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Antibiotic resistance as an actual problem of clinical pharmacotherapy

Annotation: Resistance to antibiotics is a phenomenon of resistance of a certain strain of initiators of various infections to the action of certain types of antibacterial drugs, and also means a decrease in the susceptibility of the culture of microorganisms to the action of the drug

Keywords: Resistance , antibiotics, clinic, pharmacotherapy

Actuality of the topic: Problem of antibiotic resistance is actual because the creation of new antibiotics as a process is inhibited, and the development of resistance in microbes does not stop for an instant.

Literary analysis: after analyzing several literature sources, we have identified several ways to overcome resistance to antibiotics in microbes:

  1. Decrease of the using of antibiotics . First of all, it is necessary to avoid the use of antibiotics. We can reach this by improving the health system and the level of hygiene of the population. For example, in such routine ways as the mandatory washing of hands by medical personnel, patients and visitors in clinics and hospitals. In addition, to reduce the use of antibiotics helps and the most ordinary education - dissemination of knowledge among the population and training of pharmacists and doctors. Sometimes it is enough, for example, to clearly understand that antibiotics are not used against viral infections.
  2. Improvement of diagnostic methods . In addition, it is worth paying more attention to improving diagnostic methods. Accurate diagnosis will certainly use existing antibiotics to treat infections caused by bacteria that are sensitive to these antibiotics, and new antibiotics should be used only when they are really needed to fight drug-resistant infections.
  3. . Development of an innovative type of targeted antibiotics . This is especially true for tuberculosis and infections caused by the most dangerous Gram-negative bacteria. We need new, innovative approaches. Some of them will be in the field of developing drugs aimed at specific types of bacteria, others - even more narrowly focused - in the field of developing drugs against drug-resistant strains of bacteria. And all this will be used in conjunction with diagnostic methods to identify pathogens. The use of such targeted drugs will also help reduce the likelihood of bacteria developing resistance to drugs in the future.
  4. Investments in antimicrobial franchise . Many pharmaceutical companies no longer support the franchise for antibiotics, mainly because of the unprofitable investment in this sector compared to other sectors, for example, with oncology. The strategy for the rational use of antibiotics also requires revision: the world needs investments in research and development of new antibiotics, but we want to use them as little as possible. Therefore, governments and international organizations such as WHO are attracting public funding and foundations of public organizations to address the problem of antimicrobial resistance .

Experiment: It is known from the analyzed literature data that the basis for the correct choice of an antibacterial preparation for pneumonia is the premature identification of the exciting strain and the establishment of its sensitivity to antibiotic drugs. We set a goal to analyze the etiological factors of community-acquired pneumonia. In the study of the causative agents of this disease, the following trends were identified: Samples for study - sputum - were obtained in 82 patients. The microorganisms detected during bacteriological examination are given in Table. 1.

We have found that the major excitatory community-acquired pneumonia in adults strains regardless of anthropometric and physiological characteristics are pneumococcs bacteria (Streptococcus pneumoniae) and Haemophilus influenzae (Haemophilus influenzae). In addition, possible etiologic triggers may be Mycoplasma pneumoniae, Escherichia coli , and Klebsiella pneumoniae . Approximately 10% of cases are associated microorganisms.

Table 1 - Pathogens of community-acquired pneumonia

Name of agent

Identified cases

Monogenic flora

Streptococcus pneumoniae

36.6%

Haemophilus influenzae

30.2%

Mycoplasma pneumoniae

19.7%

Escherichia coli

1.3%

Klebsiella pneumoniae

2.5%

Associated flora - 9.8%

Thus, we will focus on the phenomenon of antibiotic resistance in microorganisms such as pneumococcus and hemophilic rod.

в-lactam antibiotics exhibit a high in vitro efficacy against pneumococci: insensitivity (the frequency of moderately resistant and resistant strains) to amoxicillin and amoxicillin / clavulanate is 0.5 %, to cefotaxime and

cefepime - 2 %, to penicillin - 9 %. Resistance to macrolides is from 2 to 6 %. Chloramphenicol, clindamycin and rifampicin also retain relatively high activity: insensitive strains are 5, 2 and 1 %, respectively. There was no evidence of resistance to levofloxacin and vancomycin. The highest percentage of insensitive strains (27 and 33 %, respectively)

is noted for tetracycline and co-trimoxazole. Polyresistance in pneumococci (resistance to 3 or more classes of drugs) occurs in 8 % of cases.

