Drugs for CAP, VAP, and HAP (Wolff)

Question 1

What are the 2 MOAs of Fluoroquinolones and which Gram bacteria is each important for?

Answer 1

1. inhibits DNA gyrase
   
   • good for Gram NEGATIVE bacteria
   • also active against Pseudomonas
2. inhibits Topo IV
   
   • good for Gram POSITIVE bacteria
   • usually targeted by respiratory fluoroquinolones

Question 2

What is the treatment regimen for a patient that is NOT penicillin allergic vs a patient that is penicillin allergic?

Answer 2

Not allergic: amoxicillin + macrolide or doxycycline

Allergic: cephalosporins + macrolide or doxycycline

• third generation cephalosporins
• if allergic? –? use fluoroquinolone or lefamulin

Question 3

Amoxicillin + clavulanate

What is its MOA, what is it used for, what is it NOT active against, how is it administered, and what pts should NOT receive it (IM)?

Answer 3

MOA: amoxicillin inhibits bacterial cell wall synth by binding to PBPs (blocks final step of cell wall synthesis) and clavulanate inhibits beta-lactamases

• used for Gram (+) and Gram (-), but NOT active against Pseudomonas (CAP)
• oral drugs with 1-1.5 hr half-life

CI: do NOT use in patients with Infectious Mononucleosis

Question 4

Piperacillin + tazobactam

What is its MOA, what is it used for (3), what is it active against that Amoxicillin + clavulanate is NOT, and how is it administered?

Answer 4

MOA: piperacillin inhibits bacterial cell wall synthesis by binding to PBPs (blocks final step of cell wall synthesis) and tazobactam inhibits beta-lactamases

• used for Gram (+) and Gram (-) aerobic/anaerobic bacteria (CAP/HAP/VAP) and IS ACTIVE against Pseudomonas
• IV drug with 1 hr half-life

Question 5

What are 2 commonly used PARENTERAL cephalosporins and what are 2 commonly used ORAL cephalosporins?

Answer 5

Parenteral: ceftriaxone (3rd generation) and cefepime (4th generation)

Oral: cefditoren, cefpodoxime-proxetil (3rd generation)

Question 6

Cefpodoxime and Cefditoren

What is their MOA, what are they active against, how are they administered, and what are two major toxicities of use (BLA/SI)?

Answer 6

MOA: inhibits bacterial cell wall synthesis by binding to PBP and inhibiting the final step in cell wall synthesis

• active against Gram (+) and Gram (-) bacterial and is stable in presence of beta-lactamases (CAP)
• administered ORALLY, with 2-3 hr and 1.6 hr half-lives that are inc. with dec. renal function (also have multiple drug interactions)

T: beta-lactam allergy and superinfection

Question 7

Doxycycline (Tetracycline)

What is its MOA, what bacteria does it target and what is an example, and what is a major toxicity with use in children?

What drugs should Tetracyclines NOT be used with and why?

Answer 7

MOA: binds to 30s subunit of bacterial ribosome and interferes with tRNA delivery = slows the growth of peptide chain (BACTERIOSTATIC)

• targets bacteria that LACK cell walls (Mycoplasma pneumonia) and is used for CAP

T: young children will have stained developing teeth (looks dark gray)

**should NOT be used with bactericidal drugs (penicillins) as bactericidal drugs kill new cells while bacteriostatic slow down growth

Question 8

Macrolides

What is their MOA, what are 3 commonly used drugs of this family (A/C/E), and what are they effective against (2)?

What are these drugs NOT useful against?

Answer 8

MOA: bacteriostatic antibiotics that bind to the 50s subunit and block peptide chain elongation

Drugs: Azithromycin, Clindamycin, Erythromycin

• used for Gram (+) aerobic/anaerobic bacteria and atypical CAP organisms (Legionella, Mycoplasma, Mycobacteria, chlamydia)
  
  • NOT usually effective against Gram (-)

Question 9

Macrolides

How do erythromycin, clarithromycin, and azithromycin effect cytochrome P450 and how do they effect the GI system?

