34. Protein Synthesis Inhibiting Abx

Question 1

bacterial ribosome vs human ribosome?

Answer 1

bacterial: 30S + 50S = 70 S
human: 40S + 60S = 80S

Question 2

aminoglycosides mechanism of action and resistance?

Answer 2

gentamicin or amikacin

binds 30S ribosomal subunit, causes misreading or termination of genetic code, inhibits protein synthesis

unable to penetrate GP cell wall (but use for SYNERGY w/B-lactams which interfere w/cell wall synthesis and allow these to enter)

Question 3

aminoglycosides general properties/PK/PD?

Answer 3

bactericidal or bacteriostatic (depends on [ ] )

IV only, high [ ] in ear and kidneys, inactivated by acidic env’ts (low [ ] in lungs/inhibited by pH so avoid in pneumonia and not good for abscesses)

CAN’t treat adverse events! So monitor closely, qd dosing, and avoid nephrotoxins

Question 4

adverse events of aminoglycosides?

Answer 4

gentamicin, maikacin

OTOTOXICITY (peak levels, irreversible, cochlear damage: hearing loss; vestibular damage: vertigo)

NEPHROTOXICITY/tubular necrosis (variable damage, irreversible, increased risk w/radiocontrast, cyclosporine, amphotericin B, or vancomycin)

respiratory distress in pts w/myesthenia gravis

Question 5

aminoglycosides spectrum of activity and uses?

Answer 5

broad spectrum vs. GN (incl pseudomonas), innefective vs GP when used alone (synergy w/B-lactams vs S.aureus and enterococci)

NO anaerobic coverage

use for mycobacteria, YERSENIA PESTIS (plague) or FRANCISELLA TULARENSIS (tularemia)

use for enterococci (endocarditis) w/b-lactams, use for UTIs (alone), or for serious GN infections (double coverage)

Question 6

A 35 year old man is admitted with a kidney stone obstructing his right kidney. He is started on ampicillin and gentamicin. Three days into therapy, he starts complaining of difficulty hearing.
What is going on?

Answer 6

Ototoxicity; irreversible and dose-related side effect of gentamicin

Question 7

tetracyclines mechanism of action/resistance

Answer 7

action:
Binds 30S ribosomal subunit (reversible), blocks access of tRNA to mRNA, inhibits bacterial protein synthesis, lipophilic, allows entry into GN/GP

resistance:
Common; plasmid-mediated; active efflux from bacterial cell (GN/GP) or ribosomal protection proteins (GN/GP/anaerobes)

Question 8

tetracyclines general properties/PK/PD

Answer 8

doxycline, tetracycline, minocycline

Bacteriostatic (reversibly binds)

Dairy, ca++ decrease absorption; binds to tissues undergoing calcification (concentrated in teeth/bones)

Question 9

tetracyclines adverse effects, spectrum of activity and clinical indications?

Answer 9

doxycline, tetracycline, minocycline

Do not give to young kids/pregnant women; deposition into bone and primary dentition during calcification (staining of teeth, hypoplasia of teeth, stunted growth); photosensitivity

GP: Staphylococci (and some CA-MRSA) and some streptococci
GN:Broad spectrum (not pseudomonas), limited by resistance
other: Some anaerobic; use for chlamydia and mycoplasma

use: Bronchitis, CA-PNA, stis: chlamydia

Question 10

A 2nd year medical student after a grueling year of school goes to Thailand for 1 month. She is prescribed doxycline for malaria prophylaxis. 1 week into her trip he notices that his skin is burning despite using sunscreen.
What is going on?

Answer 10

Photosensitivity rash related to doxycycline

Question 11

glycylcyclines?

Answer 11

tigercycline

Semi-synthetic derivative of tetracyclines – w/structural modifications for broader coverage and overcomes resistance to tetracyclines

resistance: Rapidly may develop in GN orgs, limiting clinical use

IV only

Do not give to young kids/pregnant women; deposition into bone and primary dentition during calcification (staining of teeth, hypoplasia of teeth, stunted growth); photosensitivity; INCREASED MORTALITY RISK WHEN USE FOR USE VS PNEUMONIA

GP: Staphylococci (incl MRSA), streptococci, enterococci (incl VRE)
GN:Except pseudomonas, proteus, morgnaella
other:most anaerobes

use:
Complicated skin/soft tissue, complicated intra-abd infection, CA-PNA

Question 12

You are treating a 65 year-old women for an infected, complicated diabetic foot ulcer. Despite treatment with tigecycline and adequate surgical debridement the ulcer is not improving and in fact appears to be getting worse. She now has a fever.
What may be going on?

