GIM Week 5 Summary

Question 21

A 65 year old man with known acute myeloid leukemia presents to the emergency department with a temperature of 39⁰C and feeling unwell. A CBC yields a white blood cell count of 0.5×10⁹/L (normal range 4-12×10⁹/L), and an absolute neutrophil count of 0.1×10⁹/L (normal range 2-7×10⁹/L).

1. What syndrome is this patient exhibiting?
   This patient has febrile neutropenia, which is a medical emergency.
2. What investigations should be done?
   A full septic workup should be done to determine the source of infection:
   • Labwork: CBC, Lytes, Cr, BUN, AST, ALT, ALP, Bilirubin, Serum lactate
   • Imaging: CXR
   • Urine C&S, urinalysis
   • Blood C&S x2
   • Lumbar puncture for CSF analysis and C&S if meningitis suspected
3. What therapy should this patient receive?
   Every hospital will have specific antibiotic guidelines for febrile neutropenia, which should be followed. In general, empiric therapy should cover gram +ve and gram –ve bacteria, as well as pseudomonas species.

Resource
Freifeld AG et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious disease society of America. Clin Infect Dis. 2011, 52:e56-93.

Question 22

A 55 year-old woman is admitted from home with pneumonia.
A 55 year-old woman is admitted from home with pneumonia.

1. What are the most likely pathogens in this case?
   This woman is presenting with community-acquired pneumonia, of which the most common pathogens are Streptococcus pneumonia, Mycoplasma pneumonia, Chlamydophila pneumonia, and Hemophilus influenza. Respiratory viruses are also a major cause of pneumonia.
2. What empiric antibiotic therapy would you treat her with?
   Empiric therapy to cover these pathogens in a patient admitted to hospital (or outpatients with comorbidities) includes:
   • Macrolide + 3^rd generation cephalosporin
     • Azithromycin 500mg PO/IV q24h + ceftriaxone 1g IV q24h
   • Respiratory floroquinalone
     • Levofloxacin 750mg PO/IV q24h

   Empiric therapy with a macrolide or doxycycline alone can be used in outpatients with no comorbidities or prior antibiotic use.

3. How would your management change if this woman was HIV+ with evidence of Pneumocystis jirovecii pneumonia (PJP)?
   • TMP-SMX (septra) 15-20mg/kg PO/IV q6-8hr daily for 21d
   • Dapsone with trimethoprim can be used as an alternative therapy

   In cases of PJP in HIV+ patients, acute management involves a 21 day course of septra or dapsone + trimethoprim as an alternative (NB: The patient may get worse initially despite therapy).

   • Septra 15 or 20mg/kg/day, divided into 3 or 4 doses

   Prophylactic therapy should follow:

   • Septra 2 tab (or one double strength tablet) PO daily
   • Maintain therapy until CD4 count > 200cells/mm³

   Prophylactic therapy should also be initiated once CD4 count <200cells/mm³ or a history of oral thrush.

Resources

1. American Thoracic Society and Infectious Disease Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005, 171:388-416.
2. Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007, 44 Suppl 2:S27-72.
3. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centre for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Associaton of the Infectious Disease Society of America. 2009 Apr 10;58(RR-4):1-207; quiz CE1-4. Available at http://aidsinfo.nih.gov/contentfiles/Ivguidelines/adult_oi.pdf.

Question 23

What are the indications for initiating anti-retroviral therapy initiation in patients with HIV?
The decision to begin antiretroviral therapy in an HIV+ patient depends on the presence of one or more of the following:

• CD4 count <350 (recent evidence suggests possibly starting therapy when CD4 count is between 350-500)
• Annual decline in CD4 count is >100 cells/mm³
• Plasma HIV-1 RNA level (“viral load”) is > 100,000 copies/mL
• Patient exhibits signs/symptoms of acute HIV infection: fever, myalgia, rash, fatigue, headache, pharyngitis, cervical adenopathy, arthralgia, night sweats, diarrhea
• Co-infection with PJP, Mycobacterium avium complex, or oral thrush

An infectious disease specialist should be consulted when initiating antiretroviral therapy.

