farmacologia clinica de antibioticos de uso hospitalario

7/30/2019 FARMACOLOGIA CLINICA DE ANTIBIOTICOS DE USO HOSPITALARIO

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CLINICAL PHARMACOLOGY

ASPECT OF ANTIBIOTICUSAGE IN HOSPITALIZED

PATIENTS

Danny Suwandi

Department of Pharmacology & TherapeuticsFaculty of Medicine Hasanuddin University


2/27

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%)


3/27

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


4/27

Conventional

Antibiotics

Penicillin

Cephalosporin

Carbapenems

Quinolones

Aminoglycosides

Macrolides

Tetracycline

Nitrofurantoin, Metronidazole,

clindamycin, vancomycin,

teicoplanin, cotrimoxazole, fusidic

acid, etc.

Isoniazid, pyrazinamide, ethambutol,

rifampicin, cycloserin, etc.


5/27

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


6/27

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


7/27

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


8/27

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


9/27

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


10/27

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


11/27

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


12/27

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


13/27

concentration

time

Pattern of

concentration-

dependent killing

Eg.

Aminoglycosides

Fluoroquinolones

MIC

Cmax


14/27

Pattern of time-

dependent

killing

concentration

time

Eg.

Betalactam

Macrolides

Clindamycin MIC


15/27

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


16/27

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


17/27

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


18/27

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


19/27

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


20/27

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


21/27

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


22/27

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


23/27

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


24/27

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


25/27

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)


26/27

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


27/27

Thanks for your attention!

farmacologia clinica de antibioticos de uso hospitalario

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