Neonatal Emergencies

THE MISFITS
T- Trauma (accidental & nonaccidental) H- Heart Disease/Hypovolemia/Hypoxia E- Endocrine (congenital adrenal hyperplasia, thyrotoxicosis) M- Metabolic (electrolyte imbalance) I- Inborn Errors of Metabolism: metabolic emergencies S- Sepsis (meningitis, pneumonia, UTI) F- Formula mishaps (under or overdilution) I- Intestinal catastrophes (volvulus, intususception, NEC) T- Toxins/poisons S- Seizures

Infections of the Newborn:

Evaluation & Management

Setting Priorities
Newborn are not small children

Remember that 10 babies are worked up for each proven case

Objectives
A better understanding of Neonatal Sepsis: * Pathology * Causes * Symptoms What will I learn? * Diagnosis * Treatments

What is Neonatal Sepsis?

Clinical syndrome of bacteraemia characterized by systemic signs and symptoms of infection in the first four weeks of life.

It can cause death if not recognized and treated properly.

INCIDENCE 2- 8/1000 live births In India - 3.9 % of all intramural births - 20 30 % develop meningitis In developed countries - 1 in 1000 live births - Term - 4 in 1000 live births - Preterm - 300 in 1000 VLBW babies

More facts about Neonatal Sepsis

Term male infants 2x higher than female Pre Term have 3-10x higher incidence of infection than term Low Birth Weight [2]. As high as 13-27 per 1000 for infants weighing <1500 g mortality rate is high (13-25%) higher rates are seen in premature infants and in those with early fulminant disease

Historical Changes in Predominant Infectious Agent

1930s: Group A Strep
1940s: E.coli 1950s: Staph aureus

1970s: Group B Strep

INTRODUCTION
Infection important cause of neonatal and infant morbidity and mortality
2% of fetuses are infected in utero 10% of infants have infections in the 1st month of life

INTRODUCTION
Neonatal Infections are unique 1.) Infectious agents can be transmitted from the mother - transplacentally - ascending bacterial infections maternal chorioamnionitis, PROM, resuscitation at birth 2.) Newborn are less capable of responding to infections 3.) Clinical manifestation vary and include subclinical, mild to severe manifestations

INTRODUCTION
Neonatal Infections are unique

4.) Maternal infection is often undiagnosed during pregnancy 5.) Wide variety of etiologic agents
6.) Immature and Very Low Birth weight remain in hospital for a long time which puts them at continuous risk for acquired infections

- Maternal infection that is the source of transplacental infection is often undiagnosed during pregnancy because the mother was either asymptomatic or had nonspecific signs and symptoms. - Bacteria, viruses, fungi, protozoans and mycoplasmas.

What is sepsis?

Neonatal Sepsis

Early Onset (before 1wk of life)

Late Onset (after 1 week)

Acquired before and during delivery

Acquired after delivery

Neonatal Sepsis

Neonatal Sepsis EARLY ONSET

Predisposing factors: *Maternal group B Streptococcus (GBS) colonization (especially if untreated during labor) *Premature rupture of membranes (PROM), preterm rupture of membranes, prolonged rupture of membranes *Prematurity *Maternal urinary tract infection (3rd trimester) *Maternal Chorioamnionitis (WBC>18)

Predominant pathogens
Early Onset Sepsis
E.coli Group B streptococcus Listeria Hemophilus influenza Enterobacter aeruginosa Klebsiella pneumonia Pseudomas aeruginosa Staphylococcus aureus

Neonatal Sepsis LATE ONSET

occurs at 7-90 days of life Prematurity, prolonged hospitalization, presence of foreign bodies like umbilical catheters, ET tube, parenteral alimentation, prior use of antibiotics Predominant pathogens:
coagulase negative Staphylococcus epidermidis, Staphylococcus aureus, Candida, Enterococcus, E coli, Klebsiella, Pseudomonas aeroginosa, GBS, Serratia, Acinetobacter, Anaerobes

Community Acquired (after 4-6 weeks)

Pneumococcus Meningococcus GABHS Haemophilus influenzae (HIB) not really a problem anymore

Predominant Pathogens for Sepsis

Nelson Textbook of Pediatrics 18th edition

Causes of Neonatal Sepsis

The primary causes of Neonatal Sepsis are bacteria, such as Staphylococcus and Group Beta Strep (GBS).

Bacteria may be the cause of neonatal sepsis, but neonates are more susceptible to these bacteria for two reasons [3&6]:
Immature immune response

Genetic predisposition

Why are newborns so vulnerable to infection?

Non-specific immunity Specific immunity

What makes a neonates immune system immature?

Pathogen enters body

Neutrophils move in

Normally an immune system responds to a pathogen in a specific manner, but if there are problems with any element the immune system is unable to function properly [3&6].

Chemotaxis occurs

Opsonization causes phagocytosis

Monocytes kill pathogen

The neonate is unable to respond effectively to infectious hazards because of deficits in the physiological response to infectious agents!

1 The or

neonatal neutrophil polymorphonuclear (PMN) cell, which is vital for effective killing of bacteria, is defective in chemotaxis and killing capacity.

adherence 2 Decreased endothelial lining of

to the blood vessels reduces their ability to marginate and leave the intravascular area to migrate into the tissues.

neonatal PMNs are 4 Also, less deformable; therefore, they are less able to move through the extracellular matrix of tissues to reach the site of inflammation and infection. in the tissues, they 3 Once may fail to deaggregate in response factors. to chemotactic

limited ability 5 The neonatal PMNs

of for phagocytosis and killing of bacteria is impaired when the infant is clinically ill.

6 Lastly,

neutrophil reserves are depleted easily because of the diminished response of the bone marrow, especially in the premature infant.

Why are newborns so vulnerable to infection?

IMMUNE SYSTEM

Neutrophils Qualitative and quantitative

Complement and immunoglobulin levels decreased

T cellsantigenically nave

limited cytokine production

Neutrophils: An important cell in immunity against pathogens

Neonatal neutrophils are deficient in their ability to adhere to vessel walls at site of infection [2&6]. Further release of neutrophils depletes a neonatal storage pool because the bone marrow storage of a neonate is only 20-30% of the pool in an adult [2&6]. Neonatal neutrophils have a decreased ability to deform & migrate into tissues [2&6]. Red Blood Cells

Neutrophils

Chemotaxis
Neonatal neutrophils have decreased chemotaxis due to decreased chemoattractant Production [2&6]. Chemoattractants attract neutrophils to the site of infection [2&6]. Neonatal neutrophils therefore cannot reach the site of infection because of the chemotaxis deficiency caused by decreased chemoattractant production.

