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1 Microbiological evaluation: how to report the results Alvaro Pascual MD, PhD Infectious Diseases and Clinical Microbiology Unit. University Hospital Virgen Macarena University of Sevilla

2 BSI management Prompt pathogen identification is crucial for optimizing antimicrobial therapy in patients with BSIs. Rapid initiation of appropiate antimicrobial therapy is associated with improved outcome and decreases healthcare costs. Delays in microbiological identification increase both patient exposure to broad spectrum antimicrobial and resistance.

3 Inadequate empirical therapy of BSIs 40% of all BSIs 50% of nosocomial BSIs 70% of fungemia 8-20% after final microbiological report is issued

4 Microbiological background Difficulty in reporting microbiological data in a timely fashion. Gram stain is still the most rapid and simple test to characterize microorganisms. The physician is not always informed of preliminary microbiological reports of blood culture (Gram stain.). The physician does not always interpret Gram stain information correctly in an clinical scenario. Information comparing ways of reporting is scarce.

5 Is the Gram stain result of a positive blood culture useful?

6 Gram stain result: An example gram-positive cocci : UNHELPFUL The arrangement should be stated (pairs, chain, clusters, ) Number of bottles and sets Time to positivity

7 Gram stain result: An example gram-positive cocci in chains : Source: Pharynx or skin/soft tissue: A,B, C or G streptococci Gastrointestinal or Genitourinary tract: enterococci Susceptible or resistant to vancomycin?

8 Dilemma In Europe 2014, the Infectious Diseases Specialist is not fully recognized (Spain, Belgium, Luxembourg and Cyprus) and Clinical Microbiologists perform many of the tasks of IDs.

9 482 blood cultures in 374 patients Gram stain information by phone Definitive microbiology report on line Evaluation: Impact of the results of Gram stain on antimcrobial therapy Accuracy of Gram stain results

10 Uehara et al. Am J Clin Pathol 2009

11 In 9 episodes therapy changed after final report In 7 episodes antimicrobials inappropiate because Gram stain Acinetobacter (1) Acinetobacter (6) P. aeruginosa (3) Uehara et al. Am J Clin Pathol 2009

12 Conclusions Gram stain results facilitates the correction of empiric antimicrobial therapy. Episodes in the category of Staphylococcus spp, Pseudomonas spp and related organisms and yeasts showed perfect agreement with culture. Physicians started or changed antimicrobials suitable more frequently than in the other categories. Recognition of Acinetobacter spp by Gram stain remains a challenging problem Uehara et al. Am J Clin Pathol 2009

13 Baron et al. Cumitech 1C: Blood Cultures. ASM The single most important first test to be performed on any positive blood culture is Gram stain and the terminology used to report such results should be as descriptive as possible

14 509 episodes Medical record review: Time of blood culture extraction Time of Gram stain report Time of AST result S. aureus : 20% E. coli: 14% CNS: 13% P. aeruginosa: 12% K. pneumoniae: 5%

15

16 Conclusions Most therapy interventions occurred at the time of phlebotomy and after the notification of Gram stain by phone Release of AST data had the least impact on antimicrobial management

17 Is the method of reporting a Gram stain result of a positive blood culture relevant?

18 Methods of reporting blood cultures 1. Final identification and susceptibility report 2. Gram stain by phone Gram stain written alert + 1 or Gram stain oral alert + 1, 2 or 3.

19

20 Combined microbiological and clinical Group Group A (n: 190) Group B (n: 99) Group C (n: 89) report 297 episodes randomly selected Type of report Conventional information provided: Gram stain by phone + final report (I + S) Written-alert report on clinical chart: A + written-alert in clinical chart (opinion on patient s situation + therapeutic recomendation) Oral-alert report provided: B + direct conversation with physician E. Bouza et al. CID 2004

21 E. Bouza et al. CID 2004

22 Combined microbiological and clinical Recomendation of change in therapy Proportion of days adequate treatment report Group A Group B Group C % 53.1% P<0.001 Mean DDD P=0.03 Mean hospital stay P=0.761 Mortality rate in the late period Antimicrobial costs (mean) E. Bouza et al. CID 2004

23 Conclusions Written or oral alert with clinical advice should complement traditional microbiological report in patients with BSIs. The costs of supporting a reporting system involving ID specialist consultation and clinical microbiologist can be justified by the savings generated from decreased length of stay and decreased costs of therapy E. Bouza et al. CID 2004

24 Is there any method faster and more useful than Gram stain?

25 PNA-FISH Microarrays Multiplex PCR MALDI-TOF Rapid methods Laborious processing and few microorganism

26 Gram stain MALDI-TOF: cell pellet (1 hour later) Monomicrobial: 86% agreement 97.5% Enterobacteriaceae 13.4% AmpC-producers Polymicrobial: 1 isolate at genus level 87%

27 35.1%

28

29 Limitations Only Gram negatives (direct) Only ID consultations (more severe) Few ambulatory cases (impact?) Low ESBL- and MDR prevalence The impact of MALDI-TOF may vary according to epidemiological setting, site where bacteremia was managed, site of infection

30 Pre-post quasi-experimental study: impact of MALDI-TOF plus AS Team in BSIs. AS Team provided therapy recomendations after receiving real time notification of 1)Gram, 2)Identification (conventional or MALDI) and 3)Susceptibility.

31

32 Overnight culture

33

34

35 Limitations Only organims validated for MALDI-TOF. Lack of randomization Number and timing of blood-cultures not standardized Integrated approach (MALDI + AST): impact of each intervention?

36 Conclusion MALDI-TOF could become a vital second step beside Gram stain in guiding the empirical treatment of patients with bloodstream infections.

37 General conclusions Gram stain is still an essential tool in positive blood cultures. Written (plus oral) report from Clinical Microbiologist or ID specialist is the best approach. Uncomplicated cases: Complicated cases: Clinical Microbiologist ID specialist MALDI-TOF is currently an excellent complementary but not alternative tool. More studies needed: Gram positives, Acinetobacter, improving direct identification in blood cultures, polymicrobial,..

38

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