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Appropriate antimicrobial therapy
ผศ.สทธพร ภทรชยากล คณะเภสชศาสตร
มหาวทยาลยสงขลานครนทร
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OUTLINES
Introductions
Appropriate Empirical Therapy
Appropriate Documented Therapy
Appropriate Dose
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Introductions
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IMPORTANT RESISTANT ORGANISMS
เชอแกรมลบ ESBL-KP/EC Carbapenems (CBP)
Pseudomonas aeruginosa CBP+Abx
Acinetobacter baumannii CBP+ Abx, Colistin,Sulbactam
Stenotrophomonas maltophilia Cotrimoxazole, levoflox,tigecycline
เชอแกรมบวก Streptococcus pneumoniae Ceftriaxone, Vanco.
Staphylococcus aureus Vanco., Linezolid,Dapto.
Enterococcus spp. Vanco., linezolid
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BAD NEWS: INCREASING RESISTANT GRAM (-)
ESBL- Escherichia coli/Klebsiela pneumoniae:
2be: ดอตอ oxyimino cephalosporins แตไวตอ cefoxitin, carbapenems
และ bata-lactamase inhibitor
AmpC: ดอตอ oxyimino cephalosporins, cefoxitin, bata-lactamase
inhibitor แตไวตอ carbapenem
CTX-M: 2be กลมใหมทดอตอ cefotaxime > ceftazidime แตเรมพบ
CTX-M-15, CTX-M-55 ในประเทศไทยทดอตอ ceftazidime ดวย
KPC: 2f ดอตอ carbapenems แตไวตอ beta-lactamase inhibitor
NDM-1 ดอตอ carbapenems (metallobetalactamase; Bush 3)
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BAD NEWS: INCREASING RESISTANT GRAM (-)
MDR Acinetobacter baumannii:
Carbapenem-resistant A. baumannii (CRAB): IMP-1, OXA-
23, MBL พบในประเทศไทย
MDR Pseudomonas aeruginosa
Carbapenem-resistant P. aeruginosa (CRPA): loss of OprD
(มผลตอ imipenem มากกวา meropenem), MexOpr
system (มผลตอ meropenem มากกวา imipenem แตก
ไมเปน frank resistance)
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ASIA-PACIFIC DATA ON CARBAPENEM-R-ORGANISMS
IJAA 2011;37:225-9.
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WHAT WILL HAPPEN IF WE LET IT BE?
มลคายาตานจลชพเพมสงขนอยางมหาศาล
อตราการดอยาเพมสงขนจนถงจดท เปน MDR (multidrug resistance)
ไมรจะใชยาอะไร เกดความหลากหลายในการเลอกใชยา และใชยาอยางไมมหลกฐานทางวชาการ
ผปวยเสยชวตมากขน
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CID 2004;38(Suppl4):S341-5, *AAC 2002;46:2920-5, *JAMA 1998;280:1233-7. $EID 2002;8:802-7, $Ann Intern Med 2001;135:175-83., 1Eur Soc Clin Microbiol Infect Dis 2005;11(Suppl5):4-16
WHICH ABX ? เชอดอยา ยาททาใหเกด Selective pressure
MRSA Ceftazidime, 3rd Ceph., Ciprofloxacin, quinolones
VRE Ceftazidime $, 3rd Ceph.$,vanco.$, ciprofloxacin$, quinolones$
P. aeruginosa
- Imipenem-resistant Imipenem* , quinolones1
- MDR Ciprofloxacin, quinolones
A. baumannii
- Beta-lactam-resistant Ceftazidime, 3rd Ceph
- Carbapenem-resistant Carbapenems1 , quinolones1
- Not specified Ciprofloxacin, quinolones
ESBL-KP Ceftazidime, 3rd Ceph., Ciprofloxacin, quinolones
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DEFINED DAILY DOSE AND RESISTANCE RATE
JAC 2004;53(2):290-6.
