Neonatal Sepsis

Dr Prakash V., Dr. R. Kishore Kumar
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Neonatal Sepsis - Investigations
Septic screen
Consist of total leukocyte counts, absolute neutrophil counts, micro-ESR, immature neutrophils, and CRP are the components of septic screen and if 2 of the above mentioned parameters are positive antibiotics are to be given after sending blood culture. Septic screen are to be used to rule out sepsis rather than ruling in sepsis since it has low specificity but a higher negative predictive value.
Even though blood culture is the gold standard in the diagnosis of neonatal sepsis for quick and accurate diagnosis newer methods of are being tested. Some of the recent developments are physiomarkers and biomarkers.

Heart Rate Characteristics (HRC) and Heart Rate Variability (HRV):
Normal newborns have a beat-to-beat variability in their heart rate and is controlled by various neural inputs. Studies in neonatal sepsis have shown 2 main differences in HRC:
a) Decreased beat-to-beat variability
b) Transient decelerations in heart rate.
The Heart Rate Characteristics index (HRCi) is a statistically derived number, which can predict deterioration of the patient in the next 24 hours. Increase in HRCi predicts increasing risk of clinical deterioration.(5)

1. ACUTE PHASE REACTANTS:
a) CRP:
CRP is the commonest biomarker used in neonatal sepsis. It increases by around 6-18 hours of exposure, and peaks after 48 hours. CRP has a half-life of 18 hours, and hence falls with the resolution of acute phase reaction. CRP is highly specific, however sensitivity is low (6,7). Serial CRP monitoring increases its utility and can also be used in deciding about response as well as duration of antimicrobial therapy.
b) PROCALCITONIN:
This is another acute phase reactant which is produced by 2-4 hours of exposure, and peaks by 24-48 hours. The half life is 25-30 hours. However, there is a physiologic rise of procalcitonin in newborns in the first 2 days of life, which makes it less helpful in EOS(8). The sensitivity and specificity of procalcitonin is around 80%, with particular use in LOS.
Other acute phase reactant proteins such as a-1 antitrypsin, haptoglobin, lactoferrin, fibronectin are also being studied.
2. PRO-INFLAMMATORY CYTOKINES:
a) INTERLEUKIN-6:
Peaks by 2-3 hours of exposure, and falls back to baseline after 6-8 hours. Half life is less than 20 mins. Acute phase reactants like CRP and fibrinogen are induced mainly by IL-6.
IL-6 can also be measured in cord blood of babies with risk of sepsis. It is an early marker of sepsis and has high sensitivity and specificity in both EOS and LOS. The disadvantage is that the short half life causes many false negative results. (9)
b) INTERLEUKIN-8:
Has similar kinetics like IL-6. IL-8 can also be used in detection of EOS from cord blood.
c) TUMOR NECROSIS FACTOR ALPHA:
This is a very early pro-inflammatory cytokine which stimulates the production of IL-6. However it has a lower sensitivity and specificity in diagnosing sepsis.
3. CELL SURFACE MARKERS:
Measured by flow cytometry. Highly sensitive and specific, and the expression begins minutes after exposure. Useful in both EOS and LOS. Requires only about 0.05 ml of blood. However, the cost of sophisticated equipments is a barrier in its routine use.
1. CD11ß:
Can be detected within 5 minutes of exposure. Very high sensitivity and specificity. More useful in EOS than in LOS.
2. CD 64:
Has very high sensitivity and Negative Predictive Value of >95%. When combined with CRP or IL-6, sensitivity reaches 100%, and specificity of >80%.
3. HLA-DR:
May be used as a prognostic test, rather than a diagnostic test.

Helps in identification of the organism. Various techniques available are:
1. Whole-cell Mass Spectrophotometry (WC-MS)
2. Amplification and sequencing of 16S ribosomal nucleic acid.
3. Inter a inhibitor proteins (IAIP)
4. Real time PCR(10)


References
Neonatal Sepsis Neonatal Sepsis 09/05/2018
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