Premature Rupture of the

Membranes and Neonatal Sepsis

Neonatal Case Scenario 1

1
History

A 24 year old, G2P1, woman gave birth

vaginally to a 33 week gestation, 1500 gm,
AGA female. The woman arrived in labor
with PROM for 72 hr and a fever of 38.5° C
for which she received intrapartum
antimicrobial prophylaxis. Her previous
delivery was also preterm.

2
History (cont.)

 Apgar score was 6 and 8 at 1and 5 min

respectively. The infant needed initial
stabilization and free flow O2 for
resuscitation.
 After stabilization, the infant was taken to
the nursery for observation.

3
Q 1:
Do you think this infant was a
candidate for antibiotic administration
in the delivery room? What are the
indications for giving antibiotics in the
delivery room?

4
Answer to Q 1

It is important to note that the mother received

antibiotics not prophylactically but therapeutically
as she already had a fever with clinical signs of
chorioamnionitis.
As the mother had clinically overt symptoms and
signs of chorioamnionitis, the neonate should
receive antibiotics as soon as possible. The
indication is a high level index of suspicion of
sepsis.
5
Answer to Q 1 (cont.)

By saying “as soon as possible” it is meant that if

antibiotics are to be given in the delivery room,
there must be a person able to insert an
appropriate IV line, to calculate the dose
accurately and to give it appropriately.
We generally do not use gentamicin, which is the
antibiotic of choice for gram negative coverage,
until we know what we are treating.

6
Answer to Q 1 (cont.)

Gentamicin should be given as a drip. If you

give gentamicin as a push it may cause a
neuromuscular block and may lead to
apnea. Also, the peak level may be
exaggerated causing ototoxicity.
Ampicillin, on the other hand, can be given
as a push in the delivery room.

7
Answer to Q 1 (cont.)

If it is not possible to give gentamicin as a

drip, the second choice is to give it
intramuscularly until an IV line is secured.
But the infant should be large enough to
have a muscle bulk. Giving it IM leads to
slow absorption.
Again, it is stressed that this is not the best
choice but it is an alternative.
8
Q 2:
Are vaginal and rectal cultures routinely
taken for all pregnant women? At what
gestational age?

9
Answer to Q 2

In the USA, cultures are routinely done between 35

– 37 weeks gestation.
Question: If there is a previous history of
colonization or complications of group B
streptococcus is it appropriate to obtain more than
one culture during the pregnancy?
Answer: In case of prior damage to an infant or a
prior infant treated for infection, assume that the
culture is still positive and treat.
10
Answer to Q 2 (cont.)

It is not required to repeat the culture

because obtaining serial cultures may give
false negative culture results.

Question: Does the treatment occur at

various stages of pregnancy?

11
Answer to Q 2 (cont.)

Answer: No. If there is a positive urine

culture treat at any point. If there is a
symptomatic disease treat at any point. But
if there is chronic colonization (e.g.,
asymptomatic) give prophylactic IV
antibiotics after rupture of membranes or at
the time of labor.

12
On Admission

Vital signs were as follows:

 HR 160 bpm
 RR 55/min
 Temp 36° C
 BP 45/30 mmHg
 MAP (mean arterial pressure) 35 mmHg

13
General Examination

 The infant was pink and in generally good

condition
 Capillary refill time < 2 sec

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System Assessment

 NAD

15
Investigations

CBC
 Hb 14 gm
 Hct 41%
 WBCs 3,000/mm3
 Platelet count 200,000/mm3
 Differential count not available

16
Investigations (cont.)

 CRP negative (titre was not available)

 Chest x-ray NAD
 Serum glucose 200 mg/dl
 Blood culture was not available

17
Management

IV fluids and antibiotics were started in the

form of ampicillin and gentamicin.

18
Q 3:

Gram negative bacilli are the predominant

organisms in our units. Knowing this, would the
leucopenia and hyperglycemia found, together with
the maternal risk factors, justify the use of more
aggressive antibiotics such as ampicillin and 3 rd
generation cephalosporins such as ceftazidime
(Fortum) without obtaining blood cultures?

