MATERNAL-TO-INFANT TRANSMISSION Most Group B Streptococcal Disease cases among newborns result from mother-to-infant transmission during labor and delivery. Many women are asymptomatically colonized by group B streptococcus in the genital and gastrointestinal tracts. Colonization is not altered by or dependent on pregnancy. About half the infants born to colonized mothers are themselves colonized on the skin and mucosal surfaces as a result of passage through the birth canal or as a result of GBS ascending into the amniotic fluid. The majority of colonized infants, 98%, are asymptomatic. About 2% will develop early-onset disease, presenting with sepsis, pneumonia or meningitis in the first few days of life.
This slide shows an algorithm for the secondary prevention of early-onset GBS disease among newborns.
Neonatal sepsis 2
BY DR ASIM
Clinical syndrome of bacteremia with systemic
signs and symptoms of infection in the first
four weeks of life.
1/ evalution of newborn
2/septic work up
as SIRS plus infection
as sepsis associated with organ
dysfunction, hypo perfusion or
sepsis with arterial hypotension despite
“Early onset” 0-3 days (~75% cases)
90% show within 12 hours
Usually septicaemia and pneumonia
11% mortality, 7% morbidity
90% preventable IV Penicillin
“Late onset” 3-90 days (~25% cases)
Usually meningitis and septicaemia
8% mortality, 21% morbidity (up to 50% with
No current prevention: good hygiene/education
Vaccine: future hope for both late & early onset
Risk factor with Red flag
1/Invasive group B streptococcal infection in a previous baby
2/Maternal group B streptococcal colonisation, bacteriuria or infection in
the current pregnancy
3/Prelabour rupture of membranes
4/Preterm birth following spontaneous labour (before 37 weeks'
5/Suspected or confirmed rupture of membranes for more than 18 hours
in a preterm birth
6/Intrapartum fever higher than 38°C, or confirmed or suspected
7/Parenteral antibiotic treatment given to the woman for confirmed or
suspected invasive bacterial infection (such as septicaemia) at any
time during labour, or in the 24-hour periods before and after the
birth [This does not refer to intrapartum antibiotic prophylaxis].
8/Suspected or confirmed infection in another baby in the case of a
1/ immature immune responses.
2/ poorly developed skin and mucosal barriers to
3/ numerous entry portals for organisms via
cannulae, catheters and endotracheal tubes.
4/ continuing exposure to oppurtunistic organisms
during often a prolonged hospital stay
-Volume of 0.5 ml or more (ideally 1 ml or more)
:False –ve c/s
Small blood sample
study of nearly 300 blood c/s , 55% of culture vials
contained less than 0.5 ml of blood
Bacteria load, timing of sampling
>90% of positive cultures occur within 48 hrs of
In a 1999, autopsy study of ELBW infants
infection was primary cause of death by pathologists in
(56 of 111)
sepsis was not diagnosed prior to death for 61% of these
Consists of 5 items:
1. C-reactive protein (CRP),
2. Total leukocyte count
3. Absolute neutrophil count (ANC)
4. Immature to total neutrophil ratio
5. Micro-erythrocyte sedimentation rate
No agreement on what constitutes “normal”
WBC < 4k or >25 to 30 K
Immature:Total neutrophil ration > 0.2
Serial values, 8-12 hrs apart have high NPV
The total neutrophil count reference range in the first 60 hours of life for a group of
Points represent single values; numbers represent the number of values at the same
(From Manroe BL: The neonatal blood count in health and disease I: Reference values
Reference ranges for total neutrophil values in very low birthweight neonates
from birth to 60 hours of life (A) and 61 hours to 28 days of life (B).
(From Mouzinho A et al:
Revised reference ranges for circulatingneutrophils in very-low-birth-weight
neonates. Pediatrics 94:78, 1994.)
Neutropenia is more predictive of neonatal
sepsis than neutrophilia
:it may be present in
and periventricular hemorrhage.
= Immature neutrophils (band forms, metamyelocytes,
Mature + immature neutrophils
early predictor of sepsis.
N value = 0.16 in first 24 hours, decreasing to 0.12 by 60
Upper limit > 0.2.
