Module 6: Antimicrobial Agents Flashcards
Define antimicrobial agent
Chemotheraputic agent used for treatment of infectious diseases
What 4 criteria must an antibiotic have in order to be used?
- Selective toxicity (kill bacteria, no damage to host cells)
- Not cause allergic reaction
- Soluble in body fluids and capable of tissue penetration
- Microorganisms must not readily develop resistance
What are broad spectrum antibiotics?
Affect wide variety of bacteria, gram positive and negative
Must have action against some Enterobacteriaceae to be broad
What are narrow spectrum antibiotics?
Affects small group of bacteria
Gram positive OR negative, not both
Define bactericidal
Agent kills bacteria
Define bacteriostatic
Agent prevents bacteria from multiplying, then body defenses get rid of it
Why would a bacteriostatic agent not be used on immunocompromised patients?
There are no body defenses to get rid of the bacteria
What are the 5 possible modes of action an antibiotic may have?
- Inhibit cell wall synthesis
- Inhibit protein synthesis
- Inhibit DNA and RNA synthesis
- Inhibit cell membrane function
- Inhibit other metabolic processes
Why are agents which inhibit the cell wall synthesis of bacteria used? (2)
- Human cells don’t have a cell wall
2. Peptidoglycan in the bacteria cell wall is unique to bacteria
What is the core component of all cell wall synthesis inhibiting antibiotics? What is it made of?
Beta-lactam ring
Made of three carbons and one nitrogen molecules arranged in a ring
What do cell wall synthesis inhibiting antibiotics bind to?
Enzymes in the cell wall called Penicillin binding proteins
How do cell wall synthesis inhibiting antibiotics cause bacterial death?
The agents bind to cell wall enzymes that are the last stage of peptidoglycan synthesis, which inhibits cross-linking between the proteins
This causes weakness and eventual rupturing
Why are gram negative bacteria usually resistant to beta-lactam antibiotics?
They have a lipid layer covering the peptidoglycan layer, protecting it from the antibiotic
What are the 2 major beta-lactam antibiotic groups?
Penicillin and cephalosporins
What are the 4 groups of penicillin?
Natural, beta-lactamase resistant, extended spectrum, anti-pseudomonal
What are natural penicillins?
Penicillin where the original compound is extracted from Penicillium mold
The compound is Penicillin G or Benzylpenicillin
What spectrum does natural penicillin have?
Narrow, gram positive with a few gram negative
Is there bacterial resistance to natural penicillin? If so, how does it work?
Yes, it can be inactivated by bacteria which produces beta-lactamase (enzyme) which opens the beta-lactam ring
What is the clinical usage of natural penicillin?
Penicillin G - injection, resistant to stomach acid
Penicillin V - orally
Usually given with other drugs to improve absorption and retention
What laboratory testing is done in regards to bacterial sensitivity?
Penicillin G used to test and applied to all other natural penicillins EX: Penicillin G is sensitive, so are other penicillins (class concept)
What is class concept?
The test results for sensitivity to one antibiotics applies to all other antibiotics of the same class
How do beta-lactamase resistant penicillins work?
“Bulky” side chain added to protect the beta-lactam ring
What penicillins are included in the beta-lactamase resistant class?
Oxacillin, cloxacillin, dicloxacillin, methicillin
Is there bacteria resistance to beta-lactamase resistant penicillin? If so, how does it work?
Resistance occurs only when the bacteria develops it, by altering their penicillin binding proteins to prevent binding
What is the clinical use of beta-lactamase resistant penicillins?
Orally or injection, use determined by side chain which may alter absorption and excretion
What laboratory testing is done on beta-lactamase resistant penicillin in regards to sensitivity?
Class concept applies, oxacillin is usually used
What are extended spectrum penicillins?
Addition of NH2 (amine) groups to the side chain of penicillin allows antibiotic to penetrate the lipid layer of gram negative cells
Called aminopenicillins
What is the spectrum of aminopenicillins?
Broad, but not as effective against gram positive
What is the spectrum of beta-lactamase resistant penicillin?
Narrow gram positive, usually for Staphylococcus infections
Is there bacteria resistance to extended spectrum penicillin? If so, how does it work?
Susceptible to beta-lactamase
What laboratory testing is done on extended spectrum penicillin in regards to sensitivity?
Class concept applies, ampicillin is usually used
What are examples of extended spectrum penicillin?
Ampicillin, amoxicillin
What are anti-pseudomonal penicillins? Why are they used?
