Post on 04-Apr-2018
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CLINICAL PHARMACOLOGY
ASPECT OF ANTIBIOTICUSAGE IN HOSPITALIZED
PATIENTS
Danny Suwandi
Department of Pharmacology & TherapeuticsFaculty of Medicine Hasanuddin University
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Top 10 Causes
of Death in the
World
Coronary heart disease (12.2%)
Stroke and other cerebrovascular
diseases (9.7%) Lower respiratory infections (7.1%)
Chronic obstructive pulmonary
disease (5.1%)
Diarrheal diseases (3.7%)
HIV/AIDS (3.5%)
Tuberculosis (2.5%)
Trachea, bronchus, lung cancers
(2.3%)
Road traffic accidents (2.2%)
Prematurity and low birth weight
(2%)
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Masalah :1. Pemilihan antibiotika makin beragam
2. Penggunaan antibiotika cenderung tidak rasional Resistensi
3. Biaya kesehatan meningkat
Strategi :Pemahaman mengenai :
1. Klasifikasi anti-infeksi/antibiotika
2. Dasar-dasar penggunaan3. Akibat serta penanggulangannya
Setiap antibiotika tidak menjamin dapat digunakan pada
setiap infeksi
Perkembangan terapi antibiotika dalam 7 dasawarsa terakhir
ini sangat pesat, tetapi angka morbiditas/mortalitas penyakit
infeksi tetap tinggi
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Conventional
Antibiotics
Penicillin
Cephalosporin
Carbapenems
Quinolones
Aminoglycosides
Macrolides
Tetracycline
Nitrofurantoin, Metronidazole,
clindamycin, vancomycin,
teicoplanin, cotrimoxazole, fusidic
acid, etc.
Isoniazid, pyrazinamide, ethambutol,
rifampicin, cycloserin, etc.
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Prinsip
Pemilihan &
Pemakaian
Antibiotika
Dalam Klinik
Terapi secara EMPIRIS Berdasarkan perkiraan (educated guess)
Pola epidemiology kuman setempat
Terapi secara pasti (DEFINITIF) :Berdasarkan hasil pemeriksaan mikrobiologis
Jenis kuman
Spektrum kepekaan
Terapi Profilaksis (PREVENTIF) Penderita yang sering terpapar pada mikro
organisme tertentu untuk mencegah
terjadinya infeksi oleh mikro organisme
tersebut
Penerima organ transplan Penderita kelainan katup jantung yang akan
menjalani tindakan invasif
Tindakan bedah untuk mencegah infeksi
akibat perlukaannya
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Langkah-langkah
Proses
Keputusan
Pemilihan &
Pemakaian
Antibiotik
Penegakan diagnosa infeksi
Kemungkinan kuman penyebabnya
Apakah antibiotik benar-benar diperlukan
Alternatif
Jika diperlukan antibiotika :
Spektrum antikuman
Pola sensitifitas
Sifat farmakokinetik Ada tidaknya kontra indikasi
Ada tidaknya interaksi yang merugikan
Penentuan dosis, cara pemberian, lama
pemberian, evaluasi dan efek samping
Keadaan fisik pasien seperti : adanya
kelainan ginjal, fungsi hati, usia, berat badan
dan sebagainya
Harga
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10 Important
Questions To
Ask Before
Selecting an
Antibiotic
1. Is an antibiotic indicated?
2. Have appropriate specimens been
obtained, examined and cultured?
3. What organism are most likely?
4. If several antibiotics are available, which is
the best?
5. Is an antibiotic combination appropriate?
6. What are the important host factors?7. What is the best route of administration?
8. What is the appropriate dose?
9. Will initial therapy require modification
after culture date are returned?
