Rational Antibiotics Use

in Adult Patients with

Fever
Musofa Rusli
Dep/SMF Ilmu Penyakit Dalam – Divisi Tropik – Infeksi FKUA – RSUD Dr. Soetomo Surabaya
 C-PEPTIDE 2019

Rational Antibiotics Use

in Adult Patients with
Fever

Musofa Rusli
Dep/SMF Ilmu Penyakit Dalam – Divisi Tropik – Infeksi FKUA – RSUD Dr. Soetomo Surabaya
 Curriculum Vitae
• Nama: dr. Musofa Rusli, SpPD, FINASIM
• Tempat/ Tgl Lahir: Kediri, 29 Mei 1972
• Pendidikan:
• S1 – Pendidikan Dokter FK UNAIR (lulus 1997)
• Spesialis 1 - Ilmu Penyakit Dalam (lulus 2011)
• Posisi:
• Dosen Ilmu Penyakit Dalam FK UNAIR (Divisi Tropik-Infeksi)
• Kepala Instalasi PIPI RSUD Dr. Soetomo (2017-sekarang)
• Ketua Unit Sistem Informasi (UPeDDI) FK UNAIR (2016 – sekarang)
• Koordinator Surveilans Komite PPRA RSUD Dr. Soetomo
• Anggota Komite Farmasi & Terapi RSUD Dr. Soetomo
• Anggota Tim HIV/ AIDS RSUD Dr. Soetomo - FK UNAIR
• IPCD Pencegahan dan Penanggulangan Infeksi (PPI) RSDS
• Sekretaris IDI Cabang Surabaya (2017-sekarang)
TOPICS
• Definition
• Pathophysiology of fever
• Treating fever with antibiotics
• Prinsip penggunaan antibiotika
• Antibiotics spectrum
• Pitfalls in antibiotics use

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Definition Fever
• An elevation of body temperature
• exceeds the normal daily variation
• increase in the hypothalamic set point

• Heat conservation → vasoconstriction

• Heat production → shivering, fat
tissue thermogenesis

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 Wunderlich’s Maxim
• After analyzing >1 million axillary temperatures
from ~25,000 patients, Wunderlich identified
37.0° C (36.2-37.5) as the mean temperature in
healthy adults.
• Temperature readings >38.0° C were deemed as
“suspicious/probably febrile.”
 Normal Body Temperature
• For healthy individuals 18 to 40 years of
age, the mean oral temperature is 36.8°
± 0.4°C (98.2° ± 0.7°F)
• Low levels occur at 6 A.M. and higher
levels at 4 to 6 P.M. Thus, 37.2 oC in the
morning → fever?
• The maximum normal oral temperature
is 37.2°C at 6 A.M. and 37.7°C at 4 P.M.
• These values define the 99th percentile for healthy individuals.
Normal Body Temperature Caveats

• NORMAL: 36.8 + 0.4 oC

• Anatomic variations: rectal > oral >
tympanic > axillar
• Rectal temperatures are generally
0.4°C higher than oral readings.
• Tympanic membrane (TM) values are
0.8°C lower than rectal temperatures
Definition Pyrogens

Pyrogens → any substance that causes fever

• Endogenous
• class of biologically active proteins called
cytokines → pyrogenic cytokines
• E.g.: IL-1, IL-6, TNF-α, IFN-γ
• Exogenous
• derived from outside the host
• mainly microbes or their products: toxins

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Definition
Elevated body temperature
Hyperthermia:
• An uncontrolled increase in body
temperature that exceeds the body's
ability to lose heat → thermoregulatory
center is unchanged
• Does not involve pyrogenic molecules
• Exogenous heat exposure and endogenous
heat production
Hyperpyrexia:
• an extraordinarily high fever (>41.5ºC)
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Fever Hyperthermia Hyperpyrexia
• Infectious • Heat stroke • Most
diseases • Neuroleptic commonly
• Autoimmune Malignant Synd. occurs in
disease • Thyrotoxicosis patients with
• Malignancy • Pheochromocytoma CNS
• Status epilepticus hemorrhages
• Hypothalamic injury

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 Fever Onset
< 1 week Within 1-3 > 3 weeks
weeks
Dengue Typhoid fever Tuberculosis
Chikungunya Rickettsiosis HIV
Leptospirosis Leptospirosis CMV
Hepatitis A CMV Autoimmune disease
JEV Acute HIV Malignancies
SARS Hantavirus
Ebola Rabies
Ebola
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Of Course… the Differential is VERY
Broad:
Infection (TB, Endocarditis, Abscess, Line Infection, Sinusitis, Meningitis,
Arthritis Osteomyelitis/Wound, Infectious Diarrhea/c. Diff)

