Treatment of Bacterial Lung Infections Flashcards
Treatment of Pneumonia caused by Legionella
- 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.
Drugs for CAP
Macrolides, Tetracyclines, Fluoroquinolones, Penicillins, Carbopenems, Cephalosporins, Aminoglycosides
Macrolides
- “mycins”
- 50s ribosomal inhibitor that blocks transcription.
- Erythromycin, Azithromycin, Clarithromycin
Tetracyclines
“cyclines”
- 30s ribosomal inhibitor blocking protein synthesis.
- Doxycycline
Fluoroquinolones
“floxacins”
- DNA gyrase inhibitor preventing DNA replication.
- Levofloxacin
Penicillins
“cillins”
- blocks cell wall synthesis by inhibiting PBP
- Axoicillin + Clavulanic Acid (Augmentin)
- Pipercillin +Tazobactam (Zosyn)
Carbopenem
- Blocks cell wall cross linking
* Meropenem
Cephalosporins
“cefs” or “cephs”
- Inhibits cell wall cross linking
- Cefazolin
- Cefuroxime
- Cefatriaxone or Cefepime (anti pseudomonal activity)
Aminoglycosides
- 30s ribosomal inhibitor
* Gentamicin
Mechanism of Resistance for the Macrolides
Ribosomal methylation and mutation of the 23s rRNA.
Active reflux.
Tetracyclines
Decreased entry into and increased efflux.
Target insensitivity.
Fluoroquinolones
Mutation of DNA gyrase.
Active efflux.
Penicillins
Beta lactamases.
Altered PBP’s
Cephalosporins
Decreased permeability of gram negative outer membrane.
Active efflux.
Aminoglycosides
Drug inactivation.
Decreased permeability of gram negative outer membrane.
Active efflux.
Ribosomal methylation.
Nosocomial Pneumonia
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.
Aspiration Pneumonia
Usually gram negative bacilli.
- Indicated: Clindamycin
- Alternative: Ampicillin/ Sulfabactam
Clindamycin MOA and Resistance
MOA: 50s ribosomal inhibitor blocking translocation.
Resistance: Methylation of binding site, enzymatic inactivation.
Vancomycin MOA and Resistance
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
What is the problem with using serum levels for drug safety measurements?
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.
Time above MIC
Penicillins, Cephalosporins, Carbapenems
24hr AUC/MIC
AMinoglycosides, Fluoroquinolones, Tetracyclines, Vancomycins, MAcrolides, Clindamycin
Peak/MIC
Aminoglycosides, Fluoroquinolones
Drugs with Renal Elimination
**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
Drugs with Biliary Elimination
**No adjustment needed for renal impairment.
“No ADE is required if the liver does the work”
Azithromycin
Doxycycline
Erythromycin
Drugs with dual renal and biliary elimination
Cefatriaxone
Clindamycin
Meropenem (adjustment required in renal impairment)
Toxicity of Amoxicillin and Ampicillin
Cross reactivity with penicillin allergy
GI Distress
Maculopapular Rash
Toxicity of Azithromycin
Cholestatic jaundice.
***QT prolongation.
Toxicity of the Cephalosporins
Cross-reactivity across the whole class and partial with penicillin allergy. **Cefatriaxone causes GI distress.
Toxicity of Clindamycin
GI Distress
Toxicity of Doxycycline
GI Distress
**Teeth discoloration.
Photosensitivity
Decreased bone growth.
Toxicity of Erythromycin
- *CYP3A4 inhibitor.
- *Jaundice.
- *QT Prolongation.
Toxicity of Gentamicin
Nephrotoxicity
**Ototoxicity
Neuromuscular paralysis
Toxicity of Impinem
Partial cross reactivity with pen/ceph allergies.
*Seizures.
Toxicity of Levofloxacin
- Tendon rupture in adults
* Cartilage damage in young children
Toxicity of Linezolid
Bone marrow suppression.
**Non-specific MAO inhibitor
Toxicity of Meropenem
Partial cross reactivity with pen/ceph allergy.
*Seizures.
Toxicity of Piperacillin.
Partial cross reactivity with ceph hypersensitivity.
**Decreased coagulation.
Toxicity of Vancomycin
Nephrotoxic
*Ototoxic
“Red Man’s” Syndrome
Augmentin
Amoxicillin + Clavulanic Acid
Zosyn
Piperacillin + Tazobactam
Unasyn
Ampicillin + Sulbactam
Primaxin
Impinem + Cilastin
Should Daptomycin be used to treat pneumonia??
NO!
Treatment of Bronchitis
- 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.
Treatment of Lung Abscesses
- Clindamycin (superior to penicillin against becteroides)
- Metronidazole + Ceftriaxone (for nosocomial infections)
- *Metronidazole should not be used alone due to incomplete coverage.
Should you wait to treat?
NO. Earlier is better.
What is the usual course of therapy?
IF bad enough, can start on IV and transition to oral as improvement is seen.
Best Treatment for CAP?
A macrolide (azithromycin) or quinolone (levofloxacin) is first choice. Augmentin can also be used.
How do you approach a nosocomial infection?
First treat with broad spectrum and then tailor once the infective agent is known.
How do you approach treatment for abscess or aspiration pneumonia?
Treat for oral anaerobes.
