PHARM: Bacterial Infections Flashcards
What is the most important factor in successful treatment of pneumonia?
EARLY INTERVENTION (do not wait on blood/sputum cultures to start drug therapy)
What are the most common causes of nocosomial pneumonia?
Staph aureus
Pseudomonias aeruginosa
Klebsiella pneumoniae most frequently causes pneumonia in what patients?
Diabetics
Alcoholics
What are the top causes of pneumonia in new-borns?
Group B streptococci
E. coli
What are the top causes of pneumonia in children 6 weeks - 18 years old?
Viruses
Mycoplasma pneumoniae
Chlamydia pneumoniae
Streptococcus pneumoniae
What are the top causes of pneumonia in adults 18-40 y/o?
mycoplasma pneumoniae
streptococcus pneumoniae
What are the top causes of pneumonia in adults 40-65 y/o?
Streptococcus pneumonoiae
Haemophilus influenza
Anaerobes
Why is chronic alcohol use an independent risk factor for severe CAP?
chronic drinkers have decreased saliva production (which is an important mucosal defense)
Why is diabetes an independent risk factor for severe CAP?
the disorder neutralizes the effects of protective proteins on the surface of the lungs
What is the only antimicrobial actually labeled for use in Legionnaire’s disease?
erythromycin
What do physicians commonly use to treat Legionnaire’s disease?
azithromycin (and a respiratory quinolone like levofloxacin)
What is standard treatment for outpatient CAP?
Macrolide (erythromycin) or Doxycycline
How does treatment for outpatient CAP change if the patient uses steroids or antibiotics in the prior 3 months? *this is same treatment as you use for NURSING HOME PATIENTS
Fluoroquinolone
Amoxicillin + Clavulanic acid
2nd generation macrolide (clarithromycin) + cephalosporin
How do you treat CAP in a hospital ward?
Fluoroquinolone
Amoxicillin + Clavulanic acid
2nd generation macrolide (clarithromycin)/3rd generation macrolide (azithromycin) + cephalosporin
How do you treat ICU CAP?
3rd generation cephalosporin + macrolide
Piperacillin + Tazobactam
Fluoroquinolone
List commonly used macrolides.
Erythromycin (1st gen)
Clarithromycin (2nd gen)
Azithromycin (3rd gen)
What is the MOA of macrolides?
Bind to 23s subunit of 50s to inhibit translocation (peptidyl transferase)
What are resistance mechanisms against macrolides?
Ribosomal methylation and mutation of 23S rRNA
Active efflux
What is the major toxicity of erythromyxin?
CYP3A4 inhibitor
Cholestatic Jaundice
QT prolongation
What is the major toxicity of azithromycin?
Cholestatic jaundice
QT prolongation
List examples of tetracyclines.
Doxycycline
What is the MOA of tetracyclines
Bind to 16s subunit of 30s and weaken ribosome-tRNA interaction to prevent protein synthesis
What are resistance mechanisms against tetracyclines?
Decreased entry into bacteria
Increased efflux from bacteria
Target insensitivity
What is the major toxicities of doxycycline?
teeth discoloration
photosensitivity
decreased bone growth
Name an example of a fluoroquinolone.
Levofloxacin
What is the MOA of fluoroquinolones?
Gram Neg- inhibit DNA gyrase
Gram positive- inhibit topoisomerase IV
*prevent DNA replication
What are resistance mechanisms against fluoroquinolones?
mutation of DNA gyrase
active efflux
What is the major toxicity associated with levofloxacin?
tendon rupture (adults) cartilage damage (children)
List examples of penicillins.
Amoxicillin + Clavulanic acid
Piperacillin + Tazobactam
Why are penicillins given with clavulanic acid or tazobactam?
those are beta-lactamase inhibitors
Which beta lactams work on gram negative bacteria (can cross through the LPS-coated outer membrane)?
Penicillin G
Aminopenicillins
Later-generation cephalosporins (cefepime, ceftazidime)
What beta lactams are resistant to beta-lactamase?
Narrow spectrum penicillins (Meth, naf, ox)
Carbapenem
What is the MOA of penicillin.
Similar to D-Ala-D-Ala structure, so bind to PBP (transpeptidases) on bacteria and block cross-linking of peptidoglycan cell wall to destroy it
What are methods of resistance to penicillins?
