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Microbiology > Penicillin Family Antibiotics > Flashcards

Penicillin Family Antibiotics Flashcards

0
Q

What is the mechanism of action of beta-lactam penicillin?

A

The penicillin beta lactam ring binds and competitively inhibits the transpeptidase enzyme.
In gram negative bacterias, it passes through the porins.

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1
Q

What do all penicillin family antibiotics have in common ?

A

A beta-lactam ring.

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2
Q

What is necessary for a beta lactam penicillin to be effective?

A
  1. Penetrate the cell layers.
  2. Keep its beta lactam ring intact
  3. Bind to the transpeptidase (penicillin binding protein).
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3
Q

What are the main ways by which the bacteria defend themselves against the penicillin family?

A
  1. Gram negative bacterias alter their porins.
  2. Both gram positive and negative bacteria can have beta lactamase enzymes (the positive secrete them and the negative have them bound to their cytoplasmic membranes).
  3. They can alter the molecular structure of the transpeptidase (MRSA).
  4. They can develop the ability to actively PUMP OUT the beta lactam before it can bind to the transpeptidase enzyme. (“Efflux” pump)
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4
Q

What are the adverse effects of penicillin family antibiotics?

A
  1. All of them can cause anaphylactic (allergic) reactions - more commonly a delayed rash appears several days to weeks later.
  2. Diarrhea by destroying the natural GI flora and allowing resistant pathogenic bacteria (C.difficile) to grow in their place.
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5
Q

What are the 5 major types of penicillin ?

A
  1. Penicillin G
  2. Aminopenicillins
  3. Penicillinase resistant penicillins
  4. Anti pseudomonal penicillins
  5. Cephalosporins
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6
Q

How is penicillin G administered?

A

There are oral dosage formulations of Penicillin G, but it is usually given IM or IV in a crystalline form to increase half life.

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7
Q

Many organisms have now developed resistance to the old penicillin G, because it is sensitive to beta-lactamase enzymes. Mention some few notable examples where it is still used?

A
  1. Pneumonia caused by Streptococcus pneumoniae (however resistant strains are common).
  2. Penicillin V is an oral form of penicillin. It is acid stable in the stomach. It is commonly given for streptococcus pharyngitis caused by group A beta hemolytic streptococcus.
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8
Q

Mention the two major aminopenicillins.

A
  1. Ampicillin

2. Amoxicillin

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9
Q

What is the main difference between aminopenicillins and penicillin G?

A

They have a broader spectrum, hitting more gram negative bacteria.

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10
Q

Where is this enhanced gram negative killing of aminopenicillins attributable to?

A

To better penetration through the outer membranes of gram negative bacteria and better binding to the transpeptidase - though still inhibited by penicillinase.

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11
Q

Against what bacteria are aminopenicillins effective?

A
  1. E.coli and other enterics - however resistance has developed :
    30% of Haemophilus influenza and many of the gram negative enterics have acquired penicillinase and are resistant.
  2. One of the few drugs effective against the gram positive enterococcus.
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12
Q

How are aminopenicillins administered?

A

Both ampicillin and amoxicillin can be taken orally, but amoxicillin is more effectively absorbed orally so you will frequently use it for outpatient treatment of bronchitis, otitis media, and sinusitis.

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13
Q

When is IV ampicillin commonly used?

A

With other antibiotics such as aminoglycosides (gentamicin) for broad gram negative coverage. (The amp-gent combo!)

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14
Q

For what infections is amoxicillin the drug of choice?

A

Infections caused by Listeria.

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15
Q

What are the three main penicillinase-resistant drugs?

A
  1. Methicillin
  2. Nafcillin
  3. Oxacillin
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16
Q

Against what infection are the penicillinase-resistant drugs effective?

A

Against Staphylococcus aureus.

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17
Q

How are the penicillinase-resistant drugs usually administered?

A

IV

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18
Q

For what infections is nafcillin the drug of choice?

A

For serious staphylococcus infections :

  1. Cellulitis
  2. Endocarditis
  3. Sepsis
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19
Q

What are the two major ORAL beta-lactamase resistant penicillins?

A
  1. Cloxacillin

2. Dicloxacillin

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20
Q

Against what bacteria are oral beta-lactamase resistant penicillins effective?

A

Not good against gram negative organisms.

Used for gram positive bacteria - especially those that produce penicillinase (S.aureus).

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21
Q

Against what infections are the anti-pseudomonal penicillins particularly effective?

