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M1 PDA Block 3 (Tim) > Antimicrobials I > Flashcards

Antimicrobials I Flashcards

1
Q

What are some important considerations in choosing what antibiotic to treat a bacterial infection?

A

What the organism is.

Where the infection is located.

The status of the host.

The risk:benefit of the drug.

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2
Q

All antimicrobials can be bacteriostatic and bacteriocidal. Why are some indicated as only bacteriostatic, then?

A

Some drugs cannot achieve the bactericidal concentration in the host (without toxic side effects).

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3
Q

In what contexts are bacteriocidal drugs preferred?

A

When the host is immunocompromised.

For infections of the heart valves, meninges, bone and surfaces of implanted devices.

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4
Q

Distinguish between the dosing guidelines for antimicrobials that are time-dependent, concentration dependent, or “area” dependent.

A

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.

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5
Q

What are some sources of antimicrobial resistance?

A

Intrinsic resistance (eg cell walls).

Mutations.

Gene transfer (eg plasmids).

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6
Q

β-lactams

Are they bacteriostatic or bacteriocidal?

What is their mechanism of action?

How are they resisted?

A

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).

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7
Q

Why may β-lactams cause fever and chills when given to ill patients?

How can the normal flora block the effect of β-lactams?

A

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.

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8
Q

Describe the dosing/killing pattern of β-lactams.

Describe their frequency of dosage.

A

They are time-dependent.

They have short half-lives, and so mut be dosed very often (except for ceftriaxone).

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9
Q

Describe the kinetics (ADME) of penicillins.

A

Penicillins distribute well (except for the CSF) and are renally eliminated (anion secretion). They are short-lived (30min-3hr).

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10
Q

Penicillin

Distinguish between penicillins G and V.

What bacterial infection are they indicated for?

A

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).

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11
Q

Describe the slow-release penicillins.

A

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.

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12
Q

Oxacillin

What class of drug is it?

What are its indications?

A

Oxacillin

It is a methicillin-type drug.

It is used (IV/IM) to treat certain strains of Staphylococcus Aureus (MSSA).

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13
Q

Ampicillin

How is it administered?

What are its indications?

A

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).

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14
Q

Amoxicillin

How is it administered?

What are its indications?

A

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.

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15
Q

Ticarcillin

How is it administered?

What are its indications?

A

Ticarcillin

It is an injectable.

Good for G+, some anaerobes, and a decent range of G- (especially pseudomonas aeruginosa).

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16
Q

Piperacillin

How is it administered?

What are its indications?

A

Piperacillin

It is an injectable.

It is good against G+, some anaerobes, and several G- (Pseudomonas and Klebsiella). Useful for ticarcillin-resistant infections.

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17
Q

Describe the most common hypersensitivity seen with penicillins.

How can you screen for serious penicillin allergies?

Which penicillins are most prone to hypersensitivity?

A

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).

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18
Q

What side effects are seen with penicillins?

A

Fever (probably from bacterial lysis)

GI upset (probably from gut flora disturbance)

Enterocolitis (from C. Difficile)

Elevated liver enzymes

Hemolytic anemia

Seizures

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19
Q

β-lactamase inhibitors

Name two examples.

What is their mechanism of action?

Name two example combinations.

A

β-lactamase inhibitors

Clavulanic acid and tazobactam.

Irreversibly bind to β-lactamases to restore β-lactam function.

Amoxicillin+Clavulanate, Piperacillin+Tazobactam

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20
Q

Cephalosporins

What is their mechanism of action?

Describe their kinetics and routes of administration.

How are they resisted?

A

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.

21
Q

Cephalosporins

How are they metabolized and excreted?

What are their side effects?

A

Cephalosporins

Renal secretion via anion transporter, like the penicillins.

Allergic reaction (cross-reactive with penicillins), GI upset, liver damage and enterocolitis.

22
Q

Cefazolin

What class of drug is it?

How is it administered?

What are its indications?

What is its half-life?

A

Cefazolin

1st Generation Cephalosporin.

IV/IM injection.

Generally, gram-positive skin infections (also surgical prophylaxis).

1-2 hours.

23
Q

Cephalexin

What class of drug is it?

How is it administered?

What are its indications?

What is its half-life?

A

Cephalexin

1st Generation Cephalosporin.

Oral administration.

Mostly gram-positive skin infections, also bone/joint/UTI/respiratory/OM.

About 1 hour.

24
Q

Cefuroxime

What class of drug is it?

What are its indications?

A

Cefuroxime

2nd Generation Cephalosporin.

Bacterial meningitis (Haemophilus), but not enteric bacteria. Decent G+ and G- coverage, and CSF penetrating!

