Penicillins Flashcards
PCN MOA
Binds to transpeptidases (penicillin binding proteins)
Mimics alanine (d ala d ala) residues
Inactivates enzymes
Bacterial cell wall breakdown>wall creation —> autolysis
PCN BACTERICIDAL
Natural PCNs
PCN G- IV and IM
PCN VK- oral
Probenecid- gout drug, inhibits renal secretion of PCN, boosts PCN levels
Natural PCN resistance (3)
- Modified penicillin binding proteins
- Reduced bacterial cell penetration- GN poor penetration bc protected by outer membrane and bacteria can decrease number of porins
- Beta lactamase enzyme
Beta lactamase (penicillinase)
Bacterial enzymes
Degrade beta lactamase compounds
- PCN G and VK, other PCNs, cephalosporins
GN bacteria- found in PERIPLASM
STAPH AUREUS and GP- beta lactamase a secreted, produce more enzyme than GN
B lactamase inhibitors (4)- CAST
Clavulanic acid
Avibactam
Sulbactam
Tazobactam
Added to aminoPCNs and antistaphylococcal PCNs to expand coverage
No effect alone
PCN G and VK clinical use (3)
Narrow spectrum
- GP- GAS (strep throat) and actinomyces
- Treponema pallidum (syphillis)
- Only susceptible isolates- N meaning idiots and strep PNA
PCN AEs 4, same for cephalosporins and sulfonamides
Type 1- acute, IgE, anaphylaxis, urticaria, bronchospasm
Type 2- direct coombs + hemolytic anemia, IgE (PCN acts as happen, abs against PCN bound to RBCs)
Type 3- serum sickness (days to weeks after exposure, complement activation, IgG, fever, urticaria, LAD, arthritis)
Type 4- maculopapular rash (mc with aminoPCN and EBV pharyngitis), interstitial nephritis (PCN acts as hapten)- fever, oliguria, high BUN/Cr, eosinophils, WBC, WBC casts in urine
C diff infection
Diarrhea after abx
Abx depletes normal flora
C diff growth—> pseudomembranous colitis
Frequently caused by
- CLINDAMYCIN
- Fluoroquinolones
- Cephalosporins
- PCNs
Jarisch Herxheimer Reaction
Flu like syndrome (fever, malaise, HA, myalgia, flushing, chills) after PCN for spirochetes (classically: syphilis) d/t killed bacteria releasing toxins
Antistaphylococcal PCNs 3
Oxacillin
Nafcillin
Dicloxacillin
Methicillin was prototype
Antistaphylococcal PCN use
Remember staph and strep found on skin- Covers NON MRSA staph and most strept
Community acquired cellulitis
Impetigo- honey crusted lesions on skin in peds, caused by s aureus
Staph endocarditis
AminoPCN 2
Amoxicillin- oral
Ampicillin- IV
Penetrate porin channel of GN
Sensitive to beta lactamase enzymes
Aminopenicillin coverage 6
H influenza E. coli Proteus Salmonella Shigella Listeria (GP)
Used for:
Otitis media
Bacterial sinusitis
MENINGITIS- newborns, elderly, Listeria coverage
Aminopenicillins and maculopapular rash
MC with viral infection
Classic- EBV infection with sore throat, amoxicillin given for presumed bacterial pharyngitis, maculopapular rash
SJS and TEN common with which abx class?
