Protein Synthesis Inhibitors Flashcards
What is the MOA of clindamycin?
Inhibits protein synthesis by binding exclusively to the 50S ribosomal subunit
What are the PKs of clindamycin?
Bacteriostatic, but may be bactericidal when present at high concentrations against very susceptible organisms
What are the MOR to clindamycin?
- Altered target sites
- Active efflux
What is the general spectrum of activity of clindamycin?
- Gram + aerobes
- Anaerobes
Gram + aerobes targeted by clindamycin
– Methicillin‐susceptible Staphylococcus aureus*, and some CA‐MRSA
– Streptococcus pneumoniae (only PSSP) – resistance is developing
– Group and viridans streptococci
Anaerobes targeted by clindamycin
Peptostreptococcus Actinomyces
Propionibacterium
Clostridium spp. (not C. difficile)
How is clindamycin administered?
Oral and IV
What is the bioavailability of clindamycin?
High. 90%
What is the CSF penetration of clindamycin?
Poor
What is the main metabolic path of clindamycin?
Liver
Is clindamycin removed with hemodialysis?
Clindamycin is NOT removed during hemodialysis
What are the main uses of clindamycin?
Anaerobic infections excluding the CNS
Skin and soft tissue infection (PCN allergic patients - CA-MRSA)
Clindamycin SE
Most common: nausea, vomiting, diarrhea, dyspepsia
Rare: hepatotoxicity, neutropenia, thrombocytopenia
What are the macrolide drugs?
Erythromycin, clarithromycin, and azithromycin
MOA of macrolides
Inhibit protein synthesis by reversibly binding to the 50S ribosomal subunit which will lead to the halting of bacterial growth
Macrolide PKs
Macrolides typically display bacteriostatic activity, but may be bactericidal when present at high concentrations against susceptible organisms
Erythromycin PKs
Time‐dependent bacteriostatic activity
Clarithromycin PKs
Time‐dependent bacteriostatic activity
Azithromycin PKs
Concentration‐dependent bacteriostatic activity
How does resistance to macrolides occur?
- Altered target sites
- Active efflux
Main MOR to macrolides in US
- Active efflux
Main MOR to macrolides in EU
- Altered target sites
What is the gene for active efflux of macrolides?
Mef
What is the gene for altered target sites of macrolides?
Erm
What is the general spectrum of activity of macrolides?
- Gram positive aerobes
- Gram negative aerobes
- Anaerobes
- Atypical
Order that macrolides in decreasing effectiveness against Gram (+) aerobes.
(Clarithro>Erythro>Azithro)
Order that macrolides in decreasing effectiveness against Gram (-) aerobes.
(Azithro>Clarithro>Erythro)
What are the specific Gram + aerobes macrolides are effective for?
• Methicillin‐susceptible Staphylococcus aureus (MSSA)* • Streptococcus pneumoniae (only PSSP) – resistance is developing • Group and viridans streptococci • Bacillus spp., Corynebacterium spp.
What are the specific Gram - aerobes macrolides are effective for?
• H. influenzae (not erythro), M. catarrhalis,
Neisseria spp.
• Do NOT have activity against any Enterobacteriaceae
What macrolides have activity against Mycobacterium avium complex (MAC)?
Only azithromycin and clarithomycin
What is the oral absorption of the macrolides like?
Average to poor with clarithromycin the best at 55%
What is the CSF penetration of macrolides?
Poor
What is the elimination of erythromycin?
Erythromycin is excreted in bile and metabolized by CYP450
What are the main uses of macrolides?
• Respiratory Tract Infections
– Pharyngitis/ Tonsillitis – PCN‐allergic patients
• Uncomplicated Skin Infections
• STDs – Single 1 gram dose of azithro
• MAC – Azithromycin for prophylaxis; Clarithromycin/ Azithromycin for treatment
• Alternative of PCN allergic patients
Macrolide SE
Most common: nausea, vomiting, diarrhea, dyspepsia
Rare: allergic reaction, cholestatic hepatitis, thrombophlebitis, prolonged QTc, transient/reversible tinnitus
What is the interaction of macrolides with cytochrome P450?
Erythromycin and clarithromycin ONLY– are inhibitors of cytochrome p450 system in the liver which may increase the concentration of drugs metabolized by this enzyme
What is an example of a streptgramin?
Quinupristin/Daltopristin (Synercid®)
Quinupristin/Daltopristin MOA
Each agent acts individually on 50S ribosomal subunits to inhibit early and late stages of protein synthesis
Quinupristin/Daltopristin PKs
Each one is bacteriostatic alone, but together, they demonstrate time-dependent bactericidal activity
What are the mechanisms of resistance to quinupristin and daltopristin?
- Alterations in ribosomal binding sites (erm)
* Enzymatic inactivation
What is the general spectrum of activity of quinupristin and daltopristin?
-Gram- positive bacteria
What are the specific Gram + targets of Synercid®?
– Methicillin‐Susceptible and Methicillin‐Resistant Staph aureus and coagulase‐negative staphylococci*
– Streptococcus pneumoniae (including PRSP), viridans streptococcus, Group streptococcus
– Enterococcus faecium (including VRE)
– Corynebacterium, Bacillus. Listeria, Actinomyces
– Clostridium spp. (except C. difficile), Peptococcus, Peptostreptococcus
How is Synercid® administered?
Only parentally (IM or IV)
What is the CSF penetration of quinupristin/daltopristin?
Poor
What is the elimination of Synercid® via?
Liver
What is the main use for Synercid®?
- VRE (faecium) bacteremia
* Complicated skin and soft tissue infections due to MSSA or Streptococcus pyogenes
What is the effect of Synercid® on other drugs and how does this occur?
It can affect the elimination of other drugs because it is a Cytochrome p450 3A4 Inhibitor
Quinupristin/Daltopristin SE
Most common: venous irritation nausea, vomiting, diarrhea
Rare: rash, myalgias, arthralgias
Which one of the following statements regarding Clindamycin is true?
A. Clindamycin is readily removed by either hemodialysis
or peritoneal dialysis
B. Clindamycin is ineffective in the treatment of CNS
infections
C. Clindamycin levels in serum are non‐existent after oral
administration
D. Clindamycin’s activity is limited to Gram‐positive
anaerobes
E. Clindamycin has never been associated with causing C. difficile colitis
B. Clindamycin is ineffective in the treatment of CNS
infections
Which one of the following drugs does NOT interact with Cytochrome P‐450 enzymes? A. Erythromycin B. Azithromycin C. Clarithromycin D. Telithromycin E. Quinupristin‐Dalfopristin
B. Azithromycin
Which one of the following represents the primary mechanism of resistance to Clarithromycin in the US?
A. Mutations in Topoisomerase IV
B. Decreased affinity of clarithromycin binding proteins
present in the bacterial cell wall
C. Increased activity of an antibiotic efflux pump
D. Enzymatic inactivation
E. Alterations in the binding site on the 30S Ribosomal subunit
C. Increased activity of an antibiotic efflux pump
