Rx Antibacterials Flashcards
What is antibiotic stewardship?
- Limit inappropriate use (eg. viral URI)
- Attempt to use more narrow spectrum when possible (eg. antibiotic susceptibility charts)
- Monitor for adverse outcomes and educate about adverse effects (eg. photosensitization)
Four main subclasses of Cell wall inhibitors depending on the side chains
Penicillins- mold from Penicillium
Cephalosporins- mold from Cephalosporium
Monobactams
Carbapenems
Penicillins MOA
- Inhibit transpeptidase, preventing it from forming cross-links in peptidoglycan wall = cell lysis
“Cell wall inhibitor”- Bactericidal! - They do this by binding to Penicillin-Binding Protein (PBP)
Why are Gram negatives typically more resistant to beta-lactam antibiotics?
Gram negative bacteria have LPS layer in outer membrane, which protects the peptidoglycan wall from some beta-lactam activity
How are Clavulanic Acid and Tazobactam are beta- lactamase inhibitors?
These bacteria have a beta- lactamase enzyme that blocks beta-lactam activity
-Added to some Penicillins to counteract beta-lactamase
Most penicillins are given _____
orally
General indications for penicillin
Syphilis
Strep pharyngitis
Rheumatic fever
Skin infections - Various
Acute otitis media
Sinusitis
Diphtheria
Hospital acquired infections (ex: Pseudomonas)
These penicillins Have increased ability to cross LPS membrane in Gram negative cells, so more effective with Gram negatives.
Ampicillin (IV) and Amoxicillin (PO)
Piperacillin-Tazobactam (Zosyn) is particularly helpful against what?
Broad spectrum, “Antipseudomonal,” IV drug
Contraindications of Penicillins
Hypersensitivity reaction (rash, hives, anaphylaxis)
Skin testing is available if with Hx of rxn
Side effects with Penicillins
- Hypersensitivity rash
- Nausea/vomiting
- Diarrhea
- Can see likely non-allergic rash in patients with Mononucleosis who are prescribed an aminopenicillin (Amoxicillin).
Penicillin adverse reactions
Anaphylactic hypersensitivity reaction
Penicillin Follow up/monitoring
- Excretion is renal- dose adjustment for renal disease eg. seizures
- Creatinine at baseline; check periodically if long-term use
- May use during pregnancy, little to no known risk of fetal harm, safe during lactation (compatible with breastfeeding)
T/F MRSA and VRE are resistant to Penicillins
T
Black Box Warning for Penicillin
- Pen G benzathine/ procaine - IM injection only, Do not give IV. Cases of cardiorespiratory arrest when inadvertently given IV.
- Pay attention to the labels
Cephalosporins MOA
- Beta-lactam, like Penicillins.
- Similar MOA as Penicillins.
- Broader spectrum then PCN
- Does not kill MRSA*
- Emerging resistance due to certain β-lactamases is a concern
First generation cephalosporins
Cephalexin (Keflex) oral
Cefazolin (Ancef) IV - popular in Peds
Good for sinus infections, skin conditions
Second generation cephalosporins:
Cefoxitin (Mefoxin)
Cefuroxime (Ceftin) Oral
Cefaclor (Ceclor)
Third generation cephalosporins
Cefdinir (Omnicef)
Ceftriaxone (Rocephin) - Meningitis
Cefotaxime (Claforan)
Ceftazidime (Fortaz)
Fourth generation cephalosporin
Cefepime (Maxipime)- only
Fifth generation cephalosporin
Ceftaroline (Teflaro)- *only one that will cover MRSA
Cephalosporins Indications
Cellulitis- Cephalexin (Keflex)
Surgical prophylaxis- Cefazolin (Ancef)
Abdominal surgical prophylaxis - Cefoxitin (Mefoxin)
Otitis Media, Sinusitis, Strep throat - Cefuroxime (Ceftin) or Cefdinir (Omnicef)
Pseudomonas infections - Ceftazidime (Fortaz)
Febrile neutropenia, Sepsis - Cefepime (Maxipime)
Cephalosporin Contraindications
- Anaphylactic reaction to Penicillins = “absolute contraindication”
- Non-anaphylactic reaction to Penicillins = “relative contraindication”
Cephalosporins side effects
Stomach ache
Diarrhea
Nausea/vomiting
Cephalosporins Adverse reactions
Hematologic: Rare cases of bone marrow suppression
Nephrotoxic: Acute kidney injury
Pseudomembranous Colitis (What organism again?)
Cephalosporins Follow up and monitoring
- Creatinine at baseline, check periodically
-Older generation cephalosporins associated with bleeding disorders, so consider checking PT if chronically ill patient, anticoagulant use, or using long-term. - All can be used during pregnancy with little to no risk (caution with Ceftaroline)
- Most are either “safe” or “probably safe” during lactation
Cephalosporins PEARLS
- Third generation cephalosporins have good CNS penetration.
