Aminopenicillins are antibiotics used for antimicrobial treatment. Due to the chemical extension of penicillin with an amino group on the benzyl residue, the drug group shows a broader spectrum of activity than penicillin. Aminopenicillins are used as broad-spectrum antibiotics for various bacterial-related diseases.
What are aminopenicillins?
Aminopenicillin belongs to the group of beta-lactam antibiotics. This is structurally characterized by a four-membered lactam ring, which is formed during biosynthesis. Aminopenicillin and penicillin have the same basic structure. A substituted amino group on the benzyl radical distinguishes the two antibiotics in their chemical structure. To produce aminopenicillin, an amino group is synthesized at the α-position of benzylpenicillin. The additional amino group results in an extended range of activity and makes aminopenicillin a potent broad-spectrum antibiotic. ß-lactams (beta-lactams) such as aminopenicillin are acid fast and can be administered orally. However, the antibiotic is not resistant to ß-lactamases. ß-lactamases are found in many bacteria and reduce the spectrum of activity of aminopenicillin. ß-lactamase inhibitors prevent cleavage of the antibiotic. In combination with aminopenicillin, ß-lactamase inhibitors increase the antibiotic’s spectrum of activity. Aminopenicillins include the pharmaceuticals amoxicillin, ampicillin, pivampicillin and bacampicillin. Pivampicillin and bacampicillin are no longer prescribed. Amoxicillin and ampicillin will continue to be used to treat bacterial diseases.
Pharmacologic effects on the body and organs
Aminopenicillin binds proteins through the ß-lactam ring. Like all ß-lactam antibiotics, the ß-lactam ring is the center of action, and aminopenicillin binds identical protein structures as penicillin. The group known as penicillin-binding proteins includes the protein transpeptidase. Transpeptidase provides cross-linking of glycopeptides in a bacterial cell wall. If the enzymes are inactivated by ß-lactam antibiotics, the cross-linking of glycopeptides can no longer take place and the bacterial cell wall becomes unstable. As instability increases, water flows into the bacterium, builds up an osmotic imbalance, and the bacterium bursts. ß-lactam antibiotics such as aminopenicillin exert their bactericidal effect on bacteria that proliferate and form a cell wall. Due to the additional amino group on the benzyl radical, aminopenicillins capture more Gram-negative bacteria than penicillins. Furthermore, aminopenicillins are four to ten times more potent against Gram-negative bacteria compared to penicillins. Bacterial species targeted by aminopenicillins include Gram-positive bacteria such as enterococci, listeria, and Streptococcus faecalis. Salmonella, shigella, Haemophilus influenzae, Escherichia coli, Proteus mirabilis and Helicobacter pylori are Gram-negative bacteria that are within the spectrum of activity of aminopenicillins. While the antibiotic is effective against 60% of Escherichia coli strains and most strains of Proteus mirabilis, Haemophilus influenzae strains often exhibit resistance. Bacteria that can produce ß-lactamase are resistant to ß-lactam antibiotics. The spectrum of activity of aminopenicillins is extended when a ß-lactamase inhibitor such as tazobactam is also taken.
Medicinal use and use for treatment and prevention.
Aminopenicillins are broad-spectrum antibiotics and are given in practice for the initial treatment of bacterial infections. A broad-spectrum antibiotic is prescribed for initial treatment whenever the causative agent is unknown. For accurate and effective use of aminopenicillins, it is necessary to prepare an antibiogram and identify the bacterial strain. Aminopenicillins are mainly used for respiratory infections, urinary tract infections, sinusitis, otitis media, bacterial endocarditis, listeriosis, epiglottitis, osteomyelitis, meningitis, and soft tissue infections. Bacterial endocarditis is treated when the infection is enterococci. An aminoglycoside is administered concomitantly. Aminopenicillins are prescribed for urinary tract infections only when Proteus mirabilis, enterococci, or E. coli cause the infections. The bioavailability of an aminopenicillin depends on its chemical structure.The aminopenicillin amoxicillin is preferably administered orally and is 60 to 80 % absorbed enterally. The good bioavailability is related to a hydroxyl group substituted on the phenol ring (in the para position). Due to the chemical structure change, amoxicillin utilizes the enteric dipeptide transporter. In contrast, when the aminopenicillin ampicillin is administered orally, enteral absorption is only 30%. 70% of the active ingredient thus remains in the intestinal lumen. This leads to undesirable side effects in the gastrointestinal tract. Furthermore, the plasma level is insufficiently increased. Ampicillin is preferably administered intravenously (i.v.) or intramuscularly (i.m.) due to poor enteric absorption. Aminopenicillins bind to albumin in the human bloodstream and are excreted renally. Studies suggest that a minimal amount of aminopenicillins metabolize in the liver (hepatic).
Risks and side effects
Gastrointestinal side effects occur frequently after oral administration of aminopenicillins. In addition to diarrhea, pseudomembranous enterocolitis may occur. Other side effects include seizures and sensory and motor disturbances. These side effects often occur after high doses of antibiotics as a result of neurotoxic reactions and affect the central nervous system. In cases of infectious mononucleosis (Pfeiffer’s glandular fever) or leukemia present concurrently with infection, macular exanthema may occur as a result of aminopenicillin treatment. A serious side effect with penicillin derivatives such as aminopenicillins is anaphylactic shock. Contraindication exists in renal insufficiency, chronic lymphocytic leukemia, and penicillin allergy.
