Fever
ALINA IOVLEVA, PGY-3
Learning objectives:
1.Definition
2.Pathophysiology of temperature regulation
3. Difference between fever and hyperthermia
4. Infectious Causes of fever
5. Empiric antibiotics
6. Neutropenic Fever
7. FUO
Case
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Ms. K is a 65 year old woman with DLBCL on active chemotherapy who comes in
with persistent low grade fevers to the low 38s and new DOE. She feels otherwise
well.
T 38.1, HR 112, BP 134/76. CV exam is unremarkable and lungs are clear.
Abdomen is soft, non-tender, non-distended. RLE have 1+ pitting edema to 1/3 of
the way up the shin. Negative Homan sign.
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CXR without infiltrate. CBC and CMP unremarkable.
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US + for DVT
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Not all fever is infectious in etiology.
Body Temp Regulation
Balance between heat production and dissipation
“Normal” body temperature
-think range: 35.6oC-38.2oC, mean 36.8oC +/-0.4oC
Anatomic Variability:
-Rectal >oral by 0.4oC and > tympanic membrane by 0.8oC
-which one is right?
Physiologic variability:
-circadian rhythmicity
-age (impaired thermoregulation in elderly, blunted circadian rhythm amplitude)
-gender, activity, digestion, local inflammation, ovulation, meds, neuropsych
Fever
T>38.3oC
“a state of elevated core temperature, which is often, but not necessarily, part of
the defensive responses of multicellular organisms (host) to the invasion of live
(microorganisms) or inanimate matter recognized as pathogenic or alien by the
host.”
Benefits vs Risks of Fever
Benefits:
- present in other species, evolutionary conserved
-?increases resistance to pathogens
-positive correlation between fever and survival in G- sepsis, SBP, Candidemia
-production of cytokines
Risks:
-discomfort
-increased metabolic demands
-elevated HR/tachypnea
When to treat fever?
MI, Stroke. Fevers correlates with worse outcome
 CV/Pulm disease
Temp above 41oC
fever induced mental dysfunction in elderly
Antipyretic agents
Tylenol
NSAIDS
Aspirin
What about cooling blanket?
External cooling->shivering->increased heat production->fever
Vasospasm of coronaries
Case #2
Mr. B is 65 y.o male, with depression, chronic pain, who presented with recurrent MRSA
cellulitis
He is on Celexa and Bupropion for depression, and tramadol for pain. For MRSA cellulitis he
was started on Linezolid. Day 2 of hospitalization, he felt a bit nauseous and was given IV Zofran.
6 hours later nurse calling you to report temperature of 41.5oC. BP 170/90, HR 110. She reports
patient being agitated and confused.
Your exam significant for increased muscle tone and hyperreflexia
Dx: Serotonin Syndrome
Fever vs Hyperthermia
-Fever is a normal, controlled response to an insult; <41oC
-Hyperthermia is dysregulation of thermoregulation; >41.1oC
◦ sustained elevation in core temperature
◦ lacking the diurnal fluctuation typical of fever and normal body
temperature
◦ does not respond to antipyretic therapy
◦ Ex: heat stroke, serotonin syndrome, NMS, malignant hyperthermia
Serotonin Syndrome
Antidepressants: SSRI/MAOi
Antiemetics: Zofran, Reglan
Abx: Linezolid, Ritonavir
Analgesics: fentanyl, tramadol
Tx: supportive, cyproheptadine, benzos
Tx of hyperthermia: paralysis
Neuroleptic Malignant Syndrome
->neuroleptic medications (dopamine antagonists)
->withdrawal of L-Dopa in Parkinson’s
->Sx:
◦ slow onset
◦ Bradykinesia/akinesia
◦ Lead pipe rigidity
◦ Hyperthermia
◦ Autonomic instability
->Tx
◦ Dantrolene, Bromocriptine, Amantadine
Edward W. N Engl J Med 2005; 352:1112-1120March 17, 2005
Infectious Causes of Fever
Host
Syndrome
Bugs
Drugs
Fever in “Immunocompetent” host
Community acquired
Healthcare associated
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Hospitalization for 2+ days w/ in past 90 days
HD w/ in 30 days
NH or LTAC w/ in 30 days
IV therapy (chemo, Abx) w/in 30 days
Wound care w/ in 30 days
Family member w/ MDR pathogen
Hospital acquired
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>48 hrs since admission
HAP, VAP (>48hrs since intubation)
CAUTI
CLABSI
SSI
Geographic/Travel related
o ex. Malaria, Lyme diseases, Valley Fever
Empiric Antibiotics overview
Vanc/Zosyn
Empiric antibiotics:
Sepsis :
◦ Vanc/Zosyn or Vanc+Aztreonam+metronidazole (if anaerobic infection suspected)
Cellulitis w/ abscess:
◦ Oral: Bactrim or Doxy
◦ IV: Vancomycin
Cellulitis w/o abscess:
◦ Oral: Keflex or Bactrim
◦ IV: Vancomycin or Cefazolin
Necrotizing STI:
◦ IV: Van/Zosyn or Vanc/Aztreonam/Metronidazole
Empiric antibiotics:
Intra-abdominal infections/Biliary tree infections
◦ Oral: Augmentin or Cipro+metronidazole
◦ IV: Zosyn or Aztreonam+metronidazole
◦ Add Vanc if high suspicion for MRSA/unstable patient
CAP:
◦ Ceftriaxone/Azithro or Levofloxacin
Aspiration:
◦ Augmentin or Moxifloxacin
HCAP:
◦ Vanc/Zosyn
Empiric antibiotics:
Endocarditis
◦ Native valve: Vanc+Ceftriaxone+Gentamycin or Vanc+Gent
◦ Prosthetic valve: Vanc+Gent+ Rifampin
Joint Infection
◦ Ceftriaxone+Vanc or Aztreonam+Vanc
◦ Post-surgical: Vanc/Zosyn or Vanc/Aztreonam
Diabetic Foot
◦ Vanc/Zosyn or Vanc+Aztreonam+metronidazole
Empiric Antibiotics
Bacterial meningitis:
o Ceftriaxone and Vanc or Meropenem +Vanc
o Add Amp if elderly
Complicated UTI
o Not Cipro or Nitrofurantoin
C.Diff
o Mild: Metronidazole
o Severe: PO Vanco
o Complicated: PO Vanc +IV metronidazole
Neutropenic Fever
single oral temperature of >38.3°C (101°F) or a temperature of
>38.0°C (100.4°F) sustained for >1 hour
Neutropenia: ANC <1500-mild; ANC < 500-severe
Low vs High risk patients
Neutropenic Fever
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Obtain blood cultures (peripheral and from any port), urine cultures, C.diff,
imaging
EMPIRIC GRAM NEGATIVE coverage: carbapenems or antipseudomonal betalactam
GRAM POSITIVE coverage with vancomycin IF you suspect cellulitis, port/line
infection, PNA, or if patient is clinically unstable
FUNGAL coverage if patient has not defervesced after 4-7 days of broad spectrum
Abx.
Fever in HIV
What is latest CD4 and previous opportunistic infections?
◦ ->normal: think common infections
◦ ->low: think OI
On HAART or not? When was it started?
◦ ->IRIS
◦ Median onset 48 days
◦ Look for pre-exiting infections: crypto, PCP, TB
FEVER OF UNKNOWN ORIGIN
First described by Petersdorf and Beeson, 1961
Analyzed 100 cases from “a northeastern hospital”
They defined a fever as being of unknown origin if
patient had T>101F on several occasions over >3
weeks, for which no diagnosis has been reached
despite 1 week of inpatient investigation
FUO
Mandell
Classic FUO
Goldman and Cecil’s Medicine
Drug-induced fever
5% of cases of drug hypersensitivity reactions
Usually accompanied by exanthema, hepatic, renal or pulmonary dysfunction
Peripheral eosinophilia can be seen
Most common: beta-lactams, sulfonamides, anticonvulsants
Teaching points:
“Patient has a fever, what do you want me to do?”
◦ Evaluate patient (History, Physical, ROS, Vitals)
◦ blood cultures, urine cultures, look for the source, imaging. Tx choice based on
host/suspected organism.
◦ Review previous cultures
◦ Febrile while on antibiotics: What is missing in your coverage? Drug fever?
◦ Evaluate for non-infectious causes
Teaching points:
“This patient keeps having fever, and already got his Tylenol maximum
for the day! Can you order cooling blanket for him?”
“I measured this patient temperature, and in one ear its 38.1 and the
other one is 38.3? What should I do, which ear do you want me to
measure temperature in?”