA

Introduction

Most neonates and young infants with fever

have a benign viral illness

The goal of the evaluation is to identify

those children who are at high risk for
serious bacterial illness (eg, bacteremia,
urinary tract infection, meningitis, bacterial
gastroenteritis, pneumonia), and who
therefore require empiric antimicrobial
therapy and possibly hospitalization.

Introduction

Early detection and specific clinical

intervention has been shown to be
crucial for the improved outcome of
patients with sepsis.

However, sepsis can be difficult to

distinguish from other, non-infectious
conditions in critically ill patients with
clinical signs of acute inflammation.

Therefore; in the early phase of the

disease process; it may be difficult to
decide on the appropriate therapeutic
measures for the individual patient.

Introduction

Additional specific information may

be helpful to increase the accuracy of
sepsis diagnosis at an early stage.

A parameter which fulfils these

demands to a high degree is
procalcitonin (PCT )

Introduction

Procalcitonin (PCT) is a precursor of the

hormone calcitonin, which is involved with
calcium homeostasis, and is produced by the Ccells of the thyroid gland.

It is there that procalcitonin is cleaved into

calcitonin, and a protein residue.

It is not released into the blood stream of

healthy individuals.

With the derangements that a severe infection

with an associated systemic response brings, the
blood levels of procalcitonin may rise to 100
ng/ml. In blood serum, procalcitonin has a halflife of 25 to 30 hours

Procalcitonin : fast and highly specific

increase in bacterial infection and sepsis

One major advantage ofProcalcitonin (PCT)compared

to other parameters is its early and highly specific
increase in response to severe systemic bacterial
infections and sepsis.

Thus, in septic conditions increased PCT levels can be

observed 3-6 hours after infectious challenge.

PCT levels are usually low in viral infections, chronic

inflammatory disorders or autoimmune processes.

PCT levels in sepsis are generally greater than 1-2

ng/mL and often reach values between 10 and 100
ng/mL, or considerably higher in individual cases, thus
enabling the diagnostic differentiation between these
various clinical conditions and a severe bacterial
infection (sepsis)

PCT increase reflects the continuous development from a healthy

condition to the most severe states of disease (severe sepsis and
septic shock)

Procalcitonin : best parameter for

early sepsis diagnosis

Among the available laboratory parameters,

PCT has been shown to be the most useful.

PCT has been demonstrated to be the best

marker for differentiating patients with
sepsis from those with systemic
inflammatory reaction not related to
infectious cause

PCT versus CRP

Summary receiver operating characteristic (SROC) curves comparing
serum procalcitonin (PCT) and C-reactive protein (CRP) markers for
detection of bacterial infections versus non-infective causes of
inflammation.

PCT versus IL-6 and IL-8

Receiver operating characteristics (ROC) curves comparing serum
procalcitonin (PCT), interleukin 6 (IL-6) and interleukin 8 (IL-8) for
detection of sepsis on day of admission to ICU.

Increased Procalcitonin values : best

indicator for the severity of infection
and organ dysfunction

PCT development accurately reflects

the progression of the disease; more
reliable than other parameters

Differentiation between SIRS, sepsis, severe sepsis and septic

shock
by PCT and IL-6

Procalcitonin kinetics can be used to

assess the effectiveness of treatment

As the septic infection resolves, Procalcitonin

(PCT) reliably returns to values below 0.5
ng/mL, with a half-life of 24 hours.

Consequently, in vitro determinations of PCT

can be used to monitor the course and
prognosis of life-threatening systemic
bacterial infections and to tailor the
therapeutic interventions more efficiently e.g.,
this has been demonstrated for the monitoring
of patients with ventilator-associated
pneumonia (VAP).

Typical course of PCT serum level according to patient's response to antibiotic treatment (n=109)

Impact on therapeutic decisions and

cost reduction

Initial studies on the economic

implication of utilizing PCT in the
diagnostic process did show that
systematic use of Procalcitonin (PCT)
for sepsis diagnosis and monitoring
may also have a positive impact on the
reduction of antibiotic treatment,
therefore allowing a shorter stay in the
ICU and lower costs per case

Cost savings by reduction of AB treatment days

PCT management of antibiotic use during an epidemic of enteroviral meningitis:
Unnecessary antibiotic treatment was stopped after exclusion of the bacterial
infection.
The decision to stop antibiotic treatment at a PCT value of < 0.5 ng/mL, without
clinical counter-argument (inappropriately pretreated bacterial meningitis
excluded), resulted in saving 2.4 days of antibiotics per patient (29.000 j in 2
months).

