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73 Cards in this Set
- Front
- Back
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What structural component is present in all penicillin family antibiotics?
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Beta-lactam ring. Thus all penicillin family antibiotics have a beta-lactam ring.
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Molecular structure of penicillin
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Penicillin has a beta lactam-ring with another ring fused to it.
Imagine a roofed-house with a square side room (square) and a side-antennae off the square house. Changing the antennae or building a basement will create new types of penicillin with differenting spectrums of activity and potencies. |
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Mechanism of action of penicillin
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They not only slow the growth, they kill it and are bacteriacidal. They are effective against gram (+) and gram (-) since both have peptidoglycan in cell walls composed of repeating disaccharide units cross-linked with amino-acids (peptides).
The penicillin must evade bacterial defenses and penetrate outer cell-wall (gram negative only) to inner cytoplasmic membrane (where transpeptidase enzymes are located). Once at their target, the penicillin beta-lactam ring (side house) binds to and competitively inhibits transpeptidase enzyme. Cell wall synthesis is arrested. This is known as the penicillin binding protein. |
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Enzyme that catalyzes likage of repeating dissacharide units with amino acids
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transpeptidase (inner cytoplasmic membrane)
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In gram negative-bugs, penicillin must pass through:
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Outer cell membrane, as well as channels known as porins before accessing transpeptidase.
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To be effective, the Beta-lactam penicillin must
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1. penetrate the cell layers
2. Keep its beta-lactam ring intact 3. Bind to transpeptidase (peniccilin-binding protein) |
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Resistance to Beta-Lactam Antibiotics
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3 mechsnisms, different for gram positive and negative:
Mechanism 1) Alter porins, Gram negatives can "alter porins"--preventing penicillin from penetrating cell layers. Gram positives don't even have porins. 2. "Beta Lactamase" Gram positive AND gram-negative bacteria have beta-lactamase enzymes that cleave C-N bond in Beta-lactam ring. Gram (+) bacteria (like staph aureus) secrete beta-lactamase (penicillinase) to try to intercept the antibiotic outside the peptidoglycan wall (like a homing missile) Gram negatives have beta-lactamase bound to membranes, which destroy the beta lactam locally in periplasm (just superficial to inner membrane) 3. "Altered transpeptidase structure." Alteration of molecular structure of transpeptidase (prevents beta-lactam binding). |
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Methicillin-resistant Staphylococcus aureus (MRSA) defends itself how?
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It gains resistance to the entire class of peniccilin drugs by altering transpeptidase (PBP) structure (which resides in inner membrane)
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Possible adverse reactions to penicillins?
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Can potentially cause anaphylactic (allergic) response. This IgE mediated rx. can lead to bronchospasm, urticaria, and anaphylactic shock (loss of ability to maintain blood pressure). A delayed rash appears several days to weeks later.
All of these antibiotics can cause: 1. Diarrhea (destroys natural GI flora-->allows resistant pathogens like C. dificile to grow) |
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5 types of peniccilin
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1. Peniccilin G: (original discovered by Fleming. The Penicilium notatum mold produced a chemical that inhibited staph aureus.)
2. Aminopenicillins: beta coverage for gram negative bacteria 3. Penicillinase-resistant penicillins: Useful againts beta-lactamase producing staph aureus (an enzyme that destroys beta-lactim rings) 4. Anti-pseudomonal penicillins (Including the carboxypenicillins, ureidopenicillins, and monobactams). Wide coverage against gram negatives (including pseudomonas aeruginosa) 5. Cephalosporins: Widely used group of antibiotics that have a beta-lactam ring, are resistant to beta-lactamase, and cover a broad range of gram positive and gram-negative bacteria. Although now bacteria produce cephalosporinases, making them resistant to these too. |
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Penicillin G
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Original peniccilin.
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Aminopeniccilins
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Better coverage of gram-negatives than regular penicillin.
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Penicillinase-resistant penicillins
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Useful against beta-lactamase enzyme that destroys beta-lactam rings. Penicillinase, for instance, is produced by staphylococcus aureus.
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Anti-pseudomonal peniccilins
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(carboxypeniccilins, ureidopenicillins, and monobactams)
Wide coverage against gram-negative (and as the name implies-->coverage for pseudomonas auruginosa) |
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Cephalosporins
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Have a beta-lactam, resistant to beta lactamase, and cover a broad spectrum of gram-+ and neg bacteria (unless they make cephalosporinase)
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Monobactam is an example of
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Anti-pseudomonal penicillin
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Peniccilin G administration
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The Old "g" man.
