Invasive Staphylococcal Infections Henry F. Chambers, M.D. - PDF document

Invasive Staphylococcal Infections Henry F. Chambers, M.D. Professor of Medicine, UCSF San Francisco General Hospital Disclosures • AstraZeneca – advisory board • Cubist – research grant, advisory panel • Genentech – advisory board • Merck – stock • Theravance – advisory board

Case 1 • 45 year old man with cirrhosis due to alcohol presents with one week of fever, malaise, diffuse arthralgias and shortness of breath • T=39.1 C, P=128, BP=115/65, RR=20 • New 3/6 holosystolic murmur at the Lt. sternal border, radiating to axilla • TTE: 1 x 1.5 cm mitral valve vegetation • 2 of 2 blood cultures growing latex- agglutination test coagulase positive but tube coagulase negative staphylococci Which one of the following organism is most likely causing endocarditis in this patient? 1. Micrococcus luteus 2. Staphylococcus aureus 3. Staphylococcus epidermidis 4. Staphylococcus lugdunensis 5. None of the above, the blood cultures are contaminated

Staphylococcus lugdunensis • Coagulase negative … . – The tube “free” coagulase test is negative – The latex “bound” coagulase (i.e., clumping factor) test may be falsely positive and confuse physicians • Spectrum of disease: virulent, aggressive, similar to S. aureus . – Bacteremia, NV and PV endocarditis – Bone and joint infection – Pacemaker, other device-related infections • Susceptible to many antibiotics (only rarely mecA positive) Coagulase-negative staphylococci • Commensals, not invasive, rarely disseminate, relatively benign clinical course • Spectrum of disease – Vascular catheter-associated bacteremia – Prosthetic device (joint, valve), pacemaker, device-related infections – Neonatal sepsis – Peritoneal dialysis catheter infections • Virulence factors: biofilm formation • Multiple drug resistant (reservoir for S. aureus )

Coagulase-negative staphylococci • Therapy is NOT required if: – Positive intravascular catheter tip culture without signs of infection – Positive intravenous catheter culture with negative peripheral cultures • Catheter salvage may be an option • Removal of prosthetic device generally required for cure CoNS Prosthetic Valve Endocarditis • Prosthetic valve – TEE to assess valve ring abscess; abscess is an indication for surgery – MS CoNS: Nafcillin 2 gm q4h x 6 wks + Rifampin 300 mg q8h x 6 wks + Gentamicin 1 mg/kg q8h x 2 wks – MR CoNS: Vancomycin 30-60 mg/kg 3 divided dose instead of Nafcillin • Endocarditis with implantable cardiac devices – Device removal associated with improved 1-year survival, especially if valve is also infected – Therapy as above

Case 2 Catheter-Associated Bacteremia 38 y/o man, new CHF, alcoholic cardiomyopathy, Hct = 13. He is transfused and on hospital day 3 an upper + lower endoscopy performed. Post- procedure T = 38 o C. The site of the previous IV, d/ c’d post-procedure is tender and red. Two peripheral blood cultures are drawn. The next day he is afebrile and 1 blood culture is growing GPC in clusters. Cultures are repeated and vancomycin is administered. The following day the organism is identified as MSSA and repeat blood cultures show no growth to date. Case 2: Catheter-Associated Bacteremia Which of the following has been shown to improve outcome of S. aureus bacteremia? 1. Treatment with daptomycin instead of vancomycin for MRSA. 2. Echocardiography to rule out endocarditis. 3. Infectious diseases consultation. 4. Gentamicin combination therapy instead of single drug therapy with vancomcyin or nafcillin.

Get an Infectious Disease Consult!! • Amer J Med 123:631, 2010 • J Infect 59:232, 2009 • Emerg Infect Dis 18:1072, 2012 • Infect Dis Clin Pract 20:261, 2012 • Clin Infect Dis 46:1000, 2008 • Clin Microbiol Infect 16:1783, 2010 Case 2 Catheter-Associated Bacteremia You would 1. Continue vancomycin pending blood culture results, d/c if those are negative. 2. Switch from vancomycin to cefazolin pending blood culture results, d/c if those are negative. 3. Continue vancomycin pending blood culture results, plan to treat for at least 14 days if those are negative. 4. Switch from vancomycin to cefazolin pending blood culture results, plan to treat for at least 14 days.

