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understanding neonatal sepsis
Definition
Neonatal septicemia is defined as generalized

systemic infection of the newborn,associated with
pure growth of bacteria from one or more sites.
It is one of the most important causes of mortality
and morbidity in newborn.
Among the low birth weight & pre term
babies,neonatal septicemia is the most important
cause of mortality,especially in developing countries
including India.
According to NNPD-2,the incidence ranges from 0.1

to 4.5 percent with an overall mortality rate varying
from 22-30%.

With an estimated 25 million births occuring in India

and approximately 2% incidence of sepsis,the figure
for neonatal sepsis in India would be 5,00,000 babies
every year with about one-third,i.e.170,000 babies
succumbing to the disease.
 When pathogenic bacteria gain access into the blood

stream,

they may cause overwhelming infection without much

localization (septicemia),
may get predominantly localized to the lung
(pneumonia),
the meninges (meningitis).
Importance.
 Neonatal sepsis is the single most important cause of

neonatal deaths in the community, accounting for
over half of them.

 If diagnosed early and treated aggressively with

antibiotics and good supportive care, it is possible to
save most cases of neonatal sepsis.
Classification.
 Neonatal sepsis can be classified into two sub-types

depending upon whether the onset of symptoms is
before 72 hours of life (early onset) or later (late
onset).
Early onset sepsis
Early onset sepsis (EOS) often presents as a

fulminant, multi-system illness within 72 hours of
delivery and is mainly due to bacteria acquired before
and during delivery
Early onset sepsis manifests frequently as pneumonia

and less commonly as septicemia or meningitis.
The associated factors for early-onset sepsis include
low birth weight,
prolonged rupture of membranes > 24 hours,
foul smelling liquor,
multiple per vaginum examinations,
maternal fever,
difficult or prolonged labour,
and aspiration of meconium.
Risk factors for neonatal sepsis.
Maternal factors:
Fever,
Urinary tract infection,diarrhea,
Prolonged rupture of the membrane>24hrs,
Foul smelling amniotic fluid,
Maternal amnionitis,
Maternal genital tract infection,& genital colonization,
Socio economic factors:poor socio economic

status,poor nutrition and hygiene.
Neonatal factors:
Preterm and low birth weight,
Perinatal asphyxia,
Vigorous resuscitation,
Invasive procedures,
Congenital malformations,e.g.meningomyelocele,
Male child.
Risk factors.
Prolonged rupture of membranes(PROM):the risk is

reported to be 1% percent compared to a baseline
incidence of 0.1 to 0.5 percent.
Chorioamnionitis:increases the risk of sepsis by 2 to 3
times.
If PROM is associated with chorioamnionitis ,the risk
of sepsis increases by four fold.
Prematurity & low birth weight:pre term babies are

deficient in immunoglobulin
concentration,complement function & phagocytic
activity.
They have 3 to 10 times higher risk of developing
sepsis than term infants.
Chorioamnionitis may coexist & may trigger for
preterm labor.
Association of chorioamnionitis is and low birth
weight increases the risk of sepsis to 16 percent
compared to association with normal weight babies.
Perinatal asphyxia:asphyxia is associated with

depressed immune function.in addition,several
interventional procedures increase the risk of
infection.
Presence of low apgar score (6 or less at 5
minutes)along with prolonged rupture of membranes
has shown to increase the risk of infection by 4% &
27%.
Male gender:boys have 2 to 6 times higher risk of
development of neonatal sepsis.
Other factors:maternal fever,G.U.T.infection,poor
socio economic condition & feeding artificial milk.
Late onset sepsis.
Late-onset septicemia is caused by the organisms

thriving in the external environment of the home or
the hospital.

late onset sepsis (LOS) can present as either a

fulminant or a smoldering infection.
The infection is often transmitted through the hands

of the care-providers.

The onset of symptoms is usually delayed beyond 72

hours after birth and the presentation is that of
septicemia, pneumonia or meningitis.
The associated factors of late-onset sepsis include:
low birth weight,
lack of breastfeeding,
superficial infections (pyoderma, umbilical sepsis),
aspiration of feeds,
disruption of skin integrity with needle pricks and use

of intravenous fluids.
These factors enhance the chances of entry of

organisms into the blood stream of the neonates
whose immune defences are poor as compared to
older children and adults.
National neonatology forum of India defines neonatal

sepsis as follows;

Proven sepsis:the baby presents with clinical picture of

sepsis & isolation of pathogens from blood,csf.,urine or
other body fluids or autopsy evidence of sepsis.
Probable sepsis:newborn with clinical picture
suggestive of sepsis with one or more of the following
criteria
Existence of predisposing factors,e.g.maternal fever foul
smelling liquor or prolonged rupture of the membrane (>12
hours) or gastric polymorphs more than 6/high power field.
 Positive sepsis screen(2 of the 4 parameters to be present).
 Total leukocytes count<5,000/mm3,immature to total
neutrophil count ratio>0.2,c-reactive protein positive &
micro ESR > 15 mm/1st hour or >age in days + 3.
 Radiological evidence of pneumonia.

Sepsis syndrome:when septicemia is associated with

altered organ perfusion(hypoxia,increased blood
lactate,oliguria & altered mental state)it is termed as
sepsis syndrome.
If untreated,this condition leads to early septic shock
with decreased capillary refilling and low blood
pressure,which can be reversible with appropriate
treatment.
If untreated,this state progresses quickly into
refractory shock & leads to multi organ dysfunction.
The common organisms reported by NNPD Survey

showed 3.8 percent incidence of neonatal sepsis from
pooled hospital data with
Klebsiella,
Staph.aureus,
Esch.coli,
Pseudomonas,
Enterobacter,
Coagulase negative staphylococcus,
Acenatobacter and
Candida as the predominant organisms.
In the Indian subcontinent, the distinction between

EOS and LOS is somewhat blurred (Sundaram V et al).

The clinical presentations of EOS and LOS are

different and the risk factors are different, but the
organisms causing the EOS and LOS are similar and
so are their antibiograms (Zaidi AK et al,NNPD NETWORK).
The early & efficient diagnosis of neonatal bacterial

sepsis remains a difficult task since most of the
symptoms & signs of sepsis in the neonatal period are
of non specific nature.
The spectrum & severity of symptoms required to
decide in the evaluation of sepsis is a matter of clnical
judgement.
It is estimated that between 11 & 23 non infected
newborns are treated in neonatal intensive care
nurseries for every one with documented infection.
Clinical features
The manifestations of neonatal septicemia are often vague

and therefore demand a high index of suspicion for early
diagnosis.

The possibility of sepsis must be considered with any

clinical deterioration unless the event is readily explained
by other causes.

The most common and characteristic manifestation is
 An alteration in the established feeding behavior in late
onset sepsis,
 Respiratory distress in early onset sepsis.
understanding neonatal sepsis
The baby, who had been active and sucking well,

gradually or suddenly, becomes lethargic, inactive or
unresponsive and refuses to suckle.
Hypothermia is a common manifestation of sepsis,
whilst fever is infrequent.
Diarrhea, vomiting and abdominal distension may
occur.
Episodes of apneic spells or gasping may be the only

manifestation of septicemia.

In sick neonates, the skin may become tight giving a

hide-bound feel (sclerema) and the perfusion
becomes poor (capillary refill time of over 3 seconds).

Cyanosis may appear.
The additional features of pneumonia or meningitis

may be present depending upon the localization of
infection in different systems and organs of the body.
The evidence of pneumonia includes
tachypnea,
chest retractions,
grunting,
early cyanosis,
apneic spells in addition to inactivity and poor feeding.

Cough is unusual.
Findings on auscultation of the chest are non-specific

and non- contributory.
Meningitis is often silent, the clinical picture being

dominated by manifestations of associated
septicemia.

the appearance of excessive or high-pitched crying,
fever,
seizures,
blank look,
neck retraction,
bulging anterior fontanel are highly suggestive of

meningitis.
Classification of sick young infants
for bacterial infection(WHO).
 Convulsion,

 Fast breathing,
 Severe chest indrawing,
 Nasal flaring,
 Grunting,
 Bulging fontanelle,
 Pus draining from ear,
 Umbilical redness extending to skin,

possible
serious
bacterial
infection.

 Fever or hypothermia,
 Many or severe skin pustules,
 Lethargic or unconscious,or less than normal movement.
 Red umbilicus or draining pus,
 Skin pustules

local bacteria infection.
Laboratory diagnosis.
Sensitivity:if infection is present,how often is the test

result abnormal?

Specificty:if infection is absent,how often is the test

result normal?

Positive predictive value:if the test result is

abnormal,how often is the infection present?
Negative predictive value:if the test result is
normal,how often is infection absent?
Diagnostic tests with maximal(100%)sensitivity &

negative predictive value are desirable for diagnosis of
neonatal sepsis.

This indicates if infection were present,the result

would always be abnormal & if results were
normal,infection would always be absent.

A good specificity & positive predictive value is also

acceptable.
Diagnostic tests.
Definitive,specific

Nonspecific,diagnostic

Blood culture,

White blood cell count,

Cerebrospinal fluid

C-reactive protein(CRP),

examination & culture,
Urine culture,
Tracheal aspirates,
Polymerase chain reaction,
Latex particle agglutination
test.

Erythrocyte sedimentation

rate,
Other acute phase reactants,
Miscellaneous tests.
Definitive,specific diagnostic
tests.
Isolation of organism from blood or a central body

fluid is the standard & most specific method to
confirm the diagnosis of neonatal sepsis.
The main draw back is that,the results are available
after 48 to 72 hrs.
Another dilemma often faced by the clinicians is the
high percentage of cases(upto 40%)where no bacteria
can be isolated from blood even in highly suspected
cses of sepsis.
Blood culture.
The standard is to collect 1 ml of blood by sterile

venepuncture in a blood culture bottle.
Umblical artery catheter is preferred over umbilical
vein catheter for sampling.
The blood culture should be incubated for at least 72
hours before being considered negative.
In a study conducted by Geme JW et al,13 percent of
positive blood culture did not grow until beyond 72
hours.
The late growing organisms were anaerobes &
coagulase negative staphylococci.
Blood culture should not be considered as the final

arbiter for the clinical diagnosis of neonatal infections
because,
It is negative in 20% cases where infection was proven

by immedite post mortem culture and autopsy.
In the mildly symptomatic neonate and at the earliest
onset of septicemia,the false negative blood culture rate
would be very high.
In upto 50% of cases with congenital bacterial
pneumonia proved by tracheal aspirate culture ,blood
culture is negative.
In a prospective observational study from India, 101

cases of suspected neonatal sepsis were used to
compare the manual method of blood culture with an
automated BacT/Alert system for detection of
neonatal septicemia.
The mean times to positivity with the manual and
BacT/Alert 3D systems were 53.1 h and 14.3 h,
respectively (p <0.001)(Hasana AS,et al)
With conventional methods the detection rate is
89.1% by day 2 and 99.5% by day 4.
Cerebro-spinal fluid (CSF)
examination.
In an unstable neonate, the LP can be deferred, until

stabilization is achieved.