Imagine: Being in a dark tunnel without any direction or a way out. Finally you see light. You move towards the light and get out of the tunnel. Well this is like chemotaxis. The sun is the chemoattractant attracting you out to the world!!

Opsonization
Opsonization is the coating of a pathogen with antibodies that makes it susceptible to phagocytosis [2&6].
Opsonization

Phagocytosis is the process of cells (phagocytes) engulfing, ingesting, & destroying pathogens [2&6].
Pathogen

Neonates have a decreased amount of opsonins (antibodies that promote opsonization) [2&6].

Monocytes: Another important cell in the fight against pathogens

Monocytes are a type of White Blood Cell that ingests pathogens.

Neonates have a sufficient amount of monocytes and full capability to kill organisms [2], but because of a neonates deficiencies previously discussed very few monocytes get to the site of infection.
Image provided with permission and copyrighted by amaxa GmbH at www.amaxa.com/mission3.html

What makes a neonates immune system susceptible to sepsis?

Maturity

OR
Immaturity

Youre Right!!!!

The immaturity of a neonates immune system makes them MORE SUSCEPTIBLE to sepsis.

 Poor skin barrier

 Umbilical stump

 Poor blood-brain barrier

Not Quite! Try Again

Genetic Predisposition to Sepsis

Multiple factors play into a neonates response to infection and the possible development of sepsis. One of these factors is genetics. As science has moved into recognizing the human genome there have also been advances with finding genetic contributions to sepsis. The bodys first response to infection requires recognition of the presence of a pathogen. After recognition has occurred the body responds appropriately to resolve the problem [3&14]. Many polymorphisms have been recognized within both of these phases and they have been implicated in influencing the susceptibility to and/or outcome from sepsis [3&14].

Lets look further into these two phases to see the effect polymorphisms have on neonatal sepsis:
Recognition Phase Response Phase

Recognition Phase
The bodys initial response to infection requires recognition of the presence of a pathogen [3].

Polymorphisms in genes coding for proteins involved in the recognition of pathogens can influence the susceptibility to and/or outcome of neonatal sepsis [3].

Lets look into two of these:

Lipopolysaccharide (LPS)

Mannose-Binding Lectine (MBL)

Response Phase
After the initial recognition of a pathogen occurs the body responds by releasing elevated levels of proinflammatory cytokines followed by a release of anti-inflammatory cytokines [3]. This dual release of opposite cytokines helps the cytokines return to a baseline level and that enables the start of tissue repair to start [3]. It is generally accepted that an imbalance between proinflammatory and anti-inflammatory cytokines result in clinical manifestations of sepsis [3]. This Imbalance is due to polymorphisms in various proteins involved in the response to pathogens.

Lets look into two of these :

Tumor Necrosis Factor (TNF) Interleukin 10 (IL-10)

Lipopolysaccharide (LPS)
LPS, a major component of bacteria, is a powerful stimulator of the innate immune response [3]. LPS elicits its response by binding to a cell surface receptor that is compromised of 3 proteins [3]. One of these proteins is TLR4. TLR4 is required for LPS to respond.

When there are polymorphisms in TLR4 there is a reduced response to LPS and that enhances the susceptibility to infection!

Mannose-Binding Lectin (MBL)

MBL has two primary immunodefensive roles [3]:
involved with opsonization leads to activation of complement system, independent of antibodies.

Polymorphisms cause deficiencies in MBL level [3]. This results in decreased levels of MBL. This deficiency is associated with increased susceptibility to infections!

Tumor Necrosis Factor (TNF)

TNF is a proinflammatory cytokine that is responsible for the initial activation of the inflammatory response [3&14].

There are several polymorphisms associated with an increased secretion of TNF resulting in the susceptibility to sepsis[3].

Interleukin 10 (IL-10)
IL-10 is an anti-inflammatory cytokine produced by primarily monocytes [3]. IL-10 helps regulate the over expression of proinflammatory cytokines.

There are three polymorphisms noted that result in an over expression of IL-10. This over expression is proposed to induce immunosuppression in bacterial sepsis and therefore increasing mortality by inhibiting bacterial clearance [3].

What effect do polymorphisms have in Neonatal Sepsis?

They make a neonate less susceptible to sepsis.

They make a neonate more susceptible to sepsis.

They have no apparent effect.

Not quite! Try again.

Great answer! Youre correct!

Polymorphisms cause either an over expression or under expression of proteins and/or genes that have significant roles in the immune response to infection. This alters their ability to properly function which makes a neonate more susceptible to sepsis.

Natural course of sepsis Bacteria

Focal infection Bacteraemia

sepsis
Sepsis syndrome

Early septic shock

Refractory septic shock

MODS DEATH

pathogens can enter a neonates body in many ways !

Pathogens can enter through the prenatal, perinatal, and postnatal periods [6].
Prenatal Maternal Substance Abuse Premature Rupture of Membranes (>18 Hours) Maternal Infection Microbial Colonization at Birth Maternal Infection Vaginal Exam of Mother

Perinatal

Postnatal

Invasive Catheters Endotracheal Intubation Exposure to Nosocomial Microorganisms

Route of Infection
Prenatal infection / Transplacental / Hematogenous

Infection during delivery / Ascending / Birth

Canal

Postnatal infection / Nosocomial

Routes of Infection
Nosocomial

Transplacental/Hematogenous
Organisms (Not just TORCHS)
Syphilis Toxoplasmosis Rubella Cytomegalovirus Acute Viruses Coxsackie Adenovirus Echo Enterovirus Varicella Parvovirus* Herpes* Gonorrhea Mumps TB HIV Polio GBS Malaria Lyme

Etiology
The following are transplacentally and intrapartally transmitted:
Herpes Simplex Virus HIV Hepatitis B and C virus Tuberculosis

Ascending/Birth Canal
Organisms - GI/GU flora, Cervical/Blood
E. Coli GBS Chlamydia Ureaplasma Listeria Enterococcus Gonorrhea HPV Herpes Candida HIV Mycoplasma Hepatitis Anaerobes Syphilis

Nosocomial
Organisms Skin Flora, Equipment/Environment
Staphylococcus Coagulase neg & pos MRSA Klebsiella Pseudomonas/Proteus Enterobacter Serratia Rotavirus Clostridia C dificile Fungi

Sepsis Risk Factors

Prematurity Birth weight Term 0.1% 1,000 -1,500 g 10% <1,000 g 35% <750 g. 50% Delay enteral feeding and Prolonged TPN

Risk factors associated with neonatal sepsis

Neonatal Risk Factors
Term male infants have 2x higher than female Pre-term have a 3-10x higher incidence of infection than term Low Birth weight

Risk factors associated with neonatal sepsis

I.Risk Factors (maternal and neonatal)

