Treatment of Bacterial Lung Infections

Question 1

Treatment of Pneumonia caused by Legionella

Answer 1

• Erythromycin is the only one labelled for use.
• More commonly is Azithromycin or Clarithromycin plus a respiratory quinolone such as Levofloxacin.
• *For very ill patients, use Rifampin.

Question 2

Drugs for CAP

Answer 2

Macrolides, Tetracyclines, Fluoroquinolones, Penicillins, Carbopenems, Cephalosporins, Aminoglycosides

Question 3

Macrolides

Answer 3

• “mycins”
• 50s ribosomal inhibitor that blocks transcription.
• Erythromycin, Azithromycin, Clarithromycin

Question 4

Tetracyclines

Answer 4

“cyclines”

• 30s ribosomal inhibitor blocking protein synthesis.
• Doxycycline

Question 5

Fluoroquinolones

Answer 5

“floxacins”

• DNA gyrase inhibitor preventing DNA replication.
• Levofloxacin

Question 6

Penicillins

Answer 6

“cillins”

• blocks cell wall synthesis by inhibiting PBP
• Axoicillin + Clavulanic Acid (Augmentin)
• Pipercillin +Tazobactam (Zosyn)

Question 7

Carbopenem

Answer 7

• Blocks cell wall cross linking

* Meropenem

Question 8

Cephalosporins

Answer 8

“cefs” or “cephs”

• Inhibits cell wall cross linking
• Cefazolin
• Cefuroxime
• Cefatriaxone or Cefepime (anti pseudomonal activity)

Question 9

Aminoglycosides

Answer 9

• 30s ribosomal inhibitor

* Gentamicin

Question 10

Mechanism of Resistance for the Macrolides

Answer 10

Ribosomal methylation and mutation of the 23s rRNA.

Active reflux.

Question 11

Tetracyclines

Answer 11

Decreased entry into and increased efflux.

Target insensitivity.

Question 12

Fluoroquinolones

Answer 12

Mutation of DNA gyrase.

Active efflux.

Question 13

Penicillins

Answer 13

Beta lactamases.

Altered PBP’s

Question 14

Cephalosporins

Answer 14

Decreased permeability of gram negative outer membrane.

Active efflux.

Question 15

Aminoglycosides

Answer 15

Drug inactivation.
Decreased permeability of gram negative outer membrane.
Active efflux.
Ribosomal methylation.

Question 16

Nosocomial Pneumonia

Answer 16

Usually Gram negative organisms.

• Indicated: Impinem/Cilastin, Azotrenam, Ceftazidime
• Alternative: Meropenem, Pip/Tazo, Cefepime
• *Vancomycin can be given IV in worse case scenario.
• *Meropenem has less side effects than Impinem.
• *Cefepime is 4th gen and can work when Ceftazidime.

Question 17

Aspiration Pneumonia

Answer 17

Usually gram negative bacilli.

• Indicated: Clindamycin
• Alternative: Ampicillin/ Sulfabactam

Question 18

Clindamycin MOA and Resistance

Answer 18

MOA: 50s ribosomal inhibitor blocking translocation.
Resistance: Methylation of binding site, enzymatic inactivation.

Question 19

Vancomycin MOA and Resistance

Answer 19

MOA: Binds D-alanyl-D-alanine terminus of peptide precursor units, inhibiting peptidoglycan polymerase and transpeptidation reactions.
Resistance: Replacement od D-ala by D-lactate

Question 20

What is the problem with using serum levels for drug safety measurements?

Answer 20

Apart from interstitial tissue, serum levels do not mirror levels of the drug in the tissue. Therefore, some microbes may benefit from pharmacological sanctuary due to things such as poor penetration, prevailing pH, or local factors leading to increased rates of drug inactivation.
**Because of this drugs should be categorized as concentration dependent of time dependent.

