Fever Flashcards

1
Q

Vanco MOA, dosing, coverage?

A

MOA: inhibits peptidoglycogan polymerization

Dosing: 15-20 mg/kg
- q12h if ClCr > 50
- q24h if ClCr = 30-50
- q48h if ClCr = 15-30
- q4-7days if ESRD

Loading Dose for critically ill

Coverage: Gram+, MRSA

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2
Q

C.dif med? (1)

A

Oral Vanco

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3
Q

QT prolonging antibiotics?

A
  • Fluoronoquinolones
  • Macrolides (Erythromyocin, azithromycin)
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4
Q

MRSA covering ABX? (5)

A
  • Vanco
  • Linezolid
  • Daptomycin
  • Doxy
  • Clinda
  • Septra
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5
Q

Pseudomonas covering ABX? (5)

A
  • Pip-tazo
  • Cipro/Levo
  • Meropenem/Ertapenem
  • Ceftaz
  • Gentamaycin
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6
Q

Anaerobic covering ABX? (5)

A
  • Metronidazole
  • Pip-tazo
  • Amox/Clav
  • Clinda
  • Levo/Moxi
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7
Q

Pip-tazo coverage?

A
  1. Gram-negative including pseudomonas
  2. Gram-positive
  3. Anaerobes
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8
Q

Meningitis bugs? (3)

A

Strep pneumonia
H. influenza
N. Meningitidis

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9
Q

Meningitis drugs?

A

Age 18 - 50
- Cftx & Vanco

Age > 50
- Cftx & Vanco & Ampicillin

  • Give Dex to all first
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10
Q

Listeriosis

  1. Who is at risk?
  2. Symptoms?
  3. Treatment?
A
  1. Neonates and age > 50 ; IC patients ; pregnancy
  2. Fever GI illness ; Meningitis (confusion, LOC, personality changes)
  3. Ampicillin IV 21d
    If PCN allergy = Septra
    If pregnant = meropenem
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11
Q

Legionella

  1. Source?
  2. Who is at risk?
  3. Presentation?
  4. Treatment?
A
  1. Waterbron pathogen (even from AC)
  2. Elderly ; IC patient ; Chronic lung patient
  3. ++ sick, can progress to ARDS
  4. a) Fluorouqinolones ie. Levo/Moxi
    b) Azithro
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12
Q

Asymptomatic bacturia - who to treat? (3)

A
  1. Pregnant patient
  2. Renal transplant patient
  3. Undergoing uro procedure
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13
Q

UTI organisms (KEEPS)

A

Klebsiela
Enterrococus
E.Coli
Proteus Mirabilis
Streptococcus

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14
Q

Pneumonia differential?
- Infectious (5)
- Non-infectious (7)

A

Infectious
- viral URI
- TB
- Sarcoidosis
- Aspiration
- Endocarditis

Non-infectious
- PE
- COPDE
- Asthma
- ACS
- Sickle Cell
- Toxic exposure
- Malignancy

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15
Q

Criteria for sever CAP?

  • Minor Criteria (9)
  • Major Criteria (2)
A

Severe CAP = 1 major OR 3 minor

Major criteria:
1. invasive ventilaition
2. septic shock with pressor use

Minor criteria (CULTHH-MPR)
1. RR > 30
2. PaO2/FiO2 < 250
3. Multi-lobar
4. Confusion
5. Uremia
6. Leukopenia
7. Thrombocytopenia
8. Hypothermia
9. Hypotension

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16
Q

Risk Stratification for Dispo?
*CURB65

A

Confusion
Uremia
RR >30
BP <90
65 year old >

Max point of 5
0-1 = outpatient
2 = consider inpatient
>3 = inpatient, consider ICU

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17
Q

List 3 typical & 3 atypical pathogens that cause CAP

A

Typical:
1. S. Pneunoniae
2. H. Influenzae
3. Staph. Aureus
4. Klebsiella Pneumiae

Atypical:
1. Legionella
2. Mycoplasma
3. Chlamydophila pneumoniae

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18
Q

Outpatient management of pneumonia??

