11. Sespsis Targoviste

Infections of the NewbornInfections of the Newborn: :

Evaluation and ManagementEvaluation and Management

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Background statistics Background statistics TerminologyTerminologyWhy babies are more vulnerable Why babies are more vulnerable Risk factors Risk factors Clinical signs Clinical signs Screening Screening Workups Workups Treatment Treatment Aftermath Aftermath Prevention Prevention Future Trends Future Trends Specific Clinical EntitiesSpecific Clinical Entities

Background StatisticsBackground Statistics

Neonatal literature says: Neonatal literature says: – Actual infection rate 1-8/1000 newborns Actual infection rate 1-8/1000 newborns – LBW infection rate 1-2/100 newborns LBW infection rate 1-2/100 newborns – 5 infants die from neonatal infection every 5 infants die from neonatal infection every

minute minute – 4-5 (10%) deaths are due directly to infection 4-5 (10%) deaths are due directly to infection

but mortality as high as 25%but mortality as high as 25%– Romania – poorly control and not exactly Romania – poorly control and not exactly

report of the infectionsreport of the infections

Terminology(1)Terminology(1)BacteriemiaBacteriemia-presence of viable bacteria in the -presence of viable bacteria in the circulating blood confirmed by culturecirculating blood confirmed by culture

SepsisSepsis-clinical suspicion of infection and evidence -clinical suspicion of infection and evidence of systemic response to infection (tachycardia, of systemic response to infection (tachycardia, tachypnea, hyperthermia, or hypothermia)tachypnea, hyperthermia, or hypothermia)

Sepsis syndromeSepsis syndrome-sepsis plus evidence of altered -sepsis plus evidence of altered organ perfusion with at least one of the following: organ perfusion with at least one of the following: acute changes in mental status, oliguria, elevated acute changes in mental status, oliguria, elevated blood lactate and hipoxemiablood lactate and hipoxemia

Terminology (2)Terminology (2)Septic shock-Septic shock-Sepsis syndrome with Sepsis syndrome with hypotension that is responsive to IV fluids or hypotension that is responsive to IV fluids or pharmacologic intervention pharmacologic intervention

Refractory septic shock-Refractory septic shock-sepsis syndrome with sepsis syndrome with hypotension that last for more than 1hour and hypotension that last for more than 1hour and does not respond to IV fluids or pharmacologic does not respond to IV fluids or pharmacologic intervention and requires vasopressor supportintervention and requires vasopressor support

Multiorgan failure-Multiorgan failure-any combination of DIC, any combination of DIC, ARDS, acute renal failure, hepatobiliary ARDS, acute renal failure, hepatobiliary dysfunction, and CNS dysfunctionsdysfunction, and CNS dysfunctions

Historical Changes in Historical Changes in Predominant Infectious AgentPredominant Infectious Agent

Historical Changes in Predominant Infectious Historical Changes in Predominant Infectious AgentAgent1930: Group A Strep 1930: Group A Strep 1940: E. coli 1940: E. coli 1950: Staph aureus 1950: Staph aureus 1970: Group B Strep1970: Group B StrepFor reasons which remain unclear neonatal For reasons which remain unclear neonatal infectons in the developing nations are infectons in the developing nations are dominated by Gram-negative and Gram-dominated by Gram-negative and Gram-positive organisms, GBS only accounts 1-8% positive organisms, GBS only accounts 1-8% infantsinfants

Setting PrioritiesSetting Priorities

Newborns are not small children Newborns are not small children

Competing perceptions of parents, Competing perceptions of parents, pediatricians, house-staff, neonatology pediatricians, house-staff, neonatology

Personal responsibility, hands-on Personal responsibility, hands-on assessments are keyassessments are key

Remember that 10 babies are worked Remember that 10 babies are worked up for each proven caseup for each proven case

Neonatal VulnerabilityNeonatal Vulnerability

Immature immune system (slow to react, Immature immune system (slow to react, decreased IgG and complement production, decreased IgG and complement production, poor phagocytosis, poor migration) poor phagocytosis, poor migration) Unavoidable exposure to pathogenic Unavoidable exposure to pathogenic organisms in birth canal organisms in birth canal Peripartum stress Peripartum stress Invasive procedures Invasive procedures Exposure to highly resistant nosocomial Exposure to highly resistant nosocomial organisms in NICUorganisms in NICU

Risk FactorsRisk Factors

PROM (7X) PROM (7X) Prematurity (7X) Prematurity (7X) Maternal fever, chorioamnioitis (4X) Maternal fever, chorioamnioitis (4X) Perinatal asphyxia (4X) Perinatal asphyxia (4X) Male (2-6X) Male (2-6X) Recent colonization with GBS, Herpes, etc. Recent colonization with GBS, Herpes, etc. Multiple gestation Multiple gestation Foul smelling is not necessarily a risk factor Foul smelling is not necessarily a risk factor - usually anaerobes- usually anaerobes

Clinical Signs (1)Clinical Signs (1)

Not breathing well Not breathing well

Not feeding well Not feeding well

Not looking wellNot looking well


Respiratory Respiratory – dusky spells dusky spells – tachypnea - sensitive but nonspecific - but tachypnea - sensitive but nonspecific - but

respiratory distress in term newborn is sepsis respiratory distress in term newborn is sepsis until proven otherwise. until proven otherwise.

