Usefulness of multiplex molecular diagnostics in diagnosis and management of critical infections in Picu- A single center retrospective analysis

Abstract

Background : Sepsis forms a major cause of morbidity and mortality in children.Currently, the gold standard for diagnosis for sepsis is culture. However, they suffer from low yield, delay in providing actionable results and inability to grow fastidious organisms and fungus quickly enough to guide therapy in time. Newer molecular methods like multiplex polymerase chain reaction(PCR) systems have been recommended by Infectious Disease Society of America (IDSA) to improve the yield as well as time to intervention in these life threatening emergencies. Syndrome Evaluation System (SES) is one such test which has shown benefits in neonatal sepsis. Methods : In this retrospective case series, we analysed 57 paediatric cases admitted to our PICU during October 2015 to February 2017. The clinical presentations were sepsis, systemic infections, meningitis and febrile neutropenia. SES is a multiplex PCR based molecular diagnostics involving DNA extraction, multiplex amplification of virulence specific genes followed by sequence specific hybridization. Blood,Cerebrospinal fluid( CSF) and other focal specific samples like Bronchoalveolar Lavage(BAL), etc were tested by SES as well as routine cultures. Decision to change antimicrobial therapy was based on culture and sensitivity results, as well as SES. Outcomes were recorded. Results : 57 cases (28 males, 29 females, mean age 5.72±4.34 years) were analysed. SES and corresponding Blood cultures were done for 26 patients, of which 4 had positive blood cultures, yielding a detection rate of 15.4% vs 26.9% 7 by SES (7/26) .24 CSF and 7 other body fluid samples underwent both cultures and SES. All these cultures were negative. SES was positive in 5 (20.8%)CSF and 7 (100%) other body fluids. Overall, the yield was7.0% for cultures vs33.3% by SES. SES was positive in 89.5% and 94.7% of CRP and Procalcitonin positive cases respectively. SES was negative in 87.7% and 93.3% of CRP and procalcitonin negative cases respectively. Among CSF cell count positive and negative cases, SES was positive and negative in 30% and 81.2% cases respectively. SES results were available to us within 24 hours, as compared to 48 hours for traditional culture. Out of 19 SES positive cases, we escalated antimicrobials in 10 and de-escalated in 9. In 38 SES negatives, we de-escalated antimicrobials in 16 , escalated in 1 and made no change in remaining 21. In effect 36 /57cases (63.15%), underwent change in antimicrobial therapy based on SES results. Conclusion : In this retrospective analysis, we have seen a 4.75 fold increase in detection rates using SES, as compared to traditional culture. SES results seem to correlate with CRP and Procalcitonin. Most importantly, SES results elicited change in antimicrobial therapy in 63.15% of the cases. The fact that we de-escalated antibiotics and antivirals, with no adverse clinical course, shows that emerging molecular diagnostics like SES have good negative predictive value. We feel that molecular diagnostics in PICU setting, used in conjunction with traditional culture, may reduce antimicrobial usage and overall cost of therapy.