Question 21

Time above MIC

Answer 21

Penicillins, Cephalosporins, Carbapenems

Question 22

24hr AUC/MIC

Answer 22

AMinoglycosides, Fluoroquinolones, Tetracyclines, Vancomycins, MAcrolides, Clindamycin

Question 23

Peak/MIC

Answer 23

Aminoglycosides, Fluoroquinolones

Question 24

Drugs with Renal Elimination

Answer 24

**Adjustment need when renal impairment present. 
"Aunt Annie Can Clearly C Gentlemen In Lovely Plaid Vests"
Amoxicillin
Ampicillin
Cefazolin 
Cefapime
Cefatrazidime
Gentamicin
Impinem
Levofloxacin
Piperacillin
Vancomycin

Question 25

Drugs with Biliary Elimination

Answer 25

**No adjustment needed for renal impairment. "No ADE is required if the liver does the work" Azithromycin Doxycycline Erythromycin

Question 26

Drugs with dual renal and biliary elimination

Answer 26

Cefatriaxone Clindamycin Meropenem (adjustment required in renal impairment)

Question 27

Toxicity of Amoxicillin and Ampicillin

Answer 27

Cross reactivity with penicillin allergy GI Distress Maculopapular Rash

Question 28

Toxicity of Azithromycin

Answer 28

Cholestatic jaundice. | ***QT prolongation.

Question 29

Toxicity of the Cephalosporins

Answer 29

``` Cross-reactivity across the whole class and partial with penicillin allergy. **Cefatriaxone causes GI distress. ```

Question 30

Toxicity of Clindamycin

Answer 30

GI Distress

Question 31

Toxicity of Doxycycline

Answer 31

GI Distress **Teeth discoloration. Photosensitivity Decreased bone growth.

Question 32

Toxicity of Erythromycin

Answer 32

* *CYP3A4 inhibitor. * *Jaundice. * *QT Prolongation.

Question 33

Toxicity of Gentamicin

Answer 33

Nephrotoxicity **Ototoxicity Neuromuscular paralysis

Question 34

Toxicity of Impinem

Answer 34

Partial cross reactivity with pen/ceph allergies. | *Seizures.

Question 35

Toxicity of Levofloxacin

Answer 35

* Tendon rupture in adults | * Cartilage damage in young children

Question 36

Toxicity of Linezolid

Answer 36

Bone marrow suppression. | **Non-specific MAO inhibitor

Question 37

Toxicity of Meropenem

Answer 37

Partial cross reactivity with pen/ceph allergy. | *Seizures.

Question 38

Toxicity of Piperacillin.

Answer 38

Partial cross reactivity with ceph hypersensitivity. | **Decreased coagulation.

Question 39

Toxicity of Vancomycin

Answer 39

Nephrotoxic *Ototoxic "Red Man's" Syndrome

Question 40

Augmentin

Answer 40

Amoxicillin + Clavulanic Acid

Question 41

Zosyn

Answer 41

Piperacillin + Tazobactam

Question 42

Unasyn

Answer 42

Ampicillin + Sulbactam

Question 43

Primaxin

Answer 43

Impinem + Cilastin

Question 44

Should Daptomycin be used to treat pneumonia??

Answer 44

NO!

Question 45

Treatment of Bronchitis

Answer 45

* Mostly viral in young * Bacterial more common in older patients or those with comorbities. * Indicated: Augmentin, Azithromycin, Clarithromycin, Doxycycline * If resistance is present, us Ciprofloxacin. * *If very severe, doxy and cipro may be used IV.

Question 46

Treatment of Lung Abscesses

Answer 46

* Clindamycin (superior to penicillin against becteroides) * Metronidazole + Ceftriaxone (for nosocomial infections) * *Metronidazole should not be used alone due to incomplete coverage.

Question 47

Should you wait to treat?

Answer 47

NO. Earlier is better.

Question 48

What is the usual course of therapy?

Answer 48

IF bad enough, can start on IV and transition to oral as improvement is seen.

Question 49

Best Treatment for CAP?

Answer 49

``` A macrolide (azithromycin) or quinolone (levofloxacin) is first choice. Augmentin can also be used. ```

Question 50

How do you approach a nosocomial infection?

Answer 50

First treat with broad spectrum and then tailor once the infective agent is known.

Question 51

How do you approach treatment for abscess or aspiration pneumonia?

Answer 51

Treat for oral anaerobes.