Meropenem usage
Meropenem resistance
ciprofloxacin usage
ciprofloxacin resistance
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Appropriate Empirical Therapy
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Appropriate Empirical Therapy
Selection of Antimicrobial Agents Timing of initiation of antimicrobial
therapy
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Selection of Antimicrobial Agents
site of infection & most bacteria colonized that site patients risk factors to infected with drug
resistant pathogens e.g. prior knowledge of bacteria known to colonized a
given pt community acquired Vs hospital acquired h/o of antibiotic use other risk factors for specific drug resistant bacteria
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Selection of Antimicrobial Agents
local antibiogram severity of infections patients characteristics: Allergic history,
organ dysfunctions pharmacokinetic /pharmacodynamic of
antibiotics
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Selection appropriate ATB for empirical therapy
risk of treatment failure Vs risk of antibiotic
resistance in the future
Benefit of broad spectrum or combination
therapy
Immunocompromised hosts
Immunocompetent hosts: severe sepsis and septic
shock, IE, gram negative bacteremia
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Empirical Therapy
Inadequate treatment of infection in critically ill
patient associated with poor outcome e.g.
increased mortality, morbidity, LOS
Mayo Clin Proc 2011;86 (2):156-67
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Curr Infect Dis Rep DOI10.1007/s11908-011-0206-8
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Risk factors for ATB resistance
P. aeruginosa A. baumanii ESBL producing GNB
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Risk factors for MDR P. aeruginosa
Risk factors OR; 95%CI references
admitted to ICU room occupied by pt with MDR P. aeruginosa
2.3; 1.2-4.3 Clin Microbiol Infect 2011; 17: 1201-1208
Surgery 1.9;1.1-3.6 Clin Microbiol Infect 2011; 17: 1201-1208
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Risk factors for MDR A. baumanii
Risk factors OR; 95%CI references
admitted to ICU room occupied by pt with MDR A. baumanii
4.2; 2-8.8 Clin Microbiol Infect 2011; 17: 1201-1208
mechanical ventilator 9.3;1.1-83 Clin Microbiol Infect 2011; 17: 1201-1208
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Risk factors for IR A. baumanii bacteremia
Risk factors OR; 95%CI
Recent A. baumanii VAP 16.74,95%CI 3.16-88.79
Greater number of intra vascular devices
3.93, 95% CI 1.9-13
Infection(2010)38:173-180
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Risk factors for IR A. baumanii bacteremia
Risk factors OR; 95%CI
Longer duration of hospital stay until A.baumannii isolation
1.043; 1.003-1.084
Previous antibiotic use 5.051; 1.004-25.396
ICU stay 3.1;1.398-6.873
Infection(2010)38:173-180
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Cross-Transmission of Multi drug-Resistant A. baumannii Clonal Strains Causing Episodes of Sepsis in
a Trauma Intensive Care Unit
imipenem-resistant A.baumannii was identified in 14 hospitalized patients 40 MDR & imipenem resistant A.baumanii isolates were
recovered
Samples for culture were obtained from the environment and from the hands of HCWs 29 imipenem resistant A. baumannii isolates were recovered
from the environment, and 12 from HCWs
Infect Control Hosp Epidemiol 2008;29:410-417
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ESBL Producing GNB K.pneumoniae, E. coli
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Risk factors for infections with ESBL producing GNB
• Quinolone use (OR,2.86;95%CI,1.37- 5.97) • Cephalosporin use in the previous 90 days (OR,
2.7;95%CI 1.4 - 5.2) • Antibiotic therapy within the year preceding the
isolation of the ESBL-producing strain (OR 2.88,95%CI1.13–8.49)
• Mechanical ventilation(OR 10.56,95%CI 1.06–579.10)
• Previous exposure to > 3 class of antibiotics (OR,4.5[95%CI,1.7–75.2]
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Risk factors of Bacterial Resistance Pt admitted from community but have
Health care associated infections • Hemodialysis
• Recent hospitalization within 90 days • Recent ATB usage • Chronic immunosuppression
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Timing of initiation of antimicrobial therapy
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Timing of initiation of antimicrobial therapy
• Critically ill e.g. septic shock, FNP, meningitis:
start immediately
– Septic shock : start appropriate antibiotic within
6 hr of presentation decrease mortality
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A prospective observational study
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2,798 adults patients with severe sepsis
early broad-spectrum antibiotic treatment
lower hospital mortality
Tx within 1 hour vs. not treatment within the
first 6 hr of diagnosis (OR 0.67,95%CI 0.5-0.9)
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Timing of initiation of antimicrobial therapy
• Delayed antimicrobial administration
increased the risk of death in
hypotensive patients by 7% for every
additional hour without ATB
Crit Care Med 2006;34:1589-96
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Appropriate Documented Therapy
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Consideration regarding Appropriate documented therapy
• De-escalation of antimicrobial therapy • Susceptibility Reports: Pitfalls in
Antimicrobial Selection
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step down (de-escalate) to narrow spectrum ATB
•Decrease toxicity •Decrease cost •Prevent bacterial resistance
susceptibility test available
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De-escalation therapy
• starting with broad spectrum empirical therapy regimen, design to avoid inappropriate therapy
• a commitment (in selected patients as directed by patients clinical response & culture data ) to – change from broad to narrow spectrum therapy – reduce the duration of therapy – stop therapy
Curr Opin Crit Care 2006;12:452– 457
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De-escalation of antimicrobial therapy
Is it safe?
