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Principles of Antimicrobial Therapy
Pharm Module I
90
Medical
Graduate
05/19/2009

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Term
What is a natural substance produced by one microbe to kill other microbes?
Definition
antibiotic
Term
What are three types of antimicrobials?
Definition
antibacterial antifungal antiviral
Term
What are some factors to consider when choosing an agent to treat an infection?
Definition
cost
drug toxicity
drug kinetics
type of infection
host defense
microbe susceptibility to drug
drug dynamics
Term
What is an agent that inhibits growth of a microbe but does not kill microbes?
Definition
bacteriostatic agents
Term
Do bacteriostatic agents reduce the number of viable microbes?
Definition
does not reduce number of viable microbes
Term
What kills remaining microbes after a bacteriostatic agent has been administered?
Definition
need functional immune system to reduce remaining microbes
Term
Drugs that reversibly inhibit bacterial protein are examples of what type of agent?
Definition
bacteriostatic agent
Term
What type of agent kills susceptible microbes as well as reducing the number of viable microbes?
Definition
bactericidal agent
Term
What type of agent is exemplified by drugs that inhibit bacterial cell wall synthesis?
Definition
bactericidal agent
Term
In what conditions might a drug be bacteriostatic and bactericidal?
Definition
Many bacterial agents are bacteriostatic at low concentrations and bactericidal at higher concentrations
(A few antimicrobial agents are bactericidal against some microbes but bacteriostatic against others)
Term
The ability to *kill* microbes depends on the length of *time* concentration of antimicrobial is above what?
Definition
above the minimum *bactericidal* concentration (MBC)
Term
The ability to *inhibit* further microbe growth depends on the length of *time* concentration of antimicrobial is above what?
Definition
above the minimum *inhibitory* concentration (MIC) at the site of infection
Term
The ability to kill microbes increases as what aspect of an antimicrobial drug increases?
Definition
concentration of antimicrobial
Term
Aminoglycoside and fluoroquinolone antibiotics exhibit what pharmacodynamic principle?
Definition
concentration-dependent killing rate
Term
What pharmacodynamic principle is displayed as microbial death or inhibition of growth continues for a period of time after concentration of drug drops below the MBC or MIC at site of infection
Definition
PAE post antibiotic effect
Term
On what aspect of infection does the post-antibiotic effect depend?
Definition
Depends on antimicrobial and specific bacterial species
Term
When dealing with severe infection or immunosuppressed pts, would a bacteriostatic or bactericidal agent be more effective?
Definition
*bactericidal*
Term
Combination antimicrobial therapy involves two or more agents with what characteristics?
Definition
two or more agents with different mechanisms of action
Term
When dealing with particularly resistant microbes, infections at sites that are difficult to reach, polymicrobial infections, or when it is necessary to decrease emergence of resistance, what type of antimicrobial therapy should be used?
Definition
Combination antimicrobial therapy
Term
What type of effect is desirable when using combination antimicrobial therapy?
Definition
synergism
Term
Do most antibacterial agents use time-dependent or concentration dependent mechanisms?
Definition
time-dependent
Term
A pt presents with an infection involving gram (+), gram (-), and anaerobic bacteria. What type of antimicrobial therapy is indicated?
Definition
combination antimicrobial therapy or broad-spectrum antibiotic
Term
A pt presents with a diabetic foot infection and intra-abdominal wound infection. What type of antimicrobial therapy is indicated?
Definition
combination antimicrobial therapy or broad-spectrum antibiotic
Term
What are 4 ways in which pathogens can be identified?
Definition
site of infection
gram stain
adequate culture
host factors
Term
Community, nosocomial (hospital), age, immune status are examples of what method of identifying pathogens?
Definition
host factors
Term
Disk diffusion, broth dilution, and Etest method test what?
Definition
susceptibility
Term
Regarding the inoculum effect, susceptibility testing is done on what?
Definition
Susceptibility testing done on standard concentration (inoculum) of bacterial isolate (10^5-10^6 bacteria per mL)
Term
Regarding the inoculum effect, actual infections may have greater or lower concentration than tests?
Definition
Actual infection (usually severe) may have greater concentration
Term
Regarding the inoculum effect, if the actual MIC at site of infection is much higher than reported by lab (as sometimes happens), what could result?
Definition
this could lead to antibiotic failure
Term
Do susceptibility reports usually list whether bacteria is sensitive or resistant to antibiotics tested, or do they usually report actual MIC for each antibiotic?
