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Curriculum Vitae
• Nama: dr. Musofa Rusli, SpPD
• 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 Komite/ Tim PPI RSUD Dr. Soetomo
• Sekretaris IDI Cabang Surabaya (2017-sekarang)

KOMITE PENGENDALIAN RESISTENSI ANTIMIKROBA

PRAUD 2019 - SURABAYA

Management of Adult Patients with Fever

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

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TOPICS
• Definition
• Pathophysiology of fever
• Management of fever
• Fever of unknown origin
• Drug fever
• Role of NLR and procalcitonin

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Definition
Fever
• An elevation of body temperature that exceeds the normal
daily variation and occurs in conjunction with an increase in
the hypothalamic set point
• Heat conservation (vasoconstriction) and heat production
(shivering, fat tissue thermogenesis)
• Anatomic variations: rectal > oral > axillar

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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.
• 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.

Mackowiak, et al., JAMA 1992;268:1578

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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.”

1Wunderlich C. Das Verhalten der Eiaenwarme in Krankenheiten.

Leipzig, Germany: Otto Wigard;1868.

2Mackowiak, et al., JAMA 1992;268:1578

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Normal Body Temperature Caveats

• NORMAL: 36.8 + 0.4 oC
• Low levels at 6 AM and higher levels at 4 – 6 PM
• Thus, 37.2 oC in the morning  fever?
• Rectal temperatures are generally 0.4°C higher than
oral readings.
• Tympanic membrane (TM) values are 0.8°C lower than
rectal temperatures

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Definition
Pyrogens
Pyrogens  any substance that causes fever
• Endogenous
• class of biologically active proteins called cytokines  pyrogenic
cytokines
• related to activation of TLR
• 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 diseases Heat stroke Most commonly occurs
Autoimmune disease Neuroleptic Malignant Synd in patients with CNS
Malignancy drug-induced hyperthermia hemorrhages
serotonin syndrome
malignant hyperthermia
Thyrotoxicosis
Pheochromocytoma
cerebral hemorrhage
status epilepticus
hypothalamic injury

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Definition
Temperature-pulse relationship

• The temperature-pulse relationship is linear with an increase in heart

rate of 4.4 beats/ minute for each 1ºC
• Temperature-pulse dissociation (relative bradycardia)  typhoid fever,
brucellosis, leptospirosis, some drug-induced fevers and factitious fever
• Fever may not be present during infection in newborns, the elderly,
patients with chronic renal failure, and in patients taking corticosteroids

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Pattern of temperature changes

The pattern of temperature changes may occasionally hint at the diagnosis

Patterns:
• Continuous fever: Temperature remains above normal throughout the day and
does not fluctuate more than 1 °C in 24 hours
• Intermittent fever: The temperature elevation is present only for a certain period,
later cycling back to normal
• Remittent fever: Temperature remains above normal throughout the day and
fluctuates more than 1 °C in 24 hours
• Hectic fever  sepsis

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Fever Onset
< 1 week Within 1-3 weeks > 3 weeks
Dengue Typhoid fever Tuberculosis
Chikungunya Typhus HIV
Leptospirosis Leptospirosis CMV
JEV Ebola Autoimmune disease
SARS CMV Malignancies
Ebola Rabies
Hepatitis A Acute HIV

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Acute Fever Requiring Hospitalization

• Typhoid fever
• Dengue fever/ DHF
• Rickettsiosis
• Leptospirosis
• Chikungunya fever
• Hantavirus

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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)

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Treatment of Fever
• Antipyretics:
• Acetaminophen
• NSAIDs  side effects !
• Corticosteroids  side effects !!!
• Cool damp sponges
• Submersion should be avoided

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TREATING Fever
Antimicrobial Acetaminophen
drugs Corticosteroids NSAIDs

Anti-cytokines Antimicrobial
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drugs drugs

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Benefit and complication of fever

Benefit:
• fever is associated with release of endogenous pyrogens, which activate
the T cells and thus enhance the host defence mechanism.
• Some febrile diseases have characteristic patterns  diagnostic benefit

Complications:
• a state of catabolism  detrimental to body
• fluid and electrolyte imbalance - due to sweating and loss of minerals
• high grade fevers can lead to convulsions, brain damage, circulatory
overload and arrhythmia
• increase oxygen consumption  COPD, CHD
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Drug Fever
Definition (Mackowiak & LeMaistre, 1987):
• a disorder characterized by fever coinciding with administration of a drug and
disappearing after the discontinuation of the drug
• no other cause for the fever is evident after a careful physical examination and
laboratory investigation
• usually a diagnosis of exclusion

Important drugs related to drug fever:

• Antimicrobials: beta-lactams, sulfonamides and nitrofurantoin
• Anticonvulsant
• Minocycline
• Allopurinol
• Sympathomimetic drugs: amphetamines, cocaine
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SELECTED AGENTS ASSOCIATED WITH

DRUG-INDUCED FEVER

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Fever of Unknown Origin

Definition (Petersdorf & Beeson, 1961):
• Fever higher than 38.3ºC on several occasions
• Duration of fever for at least three weeks
• Uncertain diagnosis after one week of study in the hospital
• Classic, nosocomial, neutropenic and HIV-associated FUO (Durrack & Street, 1990)

“Classic”etiology:
• Infections: tuberculosis, infectious mononucleosis
• Malignancies
• Noninfectious inflammatory diseases (eg, vasculitis, systemic lupus erythematosus,
polymyalgia rheumatica)
• Connective tissue diseases (eg, vasculitis, rheumatoid arthritis)
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1. Infections:
• Endocarditis FUO: most common causes
• Tuberculosis
• Abdominal abscesses
• EBV/CMV infections

2. Malignancies:
• Lymphoma
• Leukemia

3. Non-infectious inflammatory disorders

• Systemic lupus erythematosus
• Polymyalgia rheumatica – giant cell arteritis
• Crohn disease

4. Miscellaneous disorders
• Habitual hyperthermia
• Drug fever
Vanderschueren S. et al. From prolonged febrile illness to Fever of Unknown
• Subacute thyroiditis Origin: The challenge continues. Arch Intern Med 2003;163:1033.

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Key Points
• History taking  finding source/ site of infection
• Physical examination
• Imaging
• Laboratory tests:
• CBC, urinalisys, BUN/ SC, SGOT/ SGPT, LED, [CRP, lactate,
procalcitonine]
• Blood/ urine/ body fluid culture
• Serology, antigen-based test

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• PCT improves the management of patients with lower respiratory tract infections
and critically ill sepsis patients, as well as patients with UTIs, postoperative infections,
meningitis, and acute heart failure with possible superinfection (i.e., pneumonia)
• PCT-guided protocol shortened length of antibiotic treatment
• PCT is far from being a perfect marker and levels must be evaluated in the context of a
careful clinical and microbiological patient assessment

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Procalcitonin (PCT) algorithm in patients with respiratory tract infections

in the emergency department

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Procalcitonin (PCT) algorithm in patients with sepsis in the

intensive care unit (ICU)

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Evidences in favor of PCT

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Kesimpulan

• Demam adalah salah satu gejala utama adanya infeksi

• Demam tidak hanya disebabkan oleh infeksi
• Penegakan diagnosis infeksi perlu anamnesis dan
pemeriksaan fisik yang benar
• Pemeriksaan lab dan imaging dapat membantu
diagnosis infeksi

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Thank You

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