Analysis of the spectrum of microflora and antibiotic resistance of the main pathogens in the pathology of ENT organs


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Abstract

Relevance. Among all purulent-inflammatory diseases, pathology of the upper respiratory tract and ear accounts for up to 15% of patients. Microorganisms play the greatest role in the occurrence of diseases of these organs. However, in recent years, the prevalence of antibiotic-resistant bacterial strains has increased sharply, which is one of the important public health problems of the 21st century according to WHO.
Goal. To study and analyze the spectrum of various microorganisms in purulent-inflammatory diseases of ENT organs and to assess their antibiotic resistance to the most commonly used groups of drugs.
Methods. Study of scientific, special and public literature; analysis of microbiological monitoring of the main biomaterial (ear discharge; upper respiratory tract discharge) of the ENT-1 department BUZ VO VOKB No. 1 for the period 2014-2019.
Results. During the time period from 2014 to 2019, with purulent-inflammatory ear diseases, the following dynamics of the microflora spectrum is observed: the leading position is occupied by the Pseudomonas aeruginosa (an increase from 12.24% to 33.89%), the share of diseases caused by Staphylococcus aureus decreases (from 32 , 65% to 10.17%), the dynamics of saprophytic staphylococcus fluctuates slightly (from 18.37% to 18.64%). In case of purulent-inflammatory diseases of the upper respiratory tract, the following can be noted: Staphylococcus aureus retains 1 position, but the percentage of diseases caused by this pathogen decreases from 41.94% to 20.96%. Streptococcus viridans and Staphуlococcus saprophyticus, which until 2016 were at 2 and 3 positions, respectively, however, in 2019 Staphуlococcus epidermidis decreases (from 10.81% to 9.97%), while Klebsiella increases (from 9.80% to 10, 99%), although diseases associated with the pathogen - Klebsiella are relatively stable.Investigating the level of resistance of the leading flora to antibacterial drugs, it turned out that the highest resistance of Staphуlococcus aureus is observed to ampicillin (35-42%); Streptococcus viridans - to oxacillin (17-23%); Staphylococcus saprophyticus - to erythromycin (47-49%); Pseudomonas aeruginosa - to ceftazidime (6-15%); Staphуlococcus epidermidis - to ampicillin (27-50%); Klebsiella pneumoniae - to fosfomycin (20%). Therefore, treatment with the listed drugs in relation to these pathogens will be the least effective.
Conclusion. Assessment of the antibiotic resistance of microflora at the present stage will allow the otorhinolaryngologist to choose the most appropriate antibacterial drugs. Monitoring the dynamics of the spectrum of microflora in inflammatory diseases caused by certain bacteria will make it possible to correctly predict the effectiveness of the treatment, reduce the number of complications in purulent-inflammatory diseases of the upper respiratory tract and ear, and reduce the transition of an acute inflammatory process into a chronic one.

Full Text

RELEVANCE

Purulent-inflammatory diseases of the upper respiratory tract and ear account for up to 15% of the total number of patients. It is noteworthy that more than half of these patients are young and able-bodied people from 25 to 50 years old. Microorganisms, as well as aggressive environmental factors (cooling, chemical and physical substances, dust, global warming, as well as a decrease in local and General immunity) play an important role in the development of ENT pathology. Antibacterial therapy is still one of the most successful in the treatment of patients with purulent-inflammatory diseases. However, the prevalence of antibiotic-resistant bacterial strains has increased dramatically in recent years [1]. According to who, the resistance of microorganisms to antibiotics is one of the most important public health problems of the XXI century [2].

