Antimicrobial treatment in 2011

Antimicrobial treatment in 2011
Pornpan Koomanachai, MD Division of Infectious Diseases and Tropical Medicine
Department of Medicine Faculty of Medicine Siriraj Hospital

ACULTY OF MEDICINE StRIRAJ HOSPITAL
Optimal Antibiotics Administration
Patient (Host) factors
Basic principles of Pharmacokinetics &
Pharmacodynamics
Types of Antibiotics
Drug selection
Appropriate use; timing and duration Organism factors: drug-resistant

ACULTY OF MEDICINE StRIRAJ HOSPITAL
Optimal Antibiotics Administration
•Patient (Host) factors

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Patient (Host) factors
– advanced age
– chronic and/or severe disease
– polypharmacy
– immunodeficiency
– received prior surgical or medical interventions (i.e., blood products, oncologic, or rheumatologic medications)

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Patient (Host) factors
– The prior use of antibiotic therapy -> increased risk
of antibiotic-resistant pathogen infection
– More severe of the illness
• extended hospital stay
• frequently of intubation
• parenteral nutrition, or other medical devices
(i.e., central venous or urinary catheters)
– Increase the risk of a hospital acquired
infection (HAI) with a drug-resistant pathogen

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Basic principles of Pharmacokinetics & Pharmacodynamics
Types of Antibiotics

Drug selection

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Basic principles of Pharmacokinetics & Pharmacodynamics
Common antibiotic pharmacokinetic and minimal inhibitory concentration (MIC) pharmacodynamic relationships

Time

Log1c CFU/Thigh at 24 Hrs 10910 CFU/Thigh at 24 Hrs
Basic principles of Pharmacokinetics & Pharmacodynamics
10 1000
24-Hr AUC/MIC
10 100 Peak/MIC
1000 ว 25 50 75 100 Time Above MIC
Ceftazidime
vs
K. pneumoniae
Levofloxacin
vs
ร. pneumoniae

(ทturuwniirnr ACUITY OF MEDICINE SIRIRAJ HOSPITAL
Basic principles of Pharmacokinetics & Pharmacodynamics
Predictors of Bacterial Eradication: Pharmacokinetic/Pharmacodynamic Profiles
Peak/MIC
r\\
L
> MIC
– Aminoglycosides
T>MIC
f\
MIC
– Beta-lactams
– Clindamycin
– Erythromycin
– Linezolid
24h-AUC/MIC

Azithromycin
Quinolones
Vancomycin

ACULTY OF MEDICINE StRIRAJ HOSPITAL
Optimal Antibiotics Administration
Time-dependent antibiotics
Optimal bacterial kill;
maximum amount of time over the MIC
1
Extended or continuous infusions of beta-lactams

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ACULTY OF MEDICINE SIRIRAJ HOSPITAL

%T>MIC < 50%

%T>MIC >40%
32
Time-dependent
%T>MIC > 50%
32
More frequent infusion
MIC,
90
8
%T>MIC = 100%
16
24
MIC
32
90
Prolonged infusion
MIC
90
VI
Continuous infusion
8
16
24
8
16
24

ACULTY OF MEDICINE StRIRAJ HOSPITAL
Optimal Antibiotics Administration
Time-dependent antibiotics
Several clinical studies:
– Extended infusion vs standard dosing beta-lactams in the acutely ill patient (include ทาeropenem, piperacillin/tazobactam and doripenem)
– The outcome: varied from no difference in clinical cure in the infusion group to a clinically significant enhanced cure rate

ACULTY OF MEDICINE StRIRAJ HOSPITAL
Optimal Antibiotics Administration
Time-dependent antibiotics
Glycopeptides: Vancomycin
– 100 courses of continuous infusion the treatment of suspected MRSA infections
– 78%of patients achieved plateau concentrations (>15mg/L) on Day 1 with minimal risk of toxicity (<35mg/L)
– Increased to 85% on Day 2 sustained for the course
– The lowest concentration; 9.3 mg/L (> MIC for most MRSA)
Guy’s and St Thomas’NHS Foundation Trust (GSTT)

