Sepsis Neonatorum

• Definition
• Symptoms
• Diagnosis
• Prognosis and Treatment
Sepsis in a newborn (sepsis neonatorum) is an infection that spreads throughout the baby’s body.
Sepsis occurs in less than 1 percent of newborns (1 out of every 100), but accounts for up to 30
percent of deaths in the first few weeks of life. Infection is 5-10 times more common in premature
newborns and in babies weighing less than 5½ pounds than in normal-weight, full-term newborns.
Complications experienced during birth, such as premature or prolonged rupture of the membranes or
infection in the mother, put the newborn at increased risk of infection.
Symptoms
The onset of what is called early-onset neonatal sepsis is within six hours of birth in over half the cases
and within 72 hours in the great majority of cases. Sepsis that begins four or more days after birth is
called late-onest sepsis, and is probably an infection acquired in the hospital nursery (a nosocomial
infection). In both types of neonatal sepsis, the infection may be only in the bloodstream, or may
spread to the lungs (pneumonia), brain (meningitis), bone (osteomyelitis), joints, or other organs in the
body.
Typical symptoms of a newborn with sepsis include:
• listlessness (a very sleepy baby)
• feeding problems
• a high OR low temperature
Other symptoms include:
• difficulty breathing, rapid breathing, or apnea (when the baby stops breathing)
• seizures
• excessive jitteriness
• repeated vomiting or diarrhea
• a swollen abdomen
Diagnosis
The organism that is causing the infection may be identified by taking cultures of the blood as well as
from other sites of the body. Urine samples are often cultured for bacteria to look for an infection in
the urinary tract. Because only small samples of blood and other body fluids are taken, sometimes no
organism is found. However, the infant may still be treated if other laboratory studies or the infant’s
clinical appearance strongly suggest an infection.
Other laboratory studies that doctors use to detect an infection include the following:
• White Blood Cell Count and Differential: When an infant is fighting an infection, their
white blood cell count may either go up, as the infant’s body produces more infection-fighting
cells, or it might also go down if the infant has used up all of their white blood cells fighting
the infection and can no longer keep up with their production of white cells. Another change
that is seen when an infant is fighting an infection is an increase in the percentage of
immature white cells. This is due to the increased production rate of white blood cells, such
that more immature white blood cells are being released into the blood stream. This higher
percentage of immature white cells is sometimes referred to as a “left-shift,” and is one of the
things that can tell the doctors that the infant has an infection.

• C-Reactive Protein (CRP): This is a laboratory test that measures a protein that is a non-
specific marker for inflammation and therefore infection. If the infant has two normal CRP
levels measured 24 hours apart, then there is a 99% chance that the infant does not have an
infection. Therefore, this test is most useful in ruling out an infection.
 • Lumbar Puncture: If the doctor suspects meningitis, which is more common if something has
grown in the baby’s blood culture, a spinal tap, or lumbar puncture will be performed. Lumbar
punctures allow the doctor to obtain a small amount of cerebrospinal fluid (CSF), which is the
protective fluid that surrounds the brain and the spinal cord. The CSF can then be cultured to
determine if the bacteria has spread to the nervous system.

The doctor, nurse practitioner, or physician’s assistant will very carefully insert a special spinal
needle between two vertebrae, or backbones, in the baby’s back at a level below where the
actual spinal cord ends, so there is no danger that the needle will come into contact with the
baby’s spinal cord. After a very small amount of fluid is removed, the needle is taken out, and
a band-aid placed on the baby’s back.

The spinal needle is inserted (left) below where the spinal cord ends (right.)
Prognosis and Treatment
Sepsis in a newborn is treated with antibiotics given intravenously. Antibiotics are often started even
before laboratory and culture results are available. The doctor may then switch to a different antibiotic
that is more specific to the baby’s infection once the results of laboratory tests are back. The length of
antibiotic treatment varies depending on the infant’s clinical status, laboratory test results, and kind of
infection. If blood cultures and other laboratory tests are all negative, antibiotics may be stopped after
48 hours of treatment. If the infant’s cultures are positive, or if the laboratory tests and clinical status
are suggestive of infection, the infant will be treated with antibiotics, usually anywhere from 7-14 days.
When appropriately treated with antibiotics and cared for in the intensive care unit, the great majority
of newborns with sepsis live without any long-term problems.

