The Culture of Culturing: Laboratory Diagnostic Stewardship

Transcription

1 The Culture of Culturing: Laboratory Diagnostic Stewardship Isabella W. Martin, MD Medical Director of Clinical Microbiology Laboratory, Dartmouth-Hitchcock Medical Center Michael S. Calderwood, MD, MPH Regional Hospital Epidemiologist, Dartmouth-Hitchcock Medical Center March 20, 2019

2 None Disclosures

3 Outline PART 1: The 21 st Century Micro Lab as a Critical Partner in Stewardship PART 2: Translating Enhanced Laboratory Capabilities into Stewardship Success

4 The Microbiology Lab is a Critical Partner in Antimicrobial Stewardship P&T Committee Clinical Microbiology Information Technology Clin Infect Dis 2007;44: ID Physician(s) Antimicrobial Subcommittee ID Pharmacist(s) Hospital Administration Infection Control and Prevention Frontline Providers

5 The Microbiology Lab is a Critical Partner in Antimicrobial Stewardship

6 The Microbiology Lab is a Critical Partner in Antimicrobial Stewardship Pre-Analytic

7 The Microbiology Lab is a Critical Partner in Antimicrobial Stewardship Analytic

8 The Microbiology Lab is a Critical Partner in Antimicrobial Stewardship Post-Analytic

9 PART 1: THE 21 ST CENTURY MICRO LAB AS A CRITICAL PARTNER IN STEWARDSHIP

10 Analytic Phase: Workflow Parasites Bacteria Viruses Fungi Mycobacteria Clin Infect Dis, 2018;66:

11 Analytic Phase: Microbiology s Quest Faster time to detection, identification and susceptibility testing of pathogens Roger Bannister, 1954

12 The Times They Are A-Changin Syndromic Testing MALDI-TOF Mass Spectrometry Total Laboratory Automation Next Generation Sequencing

13 The Times They Are A-Changin Syndromic Testing MALDI-TOF Mass Spectrometry Total Laboratory Automation Next Generation Sequencing

14 Syndromic Testing Single test to rapidly detect the microorganisms most commonly causing an infectious disease syndrome Sample-to-result (24/7 testing) Multiplex nucleic acid amplification tests Sepsis Meningitis/encephalitis Respiratory infections GI illness

15 Many Platforms Many Decisions BDMax (Becton-Dickinson) Verigene (Luminex) FilmArray (BioFire) E-Plex (GenMarkDx) xtag (Luminex) Variation in: chemistries, panel offerings, targets, workflow Sepsis panels: include major resistance determinants -meca, vana/vanb, bla KPC

16 Direct-from-Specimen for Sepsis: T2 BioSystems Bacterial Panel: -E. faecium -S. aureus -K. pneumoniae -P. aeruginosa -E. coli Yeast Panel: -Candida albicans -Candida tropicalis -Candida krusei -Candida glabrata -Candida parapsilosis

17 Faster Susceptibility Testing in Sepsis: Accelerate Pheno System (Accelerate Diagnostics) Sample: Positive blood culture Average time to identification: 90 minutes Fluorescence in-situ hybridization Average time to AST: 7-8 hours!!!

18 New Technology for AST: Morphokinetic cellular analysis

19 Reduction in Time to Result 232 blood cultures (223 monomicrobial) Overall organism identification: 95.6% sensitivity 99.5% specificity Overall antimicrobial susceptibility testing: Essential agreement 95.1% Categorical agreement: 95.5% (1 VM Error, 3 M error) Decrease in time to identification: hours Decrease in time to AST: hours J Clin Microbiol, 2018;56:e

20 Syndromic Testing LOVE IT MUST CONSIDER CAREFULLY Quick turnaround time Common pathogens covered Sensitive Specific $$$$$ Some still need traditional culture in parallel Most lack full AST Most are one size fits all? clinical relevance of all targets