Resources

1. Daar ES, Pilcher CD and Hecht FM. Clinical presentation and diagnosis of primary HIV-1 infection. Curr Opin HIV AIDS. 2008, 3:10-15.
2. Hammer SM. Management of Newly Diagnosed HIV Infection. N Enlg J Med. 2005, 353:1702-1710.
3. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.

Question 24

You are called to see a patient in emerge who was found unconscious at home with an empty bottle of whisky and an empty bottle of benzodiazepines. She is a known insulin-dependent type 2 diabetic.

1. Outline your initial management of this patient.
   The initial management of any patient with a suspected drug overdose includes the following:
   • Stabilize the ABCs
   • Ensure IV access
   • Vitals + accucheck for blood glucose
   • Call poison control
   • Obtain a history (either collateral or direct) about compliance with medications, co-ingestion, and self-harm intent
2. What labwork would you send?
   Labwork to send in this case includes:
   • CBC, lytes, Cr, BUN, blood glucose
   • Arterial blood gas
   • Toxicology screen
3. What medical therapies would you start her on?
   Administration of the “universal antidotes” should be done promptly: O₂, glucose (if low), thiamine, and naloxone.
   The following is a list of the classic toxidromes, their associated symptoms, and offending agents:

   Toxidrome	Symptoms	Agents
   Antichlorinergic	Hyperthermia, dilated pupils, dry skin/mucous membranes, agitation, hallucinations, seizures, tachycardia, urinary retention, ileus	Antihistamines Atropine Tricyclic antidepressants
   Cholinergic	Salivation, seizures, lacrimation, urinary incontinence, diarrhea, diaphoresis, bronchospasm, bronchorreah, bradycardia, emesis, excitation	Carbamates Nerve gases Organophophates
   Sympathomimetic	Hyperthermia, mydriasis, diaphoresis, tachycardia, hypertension, excitation, seizures	Amphetamines ASA Cocaine, LSD, PCP Theophyllines Sedative and alcohol withdrawal
   Narcotic & Sedative	CNS depression, respiratory depression, hypotension, miosis	Benzodiazepines Barbituates Ethanol GHB Opioids Hypnotic medications

Question 25

What is the definition of status epilepticus?
Status epilepticus is defined as continuous seizure activity for more than 5 min, or two or more discrete seizures without regaining complete consciousness in between.

Outline your management of this condition.
Treatment is aimed at stopping the seizure and stabilizing the patient:

• ABC, O₂, large bore IV insertion
• Accucheck for blood glucose: administer D50W 1 ampule IV if hypoglycemic
• First-line therapy:
  • Lorazepam 2-4mg IV q2min (up to 0.1mg/kg IV, MAX 8-10mg)
  • Diazepam 5-10mg IV (up to 0.15mg/kg IV, MAX 20-30mg) if Lorazepam not available (duration of action < lorazepam)
  • Midazolam 10mg IM (for patients >40kg) if unable to obtain IV access

If seizure activity does not resolve after 5min with first-line therapy, help should be sought immediately, and second-line therapy initiated through a second IV site:

• Phenytoin 20mg/kg IV at a rate of 25-50mg/min
• Fosphenytoin 20 PE/kg IV or IM at a rate of 100-150 PE/min

Third-line therapy (if the maximum dose of the above medications is reached) – ICU team should be consulted at this point:

• Phenobarbitol 20mg/kg IV at 50mg/min
• Midazolam 0.2mg/kg IV loading dose and then infusion of 0.05-0.5mg/kg/hr
• Propofol: 2-5mg/kg IV loading dose and then 10mg/kg/hr

Resource
Marik PE and Varon J. The management of status epilepticus. Chest. 2004, 126:582-591.