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Crit Care Med 2004;32(11): 2183-90
Prospective observational study in
121 VAP in 115 patients
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P.aeruginosa risk: late onset (>7 day intubation), COPD
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Results
• Causative pathogens was identified in 111/121 episodes (91%)
• Sensitive strains identified in 100 episodes • De-escalated rate 38% in sensitive strain • 46 episodes continue empirical therapy despite
the isolations of sensitive strain • Less chance to de-escalate ATB in non-
fermentative GNB and late onset VAP
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ICU mortality rate of pts with de-escalation therapy was sig. lower than in pts who maintained a fixed
Regimen (18% vs 43.8%, P< 0.05)
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J Trauma 2009;66: 1343- 48
Retrospective study
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Results
135 pts with VAP including some pts with septic shock (70% of pts on vasopressor)
Most common pathogens – 25 poly-microbial, 113 mono-microbial – MRSA 14%, E. coli 11%, P. aeruginosa 9%
95% with appropriate empirical therapy 77/135 de-escalation therapy 61/77 eliminating drug from combination therapy 16/77 change to narrow spectrum
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Results
Over all recurrent pneumonia rate 30%
did not differ b/w DT (27.3%) & NDT (35.1%)
Over all mortality rate 37%
did not differ b/w DT (33.8%) & NDT (42.1%)
DT= de-escalation therapy, NDT= non-de-escalation therapy
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Critical Care 2011;15:R79
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Method
• Retrospective observational cohort study • ATB de-escalation
– change from multiple drugs to single drugs if P. aeruginosa is not present
– shorten duration of therapy <5 days if culture negative & have been > 48 hrs deferevescence
– change from broad spectrum to narrow spectrum in the light of culture data
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Results
• 137 patients were included
• DT in 44 pt (32.1%)
• No difference b/w 2 groups: prior length of ICU
stay, prior ATB use, use of mechanical ventilators,
APACHEII score, modified CPIS, appropriate initial
ATB (AIT)
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Infection 2011 Apr 21. [Epub ahead of print]
Retrospective study
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Pathogens - MSSA - PSSP - E. coli & Klebsiella (ESBL-)
DT in 79 pts (39%)
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Consideration regarding Appropriate documented therapy
• De-escalation of antimicrobial therapy • Susceptibility Reports: Pitfalls in
Antimicrobial Selection
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Interpretation of Antimicrobial Susceptibility Reports: Pitfalls in
Antimicrobial Selection
ขอพงระวงในการนาผล susceptibility test มาใช ทางคลนก ตวยางกรณ susceptibility test ไมสอดคลองกบ clinical outcome
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Antimicrobial Susceptibility Report
• Susceptible, sensitive (S) ยาทใหในขนาดปกตมประสทธภาพในการรกษาการตดเชอ
• Intermediate (I) ยานาจะใชในการรกษาการตดเชอได – ถาใชยาขนาดสง หรอ ใชรกษาการตดเชอทอวยวะทยามความ
เขมขนสง
– การใชยาทมผลการทดสอบเปน I มแนวโนมจะใหประสทธภาพในการรกษาการตดเชอตากวาการใชยากรณทมผลการทดสอบเปน S
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• Resistant (R)
– ยาไมนาจะใชไดผลในการรกษา
– มผลการศกษาทางคลนกบงบอกวาเกดการรกษา
ลมเหลวเมอมการใชยาดงกลาว
Antimicrobial Susceptibility Report
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• susceptibility test เปน in vitro test ทใชกนมากทสดในการชวย guide การเลอกยาตานจลชพใหกบผปวย
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ขอพงระวงในการนาผล susceptibility test มาใชทางคลนก
►เชอแบคทเรยทนามาทดสอบตองเปนเชอกอโรคจรงไมใช
colonization หรอ contamination
►การปฏบตตามมาตรฐานทกาหนดไว
►ปจจยทตางกนระหวางหลอดทดลองกบการตดเชอใน
รางกายมนษย
►inoculum size
►drug PKPD
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Inoculum effect • Significant increase in MIC when the
number of organism inoculated is
increased
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ผลการทดสอบ in vitro ไมสอดคลองกบ clinical outcome
Salmonella spp. & Shigella spp. Vs cephalosporins
รนท 1& 2, aminoglycosides
