NEONATAL SEPSIS LAB STUDIES

Neonatal Sepsis Lab Studies:
• Blood, CSF, and urine cultures
o Aerobic cultures are appropriate for most of the bacterial etiologies associated with neonatal sepsis; however, anaerobic cultures are indicated in neonates with abscess formation, processes with bowel involvement, massive hemolysis, and refractory pneumonia.
o A Gram stain provides early identification of the gram-negative or gram-positive status of the organism for preliminary identification.
o Bacterial cultures should generally reveal the organism of infection within 36-48 hours; the subsequent initial identification of the organism occurs within 12-24 hours of the growth.
o Urine cultures are most appropriate when investigating late-onset sepsis.
o Blood and CSF cultures are appropriate for early and late-onset sepsis.
o Because of the low incidence of meningitis in the newborn infant with negative cultures, clinicians may elect to culture the CSF of only those infants with documented or presumed sepsis.

• A CBC and differential may be ordered serially to determine changes associated with the infection, such as thrombocytopenia or neutropenia, or to monitor the development of a left shift or an elevated I/T ratio. Such serial monitoring of the CBC may be useful in aiding the differentiation of sepsis syndrome from nonspecific abnormalities due to the stress of delivery

o The platelet count in the healthy newborn is rarely less than 100,000 per mm3 in the first 10 days of life. Thrombocytopenia with counts less than 100,000 may occur in neonatal sepsis, although this sign is usually observed late in the infection. MPV and PDW have been shown to be significantly elevated in infants with sepsis after 2-3 days of life. These measures may assist in determining the etiology of thrombocytopenia.

o WBC counts and ratios are more sensitive in determining sepsis, although normal WBC counts may be observed in culture-proven sepsis in as many as 50% of cases. Infants who are not infected may also have abnormal WBC counts related to the stress of delivery. A differential may be of more use in diagnosing sepsis. Total neutrophil count (PMNs and immature forms) is slightly more sensitive in determining sepsis than total leukocyte count (percent lymphocyte + monocyte/PMNs + bands). Abnormal neutrophil counts at the time of symptom onset are only observed in two thirds of infants; therefore, neutrophil count does not provide adequate confirmation of sepsis. Neutropenia is also observed with maternal hypertension, severe perinatal asphyxia, and periventricular or intraventricular hemorrhage.

o Neutrophil ratios have been more useful in diagnosing neonatal sepsis; the I/T ratio is the most sensitive. All immature neutrophil forms are counted, and the maximum acceptable ratio for excluding sepsis in the first 24 hours is 0.16. In most newborns, the ratio falls to 0.12 within 60 hours of life. The sensitivity of the I/T ratio has ranged from 60-90%, and elevations may be observed with other physiological events; therefore, when diagnosing sepsis, the elevated I/T ratio should be used in combination with other signs.

• The CSF findings in infectious neonatal meningitis are an elevated WBC (predominately PMNs), an elevated protein level, a depressed glucose level, and positive cultures. The decrease in glucose is not reflective of serum hypoglycemia. The CSF abnormalities are more severe in late onset and with gram-negative organisms. The WBC is within the reference range in 29% of GBS meningitis infections; in gram-negative meningitis, it is within the reference range in only 4%. Reference range protein and glucose concentrations are found in about 50% of patients with GBS meningitis; however, in gram-negative infections, reference range protein and glucose concentration are found in only 15-20%.

• C-reactive protein, an acute phase protein associated with tissue injury, is eventually elevated in 50-90% of infants with systemic bacterial infections. This is especially true of infections with abscesses or cellulitis of deep tissue. C-reactive protein usually rises within 24 hours of infection, peaks within 2-3 days, and remains elevated until the inflammation is resolved. The C-reactive protein level is not recommended as a sole indicator of neonatal sepsis, but it may be used as part of a sepsis workup or as a serial study during infection to determine response to antibiotics, duration of therapy, and/or relapse of infection.

• IgM concentration in serum may be helpful in determining the presence of an intrauterine infection, especially if present over a period of time.

Imaging Studies:
• Chest radiographs may depict segmental or lobar atelectasis, but they more commonly reveal a diffuse, fine, reticulogranular pattern, much like what is observed in RDS. Hemothorax and pleural effusions may also be observed.

• A CT scan may be needed late in the course of complex neonatal meningitis to document any occurrence of blocks to CSF flow, the site where the blocks are occurring, and occurrence of major infarctions or abscesses. Signs of chronic stage disease, such as ventricular dilation, multicystic encephalomalacia, and atrophy, are also demonstrated on CT scan.

• Head ultrasonograms in neonates with meningitis show evidence of ventriculitis, abnormal parenchymal echogenicities, extracellular fluid, and chronic changes. Serially, head ultrasonograms can demonstrate the progression of complications.

Procedures: Lumbar puncture is warranted for early- and late-onset sepsis, although clinicians may be unsuccessful in obtaining sufficient or clear fluid for all the studies. Infants may be positioned on their side or sitting with support, but adequate restraint is needed to avoid a traumatic tap. Because the cord is lower in the spinal column in infants, the insertion site should be between L3 and L4. If positive cultures are demonstrated, a follow-up lumbar puncture is often performed within 24-36 hours after antibiotic therapy to document CSF sterility. If organisms are still present, modification of drug type or dosage may be required to adequately treat the meningitis. An additional lumbar puncture within 24-36 hours is necessary if organisms are still present.