Inflammatory (Rheumatic Disorders, Vasculitis, Neoplasms)

Drug Fever (Beta-Lactam antibiotics, Ampho B, Chemo, Drug Interactions)

Thrombotic (DVT/PE/MI)

Neurologic (Hypothalamic disorder, Spinal Cord Injuries, ICH)

Endocrine (Thyrotoxicosis, Adrenal Insufficiency, Subacute Thyroiditis)

Gastrointestinal (IBD, Pancreatitis)

 TREATING Fever
Antimicrobial Acetaminophen
drugs Corticosteroids NSAIDs

Anti-cytokines Antibiotics
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drugs
 Key Points

• History taking → Source or site of infection? Cause of fever?

• Physical examination
• Imaging
• Laboratory tests:
• CBC, urinalysis, BUN/ SC, SGOT/ SGPT, LED, CRP, lactate,
procalcitonin
• Blood/ urine/ body fluid culture
• Serology, antigen-based test

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IN WHAT CONDITIONS SHOULD WE
USE ANTIBIOTICS?
18
Checklist Prinsip Terapi Antibiotika
1) Apakah masalah klinis/ diagnosis pasien ini?
2) Apakah merupakan penyakit infeksi bakterial?
3) Apakah ada penurunan daya tahan tubuh?
4) Apa yang menjadi organism penyebab infeksi?
5) Bahan apakah yang perlu dipakai untuk tes
diagnostik?
6) Apakah ada indikasi pengobatan non-antibiotik?
7) Apakah antibiotik tepat diberikan pada kondisi ini
(bukan self-limiting disease)?
8) Apakah dasar pemilihan antibiotika?
Spectrum of Antimicrobial Drugs Activity
• Antibiotik tidak mencapai tempat infeksi:
• Absorbsi per oral tidak baik,
• Vaskularisasi jelek di tempat infeksi,
Alasan : mengapa terapi antibiotik gagal?
• Tidak dapat menembus BBB,
• Ada benda asing,
• Inaktivasi oleh pus
• Pasien tidak membeli atau mendapat obat
• Pengobatan masih terlalu pendek
• Kuman resisten terhadap antibiotik

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The six antibiotic-resistant threats (CDC, 2016)

• Carbapenem-resistant Enterobacteriaceae (CRE)

• Methicillin-resistant Staphylococcus aureus (MRSA)
• ESBL-producing Enterobacteriaceae (extended-
spectrum β-lactamases)
• Vancomycin-resistant Enterococcus (VRE)
• Multidrug-resistant Pseudomonas aeruginosa
• Multidrug-resistant Acinetobacter baumanii
 PMK No.8
th 2015

JCI edisi 6, standard MMU.1.1:

The hospital develops and implements a program for the
prudent use of antibiotics based on the principle of antibiotic
stewardship (ASP).

KPRA RSUD Dr.Soetomo

PENATAGUNAAN ANTIBIOTIK (PGA)
= Antibiotic Stewardship (ASP)
PRINSIP PGA
• Meningkatkan kesembuhan pasien
Upaya peningkatan outcome • Terhindar dari morbiditas dan
pasien secara terkoordinasi,
untuk perbaikan kualitas mortalitas
penggunaan antibiotik, • Terhindar mis-use and over-use
meliputi: indikasi yang tepat, antibiotik
pemilihan jenis antibiotik, • Menurunkan dampak resistensi
dosis, rute, interval (AMR)
pemberian dan durasi • Penghematan biaya
penggunaannya.
IDSA, 2015

KPRA RSUD Dr.Soetomo

 WHO AWaRe categories:
(ACCESS, WATCH and RESERVE)

• ACCESS antibiotik yang direkomendasikan sebagai terapi empirik

pada kasus infeksi umum, selalu tersedia, harga terjangkau,
mutu terjaga.
• WATCH antibiotik yang berpotensi memicu resistensi,
direkomendasikan digunakan sebagai terapi empiric atau definitive
pada kasus infeksi tertentu. Penggunaannya harus dipantau
dan diawasi oleh tim PGA-SMF
• RESERVE: antibiotik yang diperuntukan sebagai pilihan terakhir,
pasien khusus dg MDRO (gawat, darurat, mengancam nyawa)
penggunaannya harus melalui kajian dan pemantauan tim PGA-
KPRA

KPRA RSUD Dr.Soetomo

KPRA RSUD Dr.Soetomo
 Pitfalls in Antibiotic Prescribing
• Treating non-infectious disease or
colonization
• Serum lactate → sepsis
• procalcitonin → bacterial infection
• Overuse of combination therapy
• Use of antibiotics for persistent fever
• Inadequate surgical therapy
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