Drug inactivation by beta-lactamase Altered PBPs (target insensitivity)
What is the major toxicities of aminopenicillins (amoxicillin and ampicillin)?
Cross reactivity with penicillin
aculopapular rash
What is the major toxicity of broad range penicillin (piperacillin)?
partial cross reactivity with ceph hypersensitivity
Decreased coagulation
List an example of a carbapenem.
Meropenem
What is the MOA of carbapenem.
similar to penicillin (because it is also a beta-lactam)
What is the major toxicity of meropenem?
partial cross-reactivity with penicillin/ceph hypersensitivity
Seizures
List some cephalosporins.
1st gen- Cefazolin 2nd gen- Cefuroxime 3rd gen- Ceftriazone 4th gen- Ceftazidime, Cefepime (have anti-pseudomonal activity)
What is the MOA of cephalosporins?
Inhibition of cell wall cross-linking
What are mechanisms of resistance to cephalosporins?
Decreased permeability of gram negative outer membrane (altered porins)
Active Efflux
What are the major toxicities of cephalosporins?
Cross-reactivity within class partial cross-reactivity with penicillin
List an example of an aminoglycoside
Gentamicin
What is the MOA of aminoglycosides?
Binds to 30s ribosomal subunit and pokes holes in membrane
What are the major mechanisms of resistance to aminoglycosides?
Drug inactivation
Decreased permeability of gram negative outer membrane
Active efflux
Ribosomal methylation
What are the major toxicities of gentamicin?
nephro- and ototoxicity
Neuromuscular paralysis
What drugs are used to treat nosocomial pneumonia?
Impenem/Cilastin
Azetronam
Ceftazidime
(all of these have activity against gram negative aerobes)
What drug is preserved to treat MRSA?
vancomycin (IV)
What drugs are used to treat aspiration pneumonia?
clindamycin
or
ampicillin/sulbactam
What class of drugs in clindamycin in?
lincosamides
What is the MOA of clindamycin?
binds to 23s of 50s and inhibits protein synthesis by blocking translocation
What are methods of resistance against clindamycin?
Methylation of binding site
enzymatic inactivation
What is the mechanism of action for vancomycin?
ONLY USEFUL IN DIVIDING Gram (+) bugs
Binds D-ala-D-ala terminus of peptide precursor and inhibits peptidoglycan polymerase and transpeptidation reaction
What are methods of resistance against vancomycin?
Replacement of D-ala by D-lactate
What are the major toxicities associated with vancomycin?
nephro- and ototoxicity
Red Man’s syndrome
What class of antibiotics has high oral bioavailability, making it easy to swap from parenteral to oral dosage?
fluoroquinolones
Which classes of antibiotics are concentration dependent? (increased conc. of drug kills bacteria at higher rate)
fluoroquinolones
aminoglycosides
(give in large doses at long intervals)
Which class of antibiotics is time dependent? (bacterial density is proportional to time that concentrations exceed the MIC)
beta-lactams (penicillins, cephalosporins, carbapenems)
Dose frequently to achieve drug level about MIC for 30-50% of the dose interval
Which antibiotics do NOT need to be dose adjusted for renal impairment (they are more biliary eliminated)?
Azithomycin Ceftriazone Clindamycin Doxycycline Erythromycin Linezolid
What antibiotic has postential for interaction with concurrent non-antimicrobial agents?
linezolid (with non-specific MAOIs)
What antibiotic is absolutely contraindicated in breastfeeding?
metronidazole
Why is daptomycin NOT used for pulmonary infections?
it distributes into lung tissue but it is INHIBITED BY SURFACTANT!
What is the most common cause of bronchitis in smokers?
H. influenzae
What treatment is indicated for bronchitis?
Amoxicillin + Clavulanic acid
Azithromycin
Clarithromycin
Doxycycline
What bacteria typically are found in lung abscesses?
Anaerobes
- Community acquired: gram pos. cocci
- Nosocomial: gram neg. bacilli
What is appropriate treatment for community acquired pulmonary abscess?
clindamycin
What is appropriate treatment for nocosomial pulmonary abscess?
methronidazole + ceftriaxone