19
Answer to Q 3

The problem with using third generation

cephalosporins or other antibiotics as first
line therapy is causing the quick
development of antibiotic resistance which
leads to fulminant septic neonates that you
are incapable of treating and you will watch
them die.

20
Answer to Q 3

This is not unique to Egypt. It is occurring in

Eastern European countries and is
developing slowly in the USA.
People gave themselves license to use
antibiotics freely and resistance developed
quickly.

21
Answer to Q 3 (cont.)

Again, there is a general agreement that

ampicillin and gentamicin are the first line of
therapy and you should respect this and
stick to it.
Furthermore, you are able to change drug
resistance patterns overtime by the judicious
and selective use of antibiotics.

22
Answer to Q 3 (cont.)

Also, you must look for simple, non-

sophisticated methods for culturing, e.g. to
culture the blood sample on liquid growth
media and check it under a microscope after
24 to 48 hours to know whether it is gram
positive or gram negative organism.

23
Answer to Q 3 (cont.)

Finally, the likelihood that this neonate had a

multidrug resistant organism is very low.
Because the infection developed in the
community, it will be antibiotic sensitive. It is
not a nosocomial infection developing in the
hospital where there would be a great
possibility of the presence of multidrug
resistant organisms.
24
Scenario

At 12 hours of age the infant became

tachycardic and hypotensive.

The vital signs had not changed except:

 The BP dropped from 45/30 to 40/15

mmHg
 The MAP dropped down to 25 mmHg

25
General Examination

 The infant was pink with a wide pulse

pressure and warm extremities
 Capillary refill time = 3 sec
 Irritable
 SaO2 80%

26
GWU Comment

A common entity remains common. In the rest of

the scenario we are not thinking of PDA.
Having desaturations with a widening pulse
pressure raises the possibility of the presence of a
PDA.
Even septic neonates develop PDA. Furthermore,
septic neonates are actually more liable to develop
PDA. If a neonate with septic shock develops a
PDA, you have to expect that the prognosis will be
worse.
27
Management

 The infant was put on nasal prong CPAP

of 5 cm H2O and a FiO2 60%.
 A volume expander was given in the form
of saline 20 cc/kg over 30 min.
 The infant received dopamine at
5 µg/kg/min. The BP didn’t improve.
Dobutamine was added at 10 µg/kg/min
and increased to 20 µg/kg/min. 28
Scenario - 2 Hours Later

Vital signs were as follows:

 HR 180 bpm
 RR 75/min
 Temp 35° C
 BP dropped further to 30/0 mmHg
 MAP 10 mmHg
29
General Examination

 The infant looked dusky with cold mottled

extremities
 Capillary refill time was delayed (5 sec.)

30
Systemic Assessment

 CNS: Lethargic
 CVS: Weak pulses
 Resp: Basal crepitations became
evident bilaterally with a Downs score
of 5 and SaO2 80%
 GIT: NAD
 Urine output: < 0.5 ml/kg/hr
31
Investigations

 Chest x-ray was repeated. It revealed

cardiomegaly and a few bilateral
heterogenous patches scattered over
both lungs.

32
Q 4:
What is the etiology of cardiomegaly in
such a case?

33
Answer to Q 4

Generally, if the general management of a septic

neonate is not appropriate, the prognosis will be
worse. Obviously, this neonate is getting into
trouble. The vital signs are deteriorating. The
temperature dropped to 35° C.
In the NICU there is no reason whatsoever that a
neonate’s temperature drops to 35° C unless the
environmental temp. is not monitored and
controlled properly.
34
Answer to Q 4 (cont.)

If this neonate’s temperature was servo controlled,

the incubator would warm up if the neonate’s body
temperature dropped, to maintain the same body
temperature.
So, either a servo control mode for controlling
temp. was not used, environmental temp. was not
controlled or supplemental ways for warming the
neonate were not used.