– apnea in normal newborn - septic w/u and apnea in normal newborn - septic w/u and supportive measures should be knee-jerk supportive measures should be knee-jerk reaction, then rule out other causes reaction, then rule out other causes

– increased A&B episodes (growing premie)increased A&B episodes (growing premie)


Feeding Feeding – not hungry not hungry – distension distension – residuals residuals – vomiting vomiting – heme-positive stools heme-positive stools – watery or mucousy stoolswatery or mucousy stools


Appearance Appearance – lethargic lethargic – mottled mottled – poor perfusion poor perfusion – temperature instability (not necessarily fever, temperature instability (not necessarily fever,

but fever is more specific) but fever is more specific) – early-onset jaundiceearly-onset jaundice


Chance Finding during Routine Tests Chance Finding during Routine Tests – Chemstrip Chemstrip – Urine dipstick - hemoglobin or sugarUrine dipstick - hemoglobin or sugar


Ominous Late Signs Ominous Late Signs – Apnea Apnea – Seizures Seizures – Hypotension/ShockHypotension/Shock


Sepsis-like Presentations: Sepsis-like Presentations: – Ductal-dependent congenital heart disease Ductal-dependent congenital heart disease – Inborn errors of metabolism (IEM)Inborn errors of metabolism (IEM)

ScreeningScreening

CBC with manual diff CBC with manual diff – WBC: up, down, or normal WBC: up, down, or normal – Left shift helpful but may be delayed Left shift helpful but may be delayed – ANC, I/T ratio ANC, I/T ratio – Unexplained thrombocytopenia Unexplained thrombocytopenia

PT/PTT suddenly abnormal PT/PTT suddenly abnormal Blood sugar may be high or low - change in pattern Blood sugar may be high or low - change in pattern ESR and CRP? Varies from center to center. ESR and CRP? Varies from center to center. CIE or Latex fixation for GBS? Numerous false CIE or Latex fixation for GBS? Numerous false positives. positives. Gastric aspirate or ET aspirate? Not very specific. Gastric aspirate or ET aspirate? Not very specific.

Workup (1)Workup (1)

Workup During First 24 Hours of Life Workup During First 24 Hours of Life – Blood culture Blood culture – Amniotic fluid or placenta culture if available Amniotic fluid or placenta culture if available – ET aspirate (if intubated) ET aspirate (if intubated) – Very low yield for LP or urine cultures in first Very low yield for LP or urine cultures in first

24 hours unless specific clinical indication 24 hours unless specific clinical indication – LP later if blood culture positive or specific LP later if blood culture positive or specific

symptoms - but note that 10-15% of babies symptoms - but note that 10-15% of babies with positive LP have negative blood cultureswith positive LP have negative blood cultures


Classic Septic Workup (> 24 hours, < 30 Classic Septic Workup (> 24 hours, < 30 days) days) – Blood culture Blood culture – LP LP – Urine - catherized or suprapubic aspirate Urine - catherized or suprapubic aspirate – ET aspirate if intubated ET aspirate if intubated – Surface cultures skin/eye/secretions Surface cultures skin/eye/secretions – Stool culture if stools abnormal Stool culture if stools abnormal – CXR CXR – Abd. X-ray if symptomaticAbd. X-ray if symptomatic


Goals of workup Goals of workup – Recover organism Recover organism – Determine specific antibiotics Determine specific antibiotics – Determine antibiotic doses Determine antibiotic doses – Determine length of therapyDetermine length of therapy

Treatment (1)Treatment (1)

Antibiotics Antibiotics

General supportive measures General supportive measures

IVIG? IVIG?

GCSF or GMCSF?GCSF or GMCSF?


General supportive measures General supportive measures – Assisted ventilation and/or oxygen as needed Assisted ventilation and/or oxygen as needed – IV and possibly arterial access IV and possibly arterial access – NPO, NG suction if needed NPO, NG suction if needed – Volume support, pressors Volume support, pressors – Transfuse if indicated Transfuse if indicated – FFP/cryo if clotting disorders FFP/cryo if clotting disorders – Thermal regulation/supportThermal regulation/support


Selection of antibiotics based on: Selection of antibiotics based on: – Age of onset Age of onset – Location (home vs hospital) Location (home vs hospital) – Maternal history Maternal history – Known colonization Known colonization – Epidemic situations Epidemic situations – etc.etc.

