empirical antibiotic therapy jnrnl.pptxy

It shows the presction of empirical antibiotic therapy

1. ASSOCIATION OF APPROPRIATE EMPIRICAL ANTIMICROBIAL THERAPY WITH IN-HOSPITAL MORTALITY IN PATIENTS WITH BLOODSTREAM INFECTIONS IN THE US By Dr. N MAHESH

2. JOURNAL CLUB TITLE “ASSOCIATION OF APPROPRIATE EMPIRICAL ANTIMICROBIAL THERAPY WITH IN-HOSPITAL MORTALITY IN PATIENTS WITH BLOODSTREAM INFECTIONS IN THE US” AUTHORS Tetsu Ohnuma , MD, MPH, PhD; Shingo Chihara , MD; Blair Costin, MD, PhD; Miriam M. Treggiari , MD, PhD, MPH; Raquel R. Bartz , MD, MMCi ; Karthik Raghunathan, MBBS, MPH; Vijay Krishnamoorthy, MD, MPH, PhD TYPE OF ARTICLE RETROSPECTIVE CROSS-SECTIONAL STUDY PUBLISHED January 4, 2023 (JAMA Network Open. 2023;6(1):e2249353)

3. STUDY DESIGN Retrospective cross-sectional study Study included premier healthcare database from 2016 to 2020 The Premier Healthcare database has information on patient demographic characteristics, hospital characteristics, date-stamped billing logs, and ICD-10 diagnosis and procedure codes This study followed STROBE GUIDELINES for cross sectional study

4. INTRODUCTION Blood stream infections are associated with short term mortality ranging from 10-30% So early empirical antimicrobial therapy is important for survival of patients with blood stream infections and sepsis Broad spectrum antimicrobial usage is associated with its resistance and adverse effects

5. INTRODUCTION But due to undertreatment resistant pathogens such as Carbapenem resistant Enterobacterales ,pan resistant Acinetobacter species have been spreading rapidly So there should be balance between over use of broad spectrum antimicrobials and undertreatment of infections

6. INTRODUCTION GRAM POSITIVE COCCI GRAM POSITIVE BACILLI STAPHYLOCOCCUS AUREUS COAGULASE NEGATIVE STAPHYLOCOCCUS BACILLUS CEREUS BACILLUS ANTHRACIS STREPTOCOCCUS PNEUMONIAE STREPTOCOCCUS PYOGENES STREPTOCOCCUS VIRIDANS CLOSTRIDIUM SPECIES ENTEROCOCCUS CORYNEBACTERIUM DIPHTERIA PROPIONEBACTERIUM LISTERIA MONOCYTOGENES GRAM NEGATIVE COCCI GRAM NEGATIVE BACILLI GONOCOCCI E.COLI MENINGOCOCCI KLEBSIELLA PROTEUS PSEUDOMONAS ACINETOBACTER ENTEROBACTER

7. INCLUSION CRITERIA Age > 18 years Positive 1 st blood culture during hospitalisation Patients who received treatment with atleast 1 new systemic antimicrobial agent within 2 days of blood sample collection

8. EXCLUSION CRITERIA Patients who received antimicrobials before blood sample collection Blood cultures showing polymicrobial infections CNS infections Gram Negative Rod infections(other than E.Coli ; Proteus; Pseudomonas; Klebsiella) Blood cultures showing anaerobic infections

9. CHARACTERISTICS 0F PATHOGENS AND SITE OF INFECTION Pathogen profile was divided into 3 categorical levels according to the type of organism Gram Negative Rods Gram Positive Cocci Candida Species This study also assessed the incidence of resistant organisms including MRSA - METHICILLIN RESISTANT STAPHYLOCOCUS AUREUS VRE – VANCOMYCIN RESISTANT ENTEROCOCCUS ESBL Gram Negative organisms CRE - CARBAPENEM-RESISTANT ENTEROBACTERALES

10. CHARACTERISTICS 0F PATHOGENS AND SITE OF INFECTION Bloodstream infections due to coagulase-negative Staphylococcus species were considered as contaminants Bloodstream infections were considered hospital acquired if the first positive blood culture was obtained after 2 days of hospital admission

11. DEFINITIONS Appropriate empirical antimicrobial therapy - I nitiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected Nonsusceptibility to initial empirical therapy - M icrobial profile that was either resistant or intermediate to the new empirical antimicrobial agent Carbapenem resistant Enterobacterales ( CRE) - Resistant to imipenem, meropenem, doripenem , or ertapenem Ceftriaxone-resistant gram negative organisms (CTX-RO) - Including Pseudomonas aeruginosa and ESBL

