Principles of Antimicrobial Therapy

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1 Principles of Antimicrobial Therapy Doo Ryeon Chung, MD, PhD Professor of Medicine, Division of Infectious Diseases Director, Infection Control Office SUNGKYUNKWAN UNIVERSITY SCHOOL OF MEDICINE

2 CASE 1 F/32 SLE since the age of 21 Medication : 1 week PTA, fever & headache Headache aggravated, diplopia Physical exam. at ER Alert Neck stiffness Bilateral lateral gaze palsy LAB CSF analysis WBC 100 /mm 3 PMN 82% Lympho 5% Glucose 33 mg/dl Protein 41 mg/dl

3 CASE 1 What will you prescribe for empirical antimicrobial therapy in this patient? 1) Ceftriaxone 2) Ceftriaxone + vancomycin 3) Penicillin G 4) Ampicillin 5) Ceftriaxone + ampicillin + vancomycin

4 Antimicrobial therapy Empirical therapy Definitive therapy (Pathogen-specific) Prophylactic therapy

5 Empirical antimicrobial therapy What is the infecting organism? Antimicrobial susceptibility of the infecting organism Host factors

6 Etiology of bacterial meningitis in Korean adults Moon SY, Chung DR, et al. Eur J Clin Microbiol Infect Dis 2010;29:793

7 Etiology of bacterial meningitis in Korean adults Moon SY, Chung DR, et al. Eur J Clin Microbiol Infect Dis 2010;29:793

8 Common underlying diseases or conditions in Listeria meningitis Old age Immunocompromised hosts

9 Etiology of bacterial meningitis in Korean adults Antimicrobial resistance of S. pneumoniae isolates 60% R to penicillin 40% NS to 3 rd G. cephalosporins Moon SY, Chung DR, et al. Eur J Clin Microbiol Infect Dis 2010;29:793

10 CASE 1 CSF culture Listeria monocytogenes

11 CASE 1 What will you prescribe for definitive antibiotic therapy based on the culture report? 1) Ceftriaxone 2) Vancomycin 3) Metronidazole 4) Ampicillin 5) Ciprofloxacin

12 CASE 2 M/76 CC: Lower back pain (onset: 8 days PTA) PI: Physical exam. Systolic heart murmur Mild percussion tenderness at lower back no fever but taking NSAIDs Weight loss of 3 kg since 3 months ago Small purpuric rash on finger tips 3 MA PMHx: Valvular heart disease

13 CASE 2

14 CASE 2 Echocardiography: Moderate eccentric MR d/t anterolateral commissure prolapse Multiple vegetations at mitral valve

15 CASE 2 What will you prescribe for empirical antimicrobial therapy in this patient? 1) Penicillin G 2) Ceftriaxone 3) Vancomycin 4) Ceftriaxone + ampicillin 5) Nafcillin + vancomycin

16 CASE 2 Blood culture : Enterococcus faecalis Antibiotics MIC Susceptibility Benzylpenicillin 4 S Ampicillin <=2 S Ampicillin/Sulbactam <=2 S Imipenem <=1 S Gentamicin High Level (synergy) R Streptomycin High Level (synergy) S Ciprofloxacin 1 S Levofloxacin 1 S Quinupristin/Dalfopristin 2 R Linezolid 2 S Teicoplanin <=0.5 S Vancomycin 1 S Tigecycline <=0.12 S

17 CASE 2 What will you prescribe for definitive antibiotic therapy based on the culture report? 1) Nafcillin 2) Ampicillin/sulbactam 3) Ceftriaxone 4) Vancomycin 5) Ampicillin + streptomycin (i.m.)

18 E. coli Antimicrobial susceptibility test CASE 2 (mg/ml) 18

19 Minimal Inhibitory Concentration (MIC) Broth dilution test bacteria/ml, overnight culture mg/ml Antibiotics MIC =? 19

20 E. coli Antimicrobial susceptibility test (mg/ml)? 20

21 Concentration (mg/ml) Relationship between pk of an antibiotic and susceptibility MIC of organism A 2 1 MIC Breakpoint organism C 0 Time (h) organism B 21

22 Minimal Bactericidal Concentration (MBC) Overnight incubation 64 (mg/ml) Antibiotic-free agar containing media MBC =? 22

23 Enterococcus faecalis Antibiotics MIC (mg/ml) MBC (mg/ml) Penicillin > 6.25 (>100 in 80%) Ampicillin < Cephalothin > 100 Vancomycin > 100 Intrinsic Resistance Penicillin, ampicillin, vancomycin: bacteriostatic Cephalosporins against enterococci Methicillin Infection site requiring bactericidal Aminoglycosides agents? Combination with AGs Acquired Synergy Resistance Ampicillin High or Level Penicillin Resistance G to AGs Vancomycin or teicoplanin HLR to Aminoglycosides 항생제의사용원칙 23

24 In vitro and Animal Models of Antibiotic Synergy Studies on Antibiotic Synergism against Enterococcus Amikacin Ampicillin Ampicillin + Amikacin Iannini PB, et al. Antimicrob Agents Chemother 1976;9:

25 In vitro and Animal Models of Antibiotic Synergy Studies on Antibiotic Synergism against Enterococcus Effect of antibiotics on the uptake of 14 C-labeled streptomycin by enterococci PCN + SM Vancomycin + SM SM SM Moellering RC, et al. J Clin Invest 1971;50:

26 CASE 3 F/43 CC: Upper back swelling after bug bite PI: Previously healthy Painful swelling of upper back days after bug bite Physical exam C 3 cm-sized erythematous swelling with fluctuance, upper back Gram stain of aspirated pus Gram positive cocci in clusters Not improved despite oral antibiotics (cefadroxil) for 5 days Febrile

27 CASE 3 What will you prescribe for empirical antimicrobial therapy in this patient? 1) Penicillin G 2) Nafcillin 3) Vancomycin 4) Ampicillin/sulbactam 5) Clindamycin

28 CASE 3 Staphylococcus aureus 28

29 MRSA prevalence in hospitals Korea Japan Taiwan HK Thailand Vietnam Malta Sri Lanka unknown Singapore < 1 % 1-5 % 5-10 % % % > 50 % Stefani S, Chung DR, et al. Int J Antimicrob Agents 2012;39: Grundmann H et al. Lancet 2006;368: Song JH, et al. ANSORP surveillance ( ) Annual report of the EARS-Net Mejia C, et al. Braz J Infect Dis 2010;14 (Suppl 2):S79-S86. 29

30 Evolution of antimicrobial-resistant S. aureus Hospitals Community Hospitals Community McDonald LC. Clin Infect Dis 2006;42:S65-71

31 Intercontinental Exchanges of CA-MRSA Clones ST72 ST8, ST59, ST80, ST30 DeLeo FR, et al. Lancet 2010; 375:

32 Antimicrobial resistance of S. aureus strains isolated from multicenter bacteremia study in Korea ( ) Antimicrobial agents CA (N=61) Resistance rate (%) CO HCA (N=107) HO (N=201) Penicillin Oxacillin Ciprofloxacin Clindamycin Cotrimoxazole CA: Community-associated CO HCA: Community-onset Healthcare-associated HO: Hospital onset Chung DR, 질병관리본부용역연구보고서 32

33 Distribution of genotype among MRSA isolates from carriers admitting to the SMC 0.9% 0.9% ST1, 6.4% 0.9% 11.3% [ 범주이름 ] [ 백분율 ] ST5, 28.5% ST72, 46.0% Chung DR, Unpublished 33

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