21 The Times They Are A-Changin Syndromic Testing MALDI-TOF Mass Spectrometry Total Laboratory Automation Next Generation Sequencing

22 Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry Species-level identification in minutes from single colony of bacteria or yeast Mayo Clin Proced, 2016;91:

23 Decreased Time to Identification N=952 isolates Average time to ID: 1.45 days earlier than standard methods J Clin Microbiol, 2012;50:3301-8

24 Other Evolving MALDI-TOF MS Applications Identification direct from positive blood culture Focused susceptibility testing Carbapenemase detection Methicillin resistance in Staph aureus Strain typing Mold identification Front Microbiol, 2018; 29: 1097 Clin Micro Newsletter, 2019;41:11-22

25 The Times They Are A-Changin Syndromic Testing MALDI-TOF Mass Spectrometry Total Laboratory Automation Next Generation Sequencing

26 Total Laboratory Automation Eur J Clin Micobiol Infect Dis 2018;37:

27 Bacteriology Workload Clin Microbiol Infect, 2011;17:655-60

28 Total Laboratory Automation -Specimen processing -Barcoding -Plating -Smart incubators -Digital plate reading stations Future: Integrated MALDI spotting

29 Bugs Grow Faster When They Are Left In Peace 41.8 hrs 40.8 hrs 18.5 hrs 16.5 hrs 17.7 hrs 13.6 hrs J Clin Microbiol, 2018;56:

30 The Times They Are A-Changin Syndromic Testing MALDI-TOF Mass Spectrometry Total Laboratory Automation Next Generation Sequencing

31 Next-Generation Sequencing (NGS) Allows sequencing of multiple individual DNA molecules in parallel regardless of composition. Interrogation of all nucleic acids in sample Generates millions to billions of reads per instrument run.

32 Promises of WGS Agnostic pathogen inquiry Direct-from-specimen Fastidious pathogens Slow-growers Possible to predict susceptibilities: Bacteria Mycobacteria Yeast Viruses Strain-typing

33 NGS: Possible Approaches Growth From Pure Culture Clinical Specimen (Microbiota + Pathogen) Clinical Specimen (Microbiota + Pathogen) Amplify Target Gene 0 0 Clin Infect Dis, 2018;66: Detect Only Bacteria Detect Only Bacteria And/Or Host Response

34 Optimizing Specimen Processing Negative Control CSF J Clin Microbiol, 2018;56:e

35 Optimizing Specimen Processing? J Clin Microbiol, 2018;56:e

36 Significant Hurdles $$$$$ Lack of standardization Platforms, data analysis pipelines, reference sequences Susceptibility testing Need comprehensive database of resistance determinants Genotype/phenotype correlation Data storage and analysis Workflow: need fast, comprehensive, validated workflows Outcomes data to justify cost

37 Boutique Laboratories Moving into the NGS Space Market directly to ordering providers Synovial fluid Plasma 1-2 day turnaround time (plus transit time) Optimal role in patient care undefined

38 Final Thoughts Laboratory technology is undergoing seismic changes: faster results but at significant cost Shortage of laboratory technologists to do the work and adopt changes Most hospital budgets operate in silos: Must partner with stakeholders to identify hospitalwide priorities and help justify increased laboratory costs

39 Looking to Another Era of Change Lee JS. When Horses Posed a Public Health Hazard. New York Times June 9, 2008

40 PART 2: TRANSLATING ENHANCED LABORATORY CAPABILITIES INTO STEWARDSHIP SUCCESS

41 Pre-Analytic (Diagnostic Stewardship): Right Test, Right Patient, Right Time Examples: Testing algorithms to limit detection of asymptomatic bacteriuria Testing algorithms to limit detection of C. difficile colonization (without clinical infection) A Rational Approach to Fever in Hospitalized Patients Evolving beyond culture if spikes

