Antibiotics: Agents Interfering with Bacterial Protein and DNA Synthesis

Question 1

Aminoglycosides

Answer 1

Streptyomycin
Tobramycin 
Gentamicin
Amikacin
Neomycin
Kanamycin

Question 2

Aminoglycosides (Mechanism of Action)

Answer 2

Bind to 30S ribosomal subunit and interfere with protein synthesis in the following 3 ways:

1. Blocking the initiation step
2. Blocking the ribosomal translocation step
3. Causing mistranslation

Question 3

Aminoglycosides - Effects

Answer 3

Rapidly bactericidal vs. many aerobic GRAM NEGATIVE bacteria
Associated with a significant POSTANTIBIOTIC EFFECT

Question 4

Streptomycin - primary clinical indications

Answer 4

2nd line agent for treatment of tuberculosis in combination with another agent (ex. INH)

Question 5

Tobramycin and Gentamicin: primary clinical indications

Answer 5

Treatment of serious systemic infections caused by Gram-negative organisms.
Often used in combination with a BETA-lactam drug because of synergistic effects and reduced emergence of resistance.

Question 6

Amikacin: primary clinical indications

Answer 6

Used in cases of resistance to tobramycin and gentamicin caused by inactivating enzymes

Question 7

Neomycin and Kanamycin: primary clinical indications

Answer 7

Limited to topical use (skin and eyes)

Question 8

Primary Toxicities of Aminoglycosides

Answer 8

Nephrotoxicity: reversible with cessation of therapy
Ototoxicity: auditory damage, vestibular damage, IRREVERSIBLE, even upon cessation of therapy
Toxicities are more likely with >5 days of therapy

Question 9

Tetracyclines (List 6)

Answer 9

Tetracycline
Oxytetracycline
Demeclocycline
Minocycline
Doxycycline
Tigecycline (glycylcyline)

Question 10

Tetracycline Mechanism of Action?

Answer 10

Bind to 30S ribosomal subunit and interfere with protein synthesis by blocking the peptide elongation step

Question 11

Effects of Tetracyclines?

Answer 11

Bacteriostatic vs. many aerobic and anaerobic Gram-POSITIVE and Gram-NEGATIVE bacteria

Question 12

PCI: Rickettsial Infections

Answer 12

TETRACYCLINES

Rocky Mountain spotted fever, typhus, and Q fever

Question 13

PCI: STI

Answer 13

TETRACYCLINES

Chlamydia, urethritis, cervicitis, and epididymititis

Question 14

PCI: Respiratory infections

Answer 14

TETRACYCLINES

Community-acquired pneumonia

Question 15

PCI: Skin and Soft-Tissue Infections

Answer 15

TETRACYCLINES

Community-acquired Staph and acne

Question 16

PCI: Infections caused by MDR Bacteria

Answer 16

Tigecycline (IV ONLY) is used for MDR intra-abdominal, skin, and soft-tissue infections, and community-acquired pneumonia

Question 17

Doxycycline

Answer 17

Doxycycline is used in the treatment of anthrax, malaria, and Lyme Disease

Question 18

Primary Toxicities of Tetracyclines:

Answer 18

GI Disturbances: Nausea, vomiting, diarrhea
Teeth and Bone: Tooth discoloration, growth deformity and inhibition in children under 8!!!
Photosensitization
Hepatotoxicity during pregnancy

Question 19

Macrolides (4)

Answer 19

Erythromycin
Clarithromycin
Azithromycin
Telithromycin (ketolide)

Question 20

Macrolide: Mechanism of Action

Answer 20

Bind to 50S ribosomal subunit and interfere with protein synthesis by blocking the RIBOSOMAL TRANSLOCATION STEP

Question 21

Macrolide: Effects

Answer 21

Generally bacteriostatic vs. aerobic Gram-POSITIVE and some Gram-NEGATIVE bacteria

Question 22

PCI of Macrolides

Answer 22

Respiratory Infections: Community-acquired pneumonia, acute exacerbations of chronic bronchitis
Skin and Soft-Tissue infections: Substitute for penicillin in allergic individuals with susceptible Staph infections
Acute otitis media
Streptococcal pharyngitis
Chlamydial infections
Diptheria
Pertussis (whooping cough)

Question 23

Toxicities of Macrolides

Answer 23

GI Disturbances
Hepatotoxicity - cholestatic hepatitis (has caused the approved use of TELITHROMYCIN to be restricted to community-acquired pneumonia)

Question 24

Example of Lincosamide

Answer 24

Clindamycin

Question 25

Clindamycin mechanism of action

Answer 25

Bind to 50S ribosomal subunit and interferes with protein synthesis by blocking the RIBOSOMAL TRANSLOCATION STEP

