Antimicrobials I Flashcards
(49 cards)
What are some important considerations in choosing what antibiotic to treat a bacterial infection?
What the organism is.
Where the infection is located.
The status of the host.
The risk:benefit of the drug.
All antimicrobials can be bacteriostatic and bacteriocidal. Why are some indicated as only bacteriostatic, then?
Some drugs cannot achieve the bactericidal concentration in the host (without toxic side effects).
In what contexts are bacteriocidal drugs preferred?
When the host is immunocompromised.
For infections of the heart valves, meninges, bone and surfaces of implanted devices.
Distinguish between the dosing guidelines for antimicrobials that are time-dependent, concentration dependent, or “area” dependent.
Time-dependent drugs should be held at about 4x MIC for a given duration.
Concentration-dependent drugs should be applied at the highest safe concentration, generally 8x MIC.
Killing dependent on both time and concentration should be dosed to maximize the area under the dosing curve. 125 “hours” is suggested for gram-negatives, 40 for gram positives.
What are some sources of antimicrobial resistance?
Intrinsic resistance (eg cell walls).
Mutations.
Gene transfer (eg plasmids).
β-lactams
Are they bacteriostatic or bacteriocidal?
What is their mechanism of action?
How are they resisted?
β-lactams
They are bactericidal.
They bind to and inhibit PBP, depriving cells of their cell wall and causing osmotic lysis.
With β-lactamases, altered PBPs, or exclusion (eg gram-negative outer membrane).
Why may β-lactams cause fever and chills when given to ill patients?
How can the normal flora block the effect of β-lactams?
The lysis of bacteria due to the action of β-lactams releases matter that can increase fever, chills, and aching.
Since β-lactamases act extracellularly, a bacterium that produces it may shield microorganisms nearby it.
Describe the dosing/killing pattern of β-lactams.
Describe their frequency of dosage.
They are time-dependent.
They have short half-lives, and so mut be dosed very often (except for ceftriaxone).
Describe the kinetics (ADME) of penicillins.
Penicillins distribute well (except for the CSF) and are renally eliminated (anion secretion). They are short-lived (30min-3hr).
Penicillin
Distinguish between penicillins G and V.
What bacterial infection are they indicated for?
Penicillin
Penicillin G is a natural product and is only available as IV/IM. Penicillin V is more acid-stable so it is orally available.
It is generally good against Gram-positives, especially strep. It can be used for spirochetes and anaerobes (except bacteroides), and it may be used in a few Gram-negatives (Neisseria).
Describe the slow-release penicillins.
Procaine/benzathine penicillin G are IM injections that allow for slow and steady release. This facilitates a steady plasma concentration despite the short half-life.
Oxacillin
What class of drug is it?
What are its indications?
Oxacillin
It is a methicillin-type drug.
It is used (IV/IM) to treat certain strains of Staphylococcus Aureus (MSSA).
Ampicillin
How is it administered?
What are its indications?
Ampicillin
Available in IV and oral formulations.
Like amoxicillin, it is used against gram-positives as well as gram-negatives. Unlike amoxicillin, it is indicated for meningitis (neisseria/listeria) and GI infections (shigella).
Amoxicillin
How is it administered?
What are its indications?
Amoxicillin
Oral dosing.
Like ampicillin, it is used against gram-positives as well as gram-negatives. Unlike ampicillin, it is the #1 treatment for Otitis media, and is an alternative treatment for Lyme disease.
Ticarcillin
How is it administered?
What are its indications?
Ticarcillin
It is an injectable.
Good for G+, some anaerobes, and a decent range of G- (especially pseudomonas aeruginosa).
Piperacillin
How is it administered?
What are its indications?
Piperacillin
It is an injectable.
It is good against G+, some anaerobes, and several G- (Pseudomonas and Klebsiella). Useful for ticarcillin-resistant infections.
Describe the most common hypersensitivity seen with penicillins.
How can you screen for serious penicillin allergies?
Which penicillins are most prone to hypersensitivity?
Most patients that are allergic just exhibit a rash.
“PRE-PEN” is a skin test that can identify serious penicillin allergies.
Natural penicillins appear to have higher reactivity (than synthetics).
What side effects are seen with penicillins?
Fever (probably from bacterial lysis)
GI upset (probably from gut flora disturbance)
Enterocolitis (from C. Difficile)
Elevated liver enzymes
Hemolytic anemia
Seizures
β-lactamase inhibitors
Name two examples.
What is their mechanism of action?
Name two example combinations.
β-lactamase inhibitors
Clavulanic acid and tazobactam.
Irreversibly bind to β-lactamases to restore β-lactam function.
Amoxicillin+Clavulanate, Piperacillin+Tazobactam
Cephalosporins
What is their mechanism of action?
Describe their kinetics and routes of administration.
How are they resisted?
Cephalosporins
Same as the other β-lactams: PBP binding.
They have good distribution (except to the CSF, generally) and are often injected (some oral).
Same as the other β-lactams: β-lactamase and PBP-alterations.
Cephalosporins
How are they metabolized and excreted?
What are their side effects?
Cephalosporins
Renal secretion via anion transporter, like the penicillins.
Allergic reaction (cross-reactive with penicillins), GI upset, liver damage and enterocolitis.
Cefazolin
What class of drug is it?
How is it administered?
What are its indications?
What is its half-life?
Cefazolin
1st Generation Cephalosporin.
IV/IM injection.
Generally, gram-positive skin infections (also surgical prophylaxis).
1-2 hours.
Cephalexin
What class of drug is it?
How is it administered?
What are its indications?
What is its half-life?
Cephalexin
1st Generation Cephalosporin.
Oral administration.
Mostly gram-positive skin infections, also bone/joint/UTI/respiratory/OM.
About 1 hour.
Cefuroxime
What class of drug is it?
What are its indications?
Cefuroxime
2nd Generation Cephalosporin.
Bacterial meningitis (Haemophilus), but not enteric bacteria. Decent G+ and G- coverage, and CSF penetrating!