GOAL
To study and analyze the spectrum of various microorganisms in purulent-inflammatory diseases of ENT organs and evaluate their antibiotic resistance to the most commonly used groups of drugs
METHODS
1. The design of the study. The study included microbiological monitoring of the main biomaterial (ear discharge; upper respiratory tract discharge) of the ENT-1 Department of the BUZ IN VOKB No. 1 for the period 2014-2019.
2. The match criteria. In the course of the study, compliance criteria were not formed.
3. Conditions of the competition. The study was conducted on the basis of BUZ IN VOKB No. 1, ENT Department-1.
4. the duration of the study was 6 months.
5. Description of the medical intervention. Study and analysis of the spectrum of microflora and antibiotic resistance of the main pathogens in the pathology of ENT organs.
6. The main outcome of the study. Identification of the main agents of purulent-inflammatory diseases of ENT organs according to Dunn biomaterial No. 1 (discharge from ear) and biomaterial No. 2 (detachable from the upper respiratory tract); study of the level of resistance leading flora to antibacterial drugs.
7. Additional outcomes of the study. Identification of additional microorganisms seeded from biomaterials #1 and #2.
8. Analysis in subgroups. No subgroups were formed during the study.
9. Methods of registration outcomes. The use of Microsoft Excel for recording and processing results.
10. Statistical analysis was performed using the software package Statistica 6.0, developed by Statsoft, USA. The format for representing quantitative data is dbf.

