Exam 3 lecture 5 Flashcards
What type of disease is cystic fibrosis
Autosomal recessive genetic disease (mother and father need to have mutation)
They have a 25% chance of having a kid with CF, 50% of being a carruier, 25% chance of neither
Average life expectancy of cyctic fibrosis
61 years (not just a pediatric disease)
What is CF caused by? Most common mutation?
Mutation in gene that encodes for CFTR protein
Most common is F508del
Compare normal cell in lung and CF lung
Normal- There is a nice equilibrium of chloride and sodium (water). Airway is think and cillia beat it easily
In CF mutation, CFTR channel is absent so chloride can not get into mucus so water can not get into it. Creates thick viscous liquid in lung, nice environment for bacteria to grow. Makes it difficult for cillia to beat out the mucus.
How is CF diagnosed
Blood spot obtained from infant called IRT (Immunoreactive trypsinogen)
Is positive IRT diagnostic for CF?
no, furtehr testing required for diagnosing
confirmative test for CF
Sweat chloride test
What value from sweat chloride test is diagnostic
> 60mEq/L is diagnostic
<30 is normal
31-59= intermediate
Describe different CFTR mutations
- normal
- Class I mutations- stop codon mutation, No CFTR modulators for this class. More severe symptoms
- Class 2- Most common mutation (del508). Protein gets made but is not made correctly. A few CFTR proteins get there but not a lot.
- Class 3- G551D is most common mutation. Protein gets made but gate is stuck shut. (gating mutation)
Class 4- R117H is most common. normal number of CFTR
Class V-reduced number of CFTR proteins reaches membrane
Name CFTR modulators
Kalydeco
orkambi
symdeko
Trikafta
Alyftrek
How does Kalydeco work? Age of patients?
CFTR potentiator
> 1 month of age
Counseling points of kalydeco
Take with fatty foods
Monitor LFT q3 months for 1 year then yearly.
Eye exam- baseline and yearly
Dose adjustment for hepatic impairement
CYP3A substrate (think about drug and food Grapefriit etc)
Approved for responsive mutations
Who is orkambi approved in?
Two copies of F508del (homozygous)
couseling for orkambi
Take with fatty food
AST/ALT/Bil q3 mo for 1 year and then years
Eye exam at baseline and then yearly
Dose adjusts in hepatic impairement
Side effects of chest tightness and SOB with initiation
Big difference between orkambi and kalydeco
Orkambi is a strong CYP3A4 inducer
Also interaction of hormonal forms of birthcontrol (drug interaction of orkambi)
1 year of age started with orkambi
What is symdeko approved in? Age
Approved for two del508 or reposnsive mutation
age>6 years
Monitoring with symdeko
Take with fatty foods
AST/ALT/Bil Q3 months for 1 year then yearly
Eye exam baseline and yearly
Dose adjustment for liver disease
No birthcontrol side effect or chest tightness
CYP3A4 substrate
Trikafta approved for? Age?
Anyone with atleast 1 d508
Age> or =2
Counseling with Trikafta
Take with fatty food
AST/ALT/Bil/Alk phose q month for 6 months and then q3 months for 12 additional months and yearly
eye exam baseline and yearly
Dose adjust for liver disease
Ivacaftor 3A4 substrate
Dosing pearl of trikafta
If miss orange tablet dose by more than 6 hrs tae orange tabs and skip evening blue tab
Alyftrek approved for?
F508del or another reposnive mutation (taken once a day)
Counseling with alyftrek
Take with fatty foods
AST/ALT/Bil/Alk Phos q month for 6 months and then q3 months for 12 additional months and then yearly
Eye exam baseline and yearly
Mortality of CF lung disease? What is it caused by?
Cause of 85% of CF deaths
Due to CFTR dysfunction CF patients have thickened mucus, hard to clear, good envt for bacteria
What is recommended for pts with CF
Airway clearence
Drugs that help us clear mucus (maintenance lung tx)
Dornase alfa
Hypertonic saline
Inhaled mannitol
Dornase alfa MOA? Age group?
Cleaves extracellular DNA from expended neutrophils in CF mucus. Reducing viscosity and promoting clearence.
Recommended for CF pts>or=6 yrs
hypertonic saline MOA
NacL clears airway by creating an osmotic gradient (draws water into airway)
Hypertonic saline recommended strength? Age group it is used in?
7% 4 ml nebulized BID (reduce percent if intoleranc eoccurs)
Recommended in all CF pts > or = 6 years
Inhaled mannitol MOA? Age approved in?
DRaws water into airway to hydrate mucus
Approved 18 yrs an dolder
Dose of mannitol? What is required before use? Side effects? What is it used for>
Dry powder 400 mg (10 capsules inhaled twice a day)
Requires tolerance test before use
Main side effects is bronchospasm, hemoptysis
Alternative to hypertonic saline
(Admonister albuertol 5-15 mins before use)
What are ANti inflammatory drugs used in CF
Azithro
Ibuprofen
MOA of azithromycin in CF? Dose? Side effects? Who is it recommended in?
MOA- immunomodulating effects
Dose- <40kg- 250 mg MWF
>40kg- 500 mg MWF
May not be tolerated due to GI side effects- dose can be reduced
Recommended in pts with chronic pseudomonas
Ibuprofen MOA? Dose? Side effects and what to montitor?
Moa- Anti inflammatory NSAID
Dose- 20-30 mg/kg (max 1600 mg/dose) BID
Check levels: Goal peak>50 mcg/ml and <100 Mcg/ml
Not well tolerated due to GI and kidney side effects
Not recommended therapies
Inhaled corticosteroids
Leukotriene modifiers (montelukast)
Oral corticosteroids
Albuterol
Ipratropium
What are pulmonary function tests
FEV1
FVC
FEF25-75
What are clinical features of CF exacerbation?
Increased cough
increased sputum production
SOB
Chest pain
Loss of appetite
weight los
decreased lung function
What are the big player pathogens seen in CF exacerbation
S. aureus
Pseudomonas
Burkholderia
stenotrophomons
E coli
What are antibiotics used for empiric IV therapy for CF in MRSA and MSSA
MRSA- only single coverage needed (Bactrim, clindamycin, vancomycin, tetracycline, linezolid)
MSSA- Only sinfgle coverage needed, cefazolin, unasyn, coverage by anti pseudomonal beta lactam
For pseudomonas in CF, What are the treatments
Double coverage needed (different MOA)
Piperacillin-tazo, imipenem-cilast, ceftazidime, meropenem, cefepime WITH Aminoglycoside (tobra or amikacin) (NOT GENTAMYCIN)
Resistance to what drug shows resistance or susceptibility to staph aureus (MSSA, MRSA)
oxicillin
oral outpatient drug for pseudomonas
ciprofloxacin/ levofloxacin (do not double cover for psudomonas in outpatient setting only in IV inpatient)
What are altered PK seen in CF pts for Beta lactams
b lactams have increased renal and non renal clearences (use max dose and prolonged infusion)
altered PK seen with CF with aminoglycosides
Increased clearence and Vd. So increase the dose and once daily dose
Changes in PK seen with CF in quinolones
No change
What to use for a patient with pseudomonas culture CF with no symptoms
Inhaled tobramycin
If patient does not tolerate tobramycin, what can we do?
Use aztreonam
What organ does the mucus from CF affect? How?
Pancreas.
Mucus obstructs exocrine ducts.
Leads to decreased amylase, lipase, protease and HCO3 output
What do we do when pancreas is injured in CF
Pancreatic enzyme (500-2500 units of lipase/kg per meal)
What dose do we strat with for pancreatic enzymes? Max dose? How/when are they adjusted?
Typically start at 1,000 units of lipase/kg/meal
Do not exceed 10,000 units of lipase/kg/day
Adjsuted based on number od stools per day, fat content of stools and growth/weight
What are the different pancreatic enzymes
Creon
Oancreaze
Zenpep
Pertzye
Viokace
What to monitor for pancreatic treatment in CF pts
Vit A,D,E,K
We want D above 30
K- monitor PT/INR
combination CF vitamins for supplementation
Aquadeks
MVW complete
DEKA essential
CF related diabetes diagnosis? Screening?
Fasting plasma- >126
2 hr plasma glucose > 2 hrs
A1c not reliable
OGTT annually.
What are the different bone and joint infections?
Osteomyelitis- Infection of the bone causing inflammation of the bone marrow and surrounding bone
Septic arthiritis-Inflammatory reaction within the joint tissue and fluid due to a microorganism
Prosthetic joint infection- Infection of a prosthetic joint and joint fluid
How important are tissue/fluid samples in bone infection? What are the commonly acquired biopsies for the different joint infections
Culture and susceptibility information is critical to guide antimicrobial tx
Osteomyelitis- bone sample/biopsy via surgery
Septic arthiritis and prosthetic joint infection- Joint aspiration with examination of synovial fluid to establish diagnosis and/or surgical intervention
Blood cultures important to help further increase likelihood of isolating pathogen
Most common organism associated with bone infections (EXAM)
Staph aureus
COmpare duration and doses of joint/bone infections to other infections? What ROA mostly?
Antibiotic therapy for bone/joint infections longer durations and higher doses because antibiotic penetration into joint is low. Commonly IV.
What are the durations of each infection?
Osteomyeltits- 4-8 wks
Septic arthiritis- 2-4 wks
Prosthetic joint infection- 6-12 wks
What are questions that we need to ask in patients with antibiotic receiving bone/joint infections
Will patient need long terms IV access for antibiotic therapy
If IV antibiotic therapy is selected, where will patient receive it (home, faccility, outpatient infusion)
If oral antibiotic is selected, will the patient adhere to the regimen if it requires multiple antibiotics and doses per day
Does patient have insurance/ability to pay for tx
What drugs can be used once a week for Bone/joint infections?
Lipoglycopeptides (dalbavancin and oritavancin)
Helpful if they can only come in once a week
What are the 3 main sections of bone
Epiphysis
Metaphysis
Diaphysis
Describe the anatomy of blood supply to bone infecttion
Nutrient arteries enter on metaphyseal side of epiphyseal growth plate
Lead to capillaries forming sharp loops in the epiphyseal grpwth plate
Capillaries lead to large sinusoidal veins that exit metaphysis
Bottom line- Blood flow slowed significantly
3 main pathways osteomyelitis develops? Describe them? (are they mono or poly microbial)
- Hematogenous spread- Microbe reaches bone via bloodstream (typically monomicrobial)
- contigous spread- Microbe reaches bone from soft tissue infection or direct inoculation (puncture wound, trauma, surgery) (commonly polymicrobial)
- Vascular insufficiency
- microbe reaches bone from soft tissue infection (most commonly associated with diabetes and vascular disease) (polymicrobial)
When is S. aureus not the most common bacteria in bone and joint infection?
Penetrating trauma. P.aeruginosa is most common in this case
signs and symptoms of osteomyelitis (acute/chronic)?
acute sx- fever, localized pain/ tenderness/ swelling decreased rang of motion
Chronic- pain, drainage, sinus tract, decreased ROM
Diagnostic consideration of osteomyelitis (lab, radiology)
Lab- elevated WBC
Radiologic- CT or MRI (MRI is standard of care)
What are the two pillars of osteomyelitis tx
Surgical intervention
Antibiotic tx
What is different about antibiotic selection in osteomyeltits
May hold antibiotic therapy initially while waiting for biopsy/surgical intervention if patient is clinically stable
What does clinically stable mean
Hemodynamically stable, no neurologic effects, no concern for additional site of severe infection
OSTEOMYELITIS EMPIRIC ANTIBIOTIC SELECTION (EXAM)
B lactam + MRSA coverage (Vanc, dapto, linezolid)
What are B lactams used for osteomyelitis (EXAM)
Cefazolin
Ceftriaxone
\Cefepime
Piperacillin/tazobactam
Ampicillin/sulbactam
Meropenem
Cipro/Levo
What are drugs that can be combined with B lactams for osteomyelitis (exam)
Vancomycin
Daptomycin
Linezolid
What do we use for anaerobic coverage for osteomyelitis
Metronidazole should be added to normal regimen
Duration of tx for osteomyelitis (vertebral osteomyelitis due to MRSA, diabetic foot infection related to osteomyelitis)
4-8 wks
Vertebral osteomyelitis due to MRSA = 8 wks
Doabetic foor infection related to osteomyeolitis
- complete resection of all infected bone/tissue= 2-5 days
- Resection of all psteomyelitis, soft tissue infection remains= 1-2 wks
- Resection performed, osteomyelitis remains= 3 wks
-No resection = 6 wks
What are some highly bioavalable oral antibiotic options for osteomyelitis for different pathogens (streptococci, MSSA, MRSA, GNRs)
Streptococci- amoxicillin, cephalexin, clindamycin (if susceptoble)
MSSA- Dicloxacin, cephalexin, cefadroxil, TMP/SMX, linezolid
MRSA- Linezolid, TMP/SMX, clindamycin
GNRs- TMP/SMX fluoroquinolones
When can we consider rifampin addition as an oral agent
MSSA, MRSA
3 main pathways for septic arthiritis
Hematogenous
Direct inoculation
Contiguous
Most common pathogen for septic arthiritis
S. aureus (Gonorrhea is also a potential Cause) Exam
Presentation and diagnosis What to note?
Painful, swollen, red, fever, chills
Monoarticular (ONLY infects 1joint)
Diagnostic consideration of septic arthiritis
Arthrocentisis
Gram stain and culture
approach to tx of septic arthritis (empiric)
Antibiotics started ASAP
Empiric antibiotic selection comparable to osteomyelitis
Proceed with pathogen direted tx once culture and susceptibility are known
tx duration for septic arthiritis in S aureus, Streptococci, N gonorrhoaea
S aureus- 4 wks
Streptococci- 2 wks
N gonorrhoea- 7-10 days
MOA of prosthetic joint
Same as the other 2
Involves development of biofilm on prosthetic. Impedes antibiotic penetration
Most common pathogen in prosthetic joint infetion
S aureus
S/s of prosthetic joint infection
Joint pain, chills, loosening of prosthesis, important to review history of prosthesis
Diagnostic consideration of prosthetic joint infection
Lab findings (WBC, ESR)
Arthrocentisis commonly done
Approach to tx of prosthetic infection
Surgical intervention
Antibiotic tx
3 general interventions surgically for prosthetic joint inefection
- debridement and retention of prosthesis
- 1 stage exchange
3.. 2 stage exchange
Approach to tx of prosthetic joint infection
Just like osteomyelitis we withold antimicrobial therapy in stable patients
Empiric selection of antibiotics similar to osteomyelitis
If gram stain avilable prior to antibiotic initiation, acceptable to sue narrowest possible agent
IV or hughly bioavailable oral is acceptable
What is added to prosthesis for retention of prosthesis in prosthetic joint infection
Rifampin
How to approach treatment of prosthetic joint infection for debridement and retention of prosthesis with duration
Pathogen directed treatment + Rifampin x 2-6 wks
Oral antibiotic treatment + Rifampib x 3 months (Hip)- 6 months (knee, other joint)
May consider long term antibiotic suppression after completion of tx
How to approach treatment of prosthetic joint infection for 1 stage exchange with duration
Pathogen directed tx + rifampin x 2-6 wks
Oral antibiotic tx + Rifampin x 3 mo
How to approach tx for 2 stage exchange of prosthetic joint infection with duration
Pathogen directed tx x 4-6 wks
How to approach treatment of prosthetic joint infection for amputation with complete removal of infected bone/hardware
Pathogen directed treatment x 24-48 hrs
What are the preferred oral agents for Prosthetic joint infections
Preferred oral agents are osteomyelitis
When do we add rifampin
Only with S aureus, never with gram negative
Compare vancomycin and daptomycin in terms of ROA,
Dapto is every 24 hrs for 6 wks at infusion clinic
Vanc is every 12 hrs for 6 wks at home
What PMN count would suggest septic arthiritis?
PMN count > 50,000
Out of daptomycin, vancomycin and dalbavancin, which of the folliwng requires central line
Daptomycin
What drugs cover MSSA for osteomyelitis? MRSA?
MSSA- Nafcillin 2 g IV Q4-6H* Cefazolin 2 g IV Q8H*
(MRSA) -Vancomycin (dose based on PK eval) Daptomycin 6-12 mg/kg IV Q24H
Linezolid 600 mg IV/PO Q12H TMP/SMX 8-12 mg/kg TMP PO daily
Dalbavancin 1500 mg IV Day 1,8
