Dr. Karatzios -- Fever in Immunocompromised

Question 1

Define febrile neutropenia

Answer 1

• Fever
  
  • ≥ 38.3 ^oC oral in a single measurement
  • 38 ^oC in 2 measurements within 1 hour

PLUS

• Low absolute neutrophil count (ANC)
  
  • ≤ 500 cells/mL

Question 2

4 causes of neutropenia secondary to cancer chemotherapy

Answer 2

• Denuded gut secondary to chemotherapy (including mucositis)
• Central line infections
• Fungal organisms
• Common organisms causing fever

Question 3

Usual pathogen of denuded gut secondary to chemo

Answer 3

Usually gram negative enteric rods

Question 4

Pathogens associated with central line infections causing neutropenia secondary to cancer chemo

Answer 4

• Usually gram positive cocci (CoNS, MSSA/MRSA)
• Pseudomonas aeruginosa

Question 5

2 fungal organisms that can cause neutropenia secondary to cancer chemo and their origins

Answer 5

• *Candida *spp. (from gut, from central line(s))
• *Aspergillus *spp. (from lungs)

Question 6

3 common organisms causing fever that can cause neutropenia secondary to cancer chemo

Answer 6

• S. pneumoniae
• Respiratory viruses
• C. difficile

Question 7

Explain the findings of unexplained fever in cancer chemo patients with febrile neutropenia

Answer 7

No bacteria ever isolated in blood culture = pieces of LPS from the gut

Question 8

2 probably causes of fever in a NEWLY diagnosed cancer patient (no chemo yet)

Answer 8

• Tumor/cancer
• Community pathogens (i.e. S. pneumoniae, respiratory viruses, etc)

Question 9

Etiology of fever without obvious symptoms in cancer chemo patients in order of what to suspect first

Answer 9

1. Bacteria coming from a denuded gut
2. Community-acquired sources
   
   • Pneumonia
   • Resp. viruses
3. If persistent, esp. while on very extensive and broad spectum ABX, think fungal illness
   
   • *Candida *spp., *Aspergillus *​spp.

Question 10

Etiology of fever in cancer patients with specific symptoms

Answer 10

• If IV site red and/or painful, central line sepsis
• If diarrhea, C. diff

Question 11

Most common cause of bacteremia in cancer chemotherapy pateitns

Answer 11

CoNS

Question 12

Etiology of fever in cancer patient with symptoms of mucositis and/or shock

Answer 12

All possible causes AND specifically Streptococcus viridans

Question 13

Chemotherapy drug that especially has a risk for causing mucositis

Answer 13

High dose Ara-C

Question 14

Minimum coverage for empiric antibiotic choice (3)

Answer 14

• Bacteria from gut, including anaerobes
• *Pseudomonas *spp.
• Staphylococcus aureus

Question 15

Pathogen against which there must be additional coverage for empiric ABX choice if there is the presence of mucositis or shock

Answer 15

Streptococcus viridans

Question 16

3 organisms to consider if you know or suspect resistance for fever in cancer patients

Answer 16

• MRSA
• ESBL
• VRE

Question 17

Empiric antibiotic for NEWLY diagnosed patient coming in with fever

Answer 17

Any antibiotic that covers community organisms causing pneumonia and sepsis (i.e. Ceftriaxone IV +/- “atypical” organism coverage)

Question 18

Empiric therapy for KNOWN cancer patients coming in with febrile neutropenia

Answer 18

• Broad spectrum beta-lactams
  
  • +/- aminoglycosides IV
  • +/- vancomycin IV depending on clinical condition
• Sometimes oral therapy used
  
  • i.e. Ciprofloxacin + Clindamycin

Question 19

3 conditions in KNOWN cancer patient with febrile neutropenia for which vancomycin IV is recommended

Answer 19

• Line sepsis
• Septic shock
• Known MRSA colonization

Question 20

When is empiric antifungal treatment administered for cancer patients with fever?

Answer 20

• Usually not given empirically IN THE BEGINNING unless there is clinical evidence for a fungal infection
• Started if fever persists past 4 days in cancer patients with febrile neutropenia (or sooner depending on evidence)

Question 21

3 signs of clinical evidence for a fungal infection requiring antifungal empiric treatment

Answer 21

• Characteristic rash
• Lung nodules on CXR
• Positive blood culture for yeast or fungus

Question 22

3 Tissues usually affected by *Candida *spp first before any blood tissue

Answer 22

• Liver
• Spleen
• Retina

Question 23

When are imaging studies for fungal infection most sensitive and why?

Answer 23

When neutropenia has resolved as abscesses will then form

Question 24

Blood count findings of cancer patient with fever which would point to invasive aspergillosis

Answer 24

• Severe neutropenia (ANC <100 cells/mL) AND
• Prolonged neutropenia (> 10 days)

Question 25

2 kinds of cancer patients most often affected by invasive aspergillosis

Answer 25

* Bone marrow transplant patients * Patients with AML ("strong" chemotherapy)

Question 26

Treatment for invasive aspergillosis in cancer patients with fever

Answer 26

Voriconazole IV until radiographic resolution (may take 1 - 2 months AT LEAST)

Question 27

2 situations which have an obvious clinical need for antiviral treatment

Answer 27

* Characteristic rash (i.e. varicella/shingles or herpes) * Severe respiratory illness (i.e. ***_influenza_***) NOTE: **No role for empiric antiviral treatment otherwise**