A.Major 1. Maternal prolonged Rupture of Membranes >24 hours 2. Intrapartum maternal fever >38 C (>100.4 F) 3. Chorioamnionitis 4. Sustained Fetal Tachycardia >160 beats per minute B.Minor 1. Intrapartum maternal fever >37.5 C (>99.5 F) 2. Twin Gestation / Multiple Gestation 3. Premature infant (<37 weeks) 4. Maternal Leukocytosis (White Blood Cell count >15000) 5. Rupture of Membranes > 12 hours 6. Tachypnea (<1 hour) 7. Maternal Group B Streptococcus Colonization 8. Low APGAR (<5 at 1 minute) 9. Low birth weight (<1500 grams)

Minor risk factors

Minor risk factors

10. Foul smelling liquor/ meconium stained 11. Maternal WBC Count >15,000 12. Maternal GBS colonization 13. Low APGAR score(<5 at 1min) 14. Multiple gestation 15. > 3 vaginal exam **1 major or 2 minor risk factors

Symptoms of Neonatal Sepsis

The symptoms of neonatal sepsis are not concrete and vary widely [9].

Tachypnea Heart Rate Changes Feeding difficulties Difficulty Breathing Temperature Instability Jaundice Irritability
Why are symptoms so broad?

Symptoms
Symptom variability occurs because of the metabolic and inflammatory processes that occur in neonatal sepsis.

A neonates symptoms are rooted in these two processes.

Lets look more into these areas:

Metabolism

Inflammation

Metabolism in Neonatal Sepsis

Sepsis can alter a neonates metabolism [11]. The Ebb & Flow Metabolic Response [11] best describes how a neonates metabolism is affected by sepsis.

Ebb Phase

Flow Phase

Ebb Flow
This is the initial phase and last only 1-3 days. This is how a neonates body initially tries to compensate for losses that occur during sepsis. The body slows things down in order to let the body recover.

The Ebb Phase consists of several clinical manifestations [11]: Hypometabolism Decreased energy expenditure Decreased cardiac output Lowered oxygen consumption Vasoconstriction

Flow Phase
This is the phase that occurs after the initial Ebb Phase. If the body doesnt recover it goes into hyperdrive. This is partly due to the exaggerated inflammatory response (further discussion in inflammatory process section). This phase leads to much of the mortality and morbidity related to neonatal sepsis [11].

The Flow Phase consists of several clinical manifestations [11]: Hypermetabolism Increased energy expenditure Increased cardiac output High oxygen consumption

What metabolic phase causes a neonates body into hyperdrive?

Hyper Phase

Flow Phase

Ebb Phase

This is not right!!

Wow! Youre so smart!!

The flow phase DOES put the neonates body into hyperdrive. This phase leads to much of the mortality and morbidity in neonatal sepsis.

Not quite. Try again.

Inflammation in Neonatal Sepsis

It is widely known that sepsis occurs because of an exaggerated systemic inflammatory response (SIR) [12].

Lets find out how this is true

Inflammatory Process

Inflammatory Process
Pathogen enters body Inflammatory mediators released (cytokines) Injury to endothelium Tissue factors released Production of thrombin Coagulation promotes clot formation Increased activity of fibrinolysis inhibitors Decreased fibrinolysis [12]

Inflammation
Overall, the imbalance among inflammation, over coagulation, and decreased fibrinolysis are the cause for the majority of deaths in sepsis [12].

Clinical presentation
Early warning signs are often non-specific and subtle easily confused with non-infective causes (e.g. apnea of prematurity, variation in environmental temperature or acute exacerbation of chronic lung disease) clinical course alarmingly fulminant septic shock + DIC death Non-specific, multi- systems/organs involved

Approach to Neonatal Sepsis

Antenatal Mothers with risk factors Symptomatic infants

Postnatal

Asymptomatic infant with risk factors

Term
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Preterm
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Clinical manifestation

The symptoms are so broad , non-specific, and acute deterioration, How to make a diagnosis as early as possible ?

Omphalitis

toxical paralytic ileus

dyspnea

Retractions

Clinical Manifestation of Transplacental Infections

Clinical Manifestation of Transplacental Infections

Clinical Manifestation of Transplacental Infections

Signs and Symptoms of infection

Signs and symptoms of sepsis

Respiratory distress
Tachypnea Retractions Grunting Nasal flaring Apnea

Abnormal skin color perfusion

Pale color or gray color Delayed capillary refill time jaundice

Signs and symptoms of sepsis

Temperature instability
Hypothermia and rarely, hyperthermia

Feeding intolerance
Vomiting Diarrhea Abdominal distention

Abnormal HR and BP
Tachycardia, bradycardia, hypotension

Abnormal neurologic status

Lethargy, hypotonia, seizures

Signs/Symptoms
Sunken fontanelle Bulging or pulsating fontanelle Neck stiffness CAN NOT be used Babies can be bacteremic but look well Presence of a cold does not change anything

Is there a diagnostic marker for neonatal sepsis?

True

False

Great answer! Youre correct!

There is NOT a specific diagnostic marker, only determinants of infection

Prevention strategy for earlyonset (GBS) disease

Vaginal/Rectal cultures at 35 to 37 weeks in ALL pregnant women

Intrapartum prophylaxis indicated Previous infant with invasive GBS OR GBS bacteriuria in current pregnancy OR Positive GBS screening culture OR Unknown GBS status AND Delivery at < 37 OR ROM 18 hours OR Intrapartum Tem 38 C ACOG Committee Opinion #279, Dec 2002

Intrapartum prophylaxis not indicated Previous pregnancy with positive culture Planned section with intact Membranes (regardless of maternal GBS culture status) Negative GBS screening culture (regardless of intrapartum risk factor)

Updated algorithm for women with threatened preterm delivery

Onset of labor OR ROM at < 37 wk, with significant risk for imminent preterm delivery

No GBS culture

GBS positive

GBS negative

Obtain vaginal & rectal GBS culture and initiate penicillin

Penicillin (IV) 48 hr (during tocolysis)

No GBS prophylaxis

No growth At 48 hr

IAP at delivery

Stop penicillin

Management of Patients with PPROM

Laboratory Diagnosis of Neonatal Sepsis 1. Direct methods - Blood culture - CSF culture - Urine culture 2. Indirect methods - Total leucocyte count - Absolute neutrophil count - Total immature neutrophils - Immature to total neutrophols - Neutrophil Morphology - Platelet count - Micro ESR - Acute phase reactants - Buffy coat examination - Smear of gastric aspirate >5 neutrophil /HPF - peripheral Smear - Toxic granules, cytoplasmic vaculation, dhole bodies. 93 - External ear canal fluid - C3d

SEPSIS SCREEN
Because none of the diagnostic tests for sepsis is able to identify infants with proven sepsis with reasonable accuracy, investigators have used combinations of laboratory tests to enhance the identification of infected neonates. Because of its high negative predictive accuracy, it can provide a greater reassurance that an infection is not present.

