Pharm: Drug Resistance

Question 1

What are some untoward effects of antibiotic use?

Answer 1

• antibiotic resistance
• adverse drug effects (ADEs)
• increased healthcare costs (due to inadequate treatment of infection/readmission)

Question 2

Define antibiotic stewardship.

Answer 2

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

Question 3

What are the 6 goals of antibiotic stewardship programs?

Answer 3

1. reduce inappropriate consumption and inappropriate use
2. reduce C. diff infections
3. improve patient outcomes
4. increase adherence/utilization of treatment guidelines
5. reduce adverse drug events
6. decrease or limit antibiotic resistance (hardest to show)

Question 4

Describe directed antibiotic therapy.

Answer 4

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)

Question 5

Describe empiric antibiotic therapy.

Answer 5

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)

Question 6

Describe the 4 tenets of appropriate antibiotic use.

Answer 6

1. treat bacterial infection, not colonization
2. don’t treat sterile inflammation or abnormal imaging without infection
3. don’t treat viral infections with antibiotics
4. limit duration of antibiotic therapy to appropriate length

Question 7

While the absolute number of antibiotic drugs is ___, the number of unique targets is ____.

Answer 7

large; small

Question 8

Name 4 examples of antibiotic-associated ADEs.

Answer 8

1. hypersensitivity/allergy
2. drug side effects
3. C. diff infection
4. antibiotic associated diarrhea/colitis

Question 9

What is the single most important risk factor for Clostridium difficile?

Answer 9

antibiotics

Question 10

Antibiotics account for ___% of drug-related adverse events.

Answer 10

19.3%

Question 11

What percent of untoward events linked to antibiotics are due to penicillin and cephalosporin drug classes?

Answer 11

approximately 50%

Question 12

What are two purposes of the antibiotic stewardship?

Answer 12

1. limit inappropriate and excessive antibiotic use

2. improve and optimize therapy for the individual affected patient

Question 13

Antibiotic stewardship is practiced at the level of the ___ and ___, and should be a core function of the ____ ____.

Answer 13

patient and healthcare facility/network; medical staff

Question 14

What are the 9 factors to consider when selecting an antibiotic?

Answer 14

1. spectrum of coverage
2. patterns of resistance
3. track record for specific infection
4. achievable concentration (serum/tissue/body fluid)
5. allergy
6. toxicity
7. formulation (IV vs. PO)
8. convenience/adherence
9. cost
   SRTCATFCC

Question 15

Of antibiotic treatment in general, what percent is empiric vs. directed therapy?

Answer 15

85% empiric

15% directed

Question 16

What are some factors contributing to so much empiric therapy?

Answer 16

• 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.

Question 17

What are 3 ways to define an infection?

Answer 17

1. anatomically
2. microbiologically
3. pathophysiologically

Question 18

What are some ways to increase directed therapy for inpatients?

Answer 18

• 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

Question 19

What are some ways to increase directed therapy for outpatients?

Answer 19

• define the infection
• obtain cultures before starting therapy
• narrow therapy often with good supporting evidence

Question 20

What are 8 additional tenets of antibiotic stewardship?

Answer 20

1. 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)
2. don’t give abx with overlapping activity (specifically, don’t double-cover gram negative rods with overlapping drugs)
3. limit duration of surgical prophylaxis to <24hrs perioperatively
4. use rapid diagnostics if available
5. solicit expert opinion
6. prevent infection: hand hygiene, catheter removal

Question 21

Antibiotic stewardship is important for what two things?

Answer 21

1. preserving existing antibiotics

2. improving patient outcomes

Question 22

Describe the 3 principal causes of the antibiotic market failure:

Answer 22

1. scientific–low hanging fruit has been plucked, development now more complex, expensive, and time-consuming
2. economic–abx are poor return on investment b/c they’re short-course therapy, imbalanced drug pricing in society not based on rational information
3. regulatory–GAIN Act

Question 23

What’s the story of Telithromycin (Ketex)?

Answer 23

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

Question 24

What is the GAIN Act?

Answer 24

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

Question 25

What’s the MOA of Teixobactin?

Answer 25

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