35
Answer to Q 4 (cont.)

Second, this neonate is becoming more

hypoperfused and so is more acidotic.
Sepsis by itself can cause acidosis. This
neonate is deteriorating with hypoxia and
acidosis contributing to the development of
persistent pulmonary hypertension which
may explain the heart failure and the
cardiomegaly found on the x-ray.
36
Management

 FiO2 was increased gradually to 90%.

NaHCO3 was given empirically at
2 meq/kg IV over 5 minutes as no blood
gases were available.

 1 ml/kg Ca gluconate 10% was also given

slowly via IV.
37
Q 5:
Would repetition of a volume expander
be beneficial at this stage?

38
Answer to Q 5

In septic shock, giving the neonate too much

fluid will not resolve the hypotension and
may lead to right sided heart failure.
The cause of hypotension here is due first to
the peripheral vasodilatation and capillary
leak associated with sepsis and secondly to
what is called ‘systemic steal’.

39
Answer to Q 5 (cont.)

‘Systemic steal’ is a shifting of blood from

the systemic to the pulmonary circulation
through the PDA. Both of these mechanisms
may lead to right sided heart failure and
pulmonary edema which is probably what
you are witnessing here.

40
Scenario

No improvement occurred in the infant’s

condition. The shock stage persisted. The
infant was given hydrocortisone 1 mg/kg
with no improvement and the infant entered
into a state of DIC with bleeding from the
GIT and oozing from puncture sites.

41
Scenario (cont.)

Fresh blood was ordered for a double

volume exchange transfusion. The infant
died before the blood was available.

42
Q 6:
What are the indications of
hydrocortisone in a case of septic
shock?

43
Answer to Q 6

We do not routinely give hydrocortisone in sepsis

except very late in terminal stages and it is not
associated with a good outcome.
We do give hydrocortisone, however, to infants
who are treated with corticosteroids and weaned
over time as in the case of infants with chronic lung
disease who are given decadron.
We give them stress doses of steroids to be able
to maintain response to stress.
44
Q 7:
Do you think this infant was a candidate
for a double volume exchange
transfusion at an earlier stage?

45
Answer to Q 7

In the USA, we do not believe in this modality of

therapy. It is understood that this is still in the
folklore of some countries including Egypt and
some European countries where they believe it
may have some benefit.
However, in the USA, we even have a concern that
exchange transfusion may disturb the circulatory
status in an infant who is already cardiovascularly
compromised.
46
Answer to Q 7 (cont.)

So, we recommend that you undergo a

randomized controlled study to evaluate this
modality of therapy with half of the infants
receiving an exchange transfusion and half
not.

47
Q 8:
What is the role of IVIG in this case and
what is the optimum time for its
administration ?

48
Answer to Q 8

This is another very controversial topic. We

do not use IVIG in treating sepsis in the
USA. Trials done have proven that it is not
effective whether therapeutically or
prophylactically.

49
Answer to Q 8 (cont.)

The only exception to this is the use of selectively

potent IVIG such as that prepared against group B
streptococcus by vaccinating donors so that they
will have a high titer of specific antibodies (e.g.,
hyperimmunoglobulin).
Otherwise, using nonspecific IVIG is not beneficial
whether early, in the middle or late in sepsis.

50
Q 9:

Is lumber puncture routinely included in the

sepsis work-up or only when frank
neurological manifestations are apparent?
If the LP shows evidence of meningitis, how
frequently should it be done, weekly or
biweekly, until the CSF is clear?

51
Answer to Q 9

Yes, lumbar puncture should be done. But, if

you are only doing it for neonates with
neurological manifestations, you are missing
the point completely.
The point is to avoid damage to the CNS
and to pick up the presence of CNS infection
long before any neurological manifestations
appear.
52
Answer to Q 9 (cont.)

So, you must obtain many negative samples for

each positive sample or else you are not doing
lumbar puncture frequently enough.
If the neonate had a positive result, it is
recommended to repeat it after one week to ten
days and it would be expected to be negative.
Repeating lumbar puncture to the same neonate
too frequently may in itself be a route of
introducing infection.
53