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San Francisco General HospitalUniversity of California San Francisco
Disclosures of Financial Relationships with Relevant Commercial Interests
• None
45 year old man, one week of back pain. He is afebrile and vital signs are normal; normal exam except for tenderness to palpation of the lower back. MRI shows L3-L4 discitis, hyperemic marrow; 1 of 3 blood cultures are positive for coagulase-negative staphylococci.Which one of the following would you recommend?A. Bone biopsy with culture as the blood isolate is likely a
contaminantB. Request a slide-coagulase test of the blood isolateC. PET-CT to look for another focus of infection for biopsyD. Fungal serologies, PPD
45 year old man, one week of back pain. He is afebrile and vital signs are normal; normal exam except for tenderness to palpation of the lower back. MRI shows L3-L4 discitis, hyperemic marrow; 1 of 3 blood cultures are positive for coagulase-negative staphylococci.Which one of the following would you recommend?A. Bone biopsy with culture as the blood isolate is likely a
contaminantB. Request a slide-coagulase test of the blood isolateC. PET-CT to look for another focus of infection for biopsyD. Fungal serologies, PPD
Duration of MRSA Bacteremia on TherapySan Francisco General 2008-12
0
20
40
60
80
100
120
140
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
N E
piso
sde
Days
63%
8% 10%4% 5%
2% 1% 4%0% 0% 0% 0%0.5% 0.5% 0.5%
81% 13% 6%
• Endocarditis, endovascular source• Metastatic infection • Retained catheter or foreign body• Vancomycin instead of β-lactam for MSSA
In patients with S. aureus bacteremia follow-up blood cultures should be obtained until negative.
A. TrueB. False
In patients with S. aureus bacteremia follow-up blood cultures should be obtained until negative.
A. TrueB. False
For patients with Staph. aureus bacteremia which one of the following statements about echocardiography is true? A. Echocardiography is not associated improved outcomes of
patients with Staph. aureus bacteremia B. Transesophageal ECHO should be obtained in all patients
with S. aureus bacteremiaC. Transthoracic and transesophageal ECHOs have comparable
sensitivities for diagnosis of Staph. aureus endocarditisD. Transthoracic and transesophageal ECHOs have comparable
specificities for diagnosis of Staph. aureus endocarditis
For patients with Staph. aureus bacteremia which one of the following statements about echocardiography is true? A. Echocardiography is not associated improved outcomes of
patients with Staph. aureus bacteremia B. Transesophageal ECHO should be obtained in all patients
with S. aureus bacteremiaC. Transthoracic and transesophageal ECHOs have comparable
sensitivities for diagnosis of Staph. aureus endocarditisD. Transthoracic and transesophageal ECHOs have comparable
specificities for diagnosis of Staph. aureus endocarditis
ECHO and Mortality in S. aureus Bacteremia
0
0.2
0.4
0.6
0.8
1
1.2
TEE TTE ECHO nos No ECHO
Adju
sted
Odd
s R
atio
VA Study: JAMA Intern Med 177:1489, 2017
12769(29)
5522(15)
2054(5.6)
18523(50)
Numbers on bars indicate number of patients (%)
Role of echocardiography and what
modality used for S. aureus bacteremia
Depends on the pre-test probability• Consider TTE in all patients with SAB
§ Possible exception: HCA + no intracardiac devices + no
On day 9 of nafcillin therapy for complicated methicillin-sensitive S. aureus bacteremia the patient has developed new neutropenia (1,000 neutrophils). MICs (μg/ml) of the blood isolate are penicillin 0.12 (S), cefazolin 0.5 (S), vancomycin 1 (S), daptomycin 0.5 (S), ceftaroline 0.5 (S). Which one of the alternative agents would you recommend? A. PenicillinB. CefazolinC. VancomycinD. Daptomycin
On day 9 of nafcillin therapy for complicated methicillin-sensitive S. aureus bacteremia the patient has developed new neutropenia (1,000 neutrophils). MICs (μg/ml) of the blood isolate are penicillin 0.12 (S), cefazolin 0.5 (S), vancomycin 1 (S), daptomycin 0.5 (S), ceftaroline 0.5 (S). Which one of the alternative agents would you recommend? A. PenicillinB. CefazolinC. VancomycinD. Daptomycin
Beta-lactam vs. Vancomycin for MSSA Bacteremia(122 VA hospital study) – Multivariable Analysis
Variable Mortality, Harzard Ratio (95% CI)
Beta-lactam vs vancomycin
0.65 (0.52-0.80)
ASP or cefazolin vs vancomycin
0.57 (0.46-0.71)
Clin Infect Dis 61:361, 2015
Penicillin for Treatment of Staph. aureus Endocarditis per AHA guidelines
• Recommended by AHA as second-line agent for native valve endocarditis
• Overall mortality no worse, may be better with cefazolin compared to ASPs (See also: Shi, BMC Infect Dis. 2018; 18:508)
• Clinical failure rates and recurrences similar
• Anxiety over the inoculum effect, which may adversely impact outcome in a subset of cefazolin-treated patients (See also Miller, Open Forum Infect Dis. 2018; 5:ofy123).