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration Concentration-dependent antibiotics
A high initial concentration is required
– Maximum bacterial ki
– Tissue penetration
Aminoglycoside once daily dose

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Loading dose (LD)
The LD = VxCp
the volume of distribution (V)
the required plasma concentration (Cp)
♦Hydrophilic agents: which disperse mainly in water
♦Lipophilic agents: greater affinity for adipose tissue

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Appropriate use; Timing and Duration
Timeliness and appropriateness of antibiotic
• Dosage
• route
• duration of administration

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ACULTY OF MEDICINE SIRIRAJ HOSPITAL

Optimal Antibiotics Administration
* Get effective antibiotic selection, right first time
* Base antimicrobial selection, empiric and targeted; local susceptibility patterns
Use broad-spectrum “but least” antibiotics early
Optimize the dose and route of administration
Administer for the shortest possible duration
Adjust/stop antibiotic to best target th
remove pressure for resistance developm
urrrTBlr’w
hogen(s)

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Initiation of antibiotic
– Within the first hour after diagnosis of severe sepsis and septic shock
• Systematic Review and Meta-Ana lysis The Efficacy of Appropriate Empiric Antibiotic Therapy for Sepsis
– inappropriate empirical antibiotic treatment is significantly associated with all causes mortality in prospective studies

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
How long should a course of antibiotic therapy last?
• The Surviving Sepsis Campaign
– The duration of therapy should typically be 7-10 days
– Longer courses may be appropriate if
– slow clinical response
– an undrainable focus of infection
• immunological deficiencies
• neutropenia

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
How long should a course of antibiotic therapy last?
• Ventilator-associated pneumonia
– Clinical effectiveness was achieved with 8 or 15 d treatment
– Significant reduction in the emergence of
ทานItiresistant pathogens in the shorter course

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Infection
Minimum duration
• VAP 8 days
• Pneumococcal meningitis 7 days
• Pneumococcal pneumonia 5 days
• Empyema/lung abscess 4-6 wks
• Endocarditis 4 wks
• Osteomyelitis 4 wks

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Organism factors:
•Drug-resistant Gram-Negative
Pathogens
•Drug-resistant Gram-Positive
Pathogens
ACULTY OF MEDICINE SIRIRAJ HOSPITAL
MDR bacterial infection
Risk Factors for MDR Pathogens for Both Nosocomial and Community-Acquired Infections
• Antimicrobial therapy in preceding 90 days
• Current hospitalization of 5 days or more
• High frequency of antibiotic resistance in the community or in the specific hospital unit
• Presence of risk factors for health care-associated pneumonia
• Hospitalization for 2 days or more in the preceding 90 days
Adapted from Am J Respir Crit Care Med. 2005;171(4):388-416.
ACULTY OF MEDICINE SIRIRAJ HOSPITAL
MDR bacterial infection
Risk Factors for MDR Pathogens for Both Nosocomial and Community-Acquired Infections
• Residence in a nursing home or extended care facility
• Home infusion therapy
• Chronic dialysis within 30 days
• Home wound care
• Family member with multidrug-resistant pathogen
• Immunosuppressive disease and/or therapy
Adapted from Am J Respir Crit Care Med. 2005;171(4):388-416.