The cellular and biochemical abnormalities in the

CSF of older patients with bacterial meningitis persist
for up to 3 days.

Gram positive bacteria clear in 36 hours of

appropriate therapy whereas gram negative bacteria
may take up to 5 days.
Apart from culture and gram stain, 4 parameters are

commonly evaluated:

total WBC count (per micro L),
percentage neutrophil count,
glucose
protein.
Traditionally, the following cut-offs have been used:
30 cells,
more than 60% of polymorphs,
glucose less than 50% of blood glucose,
protein more than 150 mg/dL in term babies and 180

mg/dL in preterm babies.
These cut-offs are no longer acceptable as they are based
on old normative data, and represent an over-simplified
approach based on single cut-off points derived from 2
standard deviation values.
Preterm infants: Treat if CSF WBC count ≥10 OR

glucose <24 OR protein >170.
Do not treat if “CSF WBC count <10 AND glucose ≥25
AND protein <170”.
For in-between results, clinical judgment will have to
be used, keeping in mind clinical features (seizures,
degree of altered sensorium, fullness of fontanelles)
and prematurity (the lower the gestation, lower
should be the threshold for diagnosis).
Term infants: Treat if CSF WBC count >8 OR glucose

<20 OR protein >120.

There is no safe cut-off at which one can recommend

“do not treat”. Clinical judgment as above would have
to be used.(The WHO Young Infant Study Group, Ahmed AS et al,
Smith PB et al, Garges HP et al)
In a neonate with meningitis not showing clinical

recovery after institution of antibiotics, LP should be
repeated after 48 hours.
If the LP is traumatic, the CSF should be sent for
gram stain and culture.
The concentration of glucose is not significantly
altered by a traumatic lumbar puncture.
Therefore a low CSF glucose in the setting of a
traumatic LP is abnormal.
Ideally, the WBC cell count must be performed

within 30 minutes of drawing the sample.

It must be noted that CSF WBC and glucose rapidly

fall with time, giving spurious results(Rajesh NT,et al).
Tracheal aspirate.
Useful in first 12 hours of life.
A positive tracheal culture may be found in 44% cases

with pneumonia were blood culture was sterile.

There is a positive co-relation of tracheal aspirate

gram stain for bacteria with clinical or pathological
pneumonia and has a 47% predictive accuracy in
bacteremic infants.
Latex particle agglutination tests:a relatively simple

test to perform but is not very sensitive.
The standard kits for group B
streptococcus,pneumococcus and meningococcus are
available & hence cannot be used routinely.
Polymerase chain reaction:a definitive
advancement,but the prohibitive cost & difficult
technique precludes its use in the routine evaluation
of neonatal sepsis.
Nonspecific diagnostic septic
screening tests.
These tests indicate infection without identifying the

infecting micro organisms.
Because of the severity of the disease,it is essential for
these indirect tests not to miss any case(have 100%
sensitivity),
To rule out convincingly sepsis when it is not
present(have a high negative value).
White blood cell count.
A total leukocyte count<5000/mm3,
Total neutrophil count<1750/mm3,
An immature to total neutrophil count ratio(I/T)of

>0.2 are suggestive of sepsis.
It has been well documented that the CBC depends

upon the infant’s age,on whether the sample is
arterial or venous,and on whether the infant is crying
vigorously.

This means that for a given infant,a test value is not a

static value;there is considerable intraindividual
variability.
In addition,maternal hypertension,perinatal asphyxia

& intra ventricular h’age may cause neutropenia.

Non specific stresses such as asphyxia,maternal fever

or stressful labor can elevate the I/T ratio.

The presence of neutrophil vacuolization or toxic

granulation are also good indicators of neonatal
sepsis.
C-reactive protein.
CRP is a rapidly responsive acute phase

reactant,synthesizd by the liver within 6-8 hrs of
stimulus of inflammatory process.
A positive CRP latex agglutination test corresponds to
plasma CRP concentration of 0.8 to 1.0 mg/dl.
A single value of negative CRP done at the outset may
not be of much significance.
Therefore,n suspected cases,a repeat CRP test is done
12 hours later is more significant.
If the test is negative negative-it almost excludes
sepsis.
Normalization of CRP is a helpful tool in determining

the response to antimicrobial therapy and duration of
treatment.

Failure to mount a CRP response is a poor prognostic

sign.
Erythrocyte sedimentation
rate.
Micro ESR is an inexpensive & easy bedside screenig

test for neonatal sepsis.

Normal values increase with postnatal age & are equal

to the day of life plus 3mm/hour upto a maximum of
15 mm/hour.

ESR is less sensitive but more specific than CRP or I/T

rato.
Other acute phase reactants
Haptoglobin & orosomucoid are acute phase

reactants that have been evaluated for diagnostic aids
for neonatal sepsis,are of limited utility because of
their slower response to infection.

A low plasma fibronectin concentration is

suggestive of neonatal sepsis,

It is also depressed by RDS & perinatal asphyxia,thus

limiting its use.
Miscellaneous tests.
Elastase-alpha-1-proteinase inhibitor

complex:raises rapidly,100% sensitive but not highly
specific.
C3D,
Endotoxin,
Direct visualization of bacteria in neutrophils
stained by acridine orange,
NBT reduction by neutrophils,
Gastric aspirate of polymorph count & culture:has
limited value,indicative of high risk because of
exposure to chorioamnionitis.
Newer diagnostic modalities.
Procalcitonin:a pro-peptide,released into the blood

3-6 hrs after endotoxin injection & increses upto 24
hours.
Very high serum procalcitonin levels are present in
neonates with proven or clinically diagnosed bacterial
infection;early decrease of these concentrations
reflects appropriate antibiotic therapy.
Compared with CRP,proclcitonin has the advantage
that it increases more rapidly.
A recent meta analysis showed that procalcitonin
showed better accuracy than the CRP test for LOS.
Cytokines and receptors.
Interleukin-6(IL-6),
Interleukin-1 receptor antagonist(IL-1ra)
The level of these two markers increases two days

before clinical diagnosis of sepsis.
IL-6 although a very early marker,the level becomes
normal later even if infection continues.
The simultaneous determination of CRP can obviate
this problem because the rise in plasma CRP levels
occurs 12 to 48 hours after the onset of infection,at a
time when IL-6 level would have fallen.
Specific leukocyte surface
antigens.
CD11b-promising marker for diagnosing early onset

sepsis.
CD64-late onset sepsis.
Preterm express CD 64 to the same degree as those
from term infants,children & adults.
G-CSF;a higher level has been found to be associated
with a sensitivity of 95 percent for prediction of sepsis
& a specificity of 73 percent if the level is >200pg/ml.
The best combination for newer markers for sepsis

would be estimation of

IL-6,IL-1ra:1-2 days before the onset of symptoms,
IL-6,IL-1ra,IL-8,CD 11b,G-CSF,TNF,CRP & hematological

indices on day 1,
CRP on the following days to monitor response to
treatment.
CD 64 is probably one of the most useful infection
markers for diagnosis of late onset nosocomial sepsis.
However,none of the current diagnostic markers are

sensitive and specific enough to influence the
judgement to withhold antimicrobial treatment
independent of the clinical findings.
Approach to a neonate with
suspected EOS.
There is no rationale for performing a “sepsis screen”

(i.e. CRP,hematological parameters, micro ESR) in
suspected EOS.
The negative predictive value (NPV) of various sepsis
screen parameters is too low to confidently rule out
EOS (Benitz WE et al, Mahale R et al,).
Procalcitonin and IL-6 are more promising than the
standard screen for the diagnosis of EOS, but they are
currently not easily available on the bedside and are
not considered standards of care.
Neonates who turn symptomatic within 72 hours

must be clinically assessed for probability of sepsis.

Twenty percent of symptomatic neonates in India

suspected to have EOS are blood culture positive
(Mahale R et al).
The following neonates need not be immediately

started on antibiotics but their clinical course must be
carefully monitored:
Those who are born without any of the known risk

factors of sepsis
preterm,

premature rupture of membranes (pPROM),
prolonged rupture of membranes (PROM) >18 hrs,
spontaneous preterm onset of labor (SPTOL),
clinical chorioamnionitis,
foul smelling liquor,
unclean vaginal examinations,
maternal fever,
maternal urinary or other systemic infections,
frequent (>3) per vaginal examinations in labor,
perinatal asphyxia,
and maternal recto-vaginal group B Streptococcus

carriage],

AND
 Chest X ray is not suggestive of pneumonia,
 Have alternative reasons to explain the symptoms.
Those symptomatic neonates with any of the known

risk factors or who have a chest X-ray suggestive of
pneumonia or do not have any alternate explanation
for the signs, must be immediately started on
antibiotics after drawing a blood culture.
Lumbar puncture (LP) for CSF examination must be
performed in all symptomatic neonates, with the
exception of premature neonates presenting with
respiratory distress at birth with no risk factors for
sepsis (Eldadah M et al, Weiss MG et al,)
The decision for performing LP should not be based
on sepsis screen results or blood culture results.
Approach to a neonate with
suspected LOS.
Neonates who become symptomatic after 72 hours

must be evaluated for LOS.

30% neonates clinically suspected to have LOS in an

NICU setting have positive blood culture (Singh SA et al).