10. What is the optimal duration of
treatment, and is development of
resistance during prolonged therapy likely
to occur?Adapted from:Richard E. Reese, Principles of
Antibiotics Use, 2000
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Site of action of
some common
antibacterialdrugs
All of the above action will exhibit
bactericidal effects, except the
action on protein synthesis and
folic acid antagonist resulting
bacteriostatic effects
For some indications combination
therapy is indicated. However the
bacteriostatic or bactericidal
agents should not be mixed
(Chris J.V. Boxtel, Drug Benefits
and Risks, 2001)
RNA synthesis
Rifampicin
Cell membran
Polymyxins Cell wall
PenicillinsCephalosporins
Vancomycin
Teicoplanin
Protein synthesis
ErythromycinAminoglycosides
Tetracycline
Linezolid
DNA synthesis
Quinolones
Folic acid
antagonist
Sulphonamides
Trimethoprim
Adapted from:
Roger Finch, Antimicrobial Therapy, Medical Progress.
Feb,2011
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An important
strategy for a
successful AMtherapy in severe
infections
Select a regiment that maximize the
rate and extent of bacterial killing
Rationale :
Suboptimal therapy maybe life
threatening in the treatment of
severe infections Slow bacterial killing will likely
give chance for the responsible
pathogen to develop resistance.
Adapted from:
Kim & Nicolau, 2002
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The concept of
Pharmacokinetic/Pharmacodynamics (PK/PD)
has been increasingly applied to
optimize the clinical use of antimicrobial agents
and delay the growth of resistant pathogens
to promote rational use of drug
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Manfaat
parameter
PK/PD bagi
penggunaan
antibiotika
dalam klinik
Penentuan dosis yang lebih benar
dan tepat
Peramalan efikasi kliniknya
Peramalan kemungkinan terjadinya
resistensi kuman selama pengobatan
Berguna bagi penentuan formulasi
pengembangan antibiotika yangbaru
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concentration
time
Relationship between
the pharmacokinetic
profile of an antibiotic
and the minimuminhibitory
concentration against
a hypothetical target
organism
C
A
B
D
A
B
C
D
Minimum inhibitory
concentration (MIC)
Time above minimum
inhibitory concentration
Peak (Cmax)
Area under the curve >
minimum inhibitory
concentration (AUC) Adapted from:Roger Finch, Antimicrobial Therapy, Medical Progress. Feb,2011
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concentration
time
Pattern of
concentration-
dependent killing
Eg.
Aminoglycosides
Fluoroquinolones
MIC
Cmax
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Pattern of time-
dependent
killing
concentration
time
Eg.
Betalactam
Macrolides
Clindamycin MIC
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Antibiotics :
The more you
use it, the faster
you lose it Antibiotic resistance are increasing
and actually around the world
Development of bacterial resistanceto antibiotics is much faster thanresearch and development of newantibiotics (Robert A. Weinstein, TheEpidemiology of AntibioticResistance, June 2007)
But doctors can improve theirprescribing practices and thats a big
effort in hospitals
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Clinical Impact of ResistanceAdapted from: Cosgrove : Clin Infect Dis. 2006, 42:S82-89
Outcomes Measure Relative Risk of WorseOutcomes for Infections with
Resistant Compared with
Susceptible Bacteria
Hospital length of stay (LOS) 1.0 1.7
Hospital charges 1.0 1.7Mortality 1.3 5.0
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US antibiotic-
resistance are
responsible for
Adapted from:
Centers for Disease Control and Prevention Bulletin.
Nov 17, 2010)
$35 billion+ in societal cost
$20 billion+ in excess healthcare cost
$8 billion+ additional hospital days
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Resistant Gram bacteria terminology
Resistant Gram-positive bacteria terminology
PRSP Penicillin resistant streptococcus pneumoniae
MDRSP Multidrug resistant streptococcus pneumoniae
MRSA Methicillin resistant staphylococcus aureus
VRSA Vancomycin resistant staphylococcus aureus
VISA (GISA) Vancomycin (Glycopeptide) intermediate staphylococcus aureus
VRE (GRE) Vancomycin (Glycopeptide) resistant enterococcus
Resistant Gram-negative bacteria terminology
ESBL-producing
enterobacteriaceae
Extended spectrum beta-lactamases producing Enterobacteriaceae e.g.