A

Healthy, no comorbidities (>5days):
- Amoxicillin 1G PO TID
- Doxy 100mg PO BID
- Azithro 500mg x1 THEN 250mg

Comorbidities/recent ABX:
- BetaLactam (ie. AmoxClav OR Cefuroxime ) AND Macrolide (Doxy OR Azithro)
-

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19
Q

Pneumonia inpatient management NON-ICU?
*Name combination AND mono therapy options

A

Combination: (beta-lactam & Macroline)
- ie. Ceftriaxone AND Azithro OR Doxy

Monotherapy: Resp fluoro
- Levo 750mg IV daily
- Maxi 400mg IV daily

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20
Q

Who gets steroids in pneumonia?

A

SEVERELY ILL only .. like if septic otherwise nobody else

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21
Q

Aspiration pneumonia RF? (6)

A
  1. LOC
  2. General anesthesia
  3. EtOH use
  4. Dysphagia
  5. NMSK disorder
  6. Structural abnormality
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22
Q

Aspiration pneumonia abx?

A
  1. Beta Lactams
  2. Clinda
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23
Q

Light’s Criteria?

A

Exudative if one or more of:
1. Pleural protein/serum protein > 0.5
2. Pleural LDH/serum LDH>0.6
3. Pleural fluid LDH level >2/3ULN

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24
Q

8 causes of Transudative Pleural effusion?

A
  1. CHF
  2. Cirrhosis with Ascites
  3. Nephrotic syndrome
  4. Peritoneal dialysis
  5. SVC obstruction
  6. PE
  7. Hypoalbumenia
  8. Myxedema
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25
Q

Causes of Exudative pleural effusion? (SO MANY)

A

Infectious
1. Bacterial PNA
2. TB
3. Lung abscess

Malignancy

Connective tissue
1. SLE
2. RA

GI
1. Pancreatitis
2. GI surgery
3. Esophageal rupture

ETC
1. Pulmonary infarct
2. Post-partum
3. Drug reaction
4. Uremia

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26
Q

3 contraindications to thoracentesis?

A
  1. Bleeding disorders
  2. Coagulopathy
  3. Pleural adhesions
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27
Q

7 Complications of thoracentesis?

A
  1. PNX
  2. Hemothorax
  3. Lung laceration
  4. Infection
  5. Hypotension
  6. Hypoxia
  7. Re-expansion pulmonary edema
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28
Q

Endocarditis RFs (7)

A
  1. Prosthetic valve
  2. heart disease (rheumatic, bicuspid, degenerative)
  3. Congenital heart disease
  4. Indwelling catheter/longterm IV
  5. IVDU
  6. Hemodialysis
  7. Intracardiac device (pacemaker)
  8. PMHX IE
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29
Q

Most common IE pathogen

A

Staph Aureus

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30
Q

4 Signs of Infective Endocarditis

A
  1. V sick (fever, malaise)
  2. Unclear Sepsis or Cardiogenic shock
  3. Valvular findings
    • new murmur
    • AV node stuff (prolonged PR/Heart block)
  4. Embolic event
    • Vegetation
    • Mitral valve involvement
    • Renal/Pulmonary emboli
    • Splenic/retinal/eye emboli
    • Skin emboli (Janeway lesions/Osler’s node/Splinter hemorrhage!)
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31
Q

Gold standard for diagnosing Infective Endocarditis

A

TTE!

*TEE after TTE

*Also brain MRI as man have cerebral emboli

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32
Q

Duke’s Criteria

A
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33
Q

Infective Endocarditis treatment (drug/dose/duration)?

A

IV Vanco 15mg/kg + Ceftriaxone 2g IV

Duration = 4-6 weeks

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34
Q

3 populations who get prophylactic IE Abx?

A
  1. Hx of IE
  2. Prosthetic valve
  3. Congenital heart disease
  • I&D in ED
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35
Q

Indications for IE surgery (Rosen’s box, 6)

A
  1. Aortic or mitral insufficiency with ventricular failure
  2. Valve perf or rupture
  3. Perivalvular extension/abscess/fistula/heart block
  4. Prosthetic valve dehiscence
  5. <10mm vegetation on anterior mitral leaflet
  6. Recurrent embolization or persistent bacteremia on therapy
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36
Q