Treatment (4)Treatment (4)Late Onset (Home) Late Onset (Home) – GBS GBS – GramNegatives GramNegatives – HerpesHerpes

Early onsetEarly onset: : – GBS GBS – E. Coli E. Coli – Listeria Listeria – Others less common: Others less common:

Herpes Herpes Staph aureus Staph aureus Strep A and D Strep A and D H. influenza H. influenza Klebsiella Klebsiella Pseudomonas Pseudomonas EnterobacterEnterobacter

Treatment(5)Treatment(5)

Late OnsetLate Onset (Hospital) (Hospital) – Staph epidermidis Staph epidermidis – Gram negatives (often resistant) Gram negatives (often resistant)

Pseudomonas, Klebsiella Pseudomonas, Klebsiella

Xanthomonas, Enterobacter Xanthomonas, Enterobacter

Serratia, Acinetobacter, etc. Serratia, Acinetobacter, etc.

– Candida (esp. if deep line)Candida (esp. if deep line)


Antibiotic selection Antibiotic selection – Early - usually Ampicillin and Gentamicin Early - usually Ampicillin and Gentamicin – Late onset for premie in hospital - Vancomycin and Late onset for premie in hospital - Vancomycin and

Gent or drugs specific to known colonization or Gent or drugs specific to known colonization or epidemic situations. Third line drugs –Cefotaxime, epidemic situations. Third line drugs –Cefotaxime, Ceftazidime, Imepenam, Piperacillin, etc. Ceftazidime, Imepenam, Piperacillin, etc.

– Abdominal catastrophes - Amp, Gent, Flagyl, etc. Abdominal catastrophes - Amp, Gent, Flagyl, etc. – Late onset home - Amp and Gent if<30 days of age, Late onset home - Amp and Gent if<30 days of age,

Amp and Cefotaxime if greater than 30 days . Amp and Cefotaxime if greater than 30 days . – Fungus - Ampho, etc.Fungus - Ampho, etc.

Aftermath(1)Aftermath(1)

How long to treat? How long to treat? – Was organism recovered? Was organism recovered? – Where was organism found? Where was organism found? – Clinical course? Clinical course? – Repeat cultures? Repeat cultures?

Sequelae? Sequelae? – Few in uncomplicated neonatal sepsis Few in uncomplicated neonatal sepsis – Frequent with NEC, gram-negative meningitisFrequent with NEC, gram-negative meningitis

Aftermath (2)Aftermath (2)

Negative cultures and course not Negative cultures and course not consistent with infection: 48-72 hours consistent with infection: 48-72 hours of treatment of treatment UTI - 7-10 days treatment, screen for UTI - 7-10 days treatment, screen for renal anomalies renal anomalies Sepsis/NEC - 10-14 days of treatment Sepsis/NEC - 10-14 days of treatment Meningitis: 14 days (GBS), 21 days Meningitis: 14 days (GBS), 21 days (gram-negative), recommend ID consult (gram-negative), recommend ID consult Osteo - prolonged treatment, get ID Osteo - prolonged treatment, get ID consultconsult

PreventionPrevention

GBS - maternal prophylaxis > 4 hrs PTD GBS - maternal prophylaxis > 4 hrs PTD

Primary or active herpes - C/S Primary or active herpes - C/S

Chlamydia - maternal prophylaxisChlamydia - maternal prophylaxis

Future TrendsFuture Trends

GCSF or GMCSF GCSF or GMCSF

Monoclonal antibodies Monoclonal antibodies

Prophylaxis - various modesProphylaxis - various modes

Specific Clinical EntitiesSpecific Clinical Entities

Gram negativeGram negativeGBS GBS Herpes Herpes Chlamydia Chlamydia Mycoplasma/Ureaplasma Mycoplasma/Ureaplasma NEC NEC ListeriosisListeriosisBotulismBotulism

Gram negativeGram negative

Gastrointestinal tract is a source of Gastrointestinal tract is a source of systemic neonatal infections caused by systemic neonatal infections caused by coliform and other Gram-negative coliform and other Gram-negative bacteriabacteria

Septic shock is most commonly Septic shock is most commonly associated with Gram-negative associated with Gram-negative bacterial sepsisbacterial sepsis

Group B Streptococcus (GBS)Group B Streptococcus (GBS)

Early onset - acquired from birth canal - Early onset - acquired from birth canal - typically pneumonia or mild septic typically pneumonia or mild septic picture but can be fulminant pneumonia picture but can be fulminant pneumonia with septic shock with septic shock Late onset - acquired from household Late onset - acquired from household contacts - more indolent presentation of contacts - more indolent presentation of fever + meningitis, sepsis fever + meningitis, sepsis Changing clinical picture over 3 decadesChanging clinical picture over 3 decades