A single episode or transient presence of one of the

above signs may not warrant any action. The more
persistent the sign the more likely it is associated with
LOS (Kudawla M et al,).
Based on clinical assessment the neonate must be

categorized into those with low probability of sepsis
or high probability of sepsis.
The rule of thumb is “low probability” represents
situations where the clinician would be willing to
withhold antibiotics if the sepsis screen is negative.
Those assessed to have a low probability of sepsis (eg.
single episode of apnea or vomiting, but otherwise
well)should undergo a sepsis screen.
Sepsis screen.
The purpose of the sepsis screen is to rule out sepsis

rather than to rule in sepsis.

Traditionally, the sepsis screen consists of 4 items:
C-reactive protein (CRP),
absolute neutrophil count (ANC),
immature to total neutrophil ratio (ITR)
and micro-erythrocyte sedimentation rate (μ-ESR).
CRP: Quantitative CRP assayed by nephelometry is
superior to CRP by ELISA and semiquantitative CRP
by a latex agglutination kit.
Cut-off value for quantitative assay is 10 mg/L.

ANC: It must be read off Manroe’s charts or
Mouzinho’s chart, depending on whether it is a term
baby or a preterm baby respectively(Kudawla M, Mouzinho
A,et al).
ITR: Value above 27% in term babies is considered

positive.18 For preterms, it is considered to be 20%.
ITR is defined as Immature neutrophils (band forms,
metamyelocytes, myelocytes) (Mature + immature
neutrophils).

μ-ESR:Value (in mm in first hour) of more than 3+

age in days in the first week of life or more than 10
thereafter is considered positive.
Two systematic reviews on sepsis screens reached the

same conclusions- that there is no ideal test or
combination of tests which achieves an LR+ ≥10 or
LR- ≤0.1, which are the benchmarks of an excellent
test (Schelonka RL et al, Da Silva O et al, Fowlie PW et al).

Among the various tests, quantitative CRP is the best,

followed by qualitative CRP and immature to total
neutrophil ratio.
If all the parameters of the sepsis screen are negative

in a neonate assessed to have low probability of LOS,
antibiotics may not be started and the neonate must
be monitored clinically.

The screen must be repeated after 12-24 hours. Two

consecutive completely negative screens are
suggestive of no sepsis.
The practice of designating the screen positive if ≥2

parameters are positive finds its origin in these
Author
Sen Spe LR LR
studies. Year Test
si

Philip
et al,

1980

Gerdes
et al,

1987

Any 2 + ve of:
ITR>0.2,
WCC<5000, CRP
>8 mg/l, ESR
>15 mm/1st hr,
Haptoglobulin
>25 mg/dl
Any 2 + ve of:
WCC
<5000/mm3, ITR
>0.2, and CRP
> 1 mg/dL

cifi

+

-

93

88

7.8

0.0
8

100

83

5.9

0
Since we now realize that CRP is the key parameter in

the sepsis screen, a pragmatic approach would be that
if the quantitative CRP alone is positive or any two
parameters of the sepsis screen are positive, a blood
culture must be drawn and empirical antibiotics must
be started.
A CSF examination must be performed.
Meningitis occurs in 3.4% cases of suspected LOS and
25% cases of culture positive LOS (Fielkow S et al,Kumar et
al,).
Neonates assessed to have a high clinical probability

of sepsis (for which the clinician is convinced that
antibiotics must be started) may not be subjected to a
sepsis screen, because a negative screen would not
alter the decision to start antibiotics.
A CSF examination must be performed.
In recent years, procalcitonin has attracted interest.
Head-to-head comparisons with CRP have shown
that procalcitonin is superior.(Malik A et al, Philip AG et al,
Gerdes JS et al,)
Urinary tract infections (UTI) in
neonates.
The signs of UTI in neonates are nonspecific and

varied.
The common clinical signs in cases of UTI in
neonates are –
failure to thrive (50%),
fever (39%),
vomiting (37%),
diarrhoea (25%),
cyanosis(23%),
jaundice (18%) and
irritability & lethargy (17%).
The yield of a routine urine culture is very less ( DiGeronimo
RJ. Tamim MM et al, Lin DS et al.).

Urine culture must always be performed on a sample

obtained by a supra-pubic puncture or by a fresh bladder
catheter.

In neonates, use of ultrasound guidance simplifies supra-

pubic aspiration and improves the diagnostic yield of
obtaining a urine specimen from 60% to almost 97%(Buys
H,et al).
Sepsis screen.
A practical positive "sepsis screen" takes into account

two or more positive tests as given below:
1. Leukopenia (TLC <5000/cmm)
2. Neutropenia (ANC <1800/cmm)
3. Immature neutrophil to total neutrophil (I/T) ratio
(> 0.2)
4. Micro ESR (> 15mm 1st hour)
5. CRP +ve
Diagnosis
Direct method:

Isolation of microorganisms from blood, CSF, urine,
pleural fluid or pus is diagnostic.
Indirect method:
There are a variety of tests which are helpful for

screening of neonates with sepsis.
The most useful and widely used is the white blood
cell count and differential count.
An absolute neutrophil count of < 1800 per cmm is an
indicator of infection.
Neutropenia is more predictive of neonatal sepsis

than neutrophilia
But it may be present in
maternal hypertension,
birth asphyxia

and periventricular hemorrhage.
Immature neutrophils (Band cells + myelocytes +

metamyelocytes) to total neutrophils ratio (l/T) > 0.20
means that immature neutrophils are over 20 percent
of the total neutrophils because bone marrow pushes
even the premature cells into circulation, to fight
infection.
Platelet count of less than 100,000 per cmm,
Toxic granules on peripheral smear,
Gastric aspirate smears showing more than 5

leucocytes per high power field are also useful
indirect evidences of infection.
The micro-ESR may be elevated with sepsis and fall of
> 15 mm during first hour indicates infection.
Acute phase reactants are also frequently used in

predicting neonatal sepsis.

The most widely used is C-reactive protein (CRP) which

has a high degree of sensitivity for neonatal sepsis.

The CRP can be affected by

asphyxia,
shock,
meconium aspiration
prolonged rupture of membranes.
There are a variety of other tests which can be used to

predict sepsis but it may be difficult to perform them
at all places and hence the clinical acumen remains
crucial.
Lumbar puncture.
If possible, lumbar puncture should be done in all

cases of late onset (>72 hours) and symptomatic early
onset sepsis because 10-15 percent of them may have
associated meningitis.
At a small hospital, one may only depend on the CSF
cells.
The implications of detecting meningitis in the

setting of septicemia include:

the need for using antibiotics with a high CSF

penetration
and provision of antibiotic treatment for at least 3
weeks, administered parenterally throughout.
Treatment
No investigation is required as a prerequisite to

start treatment in a clinically obvious case.

Early treatment is crucial.
Institution of prompt treatment is essential for

ensuring optimum outcome of neonates with sepsis
who often reach the health care facilities late and in a
critical condition.
Supportive care and antibiotics are two equally

important components of the treatment.
It should be realized that antibiotics take at least 12 to
24 hours to show any effect and it is the supportive
care that makes the difference between life and death
early in the hospital course.
Supportive care care is to
The purpose of supportive
normalize the temperature,
stabilize the cardiopulmonary status,
correct hypoglycemia,
prevent bleeding tendency.
There is no role of intravenous immunoglobulin

therapy in neonatal sepsis.
understanding neonatal sepsis
Antibiotic therapy – empirical,
upgradation and modification.
There is generally no distinction in the choice of

empirical antibiotics, be it suspected EOS or LOS as
the bacterial and sensitivity profile in India seems to
be is similar in both situations(Sundaram V et al, Zaidi AK et
al, NNPD network.).

Starting empirical antibiotics.
As the profile of organisms is similar for EOS and

LOS, the following policies can be used irrespective of
whether it is EOS or LOS.
Policy for community acquired sepsis (Paul VK,et al)
Ampicillin + Gentamicin/Amikacin (empirical)
If evidence of staphylococcus : Cloxacillin +

Gentamycin/Amikacin
If evidence of meningitis: Add Cefotaxime.
Policy for nosocomial sepsis:
It is not possible to suggest a single antibiotic policy

for use in all newborn units.
Every newborn unit must have its own antibiotic
policy based on the local sensitivity patterns and the
profile of pathogens.
Preferably choose Penicillin plus an Aminoglycoside
combination.
Cephalosporins rapidly induce the production of
extended spectrum β-lactamases (ESBL),
cephalosporinases and fungal colonization.
Antibiotic therapy
Antibiotic therapy should cover the common

causative bacteria, namely,
Escherichia coli,

Staphylococcus aureus and
Klebsiella pneumoniae.
A combination of ampicillin and gentamicin is

recommended for treatment of sepsis and
pneumonia.

In cases of suspected meningitis, cefotaxime should

be used along with an aminoglycoside.
understanding neonatal sepsis
understanding neonatal sepsis
In late-onset sepsis to cover nosocomial

staphylococcal infection, first line of antibiotics may
comprise of cloxacillin 100 mg per kg per day and an
aminoglycoside (gentamicin or amikacin).
In nosocomial sepsis, antibiotic sensitivity pattern of

organisms responsible for nursery infection should be
known and the antibiotic therapy should be started
accordingly.
Usually staphylococci and Gram negative bacilli

(Pseudomonas, Klebsiella) should be covered using
aminoglycoside (gentamicin or amikacin) and a third
generation cephalosporin (cefotaxime).
For resistant staphylococcal infection, vancomycin
(30 mg per kg per day) should be used.
On confirmation of sensitivity pattern, appropriate

antibiotics are used singly or in combination.
In a baby in whom the antibiotics were started on low
suspicion, these may be stopped after 3 days, if baby is
clinically well and the culture is negative.
However, if a baby appears ill even though the
cultures are negative, antibiotic therapy should be
continued for 7 to 10 days as bacterial infection can
occur with negative cultures.
The duration of antibiotic therapy in sepsis depends

upon the pathogen, site of infection and the clinical
response of the baby.
7-10 days therapy is required for soft tissue infections
or pneumonia.
Deep-seated infections (osteomyelitis) and
meningitis may require therapy for 3-6 weeks.
Upgradation of empirical
antibiotics.
Empirical upgradation must be done if the expected

clinical improvement with the ongoing line of
antibiotics does not occur.
At least 48-72 hours period of observation should be
allowed before declaring the particular line as having
failed.
If any new sign appears and/or the existing signs fail
to begin remitting, it would be considered that the
expected clinical improvement has not occurred.
Current evidence does not support the use of serial

quantitative CRP as a guide for deciding whether or
not antibiotics should be upgraded empirically.