clindamycin, macrolides หรอ tetracycline Vs CNS
infections
cefazolin ,cefoperazone, AMG
Enterococcus spp. Vs cephalosporins clindamycin,
co-trimoxazole CLSI 2011
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ผลการทดสอบ in vitro ไมสอดคลองกบ
clinical outcome • Enterbacter, Citrobacter & Serratia may develop R
during prolong therapy with 3rd cephaloosporin
– S R in 3-4 days of initiation of therapy
• MRSA Vs beta-lactam
• Heteroresistant VISA
• Inducible clindamycin resistance in S. aureus & S. pyogenes • B. pseudomallei Vs co-trimoxazole
CLSI 2011
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Heteroresistant VISA
hVISA
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VISA • S. aureus ทม vancomycin MIC 8-16 • พบครงแรกในประเทศญปน • Mechanism of resistant
– มชน peptidolycan ของผนงเซลลหนาขน – Vancomycin จบกบ D-alanineในผนงเซลล
มากขน ไปท site of action นอยลง
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Heteroresistant VISA (hVISA)
• Definition: ม VISA เปนสวนนอย (1 ใน ลาน) ในเชอทไวตอยา
–susceptibility test รายงานวาเชอไวตอยา
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Laboratory test for hVISA
• Screen test
• เลยงเชอทสงสยใน brain-heart infusion (BHI)
agar + vancomcin 4 mg/L
• Incubate ท 37o C นาน 48 hours
• >1 colony สงสย hVISA
“ มความไวและความจาเพาะเจาะจงตา”
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การทดสอบเพอยนยนวาเปน hVISA
• Population analysis profile (PAP)
– เลยงชอใน BHI agar + vancomycin ทความเขมขน 0.5, 1, 2, 2.5, 4,8 mg/L
– อบท 35o C นาน 48 ชวโมง
– colony count
– Plot graph: ความเขมขน vancomcin vs log จานวน colony
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PAP Log colony count cfu/ml
Vancomycin concentration (mg/L)
Mu 3
sample
AUC sample/AUC Mu 3 > 0.9 hVISA
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Prevalence of hVISA in ASIA Country No of MRSA
isolates No of screen (+) strian (%)
No of hVISA isolates (%)
China 84 12 (4.3) 0 India 80 16 (20) 5 (6.3)
Indonesia 114 14 (12.3) 0 Japan 231 69 (29.9) 19 (8.2)
South korea 457 192 (42%) 28 (6.1) Philipines 28 6 (21.4) 1 (3.6)
Singapore 87 2 (2.3) 2 (2.3)
Thailand 96 17 (17.7) 2 (2.1)
Total 1,349 347 (25.6) 58 (4.3)
Antmirob Agent Chemother 2004;48:4926-4928
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ความสาคญทางคลนกของ hVISA
• ผปวยลมเหลวในการรกษาดวย vancomycin ทงๆทผล susceptibility test พบวาเชอไวตอยา เมอทาการทดสอบภายหลงพบวาผปวยตดเชอ hVISA – รายงานสวนใหญเปน case report
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Clinical featured associated with bacteremia due to hVISA
Clin Infect Dis 2003;38:448-51
Clinical featured hVISA VS-MRSA p
High bacterial load (%) 5/5 (100) 10/48(21%) .001 Duration of van therapy
(mean+SD) 31+11 17+18 .02
Low serum van Ctr 5/5 (100%) 11/36 (31%) .006
Clinical van failure 5/5 (100)
1/48 (2.1%) <.001
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การดอของ S. pyogenes หรอ
S. aureus ตอยา clindamycin
แบบ inducible
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• ไวตอ clindamycin แตดอตอ erythromycin
• ดอตอยา กลม macrolide lincosamide และ
streptogramin แบบ inducible จากการทเชอม
ยน erm
• อาจจะดอตอยา clindamycin ระหวางการรกษา
ไดทงทในการทดสอบพบวาเชอไวตอยา
• double disk diffusion test (D–zone test)
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double disk diffusion test (D–zone test)
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Co-trimoxazole resistant B. pseudomallei
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JAC (2005) 55,1029-31
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Appropriate Dose of Antimicrobial Agents
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Appropriate Dose of Antimicrobial Agents
PKPD of Antimicrobial Agents
Poor outcome from inappropriate dose of ATB
Concerns of ATB dosing
ATB dose in critically ill
vancomycin dose
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PKPD of Antimicrobial Agents
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Pharmacokinetics Pharmacodynamics
Distribution
Blood/plasma
Elimination
Site of Action
Interaction with receptor Stimulus
Effect
Dose
Movement of Molecules
Cascade to effect
Vd, protein bound
ke, t1/2
F
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18 16 14 12 10 8 6 4 2 0 0
10
20
30
40
50
60
70
80
TIME (hrs)
CO
NC
ENTR
ATIO
N (µ
g/m
l) Cpeak
Area Under the Curve (AUC)
Plasma conc. vs Time curve
