Penicillins

Penicillins were the first discovered antibiotic medication.  A variety of penicillin variations have been developed that have effectiveness against various bacteria.  

Penicillins have three mechanisms of action. 

First, penicillins act as cell wall inhibitors by inhibiting transpeptidation, which weakness the cell wall strength. Second, penicillins bind to penicillin binding proteins on the surface of the bacteria, which changes the conformation and integrity of the bacterial cell wall. Third, in the absence of new cell wall production that is inhibited by penicillin, naturally produced autolysins from the bacteria degrade the bacterial cell wall.  

Bacteria have developed resistance mechanisms to penicillins.  Some bacteria secrete beta-lactamases, which are enzymes that degrade the beta-lactam ring of penicillins and render the drug ineffective.  Some bacteria have modified penicillin binding proteins, which limits the binding of penicillins.   Other resistance mechanisms are efflux pumps that efflux the drug from the bacteria and cell wall modifications that reduce penetration of penicillins into the bacteria.

Diarrhea, hypersensitivity, and nephritis are possible adverse effects.

Class Drugs

• Amoxicillin

• Ampicillin

• Dicloxacillin

• Nafcillin

• Oxacillin

• Penicillin

• Ticarcillin

• Piperacillin

Class Mechanism of Action

Three mechanisms of action:

• Cell wall inhibitor

Inhibits transpeptidation, which decreases cell wall strength/integrity

• Only effective against rapidly growing bacteria

• Inactivation of penicillin binding proteins (PBPs)

Bacteria have proteins on the surface that bind to penicillin, resulting in morphologic changes to the bacteria and weakening the structure of the cell wall

• Certain bacteria can develop resistance to penicillins by altering their proteins, so penicillins cannot interact (MRSA is an example)

• Autolysins

Many bacteria naturally produce autolysins that usually assist in performing "maintenance" function for the bacteria by degrading the cell wall.  If new cell wall is not being produced in the presence of penicillin, the autolysins aid in destruction of the cell wall.

Class Applications

Treatment of gram negative and gram positive infections

• Antimicrobial effects vary depending on drug

• See individual drugs for treatment applications

Class Adverse Effects

Resistance

• Beta-lactamase

Enzyme produced by some bacteria that hydrolyzes the beta-lactam ring, which renders the penicillin ineffective

Gram positive organisms secrete beta-lactamase

• Gram negative organisms have beta-lactamase in the periplasmic space

• Decrease penetration of drug

Some organisms' cell membrane is resistant to penetration of the penicillins, so the penicillin cannot bind to PBPs.

• Efflux pumps

Pumps decrease intracellular concentration of drug

• Modified PBPs

Alterations of the penicillin binding proteins structure, limits ability of penicillins to bind to the PBPs.

Hypersensitivity

• Rashes, angioedema, anaphylaxis

Diarrhea

• Alteration of normal gut flora causes diarrhea

• Clostridium difficile can also cause a severe form of diarrhea with use of antibiotics

Acute interstitial nephritis

Neurotoxicity

Cytopenia in long term therapy

Drug Table

Drug Name	Application	Comments	Image
Amoxicillin	Extended spectrum (compared to penicillin); Some gram negatives	Combined with clavulanic acid to treat beta-lactamase producing organisms; Resistance; Ineffective against beta-lactamase producers	"Ammo" "Ox" "Chilling"
Ampicillin	Extended spectrum (compared to penicillin); Some gram negatives	Combined with sulbactam to treat beta-lactamase producing organisms; Resistance; Ineffective against beta-lactamase producers	"Amp" "Chilling"
Dicloxacillin	Methicillin sensitive staphylococcus aureus (MSSA)	Resistance; Effective against beta-lactamase producers	"Dice" "Clocks" "Chilling"
Nafcillin	Methicillin sensitive staphylococcus aureus (MSSA)	Resistance; Effective against beta-lactamase producers	"NAFTA" "Chilling"
Oxacillin	Methicillin sensitive staphylococcus aureus (MSSA)	Resistance; Effective against beta-lactamase producers	"Ox" "Chilling"
Penicillin	Group A strepSyphilis (treponema pallidum)Gas gangrene (clostridium perfringens)	Penicillin V - oral therapy; Penicillin G - parenteral therapy; Resistance; Ineffective against beta-lactamase producers	"Pen" "Chilling"
Ticarcillin	Active against Pseudomonas aeruginosa; Effective against most gram negatives; Anaerobes	Combined with clavulanic acid to beta-lactamase producing organisms; Resistance; Ineffective against beta-lactamase producers	"Tic Tac" "Car" "Chilling"
Piperacillin	Active against Pseudomonas aeruginosa; Effective against most gram negatives; Anaerobes	Combined with tazobactam to beta-lactamase producing organisms; Resistance; Ineffective against beta-lactamase producers	"Pipe" "Chilling"