CH 6- Principles of Antimicrobial Therapy Flashcards
What is the main goal of antimicrobial therapy?
The successful treatment of infection, avoidance of drug side effects on the patient, and avoidance of resistance.
Name some resistant strains mentioned.
- Staph. Intermedius
- Campylobacter
- Salmonella
- E. coli
What percentage of annual salmonellosis cases in humans are associated with companion animals?
At least 1%
Approximately what percentage of Campylobacter jejuni infections in children are transmitted from pets?
Approximately 6%
In dogs, how are E. coli strains related to those causing infections in humans?
They are phylogenetically similar.
What percentage of canine fecal deposits in the environment contain E. coli strains related to virulent human strains?
More than 15%
What can E. coli share with other enteric pathogenic coliforms?
Mechanisms of resistance.
Define antibiotics.
Natural chemicals produced by organisms intended to suppress other organisms.
What is an antimicrobial?
Any compound that suppresses microbial growth.
What do antibacterials target?
Bacteria and fungi.
What are obligate aerobes?
Organisms that generate energy by aerobic respiration of oxygen.
Give an example of an obligate aerobe.
Pseudomonas aeruginosa.
What is the difference between facultative anaerobes and obligate anaerobes?
Facultative anaerobes prefer oxygen but can switch to fermentation; obligate anaerobes cannot tolerate oxygen.
What does the term ‘isolate’ refer to?
One colony-forming unit (CFU) of the resident population of an organism.
What is the goal of antimicrobial therapy?
Achieve sufficient concentrations of an appropriate drug at the site of infection while avoiding side effects.
List reasons why antimicrobial drugs should not be used indiscriminately.
- Increased risk of toxicity
- Cost and inconvenience
- Increased risk of superinfection
- Potential emergence of resistant microbes
What are commensals?
Microbes that appear to neither harm nor help the host.
Define a pathogen.
A microbe that is associated with and capable of causing host damage.
What does empirical antibiotic therapy rely on?
Assumptions regarding the infecting organism and its susceptibility to drugs.
What is the significance of Gram staining?
It differentiates bacteria based on the layers penetrated by the Gram stain.
What is the disk diffusion method?
A method where agar is streaked with a standardized inoculum and disks containing a drug are placed to measure zones of inhibition.
What does the ‘E test’ combine?
The simplicity of disk diffusion with the informative nature of broth dilution.
What does an antibiogram summarize?
The proportion of isolates that are susceptible or resistant to a drug.
What is the MIC?
The minimum concentration of a drug needed to inhibit microbial growth.
What is a potential issue when interpreting susceptibility results?
In vitro testing may not accurately reflect in vivo situations.
What should be considered when establishing MIC breakpoints?
- Population distributions
- Clinical pharmacology of the drug
- Drug elimination half-life
- Volume of distributions
What does a susceptible breakpoint indicate?
An isolate inhibited below a certain MIC will be designated as ‘S’.
True or False: Normal flora can become pathogenic.
True.
Fill in the blank: An organism that cannot tolerate the presence of oxygen is called an _______.
Obligate anaerobe.
What does in vitro susceptibility mean in the context of antimicrobial testing?
In vitro susceptibility refers to the effectiveness of a drug against a microorganism when tested in a controlled laboratory environment.
This may not reflect clinical efficacy in vivo.
What is an example of a mismatch in antimicrobial susceptibility?
Amikacin shows susceptibility in vitro for Enterococcus sp but is not clinically effective against it.
This highlights the importance of considering clinical efficacy.
What are extended-spectrum beta-lactamases (ESBLs)?
ESBLs are enzymes that destroy selected third and fourth-generation cephalosporins and can be induced by the presence of the drug at the infection site.
They are often not expressed in vitro.
What indicates the presence of ESBL in a culture?
A fourfold or greater reduction in cephalosporin MIC when combined with clavulanic acid versus when present as the sole drug.
This is a critical testing method for identifying ESBLs.
What is the significance of pharmacokinetics (PK) and pharmacodynamics (PD) in antimicrobial therapy?
PK is the relationship between drug concentration and exposure, while PD is the response of the organism to the drug, as estimated by MIC.
Together, they influence the efficacy of antimicrobial agents.
Define bactericidal and bacteriostatic antimicrobials.
Bactericidal: ability to kill bacteria. Bacteriostatic: ability to inhibit microbial growth.
The distinction is important for treatment decisions.
What is the minimum bactericidal concentration (MBC)?
MBC is the lowest concentration of a drug that kills a specific bacterium.
It can be determined using various methods, including broth dilution.
What factors affect antimicrobial efficacy?
