SEPSIS & BACTEREMIA as approached by an Infectious Disease specialist

1. Karen Brust, MD January 10, 2010 SEPSIS & BACTEREMIAas approached by anInfectious Disease specialist

2. OUTLINE • General introduction to blood stream infections (epidemiology, morbidity/ mortality, etc.) • Classifications • Sources • Dissemination • Management of BSI

3. DEFINITION of BSI BACTEREMIA: - viable organisms cultured from blood Red (+) BCx & Green (-) BCx Seifert, CID 2009; 28:S238-45

4. GENERAL INFO • Estimated 250,000 cases/ year • General associated mortality 16-40% • 13% will die b/c of CAUTI – assoc BSIs • Cost estimated at $25,000/ episode CDC, ’09, Scott.

5. GENERAL INFO • ALL BSI are clinically relevant • Common “contaminants” • Bacillus species, not anthracis • Coagulase negative staph • Corynebacterium species • Propionibacterium • When to be concerned about “contaminants”? • repeatedly positive blood cultures • blood cultures that match other cultures

6. GENERAL INFO • Of staph infections, >50% were MRSA • Of enterococcal, >26% were VRE • Of c. albicans, >10% were fluc resistant • Of all candida spp. 48% were glabrata & kruseii

7. BSI CLASSIFICATION • PRIMARY vs SECONDARY bacteremia • 2° - BCx in the face of a known infection • HAI vs COMMUNITY-ACQUIRED • CAUTI • CLABSI • SSI • GRAM NEG vs POSITIVE vs FUNGAL

8. Seifert, CID 2009; 28:S238-45

9. THE ID APPROACH

10. SOURCE – CASE #1 • HPI: 67 y/o WM admitted w/ 3d hx of malaise and a pre-syncopal event • PMH/PSH: htn, hlp, tob abuse, COPD, afib, diastolic dysfunction, cardiac arrest 6 yrs prior, now, s/p PM placement • MEDS: coreg, MVI, duonebs, lasix, coumadin, ASA • ALL: NKDA • SOCIAL: divorced, lives locally, no unusual field or forest exposures, +tob w/ ½ ppd x 50 yrs plus, no etoh/ drugs

11. SOURCE – CASE #1 PE: AF, 146/85, 90, 20, 100% RA GENERAL: non-toxic, well-appearing HEENT: no significant findings CV: RRR, no m/g/r RESP: CTAB, no w/c/r ABD: NABS, soft, NT/ND, benign EXT: no c/c/e

12. SOURCE – CASE #1 DATA: Blood cx: e. faecalis [(S) amp, PCN, Vanc, gent synergy] Workup so far revealed a negative TEE for valvular vegetations or lead involvement 11 Creat: 1.17 18.8 433K 32 70% N, 15% L

13. SOURCE – CASE #1 WHERE DID HIS ENTEROCOCCUS COME FROM? NEXT STEP: IMAGING

14. SOURCE – CASE #1

15. SOURCE • Important to find source b/c of high chance of relapse if underlying issue not treated • Usual culprits for MRSA: • Intravenous catheters • Intravascular devices • Soft-tissue infections • Pneumonia (especially in the face of mechanical ventilation)

16. SOURCE • CLUES? • S. bovis isolated? Think GI malignancy • Salmonella? vasc/ aneurysmal infection • Pneumococcus in a young pt? Think HIV • Recurrent meningococcus? Think terminal complement deficiency

17. THE ID APPROACH

18. DISSEMINATION - CASE #2

19. DISSEMINATION • Organism-dependent • GPC / Candida >>> GNR • Host-dependent • Immunosuppressed state w/ delayed clearance • Prosthetic material in place • Advanced age and arthritis

20. DISSEMINATION • Candidemia • Enterococcal Septicemia • Staph Bacteremia • FREQUENT SITES OF SPREAD? • Heart valves • Bone & joints • Intervertebral discs • Kidneys • Spleen

21. DISSEMINATION - Candida • RISK • Immunosuppressed status • Chronic intravenous lines • MORTALITY • 2004-2008 data suggest a crude 12 wk Mortality of 35.2% • Isolation of pathogens • C. albicans species? 45.6% • C. non-albicans? 54.4% Horn, CID ’09; 48: 1695-703.

