Penicillins

What is the mechanism of action? 

Penicillins interfere in the synthesis of the bacterial cell wall. The bacterial cell wall is made up of peptidoglycan. They bind to the penicillin-binding proteins which prevents the cross linking of peptidoglycan strands. Due to this, the bacteria is unable to form its cell wall and undergoes lysis. 

In simple words: Penicillins prevent the formation of bacterial cell wall by binding to the penicillin binding proteins. 

There are 4 major types of Penicillins 

1. Natural penicillins 
2. Antistaphylococcal penicillins 
3. Aminopenicillins 
4. Extended-spectrum penicillins 

 

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Natural Penicillins 

What are the agents in this category? 

• Penicillin VK 
• Penicillin G 

Understand the different formulations :

• Penicillin VK or Penicillin V potassium is an oral formulation; available as tablet and suspension
• Penicillin G Aqueous – IV formulation
• Penicillin G Benzathine – IM formulation
  • Brand name: Bicillin L-A 
  • It is also available in combination with penicillin G procaine under the brand name Bicillin C-R

Spectrum of Activity:

• Streptococci, Enterococci 
• Treponema pallidum (syphilis) 
• gram positive anaerobes

Key points:

• Penicillin G benzathine is NOT for IV use. It is IM only . Can be fatal if given as IV
• Penicillin G benzathine (Bicillin L-A) is the drug of choice for Syphilis 
  • Look at it as “ Syphi-LA-s” to remember that Bicillin L-A is the drug of choice

• They do not cover staphylococcus! Staphylococci produce beta-lactamases which are enzymes that bind to the antibiotic and make them ineffective. Natural Penicillins are easily broken down by beta-lactamases therefore they do not have activity against staph. 

 

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Antistaphylococcal Penicillins

What are the agents in this category? 

• Dicloxacillin – PO
• Oxacillin – IV
• Naficillin – IV/IM

Spectrum of Activity?

• As the name suggests: MSSA (Methicillin Susceptible Staphylococcus Aureus) 
• Streptococci
• Note: No enterococci coverage 

Key points:

• They do not require renal dose adjustment
• They are preferred for infections caused by staphylococci such as endocarditis, skin and soft tissue infections, bloodstream infections
• They are dosed very frequently so you will see every 4-6 hour dosing intervals 

 

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Aminopenicillins

What are the agents in this category?

• Amoxicillin (Moxatag)
• Amoxicillin/clavulanate (Augmentin) 
• Ampicillin
• Ampicillin/sulbactam (Unasyn) 

Amoxicillin and Ampicillin alone are easily broken down by beta-lactamases. However they are also available in combination with beta-lactamase inhibitors such as clavulanate and sulbactam that protect them against beta-lactamases. 

As discussed earlier staphylococci produce beta-lactamases which tells us that amoxicillin and ampicillin alone do not have activity against staph but in combination with a beta-lactamase inhibitor, they do! 

Spectrum of Activity? 

• Streptococci, Enterococci
• They also have gram negative coverage which we have not seen so far: Haemophilus, Neisseria, Proteus, E.coli and Klebsiella (HNPEK) 
• MSSA – only Augmentin and Unasyn (remember we need the beta-lactamase inhibitor to have coverage against staphylococci) 

Key points:

• Ampicillin is the drug of choice for susceptible enterococci
• Ampicillin PO has poor bioavailability and Amoxicillin PO is preferred 
• Beta-lactamase inhibitors have little to no antimicrobial activity on their own except sulbactam. (Sulbactam is active against Acinetobacter Baumannii at high doses) 

 

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Extended-spectrum penicillins

 

What are the agents in this category? 

• Piperacillin/Tazobactam (IV only) – brand name Zosyn

Spectrum of Activity? 

• VERY BROAD COVERAGE
• Streptococci, Enterococci, MSSA
• Haemophilus, Neisseria, Proteus, E.coli and Klebsiella (HNPEK)
• Citrobacter, Acinetobacter, Providencia, Enterobacter, Serratia, (CAPES)
• Gram positive anaerobes, gram negative anaerobes
• Pseudomonas 

I wouldn’t focus on memorizing all the specific names of bacteria. It is important to know that it has very broad coverage including gram negatives and that it covers pseudomonas. 

Key points: 

• It covers pseudomonas 
• High sodium content in piperacillin/tazobactam (65 mg of sodium per 1 g or piperacillin)
• High risk of acute kidney injury (AKI) when used in conjunction with other nephrotoxic drugs

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What are the major side effects?

• Hypersensitivity reactions
• Drug fever 
• GI upset, diarrhea
• Risk of Seizures (with accumulation of the drug) 

Key points:

• Higher risk of nephrotoxicity (Acute Interstitial Nephritis) with antistaphylococcal penicillins. 
• High incidence of diarrhea with aminopenicillins when given orally 

Lastly, there is one important drug interaction to know with Penicillins: Probenecid! 

Probenecid is a drug used to treat gout. It interferes in the renal excretion of the penicillins, increasing its serum concentration. Sometimes, this drug interaction is used intentionally to help increase the levels of antibiotics. 

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Practice Questions

1. Which of the following is the drug of choice for treating syphilis? 

• Penicillin VK 
• Bicillin L-A
• Bicillin C-R 
• Nafcillin
• Amoxicillin/Clavulanate

2. Which of the following has coverage against pseudomonas?

• Unasyn
• Augmentin
• Zosyn
• Oxacillin
• Nafcillin 

3. MJ is receiving Zosyn 4g IV every 8 hours. The physician wants to monitor electrolytes because zosyn may increase levels of ______. 

• Potassium 
• Sodium 
• Calcium 
• Chloride
• Magnesium 

4. Which of the following does not require renal dose adjustment? 

• Piperacillin/tazobactam
• Ampicillin/Sulbactam
• Ampicillin
• Amoxicillin
• Nafcillin

5. Which of the following has good gram negative coverage? 

• Penicillin G Benzathine 
• Dicloxacillin 
• Nafcillin
• Amoxicillin 
• Penicillin VK 

6. Which of the following has coverage against MSSA? 

• Penicillin G Benzathine
• Amoxicillin
• Ampicillin 
• Amoxicillin/clavulanate 
• None of the above 

7. Which of the following is true regarding Penicillin G Benzathine? 

• It is the drug of choice for chlamydia
• It has good gram negative coverage 
• It is active against MSSA 
• It is for IM use only 
• It is dosed once daily due to its prolonged half-life 

8. Physician needs your help to start a patient on an anti-pseudomonal agent. What do you recommend? 

• Zosyn 
• Moxatag
• Unasyn
• Augmentin
• None of the above

9. Which of the following beta-lactamase inhibitor has antimicrobial activity?

• Tazobactam
• Sulbactam
• Clavulanate
• Avibactam
• beta-lactamase inhibitors do not have anti-microbial activity

10. Which of the following is not a warning associated with penicillins?

• Clostridium difficile
• Seizures
• Anaphylaxis
• Peripheral Neuropathy
• None of the above