Answer 12

Tigecycline has a broad spectrum of activity and is approved for complicated skin and soft tissue infections; however, it has no coverage against Pseudomas/Proteus – either of which may be leading to progression of infection in this patient.

Question 13

macrolides mechanism of action and resistance?

Answer 13

(azithromycin, clarithromycin, erythromycin)

Binds to 50S ribosomal subunit, blocks translocation, inhibits bacterial protein synthesis

resistance: Decreased microbial entry, permeability, efflux pumps, target site alterations (erm gene), enzymatic drug inactivation

Question 14

macrolides general properties/PK/PD

Answer 14

Bacteriostatic

Widely dist in tissues, azithromycin has long ½ life (give qd X 5 d and covered for 1-2 weeks), erythromycin (metab by p450 system, many rx-rx interactions)

Question 15

macrolides adverse effects, spectrum of activity, and use?

Answer 15

azithromycin, clarithromycin, erythromycin)

Epigastric distress (esp erythromycin – now used mostly for motility); QT prolongation

activity:
GP:Staphylococci, streptococci (incl susceptible pneumococcus)
GN:Many, not pseudomonas
Other: Some GN anaerobes, atypicals (mycoplasma, legionella, chlamydia)

use:
azithromycin: CA-pneumonia/bronchitis, atypical pneumonia, STIs (chlamydia), traverler’s diarrhea, MAC prophylaxis in HIV/AIDs

Erythromycin: gut motility, prokinetic

Clarythromycin: (combo w/other rx) mycobacterium avium complex disease, H.pylori

Question 16

An 18-year-old college student was seen at the student infirmary for community-acquired pneumonia and given a course of antibiotics. She returns 2 days later with profuse nausea and vomiting.
What is the most likely antibiotic she was given?

Answer 16

She was most likely given a macrolide antibiotic with excellent coverage against organisms responsible for CAP and atypical pneumonia and which has the common side effect of significant GI distress.

Question 17

licosamides mechanism of action/resistance?

Answer 17

clindamycin

action:
Binds to 50S ribosomal subunit, blocks translocation, inhibits bacterial protein synthesis

resistance:
Single gene mutation (erm gene) causing MLS resistance (esp S.aureus) – suspect this on S. aureus orgs that demonstrate clindamycin susceptibilty and erythromycin resistance on antibiograms – TEST W/D TEST

Question 18

licosamides general properties/PK/PD?

Answer 18

clindamycin

Bactericidal at high doses

Good penetration of most tissues (NOT CNS)

Question 19

licosamides adverse effects, spectrum, and use?

Answer 19

clindamycin

adverse:
C. diff
Hepatotoxicity, agranulocytosis

spectrum:
GP:Staphylococci (including some CA-MRSA) and streptococci
GN:none
other:Oral anaerobes, “above the diaphragm”, Bacteroides fragilis, malaria, toxoplasmosis, Babesia

use:
CA-aspiration pna (oral anaerobes), oral/ENT infections, abscesses “above the diaphragm”, human bite wounds, s/st infections re: CA-MRSA, toxic shock syndrome due to group A strep

Question 20

80-year-old woman admitted from home following episode of syncope leading to aspiration pneumonia with cultures growing anaerobes. She is put on clindamycin and 5 days later develops severe watery, non-bloody diarrhea
What is going on?

Answer 20

C. difficile infection is the most significant adverse effect of clindamycin use

Question 21

oxasolidinones mechanism of action/resistance?

Answer 21

lenizolid and tedizolid

action:
Binds to 50S subunit, prevents 70S formation, inhibits translocation process, inhibits bacterial protein synthesis
Additional target site interactions w/peptidyl transferase binding region of rRNA (increased potency)

resistance:
Uncommon, spontaneous point mutations at drug target site, acquisition of plasmid-mediated resistance gene, cfr; tedizolid overcomes this!