Factors include:
* Drug concentration
* Inoculum size
* Resistance mechanisms
* Host defenses
These factors can vary significantly between in vitro and in vivo settings.
What is post-antibiotic effect (PAE)?
PAE is the ability of a drug to inhibit bacterial growth after it is no longer present or below MIC.
It indicates how long bacteria remain suppressed after treatment.
What distinguishes concentration-dependent drugs from time-dependent drugs?
Concentration-dependent drugs (e.g., fluoroquinolones) are most effective based on peak concentration, while time-dependent drugs (e.g., beta-lactams) are effective based on the duration of time above the MIC.
This affects dosing strategies.
What is the impact of inoculum size on antimicrobial treatment?
A larger bacterial inoculum requires a higher concentration of antimicrobial to achieve effective treatment due to increased likelihood of resistance and enzyme production.
Inoculum size is critical in determining treatment success.
What are virulence factors?
Virulence factors are proteins that enhance a bacterium’s ability to cause infection, affecting antimicrobial efficacy indirectly.
They can include adhesins, invasins, and toxins.
What is the mutant prevention concentration (MPC)?
MPC is the highest MIC of any colony-forming unit causing infection in the patient, preventing the emergence of resistant mutants.
Failure to achieve MPC can lead to resistance development.
Differentiate between inherent and acquired resistance.
Inherent resistance is due to natural characteristics of the organism, while acquired resistance arises from genetic mutations or horizontal gene transfer.
Acquired resistance is more problematic and unpredictable.
What are the primary mechanisms of antimicrobial resistance?
Mechanisms include:
* Modification of target sites
* Altered intracellular drug concentration
* Enzymatic destruction of drugs
These mechanisms can lead to treatment failure.
What factors facilitate antimicrobial efficacy in the host?
Factors include:
* Drug distribution to the infection site
* Local pH and tissue oxygen levels
* Host immune response
These can significantly impact treatment outcomes.
What happens to the activity of Erythromycin at pH levels below 7?
Erythromycin loses all its activity below pH 7
Beta-lactams also lose efficacy at pH < 6, but are less affected than Erythromycin.
How does low pH affect drug activity?
Changes in pH lead to changes in the ratio of un-ionized and thus active drug
Ionized drugs have impaired diffusibility.
What effect does low tissue oxygen tension have on white blood cell activity?
Reduces WBC phagocytic and killing activity
It slows growth of organisms, making them less susceptible to many drugs.
What are host factors that facilitate antimicrobial efficacy?
Local and systemic defenses include:
* Compounds that directly target microbes
* Healthy tissue that provides mechanical barriers
* A competent immune system
What is the significance of drug accumulation at the site of infection?
Facilitates drug efficacy and decreases resistance
Drugs may exceed 30-fold to several 100-fold based on renal and biliary excretion.
Which drugs do not accumulate at the site of infection?
Beta-lactams, aminoglycosides, and metronidazole
Chloramphenicol and selected sulfonamides show moderate accumulation.
What factors affect drug absorption?
Bioavailability is the % of an administered dose that reaches systemic circulation
Greater bioavailability leads to a greater pharmacologic response.
What is the preferred method of drug administration for critically ill patients?
IV administration
It is preferred for difficult-to-penetrate tissues.
What influences drug distribution in the body?
Drug lipid solubility, plasma binding degree, and regional blood flow
Highly bound drugs may have low extracellular fluid concentrations.
What is the blood-brain barrier’s role in drug penetration?
It actively transports antibiotics out or destroys them
CNS penetration decreases without inflammation.
What is the impact of aminoglycosides and beta-lactams on tissue distribution?
Limited distribution in extracellular tissues
Imipenem and trimethoprim/sulfonamide can achieve bactericidal concentrations in CNS.
What is the significance of drug elimination routes?
If the site of infection is also a route of elimination, higher drug concentrations can be achieved
Toxic drugs should be avoided if they compromise the organ of elimination.
What nonantimicrobial effects do antimicrobials have?
Influence on WBC function, including increased chemotaxis, phagocytosis, and cytokine production
Selected antibiotics may facilitate therapeutic success through immunomodulation.
True or False: Adverse drug events often reflect the mechanism of action of the drug.
False
The adverse event of a drug seldom reflects the MOA.
What are the characteristics of type A drug events?
Predictable and depend on maximum or peak pharmacodynamic concentration
Aminoglycosides are an exception due to their nephrotoxicity and ototoxicity.
What is the aim of antimicrobial prophylaxis?
Administering an antimicrobial agent in the absence of infection
It is indicated for anticipated infection after bacterial contamination.
What are the types of surgical wounds?
Clean, clean-contaminated, contaminated, dirty/infected
Each type has different considerations for prophylactic antibiotic therapy.
