Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
305 Cards in this Set
- Front
- Back
|
Meningitis neurological after-effects
|
seizures
hearing loss hydrocephalus |
|
|
Meninges
|
membranes that surround the brain and spinal cord
|
|
|
Separate membranes of meninges
|
1. Dura mater
2. arachnoid 3. Pia mater |
|
|
Dura mater
|
attached to skull
|
|
|
arachnoid
|
middle membrane of meninges
|
|
|
subarachnoid space
|
space between arachnoid and pia mater
|
|
|
pi mater
|
covers brain tissue
|
|
|
CSF
|
cerebrospinal gluid
fluid within the CNS that suspends brain and other CNS structures |
|
|
Where is CSF produced?
|
In the choroids plexus
|
|
|
Normal contents of CSF
|
WBC < 5 cells/m
Portein < 50 mg/dL Glucose 50-66% simultaneous serum value |
|
|
Normal WBC in CSF
|
< 5 cells/m3
|
|
|
Normal protein in CSF
|
< 50 mg/dL
|
|
|
Normal glucose in CSF
|
50-66% simultaneous serum value
|
|
|
BBB
|
Blood-brain barrier
natural barrier exchange of drugs and endogenous compounds among the blood, brain, and CSF |
|
|
What is the BBB made of?
|
consists of tightly joined endothelial cells
|
|
|
Bacterial meningitis
|
bacteria is the cause of the meningitis
|
|
|
Aseptic Meningitis
|
meningeal inflammation without evidence of bacterial infection
|
|
|
Encephalitis
|
inflammation of brain tissue
|
|
|
Sequence of events for development of meningitis
|
1. colonization of host
2. bacteria invade bloodstream 3. bacteria invade CNS |
|
|
Predisposing Risk Factors for Meningitis
|
Age > 50
immunosuppression head trauma neurosurgical patients local infection exposure to someone with meningitis anatomical or functional asplenia complement deficiency recent travel to area with endemic meningococcal disease |
|
|
Classic/Early signs and symptoms of meningitis
|
fever
nuchal rigidity altered mental status severe H/A photophobia Kernig sign + Brudzinski sign + Petechial rash (N. meningitidis only) |
|
|
Kernig sign
|
laying down, can't raise leg to 90 degrees and keep leg straight
|
|
|
Brudzinski sign
|
life up head and knees bend while lying down
|
|
|
When is petechial rash a symptoms of meningitis?
|
Only if meningitis caused by N. meningitidis
|
|
|
Meningitis Triad symptoms
|
fever, nuchal rigidity, altered mental status
|
|
|
Late signs and symptoms of meningitis
|
irritability
drowsiness seizures coma |
|
|
CSF Opening Pressure:
Normal |
75-175 mm water
|
|
|
CSF Opening Pressure:
Bacterial |
Elevated (>175)
|
|
|
CSF Opening Pressure:
Viral |
Elevated (>175)
|
|
|
CSF WBC:
Normal |
< 5
|
|
|
CSF WBC:
Bacterial |
1000-5000
|
|
|
CSF WBC:
Viral |
100-1000
|
|
|
CSF Differential:
Normal |
>90 Monos
|
|
|
CSF Differential:
Bacterial |
>80 PMNs
|
|
|
CSF Differential:
Viral |
50 Lymphs
|
|
|
CSF Protein:
Normal |
<50
|
|
|
CSF Protein:
Bacterial |
100-500
|
|
|
CSF Protein:
Viral |
30-100
|
|
|
CSF Glucose:
Normal |
50-66% simultaneous serum value
|
|
|
CSF Glucose:
Bacterial |
< 40
(<60% simultaneous serum value) |
|
|
CSF Glucose:
Viral |
<30-70
|
|
|
Meningitis Diagnosis Testing
|
History and PE
Lumbar Puncture CSF Gram stain and culture Latex agglutination PCR CT scan |
|
|
Organisms causing meningitis:
< 1 month old |
Strep agalactiae
E. coli L. monocytogenes Klebsiella |
|
|
Organisms causing meningitis:
1-23 months old |
S. pneumo
N. meningitidis S. agalactiae H. influenzae E. coli |
|
|
Organisms causing meningitis:
2-50 years old |
N. meningitidis
S. pneumoniae |
|
|
Organisms causing meningitis:
>50 years old |
S. pneumo
N. meningitidis L. monocytogenes aerobic gram - bacilli |
|
|
Persons at risk for N. meningitides
|
age group 5-29 years
close contacts |
|
|
N. meningitides serotypes
|
A, B, C, Y W135
|
|
|
Most common symptoms of N. meningitides
|
petechiae
purpuric lesions |
|
|
Post-infection immunologic reaction due to N. meningitides
|
10-14 days after onset of disease
fever, arthritis (large joints), pericarditis Occurs even with successful treatment |
|
|
Risk factors for S. pneumo caused meningitis
|
repeated episodes of otitis media
CSF leaks fracture of sinuses |
|
|
Common complications due to S. pneumo caused meningitis
|
coma seizures
(neuro complications) |
|
|
Risk factors for H. influenzae caused meningitis
|
otitis media
paranasal sinus infections CSF lead |
|
|
Persons at risk for developing meningitis caused by gram - organisms
|
CNS trauma
|
|
|
Causes of Viral meningitis
|
enteroviruses
coxsackieviruses cytomegalovirus (CMV) herpes simplex virus (HSV) |
|
|
Causes of Fungal meningitis
|
cryptococcus neoformans
|
|
|
Goals for bacterial meningitis treatment
|
eradicate invading organism
alleviate symptoms prevent neurologic sequelae |
|
|
When to give empiric antibiotics for suspected meningitis
|
Give for at least 48-72 hrs or until meningitis is ruled out
DO NOT delay initiation once meningitis is suspected Higher doses used |
|
|
Factors affecting penetration of antibiotics into the CSF
|
inflammation of the meninges
antibiotic characteristics |
|
|
Which antibiotic is more likely to penetrate CSF?
low MW vs. High MW |
low molecular weight
|
|
|
Which antibiotic is more likely to penetrate CSF?
Non-ionized at physiologic pH vs. ionized |
Non-ionized
|
|
|
Which antibiotic is more likely to penetrate CSF?
water soluble vs. lipid soluble |
lipid soluble
|
|
|
Which antibiotic is more likely to penetrate CSF?
protein bound vs. non-protein bound |
non-protein bound
|
|
|
Antibiotic therapy for meningitis in patients < 1 month old
|
Ampicillin PLUS cefotaxime
|
|
|
Antibiotic therapy for meningitis in patients 1-23 months old
|
3rd generation cephalosporin (ceftriaxone or cefotaxime) PLUS vancomycin
|
|
|
Antibiotic therapy for meningitis in patients 2-50 years old
|
3rd generation cephalosporin (ceftriaxone or cefotaxime) PLUS vancomycin
|
|
|
Antibiotic therapy for meningitis in patients > 50 years old
|
Ampicilling PLUS 3rd generation ceph. (ceftriaxone or cefotaxime) PLUS vancomycin
|
|
|
Duration of treatment for meningitis caused by:
N. meningitides H. influenzae |
7 days
|
|
|
Duration of treatment for meningitis caused by:
S. pneumo |
10-14 days
|
|
|
Duration of treatment for meningitis caused by:
S. agalactiae |
14-21 days
|
|
|
Duration of treatment for meningitis caused by:
aerobic gram - bacilli |
21 days
|
|
|
Duration of treatment for meningitis caused by:
L. monocytogenes |
>/= 21 days
|
|
|
When may Adjunctive dexamethasone therapy for meningitis help decrease neurologic sequelae?
|
infants/children with H. influenze type B meningitis
Adults with suspected S. pneumo meningitis |
|
|
How much does adjunctive dexamthasone therapy for meningitis decrease time to eradication?
|
No significant difference in time to bacterial eradication
|
|
|
When should dexamethasone be given?
|
10-20 mnutes before or at same time as 1st dose of antibiotic
|
|
|
Duration of use for dexamethasone
|
2-4 days
|
|
|
Disadvantage of using dexamthasone for meningitis therapy
|
decreases inflammation )in meninges) --> decreased amount of drug that penetrates CNS
|
|
|
Prevention for N. meningitidis caused meningitis
|
Chemoprophylaxis
Vaccination |
|
|
Chemoprophylaxis for N. meningitidis
Who gets it? What drug is given? |
Close contacts - persons with prolonged contact to infected person or secretions within 1 week before symptoms begin until 24 hrs after antibiotics are initiated
Rifampin 600 mg q12h x 4 doses |
|
|
Vaccination for N. meningitidis
|
4 serotypes: A, C, Y, W135
Conjugated vaccine Polysaccharide vaccine |
|
|
What type of vaccine is preferred for N. meningitides
|
Conjugated vaccine
|
|
|
Which N. meningitides vaccine should be given to patients > 55?
|
Polysaccharide vaccine
|
|
|
Who is recommended to receive the N. meningitides vaccine?
|
all persons age 11-18
persons 9-23 months, 2-10 years, and 19-55 at increased risk |
|
|
DOC for chemoprophylaxis for N. meningitidis
|
Rifampin 600 mg q12h x 4 doses
|
|
|
Prevention of S. pneumo caused meningitis
|
Vaccination
|
|
|
Types of vaccines for s. pneumo meningitis
|
pneumococcal polysaccaride vaccine (23-valent)
Pneumococcal conjugate vaccine (13-valent) |
|
|
Who should receive the pneumococcal polysaccharide vaccine to prevent S. pneumo meningitis?
|
>/= 65 years old and 2-64 years old with increased risk factors
|
|
|
Who should receive the pneumococcal conjugate vaccine to prevent S. pneumo meningitis?
|
All children < 23 months and children 24-59 months with chronic illness
|
|
|
PCP
|
Pneumocystis jirovecci pneumonia (previously known as pneumocystis carinii pneumonia)
|
|
|
What is PCP?
|
organism with protozoal and fungal properties
|
|
|
How is PCP classified?
|
as a fungus
|
|
|
T/F.
PCP is part of normal colonization in the lungs. |
True
|
|
|
Who is at risk for PCP?
|
Only those immunocompromised
|
|
|
PCP:
signs and symptoms |
Slow onset (days-weeks)
fever, fatigue, dyspnea, tachypnea, nonproductive cough |
|
|
Most common form of PCP
|
pneumonia
|
|
|
Common PCP coinfection
|
thrush
|
|
|
How is PCP diagnosed?
|
CXR: crushed glass appearance all over lungs
arterial blood glass (ABG) sputum culture |
|
|
What does a CXR of PCP look like?
|
crushed glass appearance all over lungs
|
|
|
1st line treatment for PCP pneumonia
|
TMP/SMX 15-50 mg/kg/day IV in 3-4 divided doses
x 21 days |
|
|
TMP: SMX
Dosing based on... |
5:1 (TMP:SMX)
Dosing based on TMP |
|
|
Most efficacious and cost-effective treatment for PCP pneumonia
|
TMP/SMX
|
|
|
What two enzymatic steps are inhibited by TMP/SMX?
|
DHFR and dihydroptenroate synthas
|
|
|
TMP/SMX:
ADRs |
photosensitivity
rash bone marrow suppression (esp. neutropenia) |
|
|
When should adjuvant steroids be given with PCP pneumonia?
|
Patients with severe PCP and PaO2 < 70 mmHg
|
|
|
When should adjuvant steroid therapy begin with PCP pneumonia?
|
within 72 hours of treatment
(for qualifying patients only) |
|
|
When should steroid regimens begin with PCP pneumonia treatment?
|
within 72 hours of treatment
|
|
|
Steroid regimen for PCP pneumonia
|
Days 1-5: Prednisone 40 mg BID
Days 6-10: Prednisone 40 mg QD Days 11-21: Prednisone 20 mg QD |
|
|
What steroid regimen should be used for patients with PCP pneumonia who are unable to take PO?
|
IV methylprednisolone (75% of PO prednisone dose)
|
|
|
What is the advantage to using adjuvant steroids in patients with PCP pneumonia?
|
Mortality rates and rates of respiratory failure reduced
|
|
|
Candidates for PCP pneumonia prophylaxis
|
CD4+ < 200 cells/micoL or history of oropharyngeal candidiasis
|
|
|
PCP Pneumonia:
Primary Prophylaxis |
TMP/SMX double strength 1 tab PO QD
OR TMP/SMX DS 1 tab TIW OR TMP/SMX SS 1 tab PO QD |
|
|
What can TMP/SMX double strength be used as a prophylaxis regimen for?
|
PCP pneumonia
toxoplasmosis some respiratory bacterial pathogens |
|
|
When should PCP pneumonia primary prophylaxis be discontinued?
|
Patients who have responded to HAART with an increase in CD4 count to > 200 for at least 3 months
|
|
|
PCP pneumonia:
Secondary prophylaxis |
Same as primary prophylaxis using TMP/SMX
|
|
|
When should PCP pneumonia secondary prophylaxis be discontinued?
|
Same as with primary prophylaxis
Patients who have responded to HAART with an increase in CD4 count to > 200 for at least 3 months |
|
|
What organism causes Toxoplasmic encephalitis?
|
Toxoplasma gondii
|
|
|
What is toxoplasma gondii?
|
intracellular parasite
passed to humans from raw/undercooked meat and by contact with feces from infected cats |
|
|
How is toxoplasma gondii classified?
|
protozoa
|
|
|
Counseling to prevent exposure to toxoplasma gondii
|
Do not eat raw/undercooked meat
Wash hands after handling raw meat, after gardening/contact with soil Wash fruits/veggies before eating raw Change cat litter box daily (by HIV neg., non-pregnant) Wash hands thoroughly after changing litter box Keep cats inside; do not adopt/handle stray cats Only feed cats canned/dried commerical food or well-cooked table food (no raw/undercooked meat) |
|
|
Toxoplasmic encephalitis:
Signs and symptoms |
CNS infection
typically associated with fever, seizures, focal neurological deficits, other symptoms associated with encephalitis |
|
|
Diagnosis of Toxoplasmic encephalitis
|
serological testing for Toxoplasma IgG
neuroradiological scans (CT/MRI) brain biopsy (reserved for patients refractory to empiric therapy) |
|
|
Toxoplasmic encephalitis:
1st line treatment |
Sulfadiazine PLUS pyrimethamine PLUS leucovorin
x at least 6 weeks |
|
|
Toxoplasmic encephalitis
Duration of treatment |
at least 6 weeks
|
|
|
Most active sulfonamide against T. gondii
|
Sulfadiazine
|
|
|
Which other sulfa drugs can be substituted for sulfadiazine for toxoplamic encephalitis treatment?
|
NONE
|
|
|
Most potent folic acid antagonist
|
pyrimethamine
|
|
|
Why is leucovorin used for Toxoplasmic encephalitis treatment?
|
AKA folinic acid
mandatory to prevent bone marrow suppression |
|
|
Toxoplasmic encephalitis:
Primary Prophylaxis Candidates |
CD4 < 100 and Toxoplasma IgG + (= previous exposure)
|
|
|
What does + toxoplasma IgG mean?
|
previous exposure to bug
|
|
|
Toxoplasmic encephalitis:
Primary prophylaxis |
TMP/SMX DS QD
|
|
|
Toxoplasmic encephalitis:
Discontinuation of primary prophylaxis |
after response to HAART and CD4 > 200 for at least 3 months
|
|
|
Toxoplasmic encephalitis:
Secondary prophylaxis (chronic suppression) |
Sulfadiazine PLUS pyrimethamine PLUS leucovorin
(also protective against PCP) |
|
|
Toxoplasmic encephalitis:
Discontinuation of secondary prophylaxis (chronic suppression) |
after completion of initial therapy and CD4>200 on HAART for at least 6 months
|
|
|
Toxoplasmic encephalitis:
Restarting secondary prophylaxis |
when CD4 count decreases to < 200
|
|
|
Organism causing cryptococcal meningitis
|
cryptococcus neoformans
|
|
|
What is cryptococcus neoformans?
|
encapsulated yeast
|
|
|
What is the most common life-threatening fungal infection in AIDS patients?
|
cryptococcus neoformans (cryptococcal meningitis)
|
|
|
How is cryptococcus neoformans transferred?
|
grows in pigeon droppings and nesting areas
acquired by direct inhalation disseminates from lungs to meninges in setting of compromised T-lymphocytes function |
|
|
Cryptococcal meningtis:
Signs and symptoms |
progressive development of frever and/or H/A, neck stiffness, photophobia, CNS changes
disseminated disease (skin, pulmonary) |
|
|
Cryptococcal meningtis:
Diagnosis |
brain imaging
lumbar puncture cryptococcal CSF antigen Gram stain and culture |
|
|
Cryptococcal meningtis:
1st line treatment |
Induction: ampho. B deoxycholate PLUS flucytosine (5-FC0 x at least 2 weeks
Maintenence: fluconazole 400mg/day x 8 more weeks Chronic suppression: fluconazole 200 mg/day until CD4 increases |
|
|
Cryptococcal meningtis:
Duration of treatment |
Induction: at least 2 weeks
Maintenance: 8 more weeks Chronic suppression: until CD4 counts increase |
|
|
CNS penetration of ampho. B
|
very good penetration
|
|
|
Ampho. B ADEs
|
high risk of renal failure
infusion reactions alter electrolytes |
|
|
Ampho. B formulations
|
ampho. B deoxycholate: 0.7 mg/kg/day
Lipid formulation: liposomal ampho. B (ABLC): 5mg/kg/day |
|
|
What other meds are recommended for use with ampho. B?
|
Saline bolus 500 mL pre and post ampho infusion
Diphenhydramine and APAP 30 min pre-ampho Meperidine to treat/prevent rigors and/or add hydrocortisone IV to ampho bag |
|
|
Cryptococcal meningtis:
Primary prophylaxis |
Not recommended
|
|
|
Cryptococcal meningtis:
Secondary Prophylaxis (chronic suppression) |
Fluconazole 200 mg QD
|
|
|
Cryptococcal meningtis:
Discontinuation of secondary prophylaxis |
after completion of initial therapy, patients must be asymptomatic and have sustained increase in CD4>200 after HAART for at least 6 months
|
|
|
Cryptococcal meningtis:
Restarting secondary prophylaxis |
when CD4 decrease to < 200
|
|
|
MAC
|
Mycobacterium avium complex/infection (MAI)
|
|
|
What is organims is MAC comprised of?
|
mycobacterium avium and mycobacterium intracellulare
|
|
|
Where is MAC found?
|
ubiquitous in nature
commonly inhabiting soil and water |
|
|
MAC process of colonization in body
|
begins with colonization of intestinal or respiratory tracts after organism ingestion or inhalation
subsequent development of localized infection and sometimes seeding of blood |
|
|
MAC:
signs and symptoms |
typically a multiporgan system (disseminated) disease in AIDS patients
fever, night sweats, anorexia, weight loss occurs in most D, abdominal pain, increased LFTs, anemia, neutropenia, thrombocytopenia hepatomegaly, splenomegaly, lymphadenopathy |
|
|
MAC:
Diagnosis |
Gold standard: culture
some patient with - blood culture have + liver, bone, marrow, or lymph node biopsies which confirm diagnosis |
|
|
T/F.
A blood culture - for MAC definitively rules out MAC. |
False
some patient with - blood culture have + liver, bone, marrow, or lymph node biopsies which confirm diagnosis |
|
|
How long does it take for MAC to grow?
|
2-6 weeks
|
|
|
What helps confirm a presumptive MAC diagnosis?
|
clinical improvement on empiric therapy
|
|
|
MAC:
1st line treatment |
Clarithromycin 500 mg BID PLUS ethambutol 15 mg/kg/day
May consider rifabutin (many ADEs) |
|
|
T/F.
MAC treatment has a higher efficacy if rifabutin is added. |
False.
|
|
|
Ethambutol:
common ADE |
ocular nephritis
|
|
|
MAC:
Discontinuation of treatment therapy |
Completion of at least 12 months treatment, remain asymptomatic and have CD4 cound > 100 for at least 6 months on HAART
negative cultures |
|
|
MAC:
restarting therapy |
CD4 < 100
|
|
|
MAC:
candidates for primary prophylaxis |
CD4 < 50
|
|
|
MAC:
primary prophylaxis |
Azithromycin 1200 mg Qweek
|
|
|
MAC:
discontinuation of primary prophylaxis |
CD4 > 100 for at least 3 months
|
|
|
Cytomegalovirus Disease
|
enveloped double-stranded DNA virus
member of herpes virus family |
|
|
Can CMV become latent within infected cells?
|
Yes
|
|
|
How is CMV trasmitted?
|
through infected body fluids (mainly congenital and sexual contact)
|
|
|
Most common form of CMV in AIDS patients
|
CMV retinitis
|
|
|
Where can CMV manifest?
|
various organ systems
esophagitis, colitis, neurologic CMV |
|
|
What can happen if CMV retinitis is left untreated?
|
Will rapidly progress to retinal necrosis and permanent blindness
|
|
|
CMV:
Signs and symptoms |
visual changes
flashes of light blurred vision blind spots (floaters) |
|
|
CMV:
Diagnosis |
clinical diagnosis
cluture and antigen detection most sensitive methods for detecting CMV |
|
|
CMV treatment:
CMV retinitis (immediate sight-threatening lesions) |
Ganiciclovir intraocular implant
PLUS valganciclovir 900 mg PO BID x 14-21 days THEN valganciclovir 900 mg PO QD 1 dose of intravitreal ganciclovir may be given immediately after diagnosis until implant can be placed |
|
|
CMV treatment:
CMV retinitis (small peripheral lesions) |
Valganciclovir PO 900 mg BID x 14-21 days
THEN Valganciclovir PO 900 mg QD |
|
|
CMV Treatment:
CMV esophagitis or colitis |
Ganciclovir IV OR foscarnet IV x 21-28 days or until resolution of sx
If PO adequate, use valganciclovir PO Maintenence therapy usually not necessary, but should be considered after relapses |
|
|
CMV treatment:
CMV neurological disease |
PROMPT initiation of treatment
Combo of ganciclovir IV PLUS foscarnet IV to stabilize disease and max response Continue until symptomatic improvement Maintenance therapy: PO valganciclovir PLUS IV foscarnet continued lifelong unless evidence of immune recovery |
|
|
CMV retinitis:
Suppression (secondary prophylaxis) |
valganciclovir 900 mg QD
OR ganciclovir implant (may be replaced q6-8months if CD4 reamins <100) PLUS valganciclovir 900 mg QD until immune recovery |
|
|
CMV retinitis:
D/C secondary prophylaxis |
CD4>100 for at least 3-6 months on HAART
|
|
|
CMV retinitis:
restarting secondary prophylaxis |
when CD4 <100
|
|
|
CMV treatment:
duration of induction therapy |
14-21 days
|
|
|
CMV:
primary prophylaxis |
controversial (expensive, toxic, resistance)
considered for pts with CD4 <50 and CMV IgG + Give PO ganciclovir or valganciclovir Fundascopic exams by ophthalmologist |
|
|
Candidiasis causing organism
|
Candida species
yeast, part of normal flora in immunocompetent and immunocompromised hosts |
|
|
Where can candida be found?
|
skin
mucosal surfaces (mouth, pharynx, vagina) |
|
|
Most candidiasis caused by which form of candida?
|
C. albicans
increasing frequency with C. topicalis, C. glabrata, C. parapsilosis, C. krusei |
|
|
What causes candidiasis?
|
overgrowth of normal flora due to breakdown in local defenses
|
|
|
Candidiasis:
signs and symptoms |
mouth pain, pain with swallowing, difficulty eating
white plaques on buccal surfaces, palate, and tongue Esophageal cand. may ave more severe symptoms (dysphagia, odynophagia, esophageal ulceration, anorexia) |
|
|
Candidiasis:
Diagnosis |
surface scraping for Gram stain
Presence and extent of esophageal plaques identified through bronchoscopy |
|
|
Are fungal cultures helpful when diagnosis candidiasis?
|
No
useful in determining species of candida in patients who fail therapy |
|
|
Oral candidiasis treatment
|
fluconazole 100mg/day
OR nystatin 500,000 U swish/swallow QID OR clotrimazole troches 10 mg 5x/day |
|
|
Vaginal candidiasis treatment
|
fluconazole 150 mg x 1
OR topical azoles x 3-7 days |
|
|
Esophageal candidiasis treatment
|
Systemic therapy
fluconazole preferred, 100-200 mg/day OR posaconazole 400 mg BID |
|
|
Can you use topical treatment with nystatin or clotrimazole for esophageal candidiasis?
|
No
|
|
|
Candidiasis prophylaxis (chronic maintenance)
|
increases risk of azole resistance
may consider in patients with documented history of esophageal candidiasis and multiple episodes Fluconazole 100-200 mg/day |
|
|
Candidiasis primary prophylaxis
|
not recommended
|
|
|
TMP/SMX ADEs
|
GI disturbances (eg, anorexia, nausea, vomiting) and allergic skin reactions (eg, rash, urticaria)
|
|
|
Sulfadiazine ADEs
|
H/A, depression, insomnia, pruritis, phostosensitivity, anorexia, N, V, D, tinnitus
|
|
|
Pyrimethamine ADEs
|
anorexia, V, thrombocyopenia, hypersensitivity
|
|
|
Amphotericin ADEs
|
CNS: Headache.
GI: Anorexia; nausea; vomiting; diarrhea; dyspepsia; cramping; epigastric pain. Hematologic: Normochromic anemia; normocytic anemia. Local: Pain at the injection site with or without phlebitis or thrombophlebitis. Musculoskeletal: Generalized pain, including muscle and joint pains. Pulmonary: Hypotension; tachypnea |
|
|
Fluconazole ADEs
|
N, V, D, H/A, rash, abdominal pain
|
|
|
Clarithromycin ADEs
|
abnormal taste, N, D, H/A, abdominal pain, dyspepsia
|
|
|
Azithromycin ADEs
|
N, D, chest pain, dizziness, H/A, photosensitivity, rash
|
|
|
Ethambutol ADEs
|
optic neuritis
|
|
|
Ganciclovir/Valgancyclovir ADEs
|
anemia, diarrhea, graft rejection, nausea, neutropenia, pyrexia, thrombocytopenia, tremor, and vomiting
|
|
|
Flucytosine ADEs
|
confusion, photosensitivity, rash, renal failure, H/A, peripheral neuropathy, respiratory arrest
|
|
|
Basic forms of fungi
|
Yeast
Moulds |
|
|
Yeast
|
solitary forms of fungi that reproduce by budding
|
|
|
How do yeast reproduce?
|
budding
|
|
|
What do yeast look like?
|
moist, shiny appearance
|
|
|
Moulds
|
multi-cellular fungi
consist of many branching hyphae reproduce by translocation or existing hyphae to a new area or through spore formation and spread |
|
|
How do moulds reproduce?
|
translocation or existing hyphae to a new area or through spore formation and spread
|
|
|
What do moulds look like?
|
fuzzy appearance
|
|
|
Dimorphic fungi
|
Can exist in either yeast or mould form
|
|
|
Dimorphic fungi at room temperature
|
mould-like
|
|
|
Dimorphic fungi at body temperature
|
yeast-like
|
|
|
What is another name for dimorphic fungi? Why are they sometimes called this?
|
endemic fungi
cause infections endemic to certain regions of the world |
|
|
Yeast species
|
Candida
Cryptococcus |
|
|
Mould species
|
Aspergillus
Zygomycetes Fusarium Scedosporium |
|
|
Dimorphic fungi species
|
Coccidioides
Blastomyces Histoplasma Paracoccidiodes |
|
|
T/F.
Fungi are a cross between bacterial and human cells |
True
|
|
|
Do fungi have a cell wall?
|
Yes
|
|
|
What is fungi cell wall made of?
|
chitin (beta-(1,4)-linked N-acetylglucosamine residues)
|
|
|
Do fungi cell walls contain peptidoglycan?
|
No
|
|
|
Do fungi have a cell membrane inside of their cell wall?
|
Yes
|
|
|
Ergosterol
|
embedded in fungal cell membranes
analogue to cholesterol found in human cell membranes |
|
|
Polyenes
|
Ampho B
Lipid formulations of ampho B topical nystatin |
|
|
Main amphotericin toxicities
|
nephrotoxicity
infusion-related reactions |
|
|
How can amphotericin B toxicities be avoided?
|
Use lipidd formulation
|
|
|
Ampho B lipid formulations
|
ampho B colloidal dispersion
Ampho B lipid complex Liposomal ampho B |
|
|
Polyenes MOA
|
bind to ergosterol in cell membrane of fungi
disrupt cell membrane causes pore leading to leakage |
|
|
Polyenes:
fungicidal or fungistatic |
fungicidal
|
|
|
Polyenes Target
|
cell membrane
|
|
|
Azoles target
|
Cell membrane
|
|
|
Echinocandins target
|
cell wall
|
|
|
Antimetabolites target
|
DNA/RNA synthesis
|
|
|
Ampho B, Nystatin:
spectrum |
most Candida
most Aspergillus Cryptococcus neoformans dimorphic fungi many moulds some Zygomycetes |
|
|
What Candida species does ampho B and nystatin not work well against?
|
Candida lusitaniae
|
|
|
Ampho B, nystatin:
ADEs |
nephrotoxicity
infusion-related reactions (fever, chills, rigors) electrolyte disturbances (decrease Mg, K, Ca) |
|
|
How does ampho B cause nephrotoxicity?
|
direct effects on distal tubule and indirect effects through vasoconstriction of afferent arteriols
leads to wasting of Mg and K |
|
|
What can be done to prevent nephrotoxicity from ampho B?
|
make sure patient is hydrated
give pre and post infusion saline boluses |
|
|
What should be done to minimize infusion-related reactions due to ampho B?
|
Give pre-meds (APAP, diphenhydramine)
Give meperidine if needed and/or hydrocortisone |
|
|
ampho B formulations:
dosing |
Ampho B deoxycholate: 0.5-1.5 mg/kg/day
Lipid formulations: 3-6 mg/kg/day |
|
|
Why is meperidine sometimes given with ampho B?
|
To treat rigors associated with infusion
|
|
|
Why is nystatin only given topically?
|
poor tolerance when given systemically
|
|
|
Drug interactions with ampho B
|
increase nephrotoxicity with other nephrotoxic agents (aminoglycosides, cyclosporine)
|
|
|
Ampho B:
DOC for.... |
cryptococcal meningitis
serious forms of other fungal infections (dimorphic fungi, some mould infections) |
|
|
Why has ampho B use with candidiasis and aspergillosis declined?
|
availability of newer, safer agents
|
|
|
Antimetabolites
|
Flucytosine (5-FC)
|
|
|
Primary role of flucytosine
|
combination with ampho B for cryptococcal disease
|
|
|
Antimetabolites (flucytosine): MOA
|
interferes with DNA synthesis
enters fungal cell, converts to fluoruracil, competes with uracil, interferes with fungal RNA and protein synthesis |
|
|
Flucytosine Spectrum
|
in combo with ampho B: cryptococcus neoformans, most Candida species
|
|
|
Flucytosine:
ADEs |
bone marrow suppression (esp. in high doses for long periods)
GI/CNS effects: H/A, confusion, ataxia, hallucinations |
|
|
When should peak concentration of flucytosine be checked?
|
2 hours after dose given
|
|
|
What values are more important than drug levels when monitoring for toxicity with flucytosine?
|
hematologic values
|
|
|
Drug interactions with flucytosine
|
increased effect with ampho B = increased risk of flucytosine toxicity with ampho B
|
|
|
Does flucytosine need to be adjusted for renal failure?
|
Yes
|
|
|
When should flucytosine therapy be reconsidered?
|
If hematologic toxicity develops
change med if WBCs decrease |
|
|
Azoles
|
itraconazole
fluconazole voriconazole posaconazole |
|
|
Azoles: MOA
|
broad spectrum
inhibit fungal cytochrome P450, decreasing ergosterol production |
|
|
Azoles:
fungicidal vs. fungistatic |
fungistatic
|
|
|
Triazoles
|
voriconazole
posaconazole |
|
|
Itraconazole Spectrum
|
C. albicans
C. tropicalis C. parapsilosis C. lusitaniae Cryptococcus neoformans Aspergillus sp. many dimorphic fungi |
|
|
Fluconazole Spectrum
|
C. albicans
C. tropicalis C. parapsilosis C. lusitaniae Cryptococcus neoformans Coccidioides immitis Some C. glabrata |
|
|
Voriconazole Spectrum
|
C. albicans
C. tropicalis C. parapsilosis C. lusitaniae Aspergillus sp many other moulds Some C. glabrata, krusei, albicans that are fluconzole-resistant Fusarium Sp |
|
|
Posaconazole Spectrum
|
C. albicans
C. tropicalis C. parapsilosis C. lusitaniae Aspergillus sp Zygomycetes sp. Many moulds Dimorphic fungi Some C. glabrata Some Fusarium sp |
|
|
Which azole does NOT have activity against Aspergillus?
|
Fluconazole
|
|
|
Which azole has activity against Zygomycetes?
|
Posaconazole
|
|
|
Itraconazole:
ADEs |
hepatotoxicity
negative inotrope (CI with HF) Strong inhibitor of 3A4 QTc prolongation possible |
|
|
Fluconazole:
ADEs |
hepatotoxicity, rash
lower propensity for drug interactions (strong inhibitor of 2C9, 2C19, moderate inhibitor of 3A4) QTc prolongation possible |
|
|
Voriconazole:
ADEs |
hepatotoxicity, rash
visual effects (wavy lines)(go away with cont. use) hallucinations Interactions (moderate inhibitor of 2C9, 3A4) |
|
|
Posaconazole:
ADEs |
hepatotoxicity, rash
GI disturbances QTc prolongation possible Interactions (strong inhibitor of 3A4) |
|
|
Itraconazole formulations
|
Capsules have lower F than solution, less preferred for systemic fungal infections
|
|
|
Itraconazole administration
|
Capsules: always take with full meal
Solution: take on empty stomach Take with soda if also taking PPIs (PPIs may decrease absorption) |
|
|
Itraconazole DOC for...
|
some dimorphic infections (histoplasmosis)
|
|
|
Does fluconazole need to be adjusted for renal function?
|
Yes
|
|
|
Fluconazole and C. glabrata
|
Poorly active against C. glabrata
If using for this, check susceptibilities and give 800 mg/day |
|
|
Fluconazole bioavailability:
High or low |
High
|
|
|
T/F.
All species of candida are fluconazole-susceptible. |
False
|
|
|
Voriconazole:
formulations |
IV: contains cyclodextrin vehicle that accumulates in renal dysfunction, may be nephrotoxic
|
|
|
When is IV voriconazole contraindicated?
|
CrCl < 50
Use oral formulation |
|
|
How is voriconazole eliminated?
|
hepatically
|
|
|
Is voriconazole useful for treatment of candiduria?
|
no
|
|
|
Voriconazole DOC for...
|
invasive aspergillosis
|
|
|
Posaconazole:
formulation |
only available as oral suspension
|
|
|
Posaconazole:
Administration |
give with food to increase absorption
foods high in fat improve absorption |
|
|
Posaconazole:
Utility |
prophylaxis in high-risk patients
zygomycetes infections |
|
|
Echinocandins
|
Caspofungin
Micafungin Anidulafungin |
|
|
Echinocandins:
Pros (vs. other antifungals) |
very well tolerated
excellent activity against Candida fewer drug interactions than azoles safer than polyenes great activity against fluconazole-resistant yeasts |
|
|
Echinocandins: MOA
|
inhibit synthesis of beta-1,3-glucan component of cell wall
destroys stability of membrane |
|
|
Echinocandins:
fungicidal vs. fungistatic |
fungicidal: Candida
fungistatic: Aspergillis |
|
|
Echinocandins Spectrum
|
C. albicans
C. tropicalis C. lusitaniae C. glabrata C. krusei Aspergillus Some C. parapsilosis |
|
|
Which antifungals have activity against C. krusei?
|
Echinocandins
|
|
|
Which antifungals have activity against Aspergillus?
|
Echinocandins
Voriconazole Posaconazole Itraconazole Ampho B Nystatin |
|
|
Echinocandins:
ADEs |
mild histamine-mediated infusion-related reactions (not common, just slow infusion rate)
|
|
|
Caspofungin:
ADEs |
increase LFTs
GI disturbances |
|
|
Micafungin:
ADEs |
GI disturbances
increase LFTs |
|
|
Anidulafungin:
ADEs |
Diarrhea
hypokalemia |
|
|
Echinocandins:
formulations |
all only available IV
|
|
|
Difference between echinocandins
|
minor differences, mostly PK
|
|
|
How are echinocandins eliminated?
|
Caspofungin and micafungin: hepatic elimination by non-Cyp450 metabolism
Anidulafungin: degrades in plasma, avoids hepatic elimination |
|
|
Echinocandins:
drug interactions |
interactions minor
cautious when using caspofungin/micafungin with immunosuppressants (cyclosporine with caspofungin) (sirolimus with micafungin) |
|
|
Echinocandins:
Uses |
Becoming DOC for invasive candidiasis, esp. if pt. unstable
Treat invasive aspergillosis (not as much evidence yet as voriconazole/ampho B) |
|
|
Echinocandin transition after empiric therapy
|
echinocandins very expensive so transition to fluconazole if strain of Candida susceptible
|
