Jimma University Hospital - Neonatal Unit Guidelines Guideline No.

D1

Title: THERAPEUTIC GUIDELINES IN NEONATAL INFECTION

Version: 1
Date: October 2008
Review date: October 2010
Approval: Neonatal Guidelines and Working Practices Group 7/11/08
and Special Paediatric Departmental Meeting 12/11/08
Author: Dr Netsanet Workneh
Job title: Senior Paediatric Resident
Distribution: Neonatal Unit
Risk managed: Treatment of neonatal infection, and
Prevention of inadvertent use of antibiotics and development of
drug resistant bacteria.

Introduction / Background

Neonatal infection is a major cause of mortality and morbidity. In UK the incidence of early infection
(<48hours) is approximately 2-3 per 1000 live births with a mortality of 15%. The incidence of
meningitis in these infants is 23% [1]. The incidence of late infections (after 48 hours) is 4.4 per 1000
live births with a mortality rate of 9%. The incidence of meningitis in these infants is 9% [1]. Most
sepsis on the neonatal unit is late sepsis in preterm infants and life threatening late-onset infections
in term infants are rare. In UK the commonest organism causing sepsis on the neonatal unit is
coagulase negative Staphylococcus reflecting the fact that most infection is late in onset and
probably nosocomial.

A retrospective record review of the 542 infants admitted to the neonatal unit of the Ethio-Swedish
Children's Hospital in Addis Ababa, Ethiopia, with sepsis in 1992-93 was conducted. There were 322
neonatal deaths (15% of total admissions) in the study period. Bacteremia was confirmed only in
151 children (28%). The incidence of sepsis was 11/1000 live births. 195 children died, for a case
fatality rate of 36%.

This included 59 deaths from "proven sepsis" (39%) and 136 (61%) from "presumptive sepsis." The
most common etiologic agent was Klebsiella (38% of cases), which is resistant to most available
antibiotics.

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Jimma University Hospital - Neonatal Unit Guidelines Guideline No. D1

Signs and symptoms most often encountered included poor feeding (83%), temperature instability
(63%), and respiratory distress (33%). low birth weight was a predisposing factor for both the
development of sepsis and neonatal mortality (2).

Symptoms and signs of infection are notoriously vague and ill defined, and range from jaundice, to
respiratory distress, to septic shock. Although the commonest symptom is a non-specific going off
when the mother or an experienced nurse feels the infant is just not right. It is important to have a
low threshold for starting antibiotics particularly in preterm infants.

Classification

1. Early Sepsis ( less than 72 hrs of age)

The commonest organisms in this group of infants are (in order of decreasing frequency):
Group B Streptococcus
Escherichia coli (E. coli),
Streptococci other than Group B
Staphylococcus aureus
Haemophilus influenzae
Listeria monocytogenes
Gram negative anaerobes
Fungi
Chlamydia trachomatis

2. Late Onset Sepsis

The commonest organisms in this group of infants are (in order of decreasing frequency):
Coagulase negative Staphylococcus
Staphylococcus aureus
Enterococcus / group D Streptococcus
Group B streptococcus
Enterobacter, Escherichia coli,
Klebsiella, Pseudomonas, Other Gram negatives
Candida albicans

Management of sepsis
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Jimma University Hospital - Neonatal Unit Guidelines Guideline No. D1

- Establish an IV line and give only IV fluid at maintenance volume according to the babys age for
the first 12 hours.
- Take a blood sample for culture and sensitivity, if possible,
- measure haemoglobin, if the haemoglobin is less than 10 g/dl (haematocrit less than 30%), give a
blood transfusion.
- Treat convulsions, if present

Investigations
Blood Culture
Full blood count (FBC) and C-Reactive protein (CRP) or ESR
CXR
Lumbar puncture - Diagnosis is suggested by
- a CSF protein > 150 mg/dL,
- glucose < 30 mg/dL (less than 70% of serum blood sugar ),
- > 30 leukocytes/mL for preterm newborns and >15 leukocytes/mL for
term babies and a positive Gram stain or culture.

