Pharm: Drug Resistance Flashcards
What are some untoward effects of antibiotic use?
- antibiotic resistance
- adverse drug effects (ADEs)
- increased healthcare costs (due to inadequate treatment of infection/readmission)
Define antibiotic stewardship.
a system of informatics, data collection, personnel, and policy/procedures which promotes the optimal selection, dosing, and duration of therapy for antimicrobial agents throughout the course of their use
What are the 6 goals of antibiotic stewardship programs?
- reduce inappropriate consumption and inappropriate use
- reduce C. diff infections
- improve patient outcomes
- increase adherence/utilization of treatment guidelines
- reduce adverse drug events
- decrease or limit antibiotic resistance (hardest to show)
Describe directed antibiotic therapy.
when the infection is well-defined, can use one (seldom two) narrow spectrum antibiotic; will usually see fewer ADEs and it’s cheaper (compared to empiric)
Describe empiric antibiotic therapy.
when the infection is not well-defined, will use multiple broad spectrum antibiotics; will usually see more ADEs and it’s more expensive (compared to directed)
Describe the 4 tenets of appropriate antibiotic use.
- treat bacterial infection, not colonization
- don’t treat sterile inflammation or abnormal imaging without infection
- don’t treat viral infections with antibiotics
- limit duration of antibiotic therapy to appropriate length
While the absolute number of antibiotic drugs is ___, the number of unique targets is ____.
large; small
Name 4 examples of antibiotic-associated ADEs.
- hypersensitivity/allergy
- drug side effects
- C. diff infection
- antibiotic associated diarrhea/colitis
What is the single most important risk factor for Clostridium difficile?
antibiotics
Antibiotics account for ___% of drug-related adverse events.
19.3%
What percent of untoward events linked to antibiotics are due to penicillin and cephalosporin drug classes?
approximately 50%
What are two purposes of the antibiotic stewardship?
- limit inappropriate and excessive antibiotic use
2. improve and optimize therapy for the individual affected patient
Antibiotic stewardship is practiced at the level of the ___ and ___, and should be a core function of the ____ ____.
patient and healthcare facility/network; medical staff
What are the 9 factors to consider when selecting an antibiotic?
- spectrum of coverage
- patterns of resistance
- track record for specific infection
- achievable concentration (serum/tissue/body fluid)
- allergy
- toxicity
- formulation (IV vs. PO)
- convenience/adherence
- cost
SRTCATFCC
Of antibiotic treatment in general, what percent is empiric vs. directed therapy?
85% empiric
15% directed
What are some factors contributing to so much empiric therapy?
- need for prompt therapy
- delay for cultures, or difficult/negative cultures
- provider beliefs - fear of missing something, don’t believe available data, double-coverage myth, etc.
What are 3 ways to define an infection?
- anatomically
- microbiologically
- pathophysiologically
What are some ways to increase directed therapy for inpatients?
- define the infection and make a diagnosis
- obtain cultures before starting therapy
- use imaging, rapid diagnostics, and special procedures early in the course of infection
- don’t rely solely on “response to therapy” to guide decisions
- if empiric therapy is used, reassess at 48-72 hrs
What are some ways to increase directed therapy for outpatients?
- define the infection
- obtain cultures before starting therapy
- narrow therapy often with good supporting evidence
What are 8 additional tenets of antibiotic stewardship?
- re-evaluate or de-escalate therapy at 48-72hrs based on diagnosis and microbiological results, slash at care transitions (like ICU to step-down unit)
- don’t give abx with overlapping activity (specifically, don’t double-cover gram negative rods with overlapping drugs)
- limit duration of surgical prophylaxis to <24hrs perioperatively
- use rapid diagnostics if available
- solicit expert opinion
- prevent infection: hand hygiene, catheter removal
Antibiotic stewardship is important for what two things?
- preserving existing antibiotics
2. improving patient outcomes
Describe the 3 principal causes of the antibiotic market failure:
- scientific–low hanging fruit has been plucked, development now more complex, expensive, and time-consuming
- economic–abx are poor return on investment b/c they’re short-course therapy, imbalanced drug pricing in society not based on rational information
- regulatory–GAIN Act
What’s the story of Telithromycin (Ketex)?
until Ketex, the FDA required only demonstration that the drug eliminated signs of infection as reliably as the current approved abx; Ketex was approved but had a high ADE profile, was banned for 2 of its 3 approved indications
What is the GAIN Act?
act from 2012 that provides added exclusivity for abx and earmarks them for priority FDA review; mandates creation of pathogen focused antibacterial drug development pathway; also does some other things but significantly: the political pressure to limit ADEs was replaced by call to reinvigorate product development
What’s the MOA of Teixobactin?
forms a stoichiometric complex with cell wall precursors, lipid II and III; this interrupts peptidoglycan and wall teichoic acid biosynthesis as well as precursor recycling.
Binding to multiple targets within the cell wall pathways obstructs the formation of a functional cell envelope
