Neonatal Sepsis - Sepsis in Newborns

Indications for Testing

Testing for neonatal sepsis is recommended in infants with risk factors for sepsis, including preterm birth with natural onset of labor before 37 weeks of gestation and suspected or confirmed infection in another neonate of a multiple pregnancy (refer to the Quick Answers for Clinicians for more information).  Severe clinical indications that warrant testing for sepsis include apnea, seizures, a need for cardiopulmonary resuscitation or mechanical ventilation, and signs of shock.  Other clinical indications include changes in responsiveness or behavior, feeding difficulties, signs of respiratory distress, and jaundice within 24 hours of birth.  For a complete list of risk factors and clinical indications, refer to the National Institute for Health and Care Excellence guidelines. 

Clinical Definition

Neonatal sepsis is defined as a systemic infection occurring in infants 28 days or younger. Early-onset neonatal sepsis is defined as sepsis presenting within 72 hours of birth, and late-onset sepsis is defined as sepsis occurring after 72 hours. ^, 

Laboratory Testing

Initial Workup of Suspected Neonatal Sepsis

Blood Culture

Blood cultures are used to determine the presence of bacterial or fungal infection. ^,  The specimens for culture should be obtained before beginning antimicrobial therapy, unless doing so will substantially delay antimicrobial administration. ^,  The use of an aerobic culture and an anaerobic culture may optimize identification of both common neonatal pathogens and rare strict anaerobic species.  Antibiotic therapy may still be appropriate in term infants who are critically ill with negative culture results. 

Cerebrospinal Fluid Studies

Ideally, CSF studies should be performed before beginning antimicrobial therapies in newborn infants at highest risk for early-onset sepsis, in addition to blood cultures, to guide antibiotic treatment selection and duration.  The American Academy of Pediatrics (AAP) recommends that newborns with suspected sepsis have a lumbar puncture if they are stable enough for the procedure and it does not delay initiation of antibiotic therapy.  However, CSF studies are not necessary in all infants with suspected sepsis, particularly in term infants with negative blood cultures. 

Other Cultures

The Surviving Sepsis Campaign (SSC)  recommends collecting nonblood specimens (e.g., bronchoalveolar lavage, tracheal aspirate) at the earliest opportunity; depending on the suspected infection site, those specimens may have a higher yield of pathogen identification compared with blood cultures.  Early-onset sepsis cannot be diagnosed with surface cultures or gastric aspirate analysis, and urine cultures are not indicated in infants younger than 72 hours.  Blood cultures remain the standard for diagnosis. ^, 

White Blood Cell Count

The utility of white blood cell (WBC) counts is limited in neonates for the assessment of early-onset sepsis. Many clinical factors other than infection can suppress the bone marrow of neonates, thus affecting the WBC count. 

Blood Lactate

Blood lactate concentrations serve as an indirect marker of tissue hypoperfusion and are included in the definition of septic shock in adults, but the utility of blood lactate has not been well established in infants. If lactate concentrations can be obtained quickly, results can be used as part of the evaluation for sepsis-associated organ dysfunction or septic shock but should not be used to stratify children into risk categories for sepsis or septic shock.  Elevated blood lactate concentrations in children have been associated with adverse outcomes in septic shock, but no threshold has been established. 

Nonspecific Inflammatory Markers

Nonspecific inflammatory markers such as C-reactive protein (CRP) and PCT do not have a role in the initial evaluation of early-onset sepsis.  CRP and PCT concentrations can increase due to a variety of stimuli not specific to sepsis, and PCT naturally increases over the first 24 to 36 hours after birth, so single measurements are not sensitive nor specific to assess the risk of early-onset sepsis or guide care decisions. 

Monitoring

The SSC recommends daily assessment for pediatric patients with septic shock or sepsis-associated organ dysfunction for the purpose of antimicrobial therapy de-escalation. This assessment may include microbiologic assessment, PCT and blood lactate measurement, or assessment of other indicators of infection resolution.  Serial PCT measurements have been used to guide antimicrobial stewardship programs in adults with similar effectiveness in safely reducing the duration of antimicrobial therapy in neonatal populations. 

Trends in blood lactate concentrations are recommended to guide resuscitation of children with septic shock and other sepsis-associated organ dysfunction.