RESULTS
Objects (participants) of the study:
The objects of research were microbiological biomaterials: 1) ear discharge; 2) upper respiratory tract discharge for the time period from 2014 to 2019.
Main results of the study:
1. Biomaterial #1-ear discharge.
In 2014, out of 66 submitted biomaterials, 49 cases were seeded positive: Staphylococcus aureus was seeded in 32.65% of cases in the 1st place, Staphylococcus saprophyticus and Staphylococcus epidermidis in 18.37% of cases in the 2nd place, and Pseudomonas aeruginosa in 12.24% of cases in the 3rd place. In 2015, out of 85 submitted biomaterials, 60 cases were seeded positive.Pseudomonas aeruginosa was seeded in 35% of cases in the 1st place, Staphylococcus saprophyticus in 15% of cases in the 2nd place, and Staphylococcus aureus in 10% of cases in the 3rd place. In 2016, out of 82 submitted biomaterials, in 62 cases the seeding was positive, the distribution was as follows: Pseudomonas aeruginosa was sown in 30.65% of cases, Staphylococcus saprophyticus was sown in 20.97% of cases, and Staphylococcus aureus was sown in 8.06% of cases in the 1st place. In 2017, out of 84 submitted biomaterials, in 58 cases, the seeding was positive. Pseudomonas aeruginosa was also in the 1st place-in 29.31% of cases, Staphylococcus saprophyticus was seeded in 18.97% of cases, and Staphylococcus aureus was seeded in 8.62% of cases. In 2018, out of 79 submitted biomaterials, 61 cases were seeded positive: Pseudomonas aeruginosa was seeded in the 1st place-in 32.79% of cases, Staphylococcus saprophyticus was seeded in the 2nd place - in 22.95% of cases, and Staphylococcus aureus was seeded in the 3rd place – in 11.48% of cases. In 2019, out of 83 submitted biomaterials, in 59 cases, the seeding was positive.Pseudomonas aeruginosa was sown in 33.89% of cases, Staphylococcus saprophyticus was sown in 18.64% of cases, and Staphylococcus aureus was sown in 10.17% of cases in the 1st place.
2. Biomaterial #2-discharge from the upper respiratory tract.
In 2014, out of 579 biomaterials, 341 positive crops were obtained: Staphylococcus aureus (41.94%) took the first place, Streptococcus green (11.73%) took the second place, and Staphylococcus saprophyticus took the third place (8.8%). In 2015, out of 497 biomaterials, 308 positive seeding was obtained: Staphylococcus aureus took the first place (37.01%), Streptococcus green took the second place (12.01%), and Staphylococcus saprophyticus took the third place (10.06%). In 2016, 296 positive crops were obtained from 506 biomaterials: Staphylococcus aureus (29.05%) was in the first place, Staphylococcus epidermidis (10.81%) was in the second place, and Klebsiella (9.80%) was in the third place. In 2017, 289 positive crops were obtained from 514 biomaterials: Staphylococcus aureus was in the first place (24.91%), Staphylococcus epidermidis was in the second place (10.03%), and Klebsiella was in the third place (8.99%). In 2018, 304 positive crops were obtained from 529 biomaterials: Staphylococcus aureus took the first place (22.04%), Staphylococcus epidermidis took the second place (10.20%), and Klebsiella took the third place (9.87%). In 2019 of the 503 biomaterials obtained 291 positive seeding: took the first place - Staphylococcus aureus (20, and 96%), second place - Klebsiella (10,99%), the third place - Staphylococcus epidermidis (of 9.97%).
3. Exploring the leading level of resistance of microflora to antibacterial preparations in the period from 2014 to 2019 years, revealed the following values (in %, min-max):
a) the lowest resistance in Staphylococcus aureus was to amoxicillin/clavulanate (0-1%), ampicillin/sulbactam (0-2%), gentamicin (0%), linezolid (0-1%), cefoxitin (0-2%), tigecycline (0%), oxacillin (0-6%), rifampicin (0%), ciprofloxacin (0%), fusidine (0-1%), clindamycin (0-6%). Resistance to erythromycin was higher and amounted to 13-14%. The highest resistance was observed to ampicillin (35-42%).
b) the lowest resistance in Streptococcus green was to ampicillin/sulbactam (0%), vancomycin (0%), gentamicin (0-3%), levofloxacin (0-3%), linezolid (0%), tigecycline (0%), ciprofloxacin (0%), fusidin (0%). Resistance to ampicillin and norfloxacin was higher than 0-11% and 10-15%, respectively. The highest resistance was determined to oxacillin (aged 17-23%).
C) the lowest resistance in Staphylococcus saprophyticus was to clindamycin (0%), linezolid (0%), tigecycline (0%), rifampicin (0%), fusidine (0%). Increased resistance was to amoxicillin/clavulanate (4-13%), levofloxacin (9-11%), oxacillin (14-16%), ciprofloxacin (10-11%), cefoxitin (11-16%); ampicillin (23-25%), gentamicin (15-25%). The highest resistance was found to erythromycin (47-49%).
d) the lowest resistance in Pseudomonas aeruginosa was found to amikacin (0%), piperacillin (0%), cefepime (0-6%), ciprofloxacin (0-6%), cefoperazone (0%), cefoperazone/sulbactam (0%), piperacillin/tazobactam (0%). More pronounced resistance was found to imipenem (3-10%), Meropenem (7-10%), and ceftazidime (6-15%).
e) the lowest resistance in Staphylococcus epidermidis was found to amoxicillin/clavulanate (0%), linezolid (0%), tigecycline (0%), fusidine (0%). This is followed by ampicillin/sulbactam (6%), gentamicin (6-12%), cefoxitin (11%), oxacillin (11-14%), ciprofloxacin (11-16%), levofloxacin (23%), and erythromycin (25%). The most pronounced resistance was found to ampicillin (27-50%).
e) the lowest resistance in Klebsiella pneumoniae was found to the following antibiotics: amikacin (0%), imipenem (0%), Meropenem (0%), ertapenem (0%), piperacillin (0%), Ceftriaxone (0%), cefoperazone/sulbactam (0%), cefoperazone (0%), cefepime (0-5%), ceftazidime (4-6%), ciprofloxacin (4-7%). The highest resistance was found to fosfomycin (20%).
Additional findings of the study:
A. the following microorganisms were also isolated from the biomaterial "ear discharge" in 2014-2019: Enterococcus faecalis, Proteus common, Proteus wonderful, Escherichia coli, Klebsiella, Candida glabrata, Pseudomonas sp, Corynebacterium, Staphylococcus epidermidis, Streptococcus green, Citrobacter, Enterobacter, Streptococcus Green. b. The following microorganisms were also isolated from the biomaterial "upper respiratory tract discharge" in 2014-2019: Pseudomonas aeruginosa, Enterobacter, Staphylococcus epidermidis, Klebsiella, Pseudomonas sp, Enterococcus faecalis, Escherichia coli, Candida albicans, Streptococcus β-haemolyticus, Proteus wonderful, Citrobacter, Candida tropicalis, Candida glabrata, Streptococcus pyogenes, Proteus common, Candida krusei.
There were no adverse events.