Limitation- many noninfectious processes, including
prolonged induction with oxytocin, stressful labor, and
even prolonged crying, are associated with increased I:T
Weitkamp, J-H and Aschner, J.L. Neoreviews, 2005, 6(11):e508-15
Acute phase reactant, stimulated by IL-6
Production occurs ~ 4-6 hrs after stimulation
Peaks at 36-48 hrs
Half Life of ~ 19 hrs
-Single level often not helpful in determining infection
-Serial measurements may be beneficial in determining duration
of antibiotics in certain cases (eg: maternal incomplete
antibiotic treatment, high index of suspicion for sepsis but
-Two CRP levels < 10 mg/L taken at least 8 hrs after
presentation and 24 hrs apart have high NPV. (Benitz, W. et
al. Pediatrics 1998, 102(e41):1-10)
-Sensitivity of serial CRP testing is lower for bacteremia due to
gram-positive than to gram-negative bacteria
elevated CRP on day 1 and/or day2, identify most case of sepsis
Positive Value (mm in first hour) > 3+ age in days (first week of
life) > 10 thereafter
Limitation- increased in noninfectious (anemia, hyperglycemia)
-Values vary inversely with the
•-noninfectious processes, including asphyxia,
aspiration pneumonia, and respiratory distress syndrome.
positive predictive value 88.9%
negative predictive value 99.8%
PCR: under investigation
for bacterial and fungal
amplification of 16S rRNA,
a gene universally present in
bacteria but absent in
Results in 9 h of sample
Incidence of neonatal meningitis 0.25 to 1
per 1000 live births
Blood culture negative in up to 50% of
Does not seem warranted in routine
evaluations (for perinatal risk factors,
Useful for those with evidence of sepsis
(who can tolerate procedure and in
those whom longer courses of
Traumatic LP: > 1000 RBC/mm3
1 WBC:100 to 500 RBC in normal spinal fluid
Difficult to Interpret
Observed:Predicted WBC Ratio based on
peripheral blood ratio.
O:P <0.01, WBC:RBC < 1:100 and absence of
pleocytosis high PPV for absence of
Mazor, S. et al. Pediatrics 2003, 111:525-8.
1/In EOS - a positive blood culture or clinical
picture consistent with septicemia.
2/In late onset sepsis, LP should be done in all
infants prior to starting antibiotics
> 32 WBC/mm3
> 60% PMN
glucose < 50% - 75% of serum
protein > 150 mg/dl
organisms on gram stain
detectable within 2 to 4 hours after a trigger
peaks by 12 to 24 hours.
parallels -closely the severity of the inflammatory
higher levels associated with more severe disease
declining levels with resolution of illness.
In the absence of an ongoing stimulus, ProCT is eliminated
with a half-life of 24 to 35 hours, making it suitable for
ProCT level of >2.0 ng/mL ---predicts sepsis and
>10 ng/mL ---septic shock.
>20 ng/mL --- guarded prognosis.
The higher the ProCT level -----worse the prognosis.
When sepsis has been successfully treated, ProCT levels
should fall with a half-life of 24 to 35 hours.
Identification of secondary septic events –
elevated noninfectious ProCT level, ProCT levels should
fall at a predictable pace in the absence of secondary
Limitation - ProCT levels that are elevated in noninfectious
conditions like after cesearean section, resuscitation at
birth, perinatal steroid exposure
BUT should start falling within 48 hours . Persistent high
levels or secondary peaks suggest secondary infection.
1/In babies given antibiotics because of risk factors for
infection or clinical indicators of possible infection,
measure the C-reactive protein concentration 18–24 hours
2/ lumbar puncture to obtain a cerebrospinal fluid sample
in a baby who did not have a lumbar puncture at
presentation who is receiving antibiotics, if it is safe to do
so and if the baby:
a/has a C-reactive protein concentration of 10 mg/litre or
b/has a positive blood culture, or
c/does not respond satisfactorily to antibiotic treatment.
●The choice of empirical
antibiotics is dependent on:
Protocols, Organsim/local prev
●The duration of therapy is
dependent upon culture results,
clinical course, and organism.
of ampicillin and gentamicin is effective in
treating most of the common pathogens(GBS/
2/Serum gentamicin levels are not required if
renal function is normal and a treatment course
of only 48 hours is anticipated
*If a 2nd gentamicin is to be given measure
the trough blood gentamicin concentration
immediately before giving the second dose.
Consider before 3rd dose.
* Hospital services should make it available
in time to inform the next dosage decision
(e.g, within 30 hours of sampling).
Consider in selected babies :
2/macrosomia (BW more than 4.5 kg)
3/ unsatisfactory response to treatment
4/proven Gram-negative infection.
Measure peak concentrations 1 hour after
starting the gentamicin infusion.
If a baby has a Gram-negative or staphylococcal
infection, consider increasing the dose of
gentamicin if the peak concentration is less than
(LP) should be performed:
* TRT more than 48 hours without a positive blood
culture (presumed sepsis).
