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Approach to Fever Work Up Fever Cases

Approach to Fever Work Up Fever Cases. Pedro M. Calderon PGY-3. Learning Objectives. Definition of pyrexia, hyperpyrexia hyperthermia Pathophysiology of fever Evaluate best methods to measure temperature Diagnostic and therapeutic approach for fever in select patient populations

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Approach to Fever Work Up Fever Cases

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  1. Approach to Fever Work Up Fever Cases Pedro M. Calderon PGY-3

  2. Learning Objectives Definition of pyrexia, hyperpyrexia hyperthermia Pathophysiology of fever Evaluate best methods to measure temperature Diagnostic and therapeutic approach for fever in select patient populations Review of IDSA guidelines for important select clinical conditions that cause fevers

  3. DEFINITION • Normal temperature 36.5ºC - 37.5ºC • Lowest temperature at 6 AM • Highest at 4 - 6 PM • Diurnals variations are maintained during illness • Hypothalamus control • Heat producers: muscle and liver • Heat dissipators: skin and lungs • Fever • A.M. temperature > 37.2 C • P.M. temperature > 37.7 C • Hyperpyrexia • Temp > 40.0ºC -41.5ºC • Each 1○C increase = 13% increase O2 consumption (without shivering) Journal of Infection and Public Health (2011) 4, 108—124

  4. Fever Variations • Hyperpyrexia • Temp > 40.0ºC -41.5ºC • Severe infections • CNS hemorrhage • Hyperthermia (Heat stroke) • Does not involve intrinsic body pyrogens • Exertional vs non-exertional • Skin: "hot and dry" • Drug induced hyperthermia • Malignant hyperthermia • Neuroleptic malignant syndrome • Serotonin syndrome

  5. Where and When to Measure • Where to measure • Women and ovulation • Lower temp 2 weeks before ovulation • Raises by 0.6 during • Higher temperatures after eating

  6. Steroids Exogenous Pyrogens Antipyretics

  7. Fever symptomatology* • Related to phases of fever • Initiation phase • Elevation of set point  chills/shivering/rigors • Plateau phase • Tc = Set point • Defervescence • Tc > set point • Patient feels warm  sweating Tc = Core Temp

  8. Etiologies • Non-infectious causes of fevers • Connective tissue disease • Malignancy • Medications • Myocardial infarction • Pulmonary embolism • Fever curve/height does not correlate with etiology • Fever > 39.4 F = Greater concern  infection • Fever > 40.8 = Tissue damage • Fever within 48 hours of admission is often caused by organisms found in the community

  9. Use of Fever Patterns is Controversial • Therapies may interfere with the generation of fevers • NSAIDS, steroids, etc. • Continuous fever • Drugs, RMSF, gram negative pneumonia • Remittent fever • Malaria, Legionella • Intermittent fevers • Endocarditis, peritonitis, sepsis, TSS • Do not use fever patterns alone to make a diagnosis

  10. Etiology – Cont’d • Likelihood that fever is due to bacterial infection: • Advanced age • Indwelling catheter • Nursing home residency • Leukocytosis • Elevated ESR • Diabetes • Identification of source complicated if difficult history and physical examination • Understand potential causes of fever • Studied approach

  11. Common Acute Febrile Diseases May Be Nonfocal

  12. General Approach to the Patient EPIDEMIOLOGY Host Factors Age Sex Local Defenses Phagocytes Complement Antibodies Cellular Immunity Recent Remote Social Risks Clinical Manifestations Physical Exam

  13. General Work up of Fever

  14. Fever: General Diagnostic ApproachClinical Microbiology General Principles • Blood cultures • Mandatory if new fever* • Clinical findings cannot exclude bacteremia • 2 sets from two different sites • 30-60 mins apart • Peripheral always preferred • Contamination vs bacteremia • Volume matters • 3% ↑ Sensitivity per mL • Contamination: • Staph epidermidis, Staph hominis, Bacillus spp, Corynecbacterium • Gram negative, fungi, and anaerobes are always pathogenic • Document clearance of bacteremia!