For early onset

Antibiotic ampicillin and gentamicin
Duration: If positive cultures minimum 7 days (7-10 days).
If negative cultures, and clinically well, with normal CRP or ESR stop after 48 hours
If negative cultures, but not clinically well, abnormal CXR or elevated CRP discuss with Neonatal
Consultant.
- If no improvement after 48 hours, or worsens, discuss with Consultant and after repeating blood
cultures ( if possible) and considering further investigations, consider changing to: ceftriaxone and
gentamicin

For late onset

Antibiotic ampicillin and gentamicin
- in certain cases were patient is critically sick or staphylococcal infection is likely (pustular skin rash,
osteomylitis ) start with triple antibiotics (cloxacilline ampicillin and gentamicin)
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Jimma University Hospital - Neonatal Unit Guidelines Guideline No. D1

- If no improvement after 48 hours, or the infants condition worsens consider changing antibiotics to:
cloxacillin, ceftriaxone and gentamicin
- If no improvement with the above three drugs start on
vancomycin and gentamicin

Treatment of neonatal sepsis with meningitis

Antibiotics the same as for sepsis, but with higher dose and prolonged duration: give the antibiotics
for 21 days.

Multiple findings ( sepsis, prematurity or asphyxia)

In developed countries over the last decade, the role of supportive laboratory tests such as CRPs
and differential white cell counts in addition to blood culture has increased, and decisions about
therapy may be based on information gained from multiple sources. In settings where this
investigations are not available it is important to stop antibiotics promptly when indicated (based on
WHO guide line) so as not to prolong antibiotic exposure and increase the antibiotic burden and thus
increase the likelihood of the development of resistant organisms.

Review the findings from the general history and examination and follow the following guide
to decide on when to start antibiotics and when to discontinue the antibiotics

Look especially for a history of:

- Complicated or difficult labour or birth (e.g. fetal distress);
- Prolonged labour; inadvertent
- Failure of baby to spontaneously breathe at birth;
- Resuscitation of baby at birth;
- Maternal uterine infection or fever any time from the onset of labour to three days after
birth;
- Rupture of the mothers membranes for more than 18 hours before birth;
- preterm delivery;

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Table 1. Findings common to sepsis and asphyxia

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Jimma University Hospital - Neonatal Unit Guidelines Guideline No. D1

IF SEPSIS IS SUSPECTED

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- If the baby has two or more Category A findings OR three or more Category B findings,
treat for sepsis.

- If the baby has one Category A finding and one Category B finding OR two Category B
findings, treat any specific sign (e.g. breathing difficulty) but do not begin treatment for sepsis.
Observe the baby for additional signs of sepsis, reassessing the baby every two hours for 12
hours.

- If additional signs of sepsis are found at any time during the observation period, treat for
sepsis.

- If no additional signs of sepsis are found during the observation period but the initial signs
have not improved, continue observation for 12 more hours.

- If the initial signs of sepsis improved during the observation period, reassess the baby
every four hours for an additional 24 hours. If improvement continues, the baby is feeding well,
and there are no other problems requiring hospitalization, discharge the baby.

Table 2. Summary of decision-making pathway to distinguish sepsis from asphyxia

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 Jimma University Hospital - Neonatal Unit Guidelines Guideline No. D1

Babys Age and Findings More Treat for

Mothers History Consistent with
Baby three days old or Asphyxia Sepsis and asphyxia
less
and maternal history Sepsis Sepsis
suggestive of sepsis
Asphyxia asphyxia
Baby three days old or
less and maternal
sepsis Possible sepsis (review
history not suggestive of
for
sepsis
presence of Category A
OR
or B
Baby became ill on day 4
findings
or later

If there is severe breathing difficulty (respiratory rate more than 90 and presence of grunting
or chest indrawing) - treat for sepsis.

Table 2. Classification of breathing difficulty

Term newborns with history of prolonged rupture of membranes without uterine infection or
fever
-If possible take a blood sample, and send it to the laboratory for culture

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and sensitivity, but do not start antibiotics.

Observe for signs of sepsis (e.g. poor feeding, vomiting, breathing difficulty every four hours for 48
hours.
If the blood culture is negative, the baby still has no signs of sepsis after 48 hours and is feeding
well, and there are no other problems requiring
hospitalization:- Discharge the baby
If the blood culture is positive or if the baby develops signs of sepsis,
treat for sepsis
If the blood culture is not possible, observe the baby for an additional three days. If the baby
remains well during this time, discharge the baby.
- Explain to the mother the signs of sepsis, and ask her to return with the baby if the baby develops
any signs of sepsis.