Tuberculosis

  1. pathogen
  2. S&S
  3. Populations at risk (9) - ROSENS BOX
  4. Diagnosis
  5. Treatment in ED
  6. TB treatment regiment
  7. Sites of extra pulmonary TB (7)
  8. Complications of TB
A
  1. Mycoplasma tuberculosis
  2. Persistent cough, weight loss, night sweats, hemoptysis, fever, weakness
  3. IVDU, HIV/AIDS, high risk immigrants, alcoholism, undomiciled, close contact with TB patient, older adult, LTC, occupational exposure
  4. AFB (acid fast bacillus) smear, 3 different sputum samples in 3 different days ..
    GOLD STANDARD IS CULTURE
  5. Isolation, PPE, CXR, HIV serology
  6. Isoniazide, Rifampin, Pyrazinamide, Ethambutol
  7. Lymphadenitis, Bones/joints, Kidney, Genitals, GI, CNS, Multisystem
  8. Pericarditis, Hemoptysis, Pneumothorax, Pleural effusion, Empyema, Superimposed fungal infection, ^ Extrapulmonary TB
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37
Q

Rashes:

Macule VS patch
Papule VS plaque
Vesicle VS Bulla
Petichiae VS Purpura

A

Macule: flat, < 0.5cm
Patch: flat, > 0.5cm

Papule: raised, <0.5cm
Plaque: raised, >0.5cm

Vesicle: fluid-filled, <0.5cm
Bulla: fluid-filled, > 0.5cm

Petichiae: flat, non-blanch, <0.5cm
Purpura: mb palpable, non-blanchable, >0.5cm

38
Q

Scarlet fever:

  1. What pathogen?
  2. What is the rash like?
  3. Treatment?
A
  1. Group A strep
  2. Sandpaper like
  3. ABX: PenV! (if allergic, macrolides or cephalosporin)
39
Q

What is Erythema Multiforme rash like? Why does it come on?

A
  1. Target lesions
  2. Characteristically on palms and soles but can be anywhere
  3. Comes on from viral, bacterial, fungal or drug reaction
40
Q

TEN vs SJS:

  1. Differences?
  2. Causes?
  3. Presentation?
  4. Treatment?
A
  1. TEN <10% ; SJS >30%
  2. Drug rxn to: sulfa, penicillin, NSAIDs, Aspirin, Carbemazapine, Kepra etc
  3. Starts w fever, malaise, sore throat.. then abrupt macular rash that’s like target lesions .. then Nikolsky sign, painful..mucus membrane involvement, conjunctivae and cornea (can cause blindness) and then systemic involvement with Rena, resp, GI
  4. Stop the offending agent!
    Can transfer to burn centre
    If severe, can do steroids, IVIG
41
Q

Toxic Shock Syndrome:

  1. Causative organism
  2. Causative agents
  3. 4 criteria for diagnosis
  4. Rash
  5. Treatment
A
  1. Staph aureus
  2. Historically tampon use, but also nasal packing, abscess, post-op setting, pharyngitis etc..
  3. Fever of at least 38.9 ; Hypotension w SBP < 90 ; Rash ; involvement of at least 3 organ systems!
  4. diffuse, blanching, macular, erythroderma. non-exudative mucus membrane infl.
  5. IV Vanco, Clinda, linezolid, meropenem or pip-tazo
42
Q

Staphylcoccal Scalded Skin Syndrome

  1. Organism?
  2. Age range?
  3. Progression of disease?
  4. Time range?
  5. Treatment?
A
  1. Staph lol
  2. Under 6 years of age
  3. Starts around mouth/belly button –> erythema and crusting –> goes down the body –> followed by bulla –> lesions dry up
  4. 3-7 days! (less than 1 week)
  5. IV ABX covering for gram + (Oxacillin, Vanco) or if allergic (cefuroxime)
43
Q

Thrombotic Thrombocytopenic Purpura (TTP) Pentad:

A
  1. Fever
  2. Thrombocytopenia
  3. Anemia (MAHA)
  4. Renal involvement
  5. CNS involvement
44
Q

ERISYPILAS

  1. Symptoms?
  2. Pathogen?
  3. Treatment?
  4. Difference between cellulitis vs Lympangitis?
A
  1. Raised, clear demarcation, superficial dermis
  2. Strep, Staph. Aureus (most commonly by Streptococcus pyrogens)
  3. Rest, elevate, Abx (Penicillin, Azithro, Cephalexin, Cefazolin)
  4. Cellulitis is in deep dermis, so borders are more poorly defined.
    Lumpangitis is also deep dermis and can have lymphadenopathy
45
Q

Cellulitis criteria for admission (5)

A
  • Toxic
  • Large area
  • Rapidly progressing
  • Not responding to enteric tx
  • Comorbidities (immunocomp, diabetic infection)
46
Q

Diabetic foot infection most common pathogen?

