Antimicrobial Therapies, Cell Wall Inhibitors Part 2

Are beta lactams time dependent or concentration dependent?

Time dependent

What happens as you progress through each of the generations of cephalosporins?

More gram negative coverage

What are the 1st generation cephalosporins?

• Cephalexin (Keflex)
• Cefazolin (Ancef)

What is the spectrum of activity of 1st generation cephalosporins?

• MSSA
• Proteus mirabilis
• E.coli
• Klebsiella pneumoniae

What are the 1st generation cephalosporins the preferred treatment for?

• Skin-soft tissue infections
• Strep pharyngitis (PO)
• Uncomplicated cystitis
• Surgical site prophylaxis (cephalexin)

Is renal dose adjustment required for 1st gen cephalosporins?

Yes

What are the "true" 2nd gen cephalosporins?

Cefuroxime (Ceftin, Zinacet)

What is the spectrum of activity of the "true" 2nd gen cephalosporins?

1st gen + Hib and some Neisseria

What are the "true" 2nd gen cephalosporins the preferred treatment for?

• Respiratory tract infections
• Skin soft tissue infections
• UTIs

Is renal dose adjustment required for the "true" 2nd gen cephalosporins?

Yes

What are the "cephamycin" 2nd gen cephalosporins?

Cefoxitin (Mefoxin)

What is the spectrum of activity of the "cephamycin" 2nd gen cephalosporins?

Gram pos and neg including anaerobes (bacteroides)

• Only cephalosporin that covers Gneg Bacteroides!!!

What are the "cephamycin" 2nd gen cephalosporins the preferred treatment for?

• Bowel surgery prophylaxis
• Intra-abdominal infections

Is renal dose adjustment required for the "cephamycin" 2nd gen cephalosporins?

Yes

What is the only 3rd gen cephalosporin with pseudomonas coverage?

Ceftazidime (Fortaz)

What are the 3rd generation cephalosporins?

• Ceftriaxone (Rocephin)
• Ceftazidime (Fortaz)
• Cefdinir (Omnicef)

For CNS infections, what 3rd generation cephalosporin should you give? What dose and frequency?

Ceftriazone 2g q 12 hrs

For enterococcus facaecalis, what should you give? What dose and frequency?

Ampicillin + Rocephin 2g q 12 hrs

What is the spectrum of activity of the 3rd gen cephalosporins?

Good gram positive and gram negative coverage

What are the 3rd gen cephalosporins the preferred treatment for?

• UTI
• Pneumonia
• Meningitis (Ceftriaxone)
• Neisseria gonorrhea (Ceftriaxone)

Is renal dose adjustment required for the 3rd gen cephalosporins?

Yes except ceftriaxone (Rocephin)

What carries a high risk for C.diff infection?

3rd gen cephalosporins

What is a side effect of Cefdinir?

If administered with iron, red colored stools

What is the BBW of ceftriaxone?

Administration with calcium containing IV products (lactated ringers) = inc risk of calcium precipitation in vivo

What are the 4th generation cephalosporins?

Cefepime (Maxipime)

What is the spectrum of activity of the 4th gen cephalosporins?

Good gram positive and gram negative coverage including pseudomonas(!!!!), enterobacter, serratia

What are the 4th gen cephalosporins the preferred treatment for?

Hospitalized patients with risk factors for gram negative organisms

Is renal dose adjustment required for 4th gen cephalosporins?

Yes

What are the 5th gen cephalosporins?

Ceftaroline (Teflaro)

What is the spectrum of activity of 5th gen cephalosporins?

Similar to 3rd gen + MRSA coverage

What are the 5th gen cephalosporins the preferred treatment for?

• MRSA skin/soft tissue infections
• CAP
• Reverse therapy for pts with risk factors for MRSA

Is renal dose adjustment required for the 5th gen cephalosporins?

Yes

What are the cephalosporin combo products?

• Ceftazidime-avibactam (Avycaz)
• Ceftolozane-tazobactam (Zerbaxa)
• Cefepime-enmetazobactam (Exblifep)

What is Cefepime-enmetazobactam (Exblifep) used for?