Question 22

oxasolidinones general properties/PK/PD?

Answer 22

lenizolid and tedizolid

Bacteriostatic

100% bioavailability, PO or IV

Question 23

oxasolidinones adverse effects, spectrum and use?

Answer 23

adverse:
Bone marrow suppression (thrombocytopenia w/prolonged use – monitor CBC), inhibits monoamine oxidase activity (lead to serotonin syndrome when given in conjunction w/SSRIs – can be fatal), lactic acidosis (serotonin syndrome NOT SEEN with tedizolid)

spectrum:
GP:Staph (incl MRSA), strep, enterococci (incl VRE)
GN:none
other:No anaerobic, mycobacteria some activity

use:
VRE infections, nosocomial pneumonia due to MRSA, complicated skin/ST infections

Question 24

A 45-year-old man who receives hemodialysis through a permanent intravenous catheter is admitted with recurrent low grade fevers. Blood cultures grow vancomycin-resistant Enterococcus faecalis. The catheter was removed and he received several days of an IV antibiotic. He is now being discharged and you want to send him home on an oral agent?
What are your choices?

Answer 24

Linezolid has activity against VRE and is 100% bio-available in the oral formulation.

Question 25

mupirocin mechanism of action/resistance?

Answer 25

action:
Binds tRNA synthetase (reversible), inhibits protein and RNA synthesis

resistance:
Presence of second, plasmid-encoded tRNA synthetase that retains activity in presence of Rx

Question 26

mupirocin general properties, PK, PD?

Answer 26

Weaker activity vs normal skin flora contributes to clinical use as these are important natural defense vs infection

Topical only – formulated in polyethylene glycol water-miscible ointment base, not appreciably absorbed via skin

Question 27

muripocin adverse effects? spectrum? use?

Answer 27

adverse:
Not significant (very low affinity for human tRNA synthetase); propylene glycol base may irritate mucous membranes or broken skin (contact dermatitis)

spectrum:
GP:S. aureus, other strep and staph
None vs enterococci
GN:none
other:
No anaerobic coverage

use:
skin infections, MRSA decolonization of nares, prophylaxis vs catheter-related infection (Abx-coated catheters)

Question 28

imidazoles mechanism of action?

Answer 28

metronidazole, tinidazole

Enters bacteria by diffusion, production of free radicals leads to cytotoxic effects

Question 29

imidazoles adverse effects?

Answer 29

metronidazole, tinidazole

Metallic tasete; CNS: vertigo, HA, confusion, psychosis; disulfram-like effect w/alcohol (vomiting, flushing)

Question 30

imidazoles spectrum and use?

Answer 30

metronidazoles, tinidazole

spectrum:
Anaerobes: below the diaphragm (classic, not absolute), including Bacteroides fragilis, protozoa (trich, amoeba, giardia)
(NO GP OR GN)

use:
Anaerobic infections (C.diff, intra-abdominal infections/abscesses), protozoa (trich/BV, amoebiasis, giardiasis), crohns, bacterial overgrowth

Question 31

A 24-year-old college student is taking metronidazole for bacterial vaginosis. Last night she attended a party to celebrate end of year exams. This morning she has profuse vomiting and facial flushing.
What is going on?

Answer 31

She is most likely having a Disulfram reaction caused by the combination of metronidazole and ETOH

Question 32

what is the most commonly used Abx in general practice?

Answer 32

azithromycin

Question 33

adverse effects:
eminoglycosides?
tetracyclines?
ery/azithromycin?
clindamycin?
linezolid?

Answer 33

Aminoglycosides: Oto/Nephrotoxicity

Tetracylcines: Bone/teeth and photosensitivity

Ery/Azithromycin: GI, QT prolongation

Clindamycin: C. difficile Infection

Linezolid: BM suppression, Serotonin Syndrome

Question 34

which RNA/DNA inhibitors cover anaerobes?

Answer 34

clindamycin, metronidazole, tigecycline, tetracyclines, macrolides

Question 35

which RNA inhibitors are GP only?

Answer 35

linezolid, mupriocin