A

Gram + (Staph, strep)

  • Unless chronic wound, then can be polymicrobial
  • Swabs not reliable
47
Q

Dog bites: who gets abx? (3)

A
  1. Area of body (Hands/face/genitals)
  2. Deep/severe bites
  3. Comorbidities
48
Q

Indication for ABX for abscess? (8)

A
  • Multiple lesions
  • Extensive/rapid cellulitis
  • Difficult area to I&D
  • Poor response to I&D
  • Poor follow up
  • Systemic illness
  • Comorbidities / Immunocompromised
  • Extremes of age
49
Q

Necrotizing Fasciitis

  1. Location?
  2. Type 1 vs Type 2?
  3. Signs/symptoms?
A
  1. Subcutaneous tissue
  2. Type 1 = polymicrobial
    Type 2 = Single organism (usually GAS, Staph)
  3. Vague like fever, malaise, Cellulitis, oedema, pain out of proportion, rapidly spreading
  4. OR for debridement! + Sepsis tx with IVF and ABX (Clinda + Pip-tazo + Vanco all MAX doses)
50
Q

MRSA RFs?

A
  1. Abx
  2. HIV
  3. IHD
  4. LTC
  5. MSM
  6. First Nations
  7. Sports
  8. Close quarters
51
Q

Innate vs Adaptive Immunity?

A

Innate - first line, quick, physical barriers, inflammatory response

Adaptive:
1. Humoral = B cell recognizes antigens –> causes antibody production –> activates IgG,IgM, Complement Cascade

  1. Cell-mediated immunity: Antigen-presenting cells sequester antigens and antibodies and present them to T-cells through MHC –> T cells become activated:
    CD4 = helper cells
    CD8 = killer cells
52
Q

Reasons for being immunocompromised?

“TRASH CLIP’D”

A

Transplant
Renal failure
Alcohol
Steroids
Hiv
Chemo
Liver failure
Immunosuppressed
PVD
Diabetes

53
Q

List 3 conditions in which humoral immunity is suppressed:

A
  1. CLL
  2. MML
  3. SLE or RA
54
Q

Who is at risk of getting encapsulated bacterial infections?

A

Asplenic (ie sickle cell or surgical dz) or Hyposplenic (ie thallasemia, HIV, CA) patients

55
Q

List 4 conditions in which cell-mediated immunity is suppressed:

A
  1. Cancer (Hodgkin’s)
  2. Chemo
  3. HIV
  4. Steroid use
56
Q

List 4 bacteria, 4 viruses and 4 fungal infections that those w cell-mediated immunity are more prone to:

A

Bacterial (intracellular)
1. Mycobacterium TB
2. Listeria
3. Salmonella
4. Legionella

Viruses:
1. CMV
2. Varicella
3. HSV
4. EBV

Fungal:
1. Candida
2. Aspergillus
3. Cryptoccocus
4. Pneumocytosis juroveci

57
Q

Neutropenia definition:

  1. Identify fever thresholds (2)
  2. ANC cut-offs for: neutropenia vs severe vs profound
A
  1. Single oral fever of >38.3 OR >38 over 1 hour
  2. Neutropenia: < 1000cells/uL
    Severe: < 500
    Profound < 100

*As ANC goes down, incidence and severity of infection in CA pts go up

58
Q

Who is at increased risk of Febrile Neutropenia? (6)

A
  1. Heme malignancy > solid
  2. Type of chemo
  3. 1st or 2nd cycle of chemo
  4. Severity of ANC
  5. Duration of neutropenia
  6. Comorbid illness
59
Q

Top 3 most common sites of infection in febrile neutropenic patients?

A
  1. Lungs and mouth/pharynx
  2. GI tract
  3. Skin
60
Q

Top 2 most common sites of infection in FN patients associated with bacterimia?

