1. 1 25th ECCMID - 2007, Munich, Germany Magnitude of bacteremia predicts one-year mortality Kim O. Gradel 1, Henrik C. Schønheyder 1,2, Mette Søgaard 1, Claus Dethlefsen 1, Henrik Nielsen 1 1 Aalborg Hospital, Aarhus University Hospital, Denmark 2 Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

2. 2 25th ECCMID - 2007, Munich, Germany Prognostic bacteremia studies with magnitude of bacteremia 8 studies: –Old (range 1952-1995)‏ –Few patients (range 20-464)‏ –Often selected patient groups and bacteria –No multivariable analyses used –Only in-hospital mortality reported –Prognosis generally worsened with higher magnitude of bacteremia

3. 3 25th ECCMID - 2007, Munich, Germany Study type One-year follow-up study Population based Registry study: –Registries linked via the personal identification number (unique number given to all Danish residents)‏

4. 4 25th ECCMID - 2007, Munich, Germany Setting North Jutland County, Denmark Background population: ~500,000 residents (~9% of Denmark’s population)‏ All acutely ill patients admitted to the nearest hospital in their county Centralized clinical microbiology service

5. 5 25th ECCMID - 2007, Munich, Germany Registries North Jutland Bacteremia Registry –Microbiological and clinical data Hospital Discharge Registry –Discharge diagnoses, coded by physicians Civil Registration System –Vital status, incl. date of emigration and death

6. 6 25th ECCMID - 2007, Munich, Germany Inclusion criteria Study period: 1996-2004 Adults (16 years and older) Mono-microbial bacteremias First-time bacteremias

7. 7 25th ECCMID - 2007, Munich, Germany Blood culture system, I BacT/Alert® Automatic colometric detection of CO 2 produced by growing micro-organisms Incubation up till 7 days ~30 mL blood in each specimen, distributed equally in 3 bottles (2 aerobic, 1 anaerobic)

8. 8 25th ECCMID - 2007, Munich, Germany Blood culture system, II

9. 9 25th ECCMID - 2007, Munich, Germany Blood culture system, III

10. 10 25th ECCMID - 2007, Munich, Germany Aims 1.Is ”Magnitude of bacteremia” (bacterial growth in 1, 2, or 3 blood culture bottles) associated with short-term and long-term all-cause mortality? 2.Is this consistent within strata: –Age –Comorbidity –Speciality (medical, surgical)‏

11. 11 25th ECCMID - 2007, Munich, Germany Variables Primary exposure: 1, 2, or 3 bacteria positive blood culture bottles in the patient’s initial blood culture (BC) set (BC index 1 [ref.], 2, or 3) Outcome: All-cause mortality Covariates: –Age –Gender –Charlson comorbidity score –Speciality –Acquisition of infection –Focus

12. 12 25th ECCMID - 2007, Munich, Germany 6 Tumor, metastatic AIDS 3 Moderate/severe liver disease 2 Hemiplegia Diabetes (type 1 and 2), with complications Any tumor Leukaemia Lymphoma 1 Myocardial infarction Congestive heart failure Peripheral vascular disease Cerebrovascular disease Dementia Chronic pulmonary disease Connective tissue disease Ulcer disease Mild liver disease Diabetes (type 1 and 2), without complications ScoreDisease category Charlson comorbidity index Overall score: 1Overall score: 0Overall score: 2Overall score: 4

13. 13 25th ECCMID - 2007, Munich, Germany Methods BC index distribution, overall and stratified Kaplan-Meier survival curve estimates, overall and stratified Cumulative mortality, standardized to the age and comorbidity distribution in the BC index 1 group Cox-regression analyses: –Crude –Adjusted, overall –Adjusted, stratified

14. 14 25th ECCMID - 2007, Munich, Germany Study population 6406 patients 53.6% males Median age: 72 years

