Pharm 2: Appropriate Antibiotic Use

Question 1

What is the fundamental problem with antimicrobial therapy today?

Answer 1

the ability of the microbe to adapt to the presence of the drug, thus circumventing the therapeutic intent.

Question 2

Infection with C. difficile is associated with recent use of antimicrobial medications and with residence in hospitals. Most C. difficile–associated disease (CDAD) cases are acquired in healthcare settings, and as many as 90% of cases may be associated with antimicrobial drug use. High C. difficile death rates call attention to the importance of proper infection control practices in hospitals and long-term care facilities and the judicious use of antimicrobial medications. Further research is needed to explore current questions concerning which antimicrobial medications, if any, will lead to CDAD.
Infections such as septicemia, pneumonia, and urinary tract infections were commonly reported in conjunction with C. difficile–related deaths. For some of these patients, the administration of antimicrobial medications to treat infections from other pathogens may have paved the way for infection with C. difficile. However, other risk factors are known, so that in many cases the careful use of antimicrobial agents may not be enough to prevent C. difficile infection. HIV infection was only reported in a small fraction of CDAD–related deaths. However, immunosuppression and the use of prophylactic antimicrobial drugs in persons with AIDS may increase the risk for CDAD, and the effects of HIV should not be overlooked. In persons 25–54 years of age, in whom HIV infection is most common, HIV infection was reported in approximately one tenth of CDAD-related deaths. Thus, HIV can considerably increase C. difficile death rates for demographic groups in which HIV prevalence is high.

Answer 2

Infection with C. difficile is associated with recent use of antimicrobial medications and with residence in hospitals. Most C. difficile–associated disease (CDAD) cases are acquired in healthcare settings, and as many as 90% of cases may be associated with antimicrobial drug use. High C. difficile death rates call attention to the importance of proper infection control practices in hospitals and long-term care facilities and the judicious use of antimicrobial medications. Further research is needed to explore current questions concerning which antimicrobial medications, if any, will lead to CDAD.
Infections such as septicemia, pneumonia, and urinary tract infections were commonly reported in conjunction with C. difficile–related deaths. For some of these patients, the administration of antimicrobial medications to treat infections from other pathogens may have paved the way for infection with C. difficile. However, other risk factors are known, so that in many cases the careful use of antimicrobial agents may not be enough to prevent C. difficile infection. HIV infection was only reported in a small fraction of CDAD–related deaths. However, immunosuppression and the use of prophylactic antimicrobial drugs in persons with AIDS may increase the risk for CDAD, and the effects of HIV should not be overlooked. In persons 25–54 years of age, in whom HIV infection is most common, HIV infection was reported in approximately one tenth of CDAD-related deaths. Thus, HIV can considerably increase C. difficile death rates for demographic groups in which HIV prevalence is high.

Question 3

What is antibiotic stewardship?

Answer 3

a coordinated and concerted effort by all facets of the healthcare community to use antimicrobials more wisely and effectively using data collection, personnel, etc.

Question 4

What are the six main goals of the antibiotic stewardship program?

Answer 4

1. reduce antibiotic consumption and inappropriate use
2. reduce Clostridium difficile 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 5

What are the 9 factors that need to be considered when selecting an antimicrobial regimen.

Answer 5

1. spectrum of coverage
2. patterns f resistance
3. evidence of track record for the specified infection
4. achievable serum tissue or body fluid
5. Allergy
6. Toxicity
7. Formulation (IV vs. PO); if PO assess bioavailability
8. Adherence/convenience
9. Cost

Question 6

T or F. In most medical centers only 15-20% of therapy is directed leaving 80-85% as empiric.

Answer 6

T.

Question 7

What are some of the characteristics of empiric therapy?

Answer 7

infection not well defined
broad spectrum
multiple drugs
evidence usually only 2 RCTs
more adverse reactions
more expensive

Question 8

What are some of the characteristics of directed therapy?

Answer 8

infection well defined
narrow spectrum
one, seldom two drugs
evidence strong
less adverse reactions
less expensive

Question 9

Why is the bulk of therapy empiric?

Answer 9

need for prompt therapy with certain infections (life or limb threatening infections)

cultures difficult to do to provide microbiologic definition

negative cultures

provider beliefs (fear or error missing something, not believing culture data available)

Question 10

What are some methods that allow increased use of directed therapy?

Answer 10

define the infection by location, presentation, and by the causative agent

obtain cultures before starting antibiotics
using imagine, rapid diagnostics, and special procedures early in the course of infection

have the courage to make a diagnosis

do not rely solely on “response to therapy” to guide therapeutic decisions; follow recommended guidelines

If empiric therapy is started, reassess at 48-72 hrs

Question 11

Basic Tenets:

1. treat bacterial infection, NOT colonization- Significantly, the presence of bacteria (colonization) does not indicate an infection if that microbe would reasonably be located at that anatomical site.
2. Don’t treat sterile inflammation or abnormal imagine without infection- Inflammation is not always the result of microbial infection
3. Don’t treat viral infections with antibiotics- And there in no point in treating a viral infection with an antimicrobial agent.
4. limit duration of antibiotic therapy to the appropriate length- Targets in microbes and for viral replication are completely different and many viral infections, e.g., the common cold are self limiting in their duration anyway.

Answer 11

Basic Tenets:

1. treat bacterial infection, NOT colonization- Significantly, the presence of bacteria (colonization) does not indicate an infection if that microbe would reasonably be located at that anatomical site.
2. Don’t treat sterile inflammation or abnormal imagine without infection- Inflammation is not always the result of microbial infection
3. Don’t treat viral infections with antibiotics- And there in no point in treating a viral infection with an antimicrobial agent.
4. limit duration of antibiotic therapy to the appropriate length- Targets in microbes and for viral replication are completely different and many viral infections, e.g., the common cold are self limiting in their duration anyway.

Question 12

Re-evaluation of treatment is always valuable and “double coverage” with drugs that completely overlap in terms of the spectrum of antimicrobial activity is a useless but potentially harmful pusuit.

Answer 12

Re-evaluate, de-escalate or stop therapy at 48-72 hrs based on diagnosis or microbiologic results

Re-evaluate, de-escalate or stop therapy with transitions of care (e.g. ICU to step-down or ward)

Don’t give antibiotics with overlapping activtiy

Dont “double-cover” gram-neg. rods with 2 drugs with overlapping activity

Question 13

Other tenets of antibiotic stewardship

Answer 13

limit duration of surgical prophylaxis to

Question 14

reasons for the present dearth in availability of new antimicrobial agents.

Answer 14

scientific, economic, regulatory

Question 15

Scientific reason for lack of new antibiotics

Answer 15

From a drug discovery perspective, the pharmaceutical community has already harvested the “low hanging fruit”, that is to say they have exploited the easy drug targets and the microbes have duly responded with mechanisms of resistance. From this point forward drug discovery will undoubtedly be more complex and expensive.

The problem of resistance is compounded by the small number of novel antibiotics in development. This slide shows the number of new systemic antibiotics approved by the FDA over the 5-year period ending in March 2011. Despite increasing antimicrobial resistance in both outpatient and inpatient populations, there has been a decreasing number of novel antimicrobial agents developed in the last 2 decades. This has been labelled as a public health crisis by the Infectious Diseases Society of America, the Centers for Disease Control and Prevention and other governmental agencies.

What we need to discover are new unique targets for which resistance has not yet developed.

Question 16

Economic reason for lack of new antibiotics

Answer 16

What about the economics of drug development in this arena? Basically, as the narrative states, antimicrobials represent a very poor return on investment compared to drugs that might be used on a chronic basis in large numbers of patients.