Considerations for antibiotic therapy. Christoph K. Naber Interventional Cardiology Heartcenter - Elisabeth Hospital Essen

Transcription

1 Considerations for antibiotic therapy Christoph K. Naber Interventional Cardiology Heartcenter - Elisabeth Hospital Essen

2 Infective Endocarditis There will never be a cure for this malignant disease! Sir William Osler Gulstonian Lectures

3 Endocarditis: Mortality 1885 Osler Osler Triad 1949 Christie: Penicillin 1956 Vancomycin 1961 Kay: Surgery Ampicillin Methicillin Oxacillin 1988 Erbel: TEE 1994 Durack Duke Criteria % Hunter % Hasbun % Wallace % Cabell % Hoen 2002

4 Effective Antibiotic Therapy Effective antibiotic therapy Ineffective antibiotic therapy

5 Effective Antibiotic Therapy 1. Targeted therapy 2. Appropriate concentration at site of infection 3. Appropriate timing of administration of antiobiotics 4. Bactericidal antibiotics & combination therapy? 5. Ambulatory therapy possible?

6 Culturnegative Endocarditis Author Year Incidene % Tunkel / Lamas / Hogewik /99 12 Rognon / Sandre / Werner / Hoen Block / /

7 Culturenegative Endocarditis Author, Year Abraham, 1984 n 20 Previous antibiotics 16 Fastidious bacteria n.g. Noninfectious n.g. Pesanti, Hoen, n.g. Lamas, n.g. Werner, All (46%) 52(15%) 20(6%)

8 Embolic Risk n=207 Steckelberg et al. Ann Int Med

9 Effective Antibiotic Therapy 1. Targeted therapy 2. Appropriate concentration at site of infection - i.v. versus p.o.? - renal function? 3. Appropriate timing of administration of antiobiotics 4. Bactericidal antibiotics & combination therapy? 5. Ambulatory therapy possible?

10 Endocarditis = Biofilm Infection

11 Endocarditis = Biofilm Infection antibiotic agents antibodies biofilm free floating planctonic bacteria phagozyte device surface peri-device tissue Modified from Trampuz et al. 2003

12 Effective Antibiotic Therapy 1. Targeted therapy 2. Appropriate concentration at site of infection - i.v. versus p.o.? - renal function? 3. Appropriate timing of administration of antiobiotics 4. Bactericidal antibiotics & combination therapy? 5. Ambulatory therapy possible?

13 Concentration Effective Antibiotic Therapy Betalactams (Time over MIC) Aminoglycosides (Peak Concentration) Quinolones (area under the curve) MIC Time Time Time Aministration: 6 times / day once daily 1-2 times / day

14 Effective Antibiotic Therapy 1. Targeted therapy 2. Appropriate concentration at site of infection - i.v. versus p.o.? - renal function? 3. Appropriate timing of administration of antiobiotics 4. Bactericidal antibiotics & combination therapy? 5. Ambulatory therapy possible?

15 Effective Antibiotic Therapy 1. Targeted therapy 2. Appropriate concentration at site of infection - i.v. versus p.o.? - renal function? 3. Appropriate timing of administration of antiobiotics 4. Bactericidal antibiotics & combination therapy? 5. Ambulatory therapy possible?

16 IE Stages of Disease

17 OPAT Andrews MM, von Reyn CF. Patient selection criteria and management guidelines for outpatient parenteral antibiotic therapy for native valve infective endocarditis. Clin Infect Dis 2001;33: Monteiro CA, Cobbs CG. Outpatient management of infective endocarditis. Curr Infect Dis Rep 2001;3: Huminer D, Bishara J, Pitlik S. Home intravenous antibiotic therapy for patients with infective endocarditis. Eur J Clin Microbiol Infect Dis 1999;18:

18 International Collaboration on Endocarditis ~1700 prospective infective endocarditis cases from 16 countries 21% S. aureus 32% Coagulase-negative staphylococci 11% S. bovis Viridans streptococci Enterococcus spp 18% 7% 11% Other pathogens/ culture negative CK Naber et al. EHJ Suppl. 2006

19 Francioli P, Ruch W, Stamboulian D. Clin Infect Dis 1995;21: Francioli P, Etienne J, Hoigne R, Thys JP, Gerber A. JAMA 1992;267: Sexton DJ, Tenenbaum MJ, Wilson WR, Steckelberg JM, Tice AD, Gilbert D, Dismukes W, Drew RH, Durack DT. Clin Infect Dis 1998;27:

