The role of amoxicillin in the treatment of common community-acquired infections

In recent decades the number of antibacterial agents has increased steadily. This doctor's arsenal includes a wide range of antibiotics that are active against, essentially all pathogenic bacteria. At the same time it became obvious downside widespread use of antibiotics - increasing resistance of pathogens.

Under these conditions, the question arises: how to treat antibiotic 30-40 which already used in clinical practice?

Experts have long come to the conclusion that the key to the success of therapy is not the novelty of the antibiotic and its rational choice. Not all pathogens exhibit a high resistance to antibacterial agents. In some cases, possible resistance can be overcome by increasing the dose or changing patterns of use of the drug. An example is the aminopenicillin, which for many years remain the choice of means in the treatment of a variety of community-acquired infections.

Amoxicillin or ampicillin?

Aminopenicillins have a similar spectrum of action, which includes some gram-positive and gram-negative bacteria. In vitro amoxicillin significantly superior to ampicillin for activity against pneumococcus, but is less active against enterococci, form the basis of the normal intestinal microflora.

Two aminopenicillin significantly different pharmacokinetic properties.

Amoxicillin is well absorbed in the gastrointestinal tract and has a high stability and bioavailability. Bioavailability ampicillin is not constant, in the preparation of the Russian manufacture it is approximately 20%, while that of amoxicillin is always greater than 50%. Food intake did not significantly affect the bioavailability of amoxicillin and ampicillin absorption worsens.

Among the current forms of amoxicillin highest bioavailability (93%) has Flemoxin Solutab, which is produced in the form of soluble tablets, microgranules containing the active ingredient. In one study, the maximum plasma concentration of amoxycillin Flemoxin Solutab after administration was achieved 30 minutes earlier and was 30% higher than after administration of amoxicillin capsules.

The tablets may be swallowed whole or taken as a solution. Furthermore, Flemoxin Solutab be administered 2 times a day, while other preparations of amoxicillin should be taken 3-4 times per day. Although amoxicillin is produced only in the form of oral, but if necessary can be sequential therapy, which begins with intramuscular or intravenous ampicillin followed by oral amoxicillin. This approach can significantly reduce costs associated with parenteral therapy.

In recent years, in predicting the effectiveness of antibiotics account for the ratio of their pharmacokinetic and pharmacodynamic properties. For beta-lactams, the main criterion is the time interval during which the serum level is above the minimum inhibitory concentration (MIC) for the pathogen - T> MIC (it should be ≥ 50%).

Good and stable bioavailability determines achieving higher drug levels in serum and longer conservation. Accordingly, on the clinical efficacy of amoxicillin may exceed ampicillin even with comparable activity of the two drugs in vitro. In Western countries, it is the most widely used amoxicillin, ampicillin instead. Russian doctors are still often prefer the latter, which can be explained only by the lack of awareness of the benefits of amoxicillin (in this case, the cost does not matter, as amoxicillin in any form related to affordable medicines, and to improve the results of treatment should provide cost savings).

Is there resistance to amoxicillin is increasing?

One of the main indications for the purpose of amoxicillin are infections caused by S.pneumoniae. In recent years, the spread of pneumococcal strains with reduced susceptibility to penicillin. In some countries, the proportion of such strains as high as 60%, and many of them are resistant to various antibiotics.

In Russian level of resistance to penicillin pneumococci than 10%, while in most cases show a moderately resistant strains that remain sensitive to amoxicillin. As part of a multicenter study of Pegasus in 1999-2005. studied the sensitivity of about 1,700 clinical isolates S.pneumoniae, isolated in our country.

During this period, all of the pathogen strains were susceptible to amoxicillin (the proportion of strains with moderate resistance less than 1%), and for the last 2 years, the situation has not changed. By activity against pneumococcus amoxicillin was comparable to ceftriaxone and levofloxacin, while the frequency of resistance to tetracycline was about 24%, to co-trimoxazole -11% -6% to macrolides. It should be noted that no pneumococci produce enzymes that destroy penicillins, so amoxicillin in combination with clavulanic acid suspected pneumococcal infection is meaningless.