In case the neonate is extremely sick or deteriorating

very rapidly and the treating team feels that the
neonate may not able to survive 48 hours in the
absence of appropriate antibiotics, a decision may be
taken to bypass the first line of antibiotics and start
with the second-line of antibiotics.
Antibiotic therapy once culture
report is available.
It must first be assessed whether the positive blood

culture is a contaminant. The following are suggestive
of contamination:
growth in only one bottle (if two had been sent),
growth of a known non-pathogen: eg. aerobic spore

bearers ,
mixed growth of doubtful significance and
onset of growth beyond 96 hours in the absence of a
history of prior exposure of antibiotics in the 72 hours
before sending the blood culture.
If the growth is a non-contaminant, the antibiotic

sensitivity must be assessed to decide whether
antibiotics need to be changed or not.
The following guidelines would allow a rationale use
of antibiotics:
If the organism is sensitive to an antibiotic with a

narrower spectrum or lower cost, therapy must be
changed to such an antibiotic, even if the neonate was
improving with the empirical antibiotics and/or the
empirical antibiotics are reported sensitive.
If possible, a single sensitive antibiotic must be used,

the exception being Pseudomonas for which 2 sensitive
antibiotics must be used.
If the empirical antibiotics are reported sensitive, but
the neonate has worsened on these antibiotics, it may
be a case of in vitro resistance.
Antibiotics may be changed to an alternate sensitive
antibiotic with the narrowest spectrum and lowest cost.
If the empirical antibiotics are reported resistant but

the neonate has improved clinically, it may or may not
be a case of in-vivo sensitivity.
In such cases are careful assessment must be made
before deciding on continuing with the empirical
antibiotics.
One must not continue with antibiotics with in vitro
resistance in case of Pseudomonas, Klebsiella and
MRSA; and in cases of CNS infections and deep-seated
infections.
If no antibiotic has been reported sensitive, but one or
more has been reported ‘moderately sensitive’, therapy
must be changed to such antibiotics at the highest
permissible dose. Use a combination, in such cases.
Duration of antibiotics.
Culture positive sepsis: Give sensitive antibiotics for

total duration of 10-14 days.
There is no definitive published literature regarding
the optimum duration of antibiotics for neonatal
sepsis.
neonates infected by Staphylococcus aureus require
14 days of antibiotics.
infected by non-Staphylococcus aureus organisms,
without meningitis or deep-seated infections, and
who become completely asymptomatic by day five,
one may consider a shorter duration of antibiotics.
Culture negative sepsis:
Asymptomatic neonate at risk of EOS: stop

antibiotics
Suspected EOS or LOS and the neonate becomes
completely asymptomatic over time: stop antibiotics.
Suspected EOS or LOS and the neonate improves but
does not become asymptomatic: repeat a CRP assay
(Ehl S et al, Engle WD et al, Saini SS et al)

If CRP + ve: continue antibiotics
If CRP –ve: stop antibiotics

Suspected EOS or LOS and the neonate have not

improved or have worsened: upgrade antibiotics as
per the empiric antibiotic policy. Simultaneously,
alternative explanations for the clinical signs must be
Culture-proven meningitis:
Gram stain-proven meningitis or meningitis

suspected on CSF examination:
Give total of 21-day course of parenteral antibiotics
that cross uninflamed meninges.
Anti-meningitic doses must be used throughout the
course and use only antibiotics with a proven in vitro
sensitivity.
Monitoring protocol following
diagnosis of meningitis:
At least twice weekly head circumference monitoring,
Input/Output monitoring, daily weight monitoring (for

SIADH),
Daily neurological examination (focal neurological
deficits),
Hearing screen after 4-8 weeks,
Ultrasound head in the first week and at the end of
antibiotic therapy (look for ventricular size, ventricular
wall enhancement, midline shift, intraventricular debris).
Ventriculitis may require 6 weeks of antibiotics.
CECT head may be required in case of rapidly rising OFC
with suspicious USG, focal seizures, focal neurological
deficits or infection with Citrobacter koseri and
Enterobacter sakazakii.
UTI
May be treated for 7-14 days. This duration has no

evidence to back it.
Start empirical treatment with
Cefotaxime/Ceftriaxone plus Amikacin, and modify as
per culture report.
Nalidixic acid or nitrofurantoin should not be used to
treat UTI since they do not achieve therapeutic
concentrations in the renal parenchyma and blood
stream.
UTI occurring in the setting of generalized septicemia

may not be associated with VUR or malformations.
However, an isolated UTI could be associated with
these conditions.

Hence, after treatment of isolated UTI, all cases must

be started on Amoxycillin 10 mg/kg once a day oral
prophylaxis, till such time that a renal ultrasound,
MCU and DMSA scan are performed to exclude VUR
or malformations.
Proven bone or joint infections:
Must be treated for at least 6 weeks.
Start empirical treatment with Cloxacillin or

Vancomycin (plus an aminoglycoside for first 1-2
weeks) and modify as per culture report.

Of this, at least 4 weeks must constitute parenterally

administered antibiotics. The rest of the course may
be enterally administered.
Adjunctive therapies:
a) Intravenous immunoglobulins (IVIG): The

currently available evidence does not support the use
of IVIG. The currently undergoing International
Neonatal Immunotherapy Study is expected to be
provide some important and definitive information in
this aspect(The INIS Study).
b) Colony stimulating factors: There is currently
no evidence to support the use of colony stimulating
factors either as a treatment modality or as a
prophylaxis therapy.
c) Blood Exchange Transfusion (BET): BET may be

performed in a case of deteriorating sepsis with
sclerema provided the general condition of the baby
allows the procedure .
Superficial infections with local
Superficial infections can be treated

application of antimicrobial agents.
Pustules can be punctured with sterile needles and
cleaned with spirit or betadine.
Purulent conjunctivitis can be treated with neosporin
or chloramphenicol ophthalmic drops.
Oral thrush responds to local application of
clotrimazole or nystatin (200,000 units per ml) and
hygienic precautions.
Superficial infections must be adequately managed; if
neglected they can lead to sepsis or even an epidemic.
Prevention of infections
A good antenatal care goes a long way in decreasing

the incidence, morbidity and mortality from neonatal
sepsis.
All mothers should be immunized against tetanus.
All types of infections should be diagnosed early and
treated vigorously in pregnant mothers.
Babies should be fed early and exclusively with

expressed breast milk (or breastfed) without any
prelacteal feeds.

Cord should be kept clean and dry. Unnecessary

interventions should be avoided.
Hand washing
This is the simplest and the most effective method for

control of infection in the hospital.
All persons taking care of the baby should strictly
follow hand washing policies before touching any
baby.
The sleeves should be rolled above the elbows. Rings,
watches and jewellery should be removed.
Wash hands up to elbows with a thorough scrub for 2

minutes with soap and water taking care to cover all
areas including the under surface of well trimmed
nails.
Rinse thoroughly with running water. Dry hands with
sterile hand towel/paper towel.
Wash hands up to the wrist for 20 seconds in
between patients.
Hands should be rewashed after touching
contaminated material like one’s face, hair, papers
etc.
It is preferable to use bar soaps rather than liquid

soaps as the latter tend to harbor organisms after
storage.
In emergency situations bactericidal and virucidal
solutions like Sterillium can be used to clean hands
before touching babies.
Surgical, elbow- operated taps should be used in the
hospitals for hand washing.
Prevention of infection in hospital
The nursery environment should be clean and dry

with 24 hour water supply and electricity.
There should be adequate ventilation and lighting.
The nursery temperature should be maintained
between 30+2°C.
Overcrowding should be avoided.
All procedures should be performed after wearing

mask and gloves.
Unnecessary invasive interventions such as needle
pricks and setting up of intravenous lines should be
kept to the barest minimum.
There should be no compromise in the use of
disposables. Stock solutions for rinsing should be
avoided.
Every baby must have separate thermometer and

stethoscope and all barrier nursing measures must be
followed.
Strict house-keeping routines for washing,
disinfection, cleaning of cots and incubators should
be ensured and these policy guidelines should be
available in the form of a manual in the nursery.
The use of prophylactic antibiotics for prevention of

nosocomial infections is strongly condemned.

They are not only useless but also dangerous because

of the potential risk of emergence of resistant strains
of bacteria.
Control of outbreak
General measures for the control of an outbreak

include

detailed epidemiological investigations,
increased emphasis on hand washing,
review of protocols,
procedures and techniques,
disinfection and sterilization of nursery
assessment of the need for additional measures.
The nursery may be fumigated using formalin 40%

and potassium permanganate (70 gms of KMNO4
with 170 ml of formalin for 1000 cubic feet area).
Alternatively, bacillocid spray for 1-2 hours may be
used. Linen and cotton should be washed thoroughly,
dried and autoclaved.
Use of disposable items for invasive and non- invasive

interventions (catheters, probes, cannulae, chest
tubes etc.) though costly, reduces the risk of
infection.
Depending upon the pathogen and type of outbreak,
culture surveys of susceptible patients, cohorting of
infants in nursery and a review of antibiotic policy
may be necessary.
Most of the times a scrupulous reinforcement of
general control measures may be sufficient to stop the
outbreak.
understanding neonatal sepsis
understanding neonatal sepsis
understanding neonatal sepsis
Conclusion
In conclusion, manifestations of neonatal sepsis are

non-specific.
A high index of suspicion with or without lab
evidences of infection is the key for early diagnosis.
Prompt institution of antibiotic therapy and
supportive care will save most of the cases of neonatal
sepsis.
Take home messages.
In India, both early and late onset sepsis are caused

by similar organisms with similar antibiotic
sensitivities.
Clinical features of neonatal sepsis are non-specific
and any unexplained clinical deterioration should be
investigated for sepsis.
There is no role of performing sepsis screen in early
onset neonatal sepsis.
Lumbar puncture (LP) for CSF examination must be
performed in all symptomatic neonates being
initiated on antibiotics, with the exception of
premature neonates presenting with respiratory
The traditional cut-offs for interpretation of

cerebrospinal fluid values are based on relatively old
studies with methodological problems.
A new set of guidelines for interpretation is proposed.
Routine urine culture in all neonates with nonspecific symptoms is not recommended.
Every newborn unit must have its own antibiotic

policy based on the local sensitivity patterns and the
profile of pathogens.
Apart from appropriate antibiotics, the survival of a
sick septic newborn often depends upon aggressive
supportive care.
There may be a potential role of intravenous

immunoglobulins in treatment of neonatal sepsis but
larger studies are required.
There is currently no role for the use of colony
stimulating factors.
THANKS