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Antibiotics
For
Drug-Resistant GN Infection

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics For
Drug-Resistant GN Infection
Carbapenem
Colistin
Tigecycline
Combination therapy
ACULTY OF MEDICINE StRIRAJ HOSPITAL
Carbapenem
Ertapenem Imipenem Meropenem Doripenem
I/C Community settings Empirical Rx of serious infections in previously multiple ATBs use
intraabdominal or skin Polymicrobial infection
and soft tissue Suspected MDR or ESBL producer, Amp c producer GNR
infection MDR p. aeruginosa infection
Out patient ATB Rx
C/I Relative contraindication to prior hypersensitivity type I to (3 lactams
Dose
loading
dose 1 g IV 1 g IV (> 1 g, epileptogenic) 2 g IV 500 mg (1 g ?) IV
maintenance
dose 1 g IV once daily 500 mg-1 g IV q 6 h (max 4 g/d) 1-2 g IV q 8 h (max 6 g/d) 500 mg IV q 8 h (1 g IV q 8 h ?)
prolonged
infusion NA (3Vh) (3h) (3-4 h)
Renal dose adjustment Yes Yes
Zhanei GG et ai. Drugs 2007;67:1027-52, Yes Yes
Chahine EB et ai. Am J Health-Syst Pharm 2010;67:2015-24,
Mandell’s Priniciples and practice of infectious disease 7th 2010
ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Carbapenem
Ertapenem Imipenem Meropenem Doripenem
Common Phlebitis Phelbitis Phlebitis Headache, insomnia
ADRs GI upset GI upset GI upset GI upset
Rash Rash Rash Elevated liver enz.
Pruritus Pruritus Pruritus Phlebitis
Epilepto-
genicity Less 0.5-2%
Risk factors: renal ds, pre-exisitina CNS ds or infection, Hx of seizure, high dose ( > 4 g/d) Less Less
Special Lowest collateral Intraabdominal infection แร FDA approved for Similar structure to
issues damage to
p. aeruginosa, A. baumannii suspected enterococcal coninfection
Resist to imipenem + Resist to meropenem, or doripenem Rx of CNS infection meropenem
In vitro: MIC90 for P. aeruginosa 2-4 times lower than meropenem, but limited clinical data
Not substituted to older carbapenems
Zhane! GG et at. Drugs 2007-,67:1027-52, Chahine EB et at. Am J Health-Syst Pharm 2010;67:2015-24

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Carbapenems
• For ESBL and AmpC-producing organisms
• BUT! not for
– Carbapenem-resistant p. aeruginosa and Acinetobacter sp.
– Intrinsically carbapenem-resistant
Stenotrophomonas maitophiiia and £ faecium
ก ฑบพา*พรํffiTYymmrm mr>ไ ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Spectrums:
– Some GN Enterobacteriaceaes, A. baumannii, p. aeruginosa
– Poor activity against Serratia spp., Burkhoideria spp., Proteus spp., Salmonella spp., Aeromonas spp.
– No activity against GP, most anaerobes
Indication
Preserved for infection from MDR or pan-DR A. baumannii,
P. aeruginosa, or enterobacteriaceaes
Contraindication:
polymyxin allergy
Li J et ai. Lancet Infect Dis 2006;6:589-601 Mandell’s Prinicipies and practice of infectious disease 7th 2010

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ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Colistin Adverse effect
• Nephrotoxicity (10% – 20%) Acute tubular necrosis
• Neurotoxicity (7%) : Dizziness, weakness, facial paresthesia, vertigo, etc.
• Dose dependent & reversible

Risk factors of
nephrotoxicity
• Previous renal insufficiency
• Duration of treatment
Concomitant use of other nephrotoxic drugs

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Colistin
Key therapeutic options for carbapenem-resistant organisms ** p. aeruginosa, A. baumanniiand carbapenemase producing Enterobacteriacae BUT! not for
– Organisms inherently resistant to polymyxins include Serratia sp., Proteus sp., Stenotrophomonas maltophilia, Burkholderia cepacia and Ftavobacterium sp.

