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
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
3PMN 82%
Lympho 5%
Glucose 33 mg/dl
Protein 41 mg/dl
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
Antimicrobial therapy
• Empirical therapy
• Definitive therapy (Pathogen-specific)
• Prophylactic therapy
Empirical antimicrobial therapy
• What is the infecting organism?
• Antimicrobial susceptibility of the infecting organism
• Host factors
Etiology of bacterial meningitis in Korean adults
Moon SY, Chung DR, et al. Eur J Clin Microbiol Infect Dis 2010;29:793
Etiology of bacterial meningitis in Korean adults
Moon SY, Chung DR, et al. Eur J Clin Microbiol Infect Dis 2010;29:793
• Old age
• Immunocompromised hosts
Common underlying diseases or conditions in Listeria meningitis
• Antimicrobial resistance of S. pneumoniae isolates – 60% R to penicillin
– 40% NS to 3
rdG. cephalosporins
Etiology of bacterial meningitis in Korean adults
Moon SY, Chung DR, et al. Eur J Clin Microbiol Infect Dis 2010;29:793
CASE 1
• CSF culture
Listeria monocytogenes
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
CASE 2
• M/76
• CC: Lower back pain
(onset: 8 days PTA)
• PI:
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
• Physical exam.
– Systolic heart murmur
– Mild percussion tenderness at
lower back
CASE 2
CASE 2
Echocardiography:
• Moderate eccentric MR d/t anterolateral commissure prolapse
• Multiple vegetations at mitral valve
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
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
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
CASE 2
E. coli
(mg/mL)
Antimicrobial susceptibility test
19
Broth dilution test
Minimal Inhibitory Concentration (MIC)
4 8 16 32 64 mg/mL
1 2 0.5
MIC = ?
Antibiotics 105 – 106 bacteria/mL, overnight culture
20
E. coli
(mg/mL)
?
Antimicrobial susceptibility test
21
Relationship between pK of an antibiotic and susceptibility
1 2 3 4 5
0
C onc en tra tion ( m g/m L)
Time (h)
MIC of organism A
organism B
organism C MIC
Breakpoint
22
MBC = ?
Overnight incubation
64 (mg/mL)
8 16 32
4
Antibiotic-free agar containing media
Minimal Bactericidal Concentration (MBC)
항생제의 사용 원칙 23
Enterococcus faecalis
Antibiotics MIC (mg/ml) MBC (mg/ml) Penicillin 0.4 – 12.5 > 6.25 (>100 in 80%)
Ampicillin <0.4 – 3.1
Cephalothin 12.5 – 25 > 100
Vancomycin 0.78 – 3.1 > 100
Intrinsic Resistance
Cephalosporins Methicillin
Aminoglycosides
Acquired Resistance
Ampicillin or Penicillin G Vancomycin or teicoplanin HLR to Aminoglycosides
• Penicillin, ampicillin, vancomycin:
bacteriostatic against enterococci
• Infection site requiring bactericidal agents?
• Combination with AGs Synergy
• High Level Resistance to AGs
In vitro and Animal Models of Antibiotic Synergy
Studies on Antibiotic Synergism against Enterococcus
Iannini PB, et al. Antimicrob Agents Chemother 1976;9:448–51 24
Amikacin
Ampicillin
Ampicillin + Amikacin
In vitro and Animal Models of Antibiotic Synergy
Studies on Antibiotic Synergism against Enterococcus
Effect of antibiotics on the uptake of 14C-labeled streptomycin by enterococci
Moellering RC, et al. J Clin Invest 1971;50:2580–4 25
PCN + SM
SM
SM Vancomycin + SM
CASE 3
• F/43
• CC: Upper back swelling after bug bite
• PI:
Previously healthy
Painful swelling of upper back days after bug bite
Not improved despite oral antibiotics (cefadroxil) for 5 days
Febrile
• Physical exam.
– 38.5C
– 3 cm-sized erythematous swelling with fluctuance, upper back
• Gram stain of aspirated pus
– Gram positive cocci in clusters
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
Staphylococcus aureus
CASE 3
Stefani S, Chung DR, et al. Int J Antimicrob Agents 2012;39:273-82 Grundmann H et al. Lancet 2006;368:874-85 Song JH, et al. ANSORP surveillance (2005-2006)
Korea Japan
Singapore
HK Taiwan
< 1 % 5-10 % 10-25 % 25-50 % > 50 % Sri Lanka
MRSA prevalence in hospitals
29
1-5 %
Mejia C, et al. Braz J Infect Dis 2010;14 (Suppl 2):S79-S86.
Annual report of the EARS-Net. 2009.
Malta
unknown
Vietnam Thailand
Evolution of antimicrobial-resistant S. aureus
McDonald LC. Clin Infect Dis 2006;42:S65-71
Hospitals Community
Hospitals
Community
31
ST8, ST59, ST80, ST30
Intercontinental Exchanges of CA-MRSA Clones
DeLeo FR, et al. Lancet 2010; 375: 1557–68
ST72
32
Antimicrobial resistance of S. aureus strains
isolated from multicenter bacteremia study in Korea (2012-13)
Antimicrobial agents
Resistance rate (%)
CA
(N=61)
CO HCA
(N=107)
HO
(N=201)
Penicillin 85.2 92.5 91.5
Oxacillin 35.5 50.5 75.1
Ciprofloxacin 11.3 43.0 60.7
Clindamycin 16.4 25.2 34.3
Cotrimoxazole 3.3 4.7 3.5
Chung DR, 질병관리본부 용역 연구보고서 CA: Community-associated
CO HCA: Community-onset Healthcare-associated HO: Hospital onset
33
Distribution of genotype among MRSA isolates from carriers admitting to the SMC
ST72, 46.0%
ST5, 28.5%
[범주 이름]
[백분율]
ST1, 6.4% 0.9%
0.9% 0.9%
11.3%
Chung DR, Unpublished