Definition
Usually susceptibility reports only list whether bacteria is sensitive or resistant to antibiotics tested; do not list actual MIC for each antibiotic
Term
Are bacteria usually reported as being sensitive to a single antibiotic or multiple antibiotics?
Definition
Usually bacteria is reported to be sensitive to multiple antibiotics
Term
In selecting an agent and dose is it more desirable to have a wide or narrow margin between achievable serum concentration and the MIC or MBC?
Definition
wide margin between achievable serum concentrations and the MIC or MBC
Term
Is it more desirable to select the most narrow or the broadest spectrum agent?
Definition
*Always try to select most narrow spectrum agent*
Term
Is the resistance seen in many bacterial species over the last 50 years of antibiotic era and example of acquired or intrinsic resistance?
Definition
Acquired resistance via gene transfer; a new 'gene pool' has been created
Term
Resistance of gram-negative bacteria to vancomycin is an example of what type of resistance?
Definition
intrinsic resistance
Term
Enteric bacterial resistance to penicillin is an example of what type of resistance?
Definition
intrinsic resistance
Term
Anaerobic bacterial resistance to aminoglycosides is an example of what type of resistance?
Definition
intrinsic resistance
Term
Experiments demonstrating multiple drug resistance processes involved newly hatched chickens fed how much oxytetracycline?
Definition
*subtherapeutic* amounts of oxytetracycline
Term
In the experiment demonstrating multiple drug resistant processes, what occurred in human intestinal E. coli of farm family members after 6 mos?
Definition
human intestinal E. coli now MDR (multi-drug resistant) although family not taking antibiotics or eating chickens. (Intestinal flora of control chickens and farm neighbors remained normal)
Term
According to Stuart Levy, MD, "Antibiotics are unique among pharmaceuticals in that they treat" who?
Definition
"populations as well as individuals. One's bacteria is not solely one's own. Rather they are shed, excreted, and otherwise spread into the environment, where they become part of a common pool."
Term
Regarding genetics of bacterial resistance, are point mutations on a chromosome a fast or slow process?
Definition
slow process
Term
Regarding genetics of bacterial resistance, is genetic transfer via plasmids a fast or slow process?
Definition
fast process
Term
Regarding genetics of bacterial resistance, is transfer of genetic information via transposons a fast or slow process?
Definition
very fast process
Term
What are strands of DNA with 100-300 genes that are able to duplicate and pass between cells of like or unlike species?
Definition
plasmids
Term
What effect involves differences in concentrations in vitro and in vivo samples?
Definition
inoculum effect
Term
What are small gene strands able to jump from chromosome to plasmid and from cell to cell?
Definition
transposon
Term
Where do multiple drug resistant (MDR) genes link together?
Definition
on the transposon
Term
What are the 3 mechanisms of antibiotic resistance?
Definition
1. Decreased drug entry into the cell
2. Inactivation of drug
3. Alteration of drug target site
Term
What mechanism of antibiotic resistance involves less penetration through porons and greater efflux of antibiotics from cell (tet M)?
Definition
decreased drug entry to cell
Term
What mechanism of antibiotic resistance involves beta-lactamase enzymes in periplasmic space and acetylating enzymes against aminoglycosides?
Definition
inactivation of drug
Term
What mechanism of antibiotic resistance involves penicillin binding proteins (PBP), ribosomes, and DNA gyrase?
Definition
alteration of drug target site
Term
Is an oral or parental route of administration safer?
Definition
oral is safest route
Term
Bioavailablity, drug/nutrient interactions preventing absorption, and GI irritability are limitations of what route of administration?
Definition
oral
Term
What is the fastest route of administration giving the highest concentrations?
Definition
parenteral
Term
Toxicity (including catheter infections), complexity of care, and cost are limitations of what route of administration?
Definition
parenteral
Term
What route of administration is ideal?
Definition
Ideally, use effective parenteral agent that can also be directy converted to oral form.
(some antibiotics can only be given parenterally or orally)
Term
Are high or low antibiotic concentrations expected in well-perfused tissues (plasma, mm, kidney, etc.)?
Definition
High antibiotic concentrations and successful treatment expected in well-perfused tissues (plasma, mm, kidney, etc.)
Term
Are high or low antimicrobial concentrations expected at infection sites not readily penetrated by most antimicrobials (bone, brain, prostate, abscesses, infected heart valves, etc.)?
Definition
Low antimicrobial concentrations and increased failure rates expected at infection sites not readily penetrated by most antimicrobials (bone, brain, prostate, abscesses, infected heart valves, etc.)