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Colistin: dose and administration
Suggested Dosing of Colistin based on PK/PD
• Cr. Clearance > 50 ml/min
300 mg, then 150 mg q 12 h or 100 mg q 8 h
• Cr. Clearance 41 — 50 ml/min
300 mg, then 150 mg q 12 h or 75 – 100 mg q 8 h
• Cr. Clearance 31 — 40 ml/min 300 mg, then 75 – 100 mg q 12 h
• Cr. Clearance 21 – 30 ml/min
300 mg, then 75 mg q 12 h or 150 mg q 24 h
• Cr. Clearance 11 – 20 ml/min 300 mg, then 100 mg q 24 h
Thamlikitkul V., Koomanachai p., 2011, unpublished data

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Tigecydine
Derived from minocycline, similar to tetracycline Very broad spectrum พtith bacteriostatic activity
– GP include MRSA, E faecaiis, E faecium, and VRE
– GN include ESBL producing E coii, Klebsiella spp., (A. baumannii, Serratia spp.) ร. maltophilia
– Anaerobes, atypical pathogens
– No activity against p. aeruginosa, Proteus spp.
Contraindication: hypersensitivity to tetracycline, pregnancy, severe hepatic impairment
• FDA approved: cSSSI, cIAI, CAP
Kasbekar N et at. Am J Hea/th-Syst Pharm 2006;63:1235-43

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Tigecydine
Loading dose: 100 mg IV infusion 30-60 min
• Maintenance dose: 50 mg IV q 12 h
• Hepatic dose adjustment
Severe liver impairment or C-P class C: 100 mg IV loading then maintenance dose 25 mg IV q 12 h
• Common ADR: GI disturbance
• Not recommended: UTI and Bacteremia
Kasbekar N et al. Am J Health-Syst Pharm 2006;63:1235-43 Peterson LR. International Journal of Antimicrobial Agents 2008;32:S215-22

ACULTY OF MEDICINE StRIRAJ HOSPITAL
MDR bacterial infection
Acinetobacter baumannii
ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics against MDR A. baumannii
Antibiotics In vitro activities Clinical efficacy Limitation of usage
Colistin vv vv -Nephrotoxicity -Renal dysfunction: dose adjustment
Tigecycline vv วฺ
Case report or Salvage therapy with colistin -Low serum concentration -Not enough clinical data
Sulbactam
combination พ V -Increasing of resistant
Fosfomycin V วฺ -Not enough clinical data

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics against MDR A. baumannii
Combination therapy
• Insufficient clinical data
• Polymyxins and carbapenems
(even in the presence of carbapenem resistance)
• Polymixin and tigecycline
• Polymyxin; in vitro synergism together with or sulbactam/ampicillin, or rifampicin

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics against MDR A. baumannii
Colistin in Combination Therapy
• Few comparative studies have analysed.
– No clinical benefits for combination (colistin plus amikacin or y^-lactams) therapy in critically ill patients with severe infections by p. aeruginosa
Clin Infect Dis 2003;37:el54-60
No superiority for the association of meropenem-colistin vs colistin alone
Clin Microbiol Infect2006;12:1227-30

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics against MDR A baumannii
Colistin in Combination Therapy
• The clinical response in the patients who received colistin alone was 84.8% and in those who received colistin with other antibiotics (aminoglycosides, or carbapenems) was 77.8%
IntJ Infect Dis. 2007Sep;11(5):402-6
• Good response rate (100% of patients, 26/26) from colistin plus rifampicin (lOmg/kg ql2h)
(No control group, limited number of patients)
J Infect2006;53:274-8

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics against MDR A. baumannii
Aerosolized Colistin
• Adjunct to systemic treatment
• Current published data; too limited to allow determination
• Dosing 75-300 mg/d q 12-24h
• Adverse effect
– Induce bronchospasm
– Other minor symptoms:
cough, sore throat, chest tightness
Crit Care 2005;9:R53-9

