biofire presentation.pptx

multiplex pcr and early diagnostics for sepsis

1. Biofire: Utility in critical care Dr Aditya Nath Shukla Regency Healthcare Kanpur

2. Sepsis and mortality Key contributor to mortality ( 10-45%) Prompt recognition and appropriate management is key to success Early initiation of appropriate antimicrobials is key to survival Early identification of pathogen is key Conventional diagnostic methods have prolonged TAT Need for rapid diagnostics

3. A Fast Diagnosis Can Ensure Timely Treatment, Which May Reduce Mortality Mortality rate (%) Mortality Rate of Sepsis, Severe Sepsis, and Septic Shock 1 Timely treatment is essential to prevent the progression of sepsis to septic shock and reduce mortality 1 -3 Alberti C et al, for the European Sepsis Study Group. Am J Respir Crit Care Med . 2005;171(5):461-468. Shorr AF et al. Crit Care Med . 2011;39(1):46-51. Moore LJ et al. Surg Clin North Am . 2012;92(6):1425-1443.

4. Sepsis and antimicrobial resistance Delay in appropriate antimicrobials is directly related to mortality Explosion in use of broad spectrum antibiotics Hesitancy and resistance to de escalate antibiotics Emergence of antibiotic resistance Not all sepsis is because of bacteria (high TAT for cultures) Need to conserve use of antibiotics to prolong them

5. Goals of Rapid Diagnostic Testing (RDT) Decreases time to identification of pathogen from days to hours Can distinguish between viral vs bacterial infections Allows streamlining to appropriate therapy Facilitate the decision about whether or not to prescribe antibiotics Prevent the use of unnecessary antibiotics .

6. Goals of Rapid Diagnostic Testing (RDT) Facilitates de-escalation Decreased antimicrobial resistance Many studies have shown decreased Duration of illness Length of stays Costs 30-day all cause mortality .

7. Impacts of rapid diagnostic testing in optimizing antimicrobial selection Source: adapted from Goff, DA et al. (2012) Using rapid diagnostic tests to optimize antimicrobial selection in antimicrobial stewardship programs. Pharmacother 32(8): 677-687.

8. Rapid Diagnostic tests Gram-positives, Gram-Negatives, Yeast PCR (polymerase chain reaction) GeneXpert (Cepheid); FilmArray ( Biofire ) & others Turnaround time @60min PNA FISH (peptide nucleic acid fluorescence in situ hybridization) GNR Traffic Light PNA FISH ( AdvanDx ), Yeast Traffic Light PNA FISH ( AdvanDx ) Turnaround time @90min Nucleic Acid Verigene ( Nanosphere ) Turnaround time @120 – 150min MALDI-TOF matrix-assisted laser desorption ionization-time of flight MALTI Biotyper (Bruker Daltonics ); VITEK MS ( bioMerlieux ) Turnaround time 10-30min; very expensive; no resistance markers

9. BIOFIRE Multiplex realtime PCR assay Syndromic approach to identification of pathogen Tests for a comprehensive group of targets Targets updated over period of time with new emerging pathogens of concern Identification of mechanism of resistance Results are fast and accurate if performed appropriately

10. Tests for a variety of pathogens that cause respiratory, blood, and gastrointestinal infections, as well antimicrobial resistance genes Comprehensive Run time of about 1 hour Fast 2 minutes of hands-on time Easy FilmArray: The Fastest Way to Better Results

11. Biofire film array panels Tests for viruses, bacteria, yeast, parasites and resistance genes Panels available: Respiratory Blood culture identification Gastrointestinal Meningitis/ encephalitis Pneumonia Bone and joint infection

12. Respiratory panel Under EUA by FDA 15 viruses and 4 bacteria including (SARS COV 2) Sample nasopharyngeal swab TAT45 min Identified

13. Comparative study pre and post implementation of rapid respiratory panel ( Biofire) Patiients > 3months of age Acute respiratory illness Prior to implementation of RRP all patients were subjected to PCR for RSV, Influenza A & B, Para influenza 1-3

14. Shorter time to identification of pathogen Shorter time duration of antibiotic use Shorter length of hospital stay Shorter time of isolation stay