3/If treatment is continued longer than 48 hours,
and meningitis has been excluded, the ampicillin
regimen can be changed to 75 mg/kg every 12
3/ If treatment is continued longer than 48 hours,
and no LP has been performed (or if the infant has
meningitis), the ampicillin dose should be changed
to 75 mg/kg 6/hrly.
ampicillin + cefotaxime :
1/is not more effective
2/cephalosporin-resistant strains (eg,
cloacae, Klebsiella, and Serratia specie.
3/ 1.5-fold increase in mortality rate (4.2
versus 1.9 percent, adjusted odds ratio 1.5,
95% CI 1.4-1.7)
*duration of therapy is generally 10 days .
*most improve clinically within 24 to 48 hours.
*The (I/T ratio) usually are abnormal for the first few days and begin to normalize
by 72 hours . *(CRP), to monitor treatment. Serum CRP initially rises 24 to 48
hours and begins to decrease after 48 to 72 hours in responsive infants .
Negative culture —
*automated blood c/s systems identify 97% at 24 hours, and 99 percent at 36
Thus, empiric antibiotic therapy should be discontinued in the well-appearing
infant after 48 hours .
*clinical condition remains concerning , ABS can be extended until anothr
diagnosis/ or to complete a 10-days trt .
*CRP measurements can be useful in identifying infants who are more likely to
have clinincal sepsis and –ve c/s.
Follow-up testing — A repeat blood c/s after 24 to 48 hours of therapy is obtained
to determine the response. Failure to sterilize the bloodstream suggests that the
antimicrobial(s) chosen are not active against the infecting pathogen or that there
is an unrecognized focus of infection
Rehospitalized from home-
*low risk of resistance
*Ampi genta is empirical treatmet.
(study from the HPA voluntary surveillance scheme
in 96 percent of isolates from late-onset
bacteremia were susceptible to the combination
of amoxicillin and gentamicin )
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 + Aminoglycoside
BE Aware--Cephalosporins rapidly induce the
production of extended spectrum β-lactamases
(ESBL), cephalosporinases and fungal colonization.
*Empiric antibiotic treatment varies between neonatal
intensive care units and countries
*no consensus guidelines on the choice of empiric antibiotics.
*There are also no definitive guidelines on classification of
CoNS as true sepsis or contaminant, the removal of indwelling
catheters or the duration of antibiotics for late onset sepsis
*The initial choice
1/ likely pathogens, 2/ susceptibility patterns in particular nursery 3/
presence of an apparent source of infection (eg, skin, joint, central
line, or bone involvement).
There has been an increasing emergence of infections in preterm
infants caused by antibiotic-resistant gram-negative bacteria .
As an example, in one study from the National Institute of Child
Health and Human Development (NICHHD) Neonatal Research
Network, 85 percent of early-onset Escherichia coli (E coli)
infections were resistant to ampicillin .
1/very low birth weight (birth weight <1500 g)
2/ exposure to third generation cephalosporins.
Two mechanisms :
a/●Chromosomally-encoded or plasmid-derived AmpC beta-
b/●Plasmid-mediated extended-spectrum beta-lactamases (ESBLs)
Organisms that produce ESBLs, primarily E Coli and Klebsiella
species, are resistant to penicillins, cephalosporins, and
monobactams, and can be resistant to aminoglycosides.
Guidelines for the treatment of the most common causative organisms of
neonatal sepsis are provided below.
● (GBS) is uniformly susceptible to penicillin. Thus, when GBS is identified as
the sole causative organism, we recommend that antimicrobial therapy be
changed to penicillin G alone .
●Escherichia coli – In (E. coli) sepsis sensitive to ampicillin who have improved
clinically and in whom meningitis has been excluded, ampicillin monotherapy is
administered for a 10- to 14-day course.
For patients with ampicillin-resistant E. coli, the choice of definitive therapy
includes an aminoglycoside, such as gentamicin, or cefotaxime.
However, in our practice, we prefer the use of cefotaxime over gentamicin in
patients with ampicillin-resistant E. coli because of the potential ototoxicity and
nephrotoxicity associated with gentamicin and the need to monitor gentamicin
*meropenem - extended-spectrum beta-lactamase producing organisms.
-Other gram-negative bacilli – Nonmeningeal infections caused by E. coli,
Klebsiella, Proteus, Salmonella, or Shigella can be treated with a single
agent, such as ampicillin or cefotaxime, based upon the antimicrobial
-Many experts suggest treatment with both a beta-lactam antimicrobial
agent (eg, ampicillin or piperacillin-tazobactam) and an aminoglycoside
for bacteremic infections caused by Enterobacter, Serratia, or
Pseudomonas. Infections due to ESBL organisms, or those with
hyperproduction of beta-lactamases, should be treated
-Listeria monocytogenes – ampicillin and gentamicin is more effective
than ampicillin alone in vitro and in animal models of Listeria infection,
and is used for initial therapy.
