Exam 3 Antimicrobials 10/26 Flashcards
Ketolides
telitromycin (Ketek), new drug with different ring structure from Erythromycin; used for infection when resistant to macrolides
Oxazolidinones
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)
The Acquisition of Drug Resistance
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
An Urgent Problem
“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
Urgent threats
Clostridium difficile
Carbapenem-resistant Enterobacteriaceae
Drug-resistant Neisseria gonorrhoeae
Serious threats
Multidrug-resistant Acinetobacter
Drug-resistant Campylobacter
Fluconazole-resistant Candida
Many more
Concerning threats
Vancomycin-resistant Staphylococcus aureus
Erythromycin-resistant Group A Streptococcus
Clindamycin-resistant Group B Streptococcus
How Does Drug Resistance Develop?
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
The Acquisition of Drug Resistance
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
Natural Selection and Drug Resistance
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
Interactions Between Drug and Host
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
Examples of Superinfection
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.
Considerations in Selecting an Antimicrobial Drug
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
Identifying the Agent
Identification of infectious agent should be attempted as soon as possible
Specimens should be taken before antimicrobials are initiated
Testing for Drug Susceptibility
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
The MIC and Therapeutic Index
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
The Antimicrobial Drug Dilemma
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.
