Neonatal sepsis is a major cause of neonatal mortality in Sri Lanka. Early diagnosis and treatment with antibiotics and supportive care can save most babies. Preventive strategies like reducing invasive interventions, promoting breastfeeding, and proper hand hygiene can reduce the occurrence of neonatal sepsis. Antibiotic usage should be rationalized to prevent resistance. The document then defines neonatal sepsis and its types, risk factors, clinical features, diagnostic evaluations, and management guidelines including empirical antibiotic therapy and duration of treatment for different types of sepsis like pneumonia and meningitis.

1. NEONATAL SEPSIS ANDANTIBIOTIC THERAPYIN NEWBORNS.
In Sri Lanka 20% of neonatal mortalityisdue tosepsis.
If diagnosedearlyandtreatedwith goodsupportive care and antibiotics,itis possible tosave most
babieswithneonatal sepsis.
 Decreasinginvasive interventions,
 promoting breastfeeding,
 maintainingproper hand hygiene ,are the bestpreventivestrategiestoreduce the occurrence
of neonatal sepsis.
Antibioticuse shouldbe rationalizedandstandardizedinordertoreduce inappropriate usage and
emergence of multi resistantorganisms.
Definitions
Neonatal sepsisisaclinical syndromecharacterizedbysignsandsymptomsof infectionwithorwithout
accompanyingbacteraemiainthe firstmonthof life.Itencompassesvarioussystemicinfectionsof the
newbornsuchas
 septicaemia
 meningitis
 pneumonia
 arthritis
 osteomyelitis
 urinary tract infections(UTIs)
Early onset sepsis(EOS)
Suspectedsepsis within72 hoursof birth. The source of the pathogenisthe maternal genital tractor
the deliveryarea.Commonestpathogensare
 Streptococci (mainlyGroupB Streptococci;GBS)
 E.coli,coliform and other gram negatives
 Listeria monocytogenes
Respiratorydistressdue tocongenital(intrauterine) pneumoniaisthe predominantmanifestationof
EOS.
Signsand symptomsof infectionwith
or without accompanying bacteraemia

2. Late onset sepsis(LOS)
It usuallypresentsafter72 hoursof age ,The source of infection,
 Staphylococcus aureus
 Gram-negative bacilli - Klebsiella,Escherichiacoli,othercoliforms
 Serratia
 Pseudomonas
 Coagulase negative staphylococcus (CONS)
LOS commonlypresentsassepticaemia,pneumoniaormeningitis.
Risk factors for sepsis
Early-onsetsepsisiscausedbyorganismsprevalentinthe maternal genitaltractor inthe deliveryarea.
The risk factorsfor early-onsetsepsisinclude:
 Maternal pyrexia>38°C or otherevidence of infection
 Prolongedrupture of membranes(ROM>18hrs)
 Foul smellingliquor( suspectedchorioamnitis)
 Spontaneouspretermdelivery(<37weeks)
 Verylowbirthweight(<2500g)
 Prolongedordifficultdeliverywithinstrumentationor≥3 vaginal examinationsin24 hoursor
presence /removal of cervical suture
 Maternal UTI inthe thirdtrimester
Late-onsetsepsisiscausedbythe organismsthrivinginthe externalenvironmentof the home orthe
hospital.The infectionisoftentransmittedthroughthe handsof the care-providers. Mostly nosocomial
infection:
The associatedfactorsof late-onsetsepsisinclude:
 Verylowbirthweight,prematurity
 Lack of breastfeeding
 Delayedenteral feeding
 Frequenthandling/extensive resuscitationwithorwithoutinvasiveprocedures
 Disruptionof skinintegritywithneedlepricksanduse of intravenousfluids
 Poorhygiene
 Poormaintenance of asepsisin the neonatal unit, mechanical ventilation
 includingimproperhandwashingtechniques
 Superficial infections(eg;skinandumbilical sepsis)
 Previousorprolongedhospitalization
Factor that increase communityacquiredLOS