Lab diagnostic criteria

SEPTIC SCREEN if 3 are abnormal chance of infection 90% A) TLC>20,000 or <5000 B) Bands >20% or band: neutro>0.2 C) abnormal neutrophils-toxic granules D) micro ESR>15mm/1st hr E) CRP >6mcg/ml Others- elevated haptoglobin, alpha1antitrypsin fibrinogen

Components

Abnormal values

Total leukocyte count Absolute neutrophil count Immature /total neutrophil Micro-ESR C reactive protein (CRP)

<5000/mm3 <1750/mm3 >0.2 >10 mm in 1st hour >1mg/dL

o CRP: It is done by quantitative ELISA or by a bedside semiquantitative latex agglutination kit. More than 1 mg/dL is positive.
o ANC: It must be read off Manroes charts, Schelonkas chart or Mouzinhos chart, depending on whether it is a term baby or a preterm baby respectiveIy.

o ITR: It is considered to be positive if>20%. ITR is defined as

Immature PMN (band forms, metamyelo & myelocytes) Mature + immature neutrophils

Mature neutrophil

Band cell
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o ESR, Value (in mm in first hour)> 3+age in days in the 1

wk of life or >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. Among the various tests, quantitative CRP is the best, followed by qualitative CRP and ITR. 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 12-24h. Two consecutive completely negative screens are suggestive of no sepsis.

 Since CRP is the key parameter in the sepsis screen, a pragmatic approach is that if the 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. Neonates assessed to have a high clinical probability of sepsis 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.

SCREEN FOR SEPSIS At Birth Major risk factors 1. Rupture of membranes > 24 hours 2. Maternal intrapartum fever > 100.40 F 3. Chorioamninitis Minor risk factors 1. Rupture of membrane > 12 hours 2. Maternal intrapartum fever > 99.50 F 3. Maternal WBC > 15000 / mm3 4. Low apgar score(< 5 at 1 min, < 7 at 5 min) 5. LBW ( < 1500 g ) 6. Preterm labour ( < 37 weeks) 04/09/2013 100

Sepsis screen
A positive sepsis screen result was defined as two or more abnormal test results.
Sensitivity = 93% Positive predictive accuracy of 39%

< 2 abnormal results = 99% negative predictive accuracy

Sepsis screen Blood culture LP Revised guideline for empirical treatment of meningitis based on csf parameter
Among neonates with suspected sepsis Among neonates with blood culture proven sepsis WBC >10 OR Glucose <25 OR Protein >170

Preterm babies
WBC >25 AND protein >170 OR WBC>100 OR Cut-off values to diagnose meningitis Glucose <25 Term babies

WBC >21 OR Glucose <20

WBC >8 OR Glucose <20 OR Protein >120

Lab Dilemmas- Urine collection

Dont use bag urines!
A negative culture on a bag urine is negative A positive means nothing

Cath or Suprapubic aspirate?

SPA- any growth is considered a positive Cath
Can have false positives, especially if uncircd male New debates on what constitutes a positive culture Most references use >10K CFUs as positive, some use as little as 1K (equals one plaque) Microbiologists feel we should use 100K on all samples regardless of source

Lab Dilemmas- The Bloody Tap

The Bloody Tap

Dont ask me, you should have gotten it right the first time

The Bloody Tap

No right answer Results can vary based on the amount of blood in amount of CSF, what is the HCT, what is the peripheral WBC count etc. Some use CBC to CSF ratios. Sometimes seems like too many WBCs or seems OK Sometimes just need to re-tap

Radiology
X-ray chest X-ray Abdomen CT scan Neurosonogram

Urine analysis

Are you sure? Try again!

Diagnosis
The diagnosis of systemic infection in the newborn is difficult to establish on the basis of clinical findings alone. Any infant who suddenly changes for the worse should be suspected for sepsis.

PIDJ April 2005

Study in India found that any two of these signs had an almost 100% sensitivity for sepsis and over 90% mortality Reduced sucking Weak cry Cool extremities Vomiting Poor tone Retractions

Risk factor IP per vaginal examinations >3 Clinical chorioamnionitis BW <1.5kg

Score 6 6 3

Male gender
Not received IP antibiotics Gestation <30 wks

3
2 2

If -

score 0-6 monitoring 7 or >7 antibiotics , blood culture Extreme risk factor prom>72hr -prolonged labor>24hr -unclean vaginal exam - Maternal septisemia

SoWhat Do We Do?
An excellent HISTORY
Especially with well-appearing infant, diagnosis and level of concern likely determined by history Birth hx, PNC, recent Abx use, perinatal exposures, h/o hyperbilirubinemia

Problems with the history

Inconsistent presentation amongst febrile infants Several clinical parameters have been studied as predictors of SBI
None have been found to be 100% sensitive and specific for infants <2months old

The Physical Exam

Again.
Most are well-appearing

2 large studies:
747 febrile 1-2months old infants 66% Well-Appearance DOES NOT rule out appeared well to the MD despite having SBI SBI Similar study of 1-3 months old infants those with SBI could not be weeded out from those without by appearance alone

Deciding on Management
What does the literature say?
Rochester criteria Rochester Criteria Philadelphia Criteria Boston Criteria More widely accepted Philadelphia criteria No source for fever Observation Score WBC<20,000 Previously healthy WBC<15,000 UA <10 WBC/HPF Full Boston criteria Band:Seg <0.2 term CSF analysis < 10WBC
No prior or current Abx Nontoxic WBC 5,000-15,000 <1,500 bands UA <10 WBC/HPF Stool <5 WBC/HPF (if diarrhea) UA <10 WBC/HPF Normal CXR All criteria missed diagnosis of SBI CSF analysis <8 WBC CXR olds in <1 Normal month

1. Low birth weight (<2500 grams) or prematurity

2. Febrile illness in the mother with evidence of bacterial infection within 2 weeks prior to delivery.
3. Foul smelling and/or meconium stained liquor. 4. Rupture of membranes >24 hours. 5. Single unclean or > 3 sterile vaginal examination(s) during labor 6. Prolonged labor (sum of 1st and 2nd stage of labor > 24 hrs) 7. Perinatal asphyxia (Apgar score <4 at 1 minute) Presence of foul smelling liquor or three of the above mentioned risk factors warrant initiation of antibiotic treatment. Infants with two risk factors should be investigated and then treated accordingly.

How is Neonatal Sepsis Diagnosed?

There is no definite marker in neonatal sepsis, but there are determinants of infection.