A

Against the gram negative and difficult to destroy Pseudomonas aeruginosa.
Also active against anaerobes (Bacteroides fragilis) and many gram positives (without penicillinase).

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22
Q

What drugs are used against Pseudomonas aeruginosa pneumonia and sepsis?

A

Carboxypenicillins : Ticarcillin and Carbenicillin

Ureidopenicillins : Piperacillin and Mezlocillin

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23
Q

Mention some disadvantages of Carbenicillin.

A
  1. Low activity thus need for high dosages.
  2. High sodium load.
  3. Platelet dysfunction.
  4. Hypokalemia.
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24
Q

What are the main combinations of beta lactamase inhibitors with penicillins?

A
  1. Amoxicillin with clavulanic acid = Augmentin
  2. Ticarcillin with clavulanic acid = Timentin
  3. Ampicillin with sulbactam = Unasyn
  4. Piperacillin with tazobactam = Zosyn
25
Q

Against what infections are the beta lactamase inhibitors with penicillins effective?

A

They provide coverage against gram positive beta lactamase producing (S.aureus), gram negatives (Haemophilus influenza), and anaerobes (Bacteroides fragilis).

26
Q

What are the three main advantages of the cephalosporins over the penicillins?

A
  1. The addition of a new basement makes the beta lactam ring much more resistant to beta lactamases (but now susceptible to cephalosporinases!).
  2. A new R-group side chain (another antenna-cable TV if you will) allows for double the manipulations in the lab. This leads to all kinds of drugs with different spectrums of activity.
27
Q

Against what infections are the newer generations of cephalosporins INeffective?

A

Against gram positives. They have greater ability to kill more gram negatives.

28
Q

What important bacteria are resistant to cephalosporins?

A
  1. MRSA - because it has changed the structure of its penicillin binding protein (transpeptidase).
  2. The enterococci (including streptococcus faecalis).
29
Q

Mention some important first-generation cephalosporins.

A
  1. Cephalothin
  2. Cephapirin
  3. Cephadrine
  4. Cephalexine
  5. Cefazolin (also the only IV first generation cephalosporin).
30
Q

Mention some important second generation cephalosporins.

A
  1. Cefamandole
  2. Cefaclor
  3. Cefuroxime
  4. Cefmetazole
  5. Cefonicid
  6. Cefprozil
  7. Cefoxitin
  8. Cefotetan
31
Q

Mention some important third generation cephalosporins.

A
  1. Ceftriaxone
  2. Ceftazidime
  3. Cefixime
  4. Cefdinir
  5. Cefpodoxime
  6. Cefditoren
  7. Cefotaxime
  8. Ceftizoxime
  9. Ceftibuten
32
Q

Mention the one fourth generation cephalosporin.

A

Cefepime

33
Q

Mention the newest kid on the block - the fifth generation cephalosporin.

A

Ceftaroline - the only cephalosporin with activity against MRSA.

34
Q

What are the adverse effects of cephalosporins?

A

Ten percent of patients who have allergic reactions to penicillin will also have a reaction to cephalosporins. (The same allergic reactions with penicillin)

35
Q

Where do we use first generation cephalosporins?

A
  1. Against staphylococcal and streptococcal infections when penicillin cannot be tolerated (allergy).
    Excellent gram positive coverage.
  2. Surgeons love to give these drugs before surgery to prevent infection from the skin.
36
Q

What advantage have the second gen cephalosporins compared to the first gen cephalosporins?

A

They cover more of the gram negative rods than the first generation.

37
Q

What is the main use of Cefuroxime (2nd gen cephalosporin)?

A
  1. It has good coverage against BOTH Streptococcus pneumoniae and Haemophilus influenzae - ideal agent for community acquired bacterial pneumonia.
  2. Also good for sinusitis and otitis media (often caused by H.influenza and Moraxella catarrhalis).
38
Q

What are the three 2nd gen cephalosporins that have anaerobic coverage?

A
  1. Cefotetan
  2. Cefoxitin
  3. Cefmetazole
39
Q

Where do we use 3rd gen cephalosporins?

A

Primarily for inpatient treatment of :

  1. Community acquired pneumonia
  2. Meningitis
  3. Pyelonephritis (urinary tract infection that has gone to involve the kidneys).
40
Q

Where do we use the 4th gen cephalosporins?

A

The 4th gen cefepime is an extended 3rd gen cephalosporin with a little added muscle against gram-positives and the terrible P.aeruginosa.