3.  Poorhygiene
 Poorcord care
 Bottle feeding
Clinical features
Signsmaybe subtle and,althoughdifficulttodefine,amotheror nurse mayreport thata baby is simply
‘not right’.
Frequentearlysigns
• Isolated tachypnoea(respiratoryrate sustainedabove 60breaths/minwithminimal recessions)and
• feedingdifficulties (notfeedingorpoorsuck) are the most frequentearlysignsof infection.
Other signs
• Hypo or hyperthermiafollowingexclusionof environmental causesanddehydrationaxillary
temperature above 37.5°Cor below36.0°C
• Irritability– mayindicate the presence of meningitis.
• Skin– Petechiae,septicfoci,paronychiaoromphalitis.
• Poorcutaneouscirculation - mottlingand delayedcapillaryfilling(>3seconds).
• Jaundice - Unexplainedjaundice;inthe absence of otherexplanations,jaundice mayindicate aurinary
tract infection.
• Cardiovascular–heart rate ≥160 beats/min; low pulse volume , hypotensionor shock
• Gastrointestinal –vomiting,diarrhoea,abdominal distension
• Respiratory –Apnoea,cyanosis,gruntingand dyspnoea.Forventilatedbabies,anincrease in
ventilation requirementsoftenaccompaniessepsisaswell as pneumonia.
• Central nervoussystem- A high-pitchedcry,neck retraction, bulgingfontanelleandconvulsionsare
late featuresof neonatal meningitis.
• Haemorrhagicdiathesis- petechiaeandbleedingfrom puncture sitesdue to DIC;thrombocytopaenia
withoutDICiscommoner.Bleedingfromthe gutor the renal tract are late signsof sepsis.
• Sclerema- diffuse hardeningof the subcutaneoustissue resultinginatightsmoothskinthat feels
boundto the underlyingstructures;oftenassociatedwithgramnegativeinfection
• Tone – maybe hypotonic

4. Examination shouldinclude assessmentof
 Hydration
 Murmurs or triple rhythm – congenital heartdiseaseand
 endocarditis/myocarditis
 Abdomen –distensionandrigidity,masses,bowel
 sounds,organomegaly
 Spinal columnfordefects
 Limbsfor signsof osteomyelitisandsepticarthritis
Septicscreening
Partial:
 Bloodculture (shouldbe performinall goldstandard )
 Total leukocyte countabsolute neutrophil count,immature ortotal neutrophil ratio
 C reactive proteins
 Urine culture
 Chestx ray
 Deepswabculture
All thisinclude without LP- LP isindicate inthe presence ofa positive bloodculture or ifthe clinical
picture isconsistentwith septicemic.LP coldbe postponedin a critically sick neonate- performsan
interval LP whenthe baby is stable.
Other investigation
•Serumbilirubin –if jaundice present
•Serumelectrolytes
•Bloodsugar
Meningitis
About25-30% of septicemicneonatesmayhave meningitiswhichisoftensilentwithoutsignsof
meningeal irritation.
Diagnosis;
Full sepsisscreen:
 Bloodculture*
 Full bloodcount*
 CRP/microESR*
 Urine Culture

5.  CSF examination
 CXR
*Partial sepsisscreen
Direct methodof diagnosis:Isolationof microorganismsfromblood,CSF,urineorpusisdiagnostic.In
clinicallysuspectedcasesof sepsis,
bloodculture shouldbe sentprior to starting antibiotics.
Indirectmethod of diagnosis:
There are a varietyof testswhichare helpful forscreeningof neonates withsepsis.
 Total leukocyte count (TLC): A total leucocyte countbelow 5000/cu mm.
 An absolute neutrophil count (ANC) of < 1800 percu mmis an indicatorof infection.
Neutropeniais more predictiveof neonatal sepsisthanneutrophilia.
 Immature neutrophils (Bandcells+myelocytes+metamyelocytes)to total neutrophilsratio
(lTR) > 0.20 meansthatimmature neutrophilsare over20 percentof the total neutrophils.This
happensbecause bone marrowpusheseventhe immature cellsintocirculation,tofight
infection.
 C-reactive protein(CRP):- A single negative CRP doesnot exclude sepsis.CRPhas a lag phase
to respond especiallyinpre-termneonates(upto48 hours to achieve highestlevelsin
extremelylowbirth weightinfants).Therefore serial CRPs are more useful.
CRP ishelpful inexcludinginfectionif 2values more than24 hoursapart withfirstsample being
takenmore than 12-24 hours afteronsetof symptomsare normal

6. - The CRP can alsobe positive inotherconditions like prolongedrupture of membranes,
maternal feverduringlabour,fetal distress,perinatal asphyxia,shock,intraventricular
haemorrhage, pneumothorax,andmeconiumaspiration pneumonitis.
A negative sepsisscreenhelpsto rule out sepsis;a positive screenmay not be confirmatory
whenblood culture is negative.Therefore a practical positive “sepsisscreen” takesinto
account two or more positive testsout of the five givenbelowin bloodculture negative
babies:
1. Leukopenia(TLC<5000/cumm)
2. Neutropenia(ANC<1800/cumm)
3. Immature neutrophil tototal neutrophil (I/T) ratio(>0.2)
4. Micro ESR (> 15 mm 1st hour)
5. CRP +ve (>10mg/L)
The CSF glucose level issometimesgivenasa percentage of the serum glucose done at least30
minutesprior to the lumbar puncture: normal 0.6 (60%).
Management
Supportive care and atibioticsare two equallyimportant componentsof the management.
The supportive care includes:
Performsepsisscreenif,
- Sepsisissuspectedclinicallyor
- there are ≥two riskfactors inan asymptomatic
baby