Ctrough
VD, CL
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Pharmacodynamics
• relationship b/w serum conc & pharmaco. & toxicological effects of drugs • Antibiotic: ability of drug to kill or inhibit
growth of microorganism MIC, MBC Bactericidal Activity
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Bactericidal Activity
Concentration dependent killing
Concentration independent killing
(time dependent)
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Concentration dependent killing
The higher the drug concentration, the greater the rate and extent of
bactericidal activity
e.g. Aminoglycoside, Quinolones, Metronidazole
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Concentration independent
(time dependent) killing
Saturation of the killing occurs at around 2 - 4 times MIC
e.g. Beta-lactams, Glycopeptides, Clindamycin, Macrolides
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conc. dependent (Cmax/MIC) e.g. Aminoglycosides
24-hr AUC/MIC (AUIC)
Vancomycin, Quinolones
Time dependent (%T>MIC)
Beta-lactam
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Pharmacokinetic/Pharmacodynamic Parameters Associated with Antibiotic
Efficacy
Time (hours)
Con
cent
ratio
n
MIC
0
Cpeak:MIC - Aminoglycosides (8:1)
AUC:MIC -Fluoroquinolones gram (-) > 125 gram (+) > 30 -Vancomycin (> 1400 )
%Time > MIC - pencillin (>50%) - cephalosporin (>70%) - carbapenem (>40%)
Clin Infect Dis 1998;26: 1-12 Curr Infect Dis Rep. 2011 Jul 30.
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Monte Carlo Simulation (MCS)
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Monte Carlo Simulation
• incorporates the variability in PK parameters & the natural MIC distribution with in a bacterial population
• This technique can be used to develop interpretive susceptibility criteria based on PK–PD principles (PK–PD breakpoints)
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Monte Carlo Simulation
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Monte Carlo Simulation
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PTA = probability of target attainment The probability that the simulated subjects can attain the predefined PK/PD target such as 40%T>MIC for a given range of MICs
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Poor outcome due to inappropriate ATB dosing
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Poor outcome from inadequate dose of antibiotic
Meta-analysis of 57 RCTs to evaluate
efficacy & safety of cephalosporins1
26% increased in 30 day mortality for pts
treated with cefepime compared to other
cephalosporins
Due to low dose (1- 2 gm q 12 of cefepime)
Lancet Infect Dis 2007;7:338-48
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Poor outcome from inadequate dose of antibiotic
GNB Bacteremia
Cefepime Dose 1-2 gm q12
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Poor outcome from inadequate dose of antibiotic
• high mortality rates associated with infections due to less susceptible GNB when treated with broad spectrum beta-lactams
P. aeruginosa bacteremia
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ATB dose in critically ill patients (severe sepsis & septic shock)
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PK of ATB in severe sepsis/septic shock
PK of ATB are profoundly altered may result in
inadequate drug concentration
increased mortality, spread of resistance
Dose use in sepsis derive from healthy
volunteer or less severe patients
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PK of hydrophilic ATB (beta-lactam, AMG, vancomycin) in severe sepsis/septic shock
Decrease ATB level Increased VD due to: interstitial fluid shift ,increase
cardiac output Decrease albumin increase free drug
increase total CL Hyperdynamic state increase renal blood flow
increase CL Increase ATB level, accumulation
Organ failure e.g. renal, liver
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Methods Open, prospective, multicenter study 80 patients with severe sepsis/septic
shock All the patients included in the study
received a first dose of ATB 2 g ceftazidime or cefepime 4 g/0.5 g piperacillin-tazobactam 1 g meropenem
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Methods Obtain serum concentration after first dose
Simulation using the PK parameters from this