Necrotizing Enterocolitis (NEC)Necrotizing Enterocolitis (NEC)

Distension, residuals (particularly bilious residuals), Distension, residuals (particularly bilious residuals), heme + stools heme + stools X-ray picture - pneumotosis intestinalis, portal air, X-ray picture - pneumotosis intestinalis, portal air, free air, fixed loops, etc. free air, fixed loops, etc. Supportive measures: antibiotics, volume + Supportive measures: antibiotics, volume + pressors, TPN, NPO, NG suction, etc. pressors, TPN, NPO, NG suction, etc. Surgery indicated if free air, peritonitis, falling WBC Surgery indicated if free air, peritonitis, falling WBC or platelet count or platelet count First 24-48 hours is crisis period First 24-48 hours is crisis period Long-term damage is frequent - strictures, Long-term damage is frequent - strictures, obstruction, malabsorbtion, dysmotility obstruction, malabsorbtion, dysmotility Separate noon lecture for housestaff on this topicSeparate noon lecture for housestaff on this topic

Herpes SimplexHerpes Simplex

Birth to 1 month of age Birth to 1 month of age Transmission: birth canal, postpartum contact, Transmission: birth canal, postpartum contact, transplacental (rare) transplacental (rare) Risk factors: primary infection > 2ndary infection, Risk factors: primary infection > 2ndary infection, PROM 18 hrs, instrumentation (e.g. scalp monitor), PROM 18 hrs, instrumentation (e.g. scalp monitor), prematurity prematurity Presentation: Local disease (skin eye mouth), Presentation: Local disease (skin eye mouth), disseminated disease (only 30% have skin lesions ), disseminated disease (only 30% have skin lesions ), neurologic disease neurologic disease Diagnosis: Culture Diagnosis: Culture Treatment: Acyclovir Treatment: Acyclovir Prognosis: neurological disease 50% mortality, Prognosis: neurological disease 50% mortality, disseminated 80% mortalitydisseminated 80% mortality

Chlamydia TrachomatisChlamydia Trachomatis

Transmission: birth canal. 20-30% lower SES Transmission: birth canal. 20-30% lower SES are carriers, 50% of infants get infected are carriers, 50% of infants get infected Risk factors: Colonized mom, PROM, Risk factors: Colonized mom, PROM, prematurity prematurity Presentation Presentation – 25-50% conjunctivitis - most common cause 25-50% conjunctivitis - most common cause – 5-20% pneumonia - gradual onset at 3-12 weeks, 5-20% pneumonia - gradual onset at 3-12 weeks,

stacatto cough, tachypnea, rales, usually afebrile stacatto cough, tachypnea, rales, usually afebrile

Diagnosis: IFA, ELISA, Giemsa stain, CXR Diagnosis: IFA, ELISA, Giemsa stain, CXR interstitial interstitial Treatment: ErythromycinTreatment: Erythromycin

Ureaplasma/MycoplasmaUreaplasma/Mycoplasma

Transmission: birth canal, 40-80% carriers Transmission: birth canal, 40-80% carriers for ureaplasma, 21-50% mycoplasma for ureaplasma, 21-50% mycoplasma

Presentation: non-acute pneumonia, ? Presentation: non-acute pneumonia, ? meningitis, ? associated with stillbirths and meningitis, ? associated with stillbirths and chronic lung disease chronic lung disease

Treatment: Erythromycin for symptomatic Treatment: Erythromycin for symptomatic ureaplasma infections, no really good ureaplasma infections, no really good treatment for mycoplasma (tetracycline is treatment for mycoplasma (tetracycline is contraindicated)contraindicated)

ListeriosisListeriosis

Infections in newborns has a bimodal Infections in newborns has a bimodal distribution,with early-oset septicemic infection distribution,with early-oset septicemic infection associated with low birth weight,obstetric associated with low birth weight,obstetric complications and maternal colonisationscomplications and maternal colonisations

Late onset disease tends to occur in infants with Late onset disease tends to occur in infants with normal birth weight, with meningitis as a normal birth weight, with meningitis as a prominent finding, and is frequently associated prominent finding, and is frequently associated with maternal colonisation or obstetric with maternal colonisation or obstetric complicationscomplications

Infant BotulismInfant Botulism

Typical history is 3-6 week old infant with Typical history is 3-6 week old infant with history of constipation and poor feeding history of constipation and poor feeding progressing to apnea progressing to apnea

Endemic in California, Utah, Pennsylvania Endemic in California, Utah, Pennsylvania

Raw honey has been implicated in some cases Raw honey has been implicated in some cases

Supportive therapy esp. ventilatory Supportive therapy esp. ventilatory assistance, IV nutrition assistance, IV nutrition

No aminoglycosides!No aminoglycosides!

11. Sespsis Targoviste

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