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Appropriate antimicrobial therapy

ผศ.สทธพร ภทรชยากล คณะเภสชศาสตร

มหาวทยาลยสงขลานครนทร

OUTLINES

Introductions

Appropriate Empirical Therapy

Appropriate Documented Therapy

Appropriate Dose

Introductions

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

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)

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)

ASIA-PACIFIC DATA ON CARBAPENEM-R-ORGANISMS

IJAA 2011;37:225-9.

WHAT WILL HAPPEN IF WE LET IT BE?

มลคายาตานจลชพเพมสงขนอยางมหาศาล

อตราการดอยาเพมสงขนจนถงจดท เปน MDR (multidrug resistance)

ไมรจะใชยาอะไร เกดความหลากหลายในการเลอกใชยา และใชยาอยางไมมหลกฐานทางวชาการ

ผปวยเสยชวตมากขน

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

DEFINED DAILY DOSE AND RESISTANCE RATE

JAC 2004;53(2):290-6.

Meropenem usage

Meropenem resistance

ciprofloxacin usage

ciprofloxacin resistance


Selection of Antimicrobial Agents Timing of initiation of antimicrobial

therapy

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

Selection of Antimicrobial Agents

local antibiogram severity of infections patients characteristics: Allergic history,

organ dysfunctions pharmacokinetic /pharmacodynamic of

antibiotics

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

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

Curr Infect Dis Rep DOI10.1007/s11908-011-0206-8

Risk factors for ATB resistance

P. aeruginosa A. baumanii ESBL producing GNB

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

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

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

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

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

ESBL Producing GNB K.pneumoniae, E. coli

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]

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

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

A prospective observational study

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)


• 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

Appropriate Documented Therapy

Consideration regarding Appropriate documented therapy

• De-escalation of antimicrobial therapy • Susceptibility Reports: Pitfalls in

Antimicrobial Selection

step down (de-escalate) to narrow spectrum ATB

•Decrease toxicity •Decrease cost •Prevent bacterial resistance

susceptibility test available

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

De-escalation of antimicrobial therapy

Is it safe?

Crit Care Med 2004;32(11): 2183-90

Prospective observational study in

121 VAP in 115 patients

P.aeruginosa risk: late onset (>7 day intubation), COPD

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

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)

J Trauma 2009;66: 1343- 48

Retrospective study

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

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

Critical Care 2011;15:R79

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

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)

Infection 2011 Apr 21. [Epub ahead of print]

Retrospective study

Pathogens - MSSA - PSSP - E. coli & Klebsiella (ESBL-)

DT in 79 pts (39%)

Consideration regarding Appropriate documented therapy

• De-escalation of antimicrobial therapy • Susceptibility Reports: Pitfalls in


Interpretation of Antimicrobial Susceptibility Reports: Pitfalls in


ขอพงระวงในการนาผล susceptibility test มาใช ทางคลนก ตวยางกรณ susceptibility test ไมสอดคลองกบ clinical outcome

Antimicrobial Susceptibility Report

• Susceptible, sensitive (S) ยาทใหในขนาดปกตมประสทธภาพในการรกษาการตดเชอ

• Intermediate (I) ยานาจะใชในการรกษาการตดเชอได – ถาใชยาขนาดสง หรอ ใชรกษาการตดเชอทอวยวะทยามความ

เขมขนสง

– การใชยาทมผลการทดสอบเปน I มแนวโนมจะใหประสทธภาพในการรกษาการตดเชอตากวาการใชยากรณทมผลการทดสอบเปน S

• Resistant (R)

– ยาไมนาจะใชไดผลในการรกษา

– มผลการศกษาทางคลนกบงบอกวาเกดการรกษา

ลมเหลวเมอมการใชยาดงกลาว

Antimicrobial Susceptibility Report

• susceptibility test เปน in vitro test ทใชกนมากทสดในการชวย guide การเลอกยาตานจลชพใหกบผปวย