Question 26

Clindamycin Effects

Answer 26

Bacteriostatic vs. aerobic and anaerobic Gram-positive bacteria

Question 27

Clindamycin PCI

Answer 27

skin and soft-tissue infections

Question 28

Toxicities of Clindamycin

Answer 28

Diarrhea Pseudomembranous colitis caused by C. difficile Skin rashes

Question 29

Example of Streptogramins

Answer 29

Quinupristin/Dalfopristin

Question 30

Mechanism of action of Streptogramins

Answer 30

Bind to 50S ribosomal subunit and interfere with protein synthesis by blocking the ribosomal translocation step and inhibiting peptide elongation

Question 31

Effects of Streptogramins

Answer 31

``` Active vs. most Gram- positive bacteria • Combination is bactericidal vs. streptococci and most staphylococci, but bacteriostatic vs. enterococci. ```

Question 32

PCI of Streptogramins

Answer 32

``` Treatment of infections caused by vancomycin- resistant E. faecium (VRE) • Treatment of complicated skin infections caused by MSSA ```

Question 33

Toxicities of Streptogramins

Answer 33

Infusion related effects of the IV only combination Arthalgia Myalgias

Question 34

Example of Oxazolidinone

Answer 34

LINEZOLID

Question 35

Mechanism of Linezolid

Answer 35

``` • Binds to 50S ribosomal subunit and interferes with protein synthesis by blocking the initiation step ```

Question 36

Effects of Linezolid

Answer 36

``` • Active vs. aerobic and anaerobic Gram-positive bacteria • Bactericidal vs. streptococci, but bacteriostatic vs. staphylococci and enterococci. ```

Question 37

PCI of Linezolid

Answer 37

``` Treatment of infections caused by MDR Gram- positive bacteria (MRSA, VRE, and penicillin- resistant streptococci) ```

Question 38

Toxicity of Linezolid

Answer 38

``` Myelosuppression (leukopenia, pancytopenia, and thrombocytopenia) with treatment durations >2 weeks. ```

Question 39

Anti-Folates - Sulfonamides

Answer 39

Sulfisoxazole Sulfamethoxazole (SMX) Sulfasalazine

Question 40

Anti-Folates - Sulfonamides (Mechanism of Action)

Answer 40

Competitive antagonists of dihydropteroate synthase

Question 41

Effects of Anti-Folate-Sulfonamides

Answer 41

``` Bacteriostatic vs. numerous Gram- negative and some Gram-positive bacteria ```

Question 42

PCI of Anti-Folate-Sulfonamides

Answer 42

``` Urinary tract infections (usually in combination with other drugs) • Sulfasalazine is used in the treatment of ulcerative colitis and enteritis. ```

Question 43

Toxicities of Sulfonamides

Answer 43

``` Allergic reactions (rash, fever, urticaria, photosensitivity, GI effects) • Crystalluria • Hematuria ```

Question 44

Anti-Folates – Trimethoprim/Sulfamethoxazole (TMP-SMX) Combination

Answer 44

Trimethoprim/Sulfamethoxazole (TMP-SMX)

Question 45

TMP-SMX Mechanism of Action

Answer 45

TMP is a competitive antagonist of dihydrofolate reductase

Question 46

TMP-SMX Effects

Answer 46

``` • Like the sulfonamides, TMP is bacteriostatic vs. numerous Gram- negative and some Gram-positive bacteria • The TMP-SMX combination is bactericidal ```

Question 47

PCI of TMP-SMX

Answer 47

• Uncomplicated urinary tract infections • Pneumocystis jiroveci pneumonia • Shigellosis • Systemic Salmonella infections • Prostatitis • Acute exacerbations of chronic bronchitis

Question 48

Toxicities of TMP-SMX

Answer 48

``` With treatment duration 5 days, hematologic effects (megaloblastic anemia, leukopenia) can occur. ```

Question 49

Fluoroquinolones

Answer 49

Ciprofloxacin Lomefloxacin Levofloxacin Ofloxacin Gemifloxacin Moxifloxacin

Question 50

Fluoroquinolones Mechanism of Action

Answer 50

``` Inhibitors of topoisomerase II (DNA gyrase) in Gram- negative bacteria and topoisomerase IV in Gram-positive bacteria ```

Question 51

Effects of Fluoroquinolones

Answer 51

Bactericidal vs. both Gram-negative and Gram-positive bacteria

Question 52

PCI of Fluoroquinolones

Answer 52

``` Urinary tract infections • Ciprofloxacin is used for prevention and treatment of anthrax • Diarrhea caused by Shigella, Salmonella, and toxigenic E. coli • Soft-tissue, bone, and joint infections • Intra-abdominal infections • Respiratory tract infections (levofloxacin, gemifloxacin, and moxifloxacin are particularly effective) ```

Question 53

Toxicities of Fluoroquinolones

Answer 53

``` Generally well tolerated • GI disturbances include nausea, vomiting, and diarrhea ```