Antimicrobials I Flashcards
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!
Cefoxitin
What class of drug is it?
What are its indications?
Cefoxitin
2nd Generation Cephalosporin.
Useful against G+ and G-, and anaerobes (including Bacteroides).
Ceftriaxone
What class of drug is it?
What are its indications?
What is its half-life?
Ceftriaxone
3rd Generation Cephalosporin
Good for bacterial meningitis, gonorrhea, and lyme disease. Gram-negatives in general.
6-9 hours, very long for a cephalosporin!
Ceftazidime
What class of drug is it?
How is it administered?
What is its half-life?
Ceftazidime
3rd Generation Cephalosporin.
Very active against Pseudomonas Aeruginosa. G- in general at the expense of G+ coverage.
Short-ish (90min).
What do the “generations” of cephalosporins represent?
Increasing G- targeting. This comes at the expense of G+ efficacy (4th gen is OK, though)
Cefepine
What class of drug is it?
What is its route of administration?
What are its indications?
What is its half-life?
Cefepine
4th Generation Cephalosporin.
IV.
Similar applications as gen III (ceftazidime), but more resistant to β-lactamases and better against G+. For serious inpatient infections.
2hrs.
What drugs are (GENERALLY) effective against ESBL-expressing bacteria?
Carbapenems.
Imipenem
What are its indications?
What is its route of administration?
How can its half-life be extended?
What are its side effects?
Imipenem
For mixed, ill-defined, and strongly resistant infections (last-line). Broad-spectrum.
IV.
Coadminister with cilastatin (block renal dipeptidase hydrolysis).
Allergic reaction (cross with penicillins, cephalosporins), GI upset, seizures/dizziness/confusion.
Aztreonam
What class of drug is it?
How is it administered?
What are its indications?
What are its side effects?
Aztreonam
It is a monobactam.
IM/IV.
Useful against G- aerobic rods, especially ESBL-expressing ones. Not labeled for meningitis.
Seizures, anaphylaxis, GI upset. Transient EKG changes?
Vancomycin
What is its mechanism of action?
What are its indications?
How is it administered?
Vancomycin
It inhibits cell wall synthesis by binding D-ala-D-ala and stopping cross-linking.
Used against serious infections by gram-positives (MRSA, Strep Pneumoniae, Enterococcus) and C. Difficile.
IV (oral for C. Difficile).
Vancomycin
Which organisms are demonsrating resistance?
How is it used against bacterial meningitis?
What are its side effects?
Vancomycin
Strep and Enterococcus (passed along resistance to MRSA >> VRSA)
In combination with cephalosporin for unidentified adult meningitis.
“Redman syndrome” (histamine release), Nephrotoxicity, Ototoxicity, Phlebitis at site of administration.
Fosfomycin
What is its mechanism of action?
What are its indications?
What are its side effects?
Fosfomycin
Targets enolpyruvyl transferase to stop muramic acid production (inhibits cell wall synthesis).
UTIs caused by E. Coli and Enterococcus.
Mild headache, GI upset, vaginitis, rash.
Bacitracin
What is its mechanism of action?
How is it administered?
What are its indications?
What are its side effects?
Bacitracin
Blocks the lipid carrier involved in cell wall synthesis.
Topical only–too toxic for systemic.
Gram-positive skin infections (Staph/Strep).
Just allergic dermatitis in the topical form.
Polymyxin B
What is its mechanism of action?
How is it administered?
What are its indications?
What are its side effects?
Polymyxin B
It is a detergent that binds LPS to disrupt the membrane.
USUALLY topical, but also IV/IM, ophthalmic…
Gram-negative bacteria (binds LPS!), eg Pseudomonas.
Possible dermatitis if topical. If systemic, nephrotoxicity/neurotoxicity.
Daptomycin
What is its mechanism of action?
How is it administered?
What are its indications?
What are its side effects?
Daptomycin
Depolarizes bacteria membranes.
IV.
Skin and blood infections due to gram-positives. NOT pneumonia.
GI upset, muscle damage, fever/headache/rash/dizziness etc…
Quinolones
What is their mechanism of action?
How are they administered?
By what metric do we measure their killing?
Quinolones
Inhibition of bacterial DNA gyrase and topoisomerase.
Oral and IV.
AUC/MIC (area under curve).
Quinolones
What are their side effects?
Quinolones
Nausea, vomiting, abdominal pain and enterocolitis.
Dizziness, headache, restlessness & depression.
Rashes and photosensitivity (serious)
Long QT syndrome.
Seizures and neuropathy.
Tendon rupture.
Quinolones
What are their contraindications?
Quinolones
Not for those prone to seizures, pregnant women, or children with mild infections.
Norfloxacin
What are its indications?
Norfloxacin
Previously used for urinary infections. Less so now due to resistances.
Ciprofloxacin
What are its indications?
Ciprofloxacin
UTIs, infectious diarrhea, respiratory infections, bone/joint/skin infections. Chlamydia, and formerly gonorrhea.
Not great for gram-positives.
Moxifloxacin
What are its indications?
Moxifloxacin
Gram-positive infections, especially respiratory pneumonias and bronchitis.
Not strep throat.
Nitrofurantoin
What is its mechanism of action?
What are its indications?
What are its side effects?
Nitrofurantoin
Conversion by nitroreductase in bacteria to generate DNA-damaging free radicals.
Lower UTIs.
Here we go: NV/diarrhea, hypersensitivity, fevers/chills, neuropathy, and pulmonary reactions (fibrosis, worse in the elderly), liver toxicity, various anemias (granulocyto, leuko, megaloblastic, hemolytic with G6PDH deficiency).
Rifampin
What is its mechanism of action?
What are its indications?
What are its side effects?
Rifampin
Inhibition of bacterial RNA pol II. Bactericidal.
For TB, and prophylaxis of meningitis (neisseria/Hib)
Hepatotoxicity, strong CYP induction, orange fluids.
Fidaxomicin
What is its mechanism of action?
What are its indications?
What are its side effects?
Fidaxomicin
Non-competitive inhibitor of bacterial RNA pol. (bactericidal, like rifampin)
C. Difficile, a few other G+.
GI upset/bleeding, neutropenia.
Metronidazole
What is its mechanism of action?
What are its indications?
What are its side effects?
Metronidazole
Reduction by anaerobes to form DNA-damaging free radicals.
Anaerobes (C.Diff/Bacteroides), H. Pylori, Gardnerella, Trichinosis.
NV/diarrhea, anorexia, transient leuko/neutropenia, thrombophlebitis, bacterial/fungal superinfection, and mild ethanol intolerance.
What are the treatment options in C. Difficile enterocolitis?
Metronidazole (mild)
Vancomycin (moderate)
Metronidazole+Vancomycin (severe)
Fidaxomicin
