The experience of clinical use of amoxicillin has about 30 years. It is all the more surprising that now, in the era of the antibiotic crisis, it still (alone and in combination with clavulanic acid) remains one of the best-selling antimicrobials. What is the secret of such longevity? Where and when can we (or should we) use amoxicillin?
Penicillin is a precursor to Amoxicillin
To answer these questions, let’s turn first to history. Penicillin is considered to be the first antibiotic that has found wide clinical use. It has proven to be a highly effective treatment for infections caused by many gram-positive and anaerobic microbes. At the same time, a significant majority of gram-negative microorganisms had natural resistance to penicillin. Moreover, a number of gram-negative and gram-positive bacteria, initially sensitive to penicillin, became resistant to it over time.
Another disadvantage of penicillin was the lack of a dosage form for oral administration. The introduction into clinical practice of phenoxymethylpenicillin, which was not destroyed in the acidic environment of the stomach and was administered orally, was undoubtedly a step forward. Unfortunately, this drug was noticeably inferior to penicillin in absolute antimicrobial activity, and the spectrum of its antibacterial action did not cover microbes that had natural and/or acquired resistance (resistance) to penicillin.
For penicillins, in particular, the first three mechanisms are of the greatest importance. Moreover, the last of them — a violation of the permeability of the cell walls and membranes of bacteria for antibiotics — causes penicillins not so much acquired as natural resistance. Structural or spatial modification of targets for the action of antibiotics leads to the fact that the drug loses its ability to bind to certain components of the microbial cell and thus becomes ineffective. Figuratively, this situation can be described as follows: the doctor, prescribing an antibiotic, tries to open the bacteria’s door lock with it, like a key. But the lock is already new, and the key is old, and it no longer fits the new lock. Therefore, a new key is needed-an antibiotic. (Exceptions are possible, however: for example, an old antibiotic is not so much a “key” as a universal “master key”; or, in order to open the door lock of the bacterium, the doctor made additional efforts (say, “pressed the door”, i.e. increased the dose of the drug) or used “auxiliary means” — added another antibiotic with the ability to enhance the effect of the first, etc.)
However, natural penicillins (benzylpenicillin and phenoxymethylpenicillin) suffered the greatest damage from bacteria that acquired the ability to synthesize penicillinases. The latter are enzymes that destroy (and, consequently, inactivate) antibiotics. Staphylococci were among the first to synthesize penicillinases.
Thus, in the late 40s, medicine faced two problems. Firstly, it was necessary to develop new penicillins that would be resistant to the action of bacterial (primarily staphylococcal) penicillinases. Secondly, new penicillins were needed, effective not only against gram-positive, but also gram-negative microbes. It was not possible to create an antibiotic that would satisfy both of these requirements. However, each of the tasks was solved separately.
Resistance to bacterial penicillinases
The first antibiotic resistant to bacterial penicillinases was methicillin. Unfortunately, neither he nor the subsequent preparations of the group of penicillin-resistant penicillins (oxacillin, cloxacillin, dicloxacillin, etc.) were active against gram-negative microbes. Streptococci and pneumococci turned out to be more sensitive to natural than to penicillin-resistant penicillins. Therefore, the scope of the new group of antibiotics was actually limited to the treatment of infections caused by methicillin-sensitive staphylococci.
The discovery of broad-spectrum semi-synthetic penicillins turned out to be one of the remarkable achievements of mankind in the fight against infections. The main representatives of this group of antibiotics (the modern name of which is aminopenicillins) ampicillin and amoxicillin became available. They were destroyed by bacterial penicillinases. They did not act on Pseudomonas aeruginosa. They were inferior to benzylpenicillin in antimicrobial activity against streptococci, pneumococci and staphylococci sensitive to the latter. However, the spectrum of their action turned out to be so wide that it became possible to effectively treat most infections caused by clinically significant gram-negative microbes.
The further evolution of penicillins proceeded in two directions. On the one hand, anti-pseudomonas penicillins (carbenicillin, ticarcillin, azlocillin, meslocillin, piperacillin) were created and introduced into clinical practice. On the other hand, attempts to “protect” some well—known antibiotics from destruction by bacterial enzymes have been crowned with success. This is how “protected” penicillins appeared, which are combinations of antibiotics with inhibitors of bacterial beta-lactamases: ampicillin + sulbactam, amoxicillin + clavulanic acid.
Clinical efficacy of Amoxicillin
There is no exact data on the prevalence of penicillin-resistant pneumococci. The proportion of such pneumococci among all Streptococcus pneumoniae does not seem to exceed 4-5%, although in a number of European countries (France, Spain, Hungary) it is several times more. Pneumococci do not produce penicillinase. The resistance of these microbes to penicillin is associated with the modification of penicillin-binding proteins. However, amoxicillin, for reasons not fully understood, as a rule, retains clinical efficacy in the treatment of infections caused by penicillin-resistant pneumococci. Even if not with all such infections, and even infections of not all localizations, but in most cases amoxicillin is not only effective, and sometimes (for example, with acute otitis media) it is a means of choice. The most likely explanation is that, for some reason, this antibiotic has the greatest affinity among penicillins for penicillin-binding proteins. Do you remember the comparison with the “master key”?
For many years, only the first of the two main aminopenicillins (ampicillin and amoxicillin) was used. It’s hard to say what caused it. Do I need to change my habits? Yes, it is necessary. There are several reasons for this. And it’s not just that amoxicillin, like ampicillin, is available to the vast majority of people who do not suffer from an excess of cash. The fact is that amoxicillin is used 2-3 times a day (while ampicillin is used 4 times). Consequently, the patient’s willingness to follow the doctor’s recommendations when prescribing amoxicillin will be higher than when prescribing ampicillin. Secondly, food intake practically does not affect the absorption of the drug (unlike ampicillin). As a result, the doctor’s confidence in achieving treatment goals increases. Thirdly, with many common infections caused by penicillin-resistant pneumococci, amoxicillin makes it possible to achieve a cure, which cannot be said about ampicillin. Finally, there are numerous national and international recommendations for the empirical treatment of infections of different localizations, where of the two aminopenicillins, amoxicillin is preferred. This does not mean that ampicillin has “exhausted” itself. As a drug for parenteral use, it will serve as an effective means of fighting infections for a long time. But ampicillin for oral administration in a significant majority of cases should give way to amoxicillin.