Answer 9

E: inhibitor of cytochrome P450 metabolism
- generally safe but DOES cause epigastric pain

C: inhibitor of cytochrome P450 metabolism
- LESS GI disturbances

A: NOT an inhibitor of cytochrome P450 metabolism
- concentrates in phagocytes which slowly release bacteriostatic lvls

Question 10

Fluoroquinolones

What are 3 drugs of this family (L/G/M), what is it used for, what two drugs is it more effective than (T/M), and what is a major toxicity that can be seen with use?

Answer 10

Drug: levofloxacin (3rd gen) and gemifloxacin/moxifloxacin (4th gen)

• used for Gram (-) and Gram (+) bacteria
• more effective than Tetracycline an Macrolides for pneumonia, but should be reserved to minimize appearance of tolerance

T: can cause TENDON RUPTURE (achilles most common) in children, elderly, and anyone else stressing their tendons

Question 11

Vancomycin

What 3 things is it commonly used for and what is a major toxicity of use (RMS)?

Answer 11

• given IV for serious infections by organisms RESISTANT to penicillins (MRSA and MRSE) or in pts with Penicillin allergies AND can be used to treat C. difficile that is UNRESPONSIVE to metronidazole

T: Red Man Syndrome

Question 12

Linezolid

What is its MOA, what is it used for (2), how is it administered, what enzyme does it inhibit (MO), and what are 3 toxicities of use (T/ON/SS)?

What drug class is it in? (O)

Answer 12

MOA: OXAZOLIDINONE ABX binds to ribosomal A site to prevent tRNA binding that inhibits translation at first step of protein synthesis initiation (prevents 70s complex formation)

• used for Gram (+) including VRE and MRSA (both CAP and VAP)
• given orally or IV with 5 hr half-life and inhibits MONOAMINE OXIDASE (many drug interactions)

T: thrombocytopenia, optic neuropathy, serotonin syndrome

Question 13

Azetreonam

What is its MOA, what is it used for, how is it administered, and what are 2 toxicities of use (HS/SI)?

What drug class is it in? (MB)

Answer 13

MOA: MONOBACTAM that inhibits bacterial wall synthesis by binding to PBPs, inhibiting the last step of bacterial cell wall synthesis
- structure makes cross-allergenicity with beta-lactams unlikely

• used for Gram (-) bacteria including Pseudomonas but is NOT USEFULLY for Gram (+)
• given IM or IV with 1-2 hr half-life

T: hypersensitivity and superinfection

Question 14

Imipenem

What is its MOA, what is it used for, how is it administered, and what are 3 toxicities of use (HS/SI/CNS)?

What drug class is it in? (C)

Answer 14

MOA: CARBAPENEM that inhibits bacterial cell wall synthesis by binding to PBPs, inhibiting the final step of bacterial cell wall synthesis

• WIDE SPECTRUM of antibacterial activity to Gram (-) and Gram (+) aerobic/anaerobic bacteria AND against many MULTIRESISTANT strains (lower respiratory tract infections)
• administered IV with 1 hr half-life

T: hypersensitivity, superinfection, CNS problems

Question 15

Gentamicin

What is its MOA, what is it used for, how is it administered, and what are 2 major toxicities for use (N/O)?

What drug class is it in? (A)

Answer 15

MOA: AMINOGLYCOSIDE ABX that binds to 30s subunit of bacterial ribosome, causing misreading of tRNA that inhibits protein synthesis

• used mainly Gram (-) bacteria but also for Gram (+) Staphylococcus
• administered IM or IV with 2 hr half-life that can be extended to 40 hrs with renal failure

T: nephrotoxicity and ototoxicity

Question 16

What drug, originally used as first choice for aspiration pneumonia, is strongly linked to C. difficile colitis?

Answer 16

CLINDAMYCIN

Question 17

What are 6 organisms that commonly give rise to antibiotic resistance due to post-translational modification? (E/S/K/A/P/E)

Answer 17

E - E. coli
S - Staphylococcus
K - Klebsiella pneumoniae
A - Acintobacter
P - Pseudomonas aeruginosa
E - Enterococcus faecalis/faecium