Introduction to Antimicrobial Therapy Flashcards
Characteristics we want our antibiotics to be?
Selective toxicity
How do you determine if antimicrobial therapy is warranted?
- Is an antimicrobial agent indicated on the basis of clinical findings?
- Is it prudent to wait until such clinical findings become apparent?
- Have appropriate clinical specimens been obtained to establish a microbiologic diagnosis?
- urine samples easy
- sinusitis not so much - What are the likely etiologic agents for the patient’s illness?
- What measures should be taken to protect individuals exposed to the index case to prevent secondary cases, and what measures should be implemented to further exposure?
- Is there clinical evidence (eg, clinical trials) that antimicrobial therapy will confer clinical benefit for the patient?
- Is it indicated
- Should we treat now or until we know for sure?
- Have we done appropriate cultures/labs?
- What are the likely etiologies
- How do we protect the individual and others from infection?
- Is there evidence that antimorcobial therapy will help (clinical trials)
Once a specific microorganism is identified there are more questions?
5
- Can a narrower-spectrum agent be substituted for the initial empiric drug?
- Is one agent or a combination of agents necessary?
- What is the optimal dose, route of administration, and duration of therapy?
- What specific tests (i.e. susceptibility testing) should be undertaken to identify patients who will not respond to treatment?
- What adjunctive measures can be undertaken to eradicate the infection, (i.e. surgery, drainage of abscess, decreasing immunosuppresive therapy?)
Name some examples of resistant infection spp?
4
Imidazole resistant Candida spp
Multidrug resistant TB
Multidrug resistant malaria
Anti-viral resistant influenza
Resistance includes bacteria, viruses, fungi and protozoa.
What are two ways that resistance happens with antimicrobial therapy?
Spontaneous mutation and conjugation are random events whose incidence is independent of drug use
Mechanisms of antibiotic resistance
5
Enzymatic inactivation
Antibiotic uptake reduction
Increased antibiotic removal
Alteration of bacterial target sites
Plasmid transfer
What are three ways that antibiotic degrading enzymes work?
sulfonation, phosphorylation, or esterification
Bacterial enzymes that split the beta-lactam ring of which drugs?
4
How is this usually mediated?
penicillin, cephalosporins, carbapenems and monobactams
Usually plasmid mediated
Antibiotic resistance due to decreased permeablility occurs frequently in what kind of bacteria?
Occur frequently in gram negative bacteria
Antibiotic resistance due to target alteration occurrs how?
The binding site on the bacterial cell membrane is altered
Antibiotic resistance due to efflux pumps occur how?
Single or multidrug pumps to remove antibiotic from the intracellular space
Describe the MOA of Methicillin resistant staph aureus and why it is so dangerous?
Where is it often colonized
It becomes the “normal flora” of carriers
Often colonized in the nasal cavity
Screening and isolation precautions prior to surgical procedures
MRSA waiting for an opportunity to infect the host or others
How do we control the wave of antibiotic resistance?
First, antimicrobial agents should be used only when actually needed.
Second, narrow-spectrum agents should be employed whenever possible.
Third, newer antibiotics should be reserved for situations in which older drugs are no longer effective.
- Consider the site of infection
- When possible try to isolate the bacteria to target therapy
What is the MIC?
(Minimum inhibitory concentration)
Lowest concentration of antimicrobial that inhibits growth of bacteria.
What is the breakpoint?
The MIC that is used to designate between susceptible and resistant.
- in live hosts not in a lab
How do we determine if a bacterium is susceptible or not?
If the MIC is lower than the breakpoint the bacterium is considered susceptible. If it is higher, it is considered resistant.
If we find out a bug is not susceptible to the antibiotic we started them on what should we do?
When culture and sensitivity results are known change antibiotic if necessary
Consult antibiogram
Empiric therapy is based on what?
4
- the most likely pathogen and
- clinical trials proving efficacy
- risk factors for microbial resistance
- Medical comorbidities
If no significant risks for Drug Resistant Streptococcus Pneumoniae (DRSP)?2
If risks for DRSP?
3
Macrolide or doxycycline
Antipneumococcal fluoroquinolone
or
High-dose amoxicillin (3 gm/day) or high dose amoxicillin/clavulanate (4 gm/day) plus macrolide
Many antibiotics may be effective, but there usually are superior alternatives that show (what does drug of choice=)?
4
Greater efficacy
Lower toxicity
Narrow spectrum
Lower cost
Host Factors that Modify Drug Choice?
7
Host Defenses: Site of Infection Age Hepatic or Renal Dysfunction Pregnancy and Lactation Previous Allergic Reaction Genetic Factors
Drug levels how many times greater than the MIC are desired?
Drug levels four to eight times the MIC are often desirable.
Where is the trend going for duration of therapy and why?
Longer duration = greater resistance
going for shorter durations of therapy
Indications for Antibiotic Combinations?
5
- Initial therapy of severe infections
- Mixed infections
- Prevention of resistance
- Decreased toxicity
- Enhanced antibacterial action
Disadvantages of Combination Therapy
5
- Increased risk of toxic and allergic reactions
- Possible antagonism of antimicrobial effects
- Increased risk of superinfection
- Selection of drug-resistant bacteria
- Increased cost
Antimicrobial Effects of Antibiotic Combinations
What are the types and describe them?
3
- Additive - antimicrobial effect of combination is equal to the sum of the effects of the two drugs alone.
- Synergistic - one in which the effect of the combination is greater than the sum of the effects of the individual agents.
- Antagonistic - a combination of two antibiotics may be less effective than one of the agents
Frequency of monitoring is directly proportional to what?
severity of the infection
Important clinical indicators of successful therapy are?
2
reduction of fever and resolution of symptoms.
Monitoring therapy for clinical response
What should the clinical response show?
3
Clinical response
- Improvement in lab results
- Resolution of symptoms
- Resolution of fever or leukocytosis
Patient education points for antibiotics?
4
- Complete full course of therapy
- Do not take antibiotics prescribed for another person
- Hand washing
- Report failure to respond to therapy
Which one of the following factors is associated with the highest likelihood of resistance to antibiotic therapy?
- Patient age
- Antibiotic use within the last 3-6 months
- Location of infection
- The presence of a fever
Antibiotic use within the last 3-6 months
Which one of the following is most likely to lead to patient colonization of drug resistant bacteria?
- Exposure to antibiotics after the pathogen is eliminated
- Probiotics
- Taking an antibiotic they are already resistant to
- Use of narrow spectrum antibiotics
Taking an antibiotic they are already resistant to
Which of the following choices is recommended for reduction of antimicrobial resistance? 1, Prescribing lower doses of therapy 2. Appropriate duration of therapy 3. Use of a narrow spectrum agent 4. All of the above 5. B & C
B & C