Pathophysiology of neonatal sepsis: The infectious agents associated with neonatal sepsis have
changed over the past 50 years. S aureus and E coli were the most common infectious hazards for
neonates in the 1950s in the United States. GBS then replaced S aureus as the most common gram-
positive agent, causing early-onset sepsis during the next decades. During the 1990s, GBS and E coli
continued to be associated with neonatal infection; however, coagulase-negative S aureus is now
observed more frequently. Additional organisms, such as L monocytogenes, Chlamydia pneumonia,
Haemophilus influenzae, Enterobacter aerogenes, and species of Bacteroides and Clostridium have
also been identified in neonatal sepsis.

Meningoencephalitis and neonatal sepsis syndrome can also be caused by infection with adenovirus,
enterovirus, or coxsackievirus. Additionally, sexually transmitted diseases and viral diseases, such as
gonorrhea, syphilis, herpes simplex virus (HSV), cytomegalovirus (CMV), hepatitis, HIV, rubella,
toxoplasmosis, Trichomonas vaginalis, and Candida species, have all been implicated in neonatal
infection. Bacterial organisms with increased antibiotic resistance have also emerged and have further
complicated the management of neonatal sepsis. The colonization patterns in nurseries and personnel
are reflected in the organisms currently associated with nosocomial infection. Infants with lower birth
weight and infants who are less mature in today's neonatal intensive care units (NICUs) have increased
susceptibility to these organisms.

Staphylococcus epidermidis, or coagulase-negative Staphylococcus is increasingly seen as a cause of

nosocomial or late-onset sepsis, especially in the premature infant. It is considered the leading cause
of late-onset infections for this population. Its prevalence is related to its preference for the plastic
mediums found in cannulas and shunts, which increases its introduction via umbilical catheters and
other indwelling lines. The bacterial capsule polysaccharide adheres well to the plastic polymers of the
catheters. The adherence creates a capsule between microbe and catheter, which prevents C3
deposition and phagocytosis. Also, proteins found in the organism [AtlE and SSP-1] enhance
attachment to the surface of the catheter.

Biofilms are formed at the site from the aggregation of organisms that have multiplied with the
protection provided by the adherence to the catheter. Slimes are produced at the site from the
extracellular material formed by the organism, which provides a barrier to the host defense, as well as
antibiotic action. Therefore, it can be seen that slime production increases the difficulty to treat
coagulase-negative staphylococcal septicemia. The toxins formed by this organism have been
associated with necrotizing enterocolitis. Coagulase-negative Staphylococcus is a frequent
contaminate of blood and cerebrospinal fluid (CSF) cultures; therefore, it can be a false indicator of
coagulase-negative staphylococcal septicemia.

The neonate is unable to respond effectively to infectious hazards because of deficits in the
physiological response to infectious agents. The neonatal neutrophil or polymorphonuclear (PMN) cell,
which is vital for effective killing of bacteria, is defective in chemotaxis and killing capacity. Decreased
adherence to the endothelial lining of blood vessels reduces their ability to marginate and leave the
intravascular area to migrate into the tissues. Once in the tissues, they may fail to deaggregate in
response to chemotactic factors. Also, neonatal PMNs are less deformable; therefore, they are less
able to move through the extracellular matrix of tissues to reach the site of inflammation and
infection. The limited ability of neonatal PMNs for phagocytosis and killing of bacteria is impaired when
the infant is clinically ill. Lastly, neutrophil reserves are depleted easily because of the diminished
response of the bone marrow, especially in the premature infant.

Neonatal monocyte concentration and function are at adult levels; however, macrophage chemotaxis
is impaired and continues to exhibit decreased function into early childhood. Macrophages are
decreased in the lungs and probably also in the liver and spleen. The chemotactic and bacteriocidal
activity and the antigen presentation by these cells are not fully competent. Cytokine production by
macrophages is decreased, which may be associated with a corresponding decrease in T-cell
production.

T cells are found in early gestation in fetal circulation and increase in number from birth to about age 6
months; however, these cells represent an immature transitory population. Neonates are deficient in T
cells with the memory cell surface phenotype; however, the number of these T cells increases with
maturity as the neonate is exposed to antigenic stimuli. These antigenically naive cells do not
proliferate as readily as adult T cells when activated. Also, neonatal T cells do not effectively produce
the cytokines that assist with B-cell stimulation and differentiation and with bone marrow stimulation
of granulocyte/monocyte proliferation. A delay occurs in the formation of antigen specific memory
function following primary infection. The cytotoxic function of neonatal T cells is 50-100% as effective
as adult T cells.

The fetus has some preimmune immunoglobulin present; however, preimmune immunoglobulin is
relatively limited in fetuses compared to adults. The infant receives immunoglobulin G (IgG) prenatally
after 16 weeks of gestation; however, the infant born prematurely has less IgG due to the shorter
period of placental transmission of immunoglobulin.

