Clindamycin, Macrolides, & Synercid: 9/14

Question 1

Name the three macrolides and if they are bactericidal or bacteriostatic

Answer 1

azithromycin clarithromycin erythromycin All bacteriostatic! THINK: ACE THINK: All of them have -thromycin (throw some mo’ to the MAC)

Question 2

Describe the mechanism of action for the azithromycin, clarithromycin, and erythromycin?

Answer 2

They act by binding to the 50s ribosome and inhibiting protein synthesis

Question 3

Name the mechanism of resistance for azithromycin, clarithromycin, and erythromycin?

Answer 3

US: bacteria will express meF gene = leads to efflux of abx outside of the bacteria Europe: varied ribosomal binding site

Question 4

Name the target organisms for azithromycin, clarithromycin, and erythromycin?

Answer 4

They target atypical bacteria: -Legionella *DOC -Chlamydia -Mycoplasma AND mycobacteria AND anaerobes

Question 5

What are the clinical indications for using azithromycin, clarithromycin, and erythromycin?

Answer 5

-Respiratory tract infections: pharyngitis, sinusitis, etc -mycobacteria avium complex: prophylaxis (azithro); treatment (erythro and clarithro) -STDs -uncomplicated skin infections

Question 6

Do azithromycin, clarithromycin, and erythromycin have any activity against gram + and gram - bacteria?

Answer 6

-Yes! -gram positive aerobes: MSSA; [C > E > A] -gram negative aerobes: H. flu & Neisseria [A > C > E] -NO enterobacteriae -May be used in place of PCN in case of allergy

Question 7

What adverse effects are associated with azithromycin, clarithromycin, and erythromycin?

Answer 7

-prolonged QT syndrome: be sure to take baseline ECG and determine if a different course of action is required. -GI issues (more common with erythro)

Question 8

Which macrolide is eliminated via the CYP450 mechanism?

Answer 8

erythromycin

Question 9

Which macrolides inhibit CYP 450 enzymes?

Answer 9

-erythromycin -clarithromycin THINK: cytoChromE: has a C & E for claritho & erythro

Question 10

Drug interactions with the macrolides?

Answer 10

-anything that is metabolized via CYP 450 enzymes -notable examples: warfarin, cyclosporine, phenytoin

Question 11

azithromycin, clarithromycin, and erythromycin MOA? Mechanism of resistance? Indication? Adverse effects? Drug interactions?

Answer 11

MOA: inhibits protein synthesis by binding to ribosome Mechanism of resistance: efflux via expression of the meF gene Indication: atypical bacterial infections: STD, upper resp infections, PCN allergy for gram + and gram - infections; uncomplicated skin infections, MAC Adverse effects: prolonged QT, deafness Drug interaction: CYP450 drugs (macrolides inhibit CYP 450 enzymes)

Question 12

Describe pharmacokinetics: absorption and distribution of azithromycin, clarithromycin, and erythromycin

Answer 12

absorption: variable oral absorption; clarithro = best bioavailability from oral distribution: no CNS penetration

Question 13

What is the MOA of Clindamycin, and how does it compare to that of Quinupristin/Daltopristin?

Answer 13

Inhibits protein synthesis

Binds to 50S subunit

Generally bacteriostatic

May be cidal at high concentrations and against very susceptible orgs

SAME AS Q/D

Question 14

What is the MoR for Clindamycin?

Answer 14

Altered target sites = erm gene = HIGH level resistance

Question 15

What is the SoA for Clindamycin?

Answer 15

Gram Positive Aerobes:

• MSSA/some CA-MRSA
• PSSP
• Group and viridans streptococci

**Anaerobes**:

• Bacteroides spp
• Clostridium (NOT C. diff)
• Actinomyces
• Peptostreptococcus

Question 16

Describe the A, D and E of Clindamycin.

Answer 16

Absorption:

• IV/PO
• Both routes = rapidly/completely absorbed

Distribution:

• Good serum concentrations with both routes
• Good tissue penetration inc. bone/minimal CSF

Elimination:

• Metabolized by liver/enterohepatic cycling
• NOT removed during HD

Question 17

What are the clinical uses for Clindamycin?

Answer 17

Anaerobic Infections OUTSIDE the CNS:

• Pulmonary
• Intraabdominal, pelvic, diabetic foot ulcer (like Metronidazole)

Skin/Soft Tissue Infections:

• PCN-allergic patients
• CA-MRSA

Question 18

What are some of the major adverse effects of Clindamycin, and how do these compare to those of Quinupristin/Dalfopristin?

Answer 18

GI = MOST COMMON (same as Q/D)

Clostridium difficile colitis (requires metronidazole or oral vancomycin)- Different from Q/D

Rare = hepatotoxicity, neutropenia, thrombocytopenia (Different from Q/D)

Q/D AEs includes: Venous irritation (unlike Clinda)

Question 19

List the drug under the Streptogramin class, and the reason why it was developed.

Answer 19

Quinupristin/Daltopristin (Synercid)

Activity against resistant gram-positive bacteria (esp VRE)

Question 20

What is the MoR for Quinupristin/Daltopristin (Q/D)?

Answer 20

Alterations in ribosomal binding sites (erm gene)

Enzymatic inactivation (Different from Clinda and Macrolides)

Question 21

List the SoA and Clinical Uses for Q/D (Synercid).

Answer 21

Gram Positive Bacteria:

• MSSA/MRSA/Coag negative Staph = Complicated Skin/Soft tissue infection
• PRSP/other Streptococci = Complicated Skin/Soft tissue infection
• Enterococcus faecium (inc VRE) = bacteremia
• NO C. diff activity (like Clindamycin)

Question 22

Discuss Pharmacokinetics of Synercid.

Answer 22

Time-dependent, bacteriostatic

PAE (esp S. aureus and VRE/VSE)

Absorption = ONLY parentally

Distribution = minimal CSF penetration (like Clinda and Macrolides)

Elimination = liver and biliary excretion

Question 23

What are some possible drug interactions with Synercid, and why does it happen?

Answer 23

Cytochrome p450 3A4 Inhibitor

Ex: Antihistamines, HIV drugs, cyclosporine