Fever

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Fever

• Alina Iovleva, PGY-3

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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

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Case

• 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.
• CXR without infiltrate. CBC and CMP unremarkable.
  
• US for DVT
• Not all fever is infectious in etiology.

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Body Temp Regulation
Balance between heat production and dissipation
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Normal body temperature

• -think range 35.6oC-38.2oC, mean 36.8oC /-0.4oC
• Anatomic Variability
• -Rectal gtoral by 0.4oC and gt 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

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Fever

• Tgt38.3oC
• 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.

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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

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When to treat fever?

• MI, Stroke. Fevers correlates with worse outcome
• CV/Pulm disease
• Temp above 41oC
• fever induced mental dysfunction in elderly

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Antipyretic agents

• Tylenol
• NSAIDS
• Aspirin
• What about cooling blanket?
• External cooling-gtshivering-gtincreased heat
  production-gtfever
• Vasospasm of coronaries

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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

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Fever vs Hyperthermia

• -Fever is a normal, controlled response to an
  insult lt41oC
• -Hyperthermia is dysregulation of
  thermoregulation gt41.1oC
• 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

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Serotonin Syndrome

• Antidepressants SSRI/MAOi
• Antiemetics Zofran, Reglan
• Abx Linezolid, Ritonavir
• Analgesics fentanyl, tramadol
• Tx supportive, cyproheptadine, benzos
• Tx of hyperthermia paralysis

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Neuroleptic Malignant Syndrome

• -gtneuroleptic medications (dopamine antagonists)
• -gtwithdrawal of L-Dopa in Parkinsons
• -gtSx
• slow onset
• Bradykinesia/akinesia
• Lead pipe rigidity
• Hyperthermia
• Autonomic instability
• -gtTx
• Dantrolene, Bromocriptine, Amantadine

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Edward W. N Engl J Med 2005 3521112-1120March
17, 2005
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Infectious Causes of Fever

• Host
• Syndrome
• Bugs
• Drugs

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Fever in Immunocompetent host

• Community acquired
• Healthcare associated
• 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
• gt48 hrs since admission
• HAP, VAP (gt48hrs since intubation)
• CAUTI
• CLABSI
• SSI
• Geographic/Travel related
• ex. Malaria, Lyme diseases, Valley Fever

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Empiric Antibiotics overview

• Vanc/Zosyn

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Empiric antibiotics

• Sepsis
• Vanc/Zosyn or VancAztreonammetronidazole (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

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Empiric antibiotics

• Intra-abdominal infections/Biliary tree
  infections
• Oral Augmentin or Ciprometronidazole
• IV Zosyn or Aztreonammetronidazole
• Add Vanc if high suspicion for MRSA/unstable
  patient
• CAP
• Ceftriaxone/Azithro or Levofloxacin
• Aspiration
• Augmentin or Moxifloxacin
• HCAP
• Vanc/Zosyn

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Empiric antibiotics

• Endocarditis
• Native valve VancCeftriaxoneGentamycin or
  VancGent
• Prosthetic valve VancGent Rifampin
• Joint Infection
• CeftriaxoneVanc or AztreonamVanc
• Post-surgical Vanc/Zosyn or Vanc/Aztreonam
• Diabetic Foot
• Vanc/Zosyn or VancAztreonammetronidazole

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Empiric Antibiotics

• Bacterial meningitis
• Ceftriaxone and Vanc or Meropenem Vanc
• Add Amp if elderly
• Complicated UTI
• Not Cipro or Nitrofurantoin
• C.Diff
• Mild Metronidazole
• Severe PO Vanco
• Complicated PO Vanc IV metronidazole

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Neutropenic Fever

• single oral temperature of gt38.3C (101F) or a
  temperature of gt38.0C (100.4F) sustained for gt1
  hour
• Neutropenia ANC lt1500-mild ANC lt 500-severe
• Low vs High risk patients

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Neutropenic Fever

• Obtain blood cultures (peripheral and from any
  port), urine cultures, C.diff, imaging
• EMPIRIC GRAM NEGATIVE coverage carbapenems or
  antipseudomonal beta-lactam
• 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.

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Fever in HIV

• What is latest CD4 and previous opportunistic
  infections?
• -gtnormal think common infections
• -gtlow think OI
• On HAART or not? When was it started?
• -gtIRIS
• Median onset 48 days
• Look for pre-exiting infections crypto, PCP, TB

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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 Tgt101F on several occasions over
  gt3 weeks, for which no diagnosis has been reached
  despite 1 week of inpatient investigation

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FUO
Mandell
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Classic FUO
Goldman and Cecils Medicine
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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

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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

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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?