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understanding neonatal sepsis

  • 2. Definition Neonatal septicemia is defined as generalized systemic infection of the newborn,associated with pure growth of bacteria from one or more sites. It is one of the most important causes of mortality and morbidity in newborn. Among the low birth weight & pre term babies,neonatal septicemia is the most important cause of mortality,especially in developing countries including India.
  • 3. According to NNPD-2,the incidence ranges from 0.1 to 4.5 percent with an overall mortality rate varying from 22-30%. With an estimated 25 million births occuring in India and approximately 2% incidence of sepsis,the figure for neonatal sepsis in India would be 5,00,000 babies every year with about one-third,i.e.170,000 babies succumbing to the disease.
  • 4.  When pathogenic bacteria gain access into the blood stream, they may cause overwhelming infection without much localization (septicemia), may get predominantly localized to the lung (pneumonia), the meninges (meningitis).
  • 5. Importance.  Neonatal sepsis is the single most important cause of neonatal deaths in the community, accounting for over half of them.  If diagnosed early and treated aggressively with antibiotics and good supportive care, it is possible to save most cases of neonatal sepsis.
  • 6. Classification.  Neonatal sepsis can be classified into two sub-types depending upon whether the onset of symptoms is before 72 hours of life (early onset) or later (late onset).
  • 7. Early onset sepsis Early onset sepsis (EOS) often presents as a fulminant, multi-system illness within 72 hours of delivery and is mainly due to bacteria acquired before and during delivery
  • 8. Early onset sepsis manifests frequently as pneumonia and less commonly as septicemia or meningitis.
  • 9. The associated factors for early-onset sepsis include low birth weight, prolonged rupture of membranes > 24 hours, foul smelling liquor, multiple per vaginum examinations, maternal fever, difficult or prolonged labour, and aspiration of meconium.
  • 10. Risk factors for neonatal sepsis. Maternal factors: Fever, Urinary tract infection,diarrhea, Prolonged rupture of the membrane>24hrs, Foul smelling amniotic fluid, Maternal amnionitis, Maternal genital tract infection,& genital colonization, Socio economic factors:poor socio economic status,poor nutrition and hygiene.
  • 11. Neonatal factors: Preterm and low birth weight, Perinatal asphyxia, Vigorous resuscitation, Invasive procedures, Congenital malformations,e.g.meningomyelocele, Male child.
  • 12. Risk factors. Prolonged rupture of membranes(PROM):the risk is reported to be 1% percent compared to a baseline incidence of 0.1 to 0.5 percent. Chorioamnionitis:increases the risk of sepsis by 2 to 3 times. If PROM is associated with chorioamnionitis ,the risk of sepsis increases by four fold.
  • 13. Prematurity & low birth weight:pre term babies are deficient in immunoglobulin concentration,complement function & phagocytic activity. They have 3 to 10 times higher risk of developing sepsis than term infants. Chorioamnionitis may coexist & may trigger for preterm labor. Association of chorioamnionitis is and low birth weight increases the risk of sepsis to 16 percent compared to association with normal weight babies.
  • 14. Perinatal asphyxia:asphyxia is associated with depressed immune function.in addition,several interventional procedures increase the risk of infection. Presence of low apgar score (6 or less at 5 minutes)along with prolonged rupture of membranes has shown to increase the risk of infection by 4% & 27%. Male gender:boys have 2 to 6 times higher risk of development of neonatal sepsis. Other factors:maternal fever,G.U.T.infection,poor socio economic condition & feeding artificial milk.
  • 15. Late onset sepsis. Late-onset septicemia is caused by the organisms thriving in the external environment of the home or the hospital. late onset sepsis (LOS) can present as either a fulminant or a smoldering infection.
  • 16. The infection is often transmitted through the hands of the care-providers. The onset of symptoms is usually delayed beyond 72 hours after birth and the presentation is that of septicemia, pneumonia or meningitis.
  • 17. The associated factors of late-onset sepsis include: low birth weight, lack of breastfeeding, superficial infections (pyoderma, umbilical sepsis), aspiration of feeds, disruption of skin integrity with needle pricks and use of intravenous fluids.
  • 18. These factors enhance the chances of entry of organisms into the blood stream of the neonates whose immune defences are poor as compared to older children and adults.
  • 19. National neonatology forum of India defines neonatal sepsis as follows; Proven sepsis:the baby presents with clinical picture of sepsis & isolation of pathogens from blood,csf.,urine or other body fluids or autopsy evidence of sepsis. Probable sepsis:newborn with clinical picture suggestive of sepsis with one or more of the following criteria Existence of predisposing factors,e.g.maternal fever foul smelling liquor or prolonged rupture of the membrane (>12 hours) or gastric polymorphs more than 6/high power field.  Positive sepsis screen(2 of the 4 parameters to be present).  Total leukocytes count<5,000/mm3,immature to total neutrophil count ratio>0.2,c-reactive protein positive & micro ESR > 15 mm/1st hour or >age in days + 3.  Radiological evidence of pneumonia. 
  • 20. Sepsis syndrome:when septicemia is associated with altered organ perfusion(hypoxia,increased blood lactate,oliguria & altered mental state)it is termed as sepsis syndrome. If untreated,this condition leads to early septic shock with decreased capillary refilling and low blood pressure,which can be reversible with appropriate treatment. If untreated,this state progresses quickly into refractory shock & leads to multi organ dysfunction.
  • 21. The common organisms reported by NNPD Survey showed 3.8 percent incidence of neonatal sepsis from pooled hospital data with Klebsiella, Staph.aureus, Esch.coli, Pseudomonas, Enterobacter, Coagulase negative staphylococcus, Acenatobacter and Candida as the predominant organisms.
  • 22. In the Indian subcontinent, the distinction between EOS and LOS is somewhat blurred (Sundaram V et al). The clinical presentations of EOS and LOS are different and the risk factors are different, but the organisms causing the EOS and LOS are similar and so are their antibiograms (Zaidi AK et al,NNPD NETWORK).
  • 23. The early & efficient diagnosis of neonatal bacterial sepsis remains a difficult task since most of the symptoms & signs of sepsis in the neonatal period are of non specific nature. The spectrum & severity of symptoms required to decide in the evaluation of sepsis is a matter of clnical judgement. It is estimated that between 11 & 23 non infected newborns are treated in neonatal intensive care nurseries for every one with documented infection.
  • 24. Clinical features The manifestations of neonatal septicemia are often vague and therefore demand a high index of suspicion for early diagnosis. The possibility of sepsis must be considered with any clinical deterioration unless the event is readily explained by other causes. The most common and characteristic manifestation is  An alteration in the established feeding behavior in late onset sepsis,  Respiratory distress in early onset sepsis.
  • 26. The baby, who had been active and sucking well, gradually or suddenly, becomes lethargic, inactive or unresponsive and refuses to suckle. Hypothermia is a common manifestation of sepsis, whilst fever is infrequent. Diarrhea, vomiting and abdominal distension may occur.
  • 27. Episodes of apneic spells or gasping may be the only manifestation of septicemia. In sick neonates, the skin may become tight giving a hide-bound feel (sclerema) and the perfusion becomes poor (capillary refill time of over 3 seconds). Cyanosis may appear.
  • 28. The additional features of pneumonia or meningitis may be present depending upon the localization of infection in different systems and organs of the body.
  • 29. The evidence of pneumonia includes tachypnea, chest retractions, grunting, early cyanosis, apneic spells in addition to inactivity and poor feeding. Cough is unusual. Findings on auscultation of the chest are non-specific and non- contributory.
  • 30. Meningitis is often silent, the clinical picture being dominated by manifestations of associated septicemia. the appearance of excessive or high-pitched crying, fever, seizures, blank look, neck retraction, bulging anterior fontanel are highly suggestive of meningitis.
  • 31. Classification of sick young infants for bacterial infection(WHO).  Convulsion,  Fast breathing,  Severe chest indrawing,  Nasal flaring,  Grunting,  Bulging fontanelle,  Pus draining from ear,  Umbilical redness extending to skin, possible serious bacterial infection.  Fever or hypothermia,  Many or severe skin pustules,  Lethargic or unconscious,or less than normal movement.  Red umbilicus or draining pus,  Skin pustules local bacteria infection.
  • 32. Laboratory diagnosis. Sensitivity:if infection is present,how often is the test result abnormal? Specificty:if infection is absent,how often is the test result normal? Positive predictive value:if the test result is abnormal,how often is the infection present? Negative predictive value:if the test result is normal,how often is infection absent?
  • 33. Diagnostic tests with maximal(100%)sensitivity & negative predictive value are desirable for diagnosis of neonatal sepsis. This indicates if infection were present,the result would always be abnormal & if results were normal,infection would always be absent. A good specificity & positive predictive value is also acceptable.
  • 34. Diagnostic tests. Definitive,specific Nonspecific,diagnostic Blood culture, White blood cell count, Cerebrospinal fluid C-reactive protein(CRP), examination & culture, Urine culture, Tracheal aspirates, Polymerase chain reaction, Latex particle agglutination test. Erythrocyte sedimentation rate, Other acute phase reactants, Miscellaneous tests.
  • 35. Definitive,specific diagnostic tests. Isolation of organism from blood or a central body fluid is the standard & most specific method to confirm the diagnosis of neonatal sepsis. The main draw back is that,the results are available after 48 to 72 hrs. Another dilemma often faced by the clinicians is the high percentage of cases(upto 40%)where no bacteria can be isolated from blood even in highly suspected cses of sepsis.
  • 36. Blood culture. The standard is to collect 1 ml of blood by sterile venepuncture in a blood culture bottle. Umblical artery catheter is preferred over umbilical vein catheter for sampling. The blood culture should be incubated for at least 72 hours before being considered negative. In a study conducted by Geme JW et al,13 percent of positive blood culture did not grow until beyond 72 hours. The late growing organisms were anaerobes & coagulase negative staphylococci.