population, calculate the probability of
achieving target %T > 4 x MIC
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Increased Vd to compare with healthy volunteer
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Crit Care Med 2001;29:385-91
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Methods • Prospective comparative study in 6 patients
with septic shock and 6 healthy volunteers
• Subject receive piperacillin 4 gm IV
• Obtain serum & insterstitial fluid of smooth
muscle drug concentration
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Results
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CI = continuous infusion, II = intermittent injections ED =extended infusion; piperacillin 3-4 hr, meropenem 3 hr
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Vancomycin Dose
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Staphylococcus MIC breakpoint
MIC< 2 mg/L MIC = 4-8 mg/L MIC>16
mg/L
susceptible intermediate resistant
CLSI 2011
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penetration of vancomycin into body fluid and tissues
Sites IV dose serum conc site conc site:serum
ascites 500 mg (S) 6.9 3.6 52
bile 500 mg (S) 7.5 3.1 41
CSF - un-inflammed
500 mg 6.3 0 0
CSF-meningitis
10-15 mg/kg/dose
3.1 not available
-
pleural 500 mg (S) 7.3 3 31
sylnovial 500 mg (M) 7 5.7 81
bone 15 mg/kg/dose 22.1 2.3 13
heart valve 15 mg/kg/dose 14.2 4.2 30
*
•มรายงานจากการศกษาอนวา CSF: serum ratio ของ vancomycin ในผปวย
เยอหมสมองอกเสบ ~ 36-48% กรณเยอหมสมองไมอกเสบ ~ 0-18%
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Vancomycin failure
References Patients Results
Sakulous et al. MRSA infections High MIC -> high failure rate
•MIC <0.5 mg/L: 55% success rate
•MIC1-2 mg/L : 9.5% success rate
Hidayat et al. MRSA infections C trough = 15-20 mg/L •MIC = 2 mg/L : 62% success rate
•MIC <1 mg/L : 85% success rate
Moise Broders et al.
MRSA infections MIC = 0.5 mg/L : 22% failure rate
MIC = 1.0 mg/L : 27% failure rate
MIC =2.0 mg/L : 51% failure rate
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Possible explanation for vancomycin failure
1. PK/PD properties
2. Antibacterial activity
3. Antimicrobial resistance
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PK/PD properties
• Poor distribution to some sites of
infection
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Antibactericidal activity • In vitro and animal study
– vancomycin show less bactericidal activity
to MSSA than nafcillin
• In clinical study
– vancomycin is less effective than nafcillin
for the treatment of MSSA IE
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Antimicrobial resistance Heteroresistant VISA (hVISA)
Definition: ม VISA เปนสวนนอย (1ในลาน)
ในเชอทไวตอยา
“susceptibility test รายงานวาเชอไวตอยา”
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Recommendation for vancomycin serum concentration
โรค สถาบน คาแนะนา
HAP, VAP, HCAP 2005
IDSA, ATS • Dose 15mg/kg q 12 hrs
•Ctrough 15-20 mg/L
Meningitis 2004
IDSA •Dose 30-45 mg/kg/day
(แบงใหทก 8-12 ช วโมง)
•Ctrough 15-20
Infective Endocarditis
2005 AHA
• Dose 15mg/kg q 12 hrs
•Cpeak 30-45 mg/L
•Ctrough 10-15 mg/L
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MRSA Pneumonia
• High mortality and treatment failure rate
• การใหยา vancomycin ในขนาดทแนะนาคอ 1 กรม ทก 12 ช วโมง ใหผลการรกษาทลมเหลวถงรอยละ 40
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High failure rate with vancomycin treatment
• Low drug concentration in ELF
• Lamer et al. – vancomycin conc. in ELF = 20 % of serum
conc.
Antimicrob Agents Chemother. 1993 ;37:281-6.
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High failure rate with vancomycin treatment
กรณทผปวยทมการทางานของไตเปนปกตและไดรบ ยา vancomycin ใน ขนาดแนะนาคอ 15mg/kg ทก 12 ช วโมง
– ความเขมขนของยาตาสดของยาในเลอดประมาณ 10-15 มก/ลตร
– Serum free drug = 5-7.5 มก./ลตร (50% protein bound)
– ELF free drug = 1-1.5 มก./ลตร – ถา MRSA MIC > 1 mg/L ระดบยาใน ELF อาจไม
เพยงพอในการรกษาการตดเชอดงกลาว
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โรคตดเชออ นๆทพบการลมเหลวจากการรกษาดวย vancomycin หรอระดบยาท
site of infection อาจไมพอ – Meningitis
– IE
– Ostomyelitis
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ASHP Recommendation
Am J Health-Syst Pharm. 2009; 66:82-98
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ASHP Recommendation
Am J Health-Syst Pharm. 2009; 66:82-98