Additionally, if the mother is immunosuppressed, it is possible that less IgG can be transmitted to the
infant. The neonate is capable of synthesizing immunoglobulin M (IgM) in utero at 10 weeks of
gestation; however, IgM levels are generally low at birth, unless the infant was exposed to an
infectious agent during the pregnancy, thereby stimulating increased IgM production. IgG and
immunoglobulin E (IgE) may be synthesized in utero; however, only traces are found in cord blood at
delivery. The neonate may receive immunoglobulin A (IgA) from breastfeeding but does not secrete
IgA until 2-5 weeks after birth. Response to bacterial polysaccharide antigen is diminished and remains
so during the first 2 years of life.

Natural killer (NK) cells are found in greater concentration in the peripheral blood of neonates than in
that of adults; however, certain antigen expressivity by the cells' membranes is diminished, thereby
reducing cytolytic activity. This decreased response has been observed with infection by herpes group
viruses in the neonate.

The fetus is capable of complement protein production as early as 6 weeks gestational age; however,
wide variability exists among individual neonates in the concentration of the components of the
complement system. Some infants who were studied had comparable concentrations to adults.
Deficiencies appear to be greater for neonates in the alternative pathway than in the classic pathway.
The terminal activity for complement that leads to killing of organisms, especially gram-negative
bacteria, is inefficient. This deficiency is more marked in preterm infants. Mature complement activity
is not reached until infants are aged 6-10 months. Fibronectin, a serum protein that assists with
neutrophil adherence and has opsonic properties, is found in lower concentrations in neonates.
Therefore, neonatal sera have reduced opsonic efficiency against GBS, E coli, and S pneumoniae.

The physical and chemical barriers to infection in the human body are present in the newborn but are
functionally deficient. Skin and mucus membranes are broken down easily in the premature infant.
Neonates who are ill and/or premature are additionally at risk because of the invasive procedures that
breach their physical barriers to infection. Because of the interdependence of the immune response,
these individual deficiencies of the various components of immune activity in the neonate conspire to
create a hazardous situation for the neonate exposed to infectious threats.

Frequency:

In the US: The incidence of culture-proven sepsis is approximately 2 in 1000 live births. Of the 7-13%
of neonates who are evaluated for neonatal sepsis, only 3-8% have culture-proven sepsis. The early
signs of sepsis in the newborn are nonspecific; therefore, many newborns undergo diagnostic studies
and the initiation of treatment before the diagnosis has been determined. Additionally, because the
American Academy of Pediatrics (AAP), American Academy of Obstetrics and Gynecology (AAOG), and
Centers for Disease Control and Prevention (CDC) all have recommended sepsis screening and/or
treatment for various risk factors related to GBS diseases, many asymptomatic neonates now require
evaluation. Because the mortality rate of untreated sepsis can be as high as 50%, most clinicians
believe that the hazard of untreated sepsis is too great to wait for confirmation by positive cultures;
therefore, most clinicians initiate treatment while awaiting culture results.
Mortality/Morbidity: The mortality rate in neonatal sepsis may be as high as 50% for infants who are
not treated. Infection is a major cause of fatality during the first month of life, contributing to 13-15%
of all neonatal deaths. Neonatal meningitis, a serious morbidity of neonatal sepsis, occurs in 2-4 cases
per 10,000 live births and significantly contributes to the mortality rate in neonatal sepsis; it is
responsible for 4% of all neonatal deaths.

Race: Black infants have an increased incidence of GBS disease and late-onset sepsis. This is observed
even after controlling for risk factors of low birth weight and decreased maternal age.

Sex: The incidence of bacterial sepsis and meningitis, especially for gram-negative enteric bacilli, is
higher in males than in females.

Age: Studies have shown that premature infants have an increased incidence of sepsis. The incidence
of sepsis is significantly higher in infants with very low birth weight (<1000 g), at 26 per 1000 live
births, than in infants with a birth weight of 1000-2000 g, at 8-9 per 1000 live births. The risk for death
or meningitis from sepsis is higher in infants with low birth weight than in full-term neonates.

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.

Clinical manifestations of neonatal sepsis:

Lethargy
Refusal to suckle
Poor cry
Not arousable, comatosed
Abdominal distension
Diarrhea
Vomiting
Hypothermia
Poor perfusion
Sclerema
Poor weight gain
Shock
Bleeding
Renal failure
Particularly suggestive of Particularly suggestive of
pneumonia meningitis
Cyanosis Fever
Tachypnea Seizures
Chest retractions Blank look
Grunt High pitched cry
Apnea/gasping Excessive crying/irritability
Neck retraction
Bulging fontanel

Neonatal sepsis
Definition

Neonatal sepsis is a blood infection that occurs in an infant younger than 90 days old. Early-onset
sepsis is seen in the first week of life. Late-onset sepsis occurs between days 8 and 89.