  • 37. Blood culture should not be considered as the final arbiter for the clinical diagnosis of neonatal infections because, It is negative in 20% cases where infection was proven by immedite post mortem culture and autopsy. In the mildly symptomatic neonate and at the earliest onset of septicemia,the false negative blood culture rate would be very high. In upto 50% of cases with congenital bacterial pneumonia proved by tracheal aspirate culture ,blood culture is negative.
  • 38. In a prospective observational study from India, 101 cases of suspected neonatal sepsis were used to compare the manual method of blood culture with an automated BacT/Alert system for detection of neonatal septicemia. The mean times to positivity with the manual and BacT/Alert 3D systems were 53.1 h and 14.3 h, respectively (p <0.001)(Hasana AS,et al) With conventional methods the detection rate is 89.1% by day 2 and 99.5% by day 4.
  • 39. Cerebro-spinal fluid (CSF) examination. In an unstable neonate, the LP can be deferred, until stabilization is achieved. The cellular and biochemical abnormalities in the CSF of older patients with bacterial meningitis persist for up to 3 days. Gram positive bacteria clear in 36 hours of appropriate therapy whereas gram negative bacteria may take up to 5 days.
  • 40. Apart from culture and gram stain, 4 parameters are commonly evaluated: total WBC count (per micro L), percentage neutrophil count, glucose protein.
  • 41. Traditionally, the following cut-offs have been used: 30 cells, more than 60% of polymorphs, glucose less than 50% of blood glucose, protein more than 150 mg/dL in term babies and 180 mg/dL in preterm babies. These cut-offs are no longer acceptable as they are based on old normative data, and represent an over-simplified approach based on single cut-off points derived from 2 standard deviation values.
  • 42. Preterm infants: Treat if CSF WBC count ≥10 OR glucose <24 OR protein >170. Do not treat if “CSF WBC count <10 AND glucose ≥25 AND protein <170”. For in-between results, clinical judgment will have to be used, keeping in mind clinical features (seizures, degree of altered sensorium, fullness of fontanelles) and prematurity (the lower the gestation, lower should be the threshold for diagnosis).
  • 43. Term infants: Treat if CSF WBC count >8 OR glucose <20 OR protein >120. There is no safe cut-off at which one can recommend “do not treat”. Clinical judgment as above would have to be used.(The WHO Young Infant Study Group, Ahmed AS et al, Smith PB et al, Garges HP et al)
  • 44. In a neonate with meningitis not showing clinical recovery after institution of antibiotics, LP should be repeated after 48 hours. If the LP is traumatic, the CSF should be sent for gram stain and culture. The concentration of glucose is not significantly altered by a traumatic lumbar puncture. Therefore a low CSF glucose in the setting of a traumatic LP is abnormal.
  • 45. Ideally, the WBC cell count must be performed within 30 minutes of drawing the sample. It must be noted that CSF WBC and glucose rapidly fall with time, giving spurious results(Rajesh NT,et al).
  • 46. Tracheal aspirate. Useful in first 12 hours of life. A positive tracheal culture may be found in 44% cases with pneumonia were blood culture was sterile. There is a positive co-relation of tracheal aspirate gram stain for bacteria with clinical or pathological pneumonia and has a 47% predictive accuracy in bacteremic infants.
  • 47. Latex particle agglutination tests:a relatively simple test to perform but is not very sensitive. The standard kits for group B streptococcus,pneumococcus and meningococcus are available & hence cannot be used routinely. Polymerase chain reaction:a definitive advancement,but the prohibitive cost & difficult technique precludes its use in the routine evaluation of neonatal sepsis.
  • 48. Nonspecific diagnostic septic screening tests. These tests indicate infection without identifying the infecting micro organisms. Because of the severity of the disease,it is essential for these indirect tests not to miss any case(have 100% sensitivity), To rule out convincingly sepsis when it is not present(have a high negative value).
  • 49. White blood cell count. A total leukocyte count<5000/mm3, Total neutrophil count<1750/mm3, An immature to total neutrophil count ratio(I/T)of >0.2 are suggestive of sepsis.
  • 50. It has been well documented that the CBC depends upon the infant’s age,on whether the sample is arterial or venous,and on whether the infant is crying vigorously. This means that for a given infant,a test value is not a static value;there is considerable intraindividual variability.
  • 51. In addition,maternal hypertension,perinatal asphyxia & intra ventricular h’age may cause neutropenia. Non specific stresses such as asphyxia,maternal fever or stressful labor can elevate the I/T ratio. The presence of neutrophil vacuolization or toxic granulation are also good indicators of neonatal sepsis.
  • 52. C-reactive protein. CRP is a rapidly responsive acute phase reactant,synthesizd by the liver within 6-8 hrs of stimulus of inflammatory process. A positive CRP latex agglutination test corresponds to plasma CRP concentration of 0.8 to 1.0 mg/dl. A single value of negative CRP done at the outset may not be of much significance. Therefore,n suspected cases,a repeat CRP test is done 12 hours later is more significant. If the test is negative negative-it almost excludes sepsis.
  • 53. Normalization of CRP is a helpful tool in determining the response to antimicrobial therapy and duration of treatment. Failure to mount a CRP response is a poor prognostic sign.
  • 54. Erythrocyte sedimentation rate. Micro ESR is an inexpensive & easy bedside screenig test for neonatal sepsis. Normal values increase with postnatal age & are equal to the day of life plus 3mm/hour upto a maximum of 15 mm/hour. ESR is less sensitive but more specific than CRP or I/T rato.
  • 55. Other acute phase reactants Haptoglobin & orosomucoid are acute phase reactants that have been evaluated for diagnostic aids for neonatal sepsis,are of limited utility because of their slower response to infection. A low plasma fibronectin concentration is suggestive of neonatal sepsis, It is also depressed by RDS & perinatal asphyxia,thus limiting its use.
  • 56. Miscellaneous tests. Elastase-alpha-1-proteinase inhibitor complex:raises rapidly,100% sensitive but not highly specific. C3D, Endotoxin, Direct visualization of bacteria in neutrophils stained by acridine orange, NBT reduction by neutrophils, Gastric aspirate of polymorph count & culture:has limited value,indicative of high risk because of exposure to chorioamnionitis.
  • 57. Newer diagnostic modalities. Procalcitonin:a pro-peptide,released into the blood 3-6 hrs after endotoxin injection & increses upto 24 hours. Very high serum procalcitonin levels are present in neonates with proven or clinically diagnosed bacterial infection;early decrease of these concentrations reflects appropriate antibiotic therapy. Compared with CRP,proclcitonin has the advantage that it increases more rapidly. A recent meta analysis showed that procalcitonin showed better accuracy than the CRP test for LOS.
  • 58. Cytokines and receptors. Interleukin-6(IL-6), Interleukin-1 receptor antagonist(IL-1ra) The level of these two markers increases two days before clinical diagnosis of sepsis. IL-6 although a very early marker,the level becomes normal later even if infection continues. The simultaneous determination of CRP can obviate this problem because the rise in plasma CRP levels occurs 12 to 48 hours after the onset of infection,at a time when IL-6 level would have fallen.
  • 59. Specific leukocyte surface antigens. CD11b-promising marker for diagnosing early onset sepsis. CD64-late onset sepsis. Preterm express CD 64 to the same degree as those from term infants,children & adults. G-CSF;a higher level has been found to be associated with a sensitivity of 95 percent for prediction of sepsis & a specificity of 73 percent if the level is >200pg/ml.
  • 60. The best combination for newer markers for sepsis would be estimation of IL-6,IL-1ra:1-2 days before the onset of symptoms, IL-6,IL-1ra,IL-8,CD 11b,G-CSF,TNF,CRP & hematological indices on day 1, CRP on the following days to monitor response to treatment. CD 64 is probably one of the most useful infection markers for diagnosis of late onset nosocomial sepsis.
  • 61. However,none of the current diagnostic markers are sensitive and specific enough to influence the judgement to withhold antimicrobial treatment independent of the clinical findings.
  • 62. Approach to a neonate with suspected EOS. There is no rationale for performing a “sepsis screen” (i.e. CRP,hematological parameters, micro ESR) in suspected EOS. The negative predictive value (NPV) of various sepsis screen parameters is too low to confidently rule out EOS (Benitz WE et al, Mahale R et al,). Procalcitonin and IL-6 are more promising than the standard screen for the diagnosis of EOS, but they are currently not easily available on the bedside and are not considered standards of care.
  • 63. Neonates who turn symptomatic within 72 hours must be clinically assessed for probability of sepsis. Twenty percent of symptomatic neonates in India suspected to have EOS are blood culture positive (Mahale R et al).
  • 64. The following neonates need not be immediately started on antibiotics but their clinical course must be carefully monitored:
  • 65. Those who are born without any of the known risk factors of sepsis preterm, premature rupture of membranes (pPROM), prolonged rupture of membranes (PROM) >18 hrs, spontaneous preterm onset of labor (SPTOL), clinical chorioamnionitis, foul smelling liquor, unclean vaginal examinations, maternal fever,
  • 66. maternal urinary or other systemic infections, frequent (>3) per vaginal examinations in labor, perinatal asphyxia, and maternal recto-vaginal group B Streptococcus carriage], AND  Chest X ray is not suggestive of pneumonia,  Have alternative reasons to explain the symptoms.
  • 67. Those symptomatic neonates with any of the known risk factors or who have a chest X-ray suggestive of pneumonia or do not have any alternate explanation for the signs, must be immediately started on antibiotics after drawing a blood culture. Lumbar puncture (LP) for CSF examination must be performed in all symptomatic neonates, with the exception of premature neonates presenting with respiratory distress at birth with no risk factors for sepsis (Eldadah M et al, Weiss MG et al,) The decision for performing LP should not be based on sepsis screen results or blood culture results.
  • 68. Approach to a neonate with suspected LOS. Neonates who become symptomatic after 72 hours must be evaluated for LOS. 30% neonates clinically suspected to have LOS in an NICU setting have positive blood culture (Singh SA et al). A single episode or transient presence of one of the above signs may not warrant any action. The more persistent the sign the more likely it is associated with LOS (Kudawla M et al,).
  • 69. Based on clinical assessment the neonate must be categorized into those with low probability of sepsis or high probability of sepsis. The rule of thumb is “low probability” represents situations where the clinician would be willing to withhold antibiotics if the sepsis screen is negative. Those assessed to have a low probability of sepsis (eg. single episode of apnea or vomiting, but otherwise well)should undergo a sepsis screen.
