Antimicrobial Therapies, Cell Wall Inhibitors Part 1

What drugs are beta lactams?

• Penicillins
• Cephalosporins
• Carbapenems
• Monobactam

Are beta lactams bacteriostatic or bacteriocidal?

Bacteriocidal

MOA of beta lactams

Disrupt activity of PCN binding proteins (PBPs) = loss of bacterial cell wall = lysis of bacteria

What are the Beta Lactam Resistance Mechanisms?

• Penetration
• Porins
• Pumps
• Penicillinases (B-lactamases)
• PBPs
• Peptidoglycan

What can you use if MSSA is resistant to beta lactams due to beta lactamases?

• Nafcillin
• Ampicillin/sulbactam

What can you use if E.coli is resistant to beta lactams due to beta lactamases?

Ceftriaxone (3rd gen)

What can you use if Pseudomonas is resistant to beta lactams due to beta lactamases?

Meropenem

What can you use if MRSA is resistant to beta lactams due to reduced target affinity?

• Vancomycin
• Ceftriaxone (3rd gen)

What can you use if H.influenzae is resistant to beta lactams due to reduced concentration at target site?

Ampicillin

Should beta lactams be taken on an empty stomach?

Yes, except for ones that are known to cause GI disturbances like Augmentin

Do most beta-lactams penetrate the CNS?

Yes

When do beta lactams doses need to be adjusted?

Renal disease except Rocephin

What happens if you give a patient Probenecid?

Increases serum penicillin levels; prolongs serum penicillin levels

What are the AE of beta lactams?

• Hypersensitivity (anaphylaxis, urticarial rashes): penicillins > cephalosporins
• Neuro (encephalopathy/seizures) associated w/ high doses & renal failure (Cefepime)

What are examples of natural penicillins?

• Penicillin G (benzathine, procaine)
• Penicillin V

What is the spectrum of activity of natural penicillins?

Gram positives (NOT staph)

What infections are preferentially treated with natural penicillins?

• GAS
• Gas gangrene (clostridium perfringens)
• Syphillis

BBW of natural penicillins?

IM formulation not for IV use; cardiac arrest and death have occurred

What may be seen if IM PCN is given with secondary syphillis?

Jarish-Herxhemimer Reaction (Fever, muscle ache, HA, tachy)

What must also be given if Procaine is administered for neurosyphillis?

Probenecid

AE of natural penicillins?

N/V

What are examples of penicillinase-resistant penicillins?

• Dicloxacillin
• Nafcillin
• Oxacillin

What is the spectrum of activity of penicillinase-resistant penicillins?

Staphylococcal (Gram +)

What infections are preferentially treated with penicillinase-resistant penicillins?

MSSA/MSSE

Are renal dose adjustments required for penicillinase-resistant penicillins?

No

What do penicillinase-resistant penicillins have comparable efficacy to? Which is preferred?

Cefazolin which is usualy preferred due to lower cost and easier to administer

What are examples of aminopenicillins?

• Amoxicillin
• Ampicillin

What is the spectrum of activity of aminopenicillins?

Additional amino group increases penicillin activity to include SOME gram - organisms

What infections are preferentially treated with aminopenicillins?

• Upper respiratory infections (otitis media, sinusitis, pharyngitis)
• Listeria meningitis (ampicillin)
• H.Pylori (amoxicillin)
• CAP in combo w/ atypical coverage

Is renal dose adjustment required for aminopenicillins?

Yes

What are examples of Penicillin + B-lactamase inhibitors?

• Amoxicillin-clavulanic acid (Augmentin)
• Ampicillin-sulbactam (Unasyn)
• Piperacillin-tazobactam (Zosyn)

What is the spectrum of activity of Penicillin + B-lactamase inhibitors?

Gram -, G + (not MRSA), and anaerobes

What is the only beta lactam that covers Pseudomonas?

Piperacillin-tazobactam (Zosyn)

What infections are preferentially treated with Penicillin + B-lactamase inhibitors?

• Respiratory tract infections (otitis media, sinusitis, CAP)
• Severe resp, abdomen, skin infections & multi-drug resistant Gram neg (Zosyn)

Is a renal dose adjustment required for Penicillin + B-lactamase inhibitors?

Yes

AE of Augmentin?

Diarrhea

What has the combination of Zosyn + vancomycin been associated with?

AKI

In Penicillin allergy assessment what time frame do reactions usually occur within?

Immediately or within an hour

What is required to meet the definition of anaphylaxis?

Reaction affecting 2 or more systems (Skin, Resp, CV, GI)

What test can be done if the penicillin allergy cannot be determined based on history alone?

Pre-Pen Test (scratch --> interdermal --> oral challenge (optional))