Application of available PCT assays for various clinical

settings
(adapted from Christ-Crain & Mller ,2005)

Four Markers May Help Distinguish

Bacterial From Viral Pneumonia in Children

Dr. Massimiliano Don, from University of Udine,

Italy, and colleagues tested the utility of
C-reactive

protein
procalcitonin
erythrocyte sedimentation rate
white blood cell count
supplemented by chest X-ray, in screening of bacterial
etiology of pediatric community-acquired pneumonia in
routine clinical practice.

This study suggests that C-reactive protein,

procalcitonin, erythrocyte sedimentation
rate and white blood cell count, and their
combinations, "have a limited role in the
separation of bacterial from viral
pneumonia in children.

Any combination, however, was sufficiently

sensitive and specific to be used routinely."

Procalcitonin: a marker of severity of

acute pyelonephritis among children.

Febrile urinary tract infection (UTI) is a

common problem among children, with
diagnosis and management of acute
pyelonephritis being a challenge,
particularly during infancy.

The distinction between acute

pyelonephritis and UTI without renal
involvement is very important, because

renal infection may cause parenchymal scarring and

thus requires more aggressive investigation and followup monitoring.

the distinction is not easy among children, because

common clinical findings and laboratory parameters are
nonspecific, especially among young children.

Objectives:

The objective of the study was to determine the

accuracy of PCT measurements, compared with Creactive protein (CRP) measurements, in
diagnosing acute renal involvement during febrile
UTI and in predicting subsequent scars, as
assessed with 99mTc-dimercaptosuccinic acid
(DMSA) scintigraphy.

In an attempt to differentiate acute pyelonephritis

from febrile UTI without renal lesions in a group
of 100 children, serum levels of procalcitonin
(PCT) was measured , a new marker of infection.

Piazzale S.M. della Misericovolio Procalcitonin: a marker of severity of acute pyelonephritis among children, Pediatrics. 2004 Aug;114(2):e249-54

Materials& methods

Serum CRP levels, erythrocyte sedimentation

rates, leukocyte counts, and PCT levels were
measured for 100 children, 1 month to 13 years of
age, admitted for suspected febrile UTI (first
episode).

Renal parenchymal involvement was evaluated

with DMSA scintigraphy within 5 days after
admission.

The DMSA study was repeated 6 months later if

the initial results were abnormal.

Results:

The mean PCT level was significantly higher in

acute pyelonephritis than in UTI without renal
lesions (4.48 +/- 5.84 ng/mL vs 0.44 +/- 0.30
ng/mL).

In these 2 groups,

the mean CRP levels were 106 +/- 68.8 mg/L and 36.4 +/- 26 mg/L,
mean erythrocyte sedimentation rates were 79.1 +/- 33 mm/hour
and 58.5 +/- 33 mm/hour, and
leukocyte counts were 18 492 +/- 6839 cells/mm3 and 16 741 +/5302 cells/mm3, respectively.

For the prediction of acute pyelonephritis, the

sensitivity and specificity of PCT measurements
were 83.3% and 93.6%, respectively; CRP
measurements had a sensitivity of 94.4% but a
specificity of only 31.9%. Positive and negative
predictive values for prediction of renal
involvement with PCT measurements were 93.7%
and 83% and those with CRP measurements were
61.4% and 83.3%, respectively.

Conclusion of the study

Serum PCT levels may be a sensitive and

specific measure for early diagnosis of acute
pyelonephritis and determination of the
severity of renal parenchymal involvement.

Therefore, this measurement could be useful

for the treatment of children with febrile
UTIs, allowing prediction of patients at risk
of permanent parenchymal renal lesions.

Procalcitonin May Help Detect Serious

Bacterial Infections in Febrile Infants

The prediction of SBIs in febrile infants without

apparent source by examination remains
challenging.

In the November 2003 issue of Pediatrics, GalettoLacour and colleagues reported that a white blood
cell count cutoff value of 15,000 cells/L had a
sensitivity of 52% and specificity of 79% in the
identification of serious bacterial infection in
febrile infants aged 7 days to 36 months.

C-reactive protein has higher sensitivity of 79%

and specificity of 91% for detecting SBI in febrile
infants, according to Pulliam and colleagues in
the December 2001 issue of Pediatrics.

