Miscellaneous Antibiotics

Question 1

What is the MOA of tetracyclines?

Answer 1

They reversibly bind the 30S ribosome and prevent elongation of the polypeptide by blocking the addition of amino acids.

Question 2

How does resistance to tetracyclines occur?

Answer 2

• Efflux pumps
• Enzyme inactivation
• Ribosomal protection

Question 3

What are the pharmokinetics of tetracyclines?

Answer 3

Bacteriostatic

***Bactericidal when present at high concentrations against very susceptible organisms

Question 4

What are drugs in the tetracycline class?

Answer 4

Tetracycline
Doxycycline
Tigecycline

Question 5

What is the Gram + spectrum of action of tetracyclines?

Answer 5

• Staphylococcus aureus (primarilyMSSA)
• Streptococcuspneumoniae–PSSP (doxycycline – 83% susceptible)
• Bacillus spp, Listeria spp,Nocardia spp

Question 6

What is the Gram - spectrum of action of tetracyclines?

Answer 6

• N.gonorrhea and meningitidis
• Haemophilus influenzae (90% susceptible)
• Haemophilus ducreyi(chancroid)
• Campylobacter jejuni
• Helicobacter pylori
• Vibrio cholerae, Vibrio vulnificus
• Burkholderiapseudo mallei

Question 7

What are the holes in coverage of tigecycline?

Answer 7

Proteus

Pseudomonas

Question 8

What is the spectrum of activity of tigecycline?

Answer 8

Has a wide spectrum of action with notable ones bing MRSA, VRE, S. maltophilia

Gram-Negative Aerobes
• Acinetobacter baumannii
• Aeromonas hydrophila
• Citrobacter spp.
• Escherichia coli
• Klebsiella spp.
• Serratia marcescens
• Stenotrophomonas maltophilia
• NOT Proteus spp or Pseudomonas aeruginosa

Gram-Positive Aerobes
• Staphylococcus aureus • MSSA, MRSA
• Enterococcus spp • VRE, VSE

Anaerobes
• Clostridium perfringens
• Bacteroides spp

Question 9

What should tigecycline NOT be used for?

Answer 9

NOT for bacteremias or UTIs

Question 10

How are the tetracyclines best absorbed?

Answer 10

On an empty stomach

Question 11

What is the administration method of tetracycline and demeclocycline?

Answer 11

Oral

Question 12

What is the administration method of doxycycline?

Answer 12

IV and oral

Question 13

What is the administration method of tigecycline?

Answer 13

IV only

Question 14

Why aren’t tetracyclines a good choice for UTIs?

Answer 14

They don’t concentrate well in the bladder

Question 15

What is the CSF penetration of the tetracyclines?

Answer 15

Minimal

Question 16

What is the penetration of the prostate by tetracyclines?

Answer 16

Good

Question 17

Is dosage adjustment in renal failure necessary for tetracycline/demeclocycline?

Answer 17

Yes

Question 18

Is dosage adjustment in renal failure necessary for tigecycline/doxycycline?

Answer 18

No. But adjustment for liver failure must be made for tigecycline

Question 19

Are tetracyclines and tigecycline removed in hemodialysis?

Answer 19

No. Only minimally.

Question 20

What are the main uses of the tetracyclines?

Answer 20

Respiratory Infection
STDs
RMSF
Q fever
Lyme Disease
Polymicrobial infections (tigecycline)

Question 21

What are the SE of tetracyclines?

Answer 21

Nausea
Vomiting
Hypersensitivity
Photosensitivity

Question 22

Why should tetracyclines not be used in pregnant women?

Answer 22

Discoloration of permanent teeth and decreased bone growth in children

Question 23

What is the mechanism of sulfonamides?

Answer 23

Inhibits dihydropteroate synthetase – which inhibits incorporation of p-aminobenzoic acid (PABA) into tetrahydropteroic acid

Question 24

What are the pharmokinetics of the sulfonamides?

Answer 24

Bacteriostatic

Question 25

What is the most frequently used sulfonamide?

Answer 25

Sulfamethoxazole (SMX)

Question 26

What is the MOA of trimethoprim?

Answer 26

Inhibits dihydrofolate reductase which interferes with conversion of dihydrofolate to tetrahydrofolate

Question 27

What are the PKs of trimethoprim (TMP)?

Answer 27

Bacteriostatic

Question 28

Why is Trimethoprim-Sulfamethoxazole used?

