Ch 30: protein synthesis inhibitors

Tetracycline resistance mechanisms

Naturally occurring: Efflux pumps

Enzymatic inactivation of drug

Production of bacterial proteins that block binding of antibiotic to ribosomes

Amioglycosides (spectrum of activity)

Work against most gram-neg bacilli, including MDR

P. Aeruginosa, Klebsiella pneumoniae, enterobacter sp. (used in combo with b-lactam)

Covers gram (-), gram (+), mycobacterium,

Aminoglycosides resistance mechanisms

Efflux pumps

Decreased uptake

Modification and inactivation by plasmid-associated synthesis of enzymes

-cross resistance does not exist

Macrolides resistance

Bacteria unable to take up antibiotic

Efflux pumps

Decreased affinity of 50S ribosomal subunit for antibiotic

Plasmid-associated esterases in gram (-) organisms

Which of the following adverse effects could be employed as a therapeutic use for erythromycin

Increased GI motility

Which of the following accurately describes the difference in spectrum of activity between erythromycin and azithromycin?

Azithromycin has better activity against respiratory pathogens (H.influenza, moraxella catarrhalis) but less potent against streptococci and staphylococcal

After 5 days of clindamycin for a skin infection, a pt develops diarrhea, ab pain, and fever. Which organism would you be concerned about as a causative pathogen of diarrhea?

C diff

Chloramphenicol resistance mechanisms

Enzymes that inactivate drug

Inability to penetrate bacterial cells

Alteration of binding sites of ribosomes

A 24 y/o pregnant woman was diagnosed with CAP and will be managed outpt. Which is a safe option?

Azithromycin

A 1 month old baby has developed gray baby syndrome. Which of the following did the baby likely recieve?

Chloramphenicol

Resistance mechanisms of linezolid and tedizolid

Reduced bidning at target site

No cross resistance with other protein synthesis inhibitors

Linezolid would be a good choice for antibiotic tx in which scenario?

Pneumonia caused by drug resistant strep pneumonia

A 77 y/o woman was started on antibiotics for pneumonia. After 3 days serum creatinine doubled. Which is most likely responsible?

Tobramycin

Which should not be given to children less than 8 due to deposition in bone and teeth

Doxycycline

Which antibiotic combos is inappropriate based on antagonism at same site of action

Clindamycin and erythromycin

Tetracyclines

Demeclocycline

Doxycycline

Eravacycline

Minocycline

Omadacycline

Saretycline

Tetracycline

Tetracyclines (MOA)

Enter bacterial cell via passive diffusion or an energy dependent active transport system.

Binds reversibly to the 30S subunit of bacterial ribosomes —> inhibits bacterial protein synthesis

Doxycycline (use)

Lyme disease, acne, peptic ulcer disease, cholera, rocky mountain spotted fever, chlamydia, mycoplasma pneumonia

Minocycline (uses)

Acne, PUD

Azithromycin uses

Chlamydia

Chloramphenicol (uses)

Rocky mountain spotted fever in pregnant pts

Tetracyclines (AE)

GI, hepatotoxicity, phototoxicity, vestibular dysfunction

Tetracyclines (extra)

Contraindicated in pregnancy, breastfeeding, and children under 8

Pseudotumor cerebral (intracranial HTN) —> discontinue

Tigecycline (class)

Glycycline

Semi-synthetic derivative of minocycline

Tigecycline (MOA)

Reversibly binding to 30S ribosomal subunit inhibits protein synthesis and provides bacteriostatic actions

Tigecycline (use)

Tx of complicated SSTIs, intraabdominal infections, CAP

Tigecycline (spectrum of activity)

Broad spectrum

-MSSA and MRSA

-VRE

-multi drug resistant streptococci

ESBL gram neg bacteria

Anaerobes

Tigecycline (extra)

Not recommended in pts <8y/O

Reserved for pts in whom alternative tx not suitable —> higher mortality

Aminoglycosides

Amikacin

Gentamicin

Neomycin

Strptomycin

Tobramycin

Aminogylcosides (MOA)

Bind to the 30S subunit of bacterial ribosomes.

Interferes with construction of ribosome and cause ribosomes to misread RNA

Bactericidal

Concentration dependent

Aminoglycosides (use)

Tx of serious infections due to gram (-) bacilli

Work against gram (-), gram (+), mycobacterium, and anaerobes resistant to AGs

Gentamycin: tularemia (rabbit fever) and can be combined with ampicillin to treat serious gram (+) infective endocarditis.

Tobramycin: treats UTI or pneumonia with antipseudomonal B-lactam

Macrolides

Azithromycin

Clarithromycin

erythromycin

Macrolides (MOA)

Irreversibly bind to 50S subunit of bacterial ribosomes to inhibit translocation and bacterial protein synthesis

Generally bacteriostatic

Azithromycin (uses)

Respiratory infections d/t H. Influenza and moraxella catarrhalis and urethritis caused by chlamydia, nontuberculosis mycobacteria infection

Erythromycin (use)

Alternative to PCN G in pts with allergy

Clarithyromycin (use)

Alternative to PCN G

H. Influenzae, chlamydia, legionella, moraxella catarrhalis, h. Pylori, nontuberculosis mycobacteria infections

Fidaxomycin (uses)

Initial episode of c diff

Macrolides (AE)

Gi upset, cholestatic jaundice, ototoxicity, prolonged QT, hepatotoxicity

Macrolides spectrum of activity

Gram (+): S. Aureus, s. Pneumoniae, corynebacterium diptheria

Gram (-): Legionella pneumophilia

Spirochetes (syphilis, lyme disease), mycoplama chlamydia

Clindamycin (class)

Lincosamide

Clindamycin (MOA)

Bind to 50S subunit of ribosome to inhibit bacterial protein synthesis

Clindamycin (uses)

Community acquired MRSA

Macrolide resistant, clindamycin susceptible strep pneumonia

Clindamycin (spectrum of activity)

Gram (+): MRSA and streptococcus

Anaerobes

Clindamycin (AE)

Strongly associated with c diff

Chloramphenicol (MOA)

Reversibly binds to 50S subunit of bacterial ribosomes. Inhibits protein synthesis at petidyl transferase rxn.

Bacteriostatic

Chloramphenicol (USE)

Reserved for life threatening MDR infections where no alternative exists

Plague meningitis or endophthalmitis

Chloramphenicol (AE)

Dose related anemia, hemolytic anemia, aplastic anemia, throbocytopenia, grey baby syndrome

Chloramphenicol Spectrum of activity

Chlamydiae

Rickettsiae

Spirochetes

Anaerobes

Gram (+)

Gram (-)

Oxazolidinones

Linezolid

Tedizolid

Oxazolidinones (MOA)

Bind to the 23S ribosomal RNA of the 50S subunit of bacterial ribosomes. Inhibits formation of 70s initiation complex.

Oxazolidinones (Use)

Developed to treat gram (+) organisms (MRSA, VRE< PCN resistnat)

Linezolid: VRE, pneumonia, skin and skin structure infections

Tedizolid: skin and soft tissue infections

Oxazolidinones (spectrum of activity)

Gram (+) organisms including streptococci, enterococci, staphylococci, mycobacterium, tubuerculosis, anaerobes.