Usually given intramuscularly (but oral dose exists). Injection in crystalline form to increase half-life. The old G-man is sensitive to beta-lactamase |
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Guidelines for administration of Peniccilin G
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Old "Greg" is still used for:
1. Pneumonia caused by Streptococcus pneumoniae Peniccilin V is an oral form of peniccilin (acid stable in stomach) and good for streptococcus pharyngitis caused by group A beta-hemolytic streptococcus (since it can be orally administered). |
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2 types of Aminopeniccilins
and their mechanism |
Ampicillin and Amoxicillin. Both of which have a broader spectrum than old "G" man and hit more gram-negative bugs. It can really get through that outer membrane and bind to that transpeptidase, but aminopeniccilins are still inhibited by peniccilinase.
Useful against gram negative: E.coli, other enterics (proteus, salmonella, shigella, etc.) However many enteric gram-negative bacteria and h. influenzae (30%) have resistance. One of the drugs effective against gram (+) enterococcus. |
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Administration of ampiccilin and amoxicillin
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Both of these aminopeniccilins can be taken orally (amoxicillin more effectively absorbed p.o.-->great for outpatient bronchitis, urinary tract infections, and sinusitis caused by gram negatives.
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For broad gram-negative coverage, ampicicillin is commonly used with:
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aminoglycosides (gentamycin)
"Amp-agent" combo time! Patients with serious UTI are often infected with gram-negative enteric or enterococcus. Amp-agent gives the broad coverage you need until cultures reveal organism responsible. |
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Penicillinase-Resistant Penicillins
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Methicillin, Nafcillin and Oxacillin (they can kill staph aureus) and are usually given IV.
"i MET a NAsty OX with a beta-lactamase ring around its neck." The OX tried to defeat the ring with its Beta Lactamase "Bul-lactamase" but it failed to compete against "I Methiccilin a Nafcillinasty Ox-axacillin" |
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Methicillin, Nafcillin, and Oxacillin are exapmles of
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Peniccilinase-resistant penicillins.
Note methicilllin has a high occurence of interstitial nephritis, so it's largely discontinued, but MRSA is resistant to penicillinase-resistant antibiotics. |
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Drug of choice for staph aureus infections such as cellultis, endocarditis, and sepsis
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Nafcillin, a penicillinase-resistant penicillin.
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"Clox"acillin and di"clox"acillin spectrum
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The "Clox" were ticking when these oral beta-lactamase penicillins were discovered.
Gram positive organisms are targeted, especially if they produce penicillinase. So if a patient has infected skin wound (cellultis, impetigo, etc.) you know he probably has staph aureus or group A beta-hemolytic streptococcus. So treating with penicillin G, V, or ampicillin wouldn't cover for peniccilinase-producing Staph aureus. So you can give an "oral" cloxacillin or dicloxacillin. Staph aureus patients need this because some strains are penicillinase-producing, and you don't want to take care of them around the clock! |
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Anti-Pseudomonal Penicillins
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(Carboxypeniccilins and Ureidopeniccilins).
These have expanded gram-negative-rod coverage, especially against the difficult-to-destroy Pseudomonas Aeruginosa. They are also active against anaerobes (bacteroides fragilis--remember your surgical guy) and many gram positives. |
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Tx. of pseudomonas
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This bugger can cause devastating pneumonia and sepsis. We need James Bond to help eliminate it. Bond has 3 weapons.
He has a car (equipped with weapons), a trained tick that can home target and suck the life out of them, and megaton pipe bomb: Carboxypenicillins: (Car and Tick= CARbeniccilin and TICaracillin) Ureidopiniccilins: PIPEracillin and Mezlocillin |
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You may wish to combine anti-pseudomonal peniccilins (piperacillin, ticarcillin and carbeniccilin) with what agent to double killing power against pseudomonas?
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An aminoglycoside doubles up on Pseudomonas killing (synergism).
"Pip and gent" and "Ticar and gent" |
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Do anti-pseudomonal peniccilins kill staphylococcus aureus?
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Most staphylococcus aureus (Gr + war ships) shoot out penicillinase that are able to dismantle James Bond (Carboxypeniccilins: TIC, CAR and Ureidopeniccilins: PIPE)
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Carbeniccilin disadvantages
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This anti-pseudomonal penicillin has a lower activity and requires high doses, high sodium load, platelet dysfunction, and hypokalemia. Generally, ticarcillin / ureidopeniccilin has reduced these problems and provided activity.
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Beta-lactamase inhibitors
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Clavulanic acid, sulbactam, and tazobactam are given WITH penicillins--and together they get married and form a beta-lactamase resistant drug combo. (we don't want our lovley guest house to be destroyed)
1. Amoxicillin + Clavulanic acid= Augmentin 2. Ticaricillin and clavulanic acid= Timentin 3. Ampicillin and Sulbactam = Unasyn 4. Piperacillin and Tazobactam= Zosyn (trade name) |
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Beta-lactamase inhibitor enzymes combined with Peniccilins provide what kind of coverage?
