The Challenge of Managing Staphylococcus aureus Bacteremia

Transcription

1 The Challenge of Managing Staphylococcus aureus Bacteremia M A R G A R E T G R A Y B S P F C S H P C L I N I C A L P R A C T I C E M A N A G E R N O R T H / I D P H A R M A C I S T A L B E R T A H E A L T H S E R V I C E S P H A R M A C Y E D M O N T O N A B

2 DISCLOSURES: Speaker has no disclosures to make

3 OBJECTIVES: By the end of this talk, attendees should be able to: 1. describe the epidemiology and differences in Staphylococcal aureus infections (MSSA/MRSA) 2. determine what tests/procedures are done to investigate for complications associated with Staphylococcal aureus bacteremia 3. describe the different treatment regimens for S. aureus bacteremia 4. understand why evidence is growing to support greater involvement of infectious disease specialists in care of these patients.

4 CASE STUDY: CC: 40 yo male presented to physician with 2 week history of dysuria, decreased urinary stream and intermittent fever. PMHx: Nephrolithiasis, eczema Past Meds: None Physical Exam: Unremarkable Allergies: None Urinalysis: + leukocytes, + blood nitrites Urine Culture sent: Ultimately + S. aureus (S ciprofloxacin) Rx: Ciprofloxacin 500 mg po BID x 7 days (Dx Presumed prostatitis) Follow up: Patient completed course, but returned to ER with ongoing fever (39.5C), chills, rigors, myalgias, lightheadedness. Treatment failure? Why?

5 Staphylococcus aureus Gram positive cocci in clumps Coagulase positive Facultative aerobe can live in abscesses Commonly found as commensal organism on skin, nares, axillae, pharynx, vagina Biofilm production important consideration in deep seated infections (prosthetics) Divided into MSSA (methicillin-susceptible S. aureus) and MRSA (methicillin-resistant S. aureus) Highly virulent as pathogen (toxin production) Common cause of wide spectrum of infections Propensity to seed various areas of body (heart valves, joints, epidural space, lungs)

6 Discussion of MSSA and MRSA Methicillin-susceptible Staphylococcus aureus started as penicillin susceptible organism Resistance has developed over time with the use of antibiotics meca gene encodes alternative PBP 2A resulting in high level beta-lactam resistance Staphylococcal chromosomal cassettes (SCC) types I-XI are mobile cassettes of genes containing meca SCCmecII and SCCmecIII Large SCCs which carry resistance to multiple antibiotics (more than beta-lactams) No room for virulence and toxin producing factors SCC meciv (and others) Small SCC confers resistance to beta-lactams only: smaller size allows greater mobility Several associated virulence factors including PVL, superantigens (resulting in fever, shock), exfoliatins (scalded skin syndrome), and others

7 Staphylococcus bacteremia One of leading causes of bacteremia in hospitalized patients One of leading causes of infective endocarditis! Definitive diagnosis is by blood culture Evaluation should also include search for source of infection Consider echocardiogram to assess for infective endocarditis Echocardiography recommended for (IDSA Guidelines): MRSA bacteremia TEE preferred (A-II) Central line associated blood stream infection (CLABSI) when catheter removed and where short course therapy is considered (B-II) TEE sensitivity greater than TTE for the detection of infective endocarditis in S. aureus bacteremia

8 IDSA Recommendations for CRBSI Diagnosis Obtain blood cultures prior to start of antibiotics Repeat in 2-4 days (on antibiotic) to demonstrate clearance For suspected catheter-related blood stream infections: Collect paired samples from catheter and peripheral vein (A-II) If peripheral sample not available collect at least 2 blood samples from different catheter lumens (B-III) For diagnosis of Catheter Related Blood Stream Infection (CRBSI): Growth of same organism from both samples (A-I) When comparing catheter sample with peripheral sample colony count from catheter at least 3 times that of peripheral count OR differential time to positivity where growth from catheter noted at least 2 hours before growth from peripheral sample (A-II)