12. OUTCOMES P rimary end point - In-hospital mortality during the index hospitalization Patient demographic characteristics included age, sex, race and ethnicity and any other racial or ethnic category, payer category , comorbidities , transfer from another hospital, nosocomial infection , primary infection site , and hospital characteristics are included in outcome analysis Study also included intensive care unit admission, vasopressor use, mechanical ventilation, dialysis, creatinine, total bilirubin, and platelet count , which were collected within 2 days after blood sample collection

13. STATISTICAL ANALYSIS Descriptive statistics were used in this study to examine demographic and facility characteristics Data were presented as means and SDs, medians and interquartile range, or counts and percentages Descriptive statistics were used to estimate the frequency distribution of pathogens, antimicrobial resistance profiles, and antibiotic use To estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality - Multilevel multivariable logistic regression models with random intercepts for individual hospitals to account for clustering within hospitals are used

14. STATISTICAL ANALYSIS 3 models were taken for GNRs, GPC, and Candida species separately Additional sensitivity analysis was done by removing markers of disease severity Intensive care unit admission vasopressor use mechanical ventilation Dialysis Analyses were performed using SAS software, version 9.4 (SAS Institute)

15. RESULTS

16. RESULTS

17. RESULTS

18. Out of 32100 patients - Ceftriaxone resistant organisms-9.6% MRSA-13.9% MRSA among patient with staph aureus-43.6% VRE-0.7% Appropriate empirical antibiotic use Gram Negative Rods-94.4% Gram Positive Cocci-97% Candida species-65.1%

19. The proportions of appropriate empirical antimicrobial therapy for non resistant pathogens was higher than resistant pathogens Carbapenem resistant enterobacterales has 55.3%,Vancomycin resistant Enterococcus has 60.4% of appropriate antimicrobial therapy.

20. DISCUSSION In this study they found out that the most frequent gram positive organism was Staph aureus while most frequent gram negative organism was E.coli The proportions of appropriate empirical antimicrobial therapy was higher and better compared to other study Appropriate antimicrobial therapy was lower for resistant organisms Selecting appropriate empirical therapy for resistant organisms remains a challenge even with implementation of antibiotic steward ship program and advanced diagnostic tools

21. DISCUSSION Identification of the potential risk factors for resistant pathogens might help in improving the choice of correct empirical therapy in patients who has likelyhood for resistant infections In this study it is found out that there is low incidence of candidemia but there is discordant use of empirical antifungal therapy The decision to initiate empirical antifungal therapy needs to be made individually based on the risk factor for fungal infections such as(immunocompromised states etc)

22. According to surviving sepsis guidelines early administration of appropriate antimicrobials within one hour is effective to reduce mortality in patients with septic shock In case of sepsis without septic shock we should assess for infectious vs non infectious causes and antimicrobials to be administered within 3 hours if concern for infection persists For patients with sepsis or septic shock and high risk of MDR organisms 2 empirical antimicrobials with gram negative coverage is suggested

23. Initiating empirical therapy depends upon severity of illness, likely pathogens and their source, likelyhood of drug resistance

24. OTHER STUDIES Chanu Rhee et al study found out that most culture positive community onset sepsis do not have resistant organisms however broad spectrum antibiotics are frequently prescribed Both inadequate and unnecessary empirical therapy was associated with higher mortality Nishakantha Arulkumaran et al concluded that reducing antimicrobial care in critical care can have direct impact on reducing mortality Antimicrobials outcomes are varied ranging from drug toxicity to idiosyncratic drug reaction,dysbiosis,immune cell dysfunction.

25. OTHER STUDIES Kim O.Gradel et al study shows that inappropriate empirical antibiotic therapy was predictor of recurrent bacteremia , increased long term mortality rate following bacteremia Sameer S kadri et al concluded that discordant empirical antibiotic therapy was independently associated with increased risk of mortality Most of the incidences of mortality due to discordant antibiotic therapy occurred among the blood stream infection caused by Staph Aureus,Enterobacterales

26. LIMITATIONS OF THE STUDY Study cohort was not necessarily representative of all hospitals No other illness severity score was included – leaving a residual confounding factor Detailed information on the time to adequate source control or the time to antimicrobial administration was unavailable Unable to identify Carbapenem resistant enterobacterales using the Centers for Disease Control and Prevention (CDC) definition because information on carbapenemases was lacking Appropriate doses of prescribed antimicrobial agents was not mentioned Sample size might still have been too small to detect mortality differences for specific pathogens

27. CONCLUSION Every hospital should have their own “Antibiotic policy” depending on the hospital antibiogram Selection of antibiotics should be rationale. Appropriate empirical antibiotic therapy is associated with low in hospital mortality rate.

28. Overveiw of management of Sepsis and Septic shock patients

29. THANK YOU By Dr.n mahesh