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Broad coverage against beta-lactamse producing gram-positives (Staphylococcus aureus), gram-negatives (Haemophilus influenza), and aerobes (Bacteroides fragilis)
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Cephalosporins, and advantages over peniccilin
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>20 different different kinds of cephalosporins.
2 advantages over peniccilin: 1. new basement makes beta-lactam ring much more beta-lactamase resistant (but more susceptible to cephalosporinases) 2. New R-group side chain (another antennae-cable) allows for double the manipulations in lab. |
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Cephalosporin generations, and changes in spectrum
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3 generations: 1st, 2nd, and 3rd. The generations are based on activity against gram-negative and gram-positives.
The key concept here is we have better activity against gram negatives w/each generation (e.coli is screwed) but unfortunately, less effective against gram-positive organisms. |
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What generation of cephalosporins would be best used against streptococci and staphylococci?
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First generation. These are gram positive organisms, and the ceaphalosporins get progressively worst against gram positives with each subsequent generation.
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MRSA--cephlosporins?
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(Methicillin Resistant Staphylococcus Aureus) is resistant to ALL cephalosporins because of altered penicillin binding protein (transpeptidase).
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How does MRSA require resistance?
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Altered structure of transpeptidase
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Enterococci and cephalosporins
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Enterococci including strep faecalis are resistant to them
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4th generation antibiotic
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This would have a great gram-negative coverage like a 3rd generation, but very good gram-positive coverage!!!
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Identify all the first-generation cephalosporins
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All cephalosporins have "cef" in names, but 1st generation "cephalosporins" are the only ones with a PH.
To know the 1st generation cephalosporins, you must FIRST get a PH.D in PHarmocology. 1. cephalothin 2. cephapirin 3. cephradine 4. cephalexin Exceptions: cefazolin, cefadroxil. Cefazolin is an important 1st-gen ceaphlosporin, so don't this FAZe you-- you silly non-Ph.D. med student! |
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Cephalothin
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1st generation cephalosporin
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Cephapirin
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1st generation cephalosporin
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Cephradine
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1st generation cephalosporin
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Cephalexin
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1st generation cephalosporin
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cefazolin and cefadroxil are...
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1st generation cephalosporins
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Second-generation cephalosporins
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Have fam, fa, fur, fox, or tea in their names. After Ph.D., you would want to gather your "FAMily to celebrate! The FAMily is gathered, some wearing FUR coats, and your FOXy cousin is drinking TEA in a toast to your achievement!"
1. ceFAMandole 2. ceFAclor 3. ceFURoxime 4. ceFOXitin 5. cefoTEtan (pronounced tea-tan) Exceptions: (cefmetazole, cefonicid, cefprozil, and loracarbef). |
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Third generation cephalosporins
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Most have a T (for tri or third) in their names.
1. cefTRIaxone 2. cefTAZidime 3. cefoTAXime 4. cefTIzoxime 5. cefTIbuten (exceptions: cefixime, cefoperazone, cefpodoxin, and cefetamet) Note that cefotetan (tea) is a second generation drug and has a "T" in it |
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cefamandole, cefaclor, cefuroxime, and cefoxitin, cefotetan
& cefmetazole, cefonicid, cefprozil, and loracarbef are... |
second generation antibiotics
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ceftriaxone, ceftrazidime, cefotaxime, ceftizoxime, ceftibuten are all...
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third generation antibiotics.
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Fourth generation cephalosporins
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Cefepime
"It is the only cephalosporin with a "FEP" inits name" Cefpirome is an investigation agent that will also belong in this class. |
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Cephalosporin adverse rx.
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10% of those with allergies to penicillin will react to cephalosporin via IgE-mediated rx. or the more common rash-->weeks later.
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When to use 1st generation cephalosporins
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If you recall, 1st generations are GREAT against gram positive organisms (and this effectiveness is de-bunked with each subsequent generation).
So let's say we want to treat a gram-positive infection such as a staphyloccocal or streptococcal infection with peniccilin, but ou patient has a peniccilin allergy? Give them a 1st generation cephalosporin (yeah, the pH.D dudes). Surgeons giver before surgery to prevent skin infection as well. |
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Second generation cephalosporins:
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With added gram-negative rod coverage from the 1st generation, ceFURoxime we now hit STREP PNEUMO and H.INFLUENZA.
