Staphylococcus aureus Bacteremia

Ryan Dare, MD

Assistant Professor, UAMS

Medical Director, UAMS ASP

Co-Medical Director, Baptist Health ASP

Disclosures

• None

Objectives

• Understand and appreciate the clinical significance of S. aureus bacteremia

• Discuss appropriate workup for patients with S. aureus bacteremia

• Define treatment options for S. aureus bacteremia

Staphylococcus aureus Bacteremia (SAB)

Incidence:• 20 per 100K per year: Canada1

• 26 per 100K per year: Scandinavia2

• 39 per 100K per year Australia3

• 50 per 100K per year: United States4

• UAMS SAB admissions 2019 ytd: 75 (1 per 313 admissions)

Highest Incidence:1-2

• Older Age• African Americans• Males• Community-Onset• Hemodialysis patients• IVDUs

1. Laupland KB, Ross T, Gregson DB. 2008. Staphylococcus aureus bloodstream infections: risk factors, outcomes, and the influence of methicillin resistance in Calgary, Canada, 2000-2006. J. Infect. Dis. 198:336 –3432. Benfield T, et al. 2007. Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin. Microbiol. Infect. 13:257–2633. Collignon P, Nimmo GR, Gottlieb T, Gosbell IB. 2005. Staphylococcus aureus bacteremia, Australia. Emerg. Infect. Dis. 11:554 –561.4. Klevens RM, et al. 2007. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298:1763–1771.

What is Staph aureus????

Staph aureus virulence

What is Staph aureus bacteremia (SAB)?

Do patients with staph aureus bacteremia develop metastatic foci?

Vos et al. “Metastatic Infectious Disease and Clinical Outcome in Staphylococcus aureus and Streptococcus species Bacteremia“ Medicine. Volume 91, Number 2, March 2012.

75% of patients with SAB had evidence of metastatic foci on PET imaging.

- Endocarditis- Endovascular- Abscesses (lungs)- Spine

- Septic arthritis- Ocular

SAB Associated Mortality

• Pre-antibiotic era: 83%1

• 1981-1985: 35-36%2

• 1996-2004: 21-27%2

• 2009: 20%3

1. Mendell TH. 1939. Staphylococcic septicemia—a review of thirty-five cases, with six recoveries, twenty-nine deaths and sixteen autopsies. Arch. Intern. Med. 63:1068 –1083.

2. Benfield T, et al. 2007. Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin. Microbiol. Infect. 13:257–263.

3. Turnidge JD, et al. 2009. Staphylococcus aureus bacteraemia: a major cause of mortality in Australia and New Zealand. Med. J. Aust. 191:368–373.

20-30%Mortality

SAB Associated Mortality

Age is strongest mortality predictor1

1. Lamagni TL, et al. 2011. Mortality in patients with meticillin-resistant Staphylococcus aureus bacteraemia, England 2004-2005. J. Hosp. Infect. 77:16 –20.

Minejima, E., et al., Defining the Breakpoint Duration of Staphylococcus aureus Bacteremia Predictive of Poor Outcomes. Clin Infect Dis, 2019.

• Persistence of bacteremia is strong predictor of mortality• Every day of continued SAB is associated with a 16% increase in risk of death

SAB Associated Mortality

How do you treat SAB?

A. Penicillin

B. Nafcillin

C. Cefazolin

D. Vancomycin

E. Daptomycin

https://resistancemap.cddep.org/AntibioticResistance.php

Staph aureus Resistance

1941 penicillin

- 1942 penicillin resistance Staph aureus (PRSA)

1950s Semi-synthetic penicillins (methicillin) and cephalosporins

- 1961 Methicillin resistant Staph aureus (MRSA)

1958 Vancomycin introduced to “vanquish” Staph

- 1997 Vancomycin Intermediate resistant Staph aureus (VISA)

- 2002 Vancomycin resistant Staph aureus (VRSA)

Rate of Resistance:

- 1970 Staph aureus: <5% MRSA

- 1980 Staph aureus: 20% MRSA

- 2000 Staph aureus: 50% MRSA (95% PRSA)

- 2015 Staph aureus: 60% MRSA (LR Hospital))

- 2015 Staph aureus: 69% MRSA (LR LTACH)

- 2018 Staph aureus: 50% MRSA (LR Hospital) ?

Trends in Staph aureus infections

Jones et al. “Vital Signs: Trends in Staphylococcus aureus Infections in Veterans Affairs Medical Centers — United States, 2005–2017”. Vol 68. March 2019

Trends in SAB over last 13 years

Jones et al. “Vital Signs: Trends in Staphylococcus aureus Infections in Veterans Affairs Medical Centers — United States, 2005–2017”. Vol 68. March 2019

Trends in SAB over last 6 years

Kourtis et al. “Vital Signs: Epidemiology and Recent Trends in Methicillin-Resistant and in Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections — United States”. Vol 68. March 2019

Which antibiotic for MSSA SAB?

Cefazolin is favored over Nafcillin• Reduced mortality (OR 0.69)

• Reduced clinical failure (OR 0.56)

• Reduced nephrotoxicity (OR 0.36)

• Reduced hepatotoxicity (OR 0.12)

• Lower probability of discontinuation (OR 0.24)

Shi et al. BMC Infectious Diseases (2018) 18:508

Which antibiotic for MRSA SAB?

