Acylaminopenicillins

Acylaminopenicillins are broad spectrum antibiotics that are mainly effective against gram-negative bacteria. Their individual active ingredients are used in particular to combat so-called hospital germs such as Pseudomonas aeruginosa or enterococci. However, the acylaminopenicillins are not acid and beta-lactamase stable.

What are acylaminopenicillins?

Acylaminopenicillins are broad spectrum antibiotics that belong to the group of penicillins. A special feature of their molecular structure is the possession of a beta-lactam ring. In the case of acylaminopenicillins, however, the beta-lactam ring is not protected against attack by so-called beta-lactamase, which is produced by certain bacteria. Furthermore, the acylaminopenicillins are not stable against the influence of acids.

Acylaminopenicillins are used in particular to combat gram-negative bacteria of the Pseudomonas or Proteus species. As broad spectrum antibiotics, however, they can also work against some gram-positive bacteria.

The main representatives of the group of acylaminopenicillins are the active ingredients azlocillin, mezlocillin, piperacillin or ampicillin. Because of their beta-lactamase and acid instability, the acylaminopenicillins are administered perenterally in the form of venous or muscular infusions.

Pharmacological effect on the body and organs

Like all penicillins, acylaminopenicillins also intervene in the metabolism of bacteria. After penetrating the bacterial cell, they inhibit the build-up of the bacterial cell wall. Their beta-lactam ring opens in the cell plasma of the bacterium and, when open, binds to the bacterial enzyme D-alanine transpeptidase.

With the help of D-alanine transpeptidase, alanine residues in the cell wall of the bacterial cell are connected to one another. By blocking this enzyme, this link can no longer take place. The bacterium then loses the ability to divide further and dies in the process.

The bacterial development of antibiotic resistance to the antibiotics of the penicillins is based on the ability of the bacterium to synthesize the enzyme beta-lactamase. The beta-lactamase breaks down the beta-lactam ring of the antibiotic before it can interfere with the metabolism. The acylaminopenicillins are also not protected against attack by beta-lactamase, since the ring in the molecule is freely accessible. Nevertheless, acylaminopenicillins are able to fight resistant germs with special application.

Since acylaminopenicillins are not acid and beta-lactamase stable, they must be injected parenterally. In this way, they immediately enter the bloodstream via a venous injection. Injection into the muscle is also possible. Immediately after administration, the active ingredient penetrates the bacterium's cell and prevents the bacterial cell wall from building up further. The bacterium is not primarily killed. However, it dies because it cannot divide any further.

Acylaminopenicillins are often used in combination with beta-lactamase inhibitors to overcome the antibiotic resistance of the bacteria to be controlled. The beta-lactamase inhibitor, as the name suggests, inhibits the activity of the bacterial enzyme beta-lactamase and can thus increase the effect of the acylaminopenicillins.

The half-life of acylaminopenicillins in the body is only about one hour. 60 percent of them are then excreted via the kidneys, largely unchanged.

Medical application & use

Acylaminopenicillins are widely used as broad-spectrum antibiotics in the fight against infections with the opportunistic germs Pseudomonas aeruginosa or the enterococci. As a rule, these bacteria are not very infectious. However, they can cause serious infections in immunocompromised people.

These are mostly nosocomial infections (infections with hospital germs). These germs enter the body particularly through wounds on the skin or mucous membranes. They often cause pneumonia in patients in intensive care units. Furthermore, they can cause urinary tract diseases after urological operations or the use of permanent catheters, purulent skin infections in wounds and even sepsis.

Piperacillin has the broadest range of applications among the acylaminopenicillins and thus also among the penicillins. It works against gram-negative bacteria such as enterobacteria, Pseudomonas aeruginosa and anaerobes as well as against gram-positive germs. Although its effect against gram-positive bacteria is worse than that of some other penicillins, it is considered sufficient in the context of a broad spectrum effect.

In addition to its use in combating hospital germs, piperacillin is also used for urogenital infections, gonorrhea, abscesses in the abdominal area, pneumonia, sepsis, bacterial endocarditis, infections in wounds and burns, as well as bone and joint infections.

Piperacillin is administered both as a single preparation and in combination with beta-lactamase inhibitors. The active ingredient azlocillin, on the other hand, is particularly effective against enterococci and Pseudomonas aeruginosa. It is often used together with cephalosporin for very severe infections caused by unknown pathogens.

Mezlocillin also has a broad spectrum of activity. However, it is less effective than azlocillin in treating Pseudomonas infections. Ampicillin is also a broad spectrum antibiotic, but overall it is less effective than any other acylaminopenicillin.

Risks & side effects

In addition to the many positive effects, the use of acylaminopenicillins also carries risks in some cases. Before using them, it must always be checked whether there is hypersensitivity to penicillins. It is possible that there is a cross-allergy with other beta-lactam antibiotics. If this is the case, there is a risk of anaphylactic shock when using acylaminopenicillins. Therefore the use of acylaminopenicillins is absolutely contraindicated in the presence of penicillin hypersensitivity.

In rare cases, further undesirable side effects can occur. So-called pseudo-allergies with reddening of the skin, rashes and itching are possible.

Drug fever, eosinophilia, painless swelling of the skin (Quincke's edema), anemia, vascular inflammation, kidney inflammation or even a permanent increase in platelets are observed very rarely. Overall, the risks are roughly the same as those observed when using other antibiotics.