Exam 3 Antimicrobials 10/26 Flashcards

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1
Q

Ketolides

A

telitromycin (Ketek), new drug with different ring structure from Erythromycin; used for infection when resistant to macrolides

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2
Q

Oxazolidinones

A

linezolid (Zyvox); synthetic antimicrobial that blocks the interaction of mRNA and ribosome

Used to treat methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE)

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3
Q

The Acquisition of Drug Resistance

A

Adaptive response in which microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory; due to genetic versatility or variation; intrinsic and acquired

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4
Q

An Urgent Problem

A

“Threat Report” issued by the CDC in 2013 outlines a “potentially catastrophic” antibiotic resistance situation. We may enter a post-antibiotic era where some infections will be untreatable.

New and effective antibiotics have been slow to come to market:
- Antibiotics not economically lucrative
- Time-consuming and expensive to develop

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5
Q

Urgent threats

A

Clostridium difficile
Carbapenem-resistant Enterobacteriaceae
Drug-resistant Neisseria gonorrhoeae

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6
Q

Serious threats

A

Multidrug-resistant Acinetobacter
Drug-resistant Campylobacter
Fluconazole-resistant Candida
Many more

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7
Q

Concerning threats

A

Vancomycin-resistant Staphylococcus aureus
Erythromycin-resistant Group A Streptococcus
Clindamycin-resistant Group B Streptococcus

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8
Q

How Does Drug Resistance Develop?

A

Resistance to penicillin developed in some bacteria as early as 1940.

In the 1980s and 1990s scientists began to observe treatment failures on a large scale

Microbes become newly resistant to a drug after one of the following occurs:
- Spontaneous mutations in critical chromosomal genes
- Acquisition of entire new genes or sets of genes via horizontal transfer from another species

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8
Q

The Acquisition of Drug Resistance

A

Acquired resistance:

Spontaneous mutations in critical chromosomal genes

Acquisition of new genes or sets of genes via transfer from another species

  • Originates from resistance factors (plasmids) encoded with drug resistance, transposons
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8
Q

Natural Selection and Drug Resistance

A

Large populations of microbes likely to include drug resistant cells due to prior mutations or transfer of plasmids – no growth advantage until exposed to drug

If exposed, sensitive cells are inhibited or destroyed while resistance cells will survive and proliferate.

Eventually population will be resistant – natural selection

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9
Q

Interactions Between Drug and Host

A

Estimate that 5% of all persons taking antimicrobials will experience a serious adverse reaction to the drug – side effects

Major side effects:
- Direct damage to tissue due to toxicity of drug
- Allergic reactions
- Disruption in the balance of normal flora- superinfections possible

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10
Q

Examples of Superinfection

A

Urinary tract infection caused by E. coli treated with antibiotics:
- Lactobacilli in the female vagina are killed by the broad-spectrum cephalosporin used to treat the UTI.
- Overgrowth of Candida albicans occurs, causing a vaginal yeast infection or oral thrush.

Antibiotic-associated colitis:
- Oral therapy with tetracyclines, clindamycin, and broad-spectrum penicillins kills off normal biota of the colon.
- Overgrowth of Clostridium difficile invades the intestinal lining and releases toxins that cause diarrhea, fever, and abdominal pain.

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11
Q

Considerations in Selecting an Antimicrobial Drug

A

Identify the microorganism causing the infection

Test the microorganism’s susceptibility (sensitivity) to various drugs in vitro when indicated

The overall medical condition of the patient

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12
Q

Identifying the Agent

A

Identification of infectious agent should be attempted as soon as possible

Specimens should be taken before antimicrobials are initiated

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13
Q

Testing for Drug Susceptibility

A

Essential for groups of bacteria commonly showing resistance

  • Kirby-Bauer disk diffusion test
  • E-test diffusion test
  • Dilution tests – minimum inhibitory concentration (MIC) – smallest concentration of drug that visibly inhibits growth
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14
Q

The MIC and Therapeutic Index

A

In vitro activity of a drug is not always correlated with in vivo effect
- If therapy fails, a different drug, combination of drugs, or different administration must be considered

Best to chose a drug with highest level of selectivity but lowest level toxicity – measured by therapeutic index – the ratio of the dose of the drug that is toxic to humans as compared to its minimum effective dose

High index is desirable

15
Q

The Antimicrobial Drug Dilemma

A

Worldwide problem in the management of antimicrobial drugs:
- Seen as a “cure-all” for infections such as the common cold and acne
- In many instances these drugs have no effect or are harmful
- Nearly 200 million prescriptions for antimicrobials are written in the US every year.
- Seventy-five percent of these prescriptions are for pharyngeal, sinus, lung, and upper respiratory infections that are viral in origin.

Physicians have used a “shotgun” approach, using broad-spectrum antimicrobial therapy for minor infections:
- This has lead to superinfections and other adverse reactions.
- Caused the development of resistance in “bystander” microbes (normal biota) that were exposed to the drug as well, leading to the spread of resistant pathogens
- Growing awareness has lead to the reduction of this practice.

Tons of excess antimicrobial drugs in the US are exported to countries where controls are not as strict:
- It is common for individuals in Latin America and Asia to self-medicate with antibiotics.
- Drugs used in this way are largely ineffectual and lead to drug resistance.
- Every allied health professional should be critically aware not only of the admirable and utilitarian nature of antimicrobials, but also of their limitations.

16
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