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Issue seputar Antibiotika

Penyakit Infeksi dan


Aktivitas In vitro activity
Antibiotika
Pharmacokinetics dan pharmacodynamics

Adverse reactions

Resistensi bakteri patogen

Data klinis
Iwan Dwiprahasto
Dept of Pharmacology & Therapy FK UGM Biaya

Clinical Use of Antibiotics General goals

Aktivitas In vitro For b - lactams: time > MIC for >


40 - 60% of dosing interval

Titer Konsentrasi
Bactericidal vs. For aminoglycosides: peak to MIC
bacteriostatic
Synergy bakterisidal dalam serum &
serum jaringan ratio > 10

MIC / For fluoroquinolones: AUC/MIC > 125


MLC for gram-negatives and > 40 for
gram positives
Ambrose et al 1998

Farmakodinamik antibiotika profilaksi pada bedah Surgical site infections (SSI) di RS


Antimicrob Agent Chemother
Chemother,, 2002;46::3026-
2002;46::3026-30 Insidensi: 49,1%

C.inc

C.clos

Profil kadar gentamisin dalam serum vs waktu


Widodo & Dwiprahasto, 2006
Mencegah Surgical Site Infection Faktor yang berpengaruh terhadap terjadinya
Penggunaan Antibioti
Antibiotika
ka profilaksi secara tepat resistensi bakteri terhadap antibiotika

Perubahan flora normal

Kecenderungan untuk misuse antibiotics


Antibiotic Antibiotika
Antibiotika
Antibiotika
profilaksi: profilaksi
diberikan 1 jam
sebelum insisi pertimbangan dihentikan dalam
medik yang 24 jam setelah Lingkungan yang meningkatkan risiko
dilakukan**
dilakukan
cermat operasi

Tidak mematuhi upaya pengendalian infeksi


*Untuk vancomycin karena waktu paruhnya panjang, dapat diberikan 2 jam
sebelum insisi.

Praktek medik yang mendorong Antibiotics for the Common Cold:


Misuse of Antibiotics Any benefit?

Pemilihan dan cara pengumpulan


spesimen tidak adekuat

Pemeriksaan klinis tidak akurat

Gagal/tidak melakukan
pemeriksaan apus

Gagal menggunakan uji sensitivitas


dan jaringan

BMJ 1998;317:6524
Inappropriate Antimicrobial Therapy:
Prevalence among Intensive Care Patients

45.2%
50%
Inappropriate
34.3% Antimicrobial Therapy
40%
(n = 655 ICU patients with infection)

30%
Community-onset infection
17.1%
20% Hospital-onset infection
Hospital-onset infection after
10% initial community-onset infection

0%

Proportion of S aureus isolates resistant to methicillin recovered from clinical Patient Group
specimens of inpatients in selected European countries. Data for hospitals are
derived from Voss et al,4 and data for intensive care units from Vincent et al5
Kollef M, et al: Chest 1999;115:462-74
Antimicrobial resistance S. pneumoniae CDC NNIS Insidensi VRE
Time Trends (Thomas et al., 2002)
30
80 25,6
ICU Non-ICU 23,9
21,8
60
20
15,4
40 12,812
11,5
10
20
5,3 4,8
2,9
0 0,40,3
1993 1994 1995 1996 1997 1998 1999 2000 2001 0
89 91 93 95 97 99
Penicillin Chloramphenicol Cotrimox
(www.cdcgov/ncidod/hip/NNIS/AR Surv1198.htm.)

Mechanism of Bacterial resistant


PBP: penicillin vs gram +ve cocci
Target
DNA gyrase: quinolone
alteration ribosome: streptomycin, macrolide

beta lactamase: penicillin: gram ve bacilli


Enzymatic
AG modifying enzyme: AG acetyltransferase,
inactivation adenylation
chloramphenical
Decrease decrease permeability: OMP for b-lactam and
access to quinolone
target active efflux: tetracycline, erythromycin

alternative metabolic pathway


Miscellaneous

ANTIBIOTIC STEWARDSHIP
Balancing adequate coverage with reducing
STRATEGIES ???????? emergence of resistance
STEWARDSHIP memerlukan Tools for good antibiotic stewardship

