What are the common symptoms of MRSA nasal infections. How are MRSA nasal infections diagnosed and treated. What causes MRSA to colonize in the nasal passages. How can you prevent MRSA nasal infections.

Understanding MRSA and Its Prevalence in Nasal Passages

Methicillin-resistant Staphylococcus aureus (MRSA) is a type of staph bacteria that has developed resistance to many common antibiotics. While staph bacteria are often found harmlessly on the skin and in the nasal passages, MRSA can cause serious infections if it enters the body through breaks in the skin. The nasal cavity is a particularly common site for MRSA colonization and infection.

MRSA infections in the nose can manifest in several ways:

• Nasal vestibulitis: An infection of the front area of the nasal cavity
• Folliculitis: An infection of one or more hair follicles in the nose
• Boils or furuncles: Deep infections around hair follicles or oil glands that may drain pus

Understanding the prevalence and risks associated with MRSA nasal infections is crucial for effective prevention and treatment.

Recognizing the Symptoms of MRSA Nasal Infections

Identifying the symptoms of MRSA nasal infections early can lead to prompt treatment and prevent complications. Common symptoms include:

• Swelling and redness in and around the nose
• Crusting inside the nasal passages
• Light bleeding from the nose
• Lesions that ooze pus or fluid
• Pain or soreness in the nasal area
• Fever (in more severe cases)

Can MRSA nasal infections be mistaken for other conditions? Yes, MRSA nasal infections can sometimes be confused with other nasal conditions such as allergies or the common cold. However, the presence of pus-filled lesions and persistent symptoms are key indicators that warrant medical attention.

Factors Contributing to MRSA Nasal Colonization

MRSA can colonize the nasal passages due to various factors. Understanding these can help in prevention efforts:

• Frequent exposure to healthcare settings
• Weakened immune system
• Previous antibiotic use
• Close contact with MRSA carriers
• Poor hygiene practices

How does MRSA enter the nasal passages? MRSA typically enters the nose through direct contact with contaminated surfaces or individuals. The bacteria can then colonize the warm, moist environment of the nasal cavity, potentially leading to infection if the skin barrier is compromised.

Diagnostic Approaches for MRSA Nasal Infections

Accurate diagnosis of MRSA nasal infections is crucial for appropriate treatment. Healthcare providers typically employ the following diagnostic methods:

1. Physical examination of the nasal area
2. Review of patient symptoms and medical history
3. Collection of nasal swabs or tissue samples for laboratory testing
4. Culture and sensitivity tests to identify the specific strain of bacteria and its antibiotic resistance profile

Why is laboratory testing important for MRSA diagnosis? Laboratory testing is essential because it not only confirms the presence of MRSA but also determines which antibiotics will be effective against the specific strain, guiding treatment decisions.

Treatment Strategies for MRSA Nasal Infections

Treating MRSA nasal infections requires a targeted approach due to the bacteria’s antibiotic resistance. Common treatment strategies include:

• Topical antibiotics specifically effective against MRSA
• Oral antibiotics for more severe or widespread infections
• Nasal decolonization protocols using antiseptic solutions
• Drainage of abscesses or boils if present
• Pain management and supportive care

Are all MRSA nasal infections treated the same way? No, treatment varies depending on the severity of the infection, the specific strain of MRSA, and the patient’s overall health. Mild cases may be treated with topical antibiotics, while more severe infections might require oral or intravenous antibiotics.

Preventing MRSA Nasal Colonization and Infection

Prevention is key in managing the spread of MRSA. Effective preventive measures include:

• Practicing good hand hygiene, especially in healthcare settings
• Avoiding touching or picking the nose
• Using separate personal items like towels and razors
• Keeping wounds clean and covered
• Following proper hygiene protocols during nose piercings or other nasal procedures

Can nasal decolonization prevent MRSA infections? Yes, nasal decolonization using antiseptic solutions or antibiotic ointments can reduce the risk of MRSA infections, especially in high-risk individuals or before certain medical procedures.

Complications and Long-term Management of MRSA Nasal Infections

While many MRSA nasal infections can be effectively treated, some may lead to complications or require long-term management:

• Recurrent infections
• Spread of infection to surrounding tissues
• Development of antibiotic resistance
• Chronic nasal colonization

How are recurrent MRSA nasal infections managed? Management of recurrent infections may involve extended decolonