Antimicrobial Stewardship Flashcards
define mechanism of action
how a drug inhibits or kills bacteria
define spectrum of activity
which bacteria the drug is able to cover
does cidal or static require more drug?
static
define cidal
kills bacteria on its own and requires less drug to do so
define static
inhibits future growth of bacteria and require more drug and immune system assistance
what are 3 parameters we can use to optimize the way antibiotics kill bacteria?
- Time > MIC
- Cmax > MIC (max concentration above the MIC)
- AUC/MIC
drug concentration needs to be above the ___ for as long as possible
MIC
which drugs need to be above the MIC?
time-dependent killers
are beta lactams cidal or static?
cidal
true or false. You want to optimize time above the MIC with beta-lactams
True
list some beta-lactam drugs
penicillins, cephlasporins, carbapenemes, aztreonam (monobactam)
what routes can penicillin be given?
IV, IM, or oral
what is the drug of choice for susceptible enterococcus and listeria?
aminopenicillin
what are some examples of antistaphylcoccal penicillins?
-Nafcillin
-oxacillin
-dicloxacillin
which drug has no activity against enterococcus?
cephlasporins
Augmentin is a combination of what drugs? (PO)
amoxycillin and clavulate
Unasyn is a combination of which drugs? (IV)
ampicillin and sulbactam
what is unasyn used for?
bite wounds
Zosyn is a combination of which drugs?
piperacillin and tazobactam
which drug is known as vitamin z?
zosyn
what broad spectrum treatment is given if infection is suspected in the ER (hint: it covers MRSA and pseudomonas. You must monitor kidney function)
vancomycin and zosyn
Which drug class has no activity against enterococcus?
cephlasporins
Which cephlasporin is primarily used against gram negative bacteria but can treat some gram positive infections like strep?
Cefepime
as you move from 1st generation cephlasporins down, you lose gram ___ and gain gram ____ activity. The exception is the ___ generation
positive; negative; 5th (covers MRSA but not pseudomonas)
which drug combination is used for the most drug-resistant bacteria?
cephlasporins and beta-lactamase inhibitors
do cephlasporins + beta-lactamase inhibitors have acctivity against enterococcus?
No
List 2 cephlsporin + beta lactamase inhibitor drug combos
-ceftolozane/tazobactam (zerbaxa)
-ceftazidime/avibactam (Avycaz)
which carbapenems are seen most often?
entrapenem and meropenem
is entrapenem broad or narrow?
narrow
which carbapenem has a high rate of causing seizures?
Imipenem. It is reserved for infections with unique activity/nocardia
all carbapenems have the possibility to cause seizures by
lowering the threshold to have a seizure
Which carbapenem can treat APE (acinetobacter, pseudomonas, and enterococcus) and which carbapenem can’t?
Mertapenem can; ertapenem can’t
Which drugs are carbapenems?
-ertapenem (Invanz)
-Doripenem (doribax)
-Meroapenem (Merrem)
-Imipenem/Cilastatin (primaxin)
Do not use ___ ___ with carbapenems
valproic acid
aztreonam has gram ___ activity only
negative
Which drug has an inhaled form which is typically used for the cystic fibrosis population which are normally colonized with pseudomonas?
Aztreonam
Aztreonam combined with ____ could treat carbapenemase resistant infections
Avibactam
True or false. Aztreonam is used a lot.
False. It is not used a lot because of resistance.
Are fluroquinolones time or concentration dependent?
concentration
what is the mechanism of action for fluroquinolones?
inhibit DNA gyrase, resulting in DNA breakage
What year was the first fluroquinolone introduced?
1964
what are some potential side effects of fluoroquinolines?
-ruptures or tears of the aortta
-hypoglycemic risks
-psyhciatric risks
-joint pain, tendon rupture, anxiety, depression, altered mental status, peripheral neuropathy
What is the PK/PD of beta lactams?
T>MIC (optimize time above the MIC)
what is the PK/PD of fluroquinolones?
AUC: MIC
What is the PK/PD of aminoglycosides?
Cmax/MIC
What is the mechanism of action of aminoglycosides?
inhibits protein synthesis at the level of the ribosome
what are some ADEs of aminoglycosides?
nephrotoxicity, ototoxicity (kidneys and hearing affected… think of the meme)
True or false. Pharmacy doses aminoglycosides in a patient specific manner and they are almost always used in combination with something else
True
Aminoglycosides are almost always used for gram ____ infections
negative
what are aminoglycosides usually used to treat?
resistance or infection of the heart
what is the mechanism of action for macrolides?
they are static and inhibit protein synthesis at the ribosome
What are some ADEs of macrolides?
QTc prolongation, GI upset
with which drug do we see resistance because it is used to treat viral infections like colds?
azithromycin
what is the mechanism of action for sulfonamides?
interferes with bacterial folic acid synthesis (static)
Bactrim (the oral option for MRSA) is a combination of which drugs?
sulfamethoxozole and trimethoprim
what are some ADEs of sulfonamides?
rashes, dermatolic reactions
-monitor potassium, serum creatinine, and CBC
what is the mechanism of action of tetracyclines?
inhibit protein synthesis at the ribosome (statcic)
what is the most commonly prescribed tetracycline?
doxycycline
what are some ADEs of tetracyclines?
tooth discoloration (in children under 8), esophagitis (take with a full glass of water and sit up for at least half hour otherwise it can errode your esophagus, nausea, and photosensitivity
which drugs are not used for tick borne illness?
tetracyclines
Which drugs are not given to pregnant women to not disrupt dentition of children in utero?
tetracyclines
when in doubt
doxy it out (given to treat odd infection if they can’t figure out the infection)
glycopeptides and lipoglycopeptides are used for gram ___ infections
positive
vancomycin is used to treat which MDRO?
MRSA
what drug class does vancomycin fall under?
glycopeptides
describe some characteristics of vancomycin
-vitamin v
-mostly concentration dependent
-dosed in a patient specific manner
-Red man syndrome (not an allergy; infuse the drug slowly to prevent)
-harsh on kidneys
Which drugs are lipoglycopeptides?
dalbavancin and oritavancin
what are some characteristics of dalbavancin and oritavancin?
-longer half life
-1-2 dose treatment for skin infections
-can avoid hospital admission for IV treatment
-not always sure how to use them because they are newer
what does Linezolid treat and what must be monitored?
-gram positive and VRE
-Monitor platelets (patients are at risk of bleeding) and serotoninergic interactions
what does Daptomycin treat and what must be monitored?
-gram positive and VRE
-monitor CPK and statin use
-CPK can cause muscle pain and urine discoloration if it builds up in blood too much
What does Clindamycin treat?
-gram positive mostly
-some gram negative anaerobes
-causes antibiotic associated diarrhea and c. diff
Are IV drugs normally cidal or static?
cidal
true or false. Linezolid is an oral option for MRSA?
True
The use of what other drug may be discontinued when a patient takes daptomycin?
statin use
which drug is the second line agent after vancomycin?
daptomycin
what are 4 oral MRSA options?
-bactrum (sulfamethoxozole/trimethoprim)
-doxy
-clinda
-linezolid
what is Metronidazole used to treat?
-anaerobes (mostly gram negative)
what are some characteristics of Metronidazole?
-metallic taste
-cause nausea and vomiting
-used to be for c. diff, now only in combo if fulminant
What is nitrofuratoin used to treat?
UTIs
what are some side effects of nitrofurantoin?
-pulmonary toxicity
-not for use in elderly
Synercid is a combination of which drugs? how is it adminstered?
-clinda and delphaprstin
-horrible and causes flu like symptoms. obselete.
-can only be administered via central line and is very harsh on veins
What is an example of a glycyclcines
tigercycline (tygacil)
what is a side effect of glycyclines?
-increased mortality in pneumonia and bloodstream infections
-last line option
what are examples of polymixins?
polymistin B and colistin
what are polymixins used to treat?
only MDROs if they are used at all
what are adverse events associated with polymixins?
neurotoxicity and nephrotixicty
What information does an antibiogram provide?
-compile all isolates within the last year and describe susceptibility patterns
-provide a description of antimicrobial susceptibility for the community
-bacteria must be represented by a certain number of isolated to be reported
antibiograms are useful only for _____ selection
empiric
how much does antimicrobial resistance cost in expenditures yearly?
20 billion
how many unnecessary prescriptions are filed each year?
47 million
how many premature deaths are expected by 2050?
300 million
What are 4 mechanisms of antibiotic resistance?
- enzymes
- efflux pumps: bacteria vomits the antibiotic back out
- target site alteration: fool the antibiotic, change so it can’t bind and kill
- decreased uptake: reverse channels; don’t take up the antibiotic
which professionals are the core of antimicrobial stewardship?
ID trained MDs and PharmDs
define antimicrobial stewardship
the coordinated interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose, duration of therapy, and route of adminstration
true or false. It is now legislated that all facilities have a formal stewardship program
True
what are the basic principles of antimicrobial stewardship?
right drug, dose, route, duration
when was MRSA first detected?
1960s
when was VRE first detected?
the 1980s in Europe and 90s in USA
when were ESBLs detected?
1990s
Define antimicrobial
a substance that inhibits or kills microbes
define antibiotic
a type of antimicrobial that is synthesized by a living microorganism, usually a fungus
how are most antimicrobials administered?
IV or oral
what is the MIC?
the lowest concentration of drug that can still inhibit microbial growth
what is half-life
how long the body takes to metabolize half of a drug
what is concentration dependent activity?
achieving a higher concentration in the blood over a short time is more effective at eliminating infection than maintaining a lower concentration over a longer period.
what is the goal of concentration dependent drugs?
maximize serum or tissue drug concentrations (often allows for once daily dosing)
what are examples of concentration dependent drugs?
-aminoglycosides
-fluoroquinolones
what is time-dependent activity?
maintain drug concentrations above the MIC. Lower doses at an increased frequency over time.
what are examples of time-dependent drugs?
-natural penicillins
-vancomycin
-beta lactams
define in vitro
lab susceptibility testing
define in vivo
patient
antibiograms can help answer questions in what 2 main areas?
-clinical care
-infection prevention strategies
what does an antibiogram do?
simplifies multiple patients antimicrobial sensitivity information at an institution into a single number for pathogens of interest in an effort to monitor trends emerging in drug resistance.
how many isolates are need for an antibiogram?
at least 30
For patients with multiple positive cultures, how many isolates should be included in an antibiogram?
Only the first (regardless of body fluid tested or antimicrobial susceptibility pattern)
can surveillance isolates be used for antibiograms?
no, only diagnostic
When developing an antibiogram for s. aureus, should MRSA be included?
Yes
True or false. Antibiograms do not underestiminate the activities of drugs for multi-drug resistant strains?
False
What are some methods of antimicrobial susceptibility testing?
-agar disk diffusion (Kirby-Bauer)
-antimicrobial gradient diffusion method (e-test or d-test)
How is the spread of resistance expressed?
as episodes of newly detected colonization or infection per 100 admissions or 1000 patient days
What is the main selective pressure responsible for antimicrobial resistance?
antimicrobial use
How do patients come to possess a resistant pathogen?
by transmitting bacteria that already have a resistance gene in place or by having the bacteria acquire a gene that codes for resistance
cidal agents kill _____% while static kills ___%
99.9%; 90-99%
when a drug is cidal or static can depend on what?
the concentration a pathogen is exposed to
what are some types of toxicities that may occur as a result of taking drugs?