  15. Fever: General Diagnostic ApproachClinical Microbiology General Principles • Sputum – Gram stain and culture • Sputum vs saliva • New sputum, change in color, amount, thickness, new or progressive pulmonary infiltrate, increased RR, increased in VE, decreased oxygenation. • Urine culture • Catheter, obstruction, renal calculi, GU surgery, trauma, neutropenia • Stool culture • Nasal culture • Throat culture • Spinal fluid culture • Wound abscess culture • GU culture

  16. Case 1 55-year-old man with a history of mitral regurgitation seeks care after an episode of transient weakness in his right arm and speech difficulties. He underwent dental scaling 1 month earlier. He notes recent intermittent fevers and weight loss. On cardiac examination, his regurgitation murmur appears to be unchanged. A TTE shows a mobile, 12-mm mitral-valve vegetation and grade 2 (mild) regurgitation. Magnetic resonance imaging of the brain reveals recent ischemic lesions. How should the patient be further evaluated and treated? N Engl J Med. 2013 Jun 27;368(26):2536.

  17. N Engl J Med 2013; 368:1425-1433

  18. Fever Caused by Endocarditis: Diagnostic Studies • 3 sets (aerobic & anaerobic bottles) from different sites • One hour apart • Repeat blood cultures every 24 hours • CBC, ESR, RFP, U/A, Urine culture • ECG • Imaging

  19. Circulation 2005;111;e394-e434

  20. Fever Caused by Endocarditis:Empiric Therapy • Native valve acute bacterial endocarditis • Vancomycin +/- gentamycin • Prosthetic valve endocarditis • Vancomycin + cefepime + gentamycin • **Staphylococcal prosthetic-valve infective endocarditis, the regimen should include rifampin whenever the strain is susceptible + gentamicin • Repeat blood cultures until defervescence and blood culture negative • Fever may last a week • Duration of abx : 4-6 weeks

  21. Fever Caused by Endocarditis:Surgical Therapy • Heart failure • Uncontrolled infection • Abscess, aneurysm, dehiscence • Persistent fevers or positive blood cultures for 5-7 days • Prevention of embolism from large vegetations (10-15 mm)

  22. Case 2 57-year-old man presents with fever, chills, and new lumbar back pain 2 weeks after undergoing a prostate biopsy because of an increased PSA level. His temperature is 39.7°C; he has an enlarged, tender prostate and lumbar spine tenderness. His white-cell count is 9.1, and the CRP level is 3.43 mg/L. Urine and blood cultures reveal multidrug-resistant, extended-spectrum β-lactamase–producing Escherichia coli susceptible to imipenem. How should he be evaluated and treated? N Engl J Med 2010;362:1022-9.

  23. N Engl J Med 2010;362:1022-9.

  24. Fever Caused by Osteomyelitis:Diagnostic Work Up • ESR, CRP >95% sensitivity • Blood cultures are crucial (30 - 78%) • MRI : high signal on T2 weighted image • CT or MRI are not 100% specific • Biopsy: If blood cultures are negative or if polymicrobial is suspected • Open or CT guided • Biopsy prior to antibiotics is preferred • Drain periosteal abscess

  25. Case 3 58 year old man is hospitalized because of fever and chills for the last 2 days. He denies productive cough, shortness of breath, headaches, nausea, vomiting, abdominal pain, diarrhea, dysuria, or rash. According to his wife, he has been "acting differently" for the past 24 hours. He was recently diagnosed with AML. His leukemia is currently in remission, and he is receiving maintenance chemotherapy. He has no known drug allergies. Works at a local grocery and denies use of tobacco, alcohol or illicit drug. His temperature is 39.4 ºC, blood pressure 81/45 mm Hg, pulse is 122/min, and respirations 22/min. SaO2 96% on RA. A Hickman catheter is present in the left IJ and it shows erythema and induration over the insertion site. Two sets of blood cultures are obtained, one from a peripheral vein and second from the catheter port. 3 liters of normal saline are given IV, this improves patient's hemodynamics. CXR shows infiltrates. UA without evidence of infection.

  26. Fever and Neutropenia • Risk factors: Catheters, skin breakdown, GI mucositis, immune defects associated with malignancy • Seeding of bloodstream by GI flora* • Evaluation: Physical Exam • Teeth, eyes, skin, lungs, abdomen, rectum • Catheter sites • Avoid digital rectal examination • Work up : CBC with diff, RFP, CXR, LFTs, UA, at least two sets of blood cultures, CXR, ?C. difficile • Low threshold for ordering a CT scan • Other: • LP if confused, fungal markers*, bronchoscopy

  27. Important Cofactors in Febrile Neutropenia • Type of underlying malignancy • Abnormal antibody production • High risk for encapsulated organism infection • T cell defects (e.g., Hodgkins Lymphoma) • High risk of Intracellular infections • Breeches in host defenses related to the underlying malignancy • The direct effects of chemotherapy on mucosal barriers and the immune system

  28. Key Points About Bacterial Infections in Febrile Neutropenic Patients • Bacteria are the most frequent infectious causes of neutropenic fever • Shift from gram-negative bacteria to gram-positive bacteria • Gram-negative bacteria (eg, P. aeruginosa) are generally associated with the most serious infections • S. epidermidis is the most common gram-positive pathogen • An infectious source identified in 20 to 30 % Ann Intensive Care. 2011;1:22-22.

  29. Neutropenic Fever is a Hematologic Emergency

  30. Fever and Neutropenia Algorithm

  31. When to Add Gram Positive Coverage to the Empirical Regimen for Neutropenic Fever • Vancomycin or Linezolid* • Fever not resolved after 3-5 days • Hemodynamically instability / Sepsis • CXR with pneumonia • Blood culture with gram positive bacteria • Suspicion for serious catheter-related infection • Chills/rigors with infusion through catheter • Cellulitis around catheter • Severe mucositis if fluroquinolone as prophylaxis and ceftazidime as empiric therapy • MRSA colonization • Remember Leuconostoc, Lactobacilus, and Pediococcus not covered with vancomycin

  32. When to Add Fungal Coverage to the Empirical Regimen for Neutropenic Fever • Fungal colonizers • Candida yeast and aspergillus • Antifungal therapy after day 5-7 • Caspofungin * • Amphoterecin B • Voriconozale • Micafungin • Do not use fluconazole in this setting • Fungal coverage resolves fever in 50% of patients • Cryptococus, Fusarium, Mucor, histo, blasto, cocci • ?Duration • 14 days if source if known • Source not known: Until afebrile + ANC > 500 c/µL • Role of G-CSF, $$ • Anaerobic infections are not commonly seen

  33. Tumor and Malignancy Lymphoma, especially non-Hodgkin's* Leukemia Renal cell carcinoma (20% of cases) Hepatocellular carcinoma or other tumors metastatic to the liver Atrial myxomas (30% of cases)

  34. "“There are no shortcuts to any place worth going.” Beverly Sills

  35. Case 4 20-year-old man who had a history of IV drug use and multiple sexual partners initially presented to the ED with a chief complaint of blood per rectum when he passed stool, and chills for the prior few days. His work-up was normal, including a rapid HIV screen, and he was discharged. He returned 2 weeks later with constipation, fatigue, myalgias, decreased urination, chills, and a productive cough. His physical examination was most remarkable for temp 39.2, HIV antibody test was negative, but his laboratory tests showed an elevation of CK, amylase, and lipase. His blood count showed a normal hematocrit and white blood cell count. HIV viral load was reported as > 1,000,000 copies/mL. J Emerg Med. 2013 May;44(5):e341-4