A patient with complicated MRSA bacteremia on day 9 of
therapy with daptomycin q48h develops myalgias with a
creatinine kinase of 1250 u/L (upper limit of normal 200).
The last positive blood culture was on day 3 of therapy.
MICs (μg/ml) of the isolate are as follows: vancomycin 2
• MIC < 1.5 μg/mL (low) versus MIC > 1.5 μg/mL (high)
• Mortality low = 25.8%, high = 26.8%
• Adjusted risk difference = 1.6% (-2.3 to 5.6%), p = 0.43
Kalil, JAMA 312:1552, 2014.
• Vancomycin MIC = 1.5 to 2 μg/ml not a reliable predictor of clinical failure and not a reason to alter therapy
• Vancomycin MIC > 2 μg/ml is a reliable predictor of nonsusceptibility and clinical failure and another agent should be used
But what about that vancomycin MIC of 2 μg/ml?
36 year old female injection drug user with R hip pain, decreased ROM 2/2 pain; 2/2 blood cultures + for MSSA; CXR, right hip x-ray, CT abdomen and pelvis, MRI, TTE all normal. Treated with empirical vancomycin, blood cultures sterile after 1 day of therapy, now on day 5 of nafcillin. Pain much improved on day 7, but she still uses a cane for ambulation. Which one of the following antibiotics would you recommend for a 6 week course?
A. DalbavancinB. CeftriaxoneC. VancomycinD. Cefazolin
36 year old female injection drug user with R hip pain, decreased ROM 2/2 pain; 2/2 blood cultures + for MSSA; CXR, right hip x-ray, CT abdomen and pelvis, MRI, TTE all normal. Treated with empirical vancomycin, blood cultures sterile after 1 day of therapy, now on day 5 of nafcillin. Pain much improved on day 7, but she still uses a cane for ambulation. Which one of the following antibiotics would you recommend for a 6 week course?
A. DalbavancinB. CeftriaxoneC. VancomycinD. Cefazolin
Duration of therapy for SABDuration Indications14 days • Fever resolves by day 3
• Sterile blood culture after 2-3 days• Easily removed focus of infection• No metastatic infection (e.g., osteo)• Negative echo, no evidence of endocarditis• No predisposing valvular abnormalities • No implanted prosthetic devices• (No DM, immunosuppression)
4-6 weeks + • Failure to meet one or more of above criteria • Osteomyelitis, endocarditis, epidural abscess,
septic arthritis, pneumonia, complicated UTI
Which one of the following combinations have been shown to improve outcome of patients with S. aureus bacteremia or native valve endocarditis?
A. Anti-staphylococcal beta-lactam + gentamicin for MSSAB. Anti-staphylococcal beta-lactam + rifampin for MSSAC. Vancomycin + a beta-lactam for MRSA or MSSA, pending
culturesD. No combination regimen
Which one of the following combinations have been shown to improve outcome of patients with S. aureus bacteremia or native valve endocarditis?
A. Anti-staphylococcal beta-lactam + gentamicin for MSSAB. Anti-staphylococcal beta-lactam + rifampin for MSSAC. Vancomycin + a beta-lactam for MRSA or MSSA, pending
culturesD. No combination regimen
• 758 patients, 388 SOC and 370 SOC + rifampin• 40% deep tissue, 30% diabetics, 1y% IVDU, 6% MRSA, Mean of 62h
pre-randomization antibiotics• Primary outcome composite of treatment failure, recurrence,
death at 12 weeks
Lancet. 2017 Dec 14. pii: S0140-6736(17)32456-X. doi: 10.1016/S0140-6736(17)32456-X.
Monotherapy versus Combination Therapy for S. aureus Bactermia
• No high quality RCT has ever demonstrated improved outcomes of combination antimicrobial therapy over monotherapy
• Studies suggesting a possible benefit of combination therapy are low quality, retrospective, and based on subjective outcomes not mortality, recurrence, metastatic infections
Should ID consultation be obtained for all patients with S. aureus bacteremia?
A.YesB.No
Should ID consultation be obtained for all patients with S. aureus bacteremia?