ID exam 2 Flashcards
____________ describes the presence of bacteria in the bloodstream and is quantified by blood cultures
bacteremia
Introduction of _____________ commonly occurs due to a focal source (primary)
bacteria
Risk factors for bacteremia
age
liver disease, ESRD
functional or anatomic asplenia
immunosuppression
intravenous drug use
corticosteroid use
recent surgical procedures
trauma
urinary retention
bacteremia common gram positive pathogens
staphylococcus aureus
stretococcus pneumoniae
enterococcus spp
bacteremia common gram negative pathogens
e. coli
klebsiella spp
pseudomonas aeruginosa
salmonella spp
Sepsis is categorized by what while septic shock is categorized by what
sepsis: multi-system organ failure
septic shock: sepsis that is refractory to initial resuscitative interventions
pathophysiology of sepsis shock
hypovolemic
obstructive
distributive
cardiogenic
Decreased cardiac output causes what
decreased venous return
decreased preload
Hypotension causes what
decreased organ perfusion
increased anaerobic metabolism
Multi-organ failure categorization
progressive
additive
Etiology of distributive shock
systemic inflammatory response syndrome (SIRS)
SEPSIS
anaphylaxis
drug/toxin reactions
Distributive shock clinical presentation
dyspnea
chills
fatigue
malaise
tachypnea
tachycardia
What is SIRS (systemic inflammatory response syndrome)
-bacteremia or systemic infection may be present
-must correlate to PE and lab findings
-does not indicate sepsis w/out meeting 2 or more criteria with presence of confirmed or suspected infection
Criteria for SIRS
HR: >90bpm
Temp: <36 C or >38 C
WBC <4,000 or >12,000 cells/mm3 or >10% bands
RR >20 breaths per minute or PaO2 mmHg
SOFA score (sequential organ failure score)
not diagnostic or prognostic
multifaceted quantification
-max SOFA score
-mean SOFA score
-delta SOFA score
What is max SOFA score
sum of highest score per individuals during entire ICU stay
>15 = predicted mortality of 90%
What is mean SOFA score
average of all score for ICU stay
high averages = higher rate of mortality
What is delta SOFA score
objective marker for trending progress
qSOFA score (quick sequential organ failure assessment)
predictor of outcomes
-not diagnostic or prognostic
- >/= 2 indicates approximately 10% mortality
End Organ Damage
lactate >2 mmol/L (lead to acidosis)
systolic BP <90 mmHg (or decrease from >40)
mean arterial pressure <65 mmHg
kidney dysfunction
-creatinine >2 mg/dL
-platelets <100,000 cells/mm3
Liver dysfunction
-INR >1.5
The primary treatment of bacteremia, sepsis, and septic shock relies upon what
the eradication of the infection
-Crystalloid fluids
-Vasopressors
-Corticosteroids, +/- thiamine and ascorbic acid – highly controversial
Fluid Resuscitation
30 mL/kg of crystalloid fluid
Administered prior to other treatments
May consider colloidal fluids if initial crystalloid resuscitation fails
-Albumin
Fluid Selection
0.9% sodium chloride is historic fluid of choice
Concerns about:
-Hyperchloremic acidosis
-Sodium content
-Tonicity
Other fluid selections rather than 0.9% nacl
Recent evaluations considering buffered crystalloid solutions:
-Lactated Ringer’s solution
-Plasma-Lyte
Peripheral Line sites
hand
foot
AC fossa
Peripheral Line safe for what
most medications
fluids
blood products
Central Line: Provides venous access directly to the what
superior/inferior vena cava
What are the central line sites and what its safe for
subclavian
femoral
AC fossa
What are central lines safe for
Medications – necessary for some
Fluids
TPN
Blood products
What is mean arterial pressure
average pressure w/in artery
MAP = [(2 x DBP) + SBP] / 3
normal range 70-90 mmHg
What is cardiac output
Calculation of blood ejected from ventricle per minute
CO = SV x HR
Males = 5.6 L/min
Females = 4.9 L/min
Vasopressors
indicated in profound hypotension after failure of fluid resuscitation
-MAP is target, titrate to >65 mmHg
What are the criteria for qSOFA
Hypotension <100
AMS: GCS <13
Tachypnea: RR >22
What drug is the first line agent in septic shock
NE
-influences BP (increase HR)
-potent agonist of adrenergic receptors
What drug is the first line agent in anaphylaxis
Epi
-additive agent in sepsis and cardiogenic
-agonist of adrenergic receptors
What must you monitor for phenylephrine
peripheral venous return
What drug is generally preferred in cardiogenic shock
dobutamine
-beta agonism
-increases stroke volume
milrinone
-non adrenergic MOA
-increased cardiac output
Adverse effects of vasopressors can be reversed by what
central line preferred for continuous administration
extravasation is serious risk
reversed by:
-phentolamine
-terbutaline
-nitroglycerin ointment
Main adverse effect of vasopressors
digital necrosis
Initial therapy in shock management
hypovolemia: NE, Epi
sepsis: NE
cardiogenic: dobutamine, milrinone
What agents to use if pseudomonas is a concern in bacteremia
cefepime
piperacillin/tazobactam
ceftazidime
antipseudomonal carbapenem
What agents to use if pseudomonas is a concern in bacteremia and patients are immunodeficient and local rate of resistance is >10-20%
antipseudomonal beta lactam +
aminoglycoside
fluoroquinolone
What agents to use if MRSA is a concern in bacteremia
vanco
dapto
What agents to use if MSSA is a concern in bacteremia
nafcillin
cefazolin
Duration of therapy in bacteremia
7-14 days with antibiotics
What are the adjunctive therapies in bactermia
corticosteroids (septic shock)
Vitamin Supplementation
Ascorbic Acid
Thiamine
MOA of Vancomycin
bind D-alanyl-D-alanine preventing amino acids from being incorporated into peptidoglycan synthetase preventing cross-linking
Vancomycin ADME
poor oral, IV amin
55% protein bound
glomerular filtration dose adjust for renal patients
Vancomycin effects of age
exhibit increased tissue binding, increase Vd and half-life
decrease clearance and increase half life
ADE of vancomycin
rash
erythema
hypotension
ototoxicity
nephrotoxicity
MOA of Daptomycin
interfere with integrity of cell membrane in gram-positive bacteria. Lipopeptides bind to bacterial membranes and cause rapid depolarization of membrane potential leading to cell death
Daptomycin ADME
IV
92% protein bound
ADE of daptomycin
GI
metabolic
hematological: anemia
musculoskeletal: myalgia
nervous system
respiratory
CV
DDI in daptomycin
increase risk of statin-induced myalgias
Oxazolidinones are totally ___________ and bear no structural relationship to microbial biochemicals
synthetic
Linezolid MOA
bind to 50s ribosomal subunit
23s rRNA
interfere with A site assembly in initiation stage of protein synthesis and distorts P site
Linezolid ADME
100% bioavailability
low protein binding
non-enzymatic
kidney excretion
Linezolid ADE
N/V/D
hematologic effects
inhibition of MAO
Rifampin MOA
inhibit bacterial DNA dependent RNA polymerase by binding to polymerase subunit deep w/in DNA/RNA channel, causing blockage of elongating RNA
Rifampin ADME
80% protein bound
metabolized in liver to active metabolite
Rifampin ADE
N/V/D
discolor excreted liquids (yellow, orange, red, brown)
stain teeth and contact lens
liver disease
C. diff
thrush
Rifampin precautions
allergies
alcohol induce liver disease
decrease bacterial vaccine efficacy
not for pregnancy
Rifampin DDI
speed up removal of many drugs
decrease effectiveness of birth control
Pathophysiology of infective endocarditis
endothelial damage
platelet-fibrin deposition and form lesion
bacteremia allows bacterial colonization
form vegetation
structural abnormality in a valve
Pathological criterial for endocarditis
microorganisms by culture or histological exam of vegetation, embolized, intracardiac abscess specimen
pathological lesions
vegetation or intracardiac abscess conformed showing active endocarditis
Clinical criteria for IE
2 major
1 major, 3 minor
5 minor
Major criteria for endocarditis
positive blood cultures
evidence of endocardial involvement
echocardiogram positive (TEE)
Minor criteria for endocarditis
predisposition or IVDA
temp >38 C
vascular hemorrgaging or emboli
glomerularnephritis, osler nodes, roth spots, rheumatoid factor
microbio evidence present
Native Valve: PCN sensitive staph and strep drugs
pen G
ceftriaxone
pen G plus gentamicin
ceftriaxone plus gentamicin
vancomycin (if can not take -cillins)
Native Valve: PCN resistant staph and strep drugs
Naficillin/Oxacillin
Cefazolin
Vancomycin
Daptomycon
Native Valve: methicillin resistant staph and strep drugs
Vancomycin
Daptomycin
Enterococci Infections: Sensitive strains drugs
Ampicillin plus gentamicin
pen G plus gentamicin
ampicillin plus cefrtiaxone
vancomycin plus gentamicin
Enterococci Infections: Penicillin Resistant strains drugs
ampicillin-sulbactam plus genta
vanco plus genta
Enterococci Infections: Enterococcus Faecium Resistant strains drugs
Linezolid
Dapto (use this)
Gram negative infection drugs endocarditis
ceftriaxone
ampicillin or amp-sulbactam
cipro
Prosthetic valve: strep and staph spp penicillin susceptible drugs
pen G
ceftriaxone
Prosthetic valve: strep and staph spp oxacillin susceptible drugs
nafcillin or oxacillin
-plus rifampin or genta
vanco
-plus rifampin or genta
Prosthetic valve: strep and staph spp oxacillin resistant drugs
Vanco
-plus rifampin or genta
Culture-negative endocarditis native valve drugs
vanco plus cefepime
vanco plus ampicillin-sulbactam
Culture-negative endocarditis, early (<1 year) prosthetic valve drugs
vanco plus cefepime plus rifampin plus genta
Culture-negative endocarditis, late (>1 year) prosthetic valve drugs
vanco plus ceftriaxone
Fluoroquinolone side effects
tendon reputure
photosensitivity
Can you use moxifloxacin in children
no
Moxifloxacin ADME
well protein bound
M: glucuronide, sulfate conjugation
E: feces/urine
Clindamycin formulations
liquid, parenteral, topical
Side effect of clindamycin
C. diff
Clindamycin therapeutic uses
osteomyelitis or joint infections
pelvic inflammatory disease
Clindamycin MOA
bind to 50S ribosomal unit of bacteria
early chain elongation
Clindamycin ADME
F: 90%
D: penetrates bone
E: urine, bile
(extended half-life for hepatic failure)
Clindamycin DDI
CYP3A4 inhibitors
neuromuscular-blocking agents
macrolides
chloramphenicol
Metronidazole MOA
anaerobic organisms processing nitroreductase activity destabilize the imidazole ring
nitroso free radical
-metabolites are lethal to anaerobes (cidal action)
Metronidazole ADME
GIT complete
crosses placenta
hepatic metabolism
kidney, feces
ADE of Metronidazole
disulfram-like alcohol intolerance
deep red-brown color urine
DDI Metronidazole
antidepressants
albuterol
cancer meds
BP meds
antipsychotics
malaria, HIV
blood thinners
Purulent SSTI (skin and soft tissue infections)
furuncles (hair folicule), carbuncles, cutaneous abcesses, impetigo
-has drainage
Non-Purulent SSTI (skin and soft tissue infections)
erysipeals, cellulitis, necrotizing fasciitis
Pathophysiology of SSTI
disruption in skin barrier, inadequate blood/nutrient supply, inflammation occurs
Risk factors for SSTI
disruption or break in skin barrier***
vascular insufficiency
obesity
uncontrolled DM
IV drug abuse
poor hygiene
Pathogens for SSTI
Strep spp
S. aureus
Candida spp
MRSA
Severity of SSTI
mild - w/out systemic signs
moderate - systemic signs of infection
severe - temp >38C, HR >90, RR >24, WBC (>12 or <4), immunocompromised patient
What are purulent SSTIs caused by
S. aureus
-present with pain, erythema, edema, warmth, drainage
Treatment duration for purulent SSTI
5-14 days (mainly 5-7 days)
Treatment for mild purulent SSTI
I and D alone
Treatment for moderate purulent SSTI
I and D w/ culture and susceptibilities
TMP/SMX or Doxycycline
de-escalate to cephalexin
Treatment for severe purulent SSTI
I and D w/ culture and susceptibilities
Vanco, Dapto, Linezolid
de-escalate to cefazolin
What are non-purulent SSTIs caused by
strep pyogens
strep spp
-present with pain, erythema, edema, warmth
(NO drainage)
non-purulent SSTIs treatment duration
5-14 days
-may need extension if surgical debridement is required
non-purulent SSTIs mild treatment
(PO therapy)
Pen VK
Amox
Cephalexin
non-purulent SSTIs moderate treatment
(IV therapy)
Cefazolin
Ceftriaxone
Ampicillin
Pen G
non-purulent SSTIs severe treatment
(surgical debridement)
pip-taz, cefepime, meropenem
AND
vanco or dapto
clindamycin (plus 2 above)
linezolid (plus 1 above in place of vanco/dapto)
Clinical presentation of non-purulent SSTIs necrotizing fasciitis
erythma, warmth, edema, pain, fever, tachycardia,
-involves extremities, perineum, head/neck region
-crepitus or cracking on PE (gas in tissues)
non-purulent SSTIs necrotizing fasciitis treatment
surgical debridement to prevent injury
empiric therapy should be broad and de-esculated on results
non-purulent SSTIs necrotizing fasciitis pathogens
strep pyogenes
staphyococcus aureus
diabetic foot infections (DFI)
common cause of hospitalizations
neuropathy, uncontrolled DM, skin trauma, anatomic abnormalities
Not all DFU are _______: its important to not overtreat due to concerns for adverse effect and antimicrobial resistance
DFI
Mild clinical manifestation of DFI
at least 2
-swelling or induration
erythema >0.5 cm to < 2 cm
ulcer
tenderness/pain
warmth
purulent discharge
Moderate clinical manifestation of DFI
local infection with > 2 cm form wound margin
OR
deeper infection (abcess, osteomyelitis, fasciitis)
AND
w/out systemic sign of infection
Severe clinical manifestation of DFI
local infection with SIRS
(2: temp >38C or <36C, HR >90, RR >20, WBC >12k ot <4K)
mild pathogens and agents in antimicrobial treatment for DFI
MSSA, strep spp, MRSA
Cephalexin, Augmentin, Doxycyline, Bactrim
Pathogens in moderate and severe DFI
MSSA
strep spp
MRSA
enterobacterales
+/- anaerobes
DFI treatment in moderate to severe infection with no complicating features
augmentin
amp-sulb
cefuroxime
ceftriaxone
cefazolin
+/- metronidazole
DFI treatment in moderate to severe infection with recent antibiotics (within last 30 days)
Ceftriaxone and Vanco +/- metronidazole
DFI treatment in moderate to severe infection with macerated ulcer
pip-taz
OR
cefepime + vanco +/- metronidazole
DFI treatment in moderate to severe infection with ischemic limb/necrosis/gas forming
ceftriaxone + vanco + metronidazole/clindamycin
Duration of treatment for mild, moderate/severe, and bone/joint DFI
mild: 1-2 weeks or 10 days following surgery
moderate/severe: 2-4 weeks
bone/joint:
-resected 1-2 weeks
-debrided 1-2 weeks
-positive culture of bone margins AFTER resection: 3 wks
-no surgery/dead bone: 6 wks
Osteomyeltits common organisms
MSSA
MRSA
-present with edema, pain
Infection of bone occurs in 3 ways what are they
contiguous spread: erosion into bone or bony structures from adjacent tissue (most common)
hematogenous spread: direct inoculation from bacteria within the bloodstream
traumatic or surgical contamination
What are the 4 imagine ways of osteomyelitis
X-ray (first)
MRI (gold standard)
CT (not bone marrow edema)
Ultrasound (evaluation of soft tissue)
osteomyelitis cultures and biomarkers
Erythocyte sedimentation rate (ESR)
c-reactive protein (CRP)
Osteomyelitis aerobic gram-positive cocci and aerobic gram-negative bacilli treatment
ceftriazone + vanco
Osteomyelitis MRSA treatment
MRSA colonization pior positive cultures for MRSA
Osteomyelitis pseudomonas treatment
prior positive culture for psedomonas, gangrenous wounds, surgical procedure in prior 3 months
Osteomyelitis treatment: hematogenous, contiguous, DFI with osteo, retained implant
hematogenous: max 6 weeks
contiguous: max 6 weeks
DFI with osteo: 3-4 weeks
retained implant: 6-12 weeks
Septic arthritis common organisms
mainly s.
streptococci and gram negative bacilli
Septic arthritis pathophysiology
bacteria reach joint space, adhere to synovium causing inflammation and tissue ischemia
direct injury to cartilage tissue and purulent exudate increase joint space pressure and cause symptoms
Septic arthritis clinical presentation
fever, rigor, acute onset of warm/swollen/painful joint with limited range of motion
Septic arthritis diagnosis
ESR, CRP, WBC elevation
CT or MRI to reveal inflammation or effusion
WBC >50 in synovial fluid***
Antimicrobial therapy should be withheld if patient stable until arthrocentesis can be performed
Septic arthritis treatment
vanco, dapto, linezolid
gram negative coverage: cefepime or pip=taz (critical ill, immuno, IV drugs)
TMP/SMX, minocycline, linezolid, doxycycline, clindamycin (oral agents for stable pt)
3 weeks treatment
Common pathogens in meningitis
s. pneumonia***
n. meningitidis (A, B, C, W135, Y pathogenic, gram -)
h. influenzae tybe b (children, infants)
Pathophysiology of meningitis
meninges (direct or indirect inoculation)
inflammation in CSF, spine, ventricles)
decreased blood and CSF flow
headache, fever, nuchal rigidity, AMS
Symptoms of meningitis
headaches
altered mental status
high fever
stiff neck
phonophobia
Lab tests of meningitis
CSF culture
-absence does not rule out (factor timeline)
-presence does not confirm (identify differential diagnosis)
Considerations in lumbar puncture for meningitis
measure opening pressure
-oncotic gradient (foreign materials increase pressure)
traumatic puncture
-presence of erythrocytes in culture
-must adjust WBC count in CSF
Protein and Glucose in bacterial CSF
protein: elevated (>50)
glucose: low (<45)
<1 month therapy for meningitis
ampicillin + cefotaxime
OR
ampicillin + aminoglycoside
<1 month common bacterial pathogens for meningitis
strep agalactiae
e. coli
listeria monocytogenes
klebsiella species
1-23 month therapy for meningitis
vanco + 3rd gen cephalosporin
1-23 month common bacterial pathogens for meningitis
strep pneumoniae
neisseria meningitidis
s. agalactiae
h. influenzae
e. coli
2-50 year therapy for meningitis
vanco + 3rd gen cephalosporin
2-50 year month common bacterial pathogens for meningitis
n. meningitidis
s. pneumoniae
> 50 year therapy for meningitis
vanco + 3rd gen cephalosporin + ampicillin
> 50 year common bacterial pathogens for meningitis
s. pneumoniae
n. meningitidis
l. monocytogenes
aerobic gram negative bacilli
strep pneumoniae therapy
vanco + 3rd gen cephalosporin
neisseria meningitidis therapy
3rd gen cephalosporin
listeria monocytogenes and strep agalactiae therapy
ampicillin or pen G
haemophilus influenzae and e. coli therapy
3rd gen cephalosporin
Duration of therapy for meningitis
10-14 days
must make sure antimicrobials cross BBB
What does inflammation caused by meningitis do
increase cerebral edema/intracranial pressure
neurologic tissue damage
increase permeability of BBB
How to dose dexamethasone
give with or before antibiotics
0.15 mg/kg IV q6h
-max 10 mg/day over 4 days
Oral vanco MOA
bind D-alanyl-D-alanine preventing peptidoglycan synthetase
Oral vanco ADME
poor absorbed (good for c. diff)
feces excretion
ADE of vanco
dysgeusia (distorted taste)
neurotoxicity
MOA fidaxomicin
inhibition of RNA synthesis as mediated by RNA polymerase
-PAE for c. diff
ADME fidaxomicin
little absorption
active metabolites
feces excretion
Rifaximin MOA
inhibition of bacterial RNA synthesis by binding to beta subunit of RNA polymerase
ADME Rifaximin
poor oral
intestinal tract accumulation
feces excretion
ADE of Rifaximin
flatulence
rectal tenesumus
defecation urgency
What is the cornerstone of treating diarrhea
fluid and electrolyte replacement
What is the clinical presentation of watery diarrhea
<10 stools per day
reduced absorption metabolically
etiology of v. cholerae, ETEC, rotavirus, noroviruses
What is the clinical presentation of inflammatory diarrhea
bloody stool
>10 stools per day
mucosal invasion mechanism
etiology of shigella spp, salmonella spp, campulobacter spp, EHEC, C. diff
What are the 3 oral replacement therapies in diarrhea
pedialyte
infalyte
oralyte
Watery: Causative agent of vibrio cholerae how to get it, clinical presentation, and treatment
sewage or drinking water
lose up to 1 L every hour
Doxycycline x1 300 mg dose
Azithromycin 500 mg PO qd x 3d
Watery: Causative agent of e. coli how to get it, clinical presentation, and treatment
travelers diarrhea, food poisoning
nausea, ab cramp
Loperamide and bismuth subsalicylate
Cipro 750 mg po qd x1-3d
Azithromycin 500 mg po qd x3d
Inflammatory: Causative agent of salmonellosis enterica how to get it, clinical presentation, and treatment
gram negative bacilli
contaminated food, w/in 72 h, N/V, diarrhea after 72 h
Cipro 750 mg po qd x5-7d
Inflammatory: Causative agent of campylobacter jejuni how to get it, clinical presentation, and treatment
flagellated curved, gram negative bacilli
pain, fever, diarrhea, frequent stool
NO ANTIMOTILITY agent s
When does travelers diarrhea usually occur
w/in 10 days of traveling
Treatment for travelers diahhrea
rehydration therapy
bismuth subsalicylate 525 mg po q30 min up to 8 doses
loperamide 4 mg stat, 2 mg w/ each stool max 16mg/d
Antibiotic treatment options for travelers diarrhea
Cipro 750 mg po x1
azithromycin (first line for women and pregnant)
rifaxamin
Risk factors for C. diff
elderly
cancer patients
pt with ng tube
PPIs
exposure to antimicrobial agents
Risk factors for recurrent infection of c. diff
recurrent CDI infection w/in 6 months
>65 yo
immunocompromised
severe infection on presentation
How to prevent spread of c. diff
gloving and gowning
soap and water
separate room with dedicated toilet
What is the diagnostic criteria for c. diff
new onset >3 unformed stools in 24 h
-nucleic acid amplification test (PCR/NAAT)
-toxin A/B
When is c. diff considered HO CDI
3 days in hospital to 28 days after discharge
When is c. diff considered Co-HCFA CDI
28 days after discharge to <12 weeks
When is c. diff considered CA CDI
<12 weeks
Non-severe vs severe c. diff classification
non-severe: WBC <150,000 AND SCr <1.5
severe: WBC >150,000 OR SCr >1.5
FIdaomicin is a macrolide that is bactericidal against _____________, inhibiting RNA synthesis by RNA polymerase
c. diff
(>18 yo approved)
When to use bezoltoxumab in c. diff
bind toxin B
(BBW for CHF)
use in high risk of recurrence
C. diff mainstays of treatment
fidaxomicin
vanco
metronidazole
bezlotoxuman
hydration
discontinue anti-peristaltic meds
What to use in initial CDI episode
Fidaxomicin
OR
vanco
What to use in first CDI episode
Fidaxomicin OR vanco OR bezlotoxumab
(tapered vanco)
What to use in second or subsequent CDI recurrence
Fidaxomicin OR vanco tapered OR vanco x10d
fecal microbiota transplant
recommended to treat w/ 3 courses of antibiotics
What to use in fulminant CDI
vanco OR NG tube
if ileus ADD rectal instillation vanco
IV metronidazole added to vanco in ileus
Amphotericin B MOA
binds to sterol moiety (ergosterol) in membrane of sensitive fungi
polyenes form pores or channels that increase permeability of the membrane
Amphotericin B ADME
GI negligible
does not penetrate anything
half life of 2 weeks
urine negligible
Amphotericin B ADE
infusion site rxn
dose-limiting
What are the azoles
ketoconazole
itraaconazole
fluconazole
voriconazole
Azole MOA
inhibition of 14-alpha-sterol demethylase
impair biosynthesis of ergosterol
increase membrane permeability
Ketoconazole and Itraconazole ADME
oral route has been replaced (for keto)
liver metabolism
high rate of ADRs (for keto)
Is ketoconazole a CYP450 isozyme inhibitor
yes
Fluconazole ADME
oral, IV
only azole to get into CNS
eliminated by kidneys***
low side effects: hepatotoxicity, rash
Itraconazole ADR
hepatotoxicity
BBW heart failure because it has a negative ionotrope
Vorriconazole ADME
high oral bioavailability (also given IV)
metabolized by CYP2C19
Vorriconazole ADR
not for pregnancy
hepatotoxicity
auditory hallucinations
Posaconazole ADME
cherry suspension
take with food
high protein bound
eliminated in feces
Posaconazole DDI and ADRs
CYP3A4
increase AUC of cyclosporine and midazolam
N/V/D, hepatotoxicity
What are the echinocandins
caspofungin
anidulafungin
micafungin
echinocandins ADME
lack oral
protein bound
not for pregnancy
caspofungin ADME
catabolized by hydrolysis and N-acetylation
excreted in urine and feces
caspofungin DDIs and ADRs
cyclosporine, increase tacrolimus levels, CYP3A4
phlebitis at injection site, histamine like rxns
micafungin ADME and DDIs
linear pharmacokinetics
eliminated in feces
immunosuppressant: sirolimus, CYP3A4
micafungin ADRs
histamine release
elevated blood levels of immunosuppressant drugs, cyclosporine and sirolimus
anidulafungin ADME
cleared by slow chemical degradation
diluent for IV infusion is ethanol
Griseofulvin MOA
inhibit microtubule function disrupting assembly of mitotic spindle
Griseofulvin ADME
take with fatty meal
M: liver
E: bile
barbiturates decrease absorption
deposited in keratin precursor cells (new hair or nail growth first to free disease)
Griseofulvin ADRs and DDIs
photosensitivity
hepatic CYPs
disulfiram like reaction with ethanol
Terbinafine MOA
inhibition of fungal squalene epoxidase, blocking ergosterol biosynthesis
Terbinafine ADME
extensive first pass metabolism
highly protein bound
not for pregnancy
Terbinafine DDIs
rifampin decrease plasma
cimetidine increase plasma
Nystatin MOA
same as amphotericin B
-co admin w/ antibacterial agents or corticosteroids
Clotrimazole MOA
alter permeability of fungal cell wall and inhibits activity of enzymes w/in fungal cell
Clotrimazole DDIs
CYP450 oxidase
Miconazole ADRs
vaginal: burning, itching, irritation
cutaneous: irritation, burning, maceration
USE during pregnancy
Risk factors for fungal skin and nail infections
skin trauma
immune suppression (diabetes, HIV)
climate
occlusive clothing
poor nutrition/hygiene
poor circulation
Tinea capitis (head)
infection begins in hair follicles
inflammatory: pustules and kerions
non-inflam: yellow scaling
Tinea corporis (body, ringworm)
oval patch with inflamed border
common in children
Tinea cruris (groin, jock itch)
more in males
inflammed legions, pustules, bilateral, spares genitals
Tinea pedis (foot, athletes foot)
toes or soles of feet, wet garments
white scaly patches
red inflamed areas
Tinea unguium (nails, oncymycosis)
nail and nail bed
yellow, thick, brittle
Treatment duration for tinea capitis and tinea unguium
rx treatment
Treatment duration for tinea corporis, tinea cruris, and tinea pedis
corporis: 4 wk
cruris: 2 wk
pedis: >4 wk
Tinea pedis treatment: small, vesicles, scaling, no inflammation
topical antifungal agent (4 wks)
Tinea pedis treatment: inflammatory lesions
aluminum acetate soln (up to 1 wk)
topical antifungal agent (4 wks)
Tinea pedis treatment: wet, soggy
aluminum chloride 20-30% (up to 1 wk)
topical antifungal agent (4 wks)
Tinea pedis treatment: wet, soggy, fissures
aluminum chloride 10% (1 wk)
aluminum chloride 20-30% (up to 1 wk)
topical antifungal agent (4 wks)
What are the topical OTC antifungal agents
lotrimin ultra cream - butenafine 1%
lotrimin AF cream - clotrimazole 1%
lotrimin AF powder - miconazole nitrate 2%
cruex - miconazole 2%
lamisil AT gel - terbinafine 1%
tinactin cream - tolnaftate 1%
When to use aluminum salts
astringent: wet, soggy tinea pedis infection decrease inflammation
Tea tree oil has antifungal activity against what
c. albicans
-nail fungal infection
-athletes foot: 2bidx4wk 10%
Cure rate for honey mixture in antifungal use
for tinea corporis and tinea cruris
Alternative medicines OTC for antifungal
Vick Vapor: 48 wk (not cure)
Mustard Oil: microsporum spp, trichophyton spp
Lavender Oil: trichophton spp, c. albicans
What topicals to use in <2 years
avoid terbinafine
What topicals to use in 2-12 years
clotrimazole, miconazole, tolnaftate
What topicals to use in >12 years
clotrimazole, miconazole, tolnaftate, terbinafine, butenafine
Risk factors for fungal infections
immunosuppression:
active chemo
AIDS
high dose steroids
Clinical marker:
ANC <500 (active neutrophil count)
What is ketoconazole used for
fungal skin infections
seborrhea dermatitis (dandruff)
What is fluconazole used for
candidiasis
cryptococcus
(renal dose adjustment for po dose)
Itraconazole BBW and counseling
PPIs decrease F
take with empty stomach
ventricular dysfunction and heart failure due to QT prolongation
Voriconazole counseling points
3A4 and 2C9 inhibitor
monitor LFT, SCr, vision, serum
take on empty stomaach 1 hour ac/pc, caution when driving at night, avoid sunlight
Posaconazole counseling points
LFT, electrolytes
take with full meals
Isavucinazonium counseling points
short QT
SJS/TEN
monitor LFT, electrolytes
What are echinocandins used for
candidal infections
ADE: hepato, electrolyte, hyperglycemia
monitor: LFT, electro, glucose
Flucytosine MOA
penetrate fungal cell membrane then converted to fluorouracil
renal impairment
myelosuppression
NEVER monotherapy
What are the premedications preferred to prevent ADE in amphotericin B
NS bolus
APAP
Diphenhydramine
morphine/meperidine
What is the most common candida infection
c. albicans
(c. krusei is increasing)
Candida infection risk factors
stem or solid organ transplant, HIV, GI surgery, IV catheters, broad antibiotics
Initial therapy fo candida infections
echinocandin > ampho B, azole
What are histoplasmosis
histoplasma capsulatum
-soil, chicken feces, bat feces
treatment: ampho B (1-2 wk) then itraconazole 1-2 yr
What are blastomycosis
blastomyces spp
treat: ampho B (2-6 wk) then itraconazole 1-2 yr
What are coccidioidomycosis
coccidioides spp (valley fever)
mild mod: fluconazole
severe: ampho B > conventional
What is aspergillus
mold
mostly pulmonary infections
treatment: voriconazole then ampho B if vor is untolerated