15. Meningitis/ encephalitis panel 14 pathogens Sample CSF (0.2ml) TAT of 1 hour CSF culture positive only 75-80%, PCR can be used to rule out bacterial meningitis and thus reduce antibiotic use >10% of all viral encephalitis have normal CSF findings, all viral meningitis should be initiated with acyclovir and continued till second PCR is negative

16. ME Panel

17. 13 studies 3764 pts 3000+ pooled In analysis Senstivity 90% specificity 97% 11 % false positive ( streptococcus pneumonia) False negatives HSV1-2, enterovirus and cryptococcus Index methods ( bacterial culture, viral PCR, Cryptococcal Ag of fungal culture

18. Our experience 59 yrs male h/o fever 3 days Altered sensorium for 24 hrs Corresponding blood sugar 88mg% CSF Biofire ME panel: Found to be HIV + ve

19. Our experience Treatment modified on D1 as per CSF ME panel ART added as CD4 counts low D4 Antibiotic cover modified Patient discharged in 10 days time

20. Our experience 66 yrs old /Female Non diabetic Left D4-5 dermatomal vesicular lesions for 4 days Altered sensorium and restless 2 days MRI: non committal CSF: clear, Sugar 53, Proteins84, cells60 all mononuclear, few RBC

21. Our experience 66 yrs old /Female Non diabetic Left D4-5 dermatomal vesicular lesions for 4 days Altered sensorium and restless 2 days MRI: non committal CSF: clear, Sugar 53, Proteins84, cells60 all mononuclear, few RBC Most commonly used panel in our setup Able to identify pathogen in less than 6 hrs time Treatment titrated accordingly Able to reduce antibiotic use

22. Pneumonia panel 33 targets Semiquantitative results Sample: sputum, BAL, MiniBAL TAT 1 hr Resistance genes

23. Pneumonia panel Claimed sensitivity of 96.2% specificity of 98.3% Found to vary between 75% to 91% against cultures Data limited in ICU population ( most on antibiotics and frequent MDRO)

24. Our experience 85 years old female k/c COPD , DM2 on inhalers Presented with fever for 2 days, cough for 2 days breathlessness for 1 day CXR : Diffuse opacities bilateral lower lobes ABG: respiratory acidosis with hypoxia, intubated and ventilated Routine investigation, ET secretions for stain, C&S, Biofire pneumonia panel S Procal 2.5 ng, CRP 28 Broad spectrum antibiotics, nebulized bronchodilators, steroids other supportive management

25. Our experience

26. Our experience Tt Modified Antibiotics descalated Patient improved with routine management Weaned off ventilator

27. 24 yrs old female k/c autoimmune encephalitis, seizure disorders History of recent hospital admission for refractory status Presented with c/o fever 2 days, depressed consciousness 1 day, respiratory distress 1 day In shock with resp distress Intubated ventilated and resuscitated TLC 750, S PCT 15ng CXR Left lower lobe consolidation HRCT < B/l Basal consolidation Biofire : BAL

28. Pneumonia panel only provides semiquantitative results Does not distinguish between dead and live bacteria and virus Negative report does not totally rule out bacterial/ viral infection Concomitant cultures are needed for recovery of isolated and susceptibility results Detection of resistant genes can guide choice of initial antibiotic cover which has to be modified as per report of culture and clinical response

29. Blood culture identification panel 43 targets ( Bacteria both Gram + ve and – ve ; yeast and resistance genes TAT 1 hr Sample is positive blood culture

30. Biofire: advantages vis a vis culture Fast time to pathogen detection and identification of resistant profiles detection of virus and atypical pathogens Multiple targets at same time Detection of pathogens even with ongoing antibiotics Better utilization of antibiotics Potential positive impact on : nosocomial pneumonia management, LOS, cost of treatment, antimicrobial stewardship program, better infection control practices, prevention of spread

31. Biofire: disadvantages vis a vis culture Over detection ( problems with clinical decision making) Presence of resistant genes may not be due to true pathogen Initial cost of equipment and test panels Not widely available Needs further studies for validation of results

32. THANK YOU