-hepatotoxicity
-myelosupression
-renal toxicity
-auditory toxicity
-vestibular toxicity
-CNS toxicity
what are 3 indications for antimicrobial use?
- empiric
- pathogen directed
- prophylactic
define prophylactic
Prevents rather than treats known or suspected infection
what is the most common prophylaxis?
surgical antimicrobial prophylaxis where wound infection risk is high. For prostetic devices and patients with immunosuppresion
what are some basic principles of antimicrobial prophylaxis?
-drug spectrum should be appropriate for the organisms likely to cause infection
-usually staph or strep
-adueqate tissue levels, usually 1st gen cephlasporin, should be used from first incision onward
-duration should be as short as necessary to minimize resistance, side effects, and costs
when should antimicrobial prophylaxis be considered?
-anytime skin or mucosa is incised
-patients travelling to areas with endemic malaria
-endocarditis in ptients with high risk valvular lesions
-spontaneous bacterial peritonitis in patients with ascites
What are 2 organisms where prophylaxis may be used?
-meningococcal meningitidis
-HIV
What dosage is normally required for propphylaxis?
a single preoperative dose and sometimes one or two additional doses is surgery duration is prolonged
What is empiric therapy?
When no definitive information about a causative pathogen is available, therapy is empiric
When is empiric therapy done?
when the results of cultures are pending. Patients are usually sufficiently ill at this time.
When are cultures collected for empiric therapy?
Before therapy is started
What directs empiric therapy?
site of infection and host factors (i.e., immunocomprised) give an indication of likely pathogens which can direct empiric therapy.
Does a NAAT (PCR) provide susceptibility results?
No, a culture needs to be done for this
True or false. Nonculture results can direct therapy for pathogen with predictable susceptibility?
True (i.e., chlamydia and gonorrhea)
Which factors contribute to successful antimicrobial therapy? (hint: there are 5)
- prompt institution of an appropriate antimicrobial
- The bug factor (virulence and susceptibility)
- The drug factor (activity of the antimicrobial at a particular site of infection)
- Host factor (underlying condition and patient immunocompetence)
- site factor (infections at certain body sites like the heart are more difficult to treat)
Dose should be ___enough to be therapeutic but ___ enough to minimize toxicity
high; low
Hepatic insufficiency requires dose reduction of drugs excreted by the
Liver
Define switch therapy
switch from IV to oral after initial response to therapy
What are 3 possible effects of co-administering antimicrobials?
- some inactivate others (piperaccilin/tazobactam and aminoglycosides)
- Antigonism: inactivatoin. two antimicrobials become less effective (tetracycline and penicillin).
- Synergy: two co-administered antimicrobials are more effective
What is an example of a synergetic drug combination
endocarditis due to enterococcus. Protein inhibitory agent (aminoglycoside) with a cell wall active agent (penicillin or vancomycin) to achieve bactericidal activity
describe the microtiter brother dilution systems
trays of small volume wells consisting of various concentrations of antibiotic read with an automated commercial instrument
describe the antimicrobial gradient diffusion method (e-test or d-test)
a regent strip of gradient antimicrobial is placed on an agar plate to produce a gradient of concentrations in the medium
results of antimicrobial susceptibility testing should be based on what
susceptible, intermediate susceptible (drug is only effective at body sites where it is concentrated) and resistant
what are some mechanisms of antimicrobial resistance?
-drug inactivation and alteration in target site
-decreased permeability or efflux
-bypass of a metabolic pathway
-point mutations in genes or acquisition of new genes
most forms of resistance result from
newly acquired genes
Which organism has become resistant through decreased permeability or efflux?
pseudomonas resistant to carbapenems
Which organism has become resistant to drugs through bypass of a metabolic pathway
trimethoprim/sulfamethoxazole
What are mutations
random errors that occur during DNA replication resulting in the ubstitution of one base pair for another which may result in the subtitution of one amino acid for another in a protein structure or enzyme. Mutations occur infrequently at the correct location at the bacterial genome to cause mutation.
