Micro Made Simple- Chapter 17: Anti-Ribosomal Antibiotics

Front 1

Bacterial ribosomes

Back 1

They're smaller than ours. Bacterial ribosomes are smaller than ours.

We have an 80S particle, the bacterial ribosome consists of a 70S particle with a 50S and 30S subunit.

Obviously, 50S+30S=70S! ...

Front 2

5 important types of antibiotics that inhibit the function of the bacterial ribosome:

Back 2

CLEan TAG! Convert the ribosome to a homeplate with the 50S (big) subunit on top of the 30S (small) subunit. In baseball, the catcher makes a clean tag, and the player is out!!! CLEan on top of the base and TAG below it.

Then divide it in quadrants.

C (Chloramphenicol/Clindamycin)
L (Linezolid)
E (Erythromycin)
T (Tetracycline)
AG (Aminoglycosides)

In doing so, clean lies over the base, and TAG lies beneath the base.

Front 3

Chloramphenicol/clindamycin, linezolid, and erythromycin acts on the:

Back 3

50S subunit of the bacterial ribosome.

Front 4

Tetracycline and AminoGlycosides act on the:

Back 4

30S subunit of the bacterial ribosome.

Front 5

Which of the anti-ribosomal antibiotics cannot be absorbed orally and must be administered via IM injection?

Back 5

Aminoglycosides (which act on the 30S subunit).

Front 6

Chloramphenicol

Back 6

(The "Chlorine"). Amazing spectrum! Like imipenem, it kills MOST clinically important bacteria. (Imipenem doesn't cover MRSA).

Imagine pouring chlorine over the organisms! Postive, negative, and EVEN ANEROBIC BACTERIA are susceptible.

One of the few that can kill bacteroides fragilis.

Front 7

Clinical use of Chloramphenicol

Back 7

Rare but severe side effects limits this (otherwise excellent) drug to one of last resort (the benefits far outweigh the risks).

Examples:
1. Bacterial meningitis when organism is not yet known or patient has severe penicillin/cephalosporin allergies. Protects patient from devastating consequences of meningitis.

2. Young children/pregnant woman w/ Rocky Mountain spotted fever can't be treated with tetracycline due to side effects of tetracycline discussed on page 128. Go with Chloramphenicol.

Front 8

Chloramphenicol is what type of drug?

Back 8

Anti-ribosomal

Front 9

Clindamycin is what type of drug?

Back 9

Anti-ribosomal

Front 10

Erythromycin is what type of drug?

Back 10

Antib-ribosomal

Front 11

Adverse effects of chloramphenicol:

Back 11

1. Can of chloramphenicol-->pour down onto shaft of bone marrow. Chloramphenicol causes two types of bone marrow disease:

1. dose-related/reversible (bone marrow depression and anemia)

2. Wipes out bone marrow irreversibly, usually fatal "Aplastic Anemia."

Front 12

Aplastic anemia may result secondary to use of what anti-ribosomal drug? What are the consequences of this?

Back 12

Aplastic anemia, a usually fatal wiping-out of bon marrow,is rare (1:24,000 to 1:40,000 cases)

Front 13

Gray Baby syndrome may be the result of the use of what drug?

Back 13

Neonates are unable to fully conjugate chloramphenicol in the liver or excrete it through the kidney--> high blood levels.

This leads to toxicity with vasomotor collapse (shock), abdominal distention, and cyanosis (ashen gray discoloration).

Front 14

Clindamycin Clinical uses

Back 14

NOT gram negatives. NOT against MANY gram-positives. WHAT ELSE!!!?

ANAEROBIC BACTERIA, of course!

It's another feather in the cap of rare antibiotics that cover anaerobes (such as bacteroides fragilis).

Surgeons often use clindamycin+ aminoglycoside for penetrating wound infections of abdomen.

This combo uses aminoglycosides to cover aerobic gram negatives and clindamycin to cover the anaerobes.