«นนะน**น-เr*«nfvh”‘•ชท1ทนๆพ พฯเแ^นฆพิพสุ ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics against MDR A. baumannii
Direct instillation of antimicrobial agents into the ventricles
– Occasionally necessary in patients
– Infections that are difficult to eradicate
– The patient is unable to undergo the surgical components of therapy
– Must use with intravenous antimicrobial agents
Intrathecal Antimicrobial Agents Administered
Antimicrobial
Agent Daily Intrathecal Dose
Vancomycin 5-20 mg
Gentamicin 1-8 mg
Tobramycin 5-20 mg
Amikacin 5-50 mg
Polymyxin B 5 mg
Colistin 10 mg
Teicoplanin 5-40 mg
Quinupristin/dalfop
ristin 2-5 mg
Amphotericin B 0.1-0.5 mg
Mandell, etal. Principles and Practice of Infectious Diseases, 7th Ed(2010)

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics against MDR A baumannii
Intrathecal colistin administration
• Poorly CSF penetrate
– CSF colistin concentration is 25% of serum levels, and remained > to the MIC
EurJ din Microbiol Infect Dis2002;21:212
• Potentially safe, effective, and treatment option for MDR GNB infection
Largest series, 51 cases of A. baumannii nosocomial meningitis
– 100% (8/8) of patients treated with intravenous and IT colistin were survived (p = 0.04)
J Antimicrob Chemother 2008;61:908

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics against MDR A. baumannii
Intrathecal colistin administration
• Dosing
Variable doses ranging from 1.6 to 20 mg/day (ql2-48h)
J Infect. 2005;50:348, J Clin Microbiol. 2005;43:4916, J Anti microb Chemother. 2004;54:290
J Clin Microbiol. 2000;38:3523, Clin Infect Dis. 1999;28:916
• Neurotoxicity
– Meningeal irritation; most frequent (20%)
33% of patients had to be stop treatment 33% of patients, doses had to be reduced
– Neurological signs of meningismus with increased cell count in CSF
int J Anti microb Agents 2007;29:9-25

ACULTY OF MEDICINE StRIRAJ HOSPITAL
MDR bacterial infection
Extended-Spectrum p-Lactamases (ESBL)-producing bacteria

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Extended-Spectrum p-Lactamases;
ESBL-producing bacteria
Hydrolyze
– extended-spectrum cephalosporins
with an oxyimino side chain
– oxyimino-monobactam: aztreonam

Cefotaxime
Ceftriaxone
Ceftazidime
• Resistance to these antibiotics and related oxyimino-beta lactams

«นนะน**น-เr*«nfvh”‘•ชท1ทนๆพ พฯเแ^นฆพิพสุ ACULTY OF MEDICINE SIRIRAJ HOSPITAL
ESBL-producing bacteria
Enterbacteriaceae spp.: ESBL testing?
Epidemiology
Latin America 44.0%
Asia/Pacific Rim 22.4%
Europe 13.3%
North America 7.5%
J Antimicrob Chemother2007;60:1018
Risk factors
Increasing length of hospital or
intensive care unit (ICU) stay
More severity of clinical status
Insertion of various types of catheter or devices
Invasive procedures or surgical
interventions
oxyimino-b-lactams or fluoroquinolones,
J of Hosp Infec 2009:73;345
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ACULTY OF MEDICINE SIRIRAJ HOSPITAL

Treatment of ESBL producing gram-negative bacterial infection

Cefepime was less effective than imipenem in the clinical studies
ro activities Clinical efficacy

X
X
-Low serum concentration -Not enough clinical data
-ผก rlirrnm data Tn ‘น]ททกห-
-No clinical data to support

II
Colistin
V

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Optimal Antibiotics Administration
Antibiotics
For
Drug-Resistant GP Infection

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Antibiotics For
Drug-Resistant GP Infection
Vancomycin
Fosfomycin
Linezolid
Daptomycin
Tigecycline

ACULTY OF MEDICINE SIRIRAJ HOSPITAL

Anti-gram positive agents
Vancomycin Fosfomycin
Activity Bactericidal Bactericidal
Spectrum
Indication
Precaution

