Lecture 2: Antibiotics Part I Flashcards
How do beta-lactams work relative to bacterial physiology?
They latch onto transpeptidase enzymes, preventing the layers of peptidoglycan from sticking together.
What ABX fall under beta-lactams?
PCNs
Cephalosporins
Carbapenems
Monobactams
What does a beta-lactam ring look like?
3 carbon 1 nitrogen square with a double bond to an O.
See slide 8 for visual.
What is the MOA of a beta-lactam?
- Drug binds to pencillin-binding proteins (PBP)
- This inhibits bacterial peptidoglycan synthesis, preventing bacterial replication. (Bacteriostatic)
- Binding to PBP activates bacterial autolytic enzymes that cause cell wall lysis. (Bactericidal)
How do G+ bacteria fight back against beta-lactams?
- Reduced binding affinity to PBPs.
- Productions of beta-lactamases to cleave the abx.
How do G- bacteria fight back against beta-lactams?
- Loss of outer membrane proteins.
- Beta-lactamases in periplasmic space.
What does penicillin become if the beta-lactam ring is broken?
Penicilloic acid
What is ABX resistance classified as?
Public Health Crisis!!!
2 millions infections
23,000 deaths
What are natural penicillins first-line for?
Group A Strep Throat
Syphilis (Treponema pallidum) (Spirochetes)
N. meningiditis (sometimes)
What are some pros and cons of natural pcns?
Cons:
Susceptible to beta-lactamase
Tastes bad
Multiple doses required
Increasing resistance
Pros:
Cheap
Safe
What are antistaphylococcal PCNs indicated for as first-line?
SSTIs with S. aureus and staph epidermis
What are the antistaphylococcal PCNs?
Dicloxacillin
Nafcillin
Oxacillin
What is the purpose of methicillin?
Identifying microbial resistance.
DO NOT USE FOR TX.
What are aminopenicillins first-line treatment for?
Otitis Media:
H. influenzae
S. pneumoniae
Moraxella Catarrhalis (M. Cat)
Prophylaxis for endocarditis!
Which aminopenicillin is better for PO?
Amoxicillin. (also tastes like bubblegum so children will take it)
What is the main difference in coverage between natural PCNs and the aminoPCNs?
Increased G- coverage.
What are the advantages of AminoPCNs over natural PCNs?
Higher oral absorption and longer half-life = less frequent dosing.
Better G- coverage.
What are the PCN/Beta-lactamase inhibitor combos first-line for?
Augmentin is firstline for sinusitis, pneumonia/COPD exacerbations.
This includes S. pneumo, H. flu, and S. aureus.
How long should someone be on abx for a sinus infection?
At least 10 days, because sinus infections take longer to treat.
What are the considerations when RXing a PCN/Beta-lactamase inhibitor?
Increased Cost
Increase GI SE
Reserved for more severe infections.
What is pip/tazo indicated for?
Severe polymicrobial infections:
Genital or urinary tract
Peritonitis/ruptured viscus
SSTI
Lower respiratory tract
Septicemia
Pseudomonas
Proteus
What is cephalexin (Keflex) and what is it indicated for?
1st gen cephalosporin.
Indicated for G+ staph and strep:
Minor skin infections
Impetigo
Pharyngitis/OM (except H. flu)
G-:
E. coli in simple cystitis, esp. in pregnancy. (alt to metro)
Very affordable with QID dosing.
What is cefazolin (Ancef) indicated for?
1st gen cephalosporin.
IV/IM only.
Indicated for surgical prophylaxis (clean)
Serious MSSA infections like endocarditis, pneumonia, and UTI
Note:
Dr. G commonly uses ancef as the ortho’s go to ABX.
What is cefadroxil (Duricef, Ultracef) indicated for?
Pharyngitis/tonsillitis
PO only but longer half-life than cephalexin, has BID dosing.
Which 1st gen cephalosporin cannot be taken PO?
Ancef/Cefazolin
What are cefoxitin/cefotetan indicated for?
Prophylaxis in dirty surgeries (vaginal/colorectal)
IV only, but better G- coverage.
2nd gen cephalosporin.
What are cefuroxime/cefaclor/cefprozil indicated for?
2nd line for:
Pharyngitis
Sinusitis
OM
Upper & lower respiratory tract infections
PO only, 2nd gen cephalosporins.
What is ceftriaxone/Rocephin indicated for?
First line for N. gonorrheae.
Good pneumococcal coverage. (used with a macrolide)
Surgical prophylaxis for abdominal.
Meningitis
PID
IM/IV only.
3rd gen cephalosporin.
What are cefdinir(omnicef)/cefixime(suprax) indicated for?
Second line for upper and lower respiratory tract infections.
SSTIs
Oral only.
3rd gen cephalosporin.
Note:
First-line is aminoPCNs.
Has a lower dosing than keflex for SSTIs.
What is cefepime(maxipime) indicated for?
Severe infections
Meningitis
Anti-pseudomonal
IV/IM only
Only 4th gen cephalosporin.
What is ceftaroline(teflaro) indicated for?
VRE
MRSA
IV only.
5th? gen cephalosporin.
Which cephalosporin gen has the worst G+ coverage?
3rd gen.
Which cephalosporin gen has the worst G- coverage?
1st gen.
Which cephalosporin gen begins penetrating the CNS?
3rd gen.
What are monobactams indicated for?
Severe infections of:
Urinary tract (E. coli)
Bacteremia/septicemia caused by G- only.
INHALATION: cystic fibrosis and respiratory infections.
What is unique about a monobactam?
Inhalation route is possible.
NO coverage against G+ or anaerobes.
NO cross-reactivity with PCNs.
What is the preferred alternative to monobactams?
3rd and 4th gen cephalosporins.
Better coverage with less SE.
Why is cilastatin added to imipenem?
Prevents inactivation of imipenem in the renal tubules of the kidney.
Which carbapenem does NOT cover pseudomonas?
Ertapenem (Invanz)
What are carbapenems indicated for?
Urinary tract
Meningitis
Peritonitis/intra-abdominal infections
Resistant wounds (chronic diabetic wounds)
Osteomyelitis
IV/IM only.
What beta-lactams are most likely to cause GI SE?
Augmentin
Higher gen cephalosporins
What are the main SE of beta-lactam use?
N/V/D
Vaginal candidiasis
What adverse events are associated with beta-lactam use?
Hypersensitivites
C. diff associated colitis
Drug induced nephritis
Hematologic abnormalities: Anemia/thrombocytopenia
CNS toxicity (high dose PCN, carbapenems)
What kind of ABX are usually given to people who state they have a PCN allergy?
Broad spectrum
How many people with actual type 1 hypersensitivity reactions to PCN lose their sensitivity?
80% in 10 years.
How much of the US populations has an actual type 1 hypersensitivity to PCN?
<1%
How are most beta-lactams metabolized/excreted?
Renal.
Minimal liver metabolism
Minimal CYP450 interaction
In what beta-lactams is neutropenia a concern?
Antistaphylococcal PCNs
Carbapenems
If only > 10 days of parenteral therapy.
What pregnancy category are beta-lactams?
B
What can beta-lactams decrease the efficacy of?
OCPs