25
Q

Cefoxitin

What class of drug is it?

What are its indications?

A

Cefoxitin

2nd Generation Cephalosporin.

Useful against G+ and G-, and anaerobes (including Bacteroides).

26
Q

Ceftriaxone

What class of drug is it?

What are its indications?

What is its half-life?

A

Ceftriaxone

3rd Generation Cephalosporin

Good for bacterial meningitis, gonorrhea, and lyme disease. Gram-negatives in general.

6-9 hours, very long for a cephalosporin!

27
Q

Ceftazidime

What class of drug is it?

How is it administered?

What is its half-life?

A

Ceftazidime

3rd Generation Cephalosporin.

Very active against Pseudomonas Aeruginosa. G- in general at the expense of G+ coverage.

Short-ish (90min).

28
Q

What do the “generations” of cephalosporins represent?

A

Increasing G- targeting. This comes at the expense of G+ efficacy (4th gen is OK, though)

29
Q

Cefepine

What class of drug is it?

What is its route of administration?

What are its indications?

What is its half-life?

A

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.

30
Q

What drugs are (GENERALLY) effective against ESBL-expressing bacteria?

A

Carbapenems.

31
Q

Imipenem

What are its indications?

What is its route of administration?

How can its half-life be extended?

What are its side effects?

A

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.

32
Q

Aztreonam

What class of drug is it?

How is it administered?

What are its indications?

What are its side effects?

A

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?

33
Q

Vancomycin

What is its mechanism of action?

What are its indications?

How is it administered?

A

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).

34
Q

Vancomycin

Which organisms are demonsrating resistance?

How is it used against bacterial meningitis?

What are its side effects?

A

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.

35
Q

Fosfomycin

What is its mechanism of action?

What are its indications?

What are its side effects?

A

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.

36
Q

Bacitracin

What is its mechanism of action?

How is it administered?

What are its indications?

What are its side effects?

A

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.

37
Q

Polymyxin B

What is its mechanism of action?

How is it administered?

What are its indications?

What are its side effects?

A

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.

38
Q

Daptomycin

What is its mechanism of action?

How is it administered?

What are its indications?

What are its side effects?

A

Daptomycin

Depolarizes bacteria membranes.

IV.

Skin and blood infections due to gram-positives. NOT pneumonia.

GI upset, muscle damage, fever/headache/rash/dizziness etc…

39
Q

Quinolones

What is their mechanism of action?

How are they administered?

By what metric do we measure their killing?

A

Quinolones

Inhibition of bacterial DNA gyrase and topoisomerase.

Oral and IV.

AUC/MIC (area under curve).

40
Q

Quinolones

What are their side effects?

A

Quinolones

Nausea, vomiting, abdominal pain and enterocolitis.

Dizziness, headache, restlessness & depression.

Rashes and photosensitivity (serious)

Long QT syndrome.

Seizures and neuropathy.

Tendon rupture.

41
Q

Quinolones

What are their contraindications?

A

Quinolones

Not for those prone to seizures, pregnant women, or children with mild infections.

42
Q

Norfloxacin

What are its indications?

A

Norfloxacin

Previously used for urinary infections. Less so now due to resistances.

43
Q

Ciprofloxacin

What are its indications?

A

Ciprofloxacin

UTIs, infectious diarrhea, respiratory infections, bone/joint/skin infections. Chlamydia, and formerly gonorrhea.

Not great for gram-positives.

44
Q

Moxifloxacin

What are its indications?

A

Moxifloxacin

Gram-positive infections, especially respiratory pneumonias and bronchitis.

Not strep throat.

45
Q

Nitrofurantoin

What is its mechanism of action?

What are its indications?

What are its side effects?

A

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).

46
Q

Rifampin

What is its mechanism of action?

What are its indications?

What are its side effects?

A

Rifampin

Inhibition of bacterial RNA pol II. Bactericidal.

For TB, and prophylaxis of meningitis (neisseria/Hib)

Hepatotoxicity, strong CYP induction, orange fluids.

47
Q

Fidaxomicin

What is its mechanism of action?

What are its indications?

What are its side effects?

A

Fidaxomicin

Non-competitive inhibitor of bacterial RNA pol. (bactericidal, like rifampin)

C. Difficile, a few other G+.

GI upset/bleeding, neutropenia.

48
Q

Metronidazole

What is its mechanism of action?

What are its indications?

What are its side effects?

A

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.

49
Q

What are the treatment options in C. Difficile enterocolitis?

A

Metronidazole (mild)

Vancomycin (moderate)

Metronidazole+Vancomycin (severe)

Fidaxomicin

M1 PDA Block 3 (Tim) (13 decks)

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