Dr. Cluck Non Beta Macrolides, Tetra, Sulfonamides

Question 1

Important Macrolides

Answer 1

-Azithromycin IV, PO, OPTH - most commonly used clinically
-Erythromycin IV, IM, PO (often not used as an antibiotic - more to promote gut motility)
-Clarithromycin PO

Question 2

Spectrum of activity

Answer 2

-atypical pathogens
-Respiratory infections and STI !!!
-> Community-acquired pneumonia -> Ceftriaxone + Azithromycin

Question 3

PK of Macrolides

Answer 3

-long-halflife in Azithromycin (1x TID dose is enough)
-IV to PO conversion for Azithromycin is 1:1
-minimal CYP drug interactions

Question 4

Adverse Effect of Macrolides

Answer 4

-GI symptoms: Especially with erythromycin
-Ototoxicity (hearing loss) - never seen in practice by Cluck
-Cholestatic hepatitis - more in babies
-Arrhythmias (prolonged QT – all macrolides including azithromycin)

Question 5

Drug Interactions of macrolides

Answer 5

-Erythromycin and Clarithromycin are 3A4 substrates and thus will likely interact with ALL drugs metabolized by 3A4

-Digoxin/Ergot derivatives (all macrolides)

Question 6

Mechanism of resistance for Macrolides

Answer 6

-Ribosomal modification
-Antibiotic inactivation via enzymes (eg esterases, phosphorylases)
-Efflux pumps

Question 7

Clinical Pearls
What are macrolides used for?

Answer 7

-Erythromycin rather for GI motility than as an antibiotic
-STI: Chlamydia; respiratory: Legionella and Mycoplasma pneumonia

Question 8

Important tetracyclines

Answer 8

-Tetracycline
-Doxycycline - most often used in clinical
-Minocycline

(Azithromycin can be substituted with Doxycycline
in treating Comm. acq. pneumonia -> lower risk of C. diff infection)
Ceftriaxone + Doxycycline

Question 9

What is the main effect of Minocycline?

Answer 9

Anti-inflammatory

Question 10

Spectrum of activity Tetracyclines

Answer 10

-good coverage against gram (+)
-NOT used clinically for gram (-)
-great for atypical organisms and thick-borne-illnesses
* Rickettsia rickettsii (Rocky Mountain Spotted Fever)
* Borrelia burgdorferi (Lyme disease)

Question 11

Pharmacokinetics of Tetracyclines

Answer 11

Absorption: Absorbed orally

Distribution: Distributes well, poor CSF and urine penetration

Metabolism/Excretion: Essentially no metabolism and excreted unchanged via glomerular filtration

Question 12

Contraindications/Warnings Tetracycline

Answer 12

-Hypersensitivity
-Use of expired tetracyclines can result in Fanconi syndrome (high excretion of electrolytes)
-caution in children (cut off is 8yr)
-teeth coloring

Question 13

Adverse effects Tetracycline

Answer 13

-N/V/D, should be taken with the first bite of food
-Photosensitivity
-CNS (pseudotumor cerebri)
-Possible hepatitis
-Tooth discoloration

Question 14

Drug Interactions

Answer 14

-Antacids – chelation with aluminum, calcium, and magnesium (similar to FQ)

-oral contraceptives (possible)

Question 15

Mechanisms of Resistance

Answer 15

-Efflux pumps
-Ribosomal “protection” proteins

-These mechanism doesn’t affect Tigecycline and newer agents (Eravacycline, Omadacycline)

Question 16

Tygacil (tigecycline)

Answer 16

(-known as Glycylcycline - Minocycline derivative)
-IV only

-wide spectrum (no Pseudomonas)
-do NOT cover Proteus, Providencia, Morgonella (all same family)
-limited clinical use due to PK/PD -> should not be used in UTIs or bacteremias

Question 17

MOA of Tetracycline

Answer 17

Protein synthesis inhibitor

Question 18

Clinical Pearls
What is Tetracycline used for?

Answer 18

-commonly used in atypical infections
-some use in resistant infections such as MRSA and VRE

Question 19

What are Eravacycline and Omadacycline used for?

Answer 19

-Eravacycline: intra abdominal infections (IV)
-Omadacycline: IV, PO

Question 20

Trimethoprim-sulfamethoxazole (Sulfonamide)

Answer 20

-Bactrim
-PO, IV (restricted)
-Adverse effects: rash, blood dyscrasias, jaundice, potassium level increased (bc Trimethoprim structure is similar to triamterene = potassium-sparing diuretic); also little increase level of serum creatine (bc secretion of creatine is blocked)
-Dosing based on TMP component

Question 21

Which electrolyte is most likely to be affected by
Trimethoprim-sulfamethoxazole?

Answer 21

Potassium

Question 22

MOA of Trimethoprim-sulfamethoxazole

Answer 22

Sulfonamide inhibits Dihydropteroate synthase (competes with PABA)
-> PABA is necessary for the first step of the folic acid pathway

Trimethoprim inhibits Dihydrofolate reductase (2nd step)

Question 23

Spectrum of Activity of Bactrim

Answer 23

-good coverage of gram (+) Comm. acquired MRSA, MSSA
-not so good for hospital acq MRSA
-does NOT cover Group A Strep

-for gram (-) it depends, can be used for susceptible E.coli UTI
-DOC for Stenotrophomonas spp.

Question 24

Which parameters should be monitored for Bactrim?

Answer 24

-Renal function (little increase is normal) and complete blood count (CBC, making sure white blood cells do not drop (Leukopenia) in long-term use)

-G6PD deficiency – oxidative stress on RBCs resulting in hemolytic anemia
-> not done for Bactrim

Question 25

Clinical Pearls
Which disease states are appropriate for Bactrim?

Answer 25

-Skin soft tissues
-CA Staph
-used in atypical infections Pneumocystis pneumonia (PCP), Nocardia infections
-Enterococcus is resistant to Bactrim

Question 26

Which organism is resistant to Bactrim

Answer 26

Enterococcus