  36. Fever in Patients with HIV/AIDS • Fever almost always accompanies the acute retroviral syndrome • Drug adverse effect (Bactrim) • Lymphoma • Opportunistic disease

  37. Fever in HIV / AIDS Patients • Opportunistic infections uncommon if CD4 > 200 • TB exception • M. avium rare if CD4 > 50 • Neutropenia can develop in patients with HIV • Primary infection • Secondary infection • Bone marrow suppression of therapy • Zidovudine • HIV + Neutropenia + Fever = Infection*

  38. Predominant Causes of Fever in HIV / AIDS Patients • Bacteria: • More common in children > adults, Strep. Pneumonia, salmonella, enteric bacteria, pseudomonas, salmonella, enteric bacteria • Viruses • HSV, CMV, VZV, EPV, Adenovirus, parainfluenza, measles • Fungi • Candida, cryptococcus, histoplasma, coccidioides, pneumocystis carinii, toxoplasma, cryptosporidia, microsporida

  39. Association of Specific Sites with Fever in HIV / AIDS Patients

  40. N Engl J Med. 1999 Sep 16;341(12):893-900

  41. Acute Febrile Conditions Often Warranting Empiric Antimicrobials • Fever > 40.8 • Immunosuppresion • Neutropenia • Asplenia • Hypogammaglobulinemia • Cirrhosis • Elderly • Unstable vitals signs • Presence of prosthetic device/foreign body • Recent bite, travel

  42. DRUG FEVER • Fever coinciding with administration Disappearing after the discontinuation • Diagnosis of exclusion • 6.7% of patients admitted • Timing not always helpful: Median 8 days • HIV infection increased susceptibility to drug reactions, including fever • ↑ Serum/Urine eosinophil (<20% of patients) • Causes: Pyrogenic contaminants, hypersensitivity reactions, genetic determinants • Stop most probable offending drug first

  43. Fever and Connective Tissue Diseases Vasculitis Giant cell arteritis Adult still’s disease Polyarteritis nodosa Granulomatosis polyangitis Mixed cryoglobulinemia SLE Sarcoidosis

  44. Fever: To Lower or Not to Lower • Yes • Temperature > 40.8 ºC (Tissue damage) • Metabolic stress of fever (e.g., ACS) • No • Stimulates immune function • Decreases iron necessary for pathogen survival • Artificially lowering temperature does not allow for monitoring

  45. “The future belongs to those who believe in the beauty of their dreams.” –Eleanor Roosevelt

  46. Case 6 47 year old man with HTN, HLP, asthma, admitted to the MICU 5 days ago from ED with acute asthma attack which required intubation in the ED. Initial vitals Temp: 38.7, HR 110, BP 90/42, 95% on the vent with 50% FiO2, RR 20 (above vent). Patient has right radial arterial line, right IJ central line, sites which do not appear erythematous or indurated. Pt also has OG. Chest x-ray with new small left lower lobe infiltrate, ETT 3 cm above carina, Right central line with tip in SVC, no pneumothorax. Labs with CBC 15/12/36/253, 79% neutrophils, 2% eosinophils. RFP within normal limits. Patient is on steroids, but no antibiotics. How would you work up and manage fever in this patient?

  47. Fever in the Critically Ill Patient • 50% of patients admitted to the ICU • Fever associated with mortality in ICU • Classifications • Hyperthermia syndromes • Heat stroke, malignant hyperthermia • Infectious • Bacterial, protozoa, fungal, viral, parasitic • Non-infectious • Transfusion reactions, drugs, VTE, hematomas, MI, pancreatitis, neurogenic fever J Intensive Care Med. 2012 Sep-Oct;27(5):290-7.

  48. Fever in the Critically Ill Patient • Compromised natural host defenses • Invasive monitoring • Violation of skin barrier • Microbial colonization • Endotracheal intubation • Retards mucociliary clearance • Nasogastric tubes • Splints open GE junction  aspiration of gastric contents • TPN • Already on antibiotics  resistant infections

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