Procalcitonin May Help Detect Serious

Bacterial Infections in Febrile Infants

Procalcitonin is a new biomarker that is

being studied as a diagnostic tool to detect
infection.

In the August 2007 issue of the Pediatric

Infectious Disease Journal, Andreola and
colleagues found that the area under
receiver operating characteristic curve was
better for procalcitonin (0.82) and Creactive protein (0.85) than for white blood
cell count (0.71) and absolute neutrophil
count (0.74).

Procalcitonin May Help Detect Serious

Bacterial Infections in Febrile Infants

A new prospective, cohort,

observational study of febrile infants
up to age 90 days without identifiable
source assesses the test performance
of procalcitonin

The Frederick H. Lovejoy, Jr, MD, Resident

Research Fund and an American Academy of
Pediatrics resident research grant supported
this study.

The General Clinical Research Center at

Children's Hospital Boston (National Center for
Research Resources, General Clinical Research
Centers Program, National Institutes of Health
grant) assisted with sample processing.

Pediatrics. 2008;122:701-710

Objectives:

The study goals were to evaluate the

test performance of procalcitonin for
identifying SBIs in febrile infants not
older than 90 days of age without an
identifiable bacterial source and to
determine the optimal cutoff value to
identify infants at low risk for SBIs.

Pediatrics. 2008;122:701-710

Materials& methods

In 234 febrile infants not older than 90 days of age

(median age, 51 days) who presented to an urban,
pediatric emergency department, an automated
high-sensitivity assay was used to measure serum
procalcitonin levels.

To optimize sensitivity and negative predictive

value for the detection of SBIs, the investigators
selected an optimal procalcitonin cutoff value.

Infants were classified as having definite, possible,

or no SBIs.
Pediatrics. 2008;122:701-710

Results:

Of 30 infants (12.8%) with definite SBIs, 4 had

bacteremia, 2 had bacteremia with urinary tract
infections (UTIs), and 24 had UTIs. Of 12 infants
(5.1%) with possible SBIs, 5 had pneumonia and 7
had UTIs.
Compared with mean procalcitonin levels in infants
with no SBI (0.38 1.0 ng/mL), mean procalcitonin
levels for definite SBIs (2.21 3.9 ng/mL) and
definite plus possible SBIs (2.48 4.6 ng/mL) were
significantly higher.
For definite SBIs, the area under the receiver
operating characteristic curve was 0.82 compared
with 0.76 for definite and possible SBIs. A cutoff
value of 0.12 ng/mL had a sensitivity of 95.2%,
specificity of 25.5%, negative predictive value of
96.1%, and negative likelihood ratio of 0.19 for
identifying definite and possible SBIs. This cutoff
value accurately identified all cases of bacteremia.

Pediatrics. 2008;122:701-710

Conclusion of the study

Procalcitonin has favorable test

characteristics for detecting [SBIs]
in young febrile infants

Procalcitonin measurements
performed especially well in
detecting the most serious occult
infections.
Pediatrics. 2008;122:701-710

Conclusion of the study

The performance of procalcitonin as a single

clinical marker of infection approaches that of
popular strategies that incorporate various
laboratory studies and clinical impression scores

However, the future utility of procalcitonin likely

depends on its combination with other clinical
data; better discrimination of infants with
bacterial and viral infections could potentially
lead to more focused evaluations of febrile
infants.
Pediatrics. 2008;122:701-710

Limitations!?

Conclusion

Measurement of procalcitonin can be used as a

marker of severe sepsis and generally grades
well with the degree of sepsis although levels of
procalcitonin in the blood are very low.

PCT has the greatest sensitivity (85%) and

specificity (91%) for differentiating patients
with SIRS from those with sepsis, when
compared with IL-2, IL-6, IL-8, CRP and TNFalpha

However, the test is not routinely used and has

yet to gain widespread acceptance

Meisner M, Tschaikowsky K, Palmaers T, Schmidt J (1999). "Comparison of procalcitonin (PCT) and C-reactive protein
(CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS". Crit Care 3 (1): 4550.
BalcI C, Sungurtekin H, Grses E, Sungurtekin U, Kaptanoglu B (February 2003). "Usefulness of procalcitonin for diagnosis
of sepsis in the intensive care unit". Crit Care 7 (1): 8590

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