Preterm newborns (gestational age 35 weeks or more or birth weight 2 kg or more) with
history of prolonged rupture of membranes without uterine infection or fever
Treat for sepsis with the following modifications:
- If the blood culture is positive or if the baby develops signs of
sepsis, continue antibiotics to complete 10 days of treatment;
- If the blood culture is negative and the baby still has no signs of
Sepsis after five days of treatment with antibiotics, discontinue antibiotics;
- If the blood culture is not possible but the baby still has no signs
- of sepsis after five days of treatment with antibiotics, discontinue antibiotics.
Observe the baby for 24 hours after discontinuing antibiotics:
- If the baby remains well, is feeding well, and there are no other
problems requiring hospitalization, discharge the baby;
- Explain to the mother the signs of sepsis, and ask her to return with the baby if
the baby develops any signs of sepsis.

Baby is more than three days old (regardless of gestational age), with history of prolonged
rupture of membranes without uterine infection or fever

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- no treatment (e.g. antibiotics) or observation is needed. -

- explain to the mother the signs of sepsis and ask her to return with the baby if the baby develops
any signs of sepsis.

Term newborns with history of uterine infection or fever, with or without rupture of
membranes
Take a blood sample, and send it to the laboratory for culture and sensitivity, if possible, but do not
start antibiotics.
Observe for signs of sepsis (e.g. poor feeding, vomiting, breathing difficulty; every four hours for 48
hours.
If the blood culture is negative, the baby still has no signs of sepsis after 48 hours and is feeding
well, and there are no other problems requiring hospitalization: discharge the baby.
If the blood culture is positive or if the baby develops signs of sepsis, treat for sepsis
If the blood culture is not possible, observe the baby for an additional three days. If the baby
remains well during this time, discharge the baby.

Gestational age less than 35 weeks or birth weight less than 2 kg with history of uterine
infection or fever, with or without rupture of membranes
Treat for sepsis with the following modifications:
- If the blood culture is positive or if the baby develops signs of sepsis, continue antibiotics to
complete 10 days of treatment;
- If the blood culture is negative and the baby still has no signs of sepsis after five days of
treatment with antibiotics, discontinue antibiotics;
- If the blood culture is not possible but the baby still has no signs of sepsis after five days of
treatment with antibiotics, discontinue antibiotics.
Observe the baby for 24 hours after discontinuing antibiotics:

SKIN INFECTIONS
Wearing clean examination gloves:
- Wash the affected area(s) of skin using an antiseptic solution and clean gauze.
- Swab the pustules/blisters with 0.5% gentian violet solution;

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- Repeat four times daily until the pustules/blisters are gone. Have themother do this whenever
possible.
- Observe for signs of sepsis (e.g. poor feeding, vomiting, breathing difficulty and treat for
sepsis if found.
- Count the number of pustules or blisters, determine whether they cover
less or more than half of the body, and treat as described below:

Fewer than 10 pustules/blisters or covering less than half the body with no signs of sepsis
- observe the baby for five days:
- If the pustules/blisters clear within five days and there are no other
Problems requiring hospitalization discharge the baby.
- If most of the pustules/blisters are still present after five days but
the baby does not have signs of sepsis, give cloxacillin by mouth
according to the babys age and weight. for five days.

Ten or more pustules/blisters or covering more than half the body with no signs of sepsis
take a specimen of pus using a sterile cotton swab, and send it to the laboratory for
culture and sensitivity.
give cloxacillin im according to the babys age and weight.
assess the babys condition at least once daily for signs of improvement
- if the pustules/blisters are improving after three days of treatment with antibiotics, continue
cloxacillin to complete five days of treatment;
- If the pustules/blisters are not improving after three days of treatment with antibiotics:
- If the culture is positive, change the antibiotic according to the results of the culture
and sensitivity, and give the antibiotic for an additional five days;
- if the culture is not possible or the organism cannot be identified, continue giving
cloxacillin and also give gentamicin according to the babys age and weight for seven
days.
observe the baby for 24 hours after discontinuing antibiotics. if the pustules/blisters have
cleared, the baby is feeding well, and there are no other problems requiring hospitalization,
discharge the baby.

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Skin pustules/blisters with signs of sepsis

Treat for sepsis , but give cloxacillin IV according to the babys age and weight instead of ampicillin.

Cellulites/abscess
If there is a fluctuant swelling, incise and drain the abscess.
Give cloxacillin IM according to the babys age and weight
Assess the babys condition at least once daily for signs of improvement:
- If the cellulitis/abscess is improving after five days of treatment with the antibiotic, continue
cloxacillin to complete 10 days of treatment;
- If the cellulitis/abscess is not improving after five days of treatment with the antibiotic:
- If the culture is positive, change the antibiotic according to the results of the culture
and sensitivity and give the antibiotic for an additional 10 days;
- If the culture is not possible or the organism cannot be identified, continue giving
cloxacillin and also give gentamicin according to the babys age and weight for 10 days.

