Term
|
Definition
| presence of bacteria in bloodstream |
|
|
Term
|
Definition
| mechanical introduction by IV drug use, seeding from gingival mucosa with brushing, or spread from other sites |
|
|
Term
| What is the primary risk factor for developing nosocomial bacteremia? |
|
Definition
|
|
Term
| What are the steps of how CRBSIs begin and cause problems? |
|
Definition
1. Hosts form fibrinsheath on catheter surface
2. Bacteria colonize and produce biofilm
3. Environment ideal for bacterial growth and relatively impenetrable to PMNs, macrophages, antibodies, and antibiotics
4. Organisms can detach from the catheter and cause symptomatic infection
5. Bacterial seeding occurs |
|
|
Term
| What are the 6 risk factors of CRBSI? |
|
Definition
1. prolonged catheterization
2. frequent manipulation
3. improper/suboptimal aseptic technique
4. number of catheter lumens
5. catheter location (subclavian < internal jugular < femoral)
6. heavy skin colonization |
|
|
Term
| What are the common organisms involved in CRBSI? |
|
Definition
1. coag-neg staph
2. S. aureus
3. Enterococci
4. Gram neg bacilli, including Pseudomonas
5. Candida |
|
|
Term
| How do people with CRBSI present? |
|
Definition
1. Symptoms: fever, elevated WBC
2. Change in overall clinical status or new development of sepsis
3. Rule out other nosocomial infections by more specific diagnostic tests
4. Local inflammation at insertion site can occur but is not required for diagnosis |
|
|
Term
| How do we diagnose CRBSI? |
|
Definition
1. quantitative or semiquantitative culture of the cathetertip
PLUS
2. 2 sets of blood cultures with one drawn percutaneously |
|
|
Term
| Which of the two cultures for CRBSI diagnosis is most important and why? |
|
Definition
| **most definitive diagnosis of CRBSI is when bacterial cultures reflect growth in both catheter culture and blood culture, but that the catheter culture has significantly more colonies or much more rapid time to positive result than the blood culture. |
|
|
Term
| What are the ways in which CRBSIs can be prevented? |
|
Definition
1. Sterile barriers for catheter placement
2. Topical antiseptics(chlorhexadine, alcohol-based povidone-iodine)
3. Catheters with antibiotics for lines >5 days (chlorhexidine/silver sulfadiazine, minocycline/rifampin)
4. antibiotic lock solutions - long term catheters with recurrent infections |
|
|
Term
|
Definition
We want to cover G+: Staph, including MRSA, MRSE, and Enterococcus
1st - Vanc
2nd - high dose Dapto
NOT linezolid |
|
|
Term
When do we want to add G- coverage, including Pseudomonas, for CRBSI?
What drugs cover this? |
|
Definition
* long-term catheters, femoral, severe infection, immunocompromised
* carbapenems, BL/BLI, cefepime +/- AG |
|
|
Term
| When do we need coverage for fungal infections in CRBSI? What drugs cover? |
|
Definition
* femoral catheters, sepsis w/ risk factors (parenteral nutrition, prolonged antibiotics, severe immunosuppression, Candida colonization in multiple sites)
* REMOVE CATHETER! echinocandin(BIG GUN) or fluconazole(smaller gun) |
|
|
Term
| How do we de-escalate in CRBSI when we know the culture results? |
|
Definition
MSSA: nafcillin or oxacillin
Enterococcus: ampicillin or vanc +/- AG
G-: BL |
|
|
Term
| Duration of therapy for uncomplicated CRBSI? |
|
Definition
|
|
Term
| When do we treat CRBSI for 4-6 weeks? |
|
Definition
| if culture + >72 hours after catheter removal or patient has prosthetic material |
|
|
Term
| When do we treat CRBSI for 5-7 days? |
|
Definition
| coagulase negative staph with catheter removal can receive short course |
|
|
Term
| What is antibiotic lock therapy? |
|
Definition
| may see as adjuvant treatment for retained catheter catheters; instill high conc antibiotic into the catheter and leave 24-48 hours |
|
|
Term
| Patients with CRBSI should be followed for 6 weeks to detect late-appearing complications...like what? |
|
Definition
endocarditis
septic thrombosis
osteomyelitis
endophthalmitis |
|
|
Term
| What are the risk factors of endocarditis? |
|
Definition
1. Structural Heart Disease
- prosthetic valve
- prior endocarditis
- congenital heart disease
- rheumatic heart disease
- others: mitral valve prolapse with insufficiency, cardiomyopathy, etc.
2. Bacteremia
- IV drug use
- nosocomial infection (dental procedures) |
|
|
Term
| Common G+ of endocarditis? |
|
Definition
Strep (viridans group)
Staph (aureus and epidermidis)
Enterococci |
|
|
Term
| Common G- of endocarditis? |
|
Definition
* Enterobacteriaceae
* Pseudomonas (IV drugs, prosthetic valves, cirrhosis)
* HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) group; oropharyngeal inhabitants; blood cultures are frequently negative for 2-3 weeks |
|
|
Term
| Describe fungal causes for endocarditis including prevalence, risk, and common organisms involved. |
|
Definition
<5% - rare
risk: immunosuppressed pts; IV drug use
Candida, Aspergillus |
|
|
Term
| How do we explain negative cultures in endocarditis? |
|
Definition
* failure to culture (highly fastidious organism, very low-level bacteremia, antibiotic admin prior to culture)
* causative organism does not grow on typical culture media
* valvularvegetation that are not infectious |
|
|
Term
| Primary endocarditis pathophysiology? (detailed) |
|
Definition
1. Damage to the endothelial lining of the heart (endocardium)...most commonly from abnormal or turbulent blood flow
2. Platelets and fibrin deposit at damaged area
3. Thrombus is colonized by transient bacteremia
4. Bacteremia originates from trauma to highly colonized mucosa (mouth, GIT, genitourinary tract) or by direct inoculation (IV drug use)
5. Viridans group Strep produce dextran and S. aureus produce glycocalyx...both substances facilitate adhesion to the platelet/ fibrin matrix |
|
|
Term
| Primary endocarditis pathophysiology? (simplified) |
|
Definition
1. Damage to endothelial lining of heart
2. Platelets and fibrin deposit at damaged area
3. Thrombus is colonized by transient bacteremia
4. Bacteremia originates from trauma to highly colonized mucosa
5. Viridans group Strep produce dextran and S. aureus produce glycocalyx...both substances facilitate adhesion to the platelet/ fibrin matrix |
|
|
Term
| What are the secondary effects of endocarditis? |
|
Definition
* directvalvular, perivalvular damage
* embolization with possible seeding of remote sites
* formation of immune complexes |
|
|
Term
| Where do right-sided and left-sided lesions embolize to? |
|
Definition
Right-sided: lungs
Left-sided: kidneys, spleen, brain |
|
|
Term
| What are the different immune complexes formed during endocarditis? |
|
Definition
glomerulonephritis
osler nodes |
|
|
Term
| How do endocarditis patients present? |
|
Definition
nonspecific, variable
Symptoms: fever, chills, night sweats, weakness, dyspnea, anorexia, weight loss, myalgia, arthralgias
Signs: heart murmurs; petechiae, splinter hemorrhages, oslers nodes, janeway lesions, clubbing, roths spots |
|
|
Term
| What are the diagnostic criteria for endocarditis? |
|
Definition
* based upon Modified Duke Criteria
1. culture or histology of vegetation or cardiac abscess
2. 3 sets of blood cultures from separate sites over 24 hours(>95% yield)...save cultures for one month (HACEK)
3. Modest WBC elevation
4. ESR and CRP elevation
5. Transthoracic echocardiography (TTE) which is non-invasive and 60% sensitive; Transesophageal echo (TEE) which is more invasive and 95% sensitive |
|
|
Term
| In general, how do we treat endocarditis? |
|
Definition
1. high doses of IV agents
2. long duration of therapy (4-6 wks)
3. monitor blood cultures until negative for up to 8 weeks after the end of therapy |
|
|
Term
| What is empiric therapy for endocarditis? |
|
Definition
* Target Strep and Enterococci
* Target MRSA +/- G- if pt is acutely ill, has prosthetic valve, and/or IV drug users |
|
|
Term
Treatment for endocarditis from Strep (viridans)
MIC levels: <.12, .12-.5, >.5 |
|
Definition
MIC <.12:Pen G (Alt ceftriaxone) 4 wks
ADD Gent for synergy for 2 weeks...not in renal dsease
MIC .12-.5: use higher doses Pen G/ ceftriaxone
Gent REQ'D
MIC >.5 Ampicillin or Pen G + Gent
**If PCN allergy: Vanc |
|
|
Term
| Treatment for endocarditis from Staph. Native valve vs prosthetic valve |
|
Definition
Native Valve: Nafcillin or Oxacillin; Alternatives: cefazolin, vanc, or dapto
Treat for 6 weeks
Prosthetic Valve: 3 meds: nafcillin or vanc + rifampin + Gent(2 weeks)
Treat for over 6 weeks |
|
|
Term
Treatment of endocarditis from Enterococci
Susc, Gent-resistant, Vanc-resistant |
|
Definition
Susceptible:
Ampicillin or Pen G PLUS Gent for 4-6 weeks
Vanc + Gent for 6 wks if PCN allergy
Gent-resistant:
Streptomycin in place of Gent
Vanc-resistant:
linezolid, quinupristin/dalfopristin, dapto in place of vanc in PCN allergy |
|
|
Term
| Treatment for endocarditis from HACEK |
|
Definition
ceftriaxone or amp/sulb
ciprofloxacin as alternative for 4 wks |
|
|
Term
| When is surgery considered for endocarditis? |
|
Definition
1. hemodynamic decomposition or heart block
2. uncontrolled infection (+ cultures > 2wks)
3. fungal and G- infections
4. recurrent emboli
5. prosthetic hardware |
|
|
Term
| When is prophylaxis for endocarditis warranted? |
|
Definition
High Risk Individuals
- prosthetic valve
- prior endocarditis
- congenital heart disease
- NOT rheumatic heart disease
- NOT others: mitral valve prolapse with insufficiency, cardiomyopathy, etc.
High Risk Dental procedures |
|
|
Term
Prophylaxis recommendations
PO, NPO, PCN allergy, PCN allergy+NPO |
|
Definition
PO: amoxicillin
NPO: ampicillin or cefazolin or ceftriaxone
PCN allergy: cephalexin or clindamycin or azithromycin/clarithromycin
PCN allergy+NPO: cefazolin or ceftriaxone or clindamycin |
|
|
Term
|
Definition
| infection or inflammation of membranes covering the brain and spinal cord |
|
|
Term
|
Definition
| infection or inflammation of the brain tissue (parenchyma) |
|
|
Term
| CNS infections most commonly seen in which patients? What are the risk factors? |
|
Definition
children and elderly
Risk factors: immunosuppression, chronic disease, and placement of CSF shunts |
|
|
Term
| CNS infection pathophysiology (hematogenous and contiguous) |
|
Definition
H: bacteria colonize the nasopharynx then invade through cerebral vessels to subarachnoid space
C: secondary route, organisms spread locally from a nearby infection (mastoiditis) |
|
|
Term
| CNS infection due to host defense impairment |
|
Definition
CSF immunocompromised:
- limited phagocytosis response
- contains antiinflammatory and immune suppressant substances
Delayed activation of host defenses allows bacteria to replicate freely within CSF |
|
|
Term
| What are the pathophysiological complications of CNS infections? |
|
Definition
1. bacterial death causes release of cell-wall components that lead to release of inflammatory mediators
2. inflammatory mediators alter permeability of the BBB, causing cerebral edema and other complications (stroke, seizure)
3. eventual host respons (neutrophil activation) in response to infection contributes to detrimental effects (collateral damage) |
|
|
Term
| What are the signs and symptoms of CNS infections? |
|
Definition
vary w/ pt age and rapidity of onset
Adults: fever, headache, stiff neck/back, photophobia, meningeal irritation; possibly lethargy, altered mental status, or seizures; rapid or slow
Infants: nonspecific sx (irritability, altered sleep patterns, vomiting, change in cry, decreased oral intake, seizures)
*rash = Neisseria
*preceding respiratory sx |
|
|
Term
| What are the 2 different physical exams for determining CNS infections? Describe each. |
|
Definition
Kernig's Sign: thigh and knee are flexed and moved to extension...pain = CNS infection
Brudzinski's sign: passive flexion of the neck causes spontaneous flexion of the hips and knees |
|
|
Term
| What are the presentation complications of CNS infections? |
|
Definition
More common: seizures, hearing loss
Less common: subdural effusions, cerebral herniation, cranial nerve palsies, hydrocephalus, focal deficits(stroke problems), learning disorders, cerebral thrombus |
|
|
Term
| What are the main points of diagnosis of CNS infections? |
|
Definition
1. increased opening pressure >20cm H2O
2. increased WBCs
-bact: >100cells; >90% neutrophils
-viral:fewer neutrophils
3. Glucose
-lowered in bacterial meningitis
- >2/3 serum; bact <1/2 serum
4. Protein
-CSF protein elevated
-inflammation messes up BBB and other things can leak in |
|
|
Term
| What are the causative organisms in CNS infections? |
|
Definition
Neisseria - MOST COMMON
S. pneumo - common as secondary infection; neurologic sequelae common
H.influ - 99% decline in vacc countries
Listeria - common in pts with impaired cell-mediated immunity; infection follows colonization of GIT
G-(E.Coli) - 4th most common; only in predisposed pts
GBStrep - commmon in neonates!! |
|
|
Term
| General treatment principles for CNS infections? |
|
Definition
1. rapid initiation of appropriate antimicrobial therapy is ESSENTIAL
2. supportive therapy, including anticonvulsants for seizures
3. IV steroids for certain pts (BEFORE abx)
4. drugs must be: bacteriCIDAL and acheive adequate concs at site of infection |
|
|
Term
| Describe PK of antimicrobials in the CSF. |
|
Definition
* BBB permeability increases during infection due to separation of tight junctions and increased production of pinocytic vesicles
* over time permeability decreases
* abx cross by passive diffusion by conc gradient
* abx not metabolized w/in CSF
* elim dependent on passive diffusion
* bacteriCIDAL concs needed |
|
|
Term
| What are the determinants of CSF penetration? |
|
Definition
1. Lipid Solubility
-lipophilicity (FQs/rifampin); good CSF penetration; diffuse through transcellular
-hydrophilicity(BL/vanc); poor CSF penetration; diffuse through paracellular pathways(tight junctions)
2. MW
-smaller, simpler penetrate more easily; vanc too large to penetrate
3. Ionization
-ionized drugs(BL) have poor penetration into CSF
4. Plasma Protein Binding
-highly bound drugs have decreased penetration...only free drug penetrate CSF
5. Active Transport Pumps
-energy-dependent exit pumps may actively remove abx from CSF and this increases after inflammation subsides |
|
|
Term
1. Lipophilic agents have (good/poor) CSF penetration.
2. Ionized agents have (good/poor) CSF penetration.
3. Highly protein bound agents have (good/poor) CSF penetration.
4. Energy-dependent exit pumps may actively remove abx(BL,AG,FQ) from CSF and (increases/decreases) after inflammation subsides |
|
Definition
1.good
2.poor
3.poor
4.increases |
|
|
Term
| Which drugs can gain therapeutic levels w/ or w/o inflammation? |
|
Definition
rifampin
metronidazole
sulfonamides
trimethoprim
chloramphenicol |
|
|
Term
| Which drugs can gain therapeutic levels w/ inflammation? |
|
Definition
Pcns
cephs(3rd/4th)
carbapenems
vanc
FQs
acyclovir
fluconazole
dapto |
|
|
Term
| Which drugs canNOT gain therapeutic levels w/ or w/o inflammation? |
|
Definition
AGs
clindamycin
1st/2nd gen cephs
amphoB
ketoconazole,itraconazole |
|
|
Term
| Empiric therapy for CNS infections are based upon age. |
|
Definition
<1 mo: GBS,G-,Listeria -> ampicillin + cefotaxime or AG
1mo-4yo: Spneum,Neisseria,Hinflu
5yo-29yo: Neisseria, Spneum
30yo-60yo: Spneum, Neisseria
all these groups -> vanc + cefotaxime or ceftriaxone
>60yo: Spneum, GNR, Listeria -> vanc AND ampicillin + cefotaxime or ceftriaxone |
|
|
Term
Targeted therapy and duration for CNS infections:
1. Spneumo
2. Neisseria
3. Listeria
4. GBStrep
5. Hinflu
6. G- |
|
Definition
1. PenG, Ampicillin, cefotaxime, ceftriaxone, Vanc for 10-14 days
Alt: meropenem, FQ, chloramphenicol
2. same minus vanc for 7 days
Alt: chloramphenicol, FQ, aztreonam
3. ampicillin or PenG +/- Gent for >21 days
Alt: TMP/SMZ, meropenem
4. ampicillin or PenG +/- Gent for 14-21 days
Alt: cefotaxime or ceftriaxone
5. ampicillin, cefotaxime, or ceftriaxone for 7 days
6. cefotaxime or ceftriaxone for 21 days
Alt: cefepime, meropenem, aztreonam, FQ, TMP/SMZ |
|
|
Term
| Antibiotic Dosing for CNS infections? |
|
Definition
*in general - dosed high to adjust for decreased conc at site of infection
*cefotaxime 2gm Q4h
*ceftriaxone 2gm Q12h
*ampicillin 2gm Q4h
*vanc 30-40mg/kg/day; trough target is 15-20 mg/L |
|
|
Term
| When and how are steroids used in CNS infections? |
|
Definition
* given to children >2 mos to prevent hearing loss and neurolgoic sequellae in Spneum or Hinflu
* given to adults to improve mortality when Spneum -> dexamethasone 10mg IV Q6h x 4days
* must give steroids prior to first dose of abx to be effective
* steroids impact CSF penetration of some abx |
|
|
Term
| When is prophylaxis for CNS infections needed? |
|
Definition
* close contacts of pts infected with Neisseria or Hinflu (day care, household, nursery)
* prophylax w/ rifampin
* prophylaxis inhibits nasopharyngeal carriage of organisms before they disseminate into bloodstream
Hinflu - 600mg QD x 4 days and 20mg/kg/dose for children
**do not need prophylaxis for Hinflu if fully vaccinated
Neisseria - 600mg BID x 2 days and 10mg/kg/dose for children; Alt: ceftriaxone IV, ciprofloxacin |
|
|
Term
| What are the 3 types of diarrhea? |
|
Definition
1. Acute - sx less than 14 days
2. Persistent - sx greater than 14 days
3. Chronic - sx greater than 4 wks |
|
|
Term
| What are the causes of infectious diarrhea? |
|
Definition
1. Viral gastroenteritis
2. Antibiotic-associated diarrhea
-Cdiff (CDAD)
-osmotic (non-CDAD)
3. Traveler's diarrhea
4. Food poisoning
-C.jejuni; Staph endotoxin
5. Protozoal (O&P) |
|
|
Term
| Patient presentation of diarrhea is critical so monitor what? |
|
Definition
*freq and duration
*presence of blood or mucus, ab pain, or fever
*signs of dehydration
*general med histroy/ social support
*preg women who may infect newborn |
|
|
Term
| What circumstances may cause diarrhea? |
|
Definition
* alt H2O, raw/undercooked, raw seafood, unpast. milk
* travel to undeveloped area
* contact with unwell pts
* recent hospitalization or abx
* swimming in lake or pools
* visit to farm or contact with pets with diarrhea |
|
|
Term
| General Management of infectious diarrhea |
|
Definition
* Treatment often empiric
* Oral Rehydration Therapy (ORT)
* Antidiarrheals: anti-motility, absorbent, and anti-secretory
* Abx only if CONFIRMED infection of Shigella, Campylobacter, Yersinia
* Probiotics
* Fecal Transplantation |
|
|
Term
| Describe Oral Rehydration for infectious diarrhea |
|
Definition
* safe, simple, cheap
* superior to IV fluids...unless severe dehydration
* OTC |
|
|
Term
| Describe Salmonella-caused diarrhea. |
|
Definition
| Sx: diarrhea, ab pain, vomiting, nausea, fever 1-7 days |
|
|
Term
| Describe Shigella-caused diarrhea. |
|
Definition
| Sx: ab pain, diarrhea, fatigue, malaise, fever; mucus and blood in feces; colonic phase w/in 1-3 days where sx are intense cramps as well as freq and painful bm lasting up to 14 days |
|
|
Term
| Describe C.jejuni-caused diarrhea. |
|
Definition
| Sx: watery/bloody diarrhea, ab pain, and nausea preceded by muscle pain, headache, and fever; may last 1 day to 1 week or longer |
|
|
Term
| Describe Yersinia-caused diarrhea. |
|
Definition
| Sx: ab pain, headache, fever, diarrhea, nausea, vomiting; watery/mucoid diarrhea in children; ill for >1 wk |
|
|
Term
| Describe Listeria-caused diarrhea. |
|
Definition
* high mortality in elderly
* infection can cause febrile gastroenteritis accompanied by bacteremia and sometimes meningitis
* during preg may be complicated by amnionitis and fetal infection
* diagnosis reqs blood culture |
|
|
Term
| What is the pathogen of traveler's diarrhea? |
|
Definition
enterotoxigenic E. Coli (ETEC)
produces toxins that elevate cAMP or cGMP and cause fluid loss |
|
|
Term
| What meds are used to treat traveler's diarrhea? |
|
Definition
Antimotility: loperamide, diphenoxylate, paregoric, to increase fluid retention
*not with fever or bloody diarrhea
Only use abx (FQ) if develop 3+ loose stools in 8hr period w/ associated vomiting and abdominal cramps and bloody stools |
|
|
Term
| Describe Staph enterotoxin B-caused diarrhea. |
|
Definition
| Sx: develop w/in 6 hours although illness can appear in as little as 30 mins |
|
|
Term
| Two types of AAD (antibiotic-associated diarrhea) |
|
Definition
Non-infectious
*abx alter microbiome
*carb digestion in colon is reduced
*increased osmotic load in colon lumen *secretory diarrhea
Cdiff
*abx alter microbiome
*colonization by Cdiff
*release of toxins
*colitis and diarrhea |
|
|
Term
| Mild to Moderate to Severe Sx of Cdiff infection |
|
Definition
Mild: ab cramping w/ endoscopic findings of diffuse or patchy nonspecific colitis
Moderate: fever, dehydration, nausea, anorexia, malaise, profuse diarrhea, ab distention, cramping pain moderate leukocytosis, fecal leukocytes, diffuse, patchy colitis on endoscopy
Severe: profuse diarrhea, ab pain, fever with loss of fluids |
|
|
Term
| What are the laboratory diagnoses for Cdiff? |
|
Definition
*Stool culture
*latex agglutination to detect antigen in stools
*tissue culture assay for cytotoxicity of toxin 8
*enzyme-linked immunosorbent assay (ELISA) for toxins A and B |
|
|
Term
| What are the main antibiotics more frequently used w/ CDAD? |
|
Definition
3rd/4th gen cephs
ampicillin/amoxicillin
clindamycin
other pcns
macrolides
tetracyclines
TMP/SMZ |
|
|
Term
| What are the main antibiotics less frequently used w/ CDAD? |
|
Definition
ticar/clav
metronidazole
FQs
rifampin
5-FU
methotrexate
cyclophosphamide |
|
|
Term
| What is the CDAD treatment for initial treatment if it is mild or moderate? |
|
Definition
WBC < 15,000 and SCR <1.5xbaseline
metronidazole 500mg PO Q8h |
|
|
Term
What is the CDAD treatment for initial treatment if it is severe?
What if severe, complicated? |
|
Definition
WBC > 15,000 or SCR > 1.5x baseline
Vanc 125 mg PO Q6h
hypotension, shock, ileus, toxic megacolon
vanc 500mg PO Q6h + metro 500mg IV Q8h
may add vanc PR |
|
|
Term
What do we do for 1st and 2nd reoccurences for CDAD?
What is the reoccurence rate with vanc or metronidazole? |
|
Definition
1st - use same med that was initially used for the pt as long as it fits in the range for severity
2nd - vanc w/ taper or pulse dose
20% reoccurence rate |
|
|
Term
| What are the indications for vanc therapy over metronidazole therapy in CDAD? |
|
Definition
*no metronidazole response
*metronidazole intolerance
*prego or child < 10yo
*severe/sudden/intense CDAD |
|
|
Term
| Main points about viruses |
|
Definition
*not alive
*some crystallized
*not metabolize
*no ribosomes
*no growth
*no cell division
*DNA or RNA but not both |
|
|
Term
| What are the two cycles of viral replication? |
|
Definition
|
|
Term
| _____________ infection is the most common cause of infectious diarrhea; most commonly called ______________. |
|
Definition
Viral
rotavirus - most common in infants and young children |
|
|
Term
| Cornerstone of infectious diarrhea management should focus on _________________ status. |
|
Definition
|
|
Term
| What are the main parasites and their treatments in diarrhea? |
|
Definition
Giardia - Flagyl
Cryptosporidium - azithromycin
Entamoeba histolytica - Flagyl |
|
|
Term
| When does an uncomplicated intra-abdominal infection become complicated? |
|
Definition
| When the infection has extended from organ of origin into the peritoneal cavity. |
|
|
Term
| What is primary peritonitis and what are the two different subsets? |
|
Definition
Primary - infection of peritoneal cavity in which the GIT integrity has not been compromised; generally monomicrobial; Two subsets
1. Chronic Ambulatory Peritoneal Dialysis (CAPD) - leading complication; can lead to hospitalization or technique failure
2. Spontaneous Bacterial Peritonities (SBP) - ascites secondary to liver disease; 10-30% pts with cirrhosis |
|
|
Term
| What is secondary peritonitis and what are the two different subsets? |
|
Definition
Secondary peritonitis - infection in peritoneal cavity that results from microscopic or macroscopic perforation of a hollow viscous
1.CA - pts not currently or recently in hospital (mild to mod vs severe or high risk)
2.HA - nosocomial; pts currently or recently in hospital (severe or high risk) |
|
|
Term
| What is tertiary peritonitis? |
|
Definition
| secondary infections that fail to respond to therapy |
|
|
Term
| What are the normal host defenses against intra-abdominal infections? |
|
Definition
*mechanical clearance of organisms from peritoneum
*rapid, widespread inflammatory response(macrophage, phagocytosis)
*microscopic sequestriation |
|
|
Term
| What are the primary routes of entry for bacteria in CAPD? |
|
Definition
| *migration of organisms up the catheter and into the peritoneal space; pts can do this at home |
|
|
Term
| What are the primary routes of entry for bacteria in SBP? |
|
Definition
*translocation from bloodstream (hematogenous)
*impaired defenses (ascitic fluid, shunting of blood around liver) |
|
|
Term
| What are the secondary routes of entry for bacteria? |
|
Definition
*spread abdominal organs including GIT (breach of integrity)
Examples:
*perforation of stomach or intestines from peptic ulcer or other cause
*intestinal diseases (diverticulosis, Chrohn's disease, ulcerative colitis)
*infected organs (appendicitis, cholecystitis, necrotizing pancreatitis)
*trauma
*cancer (obstruction or perforation)
*small bowel obstruction (various causes)
*vascular hypoperfusion (bowel infarction)
*surgical contamination |
|
|
Term
| What are the main immune responses involved in intra-abdominal infections? |
|
Definition
* more profound in secondary infections
* immediate and widespread
* can cause major fluid and protein shifts into abdomen - may lead to shock and thus sepsis
* may cause slowing of GI motility or ileus
* microscopic sequestration can lead to either clearance of infection or development of abscess and adhesions |
|
|
Term
| Describe abscess formation as part of intra-abdominal infections? |
|
Definition
* chronic inflammatory process
* occur in peritoneal space or w/in/attached to organ tissues
* purulent fluid collection walled off from surrounding tissues
* may contain necrotic debris, bacteria, inflammatory cells
* neutrophils trapped in abscess die in 3-5 days
* anaerobic bacteria may proliferate in this low-oxygen environment
* bacterial products and neutrophil contents lead to liquification of the inner portion of the abscess
* organisms vary based upon site, but anaerobes are common |
|
|
Term
| What are the organisms of primary CAPD? |
|
Definition
coag neg Staph
S.aureus
Strep
Enterococci
Pseudomonas |
|
|
Term
| What are the organisms of primary SBP? |
|
Definition
E.Coli most common
Klebsiella
S pneumo (from transient bacteremias) |
|
|
Term
| What are the organisms of secondary peritonitis? |
|
Definition
* often polymicrobial
* community infections: G- such as E.Coli, Strep, Bacteroides
* nosocomial/severe infections: Candida, Enterococci, MRSA, other MDR pathogens, Pseudomonas
* Consider pathogens based on site of infection |
|
|
Term
| What are the signs/symptoms of primary peritonitis? How do we diagnose? |
|
Definition
Signs/Sx:
* ab pain, NV, decreased bowel sounds
* WBCs mildly increased
* CAPD - milder sx, with cloudy effluent
* SBP - altered mental status
Diagnosis
* fever and nonspecific sx
* CAPD: >50% PMNs (percentages)
* SBP: >250 PMNs (cell count) |
|
|
Term
| What are the signs/symptoms of secondary peritonitis? How do we diagnose? |
|
Definition
Similar to primary but generally more severe:
* generalized ab pain, guarding
* fever more common
* decreased or even absent bowel sounds
* shock
* NO Peritoneal Fluid or cultures!
Diagnosis
* clinical + radiograph(CT scan) |
|
|
Term
| What are the two ways to treat intra-abdominal infections without antibiotics? |
|
Definition
1.Supportive Care - fluid resuscitation to restore intravascular volume; address septic shock
2.Source Control - draining infected foci, abscesses, and fluid collections or surgical repair of organ damage.... seldom used in primary infections |
|
|
Term
| List general principles for empiric treatment of intra-abdominal infections. |
|
Definition
* start abx immediately upon diagnosis for secondary infections
* broad spectrum agents (G+,G-, anaerobes for secondary)
* single regimens are as effective as combos as long as they have the same spectrum of activity
* timing of abx for source control intervention is important |
|
|
Term
| Treatment for primary peritonitis of CAPD? |
|
Definition
Vanc + G- + pseudo
*vanc, AGs, cephs generally compatible
*AVOID pcns w/ AGs |
|
|
Term
| Treatment for primary peritonitis of SBP? |
|
Definition
* cefotaxime (C3) bc of less protein binding, followed by ceftriaxone (more protein bound)
* FQs
* if the pt has previously had SBP then long-term prophylaxis (FQs or TMP/SMZ) |
|
|
Term
| Treatment for Secondary CA, mild-mod intra-abdominal infection |
|
Definition
Single:
* ticarcillin/clav
* moxifloxacin
* ertapenem
* tigecycline
Combo:
* Metronidazole + cephs or FQs
*covers G-,Strep, anaerobes |
|
|
Term
| Treatment for Secondary CA, highrisk/severe or HA intra-abdominal infections |
|
Definition
Single:
carbapenems
pip/tazo
Combo:
cefepime, ceftazidime, ciprofloxacin, or levofloxacin + metronidazole
* include pseudo coverage |
|
|
Term
| Which specific meds are NOT recommended in Secondary intra-abdominal infections? |
|
Definition
* workhorse antipseudomonals
* clindamycin and cefotetan
* AGs (toxicity) |
|
|
Term
| What are the considerations related to treatments of abscesses? |
|
Definition
* bacteria may shift to stationary phase - may not respond optimally to call wall-active agents
* large abscesses aren't easily accessible to the bloodstream
- abx diffuse by conc: permeability worsens over time
- pk conc delayed: time dependent drugs better
* pH changes may also occur (AGs lose effect in acidic environment)
* draining required |
|
|
Term
| Post-surgical complications result in an estimated __________ of additional hospitalization. |
|
Definition
|
|
Term
| Infection at or near the site of incision that occurs within _______ days of surgery if NO implant placed, and within __________ if a permanent, implantable foreign body placed |
|
Definition
|
|
Term
| Where does most microbial contamination of a surgical wound come from? |
|
Definition
Endogenous - flora of pt; S aureus, S epi
Less Common: exogenous- surgical environment, surgeon, staff, etc |
|
|
Term
| What are the site-specific manifestations of surgical infections? |
|
Definition
| purulent drainage, abscess, erythema, edema, warmth, and pain |
|
|
Term
| What are the systemic manifestations of surgical infections? |
|
Definition
| leukocytosis, fever, but these are NOT diagnostic of SSI |
|
|
Term
| What are the patient-specific risk factors for surgical infections? |
|
Definition
Pt-specific risk factors impair ability to fight off infection or impair abx to get to infection
* DM/post-operative hyperglycemia
* concurrent tobacco or steroid use
* remote infection at time of surgery
* obesity
* malnutrition
* prolonged perioperative stay |
|
|
Term
| What are the procedure-related risk factors for surgical infections? |
|
Definition
* improper antimicrobial prophylaxis
* implantation of prosthetic materials
* improper perioperative preparation - cannot get all microbes away; shaving with razor
* inadequate operating room conditions
* poor surgical technique
* perioperative hypothermia and/or hypoxia |
|
|
Term
| What are the main indications for antibiotic prophylaxis? |
|
Definition
* surgeries with high infection rates
* foreign body implantation
* infection unlikely but severe consequences if occurs |
|
|
Term
| Who is in charge of identifying if a surgery has a high infection rate? |
|
Definition
| National Research Council (NRC) |
|
|
Term
| Describe identification of the 'perfect' antibiotic for surgical infections. |
|
Definition
| pathogens -> adequate concentration at incision site -> shortest effective time |
|
|
Term
| What are the main steps of antibiotic selection for surgical infections? |
|
Definition
Step 1: Pathogen identification based on surgical site location
Step 2: Select antibiotic agent based on likely pathogens, hospital and patient considerations.
Step 3: Ensure adequate blood and tissue levels for length of the surgery
Step 4: Select appropriate duration of therapy |
|
|
Term
| Pathogen identification based on surgical site location. |
|
Definition
* Cardiothoracic/Vascular/Neuro: G+ Saureus, coag neg Stap (epi)
* GI: G- E.Coli, Klebsiella, anaerobes, enterococci
* Gynecologic/Obstetric: G-, GBStrep, anaerobes, enterococci
* Orthopedic: G+ Saureus, coag-neg Staph |
|
|
Term
| Select antibiotic agent based on likely pathogens, hospital, and patient considerations. |
|
Definition
* Select abx with narrow spectrum of activity
* Cephs are most commonly used class of abx
-1st gen: cefazolin has good G+, adequate G- (PEcK)
-2nd gen(cephamycins): cefotetan, cefoxitin have anaerobe coverage, G-, limited G+
-2nd gen(true): cefuroxime has good G+, G-(HENPEcK)
* may consider Vanc in hospitals with 'high' rates of MRSA infections
* in pts with true BL or PCN allergies, may use Clindamycin or Vancomycin... great G+ but no G- coverage |
|
|
Term
| How do we ensure adequate blood and tissue levels of abx for the length of surgery? |
|
Definition
* appropriate timing and dose to keep concentration above the MIC
* administer abx w/in 1 hour prior to incision (2hrs if using vanc or FQs)
* if surgeries will last >3-4 hours, then additional doses may be needed
-redose for every 2 t1/2 for agent
* may need higher doses with higher BMI bc need better penetration into tissues
-dose 2g instead of 1g for cefazolin if >80kg |
|
|
Term
| Select appropriate duration of therapy for surgical prophylaxis. |
|
Definition
*no difference in multiple doses vs single dose prophylaxi
* stop prophylactic abx w/in 24 hours post surgery (after 48 hours in cardiothoracic surgeries) |
|
|
Term
Abx prophylaxis by organ system?
*Neurosurgery
*Cardiothoracic/Vasc/Hip or Knee Arthroplasty
*Colon
*Hysterectomy |
|
Definition
*Neurosurgery: cefazolin, vanc if BL allergy
*Cardio/Vasc/Arthroplasty: cefazolin, cefuroxime, or vanc; clindamycin or vanc if BL allergy
*Colon: cefotetan, cefoxitin, amp/sul, or ertapenem OR cefazolin or cefuroxime + metronidazole
if BL allergy: clinda+AG,FQ, or aztreonam OR metronidazole+AG or FQ
*Hysterectomy: cefotetan, cefazolin, cefoxitin, cefuroxime, or amp/sul
if BL allergy: clinda+ AG,FQ,or aztreonam, metronidazole + AG or FQ |
|
|
Term
|
Definition
| Surgical Care Improvement Project |
|
|
Term
| Describe the core measures of SCIP Inf-1-3. |
|
Definition
SCIP Inf-1: prophylaxis w/in 1hr prior to incision (2hrs if vanc or FQ)
SCIP Inf-2: prophylaxis for surgical pts
SCIP Inf-3: prophylaxis dc'd w/in 24hrs (48hrs if CV surgery) after surgery ends |
|
|
Term
| What is the definition of ADR? |
|
Definition
| a noxious, unintended, or undesired effect of a drug used for prophylaxis, diagnosis, or therapy |
|
|
Term
| What are the limits of premarketing data? |
|
Definition
*Efficacy demonstrated through 2 well-controlled studies
*Safety is less clear
-benefit must outweigh risk
-rule of too's
*too small
*too brief
*too healthy
*too homogeneous |
|
|
Term
| What are the expectations of a pharmacist in medicaiton safety? |
|
Definition
* monitor for drug safety
* therapeutic intervention to resolve issue
* report ADRs
* educate other healthcare providers
* know meds before you use them
* anticipate potential, yet unreported ADRs |
|
|
Term
| Describe drug hypersensitivity reactions. |
|
Definition
* unpredictable ADRs classified by involvement of the immune system
* occur in small number of pts
* not pharmacologic effect
* 10% of ADRs associated w/ hospitalization |
|
|
Term
| overview of pathogenesis of hypersensitivity reactions. |
|
Definition
* most antimicrobials are small molecules
* cannot cause immune response alone
* undergo haptenation
* responses to these complexes are widely varied |
|
|
Term
| Describe Type I hypersensitivity reaction. |
|
Definition
*immediate
*IgE antibodies
*mast cell/basophil degranulation
-anaphylaxis: swelling of throat and mouth, hives, tingling, itching, GI effects, hypotension, altered mental status, loss of consciousness
-angioedema: edema from increased vascular permeability, painless, nonpruritic, deep dermal, subcutaneous, submucosal tissues
-urticaria: hives and pruritis |
|
|
Term
| Describe Type II hypersensitivity reaction. |
|
Definition
*cytotoxic
*IgG/IgM antibodies
*antigenic complex binds to cell surface
*toxic reaction to cell
Example: hemolytic anemia |
|
|
Term
| Describe Type III hypersensitivity reaction. |
|
Definition
*immune complex
*IgG/IgM antibodies
*complexes widely distributed
*deposit in tissues/organs
Examples: vasculitis, arthritis, glomerulo-nephritis |
|
|
Term
| Describe Type IV hypersensitivity reaction. |
|
Definition
*cell-mediated
*delayed reaction
*t cells release cytokines
*macrophage release lytic enzymes
Examples: Steven-Johnson's syndrome
-skin/mucous membranes, nonpruritic mucocutaneous lesions, ocular/GI/resp involvement, prodrome resembles viral infection |
|
|
Term
|
Definition
*anaphylactoid reactions cause DIRECT release of inflammatory mediators
*bypass immune system
Example: histamine release - vanc |
|
|
Term
| Describe Red Man's Syndrome? |
|
Definition
Vanc
*direct degranulation of mast cells and basophils
*Sx: diffuse burning, itching, and generalized discomfort, erythematous rash, hypotension, angioedema
*Severe: chest pain, dyspnea
*w/in 30 mins of initiation, or shortly after infusion
**more common in healthier patients |
|
|
Term
|
Definition
*10% pts report this allergy
*85% of the 10% do NOT have true allergy
*PRE-PEN can test allergy: tests for major determinant and then intradermal |
|
|
Term
| Describe cross reactivity between pcns and cephalosporins. |
|
Definition
*old data (10-20%)
*newer data (2%)
*reasons for discrepancy: older cephs were more PCN-like; cross contamination of earlier products
**now cephs more safe to administer during PCN allergy
*aztreonam safe for pts with PCN allergy |
|
|
Term
| Sulfonamide allergy points |
|
Definition
3% - higher in HIV due to slow metabolizers
all 4 types of hypersensitivity reactions
structurally different than non-antibiotic sulfonamides (don't cross react) |
|
|
Term
| Cross Reactivity vs General Hypersensitivity |
|
Definition
* Pts w/ sulfa allergy were 3x more likely to have an allergic reaction to PCN
* PCN allergy pts were 4x more likely to have an allergic reaction to sulfonamides |
|
|
Term
| Avoid drug it QTc >_____ ms baseline and if the patient has possible severe ____________ heart failure. |
|
Definition
|
|
Term
| What can we modify to reduce risk of QT prolongation? |
|
Definition
K > 4.0
Mg > 2.0
*correct drug dosing |
|
|
Term
| Change meds if QTc>______ ms or if it increases >____ ms from baseline |
|
Definition
|
|
Term
| List some of the agents with QT prolongation problems. |
|
Definition
| antiarrythmics, macrolides, azole meds, FQs, terfinadine, cisapride, Bactrim, Dofetilide, sotalol |
|
|
Term
|
Definition
* describes the relationship between the drug conc and the antibacterial effect, as referenced to the MIC
* relates PK to the time course of antimicrobial effects at the site of infection |
|
|
Term
| PD provide us with what benefits and limitations? |
|
Definition
Benefits
* assist in treatment selection
* dosing to improve efficacy, prevent toxicity, decrease resistance
Limitations
* data not available for all drugs/infections
* relies on in vitro and animal modeling |
|
|
Term
|
Definition
Peak/MIC
AUC/MIC
Time above MIC
PAE |
|
|
Term
| How do we characterize drugs based on PD? |
|
Definition
* in vitro or animal studies that look at extent of kill for period of time
* drug concs controlled and varying concs evaluated
* PD indices calculated for the model
* extent of kill correlated with each PD indices to see which best predicts the drugs activity |
|
|
Term
| Which PD indices reflect conc-dependent? Time-dependent? |
|
Definition
Conc-dependent
* Peak/MIC
* AUC/MIC
Time-Dependent
* % time above MIC
* AUC/MIC (for drugs with long t1/2 or PAE such as Vanc) |
|
|
Term
Which PD index is best for each of the following drugs classes?
1. BLs
2. FQs
3. Glycopeptides
4. AGs |
|
Definition
1. BLs - %time > MIC
2. FQs - AUC/MIC
3. Glycopeptides - AUC/MIC (time-dependent)
4. AGs - Peak/MIC |
|
|
Term
|
Definition
% time > MIC
* target: 40-50% time > MIC
* large doses infreq? clearance could leave you under MIC too long...
* mod more freq dose?
* constant infusion? good if >MIC whole time |
|
|
Term
|
Definition
AUC/MIC
**AUC for 24 hours
* targets: G- >125; G+ >33.7 |
|
|
Term
|
Definition
AUC/MIC
* target >400
* troughs correlated to efficacy and decreased risk of resistance development |
|
|
Term
|
Definition
Peak/MIC...more you give the more bacteria you kill
*target 8-10 x MIC of pathogen |
|
|
Term
| What is the rationale behind PK dosing for Vanc? |
|
Definition
avoid toxicity
ensure efficacy |
|
|
Term
| What are the risk factors for nephrotoxicity (5%) in Vanc? |
|
Definition
advancing age
prolonged therapy (>3wks)
sustained troughs (>20 mg/dL)
concomitant nephrotoxins |
|
|
Term
PK parameters for Vanc?
Dist, Elim, Vd, PPB, penetration |
|
Definition
Dist: 30-60 mins
Elim: t1/2 = 6-12 hrs
Vd: 0.7 +/- .3 L/kg
PPB: 50-55%
Tissue Penetration: poor in non-inflamed meninges, decreased in DM pts' skin, poor in lungs |
|
|
Term
| What is the general dosing for Vanc? |
|
Definition
15-20 mg/kg - based on ABW
Q8-12hrs based on renal function
infusion rate: 1g/hr
loading dose: 25-30 mg/kg |
|
|
Term
| What are Ke and Vdest used to calculate? |
|
Definition
| Tau and maintenance doses |
|
|
Term
| What are the current goals for Vanc therapy? |
|
Definition
troughs = efficacy
*ALWAYS at least 10mg/L
*MIC=1, >15mg/L
*MIC=2, cannot use Vanc
*life-threatening or poor penetration (pneumo, meningitis, endocarditis): 15-20 mg/L
**Monitor AUC/MIC |
|
|
Term
| How do we adjust vanc doses? |
|
Definition
If trough low, increase dosing frequency OR proportionately increase dose
If trough high, decrease dose OR dose less frequently |
|
|
Term
| What are the 2 different dosing strategies for AGs? |
|
Definition
traditional dosing via calculations
extended-interval dosing |
|
|
Term
What are the targets for the AG amikacin?
*life-threatening infection or pneumo
*serious infection
*UTI
*endocarditis
*trough |
|
Definition
*life-threatening infection or pneumo (25-35)
*serious infection (20-25)
*UTI (15-20)
*endocarditis - not used
*trough (<8) |
|
|
Term
What are the targets for the AGs Gent/Tobi?
*life-threatening infection or pneumo
*serious infection
*UTI
*endocarditis
*trough |
|
Definition
*life-threatening infection or pneumo (8-10)
*serious infection (6-8)
*UTI (4-6)
*endocarditis (3-4)
*trough (0.5-2) |
|
|
Term
| Describe AG PK Parameters. |
|
Definition
Dist: 30 min (more rapid than Vanc)
Elim: t1/2 1.5-4 hrs (shorter than Vanc)
Vd: 0.25+/-.35 L/kg
PPB: 0-30%, negligible
Penetration: limited into meninges; lung < systemic |
|
|
Term
|
Definition
2-2.5mg/kg/dose Q8-12hrs based on IBW (
>IBW by 20%)
*adjusted for renal fxn
Amikacin starts higher (5-7.5) |
|
|
Term
|
Definition
|
|
Term
| How do we dose adjust in AGs? |
|
Definition
Peak and trough both low, proportionately increase dose as long as they are both still in range
Peak and trough both high, proportionately decrease dose
Cannot proportion if peak high and trough low or vice versa. |
|
|
Term
| Describe extended interval doses and its advantages. |
|
Definition
larger doses, less frequent
advantages:
*at least as efficacious
*less nephrotoxic
*convenient, easy to calc
*reduced cost |
|
|
Term
| What are the 4 rationale behind extended interval dosing of AGs? |
|
Definition
1. Conc-dependent killing
2. PAE - seen w/ Staph and G-; typically 2-7 hours; depends on peak concs
3. Prevents adaptive resistance - prevents down-regulation of transport
4. Less tissue accumulation - allows for low concs; drug can diffuse out of deep tissue compartments; less risk of toxicity |
|
|
Term
| Which pts are not candidates for extended interval dosing of AGs? |
|
Definition
*pregnancy - clear rapid, low dist
*burns >20% - clear rapid
*cirrhosis/ascites - clear rapid
*CrCl <30 - cannot clear
*Dialysis - cannot clear
*cystic fibrosis |
|
|
Term
| For extended interval dosing of AGs we base it on CrCl...what are these levels? |
|
Definition
CrCl >60 = 24hrs
40-59 = 36 hrs
30-39 = 48 hrs |
|
|
Term
| Use ___________ nomogram to determine dosing interval. |
|
Definition
|
|
Term
| What are the SIRS criteria? |
|
Definition
HR >90 bpm
RR >20
PaCO2 <32 mmHg
Temp >38(100.4) OR <36(96.8)
WBC >12000, <4000, OR >10% |
|
|
Term
|
Definition
| 2 SIRS criteria + infection |
|
|
Term
| How do we define severe sepsis? |
|
Definition
Sepsis + organ dysfunction, hypoperfusion, OR hypotension
*Hypotension sbp <90 or >40 reduction w/o another cause |
|
|
Term
|
Definition
| severe sepsis + hypotension despite adequate fluid resuscitation |
|
|
Term
| What are the other causes of SIRS? |
|
Definition
|
|
Term
| What are the factors leading to increased numbers of pts with sepsis? |
|
Definition
*immunocompromised
*invasive devices or procedures
*resistant pathogens
*aging population |
|
|
Term
| Where are the main sites of pathogens and what are the common pathogens involved in sepsis? |
|
Definition
Resp tract 21-68%
Intraabdominal space 14-22%
Urinary tract 14-18%
G+: Saureus, Spneumo, CONS, Enterococci
not high mortality
G-: Pseudo, E.Coli, Klebsiell, Serratia, Enterobacter, Proteus
high mortality
Fungi: candida
high mortality |
|
|
Term
| What are the two classifications of pathogens associated with high mortality rates in sepsis? |
|
Definition
|
|
Term
| What is the pathophysiology of sepsis? |
|
Definition
1.Infection
2.Release of pro-inflammatory mediators to eradicate microorganisms
-TNFa, IL1,6,8; damage to host tissue
3.Release anti-inflammatory mediators
-IL1ra,4,10; leukocytes activation
4.Imbalance between pro- and anti-inflammatory response
5.Progress to sepsis, severe sepsis, septic shock |
|
|
Term
| What comes from release of pro-inflammatory mediator? |
|
Definition
*coagulation and antifibrinolytic system activation -> vasodilation
*endothelial/leukocyte activation
*compliment activation
*ACTH release -> vasodilation |
|
|
Term
| What is the presentation of sepsis with CNS? |
|
Definition
| AMS (altered mental status) |
|
|
Term
| What is the presentation of sepsis with CV? |
|
Definition
|
|
Term
| What is the presentation of sepsis with Resp tract? |
|
Definition
increased RR
ARDS (acute resp distress syndrome) |
|
|
Term
| What is the presentation of sepsis with renal system? |
|
Definition
proteinuria
oliguria
azotemia(decreased urine output) |
|
|
Term
| What is the presentation of sepsis with liver? |
|
Definition
increased bilirubin
increased LFTs
decreased clotting factors |
|
|
Term
| What is the presentation of sepsis with GIT? |
|
Definition
mucosal ischemia
stress-related mucosal damage |