Predictors of Complicated Staphylococcus aureus Bacteremia • Community-onset • Septic shock • Persistent or secondary focus of infection • Prolonged bacteremia on therapy (>48-72h) • Fever > 3 days on therapy • Elderly patient (age > 60 years) • MRSA • Use of vancomycin instead of a β -lactam • Duration of treatment < 10-14 days Nafcillin vs. Other β -lactmas for MSSA • Cefazolin similarly efficacious and better tolerated than nafcillin/oxacillin – Antimicrob Agents Chemother 55:5122, 2011 – Clinical Infectious Diseases 59:369, 2014 – Antimicrob Agents Chemother 58:5117, 2014 – Clin Microbiol Infect 17:1581, 2011 • Ceftriaxone, other β -lactams may be less efficacious – Clin Microbiol Infect 17:1581, 2011 – Int J Antmicrob Agents 44:235, 2014 – (But see Int J Clin Pharm 36:1282, 2014)

Duration of Therapy: S. aureus Bacteremia Duration Indications 14 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 (3 wk), pneumonia (3-4 wk), complicated UTI Clin Infect Dis 49:1, 2009; Clin Infect Dis 52:285, 2011 Case 1: Catheter-Associated Bacteremia You would 1. Continue vancomycin pending blood culture results, d/c if those are negative. 2. Switch from vancomycin to cefazolin pending blood culture results, d/c if those are negative. 3. Continue vancomycin pending blood culture results, plan to treat for at least 14 days if those are negative. 4. Switch from vancomycin to cefazolin pending blood culture results, plan to treat for at least 14 days.

Case 1: Catheter-Associated Bacteremia And if those blood cultures turn positive … – Obtain an ECHO – Search for secondary or metastatic focus – Treat for a minimum of 4-6 weeks What about Echocardiography? • Consider obtaining TTE is all cases of S. aureus bacteremia and especially for the following – Positive blood cultures for 3 or more days – Intracardiac device (pacer, valve) – Secondary/metastatic focus of infection – Relapse or recurrence – Suspected endocarditis on other grounds – Some say community-onset, HD, h/o IVDU but data less convincing Circulation.132:1435-86, 2015.

The Facts about Echocardiography? • TEE is more sensitive than TTE • TEE can visualize smaller vegetations: 5 mm • TEE is better than TTE for prosthetic valve endocarditis • Few data that it improves outcome • Compliance is poor – 379 ECHOS in 877 SAB cases (43%) in one Michigan hospital* *Medicine 92:182, 2013; Lancet Infect Dis 11:208, 2001 Case 3 • 66 yo M with 4 days prior to admission • Admission exam (day 1) – VS: T 39.5C, HR 128, BP 110/60, RR 22 – 3/6 systolic murmur L sternal border – Vasculitic lesions • Labs – Admission blood cultures: MRSA, vancomycin MIC = 2 µg/ml – 2/2 blood cultures from day 3: Gram-positive cocci in clusters – Creatinine 1.2 mg/dl on admission, now 1.8 – Vancomycin trough: 17.5 µg/ml • Hospital course (day 4) – On vancomycin + gentamicin (low dose)

Case 3 You are asked to see the patient for treatment recommendations. You would 1. Continue vancomycin + gentamicin 2. Continue vancomycin + gentamicin and add rifampin 3. D/c gentamicin, continue vancomycin 4. Switch to daptomycin 5. Switch to ceftaroline FDA Approved Agents for MRSA Infections Other than ABSSSI Agent Dose Indications Daptomycin IV 6 mg/kg q24h Bacteremia, R-sided endocarditis* Linezolid PO/IV 600 mg q12h MRSA pneumonia (Also a 1 st Line agent) Vancomycin 15-20 mg/kg Serious MRSA q8-12h Infections Telavancin IV 10 mg/kg q24h HAP/VAP *DO NOT USE DAPTOMYCIN FOR PRIMARY PNEUMONIA!

First Line Choices for MRSA Bacteramia • Vancomycin • Daptomycin See, Holland et al: JAMA 312:1330, 2014 Recommended Vancomycin Dosing • For serious infections (pneumonia, bacteremia) – 15-20 mg/kg IV q8-12h (loading dose of 25-30 mg/kg) – Target trough concentrations of 15-20 µg/ml; target AUC 24 /MIC = 400 (or > 211?*) – Adjust for renal function, actual body weight • For less serious infections (SSTI): – 15 mg/kg q12h (1 gm q12h) – Routine measurement of trough not necessary Clin Infect Dis 52:285, 2011, *Antimicrob Agents Chemother 56:634, 2012

Vancomycin Target Attainment AUC/MIC = 400 vs AUC/MIC = 200 Patel, Clin Infect Dis 52:969, 2011 120" §"Mortality,"" 100" bacteremia" and"endocardiBs" 80" 200"@"15"q12h" 200"@"30"q12h" 60" **"Clinical,""""" micro"" 400"@"15"q12h" 40" response" 400"@"30"q12h" 20" 0" 0.25" 0.5" 1" 2" 4" ** Moise-Broader, Clin Pharmacokinet 43:925, 2004 (LRTI) § Brown, Antimicrob Agents Chemother 56:634, 2012 (Bacteremia) Vancomycin MICs by Method * Hsu, Int J Antimicro Agent 32:378, 2008 * MIC 4-8 µg/ml = VISA, MIC > 16 µg/ml = VRSA