Dr. Karatzios -- Fever in Immunocompromised Flashcards
Define febrile neutropenia
- 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
4 causes of neutropenia secondary to cancer chemotherapy
- Denuded gut secondary to chemotherapy (including mucositis)
- Central line infections
- Fungal organisms
- Common organisms causing fever
Usual pathogen of denuded gut secondary to chemo
Usually gram negative enteric rods
Pathogens associated with central line infections causing neutropenia secondary to cancer chemo
- Usually gram positive cocci (CoNS, MSSA/MRSA)
- Pseudomonas aeruginosa
2 fungal organisms that can cause neutropenia secondary to cancer chemo and their origins
- *Candida *spp. (from gut, from central line(s))
- *Aspergillus *spp. (from lungs)
3 common organisms causing fever that can cause neutropenia secondary to cancer chemo
- S. pneumoniae
- Respiratory viruses
- C. difficile
Explain the findings of unexplained fever in cancer chemo patients with febrile neutropenia
No bacteria ever isolated in blood culture = pieces of LPS from the gut
2 probably causes of fever in a NEWLY diagnosed cancer patient (no chemo yet)
- Tumor/cancer
- Community pathogens (i.e. S. pneumoniae, respiratory viruses, etc)
Etiology of fever without obvious symptoms in cancer chemo patients in order of what to suspect first
- Bacteria coming from a denuded gut
- Community-acquired sources
- Pneumonia
- Resp. viruses
- If persistent, esp. while on very extensive and broad spectum ABX, think fungal illness
- *Candida *spp., *Aspergillus *spp.
Etiology of fever in cancer patients with specific symptoms
- If IV site red and/or painful, central line sepsis
- If diarrhea, C. diff
Most common cause of bacteremia in cancer chemotherapy pateitns
CoNS
Etiology of fever in cancer patient with symptoms of mucositis and/or shock
All possible causes AND specifically Streptococcus viridans
Chemotherapy drug that especially has a risk for causing mucositis
High dose Ara-C
Minimum coverage for empiric antibiotic choice (3)
- Bacteria from gut, including anaerobes
- *Pseudomonas *spp.
- Staphylococcus aureus
Pathogen against which there must be additional coverage for empiric ABX choice if there is the presence of mucositis or shock
Streptococcus viridans
3 organisms to consider if you know or suspect resistance for fever in cancer patients
- MRSA
- ESBL
- VRE
Empiric antibiotic for NEWLY diagnosed patient coming in with fever
Any antibiotic that covers community organisms causing pneumonia and sepsis (i.e. Ceftriaxone IV +/- “atypical” organism coverage)
Empiric therapy for KNOWN cancer patients coming in with febrile neutropenia
- Broad spectrum beta-lactams
- +/- aminoglycosides IV
- +/- vancomycin IV depending on clinical condition
-
Sometimes oral therapy used
- i.e. Ciprofloxacin + Clindamycin
3 conditions in KNOWN cancer patient with febrile neutropenia for which vancomycin IV is recommended
- Line sepsis
- Septic shock
- Known MRSA colonization
When is empiric antifungal treatment administered for cancer patients with fever?
- 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)
3 signs of clinical evidence for a fungal infection requiring antifungal empiric treatment
- Characteristic rash
- Lung nodules on CXR
- Positive blood culture for yeast or fungus
3 Tissues usually affected by *Candida *spp first before any blood tissue
- Liver
- Spleen
- Retina
When are imaging studies for fungal infection most sensitive and why?