AminoPCNs
Sulfonamides
Cephalosporins
Amoxicillin/clavulanic acid, ampicillin/sulbactam
Increases activity against S aureus, H influenza, and anaerobes (B FRAGILIS)
Used in-
Otitis media/sinusitis (Broad spectrum)
Bite wounds (polymicrobial with anaerobes)
Antipseudomonal PCNs 2
Ticarcillin
Piperacillin
Greater porin penetration
Effective against P aeroginosa and more GN
Broad spectrum when used with b lactamase inhibitors
1. Most GP, GN (Psuedomonas) and anaerobes
NOT MRSA
Inpatients with GN sepsis/PNA
Beta lactam abx 3
Carbapenems
Aztreonam
Cephalosporins
All bind transpeptidases, prevents peotidoglycan cross linking, bacterial cell autolysis, bactericidal
Susceptible to beta lactamase enzymes
Carbapenems 4
Imipenem
Meropenem
Ertapenem
Doripenem
Most resistant to most beta lactamase enzymes
DRUG OF CHOICE FOR ESBL BACTERIA
Broad spectrum- GP, GN, Psuedomonas, Enterobacter, anaerobes, B fragilis
Extended Spectrum Beta Lactamases
Plasmid mediated
Confer R to most beta lactam abx
Found in only GN: Pseudomonas Klebsiella E. coli Enterobacter Salmonella Serration Shigella
Imipenem
Metabolized by kidneys
MUST admin with CILASTATIN to inhibit PCT enzyme dihydropeptidase I to decrease renal tox
Carbapenems AES
N/V/D
Skin rash
NEUROTOXICITY at high doses or renal failure - seizures dt inhibition of GABA RECEPTORS
lowest seizure risk with MEROPENEM
Aztreonam (monobactam)
Binds PENICILLIN BINDING PROTEIN 3- prevents peptidoglycan cross linking
PBP3 only in GN
Aztreonam only active against GN (incl pseudomonas)
Aztreonam use
IV only- inpatients
Synergistic with aminoglycosides
NO CROSS REACTIVITY IN PCN ALLERGIC PTS
Can use in PCN allergic patients
1st gen cephalosporins 2 (+PeCK)
Cefazolin
Cephalexin
Cefazolin used pre op to prevent S aureus wound infection
GP
Proteus
E. coli
Klebsiella
2nd gen cephalosporins 3 (HENS PeCK)
Cefuroxime
Cefoxitin
Cefotetan
Hib Enterobacter Neisseria Serratia Proteus E. coli Klebsiella
B fragilis (anaerobe)
Cefuroxime use
Otitis media (S PNA, H flu) UTI in peds (e coli, no fluoroquinolones in peds)
Cefoxitin/cefotetan use
IV
PID- cover Neisseria, give with doxycycline for Chlamydia coverage
Pre op in peds with appendicitis- covers E. coli, GN, some anaerobes, usually given with metronidazole
3rd gen cephalosporins 3
Ceftriaxone
Cefotaxime
Ceftazidime- covers pseudomonas
More resistance to beta lactamase enzymes
Good CSF penetration- meningitis
Ceftriaxone
Used for N gonorrhea
Commonly used in meningitis
- active against S PNA, N meningiditis
- good CSF penetration
Cefepime
4th gen cephalosporin
Hospital patients with serious GN infections
Ceftaroline
5th gen cephalosporin
Active against MRSA and VRSA
Binds PBP2a- MRSA specific PBP
No Psuedomonas coverage
Cephalosporin resistance mechanisms 3
- Modified PBPs
- Altered cell permeability
- Beta lactamase
Cephalosporin AES 6
HYPERSENSITIVITY RXN SIMILAR TO PCN: Anaphylaxis Maculopapular rash Serum sickness- fever, rash, arthritis Hemolytic anemia- drug addiction hapten Interstitial nephritis SJS/TEN
Some cross reactivity with PCNs
Vitamin K deficiency and abx
Gut bacteria produce vitamin k2
Necessary for proper clotting
Abx reduce bacterial vit k production—> increased INR and potential bleeding
Common problem for pts on WARFARIN
Hypoprothrombinemia
Cefotetan and cefazolin inhibit epoxied reductse (same as warfarin)
Decreased liver synth of clotting factors
Can prolong PT/INR
Reversible with vitamin K
Mostly in malnourished pts
Special cephalosporin AEs 3
- Nephrotoxic with aminoglycosides
- Hypoprothrombinemia
- Disulfiram reaction- EtOH with cephalosporins
Warmth, flushing, sweating
Inhibition of acetaldehyde dehydrogenase -> accumulation of acetaldehyde