20 Fragen?

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22 Gentamicin in S. aureus IE? Ann Intern Med Oct;97(4): Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts: A prospective study. Korzeniowski O, Sande MA. Single (nafcillin for 6 weeks) and combined (nafcillin for 6 weeks plus gentamicin for 2 weeks) drug regimens were compared in two separate multicenter prospective randomized trials. 48 parenteral drug addicts and 30 nonaddicts with clinically and bacteriologically documented Staphylococcus aureus endocarditis were studied. In the addicts, combined therapy effected a more rapid mean clinical response (defervescence and normalization of leukocyte count) and a reduced duration of bacteremia in patients with right-sided endocarditis. In the nonaddicts, combined therapy effected more rapid clearance of bacteremia, but was associated with a higher incidence of azotemia. The addition of gentamicin did not alter morbidity or mortality in either group.

23 Gentamicin in Sepsis 64 Studies 7586 Patients Studies comparing same beta-lactam all-cause fatality RR 1.01 (95% CI ) clinical failure RR 1.11 (95% CI ) Nephrotoxicity RR 0.30 (95% CI ) for monotherapy Paul M. et al.: Cochrane Database Syst Rev

24 Aminoglycosides and Endocarditis Death Clinical Cure Falagas et al. JAC 57 (4): 639. (2006) 24

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26 Isolates (%) Vancomycin Tolerance Tolerant MBC:MIC Ratio (n=105) 74% of hvisa isolates are tolerant to vancomycin MRSA=methicillin-resistant Staphylococcus aureus; MBC:MIC=minimum bactericidal concentration:minimum inhibitory concentration; hvisa=heteroresistant vancomycin-intermediate S. aureus. Jones. Clin Infect Dis 2006;42:S13 24

27 Vancomycin treatment success, % Vancomycin treatment success, % Vancomycin MIC in MRSA infections ,6 P=0.01 9,5 n=9 n=21 Sakoulas Vancomycin MIC 0.5 µg/ml µg/ml Vancomycin MIC 0.5 µg/ml 1.0 µg/ml 2.0 µg/ml P= n=40 n=39 Hidayat Vancomycin MIC 1.0 µg/ml 2.0 µg/ml n=21 n=17 n=25 0 Moise-Broder * Moise * *P-value not reported Success measured as eradication at end of treatment 21 n=13 n=7 n=14 1. Sakoulas G et. al. J Clin Microbiol 2004;42: Hidayat L et al. Arch Intern Med 2006;166: Moise-Broder P et al. Clin Infect Dis 2004;38: Moise P et al. Antimicrob Agents Chemother 2007;51:

28 Proportion patients, % Antibiotic treatment of MSSA bacteraemia b-lactams versus vancomycin for the treatment of MSSA bacteraemia P<0.05 Vancomycin (n=133) b-lactam (n=110) Cure Relapse Death 1. Fowler V, et al. Clin Infect Dis 1998;27:

29 Phase III S. aureus bacteraemia and infective endocarditis study Blood culture + S. aureus Study design and conduct 2 Work-up includes TEE within 5 days Daptomycin 6 mg/kg i.v. q24h Comparator Vancomycin 1 g i.v. q12h + gentamicin 1 mg/kg i.v. q8h 4 days SSP 2 g i.v. q4h + gentamicin 1 mg/kg i.v. q8h 4 days End of therapy (EOT) Outcome 6 weeks Test of cure (TOC) Outcome Primary endpoint SSP = Semisynthetic penicillin (nafcillin, oxacillin or flucloxacillin) TEE = transesophogeal echocardiography Fowler VG, et al. NEJM 2006;355:

30 Success Rate (%) Daptomycin in SAB and Right Sided Endocarditis Daptomycin 70 Vancomycin* + gentamicin Semisynthetic penicillin + gentamicin /45 14/43 33/74 28/60 MRSA MSSA.Fowler VG, et al. NEJM 2006;355:

31 Summary 1. Identify the causative microorganism 2. Use bactericidal antibiotics in an appropriate concentration as i.v. infusion 3. Treat patients generally in the hospital, even eligible candidates should be treated at least two weeks before submitted to your OPAT program 4. Cooperate with an ID specialist and/or a clinical microbiologist 5. Refer to the guidelines!