Acylaminopenicillins represent broad-spectrum antibiotics that are primarily effective against Gram-negative bacteria. Their individual active ingredients are used especially to combat so-called hospital germs such as Pseudomonas aeruginosa or enterococci. However, acylaminopenicillins are not acid- and betalactamase-stable.
What are acylaminopenicillins?
Acylaminopenicillins are broad-spectrum antibiotics that belong to the penicillin group. A distinctive feature of their molecular structure is the possession of a beta-lactam ring. However, in the case of the acylaminopenicillins, the beta-lactam ring is not protected against attack by the so-called beta-lactamase, which is produced by certain bacteria. Furthermore, the acylaminopenicillins are also not stable against the influence of acids. Acylaminopenicillins are used in particular to combat Gram-negative bacteria of the Pseudomonas or Proteus species. However, as broad-spectrum antibiotics, they can also be effective against some Gram-positive bacteria. The main representatives of the acylaminopenicillin group are azlocillin, mezlocillin, piperacillin or ampicillin. Because of their beta-lactamase and acid instability, the acylaminopenicillins are administered perenteral in the form of venous or muscular infusions.
Pharmacologic effects on the body and organs
Like all penicillins, acylaminopenicillins interfere with the metabolism of bacteria. After entering the bacterial cell, they inhibit the assembly of the bacterial cell wall. Their beta-lactam ring opens in the cytoplasm 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 are linked together in the bacterial cell. By blocking this enzyme, this linkage can no longer take place. As a result, the bacterium loses the ability to continue dividing and dies in the process. The bacterial development of antibiotic resistance to penicillin antibiotics is due to the bacterium’s ability to synthesize the enzyme betalactamase. Betalactamase cleaves the antibiotic‘s beta-lactam ring before it can interfere with metabolism. Acylaminopenicillins are also not protected against attack by betalactamase, since the ring is freely accessible in the molecule. Nevertheless, acylaminopenicillins are capable of combating resistant germs when used in a particular manner. Because acylaminopenicillins are not acid- or betalactamase-stable, they must be injected parenterally. Thus, they enter the bloodstream immediately via venous injection. Injection into the muscle is also possible. Immediately after administration, the active ingredient then penetrates the cell of the bacterium and prevents further build-up of the bacterial cell wall. The bacterium is not primarily killed. However, it dies because it cannot divide further. Acylaminopenicillins are often used in combination with beta-lactamase inhibitors to overcome the extensive 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 enhance the effect of the acylaminopenicillins. The half-life of acylaminopenicillins in the body is only about one hour. They are then excreted 60 percent largely unchanged by the kidneys.
Medical use and application
Acylaminopenicillins find versatile use as broad-spectrum antibiotics in the control of infections with the opportunistic germs Pseudomonas aeruginosa or the enterococci. As a rule, these bacteria are not very infectious. However, they can cause severe infections in immunocompromised individuals. These are usually nosocomial infections (infections with hospital germs). These germs enter the body particularly through wounds on the skin or mucous membranes. In patients in intensive care units, they often cause pneumonia. They can also cause urinary tract infections following urological surgery or the use of permanent catheters, purulent skin infections in wounds, and even sepsis. Piperacillin has the broadest spectrum of use among the acylaminopenicillins and thus also among the penicillins. It is effective against Gram-negative bacteria such as enterobacteria, Pseudomonas aeruginosa and anaerobes as well as against Gram-positive germs.While its efficacy against Gram-positive bacteria is inferior to that of some other penicillins, it is considered sufficient in the context of broad-spectrum activity. In addition to its use in combating hospital germs, piperacillin is also used for urogenital infections, gonorrhea, abdominal abscesses, pneumonia, sepsis, bacterial endocarditis, infections in wounds and burns, and 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 Pseudomonas infections. Ampicillin is also a broad-spectrum antibiotic, but overall it has less efficacy than all other acylaminopenicillins.
Risks and side effects
The use of acylaminopenicillins carries risks in some cases in addition to their many beneficial effects. Before their use, it is always necessary to check for hypersensitivity to penicillins. Thus, it is possible that a cross-allergy with other beta-lactam antibiotics is present. If this is the case, there is a risk of anaphylactic shock when acylaminopenicillins are used. Therefore, the use of acylaminopenicillins is absolutely contraindicated in case of existing penicillin hypersensitivity. In rare cases, other undesirable side effects may occur. Thus, the occurrence of so-called pseudoallergies with skin redness, rashes and itching is possible. Very rarely, drug fever, eosinophilia, painless swelling of the skin (Quincke’s edema), anemia, vascular inflammation, kidney inflammation or even a permanent increase in platelets is observed. Overall, there are about the same risks observed with the use of other antibiotics.