CRE ONLY (E.coli and Klebsiella)

What is Ceftolozane-tazobactam (Zerbaxa) good for treating?

Carbapenam-resistant pseudomonas

What are the combo cephalosporins the preferred treatment for?

• Hospitalized patients with very resistant gram negative infections
• Complicated UTIs and intra-abdominal infections need metronidazole added to the tx

Is renal dose adjustment required for the combo cephalosporins?

Yes

What are the monobactams?

• Aztreonam (Azactam)
• Aztreonam-avibactam (Emblaveo)

What is the spectrum of activity of monobactams?

No gram +; ONLY gram - including pseudomonas

What are monobactams the preferred treatment for?

Good for PCN allergy and needing Gram neg coverage

Do monobactams require renal dose adjustment?

Yes

Monobactams can be used if beta-lactam allergy EXCEPT…

if the allergy is to ceftazidime

What is the most potent abx class?

Carbapenems

What are the carbapenems?

• Meropenem-vaborbactam (Vabomere)
• Imipenem-cilastatin-relebactam (Primaxin)
• Ertapenem (Invanz)

What is the spectrum of activity of carbapenems?

• ESBL, Bacteroides, Pseudomonas, Acinetobacter, except ertapenem
• Ert(ape)nem = NO acinetobacter, pseudomonas, enterococcus

What does adding Vaborbactam and Relebactam to a carbapenem do?

• Expands the spectrum to include CRE/KPC
• Binds the beta-lactamases that specifically destroys carbapenems

What are carbapenems the preferred treatment for?

Hospitalized patients with sever infection requiring broad spectrum coverage

Do carbepenems require renal dose adjustment?

Yes

What is advantageous about Ertapenem?

It can be administered once daily, advantageous for outpatient abx administration

Why must Imipenem be combined with cilastatin?

Without cilastatin, dehydropeptidase destroys it

What risk comes with carbapenems?

Seizures (Imipenem MC)

Are glycopeptides bactericidal or bacteriostatic?

Bactericidal

What are the glycopeptides?

Vancomycin (vancocin)

What is the spectrum of activity of vancomycin?

Gram positive organisms ONLY and sometimes Enterococcus and C.diff

What is vancomycin the preferred treatment for?

• IV: Severe/resisitant gram positive infections
• PO: C.diff (drug of choice) and resistant Staph GI infections

What drug has a greater risk for nephrotoxicity than vancomycin?

Telavancin (therefore it is not used much, if ever, in practice)

What is the MOA of vancomycin?

Binds to D-alanine side chain of cell wall → lysis of cell wall

What are the adverse reactions of vancomycin?

• Redman syndrome (infusion rxn, not allergic): Stop infusion → start antihistamine → slow infusion time

• nephrotox, ototox

What is the MOA of Fosfomycin?

inhibits enzyme involved in 1st step of cell wall formation

What is Fosfomycin the preferred treatment for?

Uncomplicated UTIs (cystitis) ONLY

What is the spectrum of activity of Fosfomycin?

Staph. Saprophyticus, enterococcus, E. coli, pseudomonas

What are the lipopeptides?

Daptomycin (Cubicin)

Are lipopeptides bactericidal or bacteriostatic?

Bactericidal

What is the MOA of lipopeptides?

Binds CMem of G+ (Ca dependent) → channels form in CMem → K flows out of cell = disrupts CMem → cell death

What are the lipopeptides the preferred treatment for?

VRE (entero faecium!!!!) & MRSA ONLY

What should lipopeptides not be used for?

Pneumonia because surfactant in lungs binds daptomycin & inactivates it

What are the adverse effects associated with lipopeptides?

Associated w/ rhabdo

What is the MOA of Polymyxin B & Colistin (Coly-Mycin)?

Binds to polysaccharide layer of gram neg cell membrane

What is the spectrum of activity of Polymyxin B & Colistin (Coly-Mycin)?

Gram neg ONLY

What is Polymyxin B & Colistin (Coly-Mycin) the preferred treatment for?

Last line therapy for Gram neg infxns