15. 15 25th ECCMID - 2007, Munich, Germany BC index distribution The overall BC index distribution was U-shaped: –BC index 1: 1993 (31.1%)‏ –BC index 2: 1174 (18.3%)‏ –BC index 3: 3239 (50.6%) Generally few deviations from the overall BC index distribution within strata 92.5% were facultatively anaerobic

16. 16 25th ECCMID - 2007, Munich, Germany Kaplan-Meier mortality curves, all BC index 3 BC index 2 BC index 1

17. 17 25th ECCMID - 2007, Munich, Germany Kaplan-Meier mortality curves, medical patients (n = 3842) ‏ BC index 3 BC index 2 BC index 1

18. 18 25th ECCMID - 2007, Munich, Germany Kaplan-Meier mortality curves, surgical patients (n = 1691) ‏ BC index 3 BC index 2 BC index 1

19. 19 25th ECCMID - 2007, Munich, Germany 365-day cumulative mortality, standardized to age or comorbidity distribution as in the BC index 1 group

20. 20 25th ECCMID - 2007, Munich, Germany Cox-regression, overall results 1.4 (1.2-1.7)‏ 1.3 (1.1-1.6)‏ 0-7 days Mortality rate ratios (95% CIs) for BC index 3 (BC index 1 = reference)‏ 1.5 (1.2-1.8)‏ 1.4 (1.1-1.7)‏ 8-30 Days31-365 days 1.1 (1.0-1.3)‏ BC index, age, gender, comorbidity, speciality, acquisition of infection, focus 1.1 (0.9-1.2)‏ BC index, age, comorbidity 1.1 (0.9-1.2)‏BC index (crude)‏ Covariates

21. 21 25th ECCMID - 2007, Munich, Germany Cox-regression, age groups 1.1 (0.9-1.4)‏1.4 (1.0-1.9)‏1.1 (0.8-1.4)‏ >80 1.0 (0.8-1.2)‏1.6 (1.2-2.2)‏1.4 (1.1-1.9)‏ 65-80 1.3 (1.0-1.7)‏1.0 (0.6-1.5)‏1.5 (1.1-2.2)‏ 16-64 31-365 days8-30 Days0-7 days Mortality rate ratios (95% CIs) for BC index 3 (BC index 1 = reference)‏ Age, years

22. 22 25th ECCMID - 2007, Munich, Germany Cox-regression, comorbidity 1.0 (0.8-1.2)‏1.1 (0.7-1.6)‏1.1 (0.8-1.5)‏ 0 1.0 (0.8-1.3)‏1.7 (1.2-2.5)‏1.5 (1.1-2.0)‏ >2 1.2 (1.0-1.5)‏1.4 (1.0-1.8)‏1.4 (1.1-1.8)‏ 1-2 31-365 days8-30 Days0-7 days Mortality rate ratios (95% CIs) for BC index 3 (BC index 1 = reference)‏ Charlson score

23. 23 25th ECCMID - 2007, Munich, Germany Strengths of the study Population-based High statistical precision Complete follow-up

24. 24 25th ECCMID - 2007, Munich, Germany Limitations of the study “Magnitude of bacteremia” assessed by indirect (i.e., semi-quantitative) method Secondary data sources No information on severity of bacteremia (e.g., as described in the APACHE score system) or blood biochemistry parameters

25. 25 25th ECCMID - 2007, Munich, Germany Conclusions, I In general, BC index 3 patients had ~4% higher one-year mortality compared to BC index 1 patients For medical patients, BC index 3 was a marker of short-term mortality (~0-30 days) For surgical patients, BC index 3 was a marker of long-term mortality (beyond ~30 days)‏

26. 26 25th ECCMID - 2007, Munich, Germany Conclusions, II BC index was also associated with the cumulative mortality, but baseline patient characteristics (age, comorbidity) were more important The overall trends differed between some strata.

27. 27 25th ECCMID - 2007, Munich, Germany Thank you! Danke! Tak!