42 A Tale of Two Hospitals Hospital A: Focused on reducing urinary catheter utilization 5% reduction in catheter utilization 20% reduction in urine cultures sent CAUTI rate/1,000 device days INCREASED Hospital B: Focused on reducing inappropriate urine cultures 5% increase in catheter utilization 60% reduction in urine cultures sent CAUTI rate/1,000 device days DECREASED Infect Control Hosp Epidemiol 2018;39:1494-6

43 Moving from WTF (Why the Foley) to WTU (Why the Urine) A recent survey of U.S. hospitals participating in the SHEA Research Network found that two thirds of responding hospitals had implemented some version of reflex urine cultures But urinalysis criteria leading to culture varied greatly Most commonly >10 WBC, positive leukocyte esterase, or positive nitrite Infect Control Hosp Epidemiol 2019;40:228-31

44 Unintended Consequence? Important to note, though: The primary goal of reflex urine cultures was to reduce laboratory workload While the hope was that reflex urine cultures would reduce treatment of asymptomatic bacteriuria At least one hospital system found that eliminating reflex urine cultures actually reduced the number of urine cultures performed with a trend toward a decrease in antibiotic use J Clin Microbiol 2016;54:254-8 Am J Infect Control 2016;44:1750-1

45 Improving Indications for Ordering a Urine Culture Some hospitals have begun to publish indications for ordering a urine culture 2 out of 5 U.S. hospitals participating in the recent SHEA Research Network survey Infect Control Hosp Epidemiol 2017;38:186-8 Infect Control Hosp Epidemiol 2019;40:228-31

46 Great opportunity for education Improving Indications for Ordering a Urine Culture 61% of nurses send a urine culture based on urine appearance 73% send a urine culture based on odor IDWeek 2018, Poster 2120, Gao C et al.

47 IDWeek 2018, Poster 2119, Advani S et al. (Yale)

48 28% reduction in unnecessary urine cultures >40% reduction in CAUTIs IDWeek 2018, Poster 2119, Advani S et al. (Yale)

49 But Sometimes Folks Need a Little Nudge IP review of ICU urine cultures with calls to cancel orders not meeting guidelines In another hospital, stewardship team reviewed and found an alternative cause of fever in 100% of cases where UCx canceled IDWeek 2018, Posters 2109 (Shah M et al) and 2111 (Mena Lora AJ et al)

50 Appropriate Testing is Also Important in Diagnosing C. difficile Infection Testing is only appropriate on patients with clinical signs and symptoms of disease 3 or more loose or watery stools within 24hrs AND One or more of the following: Fever, leukocytosis, abdominal pain, nausea/vomiting, evidence of colitis on imaging or colonoscopy Infect Control Hosp Epidemiol 2010;31:431-55

51 Hold on Testing for Limited Diarrhea, Regardless of Smell In toxigenic culture-confirmed (gold standard) hospital-onset C. difficile infection, the median number of bowel movements per 24 hour period was 5 (interquartile range 4-7) J Med Microbiol 2014;63:

52 This Impacts Patient Placement, Public Reporting, and Financial Penalties Studies have found that 29-39% of patients tested for C. difficile did not have clinically significant diarrhea (felt to be underestimated given poor documentation of stool consistency) And one hospital found that 15% of the HO-CDI cases that they had publicly reported had been tested inappropriately. Clin Infect Dis 2007;45: J Clin Microbiol 2011;49: Infect Control Hosp Epidemiol 2016;37:

53

54 The Policy Works In the first year following implementation of this testing policy: 32.5% drop in total tests ordered 20.6% drop in positive results

55

56 Post-Analytic (Antimicrobial Stewardship): Right Interpretation, Right Antimicrobial, Right Time Examples: Pneumonia UTI Improving microbiology reports when cultures negative Rapid detection of respiratory viruses, Impact of selective reporting Bacteremia Incorporating rapid diagnostics into clinical decision making