  • 70. Sepsis screen. The purpose of the sepsis screen is to rule out sepsis rather than to rule in sepsis. Traditionally, the sepsis screen consists of 4 items: C-reactive protein (CRP), absolute neutrophil count (ANC), immature to total neutrophil ratio (ITR) and micro-erythrocyte sedimentation rate (μ-ESR).
  • 71. CRP: Quantitative CRP assayed by nephelometry is superior to CRP by ELISA and semiquantitative CRP by a latex agglutination kit. Cut-off value for quantitative assay is 10 mg/L. ANC: It must be read off Manroe’s charts or Mouzinho’s chart, depending on whether it is a term baby or a preterm baby respectively(Kudawla M, Mouzinho A,et al).
  • 72. ITR: Value above 27% in term babies is considered positive.18 For preterms, it is considered to be 20%. ITR is defined as Immature neutrophils (band forms, metamyelocytes, myelocytes) (Mature + immature neutrophils). μ-ESR:Value (in mm in first hour) of more than 3+ age in days in the first week of life or more than 10 thereafter is considered positive.
  • 73. Two systematic reviews on sepsis screens reached the same conclusions- that there is no ideal test or combination of tests which achieves an LR+ ≥10 or LR- ≤0.1, which are the benchmarks of an excellent test (Schelonka RL et al, Da Silva O et al, Fowlie PW et al). Among the various tests, quantitative CRP is the best, followed by qualitative CRP and immature to total neutrophil ratio.
  • 74. If all the parameters of the sepsis screen are negative in a neonate assessed to have low probability of LOS, antibiotics may not be started and the neonate must be monitored clinically. The screen must be repeated after 12-24 hours. Two consecutive completely negative screens are suggestive of no sepsis.
  • 75. The practice of designating the screen positive if ≥2 parameters are positive finds its origin in these Author Sen Spe LR LR studies. Year Test si Philip et al, 1980 Gerdes et al, 1987 Any 2 + ve of: ITR>0.2, WCC<5000, CRP >8 mg/l, ESR >15 mm/1st hr, Haptoglobulin >25 mg/dl Any 2 + ve of: WCC <5000/mm3, ITR >0.2, and CRP > 1 mg/dL cifi + - 93 88 7.8 0.0 8 100 83 5.9 0
  • 76. Since we now realize that CRP is the key parameter in the sepsis screen, a pragmatic approach would be that if the quantitative CRP alone is positive or any two parameters of the sepsis screen are positive, a blood culture must be drawn and empirical antibiotics must be started. A CSF examination must be performed. Meningitis occurs in 3.4% cases of suspected LOS and 25% cases of culture positive LOS (Fielkow S et al,Kumar et al,).
  • 77. Neonates assessed to have a high clinical probability of sepsis (for which the clinician is convinced that antibiotics must be started) may not be subjected to a sepsis screen, because a negative screen would not alter the decision to start antibiotics. A CSF examination must be performed. In recent years, procalcitonin has attracted interest. Head-to-head comparisons with CRP have shown that procalcitonin is superior.(Malik A et al, Philip AG et al, Gerdes JS et al,)
  • 78. Urinary tract infections (UTI) in neonates. The signs of UTI in neonates are nonspecific and varied. The common clinical signs in cases of UTI in neonates are – failure to thrive (50%), fever (39%), vomiting (37%), diarrhoea (25%), cyanosis(23%), jaundice (18%) and irritability & lethargy (17%).
  • 79. The yield of a routine urine culture is very less ( DiGeronimo RJ. Tamim MM et al, Lin DS et al.). Urine culture must always be performed on a sample obtained by a supra-pubic puncture or by a fresh bladder catheter. In neonates, use of ultrasound guidance simplifies supra- pubic aspiration and improves the diagnostic yield of obtaining a urine specimen from 60% to almost 97%(Buys H,et al).
  • 80. Sepsis screen. A practical positive "sepsis screen" takes into account two or more positive tests as given below: 1. Leukopenia (TLC <5000/cmm) 2. Neutropenia (ANC <1800/cmm) 3. Immature neutrophil to total neutrophil (I/T) ratio (> 0.2) 4. Micro ESR (> 15mm 1st hour) 5. CRP +ve
  • 81. Diagnosis Direct method: Isolation of microorganisms from blood, CSF, urine, pleural fluid or pus is diagnostic.
  • 82. Indirect method: There are a variety of tests which are helpful for screening of neonates with sepsis. The most useful and widely used is the white blood cell count and differential count. An absolute neutrophil count of < 1800 per cmm is an indicator of infection.
  • 83. Neutropenia is more predictive of neonatal sepsis than neutrophilia But it may be present in maternal hypertension, birth asphyxia and periventricular hemorrhage.
  • 84. Immature neutrophils (Band cells + myelocytes + metamyelocytes) to total neutrophils ratio (l/T) > 0.20 means that immature neutrophils are over 20 percent of the total neutrophils because bone marrow pushes even the premature cells into circulation, to fight infection.
  • 85. Platelet count of less than 100,000 per cmm, Toxic granules on peripheral smear, Gastric aspirate smears showing more than 5 leucocytes per high power field are also useful indirect evidences of infection. The micro-ESR may be elevated with sepsis and fall of > 15 mm during first hour indicates infection.
  • 86. Acute phase reactants are also frequently used in predicting neonatal sepsis. The most widely used is C-reactive protein (CRP) which has a high degree of sensitivity for neonatal sepsis. The CRP can be affected by asphyxia, shock, meconium aspiration prolonged rupture of membranes.
  • 87. There are a variety of other tests which can be used to predict sepsis but it may be difficult to perform them at all places and hence the clinical acumen remains crucial.
  • 88. Lumbar puncture. If possible, lumbar puncture should be done in all cases of late onset (>72 hours) and symptomatic early onset sepsis because 10-15 percent of them may have associated meningitis. At a small hospital, one may only depend on the CSF cells.
  • 89. The implications of detecting meningitis in the setting of septicemia include: the need for using antibiotics with a high CSF penetration and provision of antibiotic treatment for at least 3 weeks, administered parenterally throughout.
  • 90. Treatment No investigation is required as a prerequisite to start treatment in a clinically obvious case. Early treatment is crucial. Institution of prompt treatment is essential for ensuring optimum outcome of neonates with sepsis who often reach the health care facilities late and in a critical condition.
  • 91. Supportive care and antibiotics are two equally important components of the treatment. It should be realized that antibiotics take at least 12 to 24 hours to show any effect and it is the supportive care that makes the difference between life and death early in the hospital course.
  • 92. Supportive care care is to The purpose of supportive normalize the temperature, stabilize the cardiopulmonary status, correct hypoglycemia, prevent bleeding tendency. There is no role of intravenous immunoglobulin therapy in neonatal sepsis.
  • 94. Antibiotic therapy – empirical, upgradation and modification. There is generally no distinction in the choice of empirical antibiotics, be it suspected EOS or LOS as the bacterial and sensitivity profile in India seems to be is similar in both situations(Sundaram V et al, Zaidi AK et al, NNPD network.). Starting empirical antibiotics. As the profile of organisms is similar for EOS and LOS, the following policies can be used irrespective of whether it is EOS or LOS.
  • 95. Policy for community acquired sepsis (Paul VK,et al) Ampicillin + Gentamicin/Amikacin (empirical) If evidence of staphylococcus : Cloxacillin + Gentamycin/Amikacin If evidence of meningitis: Add Cefotaxime.
  • 96. Policy for nosocomial sepsis: It is not possible to suggest a single antibiotic policy for use in all newborn units. Every newborn unit must have its own antibiotic policy based on the local sensitivity patterns and the profile of pathogens. Preferably choose Penicillin plus an Aminoglycoside combination. Cephalosporins rapidly induce the production of extended spectrum β-lactamases (ESBL), cephalosporinases and fungal colonization.
  • 97. Antibiotic therapy Antibiotic therapy should cover the common causative bacteria, namely, Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae.
  • 98. A combination of ampicillin and gentamicin is recommended for treatment of sepsis and pneumonia. In cases of suspected meningitis, cefotaxime should be used along with an aminoglycoside.
  • 101. In late-onset sepsis to cover nosocomial staphylococcal infection, first line of antibiotics may comprise of cloxacillin 100 mg per kg per day and an aminoglycoside (gentamicin or amikacin).
  • 102. In nosocomial sepsis, antibiotic sensitivity pattern of organisms responsible for nursery infection should be known and the antibiotic therapy should be started accordingly.
  • 103. Usually staphylococci and Gram negative bacilli (Pseudomonas, Klebsiella) should be covered using aminoglycoside (gentamicin or amikacin) and a third generation cephalosporin (cefotaxime). For resistant staphylococcal infection, vancomycin (30 mg per kg per day) should be used.
  • 104. On confirmation of sensitivity pattern, appropriate antibiotics are used singly or in combination. In a baby in whom the antibiotics were started on low suspicion, these may be stopped after 3 days, if baby is clinically well and the culture is negative. However, if a baby appears ill even though the cultures are negative, antibiotic therapy should be continued for 7 to 10 days as bacterial infection can occur with negative cultures.
  • 105. The duration of antibiotic therapy in sepsis depends upon the pathogen, site of infection and the clinical response of the baby. 7-10 days therapy is required for soft tissue infections or pneumonia. Deep-seated infections (osteomyelitis) and meningitis may require therapy for 3-6 weeks.
  • 106. Upgradation of empirical antibiotics. Empirical upgradation must be done if the expected clinical improvement with the ongoing line of antibiotics does not occur. At least 48-72 hours period of observation should be allowed before declaring the particular line as having failed. If any new sign appears and/or the existing signs fail to begin remitting, it would be considered that the expected clinical improvement has not occurred.
  • 107. Current evidence does not support the use of serial quantitative CRP as a guide for deciding whether or not antibiotics should be upgraded empirically. In case the neonate is extremely sick or deteriorating very rapidly and the treating team feels that the neonate may not able to survive 48 hours in the absence of appropriate antibiotics, a decision may be taken to bypass the first line of antibiotics and start with the second-line of antibiotics.
  • 108. Antibiotic therapy once culture report is available. It must first be assessed whether the positive blood culture is a contaminant. The following are suggestive of contamination: growth in only one bottle (if two had been sent), growth of a known non-pathogen: eg. aerobic spore bearers , mixed growth of doubtful significance and onset of growth beyond 96 hours in the absence of a history of prior exposure of antibiotics in the 72 hours before sending the blood culture.