- Common surgery prophylactics: Drug of choice: Ancef
Coverage spectrum of Cephalosporins
Gram positive: Very good, esp 1st gen
Gram negative: 3rd gen very good, 2nd gen agents good
MRSA and VRE are resistant
Coverage spectrum of Penicillins
Gram positive: Very good
MRSA and VRE are resistant
Carbapenems MOA
- Beta-lactam drug, like Penicillins.
- Same MOA as Penicillins.
*Cilastatin- Prevents Imipenem breakdown by renal tubular dipeptidase (an enzyme in the proximal tubule).
Carbapenem names
Imipenem-Cilastatin (Primaxin)
Meropenem (Merrem)
Ertapenem (Invanz)
Indication for Carbapenems
- These are IV medications (only in hospital, really)
- Often reserved for resistant highly drug resistant organisms
Some bacteria which produce carbapenemases
Sepsis requires which Carbapenem
Sepsis - Meropenem
Contraindications of Carbapenems
Renal impairment with CrCl < 15
History of seizures
Side Effects of Carbapenems
Fever - This can “muddy the water” if you’re treating a patient with an infection
Adverse Reactions of Carbapenems
Neurotoxicity (seizures) - Especially Imipenem
Follow Up and Monitoring for Carbapenems
Creatinine at baseline; check periodically if long-term use
CBC and LFTs periodically if using long-term
Caution advised during pregnancy;
Considered the “big guns” of antibiotics
Carbapenems
Carbapenems coverage spectrum
Gram positive: Very good
Gram negative: Very good
Anaerobes: Very good
Pseudomonas: Very good
VRE: Good to poor
MRSA is resistant
Monobactams Mechanism of Action
Beta-lactam drug, like Penicillins.
Same MOA as Penicillins
Monobactam drug
Aztreonam (Azactam)- only by Inj
Only monobactam on the market
Indication for Monobactams
- Interestingly, inactive against Gram +
- Effective against aerobic gram negatives, including E coli, Klebsiella, Haemophilus influenzae, N meningitidis, and Pseudomonas aeruginosa. (Good for UTIs)
- Serious bacterial infection in patients with history of Penicillin anaphylaxis, such as Klebsiella Pneumoniae, Pyelonephritis, Meningitis, and Sepsis (an IV/IM drug)
Contraindications of Monobactams
- Caution if renal or hepatic impairment
- Caution if history of antibiotic-induced colitis (C.Diff)
Side Effects of Monobactams
Nausea/vomiting
Diarrhea
Injection/IV site reaction
ALT or AST elevation
Creatinine elevation
Adverse Reactions of Monobactams
Anaphylaxis
Seizures
Pseudomembranous colitis (Clostridium difficile)
Hepatitis
Thrombocytopenia
Neutropenia
Toxic epidermal necrolysis
Follow Up and Monitoring with Monobactams
Creatinine at baseline; check periodically if renal impairment
LFTs periodically
May use during pregnancy; No human data available but no risk based on high-dose animal studies
Safe during lactation
PEARLS for Monobactams
Aztreonam is another “big gun.” Because of side effects and seriousness of adverse reactions, not often used.
Penetrates the CNS very well
Vancomycin MOA
- Inhibits cell wall synthesis by attaching to the end of the peptidoglycan precursor units, thus preventing peptidoglycan construction.
- Bactericidal.
____ is considered a “Glycopeptide” Antibiotic
Vancomycin
Vancomycin Indications
Severe Gram positive infections (IV)
Sepsis (IV)
MRSA infections (IV)- some are resistant
Clostridium difficile (pseudomembranous colitis)
Contraindications for Vancomycin
Black Box Warning
Hypersensitivity to corn, as some IV formulations use dextrose
Side Effects of Vancomycin
Flushing with fast IV administration.
Triggers histamine release which can drop BP
Called “Red Man Syndrome”
Hypotension, as described above.
Nausea/vomiting
Rash
“Red Man Syndrome” is a side effect found with _____
Vancomycin
Adverse Reactions for Vancomycin
- Nephrotoxicity (6-7%)- May see increasing Creatinine.
- Neutropenia- Could be detrimental if severe infection.
- Ototoxicity- Rare
Follow Up and Monitoring for Vancomycin
Pregnancy test - See Black Box
Creatinine at baseline, then periodically (even daily if the patient is in the hospital-peak and trough levels).
Check WBC if prolonged use.
Check serum drug level periodically to avoid toxicity.
Normal is 10-20 mcg/mL (>20 at trough is toxic)
Trough = Serum level checked just before next dose
Pregnancy- See Black Box
Probably safe during lactation
Black Box Warning for Vancomycin
fetal malformations