Sepsis is a leading cause of neonatal mortality. Early and accurate diagnosis of sepsis will improve clinical outcomes and reduce overuse of antibiotics. As a significant proportion of the affected neonates are asymptomatic, early diagnosis of sepsis is often challenging. Though blood culture is the gold standard investigation for diagnosis, the positivity rate is low as it depends on blood volume inoculated, level of bacteremia and intrapartum antibiotic use. Molecular assays including polymerase chain reaction and hybridization methods have rapid detection time compared to blood culture. However, detection of pathogen DNA in the absence of viable organisms and false negative results due to the presence of inhibitors require careful scrutiny. A Point of Care (POC) test provides a rapid medical diagnosis for the treating physician in real time and is very useful in emergency situations or resource limited settings. POC tests for early sepsis detection, especially non-invasive techniques are gaining importance in the community setting.

Over 100 biomarkers have been tested for use in sepsis. Some of the important biomarkers are i) acute phase proteins like C-reactive protein (CRP), Procalcitonin (PCT), and Serum Amyloid A (SAA), ii) proinflammatory cytokines such as interleukin-6 (IL-6), iii) biomarkers of activated neutrophils and monocytes like CD64, iv) infectious organism related proteins, receptors, anti-inflammatory markers and v) biomarkers for organ dysfunction [1]. Diagnostic sensitivity can be improved by serial measurements of biomarkers and diagnostic accuracy can be enhanced using multiple markers. However, new biomarkers and POC tests require meticulous validation before being recommended for routine use.

In the article by Sharma et al. published in current issue of IJP, authors have evaluated the diagnostic accuracy of SAA and have compared the biomarker with procalcitonin for diagnosis of neonatal sepsis. Blood specimen for sepsis screen, culture, high sensitivity CRP (hs-CRP), PCT and SAA were obtained prior to initiating antibiotic therapy. Receiver operating characteristics curves were used for determining optimum cut off level of the biomarkers tested. Among 74 neonates with suspected sepsis, clinical sepsis and culture positive sepsis was noted in 37.8% and 16.2% respectively. With a cut-off level of 25.4 mg/L, SAA had sensitivity, specificity, positive predictive value and negative predictive value of 53.6%, 80.4%, 62.5% and 74.0%, respectively for diagnosis of clinical sepsis. The authors have concluded that SAA is comparable to procalcitonin and hs-CRP for diagnosis of neonatal sepsis [2]. Kinetically, SAA appears promising enough to be used as a solitary marker. However, we need to assess how birth weight and gestational age affect the neonates’ capacity to secrete SAA following sepsis before recommending the use of SAA as a POC test [3].

An ideal biomarker for sepsis is expected to increase rapidly in response to stimuli, have a continued elevation to confirm detection and decrease the requirement for repeat tests [4]. According to “ASSURED” guidelines of World Health Organization (WHO), a faultless POC test should be rapid, sensitive, specific, affordable, user friendly, equipment free and deliverable. So far, there is no perfect solitary biomarker available for routine use. A combination of biomarkers may be prudent like a fast-acting marker like IL-6 in addition to PCT and/or CRP. Omics technology and machine learning may offer useful diagnostic and prognostic models for the future [5].