7.  Maintainingtemperature,airway,breathingand circulation.May require ventilation,fluid
boluses,inotropes
 Ensure optimum oxygenation(maintainSpO290 - 94%).Aimfor highersaturationforbabiesat
high
 riskof PPHN (meconiumaspirationsyndrome) National GuidelinesforNewbornCare - Volume II
59
 Maintainnormoglycemia
 Inj VitK 1mg IV if there isactive bleedingfrom anysite;mayneedplatelets,FFPif inDIC.
 Avoid enteral feedif haemodynamically compromised,give maintenance IV fluidsbutstart
orogastric feedsas soon as hemodynamicallystable.
Antibiotictherapy
• Empirical antibiotictherapyshouldcoverthe commoncausative bacteria.If anyof the culturesprove
to be positive andasensitivitypatternisavailable antibioticsmaybe revised.
Indicationsfor antibiotics
a) Prophylaxis/empirical therapyfor “at risk babies” Prophylacticantibioticsshouldbe consideredin
followingcircumstanceswhichare riskfactorsfor earlyonsetsepsis
1. Foul smellingliquorormalodorousbaby
2. When ≥ 2 of followingriskfactorsare present
 Maternal pyrexia>38°C or otherevidence of
 infection
 Prolongedrupture of membranes(ROM>18hrs)
 Fetal distress(tachycardia,bradycardia,abnormalCTG),passage of meconiumin-uterowithno
otherexplanation)
 Spontaneouspretermdelivery(<37weeks)
 Low Apgar<7 at 5 min
 Prolongedordifficultdeliverywithinstrumentation or≥3 vaginal examinationsorpresence /
removal cervical sutures
 Maternal UTI inthe thirdtrimester
3. Unclean deliveryandcordseparation
4. PreviousbabyaffectedwithGBSandmother’srecentGBSstatus unknownornot treatedadequately
b) Suspectedsepsis
If sepsisisclinicallysuspected,antibioticsshouldbe commencedasearlyaspossible afterobtaining
relevantcultures.

8. Choice of antibiotics
Early onset sepsis
Firstline
- Benzyl Penicillin(orAmpicillin) andGentamicin
- add Cefotaxime orreplace GentamicinwithCefotaxime if meningitisis suspected
Secondline (Remembertochoose antibioticcombinationtocoverStaph.andgram negatives)
- Shouldalsoconsiderthe prevalentorganisminthe unitanditsantibioticsensitivityatthatparticular
time period
- Flucloxacillin/cloxacillinwith Amikacin/Cefotaxime.
- Include Cefotaximewithanyof the combinationsinsuspectedmeningitis
Thirdline
Meropenum;+/- Vancomycin (considerincludingVancomycinif staph/MRSA issuspectedspeciallyif
central linesare used).
Initial choice of antibioticsisjudgedbythe clinical scenarioandistherefore the responsibilityof the
medical team.Subsequentlythe antibiotictherapyshouldbe adjustedaccordingtobloodculture
reportsand/orclinical response.
Duration of antibiotic therapy
• Prophylaxis (asymptomaticbaby) –if remainswell andsepsisscreeningisnegative,includingblood
culture reportafter48 hours,stop antibiotics.
• If bloodculture ispositive andCSFisnormal,treatfor 10 days.
• Initiallysymptomaticbaby,screeningnegative andclinicallywellin48 hrs, - repeatFBC andCRP – if
negative stopantibiotic.
• Symptomaticbaby,respondedtotreatmentwithin48hrs and FBC and/or CRP positive butblood
culture negative,treatfor7-10 days.(exclude meningitisif clinicallyindicated).
• Inabove situationsif the initialCRPwashigh,itisbestto treat until itcomesback to normal.
• Beware of CRPwhichmay be persistentlyhighdue tolocal infectionsuchascannulasite infectionor
abscess.
Choice of antibioticsin special circumstances
Provenmeningitis(PositiveCSF)