Term
What are 2 ways antimicrobials are excreted?
Definition
Some antimicrobials metabolized by liver while many are excreted unchanged through bile tract or kidney
Term
What is the relevance of the CYP 450 enzyme system for metabolism?
Definition
Some antimicrobials may induce or inhibit the metabolism of other drugs that depend on the CYP 450 enzyme system for metabolism.
Term
What condition requires adjustment of doses of antimicrobials that are renally excreted?
Definition
renal failure
Term
When treating lower UTIs, are drugs preferred that are excreted via the kidneys or the biliary tract?
Definition
renally excreted antimicrobials preferred
Term
Are drugs for UTIs generally given in higher or lower doses than drugs given for systemic infections?
Definition
Doses generally lower than for systemic infections due to high concentrations in the urine- reduces chances for toxicity
Term
Regarding toxicity, how must antimicrobial drugs be balanced?
Definition
Must balance enough dose to kill microbe at site of infection but not enough to be toxic to human cells
Term
What type of reactions to antimicrobial drugs is most common?
Definition
HSN rxn most commmon (sulfa, penicillin)
Term
Toxicity is usually related to what aspect of drugs?
Definition
dose of antimicrobial agent
Term
Phlebitis from parenteral agents, photosensitivity rxns, and GI intolerance result from what aspect of antimicrobial medications?
Definition
toxicity related to dose
Term
Is renal failure a side effect of drug toxicity?
Definition
Renal failure possible for select drugs
Term
What is defined as an infection secondary to use of broad spectrum agents over a period of time?
Definition
superinfection
Term
What are the most common superinfections?
Definition
fungal infections
Term
Hepatotoxicity and serum sickness are examples of what type of reaction to antimicrobial drugs?
Definition
idiosyncraic rxn
Term
What determines the choice of antimicrobial, dose, route, duration, and whether to use a combination regimen?
Definition
Type of infection
Term
What type of infections involve bacteria that have spread to multiple organ systems and involves a greater chance of sepsis?
Definition
systemic infection
Term
Fever, chills, hypotension, shock, organ failure secondary to production of endotoxins produced by bacteria are characteristic of what condition?
Definition
shock
Term
Do blood, brain, and bone infections require mild or aggressive treatment?
Definition
aggressive
Term
What condition is defined by an absolute neutrophil count (ANC) < 500/mL^3?
Definition
immuno-incompetence (can occur after chemo, with immunosuppresive drugs such as steroids or monoclonal Ab's)
Term
Advanced diabetics being more prone to infections is an example of what type of disease state?
Definition
concomitant disease state
Term
How do infected prosthesis (jt replacements, etc) usually need to be treated?
Definition
usually need to be removed- difficult to sterilize with antimicrobials
Term
How do infected catheters usually need to be treated?
Definition
Infected catheters need to be removed- difficult to sterilize (catheters provide entry site for surface bacteria)
Term
Is the acquisition cost of drugs an example of direct or indirect costs?
Definition
direct costs
Term
Do direct or indirect costs depend on the cost of individual unit and duration of therapy?
Definition
direct costs
(can range from pennies to thousands of dollars)
Term
Are labor costs for parenteral administration (nursing and pharmacy time, bags, tubing, infusion devices, etc) examples of indirect or direct costs?
Definition
indirect costs
Term
Are monitoring costs (chemistries, cultures, pharmacokinetic analysis, etc) examples of direct or indirect costs?
Definition
indirect costs
Term
Do adverse rxns cause direct or indirect costs?
Definition
indirect costs
Term
Drug resistance,
Drug selection,
Subtherapeutic dosing,
Monotherapy,
Poor penetration at site of infection, and Inadequate duration
should be considered to prevent what?
Definition
antimicrobial failure
Term
What type of therapy is used during dental and oral procedures to prevent endocarditis in pts with valvular heart disease?
Definition
prophylactic antibacterial therapy
Term
What type of therapy is used during surgical procedures to prevent systemic infection from bacteria on the skin or in the GI tract?
Definition
prophylactic therapy
Term
What type of therapy is used in prevention of infection during invasive procedures?
Definition
prophylactic therapy
Term
When should prophylactic antibacterial therapy be given?
Definition
*Give before procedure, not during!*
Term
What type of therapy is given to prevent disease transmission to close contacts of infected persons?
Definition
prophylactic antibacterial therapy (meningococcal infection, TB, influenza)
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