EYE INFECTIONS

Eyes red, swollen, or draining pus

Red and swollen eyes or eyes draining pus may be caused by bacteria (e.g. gonococcus, Chlamydia,
staphylococcus) that are usually transmitted to the baby at the time of birth. most causes of newborn
eye problems will respond to local treatment, but gonococcal and chlamydial infections need to be
identified, as they require systemic antibiotics.
review the finding- looking especially for a history of a sexually transmitted infection in the mother.

Table 3. Differential diagnosis of conjunctivitis

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The diagnosis is definitively confirmed if a finding listed in italics is present. Findings in plain text are
supportive findings; their presence helps to confirm the diagnosis, but their absence cannot be used
to rule out the diagnosis.

General management
wearing clean examination gloves:
- clean the eyelids using sterile normal saline or clean (boiled and
cooled) water and a clean swab, cleaning from the inside edge of the
Eye to the outside edge;
- have the mother do this whenever possible;
- repeat four times daily until the eye problems have cleared.
have the mother wash the babys face once daily (or more often, if
necessary) using clean water, and dry with a clean cloth.

Red or swollen eyes and sticky eyelids but no pus draining from eyes
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If the eye problem continues for more than four days (despite the general management described
above), but there is still no pus draining from the eyes:
- Give erythromycin by mouth for 14 days;
- Apply 1% tetracycline ointment to the affected eye(s) four times daily until the eye(s) is no longer
red, swollen, or sticky.

Eyes draining pus (conjunctivitis)

take a specimen of pus, if it can be easily obtained, using a sterile cotton swab. smear the pus on a
slide, stain the slide with gram stain, and view the slide under a microscope;
- send a sample of the pus to the laboratory for culture (including possible gonococcus) and
sensitivity; determine the probable diagnosis.
If it is not possible to perform a gram stain or culture and sensitivity:
Gram stain or culture and sensitivity not possible
If the baby is less than seven days old and has not been treated with systemic antibiotics
before, treat for conjunctivitis due to gonorrhoea
Give ceftriaxone 125 mg IM in a single dose.
There is no need for antibiotic eye ointment.
Continue to clean the babys eyes and wash the babys face as described
Under general management.
If the mother and baby can stay near the health care facility, the baby
does not have to be admitted to the hospital for this treatment.
Treat the mother and her partner(s) for gonorrhoea if not already treated
Give: - ceftriaxone 250 mg IM as a single dose to the mother;
- Ciprofloxacin 500 mg by mouth as a single dose to her partner.

If the baby is seven days or older and has been previously treated unsuccessfully with
systemic antibiotics, or if the baby is less than seven days old and the problem is not
resolved after 48 hours of treatment, treat for conjunctivitis due to chlamydia
Give erythromycin by mouth for 14 days.
After cleaning the eyes, apply 1% tetracycline ointment to the affected eye(s) four times daily
until the eyes are no longer red, swollen, sticky, or draining pus.
If the mother and baby can stay near the health care facility, the baby
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does not have to be admitted to the hospital for this treatment.

Treat the mother and her partner(s) for chlamydia if not already treated
Give: - erythromycin 500 mg by mouth four times daily for seven days to the mother; -
tetracycline 500 mg by mouth four times daily for seven days to her partner- OR doxycycline
100 mg by mouth twice daily for seven days to her partner

References

1. Isaacs D, Barfield CP, Grimwood K, McPhee AJ, Minutillo C, Tudehope DI. Systemic bacterial
and fungal infections in infants in Australian neonatal units. Medical Journal of Australia
1995;162:198-201
2. Ghiorghis B. Neonatal sepsis in Addis Ababa, Ethiopia: a review of 151 bacteremic neonates.
Ethiop Med J. 1997 Jul;35(3):169-76.
3. Stoll BJ, Gordon T, Korones SB et al. Early-onset sepsis in very low birth weight neonates: a
report from the NICHHD Neonatal Research Network. Journal of Pediatrics 1996;129:1093-
1099
4. Rennie JM, Roberton NRC. Textbook of Neonatology (3rd Edition). Appendix 11.
5. WHO. .Managing newborn problems: a guide for doctors, nurses, and midwives. World Health
Organization 2003

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