Macrolides, Clindamycin & Linezolids Flashcards by Yu Ning Teoh

Name the 3 Macrolides.

Erythromycin
Clarithromycin
Azithromycin

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Name the ABs that can potentially cause Ototoxicity.

Aminoglycosides
Vancomycins
Macrolides

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[T/F] Macrolides are bacteriocidal.

F.
- bacteriostatic, arrests growth of bacteria only
- does not kill/dip the population

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How are Macrolides administered?

Oral & Parentral administration avail.

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What are Macrolides often indicated for.

Atypical microbes.
- legionella, chlamydia, mycoplasma

Also indicated for: RTIs, CAP

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How are Macrolides cleared & excreted?

Metabolised hepatically, excreted primarily via bile

pxs w hepatic dysfunction => treat cautiously
like most 50S ribosomal subunit targeting ABs (macrolides & clindamycins)

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[T/F] Clarithromycin & Azithromycin have a higher activity against atypical bacteria than Erythromycin.

True.

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[T/F] Macrolides are a good alternative to B lactams & Vancomycins

Yes. In cases of px w renal impairment esp

cuz b lactams & vancomycins are cleared renally + vancomycins are nephrotoxic

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Main issue in Macrolides (Adverse effects)

GI distress & motility
- may lead to poor px compliance
- most severe in Erythromycin
- thus, Clarithromycin & Azithromycin modified to cause less GI distress

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Briefly list the Adverse effects of Macrolides.

GI distress & motility
Hepatotoxicity
Ototoxicity (deafness)
Prolongation of QT interval => caution in pxs w pro-arrhythmic conditions

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Can Macrolides be used in pregnancy?

on par w beta lactams, aka can be given as alternative to penicillin in indivs w b-lactam allergy
crosses placenta
clearance rate in pregnancy is faster in late pregancy

Erythromycin & Azithromycin => cat B
Clarithromycin => cat C

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Clindamycin is primarily used to treat..

Anaerobic infections

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Why do Clindamycins have cross-resistance w Macrolides?

likely due to ‘erm genes’ + that the 2 act at sites of proximity
clindamycin n erythromycin not structurally related but act at sites of proximity

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Clindamycins and Macrolides not given together. Why?

they act at sites of proximity => can antagonise each others action
note: they are not structurally related despite acting on sites of proximity

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Which drug has the highest risk of causing CDAD?

Clindamycin.
- cuz clostridium is a gram pos anaerobe that is not covered by clindamycin (always)
- despite clindamycin having large gram +ve & anaerobe coverage

** thus, clindamycin contraindicated in pxs w pseudomembranous colitis or ulcerative colitis

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Clindamycin has good coverage against..

Gram +ves
Anaerobes e.g. bacteroides, clostridiodes perfringen

Primarily: 1. MRSA 2. Streptococcus 3. Anaerobes 4. Penicillin resistant anaerobic bacteria

What is resistant against Clindamycin?

Almost all aerobic Gram neg bacteria are resistant

rmb clindamycin got larger gram pos & anaerobic coverage!

[T/F] Clindamycins have good spectrum of activity against oral pathogens

True.

excellent alt to penicillin for tx of dental abscesses cuz of bacterial susceptibility to the drug
great oral absorption + low emergence of bacterial resistance & good AB levels in bone
oral infections often due to anaerobes

[T/F] Clindamycins often used for prophylaxis against endocarditis.

True.
- endocarditis prophylaxis prior to dental procedures
- in pxs w acquired valvular damage, congenital heart disease, valve replacements & cardiomyopathy
- but not for wisdom tooth surgery or joint replacement pxs

Name the ABs that have MRSA coverage.

Clindamycins
5th gen cephalosporin: Ceftaroline (only B lactam w MRSA converage)
Vancomycins
Tetracyclines
Cotrimoxazole (fluoroquinolones no longer used against staphs due to resistance)
Linezolid

Distribution of Clindamycin:

excellent bone & salivary gland penetration
well distribution into body fluids & bone
poor entry to CSF

Can Clindamycin be used during pregnancy?

Yes. Cat B

Brief adverse effects of clindamycin?

Take w full glass of water to reduce esophageal irritation
Skin rashes
CDAD
- most likely AB to cause CDAD
- C. Difficile always resistant to clindamycin
- contraindicated in pxs w pseudomembranous colitis or ulcerative colitis

Why is Clindamycin a substitute for Macrolide resistant strains?

Clindamycin is not a substrate for macrolide efflux pumps

What are some ABs that only cover gram +ve bac?

1. Linezolid 2. Vancomycin 3. P2: penicillinase-resistant penicillins

Use of Linezolid is restricted as it has coverage over strains that are resistant to other agents. Which are these specific strains?

1. Penicillin-resistant strains of S. Pneumoniae 2. Methicillin-resistant staph (MRSA) 3. Vancomycin intermediate staph 4. Vancomycin-resistant strains of staph (VRSA) 5. Vancomycin-resistant strains of enterococci (VRE) (MRSA, VRE, VRSA)

Coverage/Antimicrobial activity of Linezolid?

**Gram +ve organisms** - staphylococci - streptococci - enterococci - listeria monocytogenes + including all the super resistant strains (MRSA, VRE, VRSA)

What bacteria are intrinsically resistant to Linezolid?

**Gram-negative infections** - gram -ve pathogenic bacteria => **intrinsically resistant due to efflux pumps** that force linezolid out of the cell faster than it can accumulate

Administration of Linezolid?

Oral or IV - excellent oral bioavailibility

Distribution of Linezolid.

- well distributed through body - good penetration into CSF

Clearance and excreted of Linezolid?

- broken down by nonenzymatic oxidation to two inactive metabolites - approx 80% of dose appears in urine - no dose adjustments req in renal or hepatic dysfunction

Brief adverse effects of Linezolid

1. Bone marrow suppression - need to monitor blood counts - as thrombocytopenia has been reported in patients taking the drug for longer than 10 days 2. GI effects 3. Serotonin syndrome - due to monoamine oxidase inhibitor 4. Irreversible peripheral neuropathies & optic neuritis 5. Tongue & teeth discolouration (reversible on finishing therapy)

Contraindications of Linezolid

1. **Catheter-related bloodstream infections** 2. Do not use within 2 weeks of MAO inhibitors e.g. phenelzine 3. Avoid theramine-containing foods & serotonergic drugs -> may precipitate hypertensive crisis - e.g. aged cheese, cured/smoked meats, draft beer

Why cant Linezolids be used w catheter related bloodstream infections?

- such pxs treated w linezolid => higher chance of death - catheter related infections often caused by **gram neg** bacteria - pxs w gram neg infections or mixed(+ve & -ve) infections have higher mortality when treated w linezolid

Name the ABs that target the 50S ribosomal subunit, inhibiting protein synthesis.

1. Macrolides - penicillin substitute, effective against atypical microbes 2. Clindamycins - mostly +ves, anaerobes, MRSA, streptococcus 3. Linezolids - unique mech: binds specifically to 23S ribosomal RNA of 50S subunit - reserved class like carbapenems

CNS penetration of Macrolides?

Poor

Resistance of Macrolides occurs due to

- acquisition of erm genes => results in reduced binding of macrolides to 50S ribosomal subunit - not used as first line drugs in odontogenic infections due to resistance (higher prevalence of resistance to macrolides in anaerobic streptococci, viridans grp streptococci

Clindamycin is metabolised and excreted via?

Hepatic, extensive oxidative metabolism at the liver to inactive products - excreted as bioinactive metabolites