Escherichia coli, Klebsiella pneumoniae
MRPA (MDR-PA) Multidrug resistant pseudomonas aeruginosa
MRAB (MDR-AB) Multidrug resistant acinetobacter baumannii
Pan-resistant Pseudomonas aeruginosa/Acinetobacter baumannii
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IDSA (Infections Diseases Society of America)
supports :
Adapted from : Clinical Infection Diseases 2010:50:1081-1083
The 10x20 Initiative :Pursuing global commitments to develop
10 new antibacterial drugs by 2020
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Alih Terapi
Antibiotika
Keuntungan :
Memperpendek masa rawat
Mengurangi kejadian nosokomial melalui jarum
infus
Mengurangi komplikasi thromboflebitis
Menurunkan biaya pengobatan
Macam-macam alih terapi :
Switch Therapy
Obat IV dan oral berlainan namun potensi
antibakterinya sama
Sequential Therapy
Obat IV dan oral adalah sama dan obat oral
diserap dengan baik mis: ofloksasin
Stepdown Therapy
Obat IV dialihkan ke oral yang potensinya
lebih lemah. Mis : ceftriaxone IV ke
cefuroxime aksetil oral
Mengalihkan pengobatanIV secepatnya ke oral
pada pengobatan infeksi
tertentu di rumah sakit
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Alih Terapi
(IV-PO Switch)
dapat dilakukansetelah :
Perbaikan klinis atau parameter
infeksi lain setelah 2-3 hari
Tidak adanya indikasi lanjutan diberiantibiotika IV
Tidak ada gangguan pada saluran
cerna
Bebas demam lebih kurang dua hari Adanya perubahan leukosit, hitung
jenis dan protein fase akut ke arah
normal
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IV antimicrobials
are indicated in :
Meningitis
Intracranial abscess
Infective endocarditis
Mediastinitis
Severe infections during
chemotherapy-related neutropenia
Inadequately drained abscess and
empyema
Severe soft tissue infections
S. aureus or P. aeruginosa
bacteremia
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Antibiotic
Stewardship
Program
Optimal selection, dosage and durationof antimicrobial treatment that
Results in the best clinical outcome for
the treatment or prevention of infection With minimal toxicity to patient and
With minimal impact on subsequentresistance
Involves
Prescribing antimicrobial therapy only
when it is beneficial to the patient Targeting therapy to the desired
pathogens
Using the appropriate drug, dose andduration
A strategy to enhance patient safety by :
Minimizing exposure to drugs
Performing dose adjustments
Reducing redundant therapy
Targeting therapy to the likelypathogens
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ASP in Hospital
Authority
Objectives Control the emergence and spread of
antibiotic resistance
Optimize selection and use ofantibiotics
Cost containment
Multidisciplinary, programmatic,
prospective, interventionalapproach to optimizing the useof antimicrobial agents
The multidisciplinary team
typically includes Clinical microbiologists Infectious diseases specialists
Clinical pharmacists
Infection control practitioners
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Recommended
antibiotics for
most commonpathogens
isolates from
cultures
MRSA : vancomycin, teicoplanin, linezolid
and daptomycin
ESBL : Carbapenems, piperacillin-
tazobactum, cefaperozone-sulbactum,amoxycillin-clavulinate
Enterococcus : linezolid, teicoplanin,
vancomycin
Acinetobacter : colistin in combinations
with rifampin and imipenem, rifampin and
ampicilin-sulbactam or colistin and rifampin
only
VRE : Linezolid, daptomycin, high dose
ampicillin with aminoglycoside
Adapted from:
A.Bhagwati,
Guidelines for antibiotic usage in
common situations, Dec.2010)
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Take Home
Messages
Resistensi terhadap antibiotika tetap
berkembang pesat
Penggunaan antibiotika harus sesuaiindikasi dengan segala aspeknya
Upaya penghematan biaya penderita
di RS (terapi alih) perlu diterapkan
ATP Program penting untukdikembangkan agar menunjang
keberhasilan pengobatan dengan
antibiotika yang rasional
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Thanks for your attention!