When a neonate presents with sepsis symptoms a septic work-up is completed [2]. What is included in a septic work up? * Complete Blood Count (CBC) * Blood & Urine cultures * Lumbar Puncture (LP) * Chest X-Ray * Line cultures SEPSIS MARKERS

Well-Established Management
< 1 month old
Automatic rule out sepsis work up
CBC with differential Blood culture Urine culture
Via straight cath or suprapubic tap

CSF analysis and culture

Glucose, protein, gram stain, cell count, and culture

If clinically indicated
CXR NP aspirate
RSV/ Influenza A screen as indicated

Admit Empiric antibiotics until cultures negative for 48hrs

Maternal Risk Factors 1. Intrapartum - Maternal Infection - Purulent / foul smelling liquor - Fever (>380C) - Leucytosis (WBC >18000 / mm3) 2. 3. 4. 5. Premature rupture of membranes Prolonged rupture of membranes > 12 hours Premature onset of labour (<37 weeks Maternal UTI

6.Meconium stained liquor 7.Chorioamnionitis

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Risk factors associated with neonatal sepsis

Neonatal Risk Factors
Term male infants have 2x higher than female Pre-term have a 3-10x higher incidence of infection than term Low Birth weight Birth Asphyxia Procedures

Evaluation of asymptomatic infant for sepsis

Sepsis screen

Sepsis screen negative

Sepsis screen positive

Blood culture, LP

Begin Antibiotics
Observe for 48-72 hrs and discharge Culture positive LP abnormal Culture negative LP normal

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Treat septicaemia 10-14 days Treat for 48-72 hr Meningitis for 14-21 days and discharge 120

Management

Management

Management

Therapy
Infection should be the first thought when an infant has symptoms Aggressive treatment should begin before the diagnosis is confirmed. Therapy can be discontinued if sepsis is excluded

Treatments for Neonatal Sepsis

It is of vital importance that treatment is initiated as soon as sepsis is suspected, especially for those infants at risk.
Why????

Broad Spectrum Antibiotics (Ampicillin & Gentamycin) are the first line of defense against neonatal sepsis [2].
What are other recommendations/options?

Supportive Care - Keep the neonate warm - Start IV Fluid, Infuse 10% Dextrose 2ml / Kg stat to maintain normoglycaemia - Maintain fluid and electrolyte balance and tissue perfusion

If CRT > 3 sec infuse 10 ml / Kg normal saline

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Supportive Care - Avoid enteral feed, if sick - Start oxygen by hood, if cyanosed and support breathing - Consider exchange blood transfusion, if there is sclerema, DIC, Neutropenia

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Treatment
Antibiotics therapy
management of complications

supporting therapy
Clearance of infectious focus

Immunotherapy

Superficial Infections

- Pustules

- After puncturing, clean with betadine and apply antimicrobial

- Conjunctivitis- Chloramphenicol eye drops - Oral thrush - Local application of Nystatin or Clotrimazole

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Prevention of Infection - Exclusive breastfeeding - Keep cord dry - Hand washing by care givers - Hygiene of Baby - No unnecessary intervention - Better management of IV Lines
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- Disinfection of Equipments

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Hand Washing

- Single most important means of preventing nosocomial infections

- Very Simple
- Cheap

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Hand Washing

- Two minutes, hand washing to be done before entering baby care area

- 10 seconds hand washing to be done before and after touching every baby, and after touching unsterile surfaces and fomites

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Steps of effective hand washing

- Roll sleeves above elbow - Remove wrist watch, bangles, ring etc - Using plain water and soap, wash parts of the hand in the following sequence

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Palm and fingers (web spaces) Back of hands Fingers and Knuckles Thumbs Finger tips Wrists and forearm up to elbow
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Steps of Effective Hand Washing - Keep elbow always dependent - Close the tap using elbow - Dry hands using single use sterile paper / napkin - Do not keep long or polished nails Rinsing hands with alcohol is NOT A SUBSTITUTE for PROPER HAND WASHING

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Medication preparation ( Prepare IV fluid under aseptic conditions ) - Never use stock solution for flushing

- Do not use a single bottle for > 24 hrs

- Label bottle with date / time - After seal is removed, use betadine soaked sterile cotton to cover the stopper of bottle
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- Use disposable needle each time

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Better management of IV Lines - Thorough hand washing

- Wear gloves
- Use disposable IV cannula - Thorough skin preparation - All IV ports should be wiped with alcohol - Early identification of extravasation
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- Avoid unnecessary IV infusion

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Why is it so important to start antibiotic treatment?

If not treated as soon as sepsis is suspected a neonate is more likely to die from sepsis and its complications.

For this reason it is of vital importance that healthcare workers (nurses and physicians) notice and act upon even the most subtle changes in a neonates assessment, particularly those infants at risk (GBS+).

Antibiotic therapy

using antibiotics as early as possible choose antibiotics according to drug sensitivity giving drugs intravenously combine effective drugs to make synergism enough therapeutic course consider the possible side effects

Treatment

Initial empiric therapy for early onset sepsis

Ampicillin plus aminoglycoside (usually gentamicin or cefotaxime)

Antibiotic therapy should be tailored according to its sensitivities

L. monocytogenes -> Aminoglycoside + ampicillin Enterococci -> Amoxicillin + aminoglycoside or vancomycin GBS -> Penicillin or ampicillin S. aureus -> Penicillase resistant penicillins or cephalosporins; MRSA vancomycin, clindamycin P. aeruginosa -> Ticarcillin, carbenicillin and an aminoglycoside; Most are sensitive to Ceftazidime Gram negative enteric organisms ->Generally sensitive to aminoglycoside

Treatment
Initial empiric therapy for late onset sepsis
Ampicillin plus cefotaxime; vancomycin + gentamicin; vancomycin+cefotaxime

With minimal or no focal infection usually 7-10 days With meningitis caused by group B streptococcus or gram negative enteric bacilli at least 21 days

ANTIBIOTICS

Choice of Antibiotics Pneumonia or Sepsis

Penicillin + Aminoglycoside (Ampicillin or Cloxacillin) (Gentamicin or Amikacin)

Meningitis Ampicillin + Gentamicin or
Cefotaxime + Gentamicin or Amikacin

04/09/2013

142

Objectives

Antibiotic essentials
Which one? Rationale? Duration of treatment Practical applications

Supportive Care
Neonatal septic shock

Adjunctive therapies Follow up care

All about antibiotics - Basics

PARENTERAL ANTIBIOTICS

Empirical Antibiotic therapy

Choice of antibiotics Based on the organisms responsible for the infection in that region (local data) Based on the sensitivity patterns of the organisms in that region (local data)
REVIEW DATA 6 MONTHLY

EONS Vs. LONS

EONS /LONS in the developed world Rationale for the concept Indian data on EONS and LONS NNPD 2002-03 Different findings
EONS / LONS division ARTIFICAL No difference between EONS and LONS in our settings

Organisms causing EOS/LOS

Author / year 1. Zaidi et al PIDJ 2009 Isolates Outcome Comments WHO (Young Infant study) included 3209 isolates Klebsiella 25% 1st week of life E.Coli 15% S. aureus 18% GBS 7% 835 isolates 7 to 28 days S.Aureus 14% GBS 12% Pneumococci- 12% Klebsiella 4%

Developing countries 63 studies (1980 2007)

Home deliveries 77% Gram -ve organisms

2.