Infections of the female genital tract (septic abortions.) Alternatives to metronidazole for tx. of bac. vaginosis.

Topically useful for tx. of acne vulgaris and rosacea.

Front 15

What antibiotic can cause pseudomembranous colitis?

Back 15

CLINDAMYCIN! It destroys natural GI flora. C. dificile (if resistant) can hrow grow like a mad-hatter and secrete exotoxin into colon! This causes
1. epithelial cell death
2. colonic ulcertaions (covered with exudative membrane)

Peniccilins can do this. (Oral vancomycin or metronidazole is needed to eliminate c. difficile, but metronidazole is better because we are getting vanco resistant enterococcus.

Front 16

Killing of C. difficili (a notable pathogen for causing pseudomembranous colitis) can be treated with?

Back 16

vancomycin and metronidazole. (Metronidazole is the tx. or choice).

The VAN and METRO cruise down the GI tract, and run over ulcerative potholes of pseudomembraneous colitis and kill those offending C. difficile.

Front 17

C. difficile causes

Back 17

pseudomembraneous colitis

Front 18

Linezolid

Back 18

("Godzilla Lizard" new antimicrobial agent for stomping gram positive bugs.

Action on 50S ribosome incurs activity against gram positive organisms including those resistant to other antimicrobials.

Lizard will find a place as a last resort for vancomycin resitant enterococcus (VRE).

Front 19

Erythromycin coverage

Back 19

"A Wreath"

Gram-positive organisms absorb erythromycin 100x better than gram negative bugs.

Covers gram positive bugs, mycoplasma, and gram negatives legionella/chlamydia (atypicals)

Drug of choice for community-acquired pneumonia because it doesn't require hospitalization (coverage for strep pneumo, mycoplasma pneumoniae, and chlamydia trachomatis (TWAR STRAIN).

Front 20

If a patient with an infection with a strep or staphylococcal organism is allergic to peniccilins, what is another organism that can be used in this patient?

Back 20

Erythromycin often used as an alternative to penicillinfor strep and staph (especially for strep throat and cellultis).

Front 21

Drug of choice for Legionnire's disease

Back 21

(Erythromycin. A wreath was left on French Foreign Warrior "Legionnare" whose tombstone appears as a cross that covered gram-positive-organisms. He got a few atypicals as well (hence the cross is shaped a bit strangely).

Front 22

Erythromycin adverse effects

Back 22

One of the safest antibiotics. A prett wreath compared to the natsy chlorine of chloramphenicol. Its few side effects include:

1. Common and dose-dependent abdominal pain (GI irritation) resultin from stimulation of intestinal peristalsis

2. Rare cholestatic hepatitis. Imagine a wreath slipping into the bile duct and blocking flow.

Front 23

New drugs in the class of macrolide antibiotics

Back 23

Clarithromycin, azithromycin, and roxithromycin

Front 24

Drugs in the class of macrolide antibiotics

Back 24

Erythromycin, clarithromycin, azithromycin, and roxithromcycin.

Front 25

clarithromycin, azithromycin and roxithromycin can be used to treat:

Back 25

They can treat the same gram positive bugs as erythromycin (legionnaire's disease, strep/staph in allergic patients), but also severe staphylococcal infections, haemophilus influenzae, and even atypical mycobacterium (Mycobacterium avium-intracellulare, MAI)

Front 26

Indications for use of Azithromycin:

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1. Alternative to doxycycline for tx. of chlamydial, non-gonococcal urethritis. Single-dose by mouth. (Also community acquired pneumonia).

Front 27

Tetracycline/Doxycycline

Back 27

"The Tet Offensive"

Tetracycline chelates with milk, aluminum hydroxide, ca++ and Mg++, preventing absoprtion; however, Doxycycline is a tetracycline with poor cationic chelation (better absorbed with food). IV tetracycline no longer available.

Front 28

Clinical use of Tetra cycline?