DISCUSSION
Summary of the main research result:
A) the Leading flora in purulent-inflammatory diseases of the ear are the following microorganisms: Staphylococcus aureus, Staphylococcus saprophyticus, Staphylococcus epidermidis, Pseudomonas aeruginosa. In purulent-inflammatory diseases of the upper respiratory tract, the leading flora was also Staphylococcus aureus, Staphylococcus saprophyticus. In addition, Streptococcus viridans, Staphylococcus epidermidis, and Klebsiella.
B) as for the levels of resistance of the leading flora to antibacterial drugs, the highest resistance in Staphylococcus aureus was observed to ampicillin (35-42%), in Streptococcus viridans - to oxacillin (17-23%), in Staphylococcus saprophyticus - to erythromycin (47-49%), in Pseudomonas aeruginosa - to ceftazidime (6-15%), in Staphylococcus epidermidis - to ampicillin (27-50%), in Klebsiella pneumoniae - to fosfomycin (20%). Therefore, the effectiveness of treatment with these drugs against these pathogens will be the least effective.
Discussion of the main research result:
A) during the time period from 2014 to 2019, the following dynamics of the cause of purulent-inflammatory ear diseases were identified. Thus, the share of purulent-inflammatory ear diseases caused by Pseudomonas aeruginosa increases from 12.24% to 33.89%. However, the proportion of diseases caused by Staphylococcus aureus decreases from 32.65% to 10.17%. The dynamics of diseases caused by saprophytic Staphylococcus varies slightly - from 18.37% to 18.64%. In purulent-inflammatory diseases of the upper respiratory tract, the following dynamics can be noted: Staphylococcus aureus retains the main position, but the percentage of morbidity caused by it decreases from 41.94% to 20.96%. Streptococcus viridans and Staphylococcus saprophyticus, which were on the 2nd and 3rd place by etiological moment in 2014 - 2015, are replaced in 2016 by Staphylococcus epidermidis (from 10.81% to 9.97%) and Klebsiella (from 9.80% to 10.99%), respectively. Their dynamics are relatively stable.
B) the Main mechanisms of antibiotic resistance (AB) are:
- Destruction of the AB molecule by the action of enzymes synthesized by bacteria. Beta-lactamases destroy the beta-lactam ring of AB to form an inactive compound.
- Modification of the AB molecule. Bacteria form enzymes (transferases) that change the structure of functional groups of some AB (as a result of acetylation, phosphorylation, and adenylation, aminoglycosides, macrolides, and lincosamils can be modified and lose their activity).
- Expression of complex bacterial mechanisms capable of removing AB from the cell (found in multidrug-resistant bacteria).
- Reduced AB penetration into the cell as a result of changes in Porin proteins in the bacterial Gr(-) cell system, which disrupts AB access to the target.
- Modification of the target structure for AB. Resistance to aminoglycosides, macrolides acting at the translation level, which can be triggered by mutations in bacterial ribosomes.
- Production of alternative targets by the bacterium that are resistant to the inhibitory effect of the antibiotic [3].
Limitations of the study: the resistance of the leading flora to antibiotics was evaluated on the basis of data provided by the microbiological laboratory of BUZ IN VOKB No. 1, therefore, only those drugs to which resistance was tested in a specific laboratory were included in the study.
CONCLUSION
Monitoring the dynamics of the microflora spectrum in inflammatory pathology of the upper respiratory tract and ear during bacteriological research allows you to correctly predict the percentage of diseases caused by certain bacteria, which is especially important for the diagnosis and treatment of this pathology. Assessment of antibiotic resistance of the microflora at the present stage will allow the otorhinolaryngologist to choose the most correct antibacterial drugs necessary for the speedy recovery of the patient, as well as to prevent the development of antibiotic resistance. The wrong choice of antibacterial drugs and their unjustified combination contributes to the development of antibiotic resistance [4].

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About the authors

Sofia A. Korchagina

Author for correspondence.
Email: sophia.korchagina@yandex.ru
ORCID iD: 0000-0002-9534-3166

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