ACULTY OF MEDICINE StRIRAJ HOSPITAL

Anti-gram positive agents
Vancomycin Fosfomycin
Dose and Administration
Common ADRs

ACULTY OF MEDICINE SIRIRAJ HOSPITAL

Anti-gram positive agents
Linezolid Daptomycin
Activity Bacteriostatic Bactericidal
Spectrum
Indication
Precaution
Perry CM et ai. Drugs 2001;61:525-51 Sauermann R etai. Pharmacology2008;81:79-91 Mandell’s Prinicipies and practice of infectious disease 7th 2010

ACULTY OF MEDICINE SIRIRAJ HOSPITAL

Anti-gram positive agents
Linezolid Daptomycin
Dose and Administration
Common ADRs
Perry CM et ai. Drugs 2001;61:525-51 Sauermann R et at. Pharmacology2008;81:79-91 Mandell’s Prinicipies and practice of infectious disease 7th 2010

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
MDR bacterial infection
Enterococcusspp.
«นนะน**น-เr*«nfvh”‘•ชท1ทนๆพ พฯเแ^นฆพิพสุ ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Enterococcal infection
Risk factors
– cystoscopy
– cesarean section
– prostatectomy
– transrectal prostatic biopsy
– transjugular intrahepatic portosystemic shunt (TIPS)
– extra corporeal shock wave lithotripsy
– colonoscopy
– fiberoptic sigmoidoscopy liver biopsy
The infection usually originates from
– The genitourinary or gastrointestinal tract
– Procedures associated with the development of enterococcal endocarditis
Malignant and inflammatory lesions of the gut and biliary tract may also be the source of endocarditis
Clin Microbiol Rev 1990; 3:46-65 Medicine (Baltimore) 2007; 86:363-377 Mandeh\ etaเ Principles and Practice of Infectious Diseases, 7th Ed(2010)

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ทโนะนพnun-irnifnT^Twininji พ)โท
J ACULTY OF MEDICINE SIRIRAJ HOSPITAL

Vancomyciท- Resistant Enterococcus
(VRE)
Risk factors for VRE colonization and infection
• Prolonged hospital stays
• Exposure to intensive care units
• Post-transplantation
• Hematologic malignancies
• Exposure to antibiotics
– Vancomycin
– The extended-spectrum cephalosporins**
– Antibiotics with potent activity against anaerobic bacteria
Antibiotics against Enterococcusspp.
Antibiotics E. faecalis E. faecium VRE
Penicillin + + /- –
Ampicillin + + +/■
(if suscept.)
Pip/Tazo + +/- –
Imipenem + +/- –
Meropenem +/- – –
Microbiology (2009), 155, 1749-1757 Emerg Med Clin N Am 2008; 26:813-834 Mandell, eta!. Principles and Practice of Infectious Diseases, 7th Ed(2010)
Antibiotics against Enterococcusspp.
Antibiotics E. faecaแร E. faecium VRE
Aminoglycoside + +
(gentamicin) +
(if suscept.)
Vancomycin + + –
Linezolid + + + (bacteriostatic)
Daptomycin + + (not approved by FDA)
Tigecydine + + +/”
(limited clinical data)
Microbiology (2009), 155, 1749-1757 Emerg Med Clin N Am 2008, 26:813-834 Mandeii, etai. Principles and Practice of Infectious Diseases, 7th Ed(2010)

ACULTY OF MEDICINE SIRIRAJ HOSPITAL
Important messages
Factors influencing antimicrobial use.
• Consideration of drugs
– Dose and route of administration result in adequate drug level at the site in sufficient period
– Have bactericidal activity against the pathogenic organism
• Consideration of organisms
– MDR
– Clinical data evidence
• Consideration of host and site of infecton
– Local factors at the site
– Host defenses/host factors
– Adjunctive therapies ะ remove foreign body, drainage, immunomodulation, etc

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