Back 28

A vietnamese soldier in the "Tet offensive" gets disease by crawling in the jungle and mingling with prostitutes on leave:

1. Venereal diseases caused by "Chlamydia trachomatis"
2. Walking pneumonia caused by "Mycoplasma pneumonieae --used as an alternative to erythromycin with coverage for atypicals)
3. Animal and tick-borne disease caused by Brucella and Rickettsia (see the tick's on the Tet offensive soldier's pants).
4. Doxycycline also is an acne miracle, that soldier needs some!

Front 29

Side effects of Tetracycline/Doxycycline

Back 29

A vietcong soldier in the tet-offensive!

1. very nervous as the Tet offensive involves firepower, so he has GI irritation with nausea, vomiting and diahhrea (common side effect of tet offensive)

2. A grenade blew up near him, burning him like sunburn, The rays of light going from the explosion. Phototoxic dermatitis is a skin inflammation on exposure to sunlight following tetracycline.

3. Shrapnel has stuck in his liver: renal and hepatic toxicity. Adverse effects rare (usually occur in pregnant women receiving high doses by IV route).

4. Discolored teeth. Drug chelates to Ca2+ in the teeth and bones of babies and children <7, resulting in brown teeth and depressed bone growth. If the pregnant prostite who is carrying Cong's baby were to the take the drug, her baby's teeth would like this too!

Front 30

Aminoglycosides

Back 30

"A mean Guy"

They must diffuse across the cell wall to enter bacterial cell (thus they are often used with peniccilin, which breaks down this wall to facilitate fusion).

Front 31

Clinical uses of aminoglycosides

Back 31

Killing of aerobic gram-negative enteric organisms

The aminoglycosides are among the handful of drugs that kill the terrible Pseudomonas aeruginosa!

Front 32

Name 6 Aminoglycosides

Back 32

Most end with -mycin

1. Streptomycin: (is the oldest one in the family--many bugs are resistant to it).

2. Gentamicin: Is the most commonly used of all the aminoglycosides. It is combined with peniccilins to treat in-hospital infections. there are also many bacterial strains resistant to this drug.

3. Tobramycin-good against terrible Pseudomonas aeruginosa

4. Amikacin--Does not end with MYCIN, so it has the broadest spectrum and is good for hospital acquired infections that have developed resistance to other drugs.

5. Neomycin--very broad coverage, but too toxic (so it can only be used topically for skin infections.

6. Netilmicin (b) Preoperative coverage before GI surgery. This drug is given orally before GI surgery as it cruises down the GI tract (without being absorbed), killin' the locals. We wouldn't want spilling into the peritoneal cavity!

Front 33

Aminoglycosides

Back 33

A huge boxer, a mean guy (Aminoglycosides). He punches the opponent in the ear (eighth cranial nerve toxicity, vertigo, and hearing loss) w/ reversible hearing loss.

He also pulverizes his kidney (renal tox). (follow BUN/creatinine please)

Opponent drops to floor w/ neuromuscular blockade "curare-like effect"-->rare!

Front 34

Spectinomycin (Spectacular Spectinomycin)

Back 34

Spectinomycin SOUNDS like an aminoglycoside (But different structurally and biologically).

Acts on 30S ribosome (inhibits protein synthesis) but we don't now how.

Front 35

Clinical use of spectromycin

Back 35

Used to treat gonorrhea (caused by Neisseria gonorrhoeae) as an alternative to peniccilin and tetracycline (doxycycline). Many strains of Neisseria have developed resistance to peniccilin and doxycycline (CLE/TAG).

Front 36

Spectacular Spectinomycin

Back 36

If Mr. Gonorrhea thinks he is really cool busting up tetracycline (30S and penicillin) shoot him up with the Spectacular Spectinomycin injuection from your super spectinomycin injection gun. Give neisseria one shot in the BUTT! (along with doxycycline for chlamydia-->which acts on 30S ribosome)

Front 37

Adverse effects of spectinomycin

Back 37

Does not cause the vestibular, cochlear, and renal toxicity that aminoglycosides do.