What are penicillin antibiotics?

Definition

Penicillin is a major subclass of beta-lactam antibiotics discovered in 1928 when a culture plate became contaminated with Penicillium notatum (now called P. chrysogenum). This mold inhibited the Staphylococcus aureus that bacteriologist Alexander Fleming was culturing, and eventually the active ingredient, penicillin, was isolated. However, it took the work of other scientists to establish the practical properties of the drug, and Howard Florey and Ernst Boris Chain developed it as an antibiotic by performing clinical tests and creating a concentrated form in the late 1930s and early 1940s. Subsequent penicillins were derived from either molds or Streptomyces spp. bacteria. Crystallographer Dorothy Crowfoot Hodgkin worked out the structure of the penicillin molecule in the late 1940s, allowing the development of synthetic versions of the drug.

Penicillins are highly associated with drug allergy, affecting 6 to 8 percent of the population of the United States. Reactions range from mild rash to cardiovascular collapse, shock, and death. Health care providers should always record a person’s allergy history; people who are allergic to other beta-lactam antibiotics, such as cephalosporins, are likely also allergic to penicillins.

Mechanism of Action

The beta-lactam ring is responsible for the antibacterial actions of the penicillins. Penicillins prevent the formation of peptidoglycan, a substance crucial to the structural stability of bacteria cell walls. The weakened cell walls eventually lyse, or break apart, leading to cell death. Microorganisms that do not have a cell wall, such as
Mycoplasma
, are not susceptible to penicillins.

Drugs in This Class

Several subclasses of penicillins exist. These subclasses are natural penicillins, penicillinase-resistant penicillins, aminopenicillins, and extended spectrum penicillins. Two main factors differentiate the various penicillin products available from each other: resistance to staphylococcal penicillinase and spectrum of activity.

Staphylococcal penicillinase is an enzyme in the beta-lactamase family that inactivates certain beta-lactam antibiotics. The natural penicillins (penicillins G and V) are narrow-spectrum antibiotics used against a number of gram-positive bacteria such as streptococci. They are not resistant to penicillinase and have only limited activity against staphylococci. Penicillin G (benzylpenicillin) is unstable in stomach acid and must be given as an immediate-action injection. When formulated as insoluble benzathine and procaine salts, it may be given as a long-acting intramuscular injection. Penicillin V (phenoxymethyl penicillin) was the first oral penicillin.

The resistant penicillins (methicillin, nafcillin, oxacillin, and dicloxacillin) retain effectiveness against penicillinase-producing S. aureus. They do not, however, have a broad spectrum of activity and are only an improvement on natural penicillins in their activity against staphylococci. Even this advantage is diminishing over time with the development of methicillin-resistant S. aureus (MRSA), which refers more broadly to S. aureus strains that are resistant to all penicillins; vancomycin is the drug of choice for MRSA. Methicillin itself is no longer clinically relevant.

Aminopenicillins possess a broader spectrum of activity and are effective against some gram-negative bacteria. Ampicillin, the first drug in this category, is effective against a number of gram-negative bacteria, but not against Pseudomonas. Amoxicillin is closely related to ampicillin but has better oral absorption; it can cause gastrointestinal upset and drug-induced diarrhea. A combination of amoxicillin with clavulenic acid (Augmentin) lends some protection against penicillinase. These drugs are all available in oral dosage forms.

Subsequent broad-spectrum penicillins for intravenous use (ticarcillin and pipericillin) are active against Pseudomonas but are less active against some other gram-negative bacteria. These drugs and the aminopenicillins are as active against gram-positive cocci as are natural penicillins. Ticarcillin is often combined with potassium clavulanate and pipericillin with tazobactam to increase the resistance to penicillinase.

Impact

Penicillins remain important antibiotics for a number of conditions.
Most are inexpensive and have a reasonably favorable adverse-effect profile. The
increased prevalence of MRSA, however, particularly in hospitalized persons, has
limited the scope of penicillins in recent years.

Bibliography

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