NNPD 200203 Indian data

18 Tertiary care neonatal units

K.pneumonia-32.5% Intramural births S.aureus 13.6%

K.Pneumonia 27% Extramural births S.Aureus 15%

Original Article

Blood Culture Confirmed Bacterial Sepsis in Neonates in a North Indian Tertiary Care Center: Changes over the Last Decade
Venkataseshan Sundaram, Praveen Kumar*, Sourabh Dutta, Kanya Mukhopadhyay, Pallab Ray1, Vikas Gautam1, and Anil Narang
Department of Pediatrics and 1Department of Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India (Received March 21, 2008. Accepted December 3, 2008 ) SUMMARY: The spectrum of organisms causing sepsis is different in developing countries. Data on the recent trends of organisms causing sepsis are limited. This study was conducted in a tertiary care neonatal unit in Northern India. All inborn babies with blood-culture-positive sepsis from 1995 to 2006 were divided into two epochs, viz. 1995 to 1998 (epoch I) and 2001 to 2006 (epoch II). Organisms were grouped into early (<72 h) and late onset (72 h) sepsis groups. The overall incidence of sepsis, the incidence of sepsis stratified by weight groups, the organism profile on different days of life, sepsis-related mortality and pathogen-specific case fatality rate were calculated and compared between the two epochs. Out of 34,362 live births during the study period, organisms were isolated in 1,491 neonates. Out of these, 89% had bacterial sepsis. The incidence of neonatal bacterial sepsis increased from epoch I to epoch II (35.8/1,000 versus 40.1/1,000 live births, P < 0.05). The incidence of early onset sepsis (EOS) did not change between the epochs, but the incidence of late onset sepsis (LOS) increased from 12 to 16.5 per 1,000 live births (P < 0.001). The incidence of bacterial sepsis decreased significantly in the 1,000- to 1,999-g birth weight groups. Klebsiella pneumoniae and Enterobacter aerogenes decreased, whereas Staphylococcus aureus increased in incidence during epoch II. Non-fermenting Gram-negative bacilli emerged as a newly identified pathogen during epoch II. Sepsis-associated mortality decreased from 42 to 20%. The incidence of bacterial sepsis has decreased significantly in 1,000- to 1,999-g infants, with a significant reduction in sepsis-related mortality. New organisms have emerged in recent years. The organism profile in recent years has changed, with a significant overlap of organisms causing EOS and LOS. INTRODUCTION Neonatal infections are estimated to cause 1.6 million deaths every year globally, and 40% of all neonatal deaths of major changes in neonatal care, the study period was divided into two epochs, viz. 1995 to 1998 (epoch I) and 2001 to 2006 (epoch II). Since the changes in peri/neonatal care were gradual, the intervening period of 1999 - 2000 was

Empirical Antibiotics Based on NICU data

Ciprofloxacin / Amikacin : 75% isolates Vancomycin/Pip-tazo: 90% isolates Vancomycin/Meropenem: 95-100%
AVOID Cefotaxime as empirical first line antibiotic

Production of ESBLs Fungal colonization

Antibiotics
Timeliness of initiation
First dose Important prognostic factor Delay in antibiotics worsening outcomes

Route of administration
Only Intravenous No role for any other route Oral therapy not recommended

Dose of Antibiotics

Always check before every dose- everyday- everytime Dependent on postnatal age / weight / gestational age Standard source of information The Blue Book NICU Handbook of Protocols 4th Edition 2010 NEOFAX & LEXI COMP Pediatric & Neonatal drug dosage handbook

Newer drug dose info sources

EPOCRATES Free android & I pad app Other applications/ software

Web MD Drug Handbook

CSF penetration of commonly used antibiotics

ANTIBIOTIC Ciprofloxacin CSF penetration Good

Cefotaxime
Amikacin Gentamicin Vancomycin

Very good
Good* (inflamed meninges) Good* (inflamed meninges) Good* (inflamed meninges / continuous infusion of 60 mg/kg/day)

Pip Tazobactam
Imipenem Meropenem Amphotericin B Fluconazole

Poor (Poor penetration into CSF)

Good (Propensity for seizures) Good* (higher doses/ infusion) Poor (both conventional & Liposomal) Good

Practical points
ANTIBIOTIC Dose Shelf life Cost Vial size per day 24 hrs 125/250/ 500 mg vials Stat 100mg/2 ml vial 200mg/1 00 ml bottle 14 days* 500 mg vial Rs.3 Rs.3 0 Mode of admin IV slow push Side effects

Cefotaxime

<7d: 100-150 mg/kg/day >7d: 150-200 mg/kg/day Q8 hourly

Blunts AG peak level Na content

Amikacin

<1.5 Kg <D7: 7.5 mg/kg Others: 15 mg/kg/day Q24 hourly

Rs.7

IV infusion 1 hour

Ototoxic Nephrotoxic Renal dose modification

Ciprofloxacin 10 mg/kg/dose Q12 hourly Vancomycin Both dose and interval depend on weight and postnatal age

IV Safe in infusion neonates 30-60 min Aminophylline toxicity IV infusion 1 hour Redman syn. Oto/Nephro Precipitates with --------

Rs. 175

Practical points
ANTIBIOTIC PiperacillinTazobactam Dose Both dose and interval depend on weight and postnatal age Shelf life Cost Vial size per day 2.25 gm / Rs. 300 4.5 gm Mode of admin IV infuse 30 min Side effects Separate AG Hypokalemia Diarrhea/ skin rash False +ve DCT LFT/RFT changes Modify in renal/hepatic failure

Meropenem

20-40 500mg/ mg/kg/dose Q 8 1gm vial hourly Meningitis - 40 0.5-1 mg/kg/dse 50 mg vial 5-7mg/kg/dose 6 mg/kg/dose 200 mg/100 ml

Rs. 600

IV infuse 4 hours

Ampho B

Rs.300 Rs.2000 Rs. 50

IV infuse 4 hours

NS incompatible RFT/ K/ Mg/ CBC LFT/ Anemia/ Tpenia/ chills/ fever Vomiting/ Rashes Not with Cisapride

Fluconazole

IV slow bolus

Empirical modification of empirical antibiotic therapy

Empirical upgradation of antibiotics if no clinical improvement within 48-72 hours Extremely sick neonate Even earlier after discussing with consultant/ seniors

After POSITIVE blood c/s report

S Narrower spectrum ABx / lower cost
DOWNGRADE even if neonate was improving

Use a single sensitive antibiotic

(Exception: Pseudomonas, S.aureus, E. fecalis, Acinetobacter spp.)

S Empirical antibiotics but clinical worsening

Possibility of in vitro resistance Change antibiotics

R Empirical antibiotics but clinical improvement

Do not change antibiotics (exceptions*) Possibility of in vivo sensitivity

Duration of antibiotic therapy

Meningitis (c/s proven) : 21 days Urinary tract infections : 7-14 days Proven bone/joint infections : 6 weeks

After NEGATIVE blood c/s

Asymptomatic neonate: Stop ABx Suspected EOS/LOS, neonate improves but not fully asymptomatic:
Repeat CRP assay & re-evaluate clinical data CRP > 10 antibiotics for 7 days CRP: negative & clinical data negative Stop

Suspected EOS/LOS, neonate has worsened clinically:

Evaluate for causes other than sepsis Empirically upgrade antibiotics if sepsis suspected

 First line: Ciprofloxacin + Amikacin (covers - 75% isolates) . If meningitis is suspected, replace Ciprofloxacin. by Cefotaximesulbactam (see section D24) Second line: Vancomycin + Piperacillin-Tazobactam (covers 90% isolates) Third line: Vancomycin + Meropenem (covers - 95-100%) The antibiotic policy is reviewed periodically and may change after the next review. Cephalosporins rapidly induce the production of extended spectrum b-lactamases, cephalosporinases and fungal colonization, and hence, are best avoided as empirical antibiotics.

 Empirical upgradation must be done if the expected clinical improvement with the ongoing line of antibiotics does not occur. A minimum of 48-72 h of observation should be allowed before declaring the particular line as having failed. The duration may be longer for Vancomycin compared to the Penicillin group and Aminoglycosides 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 h 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

 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 must be adhered to: o 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. o If possible, a single sensitive antibiotic must be used, the exception being Pseudomonas for which 2 sensitive antibiotics must be used. Two sensitive antibiotics (a Penicillin + an Aminoglycoside) may also be used for S aureus and E. fecalis.

o 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. o 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 a 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, Kiebsiella and

MRSA; and in cases of CNS infections and deep-seated infections. o If no antibiotic has been reported sensitive, but one or more has been reported moderate1y sensitive, therapy must be changed to such

antibiotics at the highest permissible dose. Use a combination, in such

cases.

Now, tell me this

Highly protein bound Displaces bilirubin Risk of Kernicterus

Ref: Pediatrics 2012; 129: 1006

Management of complications
Shock

Anemia / thrombocytopenia
DIC

Cerebral edema / Seizures

Pulmonary hemorrhage

Supporting therapy
Nursing care --warm environment

--oxygen supply / Ventilatory Support

correction of acidosis and electrolyte disturbance Hydration, fluid, glucose and nutrition balance

Upcoming modalities

ADJUNCTIVE THERAPIES

Intravenous Immunoglobulin
Level of Evidence Systematic review of therapeutic RCTs in clinically suspected infection: all infants (Cochrane Database of Systematic Reviews 2010) No. of Infants 10 RCTs and quasi RCTs Outcomes and Conclusions In clinically suspected infection group: Mortality reduced typical RR 0.58 (95% CI; 0.38, 0.89); NNT 10 (95% CI; 6, 33); I2 = 0% In proven infection group typical RR 0.55 (95% CI; 0.31, 0.98); I2 = 0%

Clinically suspected infection n=378

Subsequently proven infection n=262

Systematic review of therapeutic RCTs for sepsis and septic shock: all infants (Cochrane Database Syst Rev. 2010)
Systematic review of prophylactic RCTs in preterm infants (Cochrane Database of Systematic Reviews 2010)

338

Subgroup analysis of polyclonal IVIG in neonates showed no significant reduction in mortality for standard (n = 174) and IgMenriched polyclonal IVIG (n=164)
Meta-analysis shows 3% reduction in sepsis but no effect on mortality No further similar RCTs needed

4986

Intravenous Immunoglobulin
Level of Evidence IVIG (monoclonal) (The Cochrane Library 2009) Systematic review of prophylactic RCTs of antistaphylococcal IgG in VLBW infants No. of Infants 2701 (two studies of INH A -21 and one study of Altastaph) Outcomes and Conclusions No difference shown in mortality, sepsis, or other adverse outcomes Use is not recommended

International Neonatal Immunotherapy Study NEJM 2011;365:120111

Multicentric randomized clinical trial 3493 neonates Two doses at 500 mg/ kg or matching placebo 48 hours apart No difference in sepsis /mortality No difference in long term (2yr) outcome

Granulocyte transfusion
Use justified by reduced number and abnormal function Produced by leukopheresis
Level of Evidence No. of Infants Outcomes and Conclusions
No difference shown in mortality or sepsis: more RCTs needed
Reduction in all cause mortality of borderline statistical signicance (RR 0.06, 95% CI 0.00 to 1.04; RD-0.34, 95% CI -0.60 to 0.09; NNT 2.7)

Systematic review of three therapeutic RCTs

One trial (IVIG Vs. GT)

44
35

The Cochrane Library 2011, Issue 10

GCSF & GM-CSF

Glycoprotein Deficient in premies; Resistance also described Dose 5-10mcg/kg/day for 3 days
Level of Evidence
Systematic review of seven therapeutic RCTs

No. of Infants Outcomes and Conclusions

257 No difference shown in mortality or sepsis: more RCTs needed

Subgroup analysis of three therapeutic RCTs

Systematic reviews of three prophylactic RCTs

97

?GM-CSF improves survival in sepsis with neutropenia: more RCTs needed

No difference shown in mortality or sepsis: more RCTs needed

359

Cochrane Database of Systematic Reviews 2009, Issue 3

Exchange transfusion
Removal of bacteria, endotoxins & inflammatory mediators Improved opsonic & granulocyte activity Improved O2 carrying capacity
Level of Evidence Two therapeutic RCTs No. of Infants 70 Outcomes and Conclusions Exchange transfusion improves survival in gram-negative sepsis?? more RCTs needed

Clinics in perinatology,2010

Pentoxifylline
PD inhibitor and reduces TNF Improves endothelial function and avoids excessive coagulation
Level of Evidence No. of Infants Four therapeutic RCTs 227 Outcomes and Conclusions

Signicant reduction in all cause mortality Significant reduction in duration of hospital stay, mortality in preterm/confirmed sepsis/gram negative sepsis

The Cochrane Library 2011, Issue 10

Selenium & Melatonin

Free radical scavengers
Level of Evidence Selenium Systematic review of three prophylactic RCTs No. of Infants 583 Outcomes and Conclusions ? Selenium reduces sepsis: more RCTs needed

Melatonin No RCTs in newborns One non randomized trial

10

All babies had lower serum levels of free radicals and all survived

Clinics in perinatology 2010

Glutamine
Anabolic for dividing immune and gut cells
Level of Evidence Systematic review of seven prophylactic RCTs No. of Infants 2365 Outcomes and Conclusions No difference shown in mortality or sepsis or disability free survival: More RCTs

Clin Perinatol 37 (2010) 481499

Prevention of infections
Exclusive breastfeeding Keep cord dry

Hand washing by care givers

Hygiene of baby No unnecessary interventions
181

Control of hospital infections

Hand washing by all staff

Isolation of infectious patient

Use plenty of disposable items

Avoid overcrowding
Aseptic work culture

Infection surveillance
182

Work culture
Sterile gowns and linen for babies Hand washing by all Regular cleaning of unit No sharing of baby belongings Dispose waste-products in separate bins

183

FOLLOW-UP CARE

Growth monitoring Hearing screen who received Aminoglycosides Monitoring organ dysfunction Meningitis babies on OPD F/U:
Weekly OFC Neurological examination Hearing screen (discharge + 3 months) USG Head (1st week/ End of Rx/ Follow-up) Anti-epileptics (stop before discharge/ 3 months)

If proven UTI, start AMOXICILLIN 10 mg/kg OD oral prophylaxis & plan USG KUB, MCU & DMSA

TAKE HOME MESSAGE

High index of clinical suspicion Look for Lab evidence of sepsis Empirical antibiotics Start parenteral antibiotics (intravenous). Empirical antibiotics Start early, choice, in correct dose, correct mode of administration, check CSF penetration & side effects Collect blood c/s, correlate with clinical picture & modify therapy as early as possible Provide Supportive care & monitoring (clinical & lab) keeps the baby alive & buys time for antibiotics to act Review culture reports Practise barrier nursing to prevent Crossinfection No proven role for any adjunctive therapies at present Follow-up care with focus specific monitoring also determines

Hope we can save neonates before they reach this state of NO RETURN

Treatment Recommendations
Antibiotics should be initiated after all cultures and lab work is completed to ensure proper diagnosis. All neonates will remain on IV antibiotics until blood/urine culture results come back in approximately 2-3 days. Further therapy will depend on lab work results and the neonates response to treatment.
* Every hospital/organization has an antibiotic protocol specific to their site.

Although antibiotic therapy is vital, it is just as important to continue the overall support of the neonate (i.e. respiratory & cardiac).

Summary
Neonatal Sepsis is a severe infection in neonates that has the ability to cause death if not recognized and treated appropriately. The primary causes of sepsis are pathogens, such as Staphylococcus and Group Beta Strep [2&6]. These pathogens can enter a neonates body during the prenatal, perinatal, and postnatal period [6]. Although pathogens are the culprit in sepsis, neonates have factors that make them more susceptible to sepsis. One of these factors is the immaturity of the neonates immune system [6]. The second factor is related to a possible genetic predisposition that is caused by polymorphisms [3&14]. A Neonates symptoms in sepsis are broad and vary [9]. This is due in part to the metabolic and inflammatory processes that occur in neonatal sepsis. Because symptoms are broad and not very concrete, it is of vital importance that the healthcare professional notice even the most subtle changes in a neonates assessment. When sepsis is suspected a neonate will undergo a septic work up [2], which includes lab work and xrays. After lab work is completed intravenous antibiotics are initiated immediately and will continue until lab work demonstrates no infection and the neonate shows no further symptoms.

I hope you have enjoyed your experience and have learned some new information about neonatal sepsis.

References
1. Amaxa Biosystems. (n.d.). Mission #3: Transfect human monocytes. [Online image]. Retrieved March 22, 2006 from www.amaxa.com/mission3.html 2. Bellig, L.L. & Ohning, B.L. (2004). Neonatal Sepsis. Retrieved February 8, 2006, from emedicine:http://wwwemedicine.com/ped/topic2630.htm 3. Dahmer, M.K., Randolph, A., Vitali, S., & Quasney, M.W. (2005). Genetic polymorphisms in sepsis. Pediatric Critical Care Medicine, 6(3), 61-73. Retrieved February 23, 2006 from PubMed database. 4. Farlex Inc. (n.d.). The Free Dictionary. Retrieved March 30, 2006, from www.thefreedictionary.com 5. LaRosa, S.P. (2002). Sepsis. Retrieved February 14,2006, from The Cleveland ClinicWebsite: http://www.clevelandclinicmeded.com/diseasemanagement/infectiousdisease/sepsis.htm 6. McKenney, W.M. (2001). Neonatal nursing: Understanding the neonatal immune system: High risk for infection. Crtitical Care Nurse, 21(6), 35-58. Retrieved February 14, 2006, from ProQuest database. 7. Microsoft Corp. (2006). Microsoft Clip Art. Retrieved March 30, 2006, from www.microsoftclipart.com 8. Mrozek, J.D., Georgieff, M.K., Blazer, B.R., Mammel, M.C., & Schwarzenburg, S.J. (2000). Effect of sepsis syndrome on neonatal protein and energy metabolism. [Electronic version] Journal of Perinatology, 2, 96-100.

References
9. Neonatal Handbook:Sepsis. (n.d.). Retrieved February 14, 2006, from http://www.netsvic.org.au/nets/handbook/index.cfm?doc_id=898 10. Oostdyk, R. (2005). Neutrophil. [Online image]. Retrieved April 20, 2006, from http://en.wikipedia.org/wiki/Image:Segmented_neutrophils.jpg 11. Orr, P.A., Case, K.O., & Stevenson, J.J. (2002). Metabolic response and parenteral nutrition in trauma sepsis and burns. Journal of Infusion Nursing, 25(1), 45-53. Retrieved March 7, 2006 from Ovid database. 12. Sharma, S. & Mink, S. (2004). Septic shock. Retrieved February 14, 2006, from emedicine: http://www.emedicine.com/MED/topic2101.htm 13. St. Elizabeth Hospital. (n.d.). The newborn center at St. Elizabeths. [Online image]. Retrieved March 22, 2006 from www.steliz.org/newborn_center.htm 14. Villar, J., Maca-Meyer, N., Perez-Mendez, L., & Flores, C. (2204). Bench to bedside review: Understanding genetic predisposition to sepsis. Critical Care, 8(3), 180-189. Retrieved February 23, 2006, from PubMed database.