Liu et al. CID 2011:52 (1 February)

Daptomycin dosing

Seaton RA, Menichetti F, Dalekos G, Beiras-Fernandez A, Nacinovich F, Pathan R, et al. Evaluation of Effectiveness and Safety of High-Dose Daptomycin: Results from Patients Included in the European Cubicin((R)) Outcomes Registry and Experience. Adv Ther. 2015;32(12):1192-205.

Which antibiotic for MRSA SAB?

• Daptomycin is non-inferior to Vancomycin1

• Linezolid has been associated with increased mortality relative to that with vancomycin in the treatment of catheter- related bloodstream infections*2

• The ARREST trial convincingly demonstrated that adjunctive rifampin has NO role in MRSA bacteremia or native valve endocarditis3

• The CAMERA1 trial found a decreased duration of bacteremia with a combination of vancomycin and flucloxacillin compared with vancomycin monotherapy4

1. Fowler, V. G. Jr. et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N. Engl. J. Med. 355,653–665 (2006). 2. Wilcox, M. H. et al. Complicated skin and skinstructure infections and catheter- related bloodstream infections: noninferiority of linezolid in a phase 3 study. Clin. Infect. Dis. 48, 203–212 (2009).3. Thwaites, G. E. et al. Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double- blind, placebocontrolled trial. Lancet 391, 668–678 (2017).4. Davis, J. S. et al. Combination of vancomycin and beta- lactam therapy for methicillin- resistant Staphylococcus aureus bacteremia: a pilot multicenter randomized controlled trial. Clin. Infect. Dis. 62, 173–180 (2016). 127.

Which antibiotic for MRSA SAB?

• Well designed, multicenter, RCTs are severely needed…….

What else should you do besides start antibiotics?

Basic Essentials of SAB workup

1. Always consider clinically significant:• 20-30% mortality

2. Length of bacteremia & fever is critical for workup, treatment, and prognosis• Repeat BCx q48 hours until negative• If febrile or bacteremic >72 hours, poor prognosis

3. Prompt identification and eradication of source or metastatic foci• Central lines out• Peripheral IV catheters?

4. Exclude Endocarditis• ~20% of all community acquired cases• TEE is preferred

5. Treat aggressively with IV abx for 2-6 weeks• PO abx are a NO-NO

Don’t simply worry about CLABSI….. Ever heard of a PVCR-BSI??

Risk factors associated with SAB:

- Location in AC: OR 12

- Duration >3d: OR 4

- In AC & >3d: OR 50

1. Mermel. 2017;65(10):1757–622. Blauq et al. OFID. 27 February 2019

1 2

Basic Essentials of SAB workup

1. Always consider clinically significant:• 20-30% mortality

2. Length of bacteremia & fever is critical for workup, treatment, and prognosis• Repeat BCx q48 hours until negative• If febrile or bacteremic >72 hours, poor prognosis

3. Prompt identification and eradication of source or metastatic foci• Central lines out• Peripheral IV catheters?

4. Exclude Endocarditis• ~20% of all community acquired cases• TEE is preferred

5. Treat aggressively with IV abx for 2-6 weeks• PO abx are a NO-NO

How do determine duration of abx? 2 vs 4 vs 6 weeks??

Don’t go it alone! Phone a friend!• Multiple studies have shown formal ID consultation enhances guideline-compliant

care, improves clinical outcomes, and decreases mortality in patients with SAB 1-6

• 20% reduction in in-hospital mortality by implementing a mandatory ID consultation for patients with MRSA-SAB 5

• A large multicenter cohort study including 847 SAB patients from 6 academic medical centers in North America showed ID consultation was associated with better adherence to quality measures, earlier discharge, and reduced mortality1

• A meta-analysis of 18 studies accounting for 5,337 patients with SAB revealed ID consultation was associated with reduced 30-day mortality (12.4% vs 26.1%; RR 0.5)6

• 347 UAMS patients with SAB (2014-2017) reviewed revealed guideline-compliant care was higher (93% vs 64%) in patients with ID consultation. Patients who received guideline-compliant care had decreased mortality (3% vs 18%; p<0.01). 7

1. Bai, A.D., et al., Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacterem ia: Results From a Large Multicenter Cohort Study. Clin Infect Dis, 2015. 60(10): p. 1451-61.2. Fowler, V.G., Jr., et al., Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients. Clin Infect Dis, 1998. 27(3): p. 478-86.3. Lahey, T., et al., Infectious diseases consultation lowers mortality from Staphylococcus aureus bacteremia. Medicine (Baltimore), 2009. 88(5): p. 263-7.4. Martin, L., et al., Management and outcomes in patients with Staphylococcus aureus bacteremia after implementation of mandatory infectious diseases consult: a before/after study. BMC Infect Dis, 2015. 15: p. 568.5. Tissot, F., et al., Mandatory infectious diseases consultation for MRSA bacteremia is associated with reduced mortality. J Infect, 2014. 69(3): p. 226-34.6. Vogel, M., et al., Infectious disease consultation for Staphylococcus aureus bacteremia - A systematic review and meta-analysis. J Infect, 2016. 72(1): p. 19-28.7. Lusardi et al. Internal Data.

Take Home Points

• SAB is a BAD NEWS BEARS

• Aggressive Antibiotics and workup is mandatory

• Don’t treat with PO abx and don’t treat <2 weeks

• ID consult