Neonatal Sepsis

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C.S.N.Vittal Vijayawada Neonatal Sepsis

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Bacterial Sepsis in Neonate Clinical syndrome of infection with bacterimia in first month of life. May get predominantly localized to lung (Pneumonia) May be localized to meninges (meningitis) Definition :

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Bacterial Sepsis in Neonate 24 / 1000 live births Incidence : Single most important cause of neonatal deaths in the community (>50%)

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Bacterial Sepsis in Neonate Patterns Early Onset Late Onset Within 72 hrs of birth Complicated pregnancy + Maternal Genital tract Fulminant course Pneumonia 5-50 % mortality Symptoms beyond 72 hrs of birth Complicated pregnancy + Maternal Genital tract / Environmental Slower progression Meningitis 2-6 % mortality

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Neonatal Sepsis Major Risk Factors Ruptured membranes > 24 hrs. Maternal Fever (100.4 o F(38 o C) Chorionamnionitis Sustained fetal heart rate >160/min Multiple obstetric procedures Minor Risk Factors Ruptured membranes > 12 hrs. Foul smelling liquor Maternal Fever > 99.5 o F (37.5 o C) Low APGAR < 5 at 1 min, < 7 at 5 min Prematurity Multiple gestation Presence of 1 major or 2 minor risk factors -> High Risk of Sepsis

NNF CRITERIA SUSPECT SEPSIS 1 out of 3 parameters is an indication for antibiotic therapy: 

NNF CRITERIA SUSPECT SEPSIS 1 out of 3 parameters is an indication for antibiotic therapy PREDISPOSING FACTORS like PROM, Foul smelling liquor, amnionitis, gastric aspirate showing polymorphs 5 / HPF POSITIVE SEPSIS SCREEN (2/4 parameters) TLC <5000 per cubic ml Bandemia 20% CRP >10 ng per ml Micro ESR >10mm fall in 1hr CXR showing Pneumonia

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Neonatal Sepsis Pathogenesis Infection in the birth canal Colonization of skin, umbilical stump, nasopharynx, conjunctiva, etc. Transient bacteremia Invasion of blood stream Metastatic foci Meningitis, etc.

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Neonatal Sepsis Risk factors for Late onset sepsis (LOS) Prolonged hospitalization Prematurity LBW Previous antibiotic use Invasive procedures Presence of foreign material (ET Tubes/ catheters) Lack of disposables Over crowding / understaffing

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Neonatal Sepsis Risk factors for Community acquired sepsis Bottle feeding Poor hygiene Poor cord care Over crowding

OTHER SYMPTOMS: 

OTHER SYMPTOMS Lethargy (“baby not looking well”) Refusal to suck Poor cry Not arousable Abdominal distension Diarrhea Vomiting Hypothermia (Preterm, gram -ve infections Poor perfusion (CFT >3 sec.) Sclerema (hide bound feel of skin) Poor weight gain(FTT) Excessive jaundice (DRB >2 ml per dL) Poor neonatal reflexes Shock Bleeding Renal failure NEC Common terminal events

Pathogenesis ... : 

Pathogenesis ... SIRS CARS MARS

Infection : 

Infection Systemic Inflammatory Response Syndrome (SIRS) Resp : Tachypnoea > 2 SD Hypoxia PaO 2 < 70 mm Hg CVS : Tachycardia > 2 SD Hypothermia < 2 SD or hyperthermia Peripheral Perfusion: Delayed Capillary Filling > 3 Sec. Oliguria < 0.5 ml / kg / hr Lactic acidosis Altered mental status Increased or decreased white blood count:

Infection ---> SIRS: 

Infection ---> SIRS Sepsis - Systemic response to infection with bacteria SIRS with hypotension Severe Sepsis – Sepsis with organ dysfunction, hypoperfusion or hypotension Changes in mental status, oliguria, hypoxemia or lactic acidosis

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Septic shock – Severe Sepsis with persistent hypotension despite adequate fluid resuscitation Multiple Organ Dysfunction Syndrome (MODS) – Presence of altered organ function such that homeostasis can not be maintained without intervention Death

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Local pro-inflammatory response Local anti-inflammatory response Initial insult (bacterial, viral thermal, traumatic) Systemic spillover of pro-Inflammatory mediators Systemic spillover of anti-Inflammatory mediators Systemic Reaction SIRS : Pro CARS : Anti MARS : Mixed C H A O S C V Compromise H omeostasis A ptosis M ODS S uppression of immunity

Clinical Features: 

Clinical Features General : Lethargy, jaundice Temperature instability Respiratory Distress after a period of normalcy Apnea GI: Poor feeding, vomiting, abdominal distention, bilious aspirates Temperature labiality Skin: Petechial rashes, bleeding from puncture sites Sclerema CNS: Lethargy, irritability, seizures Metabolic: Unexplained metabolic acidosis Hyperglycemia Hypoglycemia Features to system involvement

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Sepsis Screen Laboratory Studies Total neutrophil count : < 5000 / mm 3 Immature to total ratio : > 0.2 Acute Phase Reactions Micro ESR : > 15 mm in 1 st hour C Reactive Protein : > 10 mg/L Hepatoglobin Cultures Chest X-Ray Grams Stain of gastric aspirate Antigen detection methods Lumbar Puncture

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Neonatal Sepsis Total neutrophil count & Immature to total ratio: TWBC : < 5000 / micro liter or >24000 Tot. neutrophil count : < 1000 / micro liter ( Normal= 1,750 / m L) Band / Total Neutrophil : > 0.2 ( Normal = 0.16 in 1 st Day, 0.12 after 24 Hrs.) Platelet Count : < 1 Lakh/mm 3 (Normal = 1.5 to 4 Lakhs /m m 3) - Increased risk of infection Repeat TWBC & DC at 8 - 12 hrs in a symptomatic neonate may have more predictable value than single record.