When neutropenia has resolved as abscesses will then form
Blood count findings of cancer patient with fever which would point to invasive aspergillosis
- Severe neutropenia (ANC <100 cells/mL) AND
- Prolonged neutropenia (> 10 days)
2 kinds of cancer patients most often affected by invasive aspergillosis
- Bone marrow transplant patients
- Patients with AML (“strong” chemotherapy)
Treatment for invasive aspergillosis in cancer patients with fever
Voriconazole IV until radiographic resolution (may take 1 - 2 months AT LEAST)
2 situations which have an obvious clinical need for antiviral treatment
- Characteristic rash (i.e. varicella/shingles or herpes)
- Severe respiratory illness (i.e. influenza)
NOTE: No role for empiric antiviral treatment otherwise
Duration of antimicrobial/antiviral therapy for specific illness treatment
- At least 10 - 14 days AND
- Until no fever AND
- At least until ANC > 500 cells/mL
Duration of antimicrobial/antiviral therapy if no bacteremia and source identified
- Until no fever AND
- At least until ANC > 500 cells/mL
Duration of antifungal therapy if no documented disease
Treat until you can rule out hepatosplenic candidiasis and candidal retinitis
3 phases of graft versus host disease
- Pre-engraftment
- Post-engraftment (acute)
- Late phase (chronic)
2 bacterial opporunistic infections during pre-engraftment and post-engraftment phases of GVHD
- Gram negative bacilli
- Gram positiv organisms
3 viral opporunistic infections during GVHD
- Herpes simplex virus
- Respiratory viruses
- Enteric viruses
2 fungal opporunistic infections during GVHD
- Aspergillus
- Candida
2 viral opporunistic infections starting during the post-engraftment phase of GVHD
- CMV
- EBV PTLD
4 late phase opportunistic pathogens in GVHD
- Encapsulated bacteria
- Varicella Zoster virus
- Aspergillus species
- Pneumocystis
7 conditions that predispose to infection
- 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
4 pathogens usually involved in infection of those with humoral immunity dysfunction
Usually recurrent sinopulmonary infections with community organisms:
- S. pneumoniae
- H. influenzae
- *Mycoplasma *spp.
- Moraxella catarrhalis
6 pathogens usually involved in infection of those with cellular immunity dysfunction
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)
Pathogen usually involved in infection for those with complement immunity dysfunction
Recurrent *Neisseria meningitidis *infections
–> Terminal Membrane Attack Complex dysfunction
6 pathogens/infections that commonly affect those with neutropenia not due to chemo
Community organisms
- S. pneumoniae
- S. aureus
- *Mycoplasma *spp
- UTI
- Respiratory viruses
- N. meningitides
Pathogen that affects those with hyper IgE (Job) Syndrome, and its manifestations
*S. aureus *(skin and severe invasive disease)
Category of pathogens that affect those with chronic granulomatous disease (give 2 examples)
CATALASE positive organisms
- S. aureus
- *Aspergillus *spp
4 pathogens that affect those with asplenia or splenic dysfunction
Encapsulated organisms
- S. pneumonia
- H. influenzae
- N. meningitidis
Sickle cell disease = Encapsulated + *Salmonella spp (Salmonella *spp. osteomyelitis)
Neonate and young infant fever: criteria for medical emergency
Fever in babies less than 3 months old (especially less than 6 weeks old)
4 types of pathogens that can cause neonatal and young infant fever
- Maternal stool/vaginal organisms
- Maternal organisms
- Neonatal HSV disease
- Community bacteria and viruses
3 maternal stool/vaginal organisms that can cause neonatal and young infant fever
- Enteric gram negative rods
- GBS
- Listeria monocytogenes
2 maternal organisms that can cause neonatal and young infant fever
- *S. aureus *(MSSA or MRSA)
- GAS
2 manifestations of neonatal HSV disease
- Profound sepsis
- Encephalitis
Approach to febrile neonates <1 year old
- 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
Approach to febrile neonates <1 month old if suspect meningitis or a “missed LP”
Meningitis doses of ampicillin and cefotaxime (ceftriaxone)
NOTE: Some recommend adding gentamicin especially if GBS or *Listeria *spp. strongly suspected
Recommendations for empiric acyclovir for neonatal HSV disease
Currently NOT a standard of practice and does NOT appear in any neonatal sepsis/meningitis guidelines
2 treatment regimens for empiric antibiotics in febrile babies ≥ 1 month – 3 months
- Ampicillin IV + Gentamicin IV
- Ampicillin IV + Vancomycin IV + third generation cephalosporin for meningitis (Ceftriaxone IV)