Alternative Names

Sepsis neonatorum; Neonatal septicemia

Causes

A number of different bacteria, including E.coli, Listeria, and certain strains of Streptococcus, may
cause neonatal sepsis.
Early-onset neonatal sepsis most often appears within 24 hours of birth. The baby gets the infection
from the mother before or during delivery. The following increases an infant's risk of early-onset
sepsis:
• Group B Streptococcus infection
during pregnancy
• Preterm delivery
• Rupture of membranes (placenta
tissue) that lasts longer than 24
hours
• Infection of the placenta tissues
and amniotic fluid
(chorioamnionitis)
• Frequent vaginal examinations
during labor
Babies with late-onset neonatal sepsis get infected after delivery. The following increase an infant's
risk of sepsis after delivery:
• Contaminated hospital equipment
• Exposure to medicines that lead to
antibiotic resistance
• Having a catheter in a blood vessel
for a long time
• Staying in the hospital for an
extended period of time

Symptoms

Infants with neonatal sepsis may have the following symptoms:

• Body temperature changes
• Breathing problems
• Diarrhea
• Low blood sugar
• Reduced movements
• Reduced sucking
• Seizures
• Slow heart rate
• Swollen belly area
• Vomiting
 • Yellow skin and whites of the eyes
(jaundice)

Exams and Tests

Laboratory tests can help diagnose neonatal sepsis and identify the bacteria that is causing the
infection. Blood tests may include:
• Blood culture
• C-reactive protein
• White blood cell count
If a bacterial infection is strongly suspected, other tests may include lumbar puncture, urine tests, and
chest x-rays.

Treatment

Antibiotics are given to kill the bacteria. If the baby is septic and gravely ill, intravenous immune
globulin may be given.
Because early treatment is so valuable, often doctors will ordering lab tests and start treatment before
the results are even back. This practice has saved many lives.

Outlook (Prognosis)

With prompt treatment, many babies with these bacterial infections will recover completely with no
remaining problems. Nevertheless, neonatal sepsis is a leading cause of infant death. The more quickly
an infant receives treatment, the better the outcome.

Possible Complications

• Disability
• Death

When to Contact a Medical Professional

Seek immediate medical help if your infant shows symptoms of neonatal sepsis.

Prevention

Preventative antibiotics may be given to pregnant women who have a Group B Streptococcus infection
or who have previously given birth to an infant with sepsis due to the bacteria.
Preventing and treating infections in mothers, providing a clean birth environment, and delivering the
baby within 24 hours of rupture of membranes, where possible, can all help lower the chance of
neonatal sepsis.

Essential Prescribing Information

Bacimex® [IV infusion]
Claris Lifesciences [ Claris Lifesciences ]
MIMS Class : Other Antibiotics
See related Bacimex IV infusion information

Content
Metronidazole
s
Indicatio Treatment of infections caused by Bacteriodes fragilis. Prevention of post-op
ns infections due to anaerobic bacteria & treatment of amoebic abscess of the liver
& acute intestinal amoebiasis.
Dosag Adult & childn >12 yr 500 mg (100 mL). Childn <12 yr 7.5 mg/kg. All doses
e should be infused for 20 min at a rate of 5 mL/min 8 hrly.
Contraindicati Admixture w/ 10% Glucose, penicillin G, K, Ringer Lactated Soln due is
ons contraindicated to chemical incompatibility.
Special 1st trimester of pregnancy. Lactation. Monitor leucocyte count during
Precautions prolonged-use.
Adverse Drug Anorexia, nausea, abdominal pain, vomiting, vertigo, tiredness & dark
Reactions coloration of the urine if used to treat trichomoniasis & amoebiasis.
Click to view ADR Monitoring Website
Drug Warfarin, oral anticoagulants. Disulfiram.
Interactions Click here for more Interaction Checks
Pregnancy
Category (US FDA)

Category B: Either animal-reproduction studies have not demonstrated a foetal

risk but there are no controlled studies in pregnant women or animal-
reproduction studies have shown an adverse effect (other than a decrease in
fertility) that was not confirmed in controlled studies in women in the 1st
trimester (and there is no evidence of a risk in later trimesters).
MIMS
Other Antibiotics
Class
ATC J01XD01 - Metronidazole ; Belongs to the class of imidazole derivative
Classification antibacterials. Used in the treatment of systemic infections.
Poison
Rx
Schedule