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Neonatal Sepsis Cultures Blood Urine CSF ( For Late Onset type)] Two positive cultures are more significant

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Neonatal Sepsis Chest X-Ray Persistent focal changes with infiltrative process Findings similar to RDS in GBS infection

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Neonatal Sepsis Acute Phase Reactants - Sepsis Screen Positive CRP ( > 6 mg/ L or 10 times normal) Elevated hepatoglobin level Micro ESR After 14 days of age 15 mm or more for the first hour is abnormal. (Normal ESR = Age in days + 2) If all results are -ve : Probability that infection absent = 99% If all results are +ve : Probability of infection = 90%

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Neonatal Sepsis Grams Stain of gastric aspirate If > 5 neutrophils / hpf or Large number of bacteria (esp. Gram+ve cocci) in large clumps and chains Positive Result : Predictive value less

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Neonatal Sepsis Antigen detection methods Latex particle aggulutination assays for GBS and ECK1 Counter immuno electrophoresis

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Neonatal Sepsis Lumbar Puncture Valuable in symptomatic infants who have risk factors for sepsis. CSF studies prior to antibiotic therapy is preferable LP in RDS is difficult Interpretation is difficult if LP is traumatic Sometimes meningitis may be present with normal CSF picture

Normal Neonatal CSF: 

Normal Neonatal CSF TEST TERM PRETERM WBCs (per cm) Polymorphs Up to 30 60% Up to 90 60% Protein (mg/dL) Up to 150 Up to 150 Glucose (mg/dL) 35-120 25-65

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Neonatal Sepsis Miscellaneous Investigations DIC Profile Culture of catheters/ ET Tubes Maternal vaginal swab cultures, etc.

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Management

Supportive therapy: 

Supportive therapy Thermoneutral environment IV Fluids Electrolyte and acid base balance Maintain oxygen saturation Circulatory support Glucose homeostasis Treat anemia with packet Rbc Treat bleeding diathesis with FFP / platelets

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Antibiotic Therapy

Antibiotic Therapay: 

Antibiotic Therapay PROM > 12 hrs. Evidence of Chorioannionitis Delivery outside labour room Infants with 1 major or 2 minor risk factors Positive Sepsis Screen Indications:

Armamentarium: 

Armamentarium Sulfa Drugs Folic Acid Analogs The Beta-Lactams Aminoglycosides Tetracyclines Macrolides Lincosamides Streptogramins Fluoroquinolones Polypeptides Rifampin Mupirocin Cycloserine Aminocyclitol Glycopeptides Oxazolidinones … and the list is incomplete …

Which one would you choose ?: 

Which one would you choose ?

Factors to be considered in the choice of Antibiotic: 

Factors to be considered in the choice of Antibiotic Gram + ve Gram _ ve Anaerobes

Antibiotic Selection: 

Antibiotic Selection Presumptive therapy directed to most commonly encountered pathogens. 1 st Line : Ampi/Sulbactum+Aminoglycoside 2nd Line 2nd gen. Cephalosporins + Aminoglycosides 3rd Line Vancomycin + Cephalosporins Newer antibiotics

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Role of Newer drugs ?

Antibiotic Evolution: 

Antibiotic Evolution

When you can’t decide , you tend to …: 

When you can’t decide , you tend to … Resort to “Shotgun Therapy”

Bauer-Kirby Method (Agar gel diffusion method): 

Bauer-Kirby Method (Agar gel diffusion method)

Duration of Antibiotic Therapy: 

Duration of Antibiotic Therapy Culture Positive Sepsis - 14 Days Pyogenic Meningitis - 21 Days / 2 weeks after CSF sterile Culture – ve/ clinically probable sepsis screen +ve:7-10 d. Culture – ve/ clinically probable sepsis screen -ve:5-7 d. Septic Arthritis - 6 Weeks

Immunotherapy: 

Immunotherapy Immunoglobulin : IVIG 500-1000 mg/kg/dose Specific Immunoglobulins : Anti GBS Ig. Oral administration of IgA and IgG in NEC Granulocyte infusions G – CSF 10 m g/kg/d for 3 days GM – CSF 10 m g/kg/d for 5 days Double volume exchange transfusions

Supportive Therapy: 

Supportive Therapy Continued Breast Feeding Nutrition : TPN / Aminoplasma Fluid / Electrolyte balance Treatment of acidosis

Preventive Aspects of Neonatal Sepsis: 

Preventive Aspects of Neonatal Sepsis Obstetric Management strategies Screening based approach Risk factor approach Exclusive breast feeding No prelacteals Keeping the cord dry Hand washing by care givers before and after handling the baby (Single most effective measure) Hygiene of the baby Avoid unnecessary intravenous fluids, needle pricks etc.

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Risk Factors Previous GBS Preterm delivery Bacteremia Rectal & Vaginal swab c/s. at 35-37 wks. Risk Factors Intrapartum Temp. PROM > 18 hrs No intrapartum prophylaxis needed Give intrapartum penicillin Give intrapartum penicillin Give intrapartum penicillin Algorithm for early prevention of GBS

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Than Q -CSN Vittal