Pharm 19- Antimicrobials Flashcards
Outcomes in patients with deep sternal wound infections/cost
Significantly worse long-term survival
Costs between $200 and $250 to treat
What are the two major causes of device “failure” in assist devices?
Infection/sepsis
Thrombosis/Hemorrhage
MIC
Minimum Inhibitor Concentration; lowest concentration of antibiotic that inhibits bacterial growth
MBC
Minimum Bacteriocidal Concentration; lowest concentration of antibiotic that kills 99.9% of bacteria
Cidal vs. Static
Cidal kills bacterial, static just stops growth
If you mix a cidal with a static antibiotic…..
Static inhibitors growth
Cidal requires the bacteria to be dividing
So combination is less effective.
Three Major Pathogen Categories
- Gram Positive Bacteria
- Gram Negative Bacteria
- Fungi
How do penecillins and cephalosporins work?
Prevent bacterial cell wall peptidoglycan cross-linking so newly produced bacterial cell walls are “weak” and the bacteria “fall apart” (Marfan’s Disease)
These are cidal!
Marfan’s Disease
Abnormal connective tissue; can affect the heart
Cidal Antibiotics
Pencillins
Cephalosporins
How are penciilins and cephalosporins classified?
By “spectrum of activity” and resistance to B-lactamases (as well as potency, methods of administration, toxicities and dynamics)
What attachment differentiates the penicillins?
“R group”
What is a significant source of antibiotic resistance among microbes?
B-lactamase
What antibiotics are derived from mold?
Penicillins
“First Generation” Penicillins were effective against what?
Gram-positive organisms (particularly Strep)
Gram Negative Cocci
But resistance levels are high and growing
What is the archetype Penicillin?
Penicillin-G (Benzylpenicillin)
What developed in response to growing resistance among Staph? Describe the spectrum.
Anti-staphylococcal Penicillins; much narrower spectrum and are used specificially for Methicillin resistant Staph aureus and should be used sparingly
Types of Anti-Staphylococcal Penicillins
Dicoxacillin (Dynapen)
Nafcillin (Nallpe)
Oxacillin
What is no longer used clinically because to some toxic side effects?
Methicillin
Broad Spectrum Penicillins; Drug Examples
Spectrum similar to Pen-G, but more activity against gram-negatives
Resistance to broad-spectrum pens has increased dramatically (especially MRSA)
Ampicillin; Amoxicillin
What is the drug of choice for pre-cardiac surgery dental prophylaxis?
Amoxicillin
Antipseudomonal Penicillins Drugs
Carbenicillin (Geocillin)
Piperacillin (piperacil)
Ticarcillin (Ticar)
Pseudomonas Aeruginosa
very problematic, very pathogenic gram negative that readily develops resistance to antibiotics; notorious for causing blue-green pus
Antipseudomonal Penicillin Drugs are effective against what?
Pseudomonas Aeruginosa
Other gram-negative bacilli
Clavulanic Acid
B-lactam ring like the penicillins but no antimicrobial activity; suicide inibitor of bacterial B-lactamase that attaches to and permanently deactivates the enzyme
Clavulanic Acid is comibined with what?
Amoxicillin (Augmentin)
Ticarcillin (Timentin)
(work synergistically)
How can penicillins be administered?
PO, IV, SQ
How are penicillins excreted?
Kidneys (not metabolized there)
Can penicillins cross the BBB?
No, except with meningitis inflame miniges are more permeable to it, permitting rapid penetration of the drug into CSF
Cephalosporins
B-lactams essentially just like penicillins
How are cephalosporins classified?
1st, 2nd, 3rd, and 4th generation based on their resistance to the B-lactamases and their antimicrobial spectrums
What is very commonly used in open heart surgery and as part of the prime?
Cephalosporins (or vancomyocin as alternative)
1st generation Cephalosporins
Less expensive that others
Since the main open-heart infection culprits are staph and strep, no advantage found using more expensive later-generation cephalosporins for ECC prophylaxis
1st Generation Cephalosporin Drug
Cefazolin (Kefzol)
Cefazolin (Kefzol)
Typically dosed at a fixed amt (1g/circuit) or by weight (50mg/kg)
Cleared by the kidneys
Cross sensitivity with penicillins is high
2nd Generation Cephalosporins
No proven advantage over 1st generation when used in the pump prime
May provide theoretical advantage of greater VOD and slightly broader spectrum of activity
2nd Generation Cephalosporin Examples
Cefoxitin (Mefoxin)
Cefotetan (Cefotan)
Cefuroxime (Ceftin)
Vancomycin
A glycopeptide
Similar action to pens/cephs; prevents peptidoglycan polymerization in the bacterial cell wall so they “fall apart”
Spectrum of activity limited to gram positives
Reversed for use in MRSA, MRSE, enterococcal infections
MRSA
methicillin resistance staph epidermidis
How is Vancomycin excreted?
Renally
Vancomycin Side Effects
More common than pens and cephs
Fever, chills, flushing, phlebitis
Phlebitis
Inflammation of the vasculature
Aminoglycosides Derived from?
Derived from fungi (like penicillins)
Aminoglycosides ending in “mycin”
From streptomyces
Aminoglycodies ending in “micin”
from micromonospora sp.
How do aminoglycosides work?
Interefere with bacterial protein synthesis by binding to bacterial ribosomal 30S subunit…
“cidal” action
Aminoglycoside Spectrum of Activity
limited to gram negative bacteria, such as E. coli, proteus mirabilis, pseudomonas aeruginosa
When do aminoglycosides exhibit a synergistic effect?
When used with pens, cephs, vacomycin for resistance bacteria
What exhibites concentration dependent killing?
Aminoglycosides
Concentration-Dependent Killing
INcreasing concentrations of aminoglycosides kill increasing proportions of bacteria at increasing rates
How are all aminoglycosides given?
Parenterally or used topically
Do aminoglycosides penetrate CNS?
NO
Aminoglycoside DRugs
Neomycin- used only topically (too nephrotoxic)
Steptomycin- First produced. Lots of microbial resistance has developed
Tobramycin (Nebcin)-mid level microbial resistance
Gentamicin- midlevel microbial resistance
Amikacin (Amikin)- least microbial resistance, most expensive
What aminoglycoside drug has the least bacterial resistance?
Amikacin (Amikin)
How are aminoglycosides excreted?
Renally and readily become “more toxic” in the presence of renal failure
What minimzes side effects of aminoglycosides?
adequate hydration/urine output
Where do aminoglycosides concentartion?
Cross the blood/placenta barrier
Concentrate in fetal tissue
Aminoglycoside Toxicity
- Ototoxicity (Vestibular and or cochlear)
- Neuromuscular Paralysis (esp. myastenia gravis patients)
- Nephrotoxicity ranging form mild to total renal destruction