  • 109. If the growth is a non-contaminant, the antibiotic sensitivity must be assessed to decide whether antibiotics need to be changed or not. The following guidelines would allow a rationale use of antibiotics: If the organism is sensitive to an antibiotic with a narrower spectrum or lower cost, therapy must be changed to such an antibiotic, even if the neonate was improving with the empirical antibiotics and/or the empirical antibiotics are reported sensitive.
  • 110. If possible, a single sensitive antibiotic must be used, the exception being Pseudomonas for which 2 sensitive antibiotics must be used. If the empirical antibiotics are reported sensitive, but the neonate has worsened on these antibiotics, it may be a case of in vitro resistance. Antibiotics may be changed to an alternate sensitive antibiotic with the narrowest spectrum and lowest cost.
  • 111. If the empirical antibiotics are reported resistant but the neonate has improved clinically, it may or may not be a case of in-vivo sensitivity. In such cases are careful assessment must be made before deciding on continuing with the empirical antibiotics. One must not continue with antibiotics with in vitro resistance in case of Pseudomonas, Klebsiella and MRSA; and in cases of CNS infections and deep-seated infections. If no antibiotic has been reported sensitive, but one or more has been reported ‘moderately sensitive’, therapy must be changed to such antibiotics at the highest permissible dose. Use a combination, in such cases.
  • 112. Duration of antibiotics. Culture positive sepsis: Give sensitive antibiotics for total duration of 10-14 days. There is no definitive published literature regarding the optimum duration of antibiotics for neonatal sepsis. neonates infected by Staphylococcus aureus require 14 days of antibiotics. infected by non-Staphylococcus aureus organisms, without meningitis or deep-seated infections, and who become completely asymptomatic by day five, one may consider a shorter duration of antibiotics.
  • 113. Culture negative sepsis: Asymptomatic neonate at risk of EOS: stop antibiotics Suspected EOS or LOS and the neonate becomes completely asymptomatic over time: stop antibiotics. Suspected EOS or LOS and the neonate improves but does not become asymptomatic: repeat a CRP assay (Ehl S et al, Engle WD et al, Saini SS et al) If CRP + ve: continue antibiotics If CRP –ve: stop antibiotics Suspected EOS or LOS and the neonate have not improved or have worsened: upgrade antibiotics as per the empiric antibiotic policy. Simultaneously, alternative explanations for the clinical signs must be
  • 114. Culture-proven meningitis: Gram stain-proven meningitis or meningitis suspected on CSF examination: Give total of 21-day course of parenteral antibiotics that cross uninflamed meninges. Anti-meningitic doses must be used throughout the course and use only antibiotics with a proven in vitro sensitivity.
  • 115. Monitoring protocol following diagnosis of meningitis: At least twice weekly head circumference monitoring, Input/Output monitoring, daily weight monitoring (for SIADH), Daily neurological examination (focal neurological deficits), Hearing screen after 4-8 weeks, Ultrasound head in the first week and at the end of antibiotic therapy (look for ventricular size, ventricular wall enhancement, midline shift, intraventricular debris). Ventriculitis may require 6 weeks of antibiotics. CECT head may be required in case of rapidly rising OFC with suspicious USG, focal seizures, focal neurological deficits or infection with Citrobacter koseri and Enterobacter sakazakii.
  • 116. UTI May be treated for 7-14 days. This duration has no evidence to back it. Start empirical treatment with Cefotaxime/Ceftriaxone plus Amikacin, and modify as per culture report. Nalidixic acid or nitrofurantoin should not be used to treat UTI since they do not achieve therapeutic concentrations in the renal parenchyma and blood stream.
  • 117. UTI occurring in the setting of generalized septicemia may not be associated with VUR or malformations. However, an isolated UTI could be associated with these conditions. Hence, after treatment of isolated UTI, all cases must be started on Amoxycillin 10 mg/kg once a day oral prophylaxis, till such time that a renal ultrasound, MCU and DMSA scan are performed to exclude VUR or malformations.
  • 118. Proven bone or joint infections: Must be treated for at least 6 weeks. Start empirical treatment with Cloxacillin or Vancomycin (plus an aminoglycoside for first 1-2 weeks) and modify as per culture report. Of this, at least 4 weeks must constitute parenterally administered antibiotics. The rest of the course may be enterally administered.
  • 119. Adjunctive therapies: a) Intravenous immunoglobulins (IVIG): The currently available evidence does not support the use of IVIG. The currently undergoing International Neonatal Immunotherapy Study is expected to be provide some important and definitive information in this aspect(The INIS Study). b) Colony stimulating factors: There is currently no evidence to support the use of colony stimulating factors either as a treatment modality or as a prophylaxis therapy.
  • 120. c) Blood Exchange Transfusion (BET): BET may be performed in a case of deteriorating sepsis with sclerema provided the general condition of the baby allows the procedure .
  • 121. Superficial infections with local Superficial infections can be treated application of antimicrobial agents. Pustules can be punctured with sterile needles and cleaned with spirit or betadine. Purulent conjunctivitis can be treated with neosporin or chloramphenicol ophthalmic drops. Oral thrush responds to local application of clotrimazole or nystatin (200,000 units per ml) and hygienic precautions. Superficial infections must be adequately managed; if neglected they can lead to sepsis or even an epidemic.
  • 122. Prevention of infections A good antenatal care goes a long way in decreasing the incidence, morbidity and mortality from neonatal sepsis. All mothers should be immunized against tetanus. All types of infections should be diagnosed early and treated vigorously in pregnant mothers.
  • 123. Babies should be fed early and exclusively with expressed breast milk (or breastfed) without any prelacteal feeds. Cord should be kept clean and dry. Unnecessary interventions should be avoided.
  • 124. Hand washing This is the simplest and the most effective method for control of infection in the hospital. All persons taking care of the baby should strictly follow hand washing policies before touching any baby. The sleeves should be rolled above the elbows. Rings, watches and jewellery should be removed.
  • 125. Wash hands up to elbows with a thorough scrub for 2 minutes with soap and water taking care to cover all areas including the under surface of well trimmed nails. Rinse thoroughly with running water. Dry hands with sterile hand towel/paper towel. Wash hands up to the wrist for 20 seconds in between patients. Hands should be rewashed after touching contaminated material like one’s face, hair, papers etc.
  • 126. It is preferable to use bar soaps rather than liquid soaps as the latter tend to harbor organisms after storage. In emergency situations bactericidal and virucidal solutions like Sterillium can be used to clean hands before touching babies. Surgical, elbow- operated taps should be used in the hospitals for hand washing.
  • 127. Prevention of infection in hospital The nursery environment should be clean and dry with 24 hour water supply and electricity. There should be adequate ventilation and lighting. The nursery temperature should be maintained between 30+2°C. Overcrowding should be avoided.
  • 128. All procedures should be performed after wearing mask and gloves. Unnecessary invasive interventions such as needle pricks and setting up of intravenous lines should be kept to the barest minimum. There should be no compromise in the use of disposables. Stock solutions for rinsing should be avoided.
  • 129. Every baby must have separate thermometer and stethoscope and all barrier nursing measures must be followed. Strict house-keeping routines for washing, disinfection, cleaning of cots and incubators should be ensured and these policy guidelines should be available in the form of a manual in the nursery.
  • 130. The use of prophylactic antibiotics for prevention of nosocomial infections is strongly condemned. They are not only useless but also dangerous because of the potential risk of emergence of resistant strains of bacteria.
  • 131. Control of outbreak General measures for the control of an outbreak include detailed epidemiological investigations, increased emphasis on hand washing, review of protocols, procedures and techniques, disinfection and sterilization of nursery assessment of the need for additional measures.
  • 132. The nursery may be fumigated using formalin 40% and potassium permanganate (70 gms of KMNO4 with 170 ml of formalin for 1000 cubic feet area). Alternatively, bacillocid spray for 1-2 hours may be used. Linen and cotton should be washed thoroughly, dried and autoclaved.
  • 133. Use of disposable items for invasive and non- invasive interventions (catheters, probes, cannulae, chest tubes etc.) though costly, reduces the risk of infection. Depending upon the pathogen and type of outbreak, culture surveys of susceptible patients, cohorting of infants in nursery and a review of antibiotic policy may be necessary. Most of the times a scrupulous reinforcement of general control measures may be sufficient to stop the outbreak.
  • 137. Conclusion In conclusion, manifestations of neonatal sepsis are non-specific. A high index of suspicion with or without lab evidences of infection is the key for early diagnosis. Prompt institution of antibiotic therapy and supportive care will save most of the cases of neonatal sepsis.
  • 138. Take home messages. In India, both early and late onset sepsis are caused by similar organisms with similar antibiotic sensitivities. Clinical features of neonatal sepsis are non-specific and any unexplained clinical deterioration should be investigated for sepsis. There is no role of performing sepsis screen in early onset neonatal sepsis. Lumbar puncture (LP) for CSF examination must be performed in all symptomatic neonates being initiated on antibiotics, with the exception of premature neonates presenting with respiratory
  • 139. The traditional cut-offs for interpretation of cerebrospinal fluid values are based on relatively old studies with methodological problems. A new set of guidelines for interpretation is proposed. Routine urine culture in all neonates with nonspecific symptoms is not recommended.
  • 140. Every newborn unit must have its own antibiotic policy based on the local sensitivity patterns and the profile of pathogens. Apart from appropriate antibiotics, the survival of a sick septic newborn often depends upon aggressive supportive care.
  • 141. There may be a potential role of intravenous immunoglobulins in treatment of neonatal sepsis but larger studies are required. There is currently no role for the use of colony stimulating factors.
  • 142. THANKS