ขอพงระวงในการนาผล susceptibility test มาใชทางคลนก

►เชอแบคทเรยทนามาทดสอบตองเปนเชอกอโรคจรงไมใช

colonization หรอ contamination

►การปฏบตตามมาตรฐานทกาหนดไว

►ปจจยทตางกนระหวางหลอดทดลองกบการตดเชอใน

รางกายมนษย

►inoculum size

►drug PKPD

Inoculum effect • Significant increase in MIC when the

number of organism inoculated is

increased

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

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

Heteroresistant VISA

hVISA

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

Heteroresistant VISA (hVISA)

• Definition: ม VISA เปนสวนนอย (1 ใน ลาน) ในเชอทไวตอยา

–susceptibility test รายงานวาเชอไวตอยา

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”

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

PAP Log colony count cfu/ml

Vancomycin concentration (mg/L)

Mu 3

sample

AUC sample/AUC Mu 3 > 0.9 hVISA

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

ความสาคญทางคลนกของ hVISA

• ผปวยลมเหลวในการรกษาดวย vancomycin ทงๆทผล susceptibility test พบวาเชอไวตอยา เมอทาการทดสอบภายหลงพบวาผปวยตดเชอ hVISA – รายงานสวนใหญเปน case report

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

การดอของ S. pyogenes หรอ

S. aureus ตอยา clindamycin

แบบ inducible

• 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)

double disk diffusion test (D–zone test)

Co-trimoxazole resistant B. pseudomallei

JAC (2005) 55,1029-31

Appropriate Dose of Antimicrobial Agents

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

PKPD of Antimicrobial Agents

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

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

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

Bactericidal Activity

Concentration dependent killing

Concentration independent killing

(time dependent)

Concentration dependent killing

The higher the drug concentration, the greater the rate and extent of

bactericidal activity

e.g. Aminoglycoside, Quinolones, Metronidazole

Concentration independent

(time dependent) killing

Saturation of the killing occurs at around 2 - 4 times MIC

e.g. Beta-lactams, Glycopeptides, Clindamycin, Macrolides

conc. dependent (Cmax/MIC) e.g. Aminoglycosides

24-hr AUC/MIC (AUIC)

Vancomycin, Quinolones

Time dependent (%T>MIC)

Beta-lactam

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.

Monte Carlo Simulation (MCS)

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)

Monte Carlo Simulation

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

Poor outcome due to inappropriate ATB dosing

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


GNB Bacteremia

Cefepime Dose 1-2 gm q12


• high mortality rates associated with infections due to less susceptible GNB when treated with broad spectrum beta-lactams

P. aeruginosa bacteremia

ATB dose in critically ill patients (severe sepsis & septic shock)

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

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

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

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

Increased Vd to compare with healthy volunteer

Crit Care Med 2001;29:385-91

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

Results

CI = continuous infusion, II = intermittent injections ED =extended infusion; piperacillin 3-4 hr, meropenem 3 hr

Vancomycin Dose

Staphylococcus MIC breakpoint

MIC< 2 mg/L MIC = 4-8 mg/L MIC>16

mg/L

susceptible intermediate resistant

CLSI 2011

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%

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

Possible explanation for vancomycin failure

1. PK/PD properties

2. Antibacterial activity

3. Antimicrobial resistance

PK/PD properties

• Poor distribution to some sites of

infection

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

Antimicrobial resistance Heteroresistant VISA (hVISA)

Definition: ม VISA เปนสวนนอย (1ในลาน)

ในเชอทไวตอยา

“susceptibility test รายงานวาเชอไวตอยา”

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

MRSA Pneumonia

• High mortality and treatment failure rate

• การใหยา vancomycin ในขนาดทแนะนาคอ 1 กรม ทก 12 ช วโมง ใหผลการรกษาทลมเหลวถงรอยละ 40

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.

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

โรคตดเชออ นๆทพบการลมเหลวจากการรกษาดวย vancomycin หรอระดบยาท

site of infection อาจไมพอ – Meningitis

– IE

– Ostomyelitis

ASHP Recommendation

Am J Health-Syst Pharm. 2009; 66:82-98

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