Another common causative agent of community-acquired infections is H.influenzae, strains which can produce beta-lactamases, which destroy aminopenicillin. In a study of Pegasus-II resistance aminopenicillins H.influenzae among clinical strains isolated in Russia in 2003-2005., It was only 4.7%.

The main mechanism of resistance to amoxicillin M.catarrhalis also the development of beta-lactamases. This pathogen is characterized by a high level of resistance to aminopenicillins. According to a multicenter study conducted in 26 countries, only 22.7% of the strains M.catarrhalis (n = 874) were susceptible to amoxicillin. The incidence of resistance to amoxicillin / clavulanate was observed. As with all beta-lactams, aminopenicillin not have an effect on the atypical pathogens, including M.rneumoniae.

Thus, amoxicillin retains high activity against S.pneumoniae and H.influenzae, which are the causative agents of most infections of the upper and lower respiratory tract.

Infections of the lower respiratory tract

Community-acquired pneumonia

Pneumonia is the most common infectious diseases of the respiratory tract: in Russia each year at least 1 500 000 cases of pneumonia. The leading etiological factors of community-acquired pneumoniae are pneumatic Research Institute (30-50%), as well as atypical bacteria (primarily M.rpeitoniae) H.influenzae and, much more rarely - S.aureus, K.rpeitoniae and other enterobacteria.

The etiology of pneumonia depends on the age, severity, presence of concomitant diseases, and other factors. For example, children and young people a higher proportion M.rpeitoniae, and in patients with chronic obstructive pulmonary disease (COPD) and smokers, the role H.influenzae and other Gram-negative pathogens.

All foreign and domestic amoxicillin recommendations related to the means of choice in treating pneumonia. First of all it should be used in ambulatory patients under the age of 60 years, suffering from concomitant diseases (COPD, diabetes mellitus, congestive heart failure, liver cirrhosis, alcohol abuse).

Rational choice of amoxicillin is determined that it is safe and affordable drug is highly active against S.pneumoniae and inducing its resistance. In elderly patients and patients with comorbidities preference should be given amoxicillin / clavulanate, in order to overcome the possible resistance of Gram-negative pathogens.

Given the role of atypical pathogens in the etiology of community-acquired pneumonia, to the drugs of choice, along with amoxicillin, usually related macrolide antibiotics and respiratory fluoroquinolones. In recent years, many authors recommend widely used in the first stage macrolides treating community-acquired pneumonia, and include them in a combination therapy regimen in patients with severe pneumonia (for example, in combination with beta-lactam). However, the role of atypical pneumonia pathogens in the etiology appears somewhat exaggerated. G. Mills et al. summarized the results of 18 clinical trials comparing beta-lactam antibiotics and antibacterial drugs with activity against atypical pathogens, in 6749 patients with mild to moderate community-acquired pneumonia.

The authors analyzed the probability of non-response to treatment. Macrolides, fluoroquinolones, and ketolides performance had advantages over beta-lactams. It should be noted that similar results were obtained in patients with diagnosed chlamydial or mycoplasmal pneumonia.

Beta-lactams inferior comparing drugs only in patients with infections caused by Legionella spp. Possible explanations of "efficiency" beta-lactams with SARS may be misdiagnosed, spontaneous recovery, etc.

Approaches to the treatment of community-acquired pneumonia in children have some features. Numerous studies point to the importance of respiratory viruses in the development of pneumonia in children of preschool age and M.rpeitoniae - in schoolchildren.

Bacteria, including Streptococcus pneumoniae appears to play a major role in the etiology of more severe pneumonia. Differentiate typical (bacterial) and atypical (viral or mycoplasma) pneumonia in children is difficult. Some studies have noted a higher incidence of asthma attacks during a viral infection.

Some importance are the results of X-rays. The presence of the typical infiltration, particularly in combination with pleural effusion, generally indicates the nature of bacterial pneumonia. In favor of the bacterial etiology show also marked leukocytosis, elevated levels of C-reactive protein and leukocyte formula shift to the left. Given the high role in the etiology of mycoplasma pneumonia in children aged 5 to 15 years are the drugs of choice are macrolide antibiotics. In the treatment of presumed pneumococcal pneumonia in the outpatient setting shows the use of amoxicillin. If a patient responds poorly to treatment, it is necessary to add a macrolide.