ESBLs are resistant to all ______ except ____
beta-lactams except carbapenems
Define antibiotic cycling
alternate using different antimicrobials to prevent resistance
audits of the AS program can be ____ or _____
prospective or retrospective
What of the AS program can be audited?
-dosing
-whether surgical prophylaxis is used appropriately
-whether empiric is switched to pathogen directed therapy once culture results are available
What is the goal of antimicrobial stewardship?
optimize antimicrobial treatment that results in the best outcome with minimal toxicity to the patient
True or false. Antimicrobials are the only pharmaceutical therapy whose effectiveness dimishes with time and use.
True
How many deaths and illnesses annually are attributed to AMR?
23,000 deaths; 2 million illnesses
how many ER visits are due to an adverse antimicrobial reaction?
1 in 5 (140,000)
on average ______ of LTC residents will be taking antibiotics at any given time
6-10%
studies show that ____ of antibiotic prescribing may be unecessary
40-75%
ASP programs have been shown to
-improve patient outcomes
-reduce antimicrobial age related adverse events
-decrease antimicrobial resistance
up to ___ of nursing home residents received one or more courses of systemic antibitoics in a year
70%
what are the 7 core elements of antibiotic stewardship?
- leadership
- accountability
- drug expertise
- action
- tracking
- reporting
- education
describe leadership
-ASP efforts in written statements and sharing this with staff, residents, and families
-including ASP duties in positions for medical director, pharmacists, and nursing leader
-communicate prescription policies
-supporting a culture and activities that promote ASP
describe accountability
identify and appoint individuals responsible for ASP activities
describe drug expertise
estbalish relationships with pharmaicsts or other individuals with ASP training or experience:
-ID docs
-ASP leads in hospitals within the network
describe action
requiring an ab timeout for all new ab starts
-improving the evaluation and communication of signs and symptoms when infection is first suspected (SBAR tool)
describe tracking
-montior at least one process and outcome measure of antibiotic use
-determine if antibiotics are prescribed per policy
-tracking antibiotic usedto review patterns and determining the impact of stewardship efforts.
outcome measures include: days of therapy, antibitoics starts, and prevalence surveys
-monitoring clinical outcomes
describe reporting and education
-reporting: provide regular feedback on antibiotic use and resistance to relevant staff
-education: provide resources to everyone about resistance and opportunities to improve use
what are some harms associated with antimicrobial prescribing
-anaphylaxis
-c. diff
-oral and vaginal superinfection (due to disruption of flora)
-adverse drug reactions
-increased healthcare expenditures
-resident and family suffering
-potential heavier work burden
-unecessary diagnoatic testing
-toxicity
-unfaovrable perception of a facility with increased infection rates
-related costs and burdens of adding TBP
-increased risk of MDRO colonization and infection
MDRO/ARO infections could result in what compared to susceptible infections?
-greater morbidity and mortality
-extended hospitalizations
-greater use of healthcare resources
-prolonged and costlier treatments
What are the 4 moments for antimicrobial decision making?
-1. make the diagnosis
2. cultures and empiric therapy
3. duration of therapy
4. stop, narrow, change to oral
define contamination
the introduction of undesired microbes or toxins to a specimen, the environment, or equipment (i.e., urine C & S with mixed growth).
where does VRE colonize?
GI/ GU tract
where does ESBL colonize?
GI/GU tract
where does c. diff colonize?
the GI tract
contamination is common associated with improper specimen collection such as:
- urine culture (not utilizing clean catch or sterile collection)
- wound swabs: taking a specimen from necrotic, exudate, or eschar rather than wound bed
- blood cultures: improper cleaning of skin or top of collection containers
define cross contamination
part of one specimen is transferred into another (occurs if samples are improperly stored, have cracks, or are improperly handled)
