Pogue: Antimicrobials I Flashcards
Clinically important bacteria
G+
o Streptococcus spp.
o S. aureus
o Enterococcus spp.
Clinically important bacteria
G-
Enteric (3):
Proteus spp.
E.coli
K.pneumoniae)
Clinically important bacteria
G-
Sneaky gram negatives (SPICE)
Sneaky gram negatives (SPICE)
Serratia Providencia Indole (+) proteus Citrobacter Enterobacter
Clinically important bacteria
G-
Nasty gram negatives(2):
Nasty gram negatives
- P. aeruginosa
- A. baumannii
Clinically important bacteria
Anaerobes:
C.difficile
Empiric vs definitive therapy
Empiric Therapy: therapy before the causative organism is known; based off of most common pathogens
Definitive Therapy: once cultures and sensitivities are known
Bacteriocidal vs bacteriostatic
Bacteriocidal: an antibiotic makes the number of bacteria decrease
Bacteriostatic: the number of bacteria stays the same upon exposure to an antibiotic
Synergy:
1 + 1= more than 2 (ie. adding 2 drugs together has synergistic effects that make the combination better than the sum of its parts)
Pharmacokinetics and Pharmacodynamics
- Pharmacokinetics: what the body does to the drug (absorption, distribution, metabolism, excretion)
- Pharmacodynamics: what the drug does to the body (concentration-dependent vs. time-dependent killing)
Minimal inhibitory concentration (MIC)
The lowest concentration of the antimicrobial that inhibits growth (bacteriostatic effect) in the test tube
Drugs that affect cell wall synthesis:
B-lactams, Vancomycin
Drugs that affect bacterial DNA replication
Fluroquinolones
Drugs that act as folic acid inhibitors
Trimethoprim (Stops DHF A –>THF A)
Sulfonamide (Stops PABA –> DHF A)
Drugs that affect the cell membrane
Daptomycin
Protein synthesis inhibitors
50s
30s
50s Macrolides Lincosamides Linezolid Streptogramins
30s
Aminoglycosides
Tetracyclines
Mechanisms of Resistance (3):
Antimicrobial Modifying Enzymes: an example is beta-lactamases
Target Site Alterations: an example is penicillin binding protein alterations
Decreased Concentrations in a Cell:
o Efflux pumps: pump drug out
o Outer membrane porin downregulation: less drug gets into the cell
BETA-LACTAMS:
General:
Bacteriocidal:
Time-Dependent Antimicrobials:
BETA-LACTAMS:
• General:
- Most commonly used antimicrobials
- First available in the 1940s (penicillin)
Bacteriocidal: leads to rapid cell death
Time-Dependent Antimicrobials: higher doses rarely the answer in treatment
BETA-LACTAMS
MOA:
Mechanism of Action:
Inhibition of the final step of cell wall synthesis
Blocks the cross-linking of peptidoglycan (essential for structural integrity)
Process normally carried out by enzymes called penicillin-binding protins (PBPs)
Beta-lactams bind PBPs and block transpeptidation
- Not lethal itself, but part of process that will lead to rapid cell death
BETA-LACTAMS
Elimination:
Exceptions:
Renal Dosing:
Nearly every beta-lactam is eliminated renally and requires renal dosing adjustment
Exceptions:
o Ceftriaxone
o Penicillinase-resistant penicillins (Nafcillin, Oxacillin, Methicillin, Dicloxacillin)
Penicillin
Spectrum of Activity (5):
o Streptococci (S.pyogenes, S.viridans) o Enterococci (E.faecalis) o Treponema pallidum o Clostridium spp. (not C.difficile) o Other mouth anaerobes
Beta-Lactamases:
Enzymes that are secreted by the organism that hydrolyze beta-lactam antibiotics
Likely evolved from PBPs
B-lactamases that only hydrolyze penicillin are called penicillinases
Initially, penicillin was DOC for S.aureus but it has created penicillinases making them resistant
- Now only 5-10% susceptable
Benzathine Penicillin:
Use:
Long acting depot preparation that must be given IM
Only used to treat extremely susceptible bugs (Treponema pallidum¸ which causes syphilis, is a classic example)
Current Use of Penicillin (4):
Syphilis
Dental coverage (Mouth anaerobes)
Necrotizing Faciitis (S.pyogenes)
Definitive therapy for streptococcal infections
Penicillinase-Resistant Penicillins/”Anti-Staphylococcal Penicillins”:
Nafcillin - Commonly used
Methicillin - Not clinically used
Oxacillin - Commonly used
Dicloxacillin - Oral
Penicillinase-Resistant Penicillins:
Designed to overcome:
DOC for:
Strep activity?
Lacks:
- IN GENERAL: o Designed to overcome penicillinase o DOC for MSSA o Some streptococcal activity o Lacks gram negative and enterococcus activity
MRSA (Methicillin Resistant Staph Aureus):
Results from PBP2A alteration, in which the PBP has a decreased affinity for beta-lactams and can still cross-link in their presence
Such a decrease in affinity leads to resistance against ALL beta-lactams**
Aminopenicillins:
Ampicillin (IV)
Amoxicillin (PO)
- Better absorption
Aminopenicillins
HELPS bugs:
H.infleunzae
E.faecalis
L.monocytogenes
P.mirabalis
Samonella and Shigella spp.
Aminopenicillins
Clinical use:
Only static against:
Used with what for synergy against serious enterococcus infection?
Meningitis:
Enterococcal Infections: static against E.faecalis; minimal activity against E.faecium
Use with gentamicin for synergy in serious infections
Meningitis: when concern for listeria, use high dose ampicillin
- Amoxicillin (PO):
o Better absorption (hence PO formulation)
o Same clinical use as ampicillin