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What is the General Antimicrobial Mechanism of Action?
- oInhibit bacterial cell wall synthesis
- oInterfere with cell membrane function
- oDisrupt ribosomal function (protein synthesis) reversibly - generally bacteriostatic
oDisrupt ribosomal function (protein synthesis) irreversibly - generally bacteriocidal
- oInhibit nucleic acid metabolism
- oBlock enzyme pathways
When should you NOT use Antibacterial agents?
To treat Viral Diseases, because it promotes resistance and my harm the recipient
What is the Inoculum effect?
If the initial concentration of certain specific bacterial pathogens is very high--> higher than usual doses of an antimicrobial agent may be required to clear the infection
Cidal vs. Static*?
- Static requires that the host defense mechanisms are intact in order for bacteriostatic antibiotics to be effective.
Killing of bacteria continues after antibiotics are removed from the medium (usually because of the strong antibiotic binding to functional molecules within the organism)
What is Continuos dosing?
What is Bolus dosing?
What is special about Aminoglycoside Toxicity?
- Time dependent
- Level serum and tissue levels
- Concentration dependent
- Hight peaks and low troughs
-is both time and dose dependent;
What is the Goal of Antimicrobial prophylaxis?
- Use of a single effective drug to prevent infection by one specific organism,
- Example: Rheumatic Fever, for CNS shunt surgery, meningococcal meningitis prophylaxis, PCP prophylaxis
What are the multidrug resistant Gram negative bacteria?
enterobacter, citrobacter, seratia, pseudomonas, klebsiella, acinetobacter, and salmonella
What are some mechanisms of microbial resistance?
-Production of antibiotic inactivating enzymes
- -Changes in structure of target receptors (“Penicillin” Binding Proteins)
- -Increased efflux via drug transporters (Tetracycline efflux proteins)
-Decreased Microbial membrane permeability to antibiotics
(Loss of Imipenem channels in Pseudomonas)
-Changes allowing organism to bypass metabolic steps
What are the Naturally occuring Penicillins?
- Penicillin G
- Phenoxymethyl Penicillin (Pen V)
List the Penicillinase-resistant penicillins (Antistaphylococcal penicillins)
Methicillin* Poor P 0.5
- Oxacillin 30% (A) P 0.5
- Nafcillin Variable P 0.5
- Cloxacillin 50% (A) 0 0.5
- Dicloxacillin 50% (A) 0 0.5
List the “Extended-range” penicillins (More gram negative use)
Ampicillin 40% (A) P,0 1.0
- Amoxicillin 75% 0 1.0
- Ticarcillin P 1.0
- Piperacillin P 1.2
How is Penicillin excreted? what blocks this?
Which are mostly secreted in the biliary tracked?
-excreted in urine; excretion blocked by Probenecid
-Ampicillin partly and Nafcillin mostly excreted into the biliary tract
What is the mechanism of action of Penicillins?
- Interfere with cell wall synthesis, by:
- –Binding to specific receptors (penicillin-binding proteins) located in the bacterial cytoplasmic membrane
–Inhibiting transpeptidase enzymes that act to cross-link linear peptidoglycan chains
–Activation of autolytic enzymes that cause lesions in the bacterial cell wall
What is the Mechanism for Microbial resistance?
-Formation of Beta Lactamases(penicillinases) that destroy the antimicrobial agents
-Mutation of penicillin binding protein targets
-Alter porins to decrease penetrations of antimicrobial agents
What are the Narrow spectrum penicillins?
What are they sensitive to?
•Penicillin G and V
- •(Group A Strep) Strep pyogenes
- •(pneumococci) Strep pneumonia*
- •Some gram positive anaerobes*
- •(syphilis) Treponema pallidum
What are the Penicillinase – resistant penicillins?
Nafcillin, Oxacillin, Cloxacillin, Dicloxacillin
What are the Bugs that are in the Spectrum of the Extended range penicillins Ampicillin and Amoxicillin
-E. coli, Proteus mirabilis, Salmonella, Shigella, H influenzae, H. pylori
- -Strep pneumo,
- -Listeria monocytogenes
- -Moraxella catarrhalis
- -Borellia bergdorfi
What is the spectrum of activity of Extended range penicillins Ticarcillin and Piperacillin?
-Gram negative microbes especially pseudomonas*
What are some clinical uses of Penicillin?
Which infections are resistant to penicillins?
- -Rheumatic fever prophylaxis
- Staphylococcal infections
What are some clinical uses of
Ampicillin and Amoxicillin???
- -Otitis media**
- -Urinary tract infections**
- -Lyme disease
What are some clinical uses of
Ticarcillin and Piperacillin?
-Pseudomonas infections **
-Mixed intra-abdominal infections **
What are some Penicillin toxicities?
- - Allergic hypersensativity (rash)
- -drug fever
- -Elevated Hepatic transaminases
What is the blood test for Penicillin allergy?
RAST test for penicillin allergy is an important screening test.