|
|
Term
| What is the presentation of sepsis with heme? |
|
Definition
increased WBCs
decreased WBCs
decreased platelets |
|
|
Term
| What is the presentation of sepsis with metabolic/electrolytes? |
|
Definition
hyperglycemia
hypoglycemia
lactic acidosis
abnormal electrolytes |
|
|
Term
| What are some of the primary/early sx of sepsis? |
|
Definition
| fever, chills, tachycardia, tachypnea, hyperglycemia, leukocytosis, preoteinuria |
|
|
Term
| What are the complication/late sx of sepsis? |
|
Definition
| hypotension (shock), GI bleeding, lactic acidosis, hypoglycemia, leukopenia, thrombocytopenia, organ system failure |
|
|
Term
| What are the factors associated with increased mortality rates in sepsis? |
|
Definition
* shock
* rapid fatal underlying disease
* >70 yo
* G- or yeast infection
* inappropriate antibiotic therapy
* leukopenia, severe thrombocytopenia, bleeding
* multiple organ failure - severe mental status change |
|
|
Term
| How do we diagnose sepsis? |
|
Definition
* minimum two blood cultures
* 1 from percutaneous and 1 from vascular access device
* imaging exams to confirm and sample any source infection |
|
|
Term
| What is the early goal-directed therapy w/in first 6 hours? |
|
Definition
* infection source control
* central venous pressure (CVP) 8-12
- mechanically ventilated >12
* mean arterial pressure (MAP) >65
* urine output >0.5 ml/kg/hr
* central venous O2 sat >70% OR mixed venous >65%
Treatment:
1. fluid resuscitation
2. vasopressor therapy
3. antibiotic therapy w/in 1 hour |
|
|
Term
| Appropriate (broad/narrow) antimicrobial therapy needs to begin within __________ of sepsis diagnosis. |
|
Definition
|
|
Term
| In which pts will we consider combo therapy? |
|
Definition
psuedomonas infections
neutropenic pts (ANC <1500)
*for no longer than 3-5 days and de-escalate based on the sensitivity |
|
|
Term
| Reasses abx regimen daily after how many hours? What is duration of therapy? |
|
Definition
* 48-72 hours
* typically 7-10 days depending on the site of infection and overall response to therapy |
|
|
Term
| CA UTI (E.Coli, GNB, PSA) |
|
Definition
| ceftriaxone or ciprofloxacin or levofloxacin |
|
|
Term
|
Definition
| cipro or levo or ceftazidime +/- Gent |
|
|
Term
| CA Resp Tract (Spneumo, Hinflu, atypical, PSA, MRSA) |
|
Definition
Gen Med Floor: Resp FQ or BL+azithro
ICU:BL+ FQ or azith +/- vanc or linezolid |
|
|
Term
|
Definition
| antipseudo BL + levo or cipro or AG +/- vanc or linezolid |
|
|
Term
| CA Intraabdominal Infection (G-, Strep, anaerobes, PSA) |
|
Definition
tic/clav
cefoxitin
moxiflox
ertapenem
tigecycline
metronidazole + ceph or FQ |
|
|
Term
| HA Intraabdominal Infection (G-, Strep, anaerobes, PSA) |
|
Definition
pip/tazo
ertapenem
metronidazole + cefepime, ceftazidime, cipro, or levo |
|
|
Term
|
Definition
| vanc or linezolid or dapto |
|
|
Term
|
Definition
|
|
Term
| HA Catheter-related infection (MRSA, MRSE) |
|
Definition
|
|
Term
|
Definition
| antipseudo BL +/- levo or cipro or AG +/- vance |
|
|
Term
| What and who is the fluid resuscitation used in sepsis? |
|
Definition
Who: pts w/ hypotension or serum lactate >4
What:
-Crystalloids: NS or LR but not D5W bc it increases extravasc volume and we actually want to increase intravasc volume
-Colloids: hetastarch or albumin; these are more expensive, so the others ar emore commonly used |
|
|
Term
| Who needs CV support in sepsis and what is it? |
|
Definition
Who: Pts do not respond to fluid resuscitation
What: Vasopressors:NE or DA Alt: Epineph |
|
|
Term
| What is ionotropic therapy in sepsis? |
|
Definition
* Dobutamine in pts w/ myocardial dysfunction evidenced by elevated cardiac filling pressures OR low cardiac output
* Do NOT raise cardiac index to supranormal levles |
|
|
Term
| What do we do if venous O2 sat target is NOT achieved? |
|
Definition
* consider further fluid
* transfuse packed RBCs to a goal hct of >30% AND/OR
* start dobutamine (max rate 20 mcg/kg/min) |
|
|
Term
| When do we use steroids in sepsis? |
|
Definition
* if poor response to fluids and vasopressors
* in septic shock; BP <65
* ACTH stimulation test NOT needed
* Hydrocortisone max 300mg/day
* Add fludrocortisone 50mcg QD (req'd if using a steroid other than hydrocortisone) |
|
|
Term
| What is the anticoag that is no longer used? |
|
Definition
Recombinant human activated protein C (rhAPC, Xigris)
* associated w/ Prowess trial and prowess-shock which voluntary market withdrawal of Xigris due to failure to show a survival benefit |
|
|
Term
| What are the blood products that can be used in sepsis? |
|
Definition
1. RBCs: given when Hgb<7; target 7-9
2. Fresh Frozen Plasma: ONLY used for bleeding or planned invasive procedures
3. Platelet administration:
<5x10^9 regardless of bleeding
5-30x10^9 if significant bleeding
>50x10^9 for invasive procedures
4. EPO: NOT for sepsis-related anemia; for chemotherapy or renal insufficiency |
|
|
Term
| What are the main supportive therapies in sepsis? |
|
Definition
1. Glucose control: goal 140-180; monitor Q1-2hrs (Q4h for stable pts)
2. DVT prophylaxis: Heparin
3. Stress ulcer prophylaxis
4. Nutrition support
5. Mechanical ventilation
6. Hemodialysis |
|
|
Term
| How have systemic fungal infections increased in importance? |
|
Definition
* Immune-compromised patients: Organ and bone marrow transplant; Cytotoxic chemotherapy in cancer patients
* Immune suppression diseases such as AIDS
* Patients exposed to broad spectrum antibiotics
* Normal microorganisms are suppressed with fungal overgrowth
* Widespread use of indwelling medical devices
* Intravenous catheters, joint replacements
* Long-term maintenance of burn, trauma and diabetic patients |
|
|
Term
| What is the medical emphasis now on in fungal infections? |
|
Definition
| diagnosis, prevention, and treatment |
|
|
Term
| What are the main characteristics of fungi? |
|
Definition
* eukaryotic!
* nucleus w/ 2-layer membrane
* mito, golgi, ribosomes, ER, etc.
* Rigid cell wall composed of chitin and/or cellulose-like molecules like Glucan
* cell membrane contains ergosterol instead of cholesterol |
|
|
Term
| What are the two subtypes of fungi? Describe each. |
|
Definition
Yeasts: unicellular; invades human
Molds: multicellular with hyphae; free-living in environment
*some dimorphic |
|
|
Term
| Fungi are heterotrophic. What does this mean? |
|
Definition
* reliant on environment for nutrients
close contact w/ host and secrete
* digestive enzymes to further their own metabolism |
|
|
Term
|
Definition
Asexual - by mitosis and budding of daughter cell from a single parent cell
Sexual - through meiosis; 2 mating types exist that partner up to generate offspring cells
Spores - resistant to extreme environmental conditions |
|
|
Term
| What are the common species of systemic fungal infections? |
|
Definition
Candida
Aspergillus
Histoplasma
Blastomyces
Coccidioides
Cryptococcus
Pneumocystis |
|
|
Term
| Which protozoan associated with pools, water, etc commonly mistaked for fungi? |
|
Definition
|
|
Term
| Describe AmphoB structure |
|
Definition
* Polyene
* large open ring structure
* lipophilic and h-philic portions
* carboxylic and amino-sugar residues at one end
* poor solubility at neutral pH |
|
|
Term
| What are the different forms of AmphoB? |
|
Definition
* AmB: traditional deoxycholate
* ABCD: colloidal dispersion; discs of lipids
* L-AmB: liposomal; artificial lipid vesicles
* ABLC: lipid complex; phosphatidyl choline and phosphatidic acid in ribbon-like sheets |
|
|
Term
| What is the main advantage of lipid formulations? |
|
Definition
* decrease toxicity
* can also decrease tox by pre-administration of NS |
|
|
Term
| Why is Nystatin not used systemically? |
|
Definition
| toxic; only used topical and oral bc not absorbed from gut |
|
|
Term
|
Definition
* active against broad range
* binds ergosterol in fungal cell membranes
* forms pore in cell membrane that leaks ions to cause cell death |
|
|
Term
|
Definition
Absorption: very poor oral absorption; given as IV or intrathecal or topical
Dist: highly protein bound; free drug enters tissue (highest in liver and spleen); not cross BBB, but can reach CNS in inflammation; crosses placenta
M/E: elim 15 days so t1/2 = 3days |
|
|
Term
|
Definition
* Most common are acute: fever, chills, tachypnea, stridor, hypotension
* Serious: nephrotox
* hypokalemia and decreased Mg
* anemia |
|
|
Term
| Describe structures and MOA of 5-FC |
|
Definition
* fluorinated pyrimidine molecule
* resembles cytosine
* fungistatic
* enters fungal cells by a cytosine-specific permease which is NOT found in mammalian cells
* MOA based on disruption of nucleic acids in fungal organisms
5-FC -> 5FU + 5-fdUMP
* 5-fdUMP inhibits the enzyme thymidylate synthetase, thus depriving the organism of thymidylic acid |
|
|
Term
|
Definition
cryptococcus and candida
resistance readily arises when used as monotherapy, so normally used in combo with AmphoB |
|
|
Term
| ADME/PK of 5-FC...compared to AmphoB? |
|
Definition
* Well absorbed orally (Not AmphoB)
* Wide dist, including CNS/CSF
* t1/2=3-6 hrs (AmphoB longer)
* 80% dose unchanged into urine (Ampho less renal)
* needs dose adjustment in renal failure |
|
|
Term
|
Definition
* bone marrow suppression
* hepatic dysfunction
* other (GI, rash, etc.) |
|
|
Term
| Imidazole structrue and uses |
|
Definition
2 N in 5-member azole ring
Exs: ketoconazole, miconazole |
|
|
Term
| Triazole structure and uses |
|
Definition
3 N in 5-membered azole ring
Exs: fluconazole, itraconazole, voriconazole, posaconazole
**these preferred!! |
|
|
Term
|
Definition
* inhibits synthesis of cell membrane constituents
* ergosterol regulates fluidity and enzyme activity in the membrane
* blocks P450-dependent synthesis of ergosterol!!
