immunocompromised infections/fungal Flashcards
candidiasis?
candida albicans, yeast like fungi
-opportunistic
what are RF for Candida?
immunosuppressed, antibiotic use, diet stress
-those at extremes of age
how can candidiasis present?
Superficial mucocutaneous: oral candidiasis, vaginal candidiasis, diaper area candidiasis, etc.
Can also be invasive, esophageal candidiasis in AIDS, systemic dissemination, etc
May involve virtually any organ
where are most candida infections?
mucocutaneous and relatively treatable
what is the prognosis for disseminated candida infxn?
30-40% mortality
how is candida diagnoses?
superficial: wet mount, looking for hypae, pseudohyphae, or budding yease
0also blood cultures, urin cultures, biopsies
what is the tx for superficial candida infxn?
topical antifungal agents:
clotrmazole, econazole (ecoza), ciclopirox, miconazole, ketoconazole, nystatin
azole antifungals
fluconazole,
increases permeabiliity of cell membrane resulting in cell death
ADR of azole antifungals?
AT prolongation and arrhythmias
how do you tx candida infections?
parenteral antifungals such as fluconazole (IV or IM)
histoplasmosis?
fungus that grows as a yeast at body temp
hisoplasma capsulatum
where is histoplasmosis endemic?
OH, MO, MS river valley: acidic soil
-associated with renovation, construction actvities
what mammal can spread histoplasmosis?
bats!
what may you see on a CXR of a healthy person affected with histoplamsosis?
chronic granulomas (white areas, scar tissue)
-typically asymptomatic
what may you see on a CXR of an immunocompromised pt infected with histoplasmosis?
calcified nodes and nodules
what are sx of histoplasmosis infxn? (initially)
initally-pulmonary, that is often flu like and of a limited duration
Fever & chills, inspiratory chest pain (stabbing pain) and cough, joint pain, mouth sores & erythema nodosum (this is not specific only to this disease) on lower legs
but may get systemic spread and manifestations such as CNS, liver, spleen, rheumatologic, ocular, and hematologic
what are the sx of chronic phase histoplamsosis?
chest pain, cough, SOB, fever, sweating
-can cause inflammation in pericarddium, meninges, high fever
how do you dx histoplasmosis?
CXR, chest CT Bronchoscopy (get a biopsy) Biopsy Blood/urine for antigens or antibodies Spinal Tap if suspect infected CSF
what is the treatment of histoplasmosis?
usually clears up w/o tx
if sx > 1 mnth, need antifungal therapy:
Amphotericin B, itraconazole, and ketoconazole
CMV
very common, nearly everyone is infected but most ppl are asx
lifetime infxn once infected, virus dormant in most cases
how is CMV spread?
via body fluids: blood, saliva, urine, semen, and breast milk, respiratory drops
when is CMV concerning?
immunocompromised
or prego- passit on to infant via congenital or perinatal
what are clinical findings of CMV congenital infection?
(CMV inclusion disease)
- may be asx until later in life
- Jaundice, rash, low birth weight, splenomegaly, hepatomegaly & hepatic dysfunction, seizures, mental retardation, pupura, periventricular CNS calcification
what are the sx of acute acquired CMV?
fever malaise, myalagia, arthralgias, splenomegaly, abnormal liver enzyme, leukopenia, and atypical lymphocytes
*similar to EVB but no pharyngitis, respiratory sx, or heterophil antibodies
what do you think with a CMV infxn?
visual, pneumonia, GIT and hepatitic, nervous system
what are sx that may present in an immunocompromsised pt?
(think HIV comorbidity)
- CMV retinits (CD4 less than 50)
- GI manifestations
- Pulmonary manifestations (bone marrow transplant pts)
- neurological
what would an exam reveal of a pt with CMV retinitis?
neovasculariztion and proliferative lesion “pizza pie”
aggressive HIV tx can reduce this
what are CMV GI manifestations?
esophagitis, odynophagia, small bowel inflammatory ulcer, D, hematochezia, abdominal pain, weight loss, and chlangiopathy
what are neurologic CMV manifestations?
polyradiculopathy, transverse myelitis, encephalitis
what other disease may CMV infection play a role in?
IBd, atherosclerosis, breast cancer
what may be seen on diagnostic studies of pts with CMV?
lymphocytosis or leukopenia
what is the definitive diagnostic test for CMV?
culture, but its very difficult
-antigens can be deteced in blood, urine, CSF via PCR
what if CMV IgM and IgG are both negative?
No current or prior infection; no immunity, person is susceptible to primary infection
Symptoms due to another cause
OR
immune system cannot produce adequate amount of antibody (immunocompromised)
what if CMV IgM is positive and IfG is negative?
Recent active primary infection
OR person re-exposed to CMV
OR reactivation of latent CMV
*Result is NOT diagnostic of primary infection
what if IgM is postivie and IgG is positive w/ a four fold increase in titer btw acute adn convalescent samples?
-likely active primary or reactivated latent infection
what if CMV IgM is negative and IgG is postive
Past exposure, person is immune from primary infection; latent infection
what is CMV treatment?
key is prevention: limitin blood transfusions, filtering to remove elukocytes, and restricting the organ donor pool to sernegative dones
what can be give to bone marrow transplant recipients to decrease the risk of CMV?
CMVimmunoglobulin and IV ganciclovir
what are antivirals that can be given to immunocompormised pts dx with CmV?
ganciclovir, valganciclovier, foscarnet, and cidofoir
what may be seen on a a tissue biopsy of a pt with CMV?
intracytoplasmic inclusions “Owls’ eyes”
what is foscavir?
tx for CMV and HSV/VZV
-works by inhibiting viral DNA polymerase
what are ADRs of foscavir?
depletion of electrolytes (think K, Mg, Ca, Ph)
granulocytopenia, thrombocytopenia,myelosuppression
cryptococcus sp.?
-crypococcus neoformans is an encapsulated budding yeast found in soil contaminated with dried pigeon dung
how is cryptococcus transmitted?
through inhalation and causes illness in pts with cellular immune deficiency such as HIV, cancer, long-term croticosteroid therapy
what are clinical findings of Cryptococcus?
- pulmonary dz
- CNS dz
- cryptococcoma
- disseminated dz
what are features of pulmonary cryptococcus?
- fever, cough, dyspnea
- COPD, chronic steroid use, posttransplan
what would CXR of cryptococcus reveal?
nodules or pneumonitis (lung inflammation)
what are features of cryptococcal CNS dz?
- HA, meningeal sings
- occurs with CD4 count less than 50
- mental status change, cranial nerve or visual abnormalities
what is a cryptococcoma?
rare, intracerebral mass lesion that causese obstructive hydrocephalus
what are features of a disseminated cryptococcal dz?
rare, but may affect the skin, prostate, osteoarticular surface, eye, lymph tissue, or other sites
dx studies of cryptococcal dz?
- CSF
- culture
- antigen assay
- CT/MRI if suspected cryptococcoma
what would a CSF sample show if infected with cryptococcus?
variable pleocytosis (predominantly lympocytes)
- increased opeing pressure
- increased protein
- decreased glucose
what would culture show in cryptococcal dz?
budding, encapsulated fugus
what are antigen detecting asssas for cryptococcal dz?
- latex agglutination assay: india ink stain or serology
- cryptococcal antigen assay (CRAG)
- cryptococcal antigen can be detected in CSF and serum
what is the tx for cryptococcal infxn (HIV pts)
oral fluconazole for 10 wks
what isthe tx for severe cryptococcal infexxn in HIV pts
amphotericin B for the first 2 weks, the oral fluconazone
what can also be added to tx severe cryptococcal da?
flucytosine
wht is also recommended for tx in immunocompormised pts with severe cryptococcal dz?
lifelong fluconazole tx
what is recommended for non-HIV immunocompromised pts?
*mortality rate is much higher
tx with amphotericin B
what is fluctyosine?
Pyrimidine antifungal
MOA
Converted to 5-FU in the fungal cell
Inhibits fungal protein and DNA syntises
what are ADRs of flucytosine?
leukopenia and thrombocytopenia
underlying hematological disorder, radiation treatment or drugs that injure the bone marrow
rash, nausea, vomiting, diarrhea
Elevated LFTs
how does amphotericin B work?
Binds ergosterol in fungal cells, damaging cell membranes
Can bind cholesterol in mammalian cells
Static or cidal depending on concentration in tissues and susceptibility of organism
what must you be very cautious with when prescribing amphotericin B?
confusing the preparations
Conventional ampho B and liposomal (Ambisome) have different dose ranges
why is it called amphoterrible
Infusion reactions:
Acute reactions (eg, fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, tachypnea)
may occur 1-3 hours after starting infusion
usually more common with the first few doses and generally diminish with subsequent doses
Avoid rapid infusion to prevent hypotension, hypokalemia, arrhythmias, and shock
Give small test dose first
what are other bad ADR of amphotericin?
-nephrotoxicity
-anaphylaxis
-leukoencephalopathy
-hypotension
-hypoK, hypoMg
-anorexia, N, V, D,
anemia
Pneumocystis jiroveci? general features
PJP
- fungus found in the lungs of humans and many animals
- evidence of infection can be found in almost all pple
- prolly transmitted through the air and lies latent in alveoli
what pt population is more likely to be affected by PJP?
premature of dbilitated infantes in underdeveloped areas during epidems
-sporadic cases in pts w/ abnormal cellular immunity: CA, severe malnutrition, immunosuppressive drugs, irradiation, or in thouse w/ HIV/AIDs and CD4 < 200
what is the most commmon opportunistic infxn in HIV dz?
PJP
what are clinical findings of PJP?
fever, shortness of breath, nonproductive cough
- fatigue, weakness, weight loss
- may have spontaneous pneumothorax
what is the cause of recurrent pneumothorax?
previous pentamidine use
what is pentamidine?
s an antimicrobial medication used to treat African trypanosomiasis, leishmaniasis, babesiosis, and to prevent and treat pneumocystis
pneumonia (PJP)-nebulized ofrm in people with poor immune function
what are other side effects of pentamidine?
rash neutropenia abnormal liver fxn serum folate deficiency calcium imbalance hypoglycemia hyperglycemia hyponatremia nephrotoxicity fatal pancreatits
what may a PE and CXR reveal in a pt with PJP?
PE findings are disproportionate to imaging results, which show diffuse intersitial infiltrates that may be heterogeneous, miliary, or patchy
*btw 5-10% of pts have normal xray
what are dx studies done for PJP?
-blood gas
-LDH
CBC
what may blood gas levels show in pt with PJP
hypoxia, hypocapnia, reduced CO diffusion
what are LDH levels?
lactate dehydrogenase: usually found in heart, liver, skeletal muscles: nay damage, and LDH will be released into the blood stream
what will LDH levels look like in a pt with PJP
will be increased
what will a CBC show in pts with PJP
low WBC
can this organism be identified in PJP?
yes, with specfic stains of induced sputum or via bronchoalveolar lavage
what is tx of PJP
TMP-SMX; recommended for pts presenting with cough or dyspnea
what is the clinical course follwing bactrim tx of PJP
-pts often get worse at the start of tx
when do you add steroids to the tx of PJP?
when PaO2 is less than 70; prevents deteriorration and promotes oxygenations
what are hypersensitivity rxns to TMP-SMX?
(bc of sulfa)
- fever
- rash
- malaise
- neutropenia
- hepatitis,
- nephritis
- thrombocytopenia
- hyperbilirubinemia
*systematic desensitization is often successful
what is a good alternative to TmP-SMX tx?
dapsone (can also tx leprosy, dermatitis herpetiformis, toxoplasmosis
what are side effects of dapsone?
- anemia
- rash
- fever
what is a contraindication for dapsone?
do not take with didanosine (antiretroviral)
what can be used for pts that can’t tolerate bactrim or pentamidine?
atovaquone
what must you educate patients on who take atovaqoune
- take with fatty meal
- limited side effects (SJS)
PJP prophylaxis
even after a pt is successfully treated
all pts with a CD4 count of less than 200 cells should receive prophylactic treatment
bactrim