41
Q

What are the only cephalosporins that are effective against the “impossible-to-kill” P.aeruginosa?

A
  1. Ceftazidime

2. Cefepime

42
Q

Where do we use Ceftriaxone and cefotaxime?

A

Both have excellent CSF penetration - cover the common bacteria that frequently cause meningitis.
Ceftriaxone : the drug of choice in adults with meningitis + given IM for gonorrhea, as more Neisseria gonorrhoea have become resistant to penicillin and tetracycline.
Cefotaxime : first line drug in neonates and children with meningitis.

43
Q

Where do we use ceftaroline?

A

Can be used for pneumonia and skin infections, but its real beauty is its activity against MRSA.

44
Q

Mention 4 important carbapenems.

A
  1. Imipenem
  2. Meropenem
  3. Doripenem
  4. Ertapenem
45
Q

What are the carbapenems?

A

One of the newer classes of antibiotics and they have some of the broadest coverage.
They are resistant to beta lactamases, including the newer Extended Spectrum Beta-Lactamases (ESBLs).

46
Q

What antibiotic has the broadest antibacterial activity of any antibiotic known to man?

A

IMIPENEM!

47
Q

Mention some bacteria that are resistant to imipenem?

A
  1. MRSA
  2. Some Pseudomonas species
  3. Bacteria without peptidoglycan cell walls (Mycoplasma)
48
Q

What is the selective kidney enzyme inhibitor that is given with imipenem?

A

Cilastatin (inhibits a kidney dihydropeptidase that breaks down imipenem)

49
Q

What are the adverse effects of Carbapenems?

A
  1. Allergic reactions similar to those of penicillin, with about a 10% cross reactivity.
  2. Imipenem is notable for making seizures more likely by lowering one’s seizure threshold. (Avoid in patients with a history of seizures, meningitis, prior strokes, or evidence of brain masses).
50
Q

What is the advantage of meropenem and doripenem compared to imipenem?

A

Cilostatin is not needed - they are stable against the dihydropeptidase.
+ less potential for causing seizures.

51
Q

What is the advantage of ertapenem?

A

Requires only once daily IV administration.

52
Q

Where is ertapenem mainly used?

A

The drug of choice for severe diabetic foot infections (usually polymicrobic).

53
Q

What is the main difference of ertapenem compared to the other carbapenems?

A

It does not cover P.aeruginosa.

54
Q

What is the main use of Aztreonam?

A

Gram negative aerobic bacteria (including P.aeruginosa). It is a monobactam - the beta lactam ring does not bind to the transpeptidases of gram positive or anaerobic bacteria, only to the transpeptidase of gram negative bacteria.

55
Q

Mention the antibiotics that cover P.aeruginosa.

A
  • Antipseudomonal Penicillins :
    1. Ticarcillin
    2. Timentin
    3. Piperacillin
    4. Zosyn
    5. Carbecillin (no longer produced in U.S.)
  • Third gen cephalosporins :
    1. Ceftazidime
    2. Cefoperazone (no longer produced in the U.S.)
  • Fourth gen cephalosporins :
    1. Cefepime
  • Carbapenems :
    1. Imipenem
    2. Meropenem
    3. Doripenem
  • Aztreonam
  • Ciprofloxacin
  • Aminoglycosides :
    1. Amikacin
    2. Gentamicin
    3. Tobramycin
  • Polymixins
56
Q

Mention some important antibiotics that cover the anaerobes (including B.fragilis).

A
  • Penicillins with beta-lactamase inhibitor :
    1. Augmentin
    2. Timentin
    3. Unasyn
    4. Zosyn
  • Second gen cephalosporins :
    1. Cefoxitin
    2. Cefotetan
    3. Cefmetazole
  • Carbapenems (all 4)
  • Chloramphenicol
  • Clindamycin
  • Metronidazole
  • Moxifloxacin
  • Tigecycline
57
Q

Mention the antiobiotics that cover the MRSA.

A
  1. Vancomycin
  2. Linezolid
  3. Daptomycin
  4. Quinupristin
  5. Dalfopristin
  6. Tigecycline
  7. Ceftaroline
58
Q

Mention the antibiotics that cover the VRE.

A
  1. Linezolid
  2. Daptomycin
  3. Tigecycline
59
Q

Can Aztreonam be used in penicillin allergic patients?

A

Yes - there is little cross reactivity with the bicyclic beta-lactams.

Microbiology (46 decks)

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