An infectious exacerbation of COPD.

In Russia, there are more than 2 million patients with COPD, although the true number is much higher. It is established that patients with COPD are transferred from one to four or more exacerbations per year. The frequency of exacerbations is one of the most important factors determining the quality of life of patients with COPD, the rate of progression of the disease and economic costs.

In simple (uncomplicated) exacerbations of COPD represent infrequent exacerbations (<4 years) occurring in patients under the age of 65 years who have no serious comorbidities and expressed violations bronchial obstruction (forced expiratory volume in 1 second - FEV1> 50% predicted ). Signs of complications of COPD exacerbations are age ≥ 65 years, FEV1 <50% predicted, serious co-morbidities (diabetes, heart failure, impaired hepatic or renal function), frequent exacerbations (≥ 4 per year), hospitalization for an exacerbation in the previous 12 months. and / or ICs use of systemic corticosteroids or antimicrobial drugs in the previous 3 months.

The main causative agents of infectious exacerbations of COPD are H.influenzae (13-46%), S.pneumoniae (7-26%) and M.catarrhalis (9-20%), rarer H.parainfluenzae, S.aureus, P.aeruginosa and Enterobacteriaceae. The risk of detection of resistant organisms was higher in patients with complicated acute exacerbation of COPD.

Treatment with antibiotics is not indicated for all patients with acute exacerbation of COPD, since a large part of the cases, the causes of it are non-infectious factors, or viruses. Antibiotic therapy is considered justified in the presence of at least 2 of the 3 signs of acute infection (increased dyspnea, increased sputum, purulent sputum). In such cases, antimicrobials performance significantly superior to placebo.

Use amoxicillin should only be in uncomplicated exacerbations of COPD, which is characterized by pathogens sensitive to this antibiotic. In complicated exacerbations should be used inhibitor protected penicillin (amoxicillin / clavulanate).

Helicobacter pylori infection

Amoxicillin is the only beta-lactam, which is used to treat H. pylori infection. Experts of the European Group for the Study of N.rulori recommend to include it in the standard first-line therapy. Furthermore, amoxicillin other part of the circuit, particularly a bismuth-based. In recent years there has been growing resistance to various antibiotics N.rulori. For example, in some countries, including the Russian, the level of pathogen resistance to clarithromycin has reached 15-20%, and metronidazole - 35-40% that makes revise approaches to the treatment of H. pylori infection. At the same time, the activity of amoxicillin against N.rulori remains very high. In almost all countries, there are no resistant strains or their share does not exceed 1%.

Urinary tract infections

Urinary tract infections are the most common diseases in ambulatory and hospital practice. For example, the estimated number of cases of acute cystitis in Russia amounts to 26-36 million per year.

The main pathogens of uncomplicated urinary tract infections are gram-negative enteric bacteria, mainly E. coli (70-95%), and S.saprophyticus. E. coli has a natural (primary) sensitive to many antibiotics, including sulfonamides, tetracyclines, chloramphenicol, aminopenicillins. In Russia, the level of E. coli resistance to ampicillin is 30%, so the drugs of choice in the treatment of urinary tract infections is considered fluoroquinolones.

A decent alternative to it can serve as amoxicillin / clavulanate. In acute cystitis is quite effective and amoxicillin, which is determined in the urine in high concentrations. ON. Lopatkin et al. recommend using it for the first-line treatment of acute cystitis in pregnant women.

Conclusion

When choosing an antibiotic for the treatment of non-severe community-acquired infections is necessary to follow the principle of reasonable sufficiency, ie, it makes no sense to assign the powerful broad-spectrum antibiotics in cases where the same effect can be achieved using the available drugs with the necessary activity against the most likely pathogens.

Despite the many years of experience, amoxicillin retains high activity against major pathogens of the upper and lower respiratory tract, as well as N.rulori remains the drug of choice in their treatment. The effectiveness of antibacterial agents depends on their pharmacokinetic and pharmacodynamic properties, which in turn partially determined by release form.

Use of amoxicillin in the form of soluble tablets, microgranules containing the active substance (Flemoxin Solutab) provides increased bioavailability and improves results of the treatment. Important advantages of amoxicillin are safe and well tolerated, including in children.