A

Lungs (pneumonia) and anorectal

61
Q

Febrile neutropenia:

  1. Gram + most common in developed countries. Name 4 common GPCs most commonly implicated in FN patients
  2. Gram - most common in developing countries and more lethal if leading to bacteremia. Name 3 GNBs in FN patients
A
  1. Staph aureus
    Staph epidermis
    Enterococcus
    Viridans group strep
  2. E.Coli
    Klebsiella Pneumoniae
    Pseudomonas
62
Q

Risk factors for serious strep viridians infections

A
  1. Aggressive cytoreduction therapy for acute leukemia
  2. Allogenic bone marrow transplant
  3. Profound neutropenia
  4. Severe oral mucositis
  5. Prophylactic Septra, fluoroquinolone
  6. Use of antacids
  7. Pediatric age
63
Q

2 most common fungal infections in febrile neutropenia patients + where are they commonly seen?

A
  1. Aspergillus - necrotizing in lungs and sinuses
  2. Candida - skin, oral cavity, fungemia
64
Q

Cornerstone of management of febrile neutropenic patients in ED? (2)

A
  1. ABX within 60 mins of ED presentation!
    • Anti-pseudomonal like pip/tazo or Carbepenem AND Vanco if indicated
  2. Fluid resus to keep MAP > 65
65
Q

Indications for Vanco in FN patients? (7)

A
  1. Known MRSA
  2. Institution w frequent MRSA
  3. Prior fluoroquinolone prophylaxis
  4. Catheter infection
  5. C.diff
  6. Shock
  7. Oral mucositis/suspected strep virvidan
66
Q

Febrile Neutropenia Dispo: Criteria for being high risk and requiring inpatient therapy (11)

A
  1. Inpatient when FN develops
  2. Hemodynamic instability
  3. Organ failure
  4. AMS/neuro abnormalities
  5. Serious comorbid conditions
  6. Uncontrolled cancer
  7. Acute leukaemia
  8. Pneumonia
  9. Central line infection
  10. Soft tissue infection
  11. Abdo pain
67
Q

Febrile Neutropenia Dispo: Low risk criteria

(MASCC risk index score)

A
68
Q

Most common cause of bacterial infection in solid organ cancer patients? treatment?

A

Listeria ; treat with Ampicillin or Septra

69
Q

Most common cause of pneumonia in solid organ cancer patients? treatment?

A

Legionella; treat with azithro or fluoroquinolone

70
Q

SBP in pts with cirrhosis:

  • Common bacteria?
  • How to diagnose?
  • When to treat?
  • What to administer to increase survival?
A
  1. E.coli, K. pneumoniae, S. pneumoniae, Enterococci
  2. Ascitic fluid sampling and cell count
  3. PMN count of 250cells/mm3 or greater
  4. Albumin 1.5g/kg
71
Q

What bacteria are post-splenectomy patients most prone to? Treatment?

A
  1. S.pneumoniae - mostly cleared by spleen
  2. Cftx + Vanco (or levo/moxi/clinda if penicillin allergy)
72
Q

Define:

  1. Sepsis
  2. Septic shock
  3. Systemic Inflammatory Response Syndrome (SIRS)
A

Sepsis = systemic infl response with a proven microbial source

Septic shock = Sepsis with hypotension unresponsive to fluids plus organ ysf or perfusion abnormalities

SIRS: two of more of: Tachy, tachypnea, hyperthermia/hypothermia, high/low WBC, or bandemia

73
Q

qSOFA score?

A

Infection PLUS 2/3:

  1. RR > 22
  2. SBP < 100
  3. AMS

Basically, new definition of sepsis is above

74
Q

How much fluid to give for sepsis resuscitation? What kind of fluid?

A

30 mL/kg of crystalloid (Ringer’s > NS)

.. then based on clinical picture

75
Q

Fluid choice in sepsis?

5 problems with why the “other” fluid is not ideal?

A

Ringer’s Lactate

NS not ideal because:
1. Hyper-chloromic acidosis
2. Dec GFR/renal blood flow
3. IntraMucosal acidosis in GI tract
4. Delayed gastric emptying
5. Decreased smooth muscle contractility

76
Q

1 recommended vasopressor in sepsis?

A

Norepinephrine (3-30 micrograma/min)

.. followed by epinephrine and vasopressin in adjunct

77
Q

For adults with septic shock on vasopressors, target MAP according to surviving sepsis guidelines?