Potential activity against H. influenzae has the following antibiotics: aminopenicillins (ampicillin , amoxicillin), ureopenicillins (piperacillin), inhibitor- protected penicillins (amoxicillin/clavulanate, ampicillin/ sulbactam, piperacillin /tazobactam, ticarcillin /clavulanate), cephalosporins II ( cefuroxime, cefaclor), III (ceftriaxone, cefotaxime, ceftazidime) and IV (cefepime, cefpirome) generations, carbapenems, macrolides (azithromycin, clarithromycin), tetracyclines (tetracycline, doxycycline), fluoroquinolones (tsiproflok atsin, ofloxacin, pefloxacin, levofloxacin), rifampicin, chloramphenicol, trimethoprim-sulfamethoxazole. Despite the fact that penicillin, aminoglycosides, erythromycin can exhibit a mild in vitro activity against H. influenzae, therapy with these antibiotics cannot lead to microbiological or clinical efficacy during treatment. The most significant from the clinical point of view is the problem of resistance hemophilic rod to aminopenicillins due to the production of P - lactamases. Such microorganisms are usually sensitive to inhibitor - protected penicillins and cephalosporins, and for rapid detection of P - lactamase products it is sufficient to carry out a test with nitrocephrine .

In recent years, strains of H. influenzae have been described whose resistance to ampicillin is associated with a change in the target of the action of P - lactam antibiotics (penicillin-binding proteins) or a decrease in the permeability of the outer cell wall. These strains were called P - lactamasonegative ampicillin- resistant (BLNAR) and are considered insensitive to inhibitor- protected penicillins and cephalosporins such as cefaclor, cefuroxime, cefixime, ceftibutene.

Conclusions and further research prospects: Despite the discovery of new classes of antibiotics and the improvement of methods for their search, the main problem - the development of resistance in bacteria - remains unresolved. Another problem is that clinical trials greatly slow the development of drugs. They are required to meet a variety of security requirements, so their improvement and verification takes a lot of time. Yes, computer methods significantly accelerated and reduced the cost of searching for new antibiotics, but it is not yet possible to shorten the stage of clinical trials. In addition, the researchers themselves complain about the inaction of pharmacological companies and the lack of support in the development of antibiotics. They note that companies are interested in the production of a wide range of drugs and high efficiency. Therefore, studies of many promising drugs designed for specific groups of bacteria, often do not give a move, considering them unprofitable. It is possible that this will last until the moment when resistant bacteria begin to pose a real threat, that is, the number of patients will become much larger.

What, in the end, can we oppose microbial expansion? Modern research does not promise us an early and shattering victory, but they offer tactics of a gradual and inventive guerrilla war. Regular discoveries of new antibiotics, modification of old, modular constructor and combination of drugs create some variety, restraining the onslaught of bacteria. The transfer of science from the laboratory table to the computer allows us to slowly increase the rate of production of military weapons and gives us hope that in the foreseeable future we will be able to catch up with the evolution of bacteria

References

  1. Kozlov RS and others. Antimicrobial resistance Streptococcus pneumoniae in Russia: the results of a prospective multicentre study (phase A of the Pegac-I project ) // Clinical microbiology and antimicrobial chemotherapy. - 2002. - T. 4 , No. 3 . - P. 267-277 .
  2. Campos JM Haemophilus spp. In: Murrey PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RM, editors. Manual of Clinical Microbiology. 7 th ed. ASM Press; 1999. p.604-13.
  3. Felmingham D., Washington J. Trends in antimicrobial susceptibility of bacterial respiratory tract pathogens - findings of the Alexander project 1992-1996. J Chemother 1999; 11: 5-21.
  4. Jacoby GA Prevalence and resistance mechanisms of common bacterial respiratory pathogens. Clin Infect Dis 1994; 18: 951-7.
  5. Fuchs PC, Barry AL Interpretative criteria for susceptibilities of Haemophilus influenzae to ampicillin , amoxicillin and amoxicillin / clavulanate . J Clin Microbiol 1994; 32: 2846-50

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