Since strep pneumo and H. flu are community-acquired pneumonia, these are good choices for community acquired pneumonia. Also we get anerobic coverage w/3 2nd gens (ie bacteroides fragilis) which is great for surgical prophylaxis. |
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Second generation cephalosporins that kill anaerobic bacteria (such as b. fragilis)
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A fox (cefoxitin) who met (cefmetazole) an anaerobic bug for tea (cefotetan)
1. cefotetan 2. cefotoxitin 3. cefmetazole |
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Third-generation cephalosporin indications:
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Used for multi-drug resistant aerobic, gram-negative organisms that cause nosocomial pneumonia, meningitis, sepsis, and UTI. (cefepime, is sometimes called extended spectrum 3rd gen w/ added muscle against gram positives and psuedomonas)
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Which cephalosporins are effective against pseudomonas aeruginosa?
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"impossible to kill" Pseudomonas: Give it to the TAZ, the FOP, and the FEP!"
1. cefTAZidime 2. ceFOPerazone 3. ceFEPime Ceftriaxone (a 3rd generation) has the best CNS penitration and is good for meningitis. |
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1st line therapy for meningitis in neonates, children, and adults.
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Ceftriaxone (3rd generation cephalosporin)-->best CSF penetration
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Tx. of gonorrhea (neisseria gonorrhoea)
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Ceftriaxone is also given IM for gonorrhea (more Neisseria gonorrhoea have become resistant to penicillin and tetracycline)
(Recall neisseria are the pathogenic only gram-negative cocci) |
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Imipenem
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There is now a new class of beta-lactam antibiotics called "carbapenems."
Say to yourself, "I'm a pen" and picture the pen crossing out all the bacteria that are difficult to treat. The pen (imipenem) can terminate almost all of them! Imipenem has the broadest antibacterial of any antibiotic known to man!! It kills gram-negatives, gram-positives, anaerobes (pseudomonas enterococcus). MRSA is STILL resistant to this drug, along with some pseudomonas species and bacteria without peptidoglycan cell walls (Mycoplasma). |
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Imipenem mechanism
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Stable to beta-lactamases. Small and can pass through porins into periplasm. In the periplasm, it can interact with transpeptidase (similar to peniccilins and cephalosporins).
Interestingly, this drug lowers seizure theshold. |
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Imipenem resistance
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Sadly, heay use of imipenem has led to bacterial strains that have new enzymes that can HYDROLYZE imipenem, and some gram negative bacteria have squeezed down their porin channels to prevent penetration of imipenim. (and that's pretty small man!)
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Imipenim metabolism
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Normal kidney has a "dihydropeptidase that breaks imipenem down, so selective enzyme inhibitor of dihydropeptidase is co-administered. It is known as cilastin"
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"Decerebrate antibiotic"
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Imipenem! It covers almost almost everything, so you don't even have to use your cerebrum to think about what it covers!!
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Meropenem
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A newer carbapenem that is as powerful as as imipenem. It can be used interchangeably. Meropenem is stable against dihydropeptidase (no co-admin of cilastin).)
Reduced seizure risk as compared to imipenem. |
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Aztreonam structure and classification
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Magic bullet for gram-negative aerobic bacteria! It is a beta-lactam antibiotic (but it is unique in that it is a monobactam).
Like the name suggests, a monobactam ONLY has the beta-lactam ring (just the guest house!) It still has the side groups attached to the ring. As a result of this, it does not bind to transpeptidases of gram-positive anaerobic bacteria, only to the transpeptidase of gram-negative bacteria. |
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Which beta-lactam antibiotic only binds to the transpeptidase of gram negative bacteria?
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Aztreonam (A TREE=AzTREonam) has fallen through the center of our house, leaving only the square portion (guest house=beta-lactam ring). If this happened to your cute little house, it would be a negative experience. Likewise, it kills gram-negative, aerobic activity.
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Aztreonam and pseudomonas aeruginosa
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Yes it kills the tough, hospital-acquired, multi-drug resistant gram-negative bacteria such as Pseu. aeruginosa.
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Aztreonam use in patients with peniccilin allergies?
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Yes, little cross-reactivity.
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Aztreonam spectrum and administration
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Coverage is limited to gram-negative bugs, so it is used (like aminoglycoside) with an antibiotic that covers gram-positives.
So you would coadminister with the following to get powerful, broad-spectrum coverage: vancomycin or clindamycin. Vancomycin + aztreonam Clindamycin + aztreonam |
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Combo penicillin:
Amoxicillin + clavulanate |
Augmentin
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Combo penicillin:
Ticarcillin + clavulanate |
Timentin
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Combo penicillin:
Ampicillin + Sulfbactam |
Unasyn
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Combo peniccilin:
Piperacillin + Tazobactam |
Zosyn
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