A

65 mmHg

78
Q

Heart failure:

  • Decompensated vs Acute
  • Reduced EF vs Preserved EF
A

Decompensated = chronic process, slow presentation, usually overloaded

Acute = not managed as outpatient, not on Lasix, acute process led to HF (ie MI or STEMI)

HefREF = EF < 40% systolic, mb diastolic dys
HefPEF = Preserved EF, diastolic dysf

79
Q

CHF:

  1. Risk factors (7)
  2. Causes of decompensation (6)
  3. Signs on history (4)
  4. Physical exam (4)
A
  1. Age
    Smoker
    Obesity
    HTN
    DM
    Dyslipidemia
    Ischemic heart dz
  2. Ischemia
    Arrhythmia
    infection
    renal dysf
    Increased salt/water intake
    Med non-compliance
  3. Dyspnea, SOBOE, nocturnal dyspnea, orthopnea
  4. JVP distension
    Peripheral edema
    Increased WOB & Hypoxia
    Crackles on auscultation
80
Q

4 CHF XR findings

A

Revascularization
Blunting of costophrenic angles
Kerly B lines
Cardiomegaly

81
Q

CHF ED management (4)

A

BiPAP
- very good for LEFT SIDED CHF bc decreases preload! but for right sided THIS IS NOT GOOD bc it leads to hemodynamic instability

Lasix
- 1-2x home dose IV if on Lasix

Nitro

If in shock:
- small bolus + lasix/nitro
- Norepi FIRST LINE for vasopressors

82
Q

HIV modes of transmission

A

Sex without condom
Mother to baby
IVDU
Needle stick injury
Blood transfusion

83
Q

Prophylaxis (and at what CD4 count) to prevent first episode of these opportunistic infections in HIV:

  1. Pneumocystis Jiroveci Pneumonia (PJP) - fungal infection
  2. Toxoplasma gondii encephalitis - Parasite
  3. Disseminated Mycobacterium avian complex (MAC disease)
A
  1. CD4 < 200 - Septra
  2. CD4 < 100 - Septra
  3. CD4 < 50 - Azithro
84
Q
  1. Signs of acute HIV infection
  2. When does seroconversion to HIV+ happen?
  3. How long can latent HIV last?
  4. Infections to suspect HIV if CD4 > 200?
  5. What CD4 count to be AIDs defining? Some AIDs defining conditions?
A
  1. Fever, fatigue, sore throat, lymphadenopathy, myalgia .. also watch out for PCP, toxoplasmosis, CMV, oral thrush
    - this can happen up to 6 weeks after exposure
    - usually lasts for 14 days
  2. Between 4-10 weeks after exposure (>95% within 6 months)
  3. Up to 8-10 years!
  4. Oral thrush, oral hairy leukoplakia, Kaposi sarcoma, TB, shingles, bacterial pneumonia
  5. < 200
    - PCP, Toxoplasmosis, recurrent pneumonia, invasive cervical cancer, Salmonella, TB, Histoplasmosis, HSV > 1 month
85
Q

PJP classic XRAY

A

“Batwing” like appearance

86
Q

3 HIV related malignancies

A
  1. Kaposi sarcoma
  2. CNS lymphoma
  3. Cervical cancer
87
Q

List 3 serum tests for HIV

A
  1. HIV Serology. A screening CBC and CD4
  2. Absolute lymphocyte count between 1000 and 2000 cells/µL = correlate with immunosuppression
  3. CD4 count below 200!
88
Q

List 6 causes of respiratory infections in HIV

A
  1. Acute bronchitis
  2. Bacterial pneumonia
  3. Tuberculosis
  4. PJP
  5. Mycobacterium pneumonia
  6. Toxoplasma pneumonia
89
Q

3 factors increasing the risk of needle stick injuries

A
  1. Depth of injury
  2. Injury in vein or artery
  3. Needle contaminated with positive blood
90
Q

HIV treatment:

  1. PEP regiment
  2. ART, when to start?
  3. Meds and side effectS?
A
  1. 28 day course of 3-ARTs, Initiate within 72 hours. Recheck patients 6 weeks, 12 weeks, 6 months
  2. ASAP regardless of CD4 count
  3. ART
    NRTI - ie. Tenofovir (TDF) ; mitochondrial toxicity, pancreatitis, hepatitis

NNRTI - ie. sustiva ; neuro/psych side effects

Protease inhibitor - ie. Danurovir ; insulin resistance, diabetes

Integrase inhibitor - ie. Raltegravir ; insomnia, suicide