22. DISSEMINATION - Candida • HEART • Infective Endocarditis • 4% risk of seeding • EYES • Endophthalmitis • 5% risk of seeding • Important to identify in order to treat appropriately Horn, CID ’09; 48: 1695-703.

23. DISSEMINATION - Enterococcus • INCIDENCE • 2.3 episodes of bacteremia / 1000 d/c’s • MORTALITY • Crude 30 day mortality 23% • RISK of endocarditis • Higher if BSI is community-acquired • Higher if prosthetic or damaged valve • Higher in IVDU Patterson, Makki, Caballero-Granado.

24. DISSEMINATION - Staph • 4 common risk factors increasing likelihood of 2nd site of involvement: • Community-acquired infection • Skin findings • Fever at 72h • Persistent bacteremia Fowler, Arch Int Med 2003; 163: 2066-2072.

25. DISSEMINATION - Staph • Which patients are at risk? Del Rio, Ana. Patients at risk of complications of staphylococcus aureus bloodstream infections. CID 2009; 48: S246-253. Del Rio, CID 2009; 48: S246-253.

26. DISSEMINATION - Staph • DIAGNOSIS? • Heart valves - TEE • Bone & joints – MRI (vs ortho eval for tap) • Intervertebral discs – especially if arthritic • Kidneys – CT scan • Spleen – CT scan

27. DISSEMINATION - Staph • S. aureus, in general = mc pathogen IE • Right-sided IE in IVDU and left for non-IVDU • Overall estimated risk of infective endocarditis (IE) in face of s. aureus bacteremia (SAB) = 25% • TEE has a greater advantage over TTE in identifying cases • Cases in general but specific advantage in terms of complicated IE (abscess, perforation)

28. DISSEMINATION - Staph Of all SAB, 25% picked up Of the negative TTE, 20% • TEE DATA: Fowler, JACC 1997; 30: 1072-8

29. MANAGEMENT • Define the scenario • Immunosuppressed or not? • Organism? • Source? • Dissemination? • 40 y/o previously healthy female w/ MSSA bacteremia secondary to PICC line infection without metastatic dz, vs • 67 y/o neutropenic female s/p induction chemo w/ candidemia and aortic valve endocarditis

30. MANAGEMENT – by organismCandida • Start empiric therapy with an echinocandin (micafungin, caspofungin, anidulafungin) • Narrow coverage after susceptibilities return • If candida species is fluconazole susceptible, then oral abx therapy is an option • Everyone gets a TEE & an eye exam

31. MANAGEMENT – by organismEnterococcus • Start empiric therapy with a vanc • Narrow or expand coverage after susceptibilities return • If vanc sensitive: guidence by susceptibility pattern • If VRE: daptomycin preferred over linezolid • Everyone gets a TEE • But can debate if clearly nosocomial

32. MANAGEMENT – by organismMSSA or MRSA • Start empiric therapy with vancomycin • Narrow coverage after susceptibilities return • If MSSA: preferred = cefazolin or nafcillin • If MRSA, Vanc MIC of > 2: daptomycin • Special circumstances • If PCN allergic: vanc • If waxing and waning GFR: dapto • Everyone gets a TEE & a daily review of systems

33. MANAGEMENT • CLABSI • Secondary bacteremia w/out met dz • Primary bacteremia w/out metastatic dz • Immunosuppressed • Non-immunosuppressed • Infective endocarditis or equivalent * In order of treatment difficulty

34. MANAGEMENT • CLABSI • Secondary bacteremia w/out met dz • Primary bacteremia w/out metastatic dz • Immunosuppressed • Non-immunosuppressed • Infective endocarditis or equivalent * In order of treatment difficulty

35. MANAGEMENT – CLABSI • General principles • Remove focus if possible • Make an accurate diagnosis • CLABSI: growth of >15 colony-forming units (cfu) from a 5-cm segment of the catheter tip by semiquantitative (roll-plate) culture • BCx from cath tip matches peripheral BCx