GBS – ampicillin or penicillin
E .coli –cefotaxime or ampicillin + gentamycin
Klebsiella - cefotaxime or meropenam
Enterococcus –ampicillin or vancomycin +
Listeria – ampicillin + gentamycin
Psudomonas – ceftazidime or piperacillin-
tazobactum + gentamycin
Staph. Aureas – nafcillin
MRSA - Vancomycin
Implications for research
There is a lack of studies that compare different antibiotic for treating suspected
narrow versus broad spectrum antibiotic regimens for suspected LOS.
In developed countries where CONS is the commonest late onset infection, trials
may wish to compare regimens with and without vancomycin plus an
In developing countries where broad spectrum antibiotic cover is common, ongoing
surveillance of types of organisms and increasing antibiotic resistance is particularly
important to then direct randomised trials.
Any future research also needs to assess cost effectiveness and the impact of
antibiotics in different settings such as developed or developing countries and
lower gestational age groups.
There is no evidence from randomised trials in favour of any particular
antibiotic regimen for the treatment of suspected late onset neonatal sepsis
1/As skin commensals, these organisms are also common blood
culture contaminants, and there is a lack of consensus as to how
to interpret CoNS positive results.
2/In the intensive care setting the vast majority of CoNS are
resistant to methicillin and thus infants with suspected late
onset infection are typically treated with empiric broad
spectrum antibiotics that include vancomycin (Rubin 2002).
3/ There are concerns regarding unrestricted vancomycin use as
a risk factor for the development of resistant organisms,
particularly enterococci (HICPAC 1995).
4/The majority of pathogens associated with fulminant late
onset sepsis (lethal within 48 hours) have been shown to be gram
negative organisms with pseudomonas leading the table
(Karlowicz 2000; Gordon 2004 (a)).
Intravenous immunoglobulins (IVIG):
The currently available evidence does not
support the use of IVIG.
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
Lactoferrin is an iron-binding glycoprotein. It has
broad-spectrum antimicrobial activity.
A multicenter, randomized, placebo controlled trial
involving VLBW infants who received daily orally
administered Bovine lactoferrin alone (n=99, dose =
100 mg/day), in combination with Lactobacillus GG
(n=99, dose = 106 CFU/day), or placebo (n=104) for
30–45 days show that the incidence of culture-
proven sepsis was lower in the groups that received
Final and complete results from this study are
Glutamine -- most abundant amino acid in plasma and
Studies in immunocompromised adults have suggested
that intravenous parenteral nutrition supplemented
with glutamine decreases the risk of sepsis and
A recently published Cochrane systematic review
examined the effect of enteral or parenteral glutamine
supplementation on the incidence of culture-proven
invasive infection from 5 clinical trials (n= 2,240). The
meta-analysis did not reveal a statistically significant
difference between the glutamine supplemented and
control groups (RR 1.01; 95% CI 0.91, 1.13).
Activated protein C is an endogenous compound that
promotes anticoagulation and modulates the
During severe systemic infections, the levels and degree
of protein C activation are decreased;
In one study, decreased activity of activated protein C
was associated with increase mortality among neonates
The largest randomized controlled-trial of recombinant
activated protein C in children (n=477);approximately
6% young infants) failed to show an improvement in the
clinical score used at the primary outcome and in the
28-day mortality when the drug was compared to
Superficial infections can be treated with local
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
Superficial infections must be adequately managed; if
neglected they can lead to sepsis or even an
A good antenatal care goes a long way in
decreasing the incidence, morbidity and
mortality from neonatal sepsis.
All mothers should be immunized against
All types of infections should be diagnosed
early and treated vigorously in pregnant
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
This is the simplest and the most effective
method for control of infection in the
All persons taking care of the baby should
strictly follow hand washing policies before
touching any baby.
The sleeves should be rolled above the
Rings, watches and jewellery should be
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
Rinse thoroughly with running water. Dry hands with
sterile hand towel/paper towel.
Wash hands up to the wrist for 20 seconds in between
Hands should be rewashed after touching
contaminated material like one’s face, hair, papers
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.
The nursery environment should be clean and
dry with 24 hour water supply and
There should be adequate ventilation and
The nursery temperature should be maintained
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
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
They are not only useless but also dangerous
because of the potential risk of emergence
of resistant strains of bacteria.
General measures for the control of an
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.