Two groups:
1. carboxy penicillins
2. Ureidopenicillins
Used because Pseudomonas and other Enterobacteriaceae produce beta-lactamase
What spectrum to anti-pseudomonal penicillins have?
Broad, less effective against gram positives
Is there resistance to anti-pseudomonal penicillin? If so, how does it work?
Can be inactivated by beta-lactamase from Staphylococcus
What is the clinical use for anti-pseudomonal penicillin?
Used against bacteria that is resistant to other antibiotics, very expensive
Usually used with aminoglycosides for Pseudomonas
What laboratory testing is done on anti-pseudomonal penicillin in regards to susceptibility?
Class concept does not apply, each antibiotic must be tested
What are examples of anti-pseudomonal penicillins? (2 groups)
Carboxypenicillin - carbenicillin, ticaricillin
Ureidopenicillin - azlocillin, mezlocillin, piperacillin
What are beta-lactamase inhibitors?
Compounds with weak antibiotic properties but that are able to render some beta-lactamase enzymes useless
What are 2 beta-lactamase inhibitors?
Clavulanic acid - amox-clav, ticar-clav
Sulbactam - with ampicillin
What are cephalosporins?
Beta-lactam antibiotics produced as fermentation products of fungus
How many cephalosporin generations exist?
4
How are cephalosporin generations separated?
By antibacterial spectrum
What are first generation cephalosporins?
Cephalothin, cefazolin, cephalexin
What is the spectrum of first generation cephalosporins?
Broad, most gram positives and moderate gram negatives
What is the clinical use of first generation cephalosporins?
Cephalothin and cefazolin injected, cephalexin oral
More expensive than penicillin
What laboratory testing is done on first generation cephalosporins in regards to sensitivity?
Class concept generally applies, Cepahlothin usually used
What are the second generation cephalosporins?
Cefaclor, cefonicid, cefotiam, cefotetan, cefamandole, ceforanide, cefuroxime, cefoxitin
What is the spectrum of second generation cephalosporins?
Broad, increased GNB activity but decreased GP activity
None effective against Pseudomonas
What sensitivity testing is done on second generation cephalosporins?
Class concept does not apply, each one must be tested
What are the third generation cephalosporins?
Cefixime, cefotaxime, ceftizoxime, cefoperazone, ceftazidime, ceftriaxone
What is the spectrum of third generation cephalosporins?
Broad, less against GP, more against Enterobacteriaceae and Pseudomonas
What sensitivity testing is done on third generation cephalosporins?
Class concept does not apply, each must be tested
What is one clinical use for third generation cephalosporins?
Crosses the blood-brain barrier more easily than first generations
What are the fourth generation cephalosporins?
Cefipime, cefpirome
What is the spectrum of fourth generation cephalosporins?
Broad
What is aztreonam?
Beta-lactam structure with no attachments that disrupts cell wall synthesis the same way penicillin and cephalosporin does
What is azteronam used for?
Very effective against Enterobacteriaceae and Pseudomonas that are resistant to other antibiotics, but not GP or anaerobes
What are ESBL’s?
Extended spectrum beta-lactamases
Enzymes that mediate resistance to extended spectrum cephalosporins (3rd gen)
What bacteria can produce ESBL’s?
Certain GNs like E. coli, K. pneumoniae and oxytoca
What happens if a bacteria is found out to be an ESBL?
All penicillin, cephalosporins, and aztreonam are reported as resistant
What is imipenem?
Beta-lactam antibiotic with unique side chain to make it resistant to most beta-lactamase
Part of Carbapenem class
What is the spectrum of inipenem?
Broad, widest spectrum of any current antibiotic, most GNBs and anaerobes
Superbugs are resistant (MRSA, VRE)
What is vancomycin?
Belongs to glycopeptide class, not a beta-lactam and does not bind to penicillin binding sites
How does vancomycin work?
Binds to precursors of cell wall synthesis
What is the spectrum of vancomycin?
Narrow gram positive, large molecule cannot penerate GN cell wall
What is the clinical use of vancomycin?
Usually reserved for MRSA, Clostridium difficile, and resistant Enterococcus
What are potential side effects of vancomycin?
Toxic, hearing loss
What is teicoplanin?
Newer complex glycopeptide with similar spectrum to vancomycin
What antibiotics have a cell wall synthesis inhibiting mode of action?
Penicillin, cephalosporins, aztreaonam, imipenem, vancomycin, teicoplanin
What is penicillins mode of action?
Cell wall synthesis inhibition
What is cephalosporins mode of action?
Cell wall synthesis inhibition