Question 28

Duration of antimicrobial/antiviral therapy for specific illness treatment

Answer 28

* At least 10 - 14 days AND * Until no fever AND * At least until ANC \> 500 cells/mL

Question 29

Duration of antimicrobial/antiviral therapy if no bacteremia and source identified

Answer 29

* Until no fever AND * At least until ANC \> 500 cells/mL

Question 30

Duration of antifungal therapy if no documented disease

Answer 30

Treat until you can rule out hepatosplenic candidiasis and candidal retinitis

Question 31

3 phases of graft versus host disease

Answer 31

1. Pre-engraftment 2. Post-engraftment (acute) 3. Late phase (chronic)

Question 32

2 bacterial opporunistic infections during pre-engraftment and post-engraftment phases of GVHD

Answer 32

* Gram negative bacilli * Gram positiv organisms

Question 33

3 viral opporunistic infections during GVHD

Answer 33

* Herpes simplex virus * Respiratory viruses * Enteric viruses

Question 34

2 fungal opporunistic infections during GVHD

Answer 34

* Aspergillus * Candida

Question 35

2 viral opporunistic infections starting during the post-engraftment phase of GVHD

Answer 35

* CMV * EBV PTLD

Question 36

4 late phase opportunistic pathogens in GVHD

Answer 36

* Encapsulated bacteria * Varicella Zoster virus * *Aspergillus species* * *Pneumocystis*

Question 37

7 conditions that predispose to infection

Answer 37

* Humoral immunity dysfunction * Cellular immunity dysfunction * Complement immunity dysfunction * Neutropenia (not due to chemo) * Hyper IgE (Job) Syndrome * Chronic granulomatous disease * Asplenia or splenic dysfunction

Question 38

4 pathogens usually involved in infection of those with humoral immunity dysfunction

Answer 38

Usually recurrent sinopulmonary infections with community organisms: * *S. pneumoniae* * *H. influenzae* * *Mycoplasma *spp. * *Moraxella catarrhalis*

Question 39

6 pathogens usually involved in infection of those with cellular immunity dysfunction

Answer 39

Usually organisms that require cellular immunity to be killed * Intracellular organisms: * *Salmonella *spp. * *Listeria monocytogenes* * *Mycobacterium *spp. * Fungi (including *Pneumocytis jiroveci*) * Viruses * Parasites (*Toxoplasma gondii*)

Question 40

Pathogen usually involved in infection for those with complement immunity dysfunction

Answer 40

Recurrent *Neisseria meningitidis *infections --\> Terminal Membrane Attack Complex dysfunction

Question 41

6 pathogens/infections that commonly affect those with neutropenia not due to chemo

Answer 41

Community organisms * *S. pneumoniae* * *S. aureus* * *Mycoplasma *spp * UTI * Respiratory viruses * *N. meningitides*

Question 42

Pathogen that affects those with hyper IgE (Job) Syndrome, and its manifestations

Answer 42

*S. aureus *(skin and severe invasive disease)

Question 43

Category of pathogens that affect those with chronic granulomatous disease (give 2 examples)

Answer 43

CATALASE positive organisms * *S. aureus* * *Aspergillus *spp

Question 44

4 pathogens that affect those with asplenia or splenic dysfunction

Answer 44

Encapsulated organisms * *S. pneumonia* * *H. influenzae* * *N. meningitidis* Sickle cell disease = Encapsulated + *Salmonella *spp (*Salmonella *spp. osteomyelitis)

Question 45

Neonate and young infant fever: criteria for **medical emergency**

Answer 45

Fever in babies less than 3 months old (especially less than 6 weeks old)

Question 46

4 types of pathogens that can cause neonatal and young infant fever

Answer 46

* Maternal stool/vaginal organisms * Maternal organisms * Neonatal HSV disease * Community bacteria and viruses

Question 47

3 maternal stool/vaginal organisms that can cause neonatal and young infant fever

Answer 47

* Enteric gram negative rods * GBS * *Listeria monocytogenes*

Question 48

2 maternal organisms that can cause neonatal and young infant fever

Answer 48

* *S. aureus *(MSSA or MRSA) * GAS

Question 49

2 manifestations of neonatal HSV disease

Answer 49

* Profound sepsis * Encephalitis

Question 50

Approach to febrile neonates \<1 year old

Answer 50

* Presume serious bacterial infection * Full septic workup (blood, urine cultures) including LP (culture) * Inpatient followup + empiric ABX IV * CXR, nasopharyngeal viral studies, stool culture _if warranted_

Question 51

Approach to febrile neonates \<1 month old if suspect meningitis or a "missed LP"

Answer 51

Meningitis doses of ampicillin and cefotaxime (ceftriaxone) NOTE: Some recommend adding gentamicin especially if GBS or *Listeria *spp. strongly suspected

Question 52

Recommendations for empiric acyclovir for neonatal HSV disease

Answer 52

Currently NOT a standard of practice and does NOT appear in any neonatal sepsis/meningitis guidelines

Question 53

2 treatment regimens for empiric antibiotics in febrile babies ≥ 1 month – 3 months

Answer 53

* Ampicillin IV + Gentamicin IV * Ampicillin IV + Vancomycin IV + third generation cephalosporin for meningitis (Ceftriaxone IV)