36. MANAGEMENT – CLABSI • My standard approach: • Suspect a CLABSI? (Matching BCx (+) from PICC and BCx (+) from periphery) • Pull PICC & culture tip • Establish peripheral iv • The next 3 following days, obtain BCx • Start your 2 weeks of therapy from the 1st set of negative cultures

37. MANAGEMENT – CLABSI *CNS is only pathogen where “saving” the catheter is possible *Staph & candida, it is never possible IDSA guidelines, 2009

38. MANAGEMENT - CLABSI • Staph BSI, 2 weeks EXCEPT: • Diabetic, • Immunosuppressed, • Prosthetic vascular device (stents, PM, etc) • Metastatic foci of infexn, endocarditis, or suppurative thrombophlebitis • Sustained bacteremia

39. MANAGEMENT • CLABSI • Secondary bacteremia w/out met dz • Primary bacteremia w/out metastatic dz • Immunosuppressed • Non-immunosuppressed • Infective endocarditis or equivalent * In order of treatment difficulty

40. MANAGEMENTSecondary bacteremia w/out met dz • In general, 2-4 weeks • Easily “killed” bugs, shorter course • Strep pneumoniae pneumonia and bacteremia – 2 weeks • Not so easily “killed”, longer course • Staph BSI – usually 4 weeks (especially if pt high risk of metastatic dz like prosthetic valve)

41. MANAGEMENT • CLABSI • Secondary bacteremia w/out met dz • Primary bacteremia w/out metastatic dz • Immunosuppressed • Non-immunosuppressed • Infective endocarditis or equivalent

42. MANAGEMENT – Primary bacteremia w/out metastatic dz • In general, 4 weeks • Immunosuppressed: 4 wks minimum • Immunocompetent: you can debate

43. MANAGEMENT • CLABSI • Secondary bacteremia w/out met dz • Primary bacteremia w/out metastatic dz • Immunosuppressed • Non-immunosuppressed • Infective endocarditis or equivalent

44. MANAGEMENT - Infective endocarditis or equivalent • In general, 6 weeks (but dependent on bug) • Remove material when possible (Vasc sx) • Cardiothoracic surgery consultation • When to consult?

45. TAKE HOME POINTS • When in doubt, call an ID specialist • Always pay attention to cultured organisms, even “contaminants” • Find the source; when found, can the source be removed? • Don’t forget your surgical colleagues • Err on the side of longer treatment

46. QUESTIONS?

47. ABBREVIATIONS(just my own, not standardized) • BCx: blood culture • BSI: blood stream infection • CAUTI: catheter-associated UTI • CLABSI: central-line associated BSI • GPC: gram positive cocci • GNR: gram negative rods • IE: infective endocarditis • IVDU: intravenous drug use • MC: most common • SSI: surgical site infection

48. REFERENCES Caballero-Granado, FJ. Attributable mortality rate and duration of hospital stay asoociated with enterococcal bacteremia. CID 2001; 32: 587-94. Del Rio, Ana. Patients at risk of complications of staphylococcus aureus bloodstream infections. CID 2009; 48: S246-253. Fowler, Vance. Clinical identifiers of complicated staphylococcus aureus bacteremia. Arch Int Med 2003; 163: 2066-2072. Fowler, Vance. Role of echocardiography in evaluation of patients with staph aureus bacteremia: experience in 103 patients. JACC 1997; 30: 1072-8 Horn, et al. Epidemiology and outcomes of candidemia in 2019 patients: Data from the prospective antifungal therapy alliance registry. Clinical Infectious Diseases 2009; 48: 1695-703.

49. REFERENCES Makki. Enterococcal bacteremia: clinical features, the risk of endocarditis, and management. Medicine 1988; 67: 248-269. Mitchell, DH. Diagnosis and management of staphylococcus aureus bacteremia. Intern Med J 2005; 35: S17-24. Patterson, JE. An analysis of 110 serious enterococcal infections. Medicine 1995; 74: 191-00 Scott II, RD. The direct medical costs of healthcare-associated infections in US hospitals and the benefits of prevention, CDC, March 2009. Seifert, The Clinical Importance of Microbiological Findings in the Diagnosis and Management of Bloodstream Infections. CID 2009; 28:S238-45. www.idsociety.org