Mengupdate
Mengupdat e pengetahuan tentang
1. Guidelines
prevalence bakteri lokal
2. Restrictions
Mengupdate pola resistensi bakteri
Mengupdate
thd antibioti
antibiotika
ka 3. Area specific practices eg: ICU/NICU/HDU

Pertimbangan biaya 4. CombinationTx

Awareness thd potensi seleksi bakteri


5. Antibiotic or Crop cycling/ rotation
resisten

Pertimbangan faktor pasien

Tools for good antibiotic stewardship


2. Restrictions
Impact of Antibiotic Restriction on Resistance
Guideline-Singapore-Antibiotics in adult.pdf

1. Guidelines GUIDELINE-use_of_antibiotics_in_paed_care.pdf

SIGN-Antibiotic prophylaxis in surgery.pdf

Strategi pengendalian resistensi bakteri

Antibiotic guideline
Hospital drug formulary untuk antiinfeksi;
Pendidikan dan regulasi peresepan;
Pemantauan dan audit penggunaan obat;
Surveillance dan sistem pelaporan pola resistensi
hospital flora;
Deteksi pasien yang terkolonisasi communicable
resistant bacteria
Promosi dan monitoring praktek pengendalian
infeksi di rumahsakit seperti hand hygiene.
3. Area specific practices eg: ICU/NICU/HDU 4. CombinationTx

ESBL-KP (Extended spectrum beta lactamase) incidence


Indications for Clinical use of Antibiotic Combinations
rate and cephalosporin use in ICUs
5 possible reasons to justify combination use
in patients with normal host defenses:
Prevention of Emergence of Resistant
Organisms
Polymicrobial Infections

Synergism

Decreased Toxicity (?)

As Initial Therapy (?)

2 possible scenarios
5. Antibiotic or Crop cycling/ rotation

Antibiotic cycling a
viable option for good
antibiotic stewardship
(crop rotation)
Unrestricted usage by Implement an
each specialist where antibiotic cycling/
any antibiotics may be
rotation policy
chosen at any times.

CROP ROTATION POLICY Implications


Antibiotika digunakan untuk suatu periode waktu yang ditetapkan (mis. 3
bulan),
bulan), dan dirotasi ke antibiotika yang lain pada periode berikutnya sp Unrestricted Rotation
akhirnya recycle
1. Everyone feels free to do as 1. Predetermined protocol needs
they please in the name of to be followed by all.
Jika pola sensitivitas keliru dari perkiraan, pola rotasi bisa diubah professional independence. 2. Junior doctors find it easier to
2. Less paper work or prescribe rationally.
monitoring needed by 3. Forum for interdepartmental
Jan--March 2004 Ciprofloxacine
Jan pharmacist/admin. cooperation/team work..
3. Pressure from many 4. More paper work/surveillance
April -June 2004 Sulperazone antibiotics likely to for compliance.
encourage development of 5. Bosses cannot be said to be
July -Sept 2004 Ceftazidime resistant bugs. biased in choice of drugs.
6. Reduce resistance rates for
Oct--Dec 2004
Oct Piperacillin/tazobactam drugs not in usebetter
survival..long term cost savings
Antimicrobial Resistance:
ANTIBIOTIC ROTATION does.. Key Prevention Strategies

improve patient survival Susceptible


Antimicrobial
Antimicrobial- Pathogen
-Resistant
Pathogen Pathogen
reduce morbidity. Prevent
Prevent
reduce overall antibiotic resistance Transmission Infection

improve antibiotic stewardship Infection


Antimicrobial
Resistance
Should translate to cost savings.
Its a good form of CME, audit and Effective
Optimize Use Diagnosis
& Treatment
interdepartmental collaboration.
Antimicrobial Use

Knowing is not enough;


Key Prevention Strategies
we must apply.
Willing is not enough; we
Prevent infection
must do.
Diagnose and treat
infection effectively

Use antimicrobials wisely

Prevent transmission
Johann Wolfgang von Goethe.
Clinicians hold the solution!