9. • Empirical therapy for earlyonsetdisease-Penicillin/ampicillin andcefotaxime
• Empirical therapy for the late onsetdisease- cefotaxime
• Definitivetherapy
GBS : Benzyl penicillinfor14 days
Gram negative meningitis:cefotaxime (oraccordingto the culture report) for21 days
CSF positive butno organismisolated- penicillin14daysand cefotaxime 21days.
Pneumonia
• Early onset pneumonia(usuallywithin48hrs)
- Penicillinorampicillinwithgentamicin (alternative optionispenicillinandcefotaxime)
- Duration: 10 days(if the organismisStaphylococcus aureus,anti- staphtherapyfor21 days)
• Late onsetpneumonia(after48 hrs especiallyinventilated babies)
- If the babyisalreadyon antibiotics,broaden spectrumtocoverCONS,pseudomonas(or antibiotics
coveringthe prevalent/colonized bacteria)
- Cefotaximeandvancomycin provide agoodcoverage
- Duration : 7-10 days
- Un-resolving,nonresponsiveneonatal pneumoniamaybe causedby Ureaplasmaurealyticumor
Mycoplasma. Erythromycin/clarithromycin isthe antibioticof choice forboththese pathogens.
Bone and joint infections
• Cefotaxime andflucloxacillin/cloxacillinare the firstline antibioticsuntilthe culture reportisavailable
• IV antibioticsshouldbe continuedfor4-6weeks.
• Vancomycincanbe consideredassecondline therapy
Superficial infections
• Umbilical cordinfection Purulentdischarge withoutperiumbilical erythema:only
local antibiotic
• Umbilical granulomadoesnot needantibiotictherapy;onlyrequirescauterization

10. • Umbilical sepsiswithearlyperiumbilical erythemamaybe treatedwithoral flucloxacillin/cloxacillin
and local therapy.
• If there issignificantperiumbilical erythemaorsignsof sepsisis/are present,startIV flucloxacillin/
cloxacillinandgentamicinorflucloxacillin/cloxacillinandcefotaxime
• If the baby issystemicallyveryunwell MRSA coverwithvancomycinandcefotaxime isabetteroption.
Skin infection
• Staph.skinsepsisshouldbe differentiatedfromnormal neonatal skinconditions.
• If in doubt,startoral therapywithflucloxacillin/cloxacillin.
• If systemicallyunwell,commence IV flucloxacillin/cloxacillinwithgentamicinorcefotaxime.
• Alternativelyforaverysickbaby,combinationof vancomycinandcefotaximeprovideasatisfactory
coverage.
Varicellainfection
• If the motherdevelopsvaricelladuringthe 3 weekspriortodelivery,there isa25% chance of her baby
developingthe illness.
• Prophylaxis:Babiesbornto motherswhodevelopvaricellabetween7daysantenatallyand7 days
postnatally,shouldreceive adose of zosterimmunoglobulin(ZIG),250mg soonafter deliveryorassoon
as possible afterthe motherbecomessymptomatic.Butthisisnotfeasible inSri Lankaas ZIG isnot
freelyavailable.Inthe absence of VZIG,normal immunolobulincanbe given.Inthe absence of both
antiviral treatmentdose (IV aciclovir20mg/kg/dose- 8hrly) canbe givenfor7 days.
Anypretermbabyborn <28weeks,exposedtovaricella (fromasource otherthanthe mother) inthe
neonatal periodshouldbe managedasabove despite maternalimmunestatus.
• Babiesbornto motherswithperinatal varicellashouldbe isolatedfromotherbabiesfrombirth.
• If a neonate developsfeaturesof varicellaevenafterreceivingprophylaxis,IV acycloviristhe
treatmentof choice
Use of bloodproduct as adjuvant therapy in the managementof neonatal sepsis.
• Routine,prophylactictreatmentwithFFPandintravenousimmunoglobulin(IVIG) interm babies,
is/are notrecommendedwhenmanagingneonatalsepsis.
• The routine administrationof IVIGtopreventortreat sepsisinverylow birthweightinfantsisnot
recommendedandthe available evidence isadequatetostate thatthere isno longera need forfurther
trialson thissubjecteither.

11. Complications
Acute-
 Subdural effusion
 Hydrocephalus
 Inappropriate ADHsecretion
Long term-
 Cerebral palsy
 Developmentaldelay
 Deafness
 epilepsy
Preventionofneonatal sepsis
It isbestto focuson practices that have beenshowntoreduce nosocomial infections( handhygiene,
nutrition,skincare andvascular access care) and improvingaculture of intensivecare that
dedicatesitself tothisgoal.
Preventionofinfectioninhospital
• Adhere to6 stepsof hand washing
• Strictasepsisduringproceduresandwhenusingcentral IV lines
• Safe birthingpractices
• Early& exclusive breastfeeding
• Earlyenteral feeds
• Maternal tetanusimmunisation
• Earlydiagnosisandprompttreatmentof all maternal infections
• Nopre-lacteal feeds
• Cordshouldbe keptcleanand dry
• Avoidover-crowding
• Maintainhygiene
• Minimize invasiveinterventionssuchasneedle pricksandIV alimentation
• Do notleave currentlyunnecessaryIV cannulae,CVPlines,catheters,ICtubes etcinsitu

12. • Nurseryenvironmentshouldbe cleananddry
• Ensure roundthe clock watersupply
• Adequate ventilation
• Maintainenvironmental temperature at28 ± 2°C
Antibioticabuse inneonatal units
 Unnecessarycare
 Prolonguse
 Multiple antibiotics
 Nonindicate use of cephalosporin