Answer 28

TMP-SMX has synergistic activity which makes it bactericidal and gives it a broader spectrum of activity.

Question 29

What is the MOA of TMP-SMX?

Answer 29

Inhibition to two different steps that lead to purine synthesis

Question 30

What are the MOR to TMP-SMX?

Answer 30

􏰀PABA overproduction 􏰀Structural change of dihydropteroate synthetase 􏰀Plasmid mediated production of drug resistant DHPS or decreased bacterial cell wall permeability to sulfonamides

Question 31

What is TMP-SMX the choice treatment for?

Answer 31

S. maltophilia

Question 32

How is TMP-SMX administered?

Answer 32

Oral and IV

Question 33

Is dose adjustment of TMP-SMX required in renal failure patients?

Answer 33

Yes

Question 34

What are the clinical uses of TMP-SMX?

Answer 34

* Acute, chronic, or recurrent infections of the urinary tract * Acute or chronic bacterial prostatitis * Skin infections due to CA-MRSA * Bacterial Sinusitis * Nocardia ****

Question 35

What are the main SE of TMP-SMX?

Answer 35

GI tract problems (nausea, etc) Leukopenia, thrombocytopenia Hypersensitivity (many have a sulfa allergy)

Question 36

What is the interaction of TMP-SMX and methotrexate?

Answer 36

Decreases the clearance of methotrexate which leads to toxicity

Question 37

What is the MOA of chloramphenicol?

Answer 37

Binds to the 50S ribosome to prevent peptide bond formation

Question 38

What are the PKs of chloramphenicol?

Answer 38

Bacteriostatic

Question 39

What bacteria does chloramphenicol have bactericidal activity towards?

Answer 39

􏰀Haemophilus influenza 􏰀 Streptococcus pneumoniae 􏰀Neisseria meningitidis

Question 40

How does chloramphenicol resistance occur?

Answer 40

- Reduced uptake - Ribosome mutation - Acetyltransferase inactivation

Question 41

Is dose adjustment for chloramphenicol required in renal failure?

Answer 41

No

Question 42

Is dose adjustment for chloramphenicol required in liver failure?

Answer 42

Yes

Question 43

Is chloramphenicol active against Pseudomonas?

Answer 43

No

Question 44

Is chloramphenicol active against S. aureus or Enterococcus?

Answer 44

No

Question 45

What are the main SE of chloramphenicol?

Answer 45

- Gray baby syndrome | - Bone marrow suppression

Question 46

What are some of the specific urinary tract agents?

Answer 46

Nitrofurantoin | Methenamine

Question 47

Nitrofurantoin MOA

Answer 47

Binds to ribosomal proteins and inhibits translation as well as bacterial respiration and pyruvate metabolism

Question 48

Methenamine MOA

Answer 48

Converted in acid pH to ammonia and formaldehyde which is a non-specific denaturant of proteins and nucleic acids

Question 49

How is nitrofurantoin resisted?

Answer 49

Production of nitrofuran reductase

Question 50

How is methenamine resisted?

Answer 50

No MOR as no formaldehyde resistance has been found

Question 51

What enhances nitrofurantoin absorption?

Answer 51

Food

Question 52

Nitrofurantoin Clinical Use

Answer 52

􏰀Acute, uncomplicated UTIs

Question 53

Methenamine Clinical Use

Answer 53

Suppression or prophylaxis against recurrent UTIs

Question 54

Nitrofurantoin Contraindications

Answer 54

􏰀Do not use for: 􏰁 Pyelonephritis 􏰁 Complicated UTI

Question 55

Methenamine Contraindications

Answer 55

􏰀Do not use for: 􏰁 Established infections 􏰁 Prophylaxis against catheter-associated UTI Elderly and those with impaired renal function

Question 56

ElNitrofurantoin Spectrum of Activity

Answer 56

``` E. coli Citrobacter, sp. Group B Streptococcus Staphylococcus saprophyticus 􏰀Enterococcus (including some strains of VRE) ```

Question 57

Methenamine Spectrum of Activity

Answer 57

NO antimicrobial activity

Question 58

Methenamine SE

Answer 58

Generally well tolerated Can have GI symptoms and a rash though

Question 59

Nitrofurantoin SE

Answer 59

* GI intolerance * Rashes * Acute pulmonary symptoms – reversible hypersensitivity phenomenon