What is the recommended duration of therapy for uncomplicated infections?
5 to 7 days or less
This is an exception for immunocompromised patients.
What is synergism in antimicrobial therapy?
Occurs when two antibiotics target different pathways, enhancing efficacy
Examples include chloramphenicol and clindamycin working on different ribosomal sites.
What is an example of antagonism in antimicrobial therapy?
Chloramphenicol and erythromycin competing for the same target sites
This could reduce the effective concentration of either drug.
What is the role of clavulanic acid in antimicrobial therapy?
Draws beta-lactamase activity away, allowing beta-lactams to work effectively
It serves as a protective mechanism for beta-lactams.
What factors should be considered in selecting prophylactic antimicrobials?
Anticipated pathogenic organism, adequate concentration at the site, and duration of therapy
The least toxic drug should be selected.
What is the impact of procedure duration on surgical site infection risk?
Longer procedures (over 90 min) increase the incidence of wound infections
Exogenous sources like surgical equipment and personnel play a role.
What is the relative flora in the trachea and bronchi?
Relatively sparse flora
Indicates low bacterial presence in these areas
What can promote bacterial colonization in wounds?
Presence of extensive tissue damage or accumulation of blood
These conditions may warrant prophylactic drug administration
Define ‘Contaminated’ wounds.
Wounds with acute, nonpurulent inflammation or gross contamination from a hollow viscus
Indicates significant bacterial presence and potential for infection
What is generally warranted for prophylaxis in certain wounds?
Prophylaxis is generally warranted
Especially when extensive tissue damage or blood accumulation is present
What is a benefit of using chlorhexidine (0.05%)?
Effective wound disinfectant
Used in dirty or infected wounds for irrigation and antiseptics
When is the use of antimicrobials indicated?
Before surgery to treat an infected or dirty wound
Can be administered systemically, topically, or both
What is more appropriately termed as therapeutic antimicrobial therapy?
Use of antimicrobials in infected or dirty wounds
Focuses on treatment rather than prevention
What are the most frequently encountered potential pathogens in surgical wounds?
- Staphylococcus spp
- E. coli
Common bacteria associated with surgical site infections
What types of organisms are typically found in the skin?
Staphylococcus spp
Dominant bacterial population in skin flora
What is the bacterial population in the oropharynx?
- Mixed population of gram+ (e.g., Staphylococcus spp, Streptococcus spp, Actinomyces pyogenes)
- Gram- organisms (e.g., Proteus, Pasteurella, Pseudomonas, E. coli)
- Anaerobic organisms
Reflects complex microbial environment in the oropharyngeal area
What is the typical bacterial presence in the stomach and small intestine?
Few organisms normally present
Indicates a relatively sterile environment
What type of organisms are found in the distal ileum and large intestine?
- Large numbers of gram- (e.g., E. coli, Klebsiella, Pseudomonas, Salmonella)
- Anaerobic organisms
High bacterial diversity in these regions
What types of organisms are found in the genitourinary tract?
- Gram+ (e.g., Staphylococcus, Streptococcus)
- Gram- (e.g., E. coli, Proteus, Pseudomonas)
Reflects dual bacterial presence in urinary and reproductive systems
What are the gram+ and gram- organisms commonly found in the lower respiratory tract?
- Gram+ (e.g., Staphylococcus, Streptococcus, A. pyogenes)
- Gram- (e.g., Pseudomonas, E. coli, Klebsiella, Pasteurella, Enterobacter)
Highlights potential pathogens in respiratory infections
What is the primary goal of prophylactic antimicrobial therapy?
Produce adequate concentrations of antimicrobials at the surgical incision site at the time of wound contamination
Essential for preventing surgical site infections
When should the IV dose of prophylactic antimicrobials be given?
30-60 minutes before incision and another dose at the completion of the procedure
Timing is crucial for effectiveness
What should be done if a surgical procedure lasts longer than 3 hours?
An additional intraoperative dose of antimicrobial should be given at approximately 2-3 hours after the initial dose
Ensures continued protection against infection
Is there a rationale for continuing antimicrobial administration longer than 24 hours after surgery in the absence of documented infection?
No
Prolonged use is not justified and may lead to complications
What are complications of inappropriate perioperative antimicrobial use?
- Reduced efficacy
- Suprainfection
- Selection of resistant bacterial pathogens
- Greater client cost
- Potential for higher incidence of drug-associated complications
Highlights the importance of proper antimicrobial stewardship
List examples of inappropriate antimicrobial use.
- Antimicrobials for clean surgical procedures
- Initiation of prophylactic antimicrobials postop
- Continuation of antimicrobials for longer than 24 hours
These practices can increase the risk of complications