57 The Power of a Simple Change A 4-hospital health system made the following change in the reporting of unrevealing respiratory cultures: ORIGINAL = Commensal respiratory flora NEW = Commensal respiratory flora only: No S. aureus/mrsa [methicillin-resistant Staphylococcus aureus] or P. [Pseudomonas] aeruginosa Led to: 5.5-fold increased odds of de-escalation in postintervention period 55% reduction in AKI No change in all-cause mortality (with trend favoring improved outcomes in post-intervention period) Open Forum Infect Dis 2018;5:ofy162

58 Sometimes Doing Less is Doing More De-escalation in the setting of culture negative pneumonia has shown similar results in other studies: Shorter hospital/icu LOS Less AKI No difference in mortality, and in some cases better mortality (with the understanding that these patients may be less sick) Has been shown for BOTH Gram positive and Gram negative targeted antibiotics Infection 2010;38: Crit Care 2011;15:R79 Chest 2019;155:53-9

59 Antibiotics Don t Treat Viruses Rapid detection of respiratory viruses leads to a reduced duration of antibiotics J Clin Microbiol 2016;54: Eur J Clin Microbiol Infect Dis 2018;37:779-83

60 Antibiotics Don t Treat Viruses Rapid detection of respiratory viruses leads to a reduced duration of antibiotics BUT Most of the impact comes from positive flu testing Decision to continue antibiotics depends on radiographic findings J Infect Dis 2017;216:936-44

61 Now You See Me, Now You Don t (Part I) In cases of acute uncomplicated cystitis due to E. coli susceptible to multiple antibiotics, one study found that SELECTIVE REPORTING led to a 67% increase in the prescribing of first-line antibiotic treatment Int J Antimicrob Agents 2017;50:258-62

62 Now You See Me, Now You Don t (Part I) Selective reporting has been associated with: Improved fluoroquinolone susceptibilities in Enterobacteriaceae within 12 months of the practice change Reductions in C. difficile J Infect Public Health 2015;8: J Clin Microbiol 2016;54:2343-7

63 Now You See Me, Now You Don t (Part II) Among non-pregnant, non-catheterized adult inpatients, the microbiology lab report on a positive urine culture was changed to: This POSITIVE urine culture may represent asymptomatic bacteriuria or urinary tract infection. If urinary tract infection is suspected clinically, please call the microbiology lab for identification and susceptibility results. Decrease in inappropriate antibiotic treatment without an increase in adverse events Infect Control Hosp Epidemiol 2018;39:814-9

64 Now You See Me, Now You Don t (Part II) Others have shown similar results withholding results on urine cultures unless a team calls Clin Infect Dis 2014;58:980-3

65 The Future of Antimicrobial Stewardship When 72hrs will be too long to act Integrating rapid diagnostics (e.g., PCR, MALDI-TOF) with antimicrobial stewardship associated with: 32-71% relative reduction in time to effective antibiotic therapy 20-48% relative reduction in the time to optimal antibiotic therapy via reductions in unnecessary broad-spectrum antibiotics 33-44% relative reduction in ICU LOS 21-34% relative reduction in hospital LOS Reduced costs % absolute reduction in mortality Clin Infect Dis 2010;51: Clin Infect Dis 2013;57: Arch Pathol Lab Med 2013;137: J Infect 2014;69: Clin Infect Dis 2014;59 Suppl 3:S Clin Infect Dis 2015;61: Clin Microbiol Rev 2016;29: J Clin Microbiol 2016;54: Clin Microbiol Rev 2018;31:e

66 Also Beneficial in Identifying Likely Contaminants More rapid identification of coagulase negative staphylococci in single positive blood culture: Reduced vancomycin days of therapy Reduced hospital LOS Reported to save $30,000 per 100 patients tested Diag Microbiol Infect Dis 2016;84:159-64

67 But Trust is Slow to Develop In a recent study, only 28% of providers made changes based on organism identification by rapid diagnostic testing Providers are more likely to escalate based on a Gram stain Providers are more like to de-escalate based on susceptibilities Change takes time and education is key Open Forum Infect Dis 2018;5:ofy308

68 QUESTIONS