Penicillins

Products

Penicillins are commercially available today in the form of film-coated tablets, capsules, as solutions for injection and infusion, as powders for preparing an oral suspension, and as syrups, among others. Penicillin was discovered in September 1928 at St. Mary’s Hospital in London by Alexander Fleming. He was working with staphylococcal cultures in Petri dishes. One of the plates had been contaminated by mold. Near the fungal colony, the staphylococci became transparent and dissolved. So the fungus formed a substance that killed the bacteria. Fleming called it penicillin. The group led by Howard Florey and Ernst Boris Chain at the University of Oxford later succeeded in purifying, isolating and producing the antibiotic. Penicillin was first produced on a large scale in the United States in the 1940s and used to treat infections. Among the earliest and natural penicillins is penicillin G (benzylpenicillin). Different active ingredients could be obtained by varying the fermentation medium.

Structure and properties

The basic structure of penicillins is 6-aminopenicillanic acid, which consists of a thiazoline ring and a beta-lactam. Lactams are cyclic amides. Beta refers to the number of carbon atoms in the ring (2). The 6-aminopenicillanic acid is composed of the two amino acids cysteine and valine. The older penicillins such as benzylpenicillin are acid labile and therefore can only be administered parenterally. Acid-stable oral penicillins have been developed that are also available orally, such as the aminopenicillin amoxicillin. Side-chain modifications have significantly altered the properties of natural penicillins (see below).

Effects

Penicillins (ATC J01C) have antibacterial properties against Gram-positive and, to some extent, Gram-negative pathogens. They inhibit bacterial cell wall synthesis by binding to the so-called penicillin-binding proteins (PBPs). PBPs include D-Ala-D-Ala transpeptidase, which is involved in the synthesis of the peptidoglycan. Penicillins are so-called suicide inhibitors because they bind irreversibly to the enzymes with the opening of the beta-lactam ring.

Indications

For the treatment of bacterial infectious diseases with susceptible pathogens.

Dosage

Penicillins usually must be administered several times daily or as an infusion because of their short half-life.

Active ingredients

The following agents are currently registered as human drugs in many countries:

In addition, there are numerous other penicillins, such as ampicillin.

Classification of penicillins

Penicillins are divided into several groups. They are formed by the variation of the side chain:

  • Natural penicillins such as benzylpenicillin are derived from -species.
  • Oral penicillins such as amoxicillin are orally bioavailable and can be taken, for example, in the form of tablets or as a suspension.
  • Acid-stable penicillins such as phenoxymethylpenicillin remain stable on contact with gastric acid.
  • Penicillinase-resistant penicillins such as oxacillin and flucloxacillin are resistant to penicillin-degrading enzymes of bacteria.
  • Aminopenicillins such as ampicillin and amoxicillin carry an amino group.
  • Broad-spectrum penicillins such as piperacillin have a broader spectrum of activity than the early agents, for example, also against pseudomonads.

Some penicillins are combined with beta-lactamase inhibitors such as clavulanic acid, sulbactam, and tazobactam to reverse resistance and increase efficacy.

Contraindications

Penicillins are contraindicated in hypersensitivity, including to other beta-lactam antibiotics. Refer to the drug label for complete precautions.

Interactions

Penicillins are organic anions and are actively secreted at the kidney. Other organic anions may competitively inhibit elimination. Probenecid was developed during World War 2 to “stretch” penicillin (pharmacokinetic booster). However, it came on the market too late to be actually used.

Adverse effects

The most common adverse effects include:

  • Gastrointestinal disturbances such as diarrhea, nausea, vomiting, abdominal pain, loss of appetite
  • Hypersensitivity reactions (allergic reactions) to anaphylaxis.
  • Candida infections of the mucous membrane, e.g. vaginal fungus and oral thrush
  • Skin rashes, see also under skin rash under amoxicillin.
  • Resistance