NEONATAL SEPSISPresenter; Joyce Mwatonoka

MD4May 2016

INTRODUCTION TYPES AND RISK FACTORS PATHOGENESIS AND PATHOPHYSIOLOGY CLINICAL MANIFESTATIONS DDx INVESTIGATIONS MANAGEMENT COMPLICATIONS PREVENTION

OUTLINE

NS is a clinical syndrome of bacteremia with systemic signs and symptoms of infection which occurs in the first month of life

As many as 2% of fetuses are infected in utero, and up to 10% of infants have infections in the 1st month of life, with a higher incidence in premature & low birth weight infants .

INTRODUCTION

1. Infectious agents can be transmitted from the mother to the fetus or newborn infant by diverse modes.

2. Newborn infants are less capable of responding to infection because of 1 or more immunologic deficiencies. Eg;

3. Coexisting conditions often complicate the diagnosis and management of neonatal infections. Eg;

4. The clinical manifestations of newborn infections vary and include subclinical infection, mild to severe manifestations of focal or systemic infection, and, rarely, congenital syndromes resulting from in utero infection. The timing of exposure, inoculum size, immune status, and virulence of the etiologic agent influence the expression of disease

WHY UNIQUE?

5. Maternal infection that is the source of transplacental fetal infection is often undiagnosed during pregnancy because the mother was either asymptomatic or had nonspecific signs and symptoms at the time of acute infectio.

6. A wide variety of etiologic agents infect the newborn, including bacteria, viruses, fungi, protozoa, and mycoplasmas

7. Immature, very low birthweight (VLBW) newborns have improved survival but remain in the hospital for a long time in an environment that puts them at continuous risk for acquired infections.

Cont…

Bacterial Viral Fungal

AETIOLOGY

EARLY ONSET SEPSIS; is defined by onset in the first week of life, with some studies limiting EOS to infections occuring in the first 72 hours due to maternal intrapartum transmission of invasive organisms. Probably because almost all cases occur before 72 hrs of life

Early-onset sepsis is ass/w acquisition of microorganisms from the mother, before or during delivery. Transplacental infection or an ascending infection from the cervix may be caused by organisms that colonize the mother’s genitourinary (GU) tract;

TYPES OF NS

Organisms most commonly ass/c EONS of term and preterm infants are GBS & E. coli (K1 Ag) - 70%

Listeria monocytogenes (gram+ rods, common in premature. apnea, RD, cyanosis & meconium stained amniotic fluid. Meningitis &sepsis. Granulomatosis infantisepticum;  a granulomatous rash present in severe cases.)

 Other streptococci (S. pyogenes, viridans group streptococci, S. pneumoniae)

Enterococci eg; Enterococcus faecalis Staphylococci (commonly S.aureus and CoNS) Non-typable Haemophilus influenzae

Cont…

Gram –ve rods; apart from E. coli they are less frequent causes of EOS; of importance among the enterobacteriacea include Enterobacter, Klebsiella & Serratia spp. Most common to premature infants n VLBW. They possess polysaccharide capsules which contribute to their virulence by preventing opsonization, phagocytosis and bacterial lysis

Cont…

MATERNAL Maternal GBS Colonization Maternal intake of contaminated foods, eg;

contamintn of refrigirated food with Listeria monocytogene

Procedures during pregnancy eg; amniocentesis Premature rupture of membranes (PROM) Preterm Delivery (<37 weeks) Prolonged rupture of membranes (>18 hours) Maternal UTI Multiple vaginal examinations Fever Chrorioamnionitis

RISK FACTORS FOR EONS

Chorioamnionitis refers to the clinical syndrome of intrauterine infection, which includes maternal fever, with or without local or systemic signs of chorioamnionitis,

Uterine tenderness Foul smelling vaginal discharge/amniotic fluid Maternal leukocytosis (>15,000cells/mm3) Maternal and/or fetal tachycardia Chorioamnionitis may also be asymptomatic, only

diagnosed by amniotic fluid analysis or pathologic examination of the placenta. Histologic chorioamnionitis is inversely related to gestational age at birth and directly related to duration of membrane rupture.

Cont…

Maternal factors associated with the development of chorioamnionitis include

Longer length of labor and membrane rupture,

Multiple digital vaginal examinations Placement of internal fetal or uterine

monitoring devices Spontaneous onset of labor, and Meconium-stained amniotic fluid

Risk factors for chorioamnionitis

INFANT FACTORS Prematurity/low birth weight 1. Immaturity of neonatal immune system,

including low Ig levels related to decreased transplacental transfer of maternal IgG.

2. Barrier function of the skin and mucus membranes is diminished in premature infants, further compromised by multiple invasive procudures; IV lies, intubation n NGT

Congenital anomalies HOW?? Complicated/instrument-assisted delivery Low apgar score of </= to 6 at 5min

Occurs at 7(4)-90 days of life and is acquired from the caregiving environment, including the normal newborn nursery, neonatal intensive care unit (NICU), or the community. Organisms that have been implicated in causing late-onset sepsis include the following:

LATE ONSET SEPSIS

1. Coagulase-negative Staphylococcus (commonest among VLBW infants)

2. Staph aureus (both MRSA & MSSA)3. Gram –ves; 1/3 of LOS infections, 50% mortality; E.Coli,  Klebsiella (commonest)  Pseudomonas (ass/c the highest mortality) Citrobacter (brain absesss n chronic CNS infections) Enterobacter Serratia4. Candida 5. HSV (Herpes Simplex Virus)

Cont…

FOR LONS Breakage of the natural barriers (skin and

mucosa) eg; cannulation Prolonged indwelling catheter use Invasive Procedures (eg. Endotracheal

intubation) Aspiration of feeds LBW Not breastfeeding

RISK FACTORS FOR LONS

1. Intrauterine infections by hematogenous transplacental transmission ; are a result of clinical or subclinical maternal infection with a variety of agents commonly;

cytomegalovirus [CMV] Treponema pallidum (syphilis) Toxoplasma gondii rubella virus varicella virus parvovirus B19

PATHOGENESIS OF EONS

Although HSV, HIV, hepatitis B virus (HBV), hepatitis C virus, and tuberculosis (TB) can each result in transplacental infection, the most common mode of transmission for these agents is intrapartum during labor and delivery with passage through an infected birth canal (HIV, HSV, HBV) or postnatal from contact with an infected mother or caretaker (TB).

However, these pathogens are not typically associated with an EOS presentation.

Cont…

Viral infections which may present as bacterial sepsis in EOS/LOS include;

HSV Enteroviruses eg; coxsackievirus and

echovirus Parechoviruses

Cont…

Fungal pathogens are rarely associated with early-onset neonatal sepsis, and Candida spp. are most likely, occurring primarily among VLBW infants. 

Candida infections may also present as congenital candidiasis that can occur in term or preterm infants, with symptoms occurring at birth or within the first 24 h of life

Cont…

2. Ascending/vertical infectionVertical transmission of bacterial agents that

infect the amniotic fluid and/or vaginal canal may occur in utero or more commonly during labor and/or delivery

Cont…

After birth, neonates are exposed to infectious agents in the nursery or in the community.

Postnatal infections may be transmitted by direct contact with hospital personnel, the mother, or other family members; from breast milk (HIV, CMV); or contaminated equipment.

The most common source of postnatal infections in hospitalized newborns is hand contamination of health care personnel.

PATHOGENESIS OF LONS

 Neonatal cells have a decreased ability to produce inflammatory cytokines, especially tumor necrosis factor and interleukin-6

In addition, they induce interlukin-10 production, which in itself is capable of inhibiting synthesis of pro-inflammatory cytokines

Neutrophil and dendritic cell functions are also reduced

 Neutrophils show a decreased expression of adhesion molecules as well as a decreased response to chemotactic factors

PATHOPHYSIOLOGY: Neonate Immunity

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

Dendritic cells have a decreased capacity of producing interleukin-12 and interferon (IFN) gamma

 The overall reduction in cytokine production in neonates also results in decreased activation of natural killer cells

Cont…

Decreased chemoattractants (infl cytokines eg; IL 1 & TNF-alpha)production in neonates

Decreased chemotaxis Decreased response to chemotactic factors Decreased adherence Decreased activation of natural killer cells Neutrophil reserves are easily depleted because of the

diminished response of the bone marrow Decreased amount of opsonins (antibodies that

promote opsonization), although they have sufficient amounts of monocytes

Over expression of IL 10 (helps to regulate the over expression of proinfl. cytokines – immunosupression)

SUMMARY

Clinical signs are non specific and are ass/c the characteristics of the causative organism, severity of infection, GA and the body’s response to the invasion.

 General sxs include lethargy, hypothermia, poor feeding, anuria and acidosis

As pneumonia is often the presenting infection in EOS, respiratory symptoms are common and may include apnea, tachypnea, grunting, nasal flaring, and intercostal retractions.

Cardiac symptoms may include cyanosis, desaturation, bradycardia, poor perfusion, reduced capillary refill, and hypotension.

CLINICAL MANIFESTATIONS

NB; septic infants commonly present with hypothermia instead of fever

DANGER SIGNS: Not feeding well, convulsions, drowsy or unconcious, movement only when stimulated or no mvt at all, fast breathing >60, grunting, severe chest indrawing, raised temp >38, hypothermia <35.5 & central cyanosis.

Cont…

Meconium aspiration syndrome RDS Necrotizing enterocolitis Congenital malaria Traumatic delivery Congenital/intrauterine pneumonia Congenital diaphragmatic hernia

DDx

Blood culture Complete blood count (CBC)-

thrombocytopaenia <100,000 & neutropenia

LP; elaveted WBC count & protein, decreased glucose

CSF culture C reactive protein, elevated Gram stain CXR to evaluate pulmonary involvement

INVESTIGATIONS

A, B, C, D Manage hypothermia Hypoglycaemia, give 2 ml/kg 10% glucose Convulsions with phenobarbital Antibiotics; first line; Ampicillin 50mg/kg & Genta; 1st wk of life; LBW 3mg/kg, Normal

BW 5mg/kg

MANAGEMENT

If at greater risk of staphylococcus inf. (extensive skin pustules, abscess or omphalitis in addition to signs of sepsis), give IV Cloxacillin and Gentamicin

Most serious cases of inf. Rx 7-10 days 2-3 days not improving change antibiotics

Cont…

Membrane ruptured > 18hrs b4 delivery Mother had fever > 38 C before/during

delivery Amniotic fluid was foul-smelling or purulent;IM/IV ampigenta for atlst 2days, continue

Rx only if there are signs of sepsis/a positive blood culture

PROPHYLACTIC ANTIBIOTICS

Fetal loss or early neonatal death Multiorgan dysfunction and or injury to the

developing brain etc

COMPLICATIONS

Avoiding unnnecessary separation of the newborn from the mother eg; baby unit

Hand washing before delivering and handling the infant

Good basic hygiene and cleanliness during deliver

Appropriate umbilical cord care Appropiate eye care

PREVENTION, EONS

Exclusive breastfeeding Strict procedures for hand-washing/alcohol

hand rubs for all staff and families before and after handling infants

Use of KMC instead of incubators Clean injection practices Removing iv drips when they are no longer

necessary

PREVENTION OF LONS

Is focused primarily on development of vaccines against GBS

In developed countries they currently screen and treat GBS infections in the 3rd trimester

CURRENT RESEARCH