-specifically demethylation of lanosterol which can also inhibit steroid synthesis |
|
|
Term
|
Definition
candida, cryptococcus, aspergillus
Ketoconazole: less used than fluconazole; less steroid synthesis effect; broader activity
Voriconazole: Aspergillus
Posaconazole: Zygomycetes |
|
|
Term
|
Definition
* moderate to excellent oral bioavailability, but food/acidity impact the absorption
* t1/2 = 6-40hrs
* voriconazole not if CrCl<50
* posaconazole: only PO; high fat meal increases absorption; avoids P450!!! |
|
|
Term
|
Definition
* CYP interactions!!
* hepatotox
* GI distress
* rash and alopecia
* CV (esp Itraconazole: inotropic effect; black box warning for pts with CHF, bc all azoles cause QT prolongation)
* visual disturbances and hallucinations
* NOT to be used in prego |
|
|
Term
|
Definition
similar to lipopeptides
caspofungin
micafungin
anidulafungin |
|
|
Term
|
Definition
inhibits the synthesis of cell wall
* specifically the B-D-glucan |
|
|
Term
|
Definition
Caspofungin/Micafungin - Aspergillus
Caspofungin/Anidulafungin - Candida
* use these only if intolerant to other therapies
* not for use against Cryptococcus bc they have modified glucan structure |
|
|
Term
| ADME and PK of echinocandins |
|
Definition
* Not absorbed from GIT, only IV route
* mostly LIVER
* highly protein bound
* do not cross BBB well
* not used for CNS/CSF infection
* t1/2 10(caspofungin) and 26(anidulafungin) |
|
|
Term
| Echinocandin ADRs and Tox |
|
Definition
* good safety profile
* phlebitis at infusion site
* rash, facial swelling w/ rapid infusion
* altered liver or renal tests
* hypersensitivity (esp Micafungin)
* hypokalemia (esp Anidulafungin) |
|
|
Term
|
Definition
Action on microtubules to disrupt mitosis
* mostly topical more than systemic |
|
|
Term
| Describe terbinafine (Lamisil) |
|
Definition
* allylamines
* used orally and topically
* inhibits conversion of squalene to lanosterol by squalene epoxidase
* hepatotox
* ADRs w/ antidepressants and cyclosporine |
|
|
Term
| What are the endemic Mycoses? |
|
Definition
Histoplasmosis
Blastomycosis
Coccidioidomycosis |
|
|
Term
| What are the opportunistic mycoses? |
|
Definition
Candidiasis
Cryptococcosis
Aspergillosis |
|
|
Term
| What are the risk factors for fungal infections? |
|
Definition
1. Organ and bone marrow transplantation
2. Cytotoxic chemotherapy
3. Indwelling intravenous catheters, burns, surgery, or trauma
4. Widespread use of potent broad-spectrum antimicrobial agents |
|
|
Term
| What are the different Candida fungi and their susceptibility to fluconazole? |
|
Definition
**Candida is 50%
o C. tropicalis, C. parapsilosis – susceptible to fluconazole
o C. glabrata – unique susceptibility
o C. krusei – resistant to fluconazole |
|
|
Term
| Describe pathophysiology of candiadiadis. |
|
Definition
• Normal flora of skin, female genital tract, and entire gastrointestinal (GI) tract
• Most infections are acquired endogenously
• Generally acquired through the GI tract or indwelling IV catheters
• Types of systemic infections include candidemia, endocarditis, peritonitis, arthritis, and CNS infection.
• Increased risk for patients who are immunosuppressed (drugs or diseases) and/or receive broad-spectrum antimicrobials |
|
|
Term
| List risk factors for invasive candidiasis. |
|
Definition
o Neutropenia
o Lymphoreticular or hematologic malignancies
o Diabetes
o Immunodeficiency diseases
o High-dose corticosteroids
o Immunosuppressants, antineoplastic agents
o Central venous catheters
o Total parenteral nutrition (TPN)
o Receipt of multiple antibiotics
o Extensive surgery (especially, surgery of GI tract)
o Burns
o Renal failure and hemodialysis
o Mechanical ventilation
o Prior fungal colonization |
|
|
Term
| List signs and symptoms of candidiasis. |
|
Definition
1. Acute onset of fever, tachycardia, tachypnea. Occassionally chills and/or hypotension.
2. Intermittent fevers and only symptomatic when febrile.
3. Progressive deterioration +/- fevers
4. Hepatosplenic: Only manifested as fever in a neutropenic patient
(< 1000 WBCs/mm3) |
|
|
Term
| Only ___________ of neutropenic patients who have candidiasis at autopsy had a positive Candida blood culture |
|
Definition
|
|
Term
| What are the clinical pearl lab tests? |
|
Definition
•Germ tube
o + identification of C. albicans within 1-2 hours
o HIV-infected individuals: C. dubliniensis
•Peptide nucleic acid (PNA) and fluorescence in situ hybridization (FISH)
o Results available within 90 minutes
o Sensitivity: 99-100%, specificity: 100% for C. albicans |
|
|
Term
| What are the main two groups of treatment? What are these based on? |
|
Definition
Recent azole exposure
OR
Severely ill (hypotension, hypoperfusion, sepsis, shock)?
YES
1. Echinocandin
2. Amphotericin B
3. Other azole (itra, vori)
NO
1. Fluconazole
2. Other azole (itra, vori)
3. Echinocandin
4. Amphotericin B |
|
|
Term
| What is the duration of therapy for candidemia? What do we need to monitor? |
|
Definition
| 2 weeks after the last positive blood culture and resolution of signs and symptoms of infection. All patients with candidemia require ophthalmologic examination to rule out candidal endophthalmitis….bc this can cause BLINDNESS!! |
|
|
Term
| Describe dose and pathogen for fluconazole? |
|
Definition
Fluconazole
• 6mg/kg/day dose for C. albicans, C. parapsilosis, C. tropicalis (S: susceptible)
• 12 mg/kg/day dose for C. glabrata (S-DD: dose-dependent susceptibility)
• Do NOT use for C. krusei (R: resistant) |
|
|
Term
| Describe Echinocandin treatment |
|
Definition
Echinocandins
• Expanded coverage against C. glabrata and C. krusei
• Less potent against C. parapsilosis
• IV formulation ONLY
• If severely ill or Recent azole tx |
|
|
Term
| Describe AmphoB treatment. |
|
Definition
Amphotericin formulations
• Active against common Candida species
• Problems with infusion-related toxicities, nephrotoxicities, etc.
• IV formulation ONLY |
|
|
Term
| Describe Aspergillus pathogens |
|
Definition
• Ubiquitous mold that grow well on soil and water
• Most commonly pathogenic species A. fumigatus, A. flavus, A. niger |
|
|
Term
| Described pathophys of Aspergillus |
|
Definition
•By inhalation of spores (airborne conidia) + impaired hose defenses
•Predisposing factors:
o prolonged neutropenia (most important)
o chronic high dose steroid therapy (30-200 mg/day of prednisone)
Corticosteroids appear to impair killing of conidia by macrophages and impair mobilization of neutrophils.
o cytotoxic agents
o recent and/or concurrent broad-spectrum antimicrobial therapy |
|
|
Term
| Describe presentation of Aspergillus infection. |
|
Definition
•Classical signs and symptoms: normally presents in lungs!
o Pleuritic chest pain
o Fever
o Hemoptysis
o friction rubs
•Organ specific symptoms of other sites of infection: CNS, liver, spleen, heart, GI tract, pericardium |
|
|
Term
| What is the treatment for Aspergillus? |
|
Definition
Empiric therapy
1st line: Voriconazole
2nd line: Amphotericin B formulation OR echinocandin (Caspofungin)
Therapy should be continued after resolution of clinical radiologic abnormalities until cultures are negative, and reversible underlying conditions have diminished.
Salvage therapy
Combination therapy with 2-3 classes of antifungals (posaconazole is another option for salvage) |
|
|
Term
| Describe epidemiology of Histoplasmosis. |
|
Definition
• Endemic in the Ohio and Mississippi River valleys (>90% may be affected in these areas)
• “Mircrofoci” include blackbird/pigeon roosts, chicken coops, bat caves, attics, old buildings |
|
|
Term
| Describe pathophys of Histoplasmosis |
|
Definition
| Spores inhaled into lung alveoli → travel to lymph nodes → spread to liver, spleen, marrow |
|
|
Term
| Describe presentation symptoms of Histoplasmosis. |
|
Definition
* Acute pulmonary: Mostly mild or asymptomatic; Higher inoculums can produce flulike pulmonary symptom
* Chronic pulmonary: Lung lesions with calcified ganulomas, fibrosis, and inflammation; Cavitation, bronchopleural fistulas, pulmonary insufficiency, and death can occur over a period of years
* Disseminated: Weight loss, weakness, fatigue, fever, hepatosplenomegaly, GI ulceration; Thrombocytopenia, anemia, leukopenia |
|
|
Term
| What is the Histoplasmosis treatment for mild to mod disease? |
|
Definition
* Treatment is usually not needed
* Symptoms > 1 month: itraconazole 200 mg tid x 3 days, then 200 mg bid
Acute pulmonary histoplasmosis: 12 weeks
Chronic cavitary pulmonary histoplasmosis: at least I year
* Newer azoles (vori, posa) have only limited data (voriconazole may be more prone to relapse according to in-vitro data) |
|
|
Term
| What is the Histoplasmosis treatment for mild to mod disease? |
|
Definition
* Lipid formulation of amphotericin B x1-2 weeks, then itraconazole 200mg tid x 3 days, then 200mg bid
* Acute pulmonary histoplasmosis: 12 wks
* Chronic cavitary pulmonary histoplasmosis: at least 1 year
* Methylprednisolone x 1-2 wks for pts w/ acute resp complications (hypoxemia, significant resp distress) |
|
|
Term
| Describe epidemiology of Blastomycosis. |
|
Definition
•Endemic to:
o Southeastern and south central states (Ohio and Mississippi river valleys)
o Midwestern states and Canadian provinces bordering the Great Lakes
•Frequently isolated from soil containing decayed vegetation, decomposed wood, or pigeon manure |
|
|
Term
| Describe clinical presentation of chronic pulmonary blastomycosis. |
|
Definition
•Chronic pulmonary blastomycosis (reactivation)
o Fever, malaise, weight loss, night sweats, chest pain, productive cough
o Often thought to have tuberculosis
o Can have symptoms of disseminated disease 1-3 years after primary pneumonia has resolved.
o Skin, bone, joint, genitourinary tract, CNS involvement occurs without pulmonary involvement in 40% of patients |
|
|
Term
| Describe acute pulmonary blastomycosis. |
|
Definition
•Acute pulmonary blastomycosis is either:
o Asymptomatic
o Self-limited disease (fever, shaking, chills with a productive, purulent cough +/- hemoptysis) |
|
|
Term
| Treatment of mild to moderate blastomycosis. |
|
Definition
| Itraconazole 200mg tid x 3days, then 200mg qdaily or bid x 6-12 months |
|
|
Term
| Treatment of life threatening blastomycosis. |
|
Definition
| AmphoB for 1-2 wks, then itraconazole 200mg tid x 3days, then 200mg QD or bid x 6-12 months |
|
|
Term
| Describe treatment for CNS disease - blastomycosis. |
|
Definition
| Lipid formulation of amphotericin B x 4-6 weeks, then Azole (fluconazole, itraconazole, or voriconazole) x 12 months OR resolution of CSF abnormalities |
|
|
Term
| Describe epidemiology of coccidiodomycosis. |
|
Definition
•Endemic areas in the US stretch from California to Texas
oAlso found in parts of Mexico and South America
• Areas with scant annual rainfall, hot summers, and sandy, alkaline soil
• No risk factors have been identified for acquiring primary disease. |
|
|
Term
| What are the risk factors for coccidiodomycosis? |
|
Definition
•Risk factors for severe, disseminated infection
o Race (Filipinos > African-American > Native American > Hispanics > Asians)
o Pregnancy (especially 2nd or 3rd trimester)
o Compromised immune system (AIDS pts, on steroids, immunosuppressive agents, chemotherapy)
o Male gender
o Neonates
o Patients with B or AB blood types |
|
|
Term
| Describe presentation for coccidiodomycosis asymptomatic pts. |
|
Definition
•Asymptomatic patients (60%)
oNon-specific symptoms (fever, cough, headache, sore throat, myalgias, fatigue)
oFine diffuse rash during the first few days of illness |
|
|
Term
| Describe presentation for coccidiodomycosis for primary pneumonia. |
|
Definition
•Primary pneumonia
oProductive cough (+/- blood streaked)
oDense homogenous hilar or basal infiltrate(s) |
|
|
Term
| Describe presentation for coccidiodomycosis for chronic, persistent pneumonia. |
|
Definition
•Chronic, persistent pneumonia(>6 wks of primary disease)
o Hemoptysis
o Pulmonary scarring
o Necrosis of pulmonary tissue with drainage of cavities or bronchopleural fistulas
o Persistent cough, fevers, and weight loss |
|
|
Term
| Describe presentation for coccidiodomycosis for valley fever. |
|
Definition
•Valley fever (25% of patients)
o Erythema nodosum and erythema multiforme
o Diffuse joint aches
o Fever
o Diffuse, mild erythroderma or macropapular rash
o Pleuritic chest pain
o Peripheral eosinophilia |
|
|
Term
| Describe presentation for coccidiodomycosis disseminated disease. |
|
Definition
•Disseminated disease (<1% of patients)
o Common sites include skin, lymph nodes, bone, meninges
o Other sites: spleen, liver, kidney, adrenal gland |
|
|
Term
| Treatment for asymptomatic coccidiodomycosis, primary resp coccidiodomycosis, disseminated CNS coccidiodomycosis . |
|
Definition
•Asymptomatic = NO treatment
•Primary respiratory or disseminated (NON-CNS) infection
o Azole antifungal (usually fluconazole)
o Amphotericin B formulation prego
Duration: month-to-years until clinical improvement and stabilization, some cases require lifelong suppressive therapy
•Disseminated CNS disease
o Fluconazole (for life)
o Itraconazole (for life)
o Amphotericin B intrathecal therapy ± fluconazole or itraconazole |
|
|
Term
| What are the predisposing factors to Cryptococcus? |
|
Definition
HIV infection
Lymphproliferative disorders (Hodgkin's lymphoma)
Sarcoidosis
Long-term steroids |
|
|
Term
| What is the presentation of primary cryptococcosis |
|
Definition
* always in lungs, usually subclinical infection
* cough, rales, SOB |
|
|
Term
| What is the presentation of cryptococcal meningitis? |
|
Definition
*Non-AIDS pts
-headache, fever, vomiting, mental status change, neck stiffness
-less common: visual disturbances, papilledema, seizures, aphasia
*AIDS pts
-fever, headache
-meningismus and photophobia less common |
|
|
Term
| What is the treatment for pulmonary mild to mod Cryptococcus? |
|
Definition
Fluconazole for 6 mos
Alt: Itraconazole, amphoB |
|
|
Term
| What is the treatment for pulmonary severe Cryptococcus? |
|
Definition
treat like CNS disease
AmphoB + flucytosine x 2wks then fluconazole 400mg x 8wks |
|
|
Term
| What is the treatment for CNS cryptococcus infection? |
|
Definition
Induction: amphoB + flucytosine x 2wks, then fluconazole 400mg x 8wks
Alt: monotherapy: itraconazole, fluconazole, amphoB
Maintenance therapy (AIDS pts)
*Fluconazole until CD4 >200
*Alt: itraconazole, amphoB |
|
|
Term
| Which of the azoles do NOT need dose adjustment for hepatic failure? |
|
Definition
fluconazole, posaconazole
vori, itra DO need hepatic dose adjustment |
|
|
Term
| Which azole is not recommended for IV due to CrCl? What is the level? |
|
Definition
Voriconazole
CrCl<50ml/min |
|
|
Term
| Which azole is not recommended to be taken with antacids due to poor bioavailability? |
|
Definition
|
|
Term
| What needs to be monitored w/ azoles? |
|
Definition
* Concomitant medications (safety as well as efficacy)
* Hepatic/renal function (ex: voriconazole- LFT, Scr)
* Unique adverse reaction (ex: voriconazole- visual disturbances, hallucination, QT prolongation) |
|
|
Term
| What needs to be monitored for echinocandins? |
|
Definition
* Hepatic function (only caspofungin)
* Unique adverse reaction: Rash, facial swelling with rapid infusion
* Phlebitis at infusion site |
|
|
Term
| Which echinocandin do we need to dose adjust for hepatic dysfunction? |
|
Definition
|
|
Term
Match the following:
Group 1
AmB Deoxycholate(AmB)
AmB Colloidal Dispersion (ABCD)
AmB Lipid Complex (ABLC)
Liposomal AmB (L-AmB)
Group 2
Fungizone
Abelcet
Ambisome
Amphotec |
|
Definition
AmB -> Fungizone 0.4-1mg/kg/d
ABCD -> Amphotec 5mg/kg/d
ABLC -> Abelcet 5mg/kg/d
LAmB -> Ambisome 3-6mg/kg/d |
|
|
Term
| What are the 2 mechanisms of nephrotox of AmphoB? |
|
Definition
Mechanism of nephrotoxicity:
1. direct damage of distal tubular membranes leading to wasting of electrolytes
2. constriction of the afferent arterioles leading to decreased glomerular filtration |
|
|
Term
| What should we monitor for AmphoB? |
|
Definition
1. infusion related reaction: fever , chills, tachypnea
Premedication
•fever/chills: NSAID ± diphenhydramine or AAP + diphenhydramine or hydrocortisone
•rigors: meperidine
2. renal function, other nephrotoxic drugs
•Hydration + Sodium repletion: infuse NS 0.5 L before and after Amphotericin B dose
•Nephrotoxicity due to Amphotercin B: decrease dose 50% or give every other day
3. electrolytes: K, Mg
4. anemia
5. Headache, nausea, vomiting, malaise, weight loss, thrombophlebitis |
|
|