9 Sites of S. aureus infection RETROSPECTIVE COHORT (N=91) JClinMicro 2006 Indwelling lines/catheters 26.4% Skin/soft tissue 13.2% Bone/joint 7.7% Respiratory 6.6% Wound 5.5% Abdominal 3.3% Urinary tract 2.2% Other 9.9% Unknown source 25.3% PROSPECTIVE COHORT (N=52 Cancer nonneutropenic patients) JClinOncol 2000 Tissue infections included wound, SSI, cellulitis, pneumonia, septic arthritis, other local infection Source: Tissue 44% Intravascular device 42% No identifiable source 13% **33% had identifiable metastatic foci of infection including 15% with infective endocarditis

10 PREDICT Risk Factors Non-validated risk prediction scoring system for endocarditis and need for TEE Scoring System on Day of S. aureus Bacteremia Diagnosis: Risk Factor Points Implantable Cardiac defibrillator 2 Permanent Pacemaker 3 Community onset bacteremia 2 Healthcare-associated bacteremia 1 Performance of Score 2: Sensitivity 64.7% Specificity 70.2% Negative predictive value 93.3%

11 PREDICT Risk Factors Scoring System for Risk on Day 3 Culture Results: Risk Factor Implantable Cardiac defibrillator 2 Permanent Pacemaker 3 Community onset bacteremia 2 Healthcare-associated bacteremia 1 Bacteremia enduring 72 hours 2 Performance of Score 3: Sensitivity 86.7% Specificity 59.2% Negative predictive value 96.9% Points

12 Treatment Remove source of infection lv lines Implanted hardware (infected) Valve(s), pacemakers Possible debridement Treatment outcomes poorer if infected material left in situ Duration of Therapy not studied 14 days? 4-6 weeks? Infectious Disease consultation

13 Treatment Options (MSSA) Beta lactams always best option Evidence of reduced mortality vs vancomycin Reduced treatment failure vs vancomycin Cloxacillin 2 g IV q4h vs Cefazolin 2 g IV q8h? Multi-centre, retrospective, cohort study (Toronto Antimicrobial Stewardship team) compared agents in Staphylococcal bacteremia related to mortality and relapse 354 patients over 4 years ( ) found no significant difference in mortality or relapse 70% patients received cloxacillin Death at 90 days: Cefazolin 20%/Cloxacillin 30% Relapse at 90 days: Cefazolin 6%/Cloxacillin 2% Case matched 90 cases from each group cefazolin had HR of 0.58 (95% CI ) for 90 day mortality

14 Treatment Options (MRSA) Beta lactams no longer an option What is strength of evidence for vancomycin? Role of vancomycin levels in managing therapy? First line therapy still considered vancomycin 15 mg/kg dosed based on renal function Consider loading dose (25-30 mg/kg) to speed time to therapeutic trough (15-20 mg/l) Daptomycin Usual dose 6 mg/kg IV daily Can dose at 8-10 mg/kg IV daily for management of resistance and for IE Can not use in setting of potential lung involvement Linezolid Bacteriostatic Treatment duration unclear as for MSSA

15 Benefit ID Consultation 4 cohort studies have shown consistent results Latest one: Retrospective cohort of 6 academic and community sites ( ) Assessed Quality of care, mortality, LOS with ID consult Quality measures included echocardiography, repeat BC, removal of infectious foci, antibiotic therapy Results: Quality Measure ID Consult No ID Consult Echocardiography 371 (73%) 91 (56%) P < Repeat BC 2-4 days 207 (41%) 107 (31%) P = Foci removal Empiric antimicrobials 474 (94%) 297 (87%) P = Treatment duration 285/422 (68%) 141/262 (54%) P = Death 104 (21%) 100 (29%) HR = 0.72 (95% CI ) NS

16 Back to Case Was this patient s infection really a S. aureus prostatitis? If not, what was source of infection? Based on understanding of infection, what treatment recommendations would you make? Any tests you would also recommend?

17 Questions? MARGARET GRAY BSP FCSHP M A RG A RET.GRAY@A LBERTAHEA LTHSERVICES.CA

18 References J Clin Microbiol 2002;Nov 40(11): Clin Infect Dis 2015; May 15;60(10):1451. Clin Infect Dis 2015 Jul 1;61(1):18. J Clin Microbiol 2006 Apr;44(4):1342. J Clin Oncol 2000 Mar;18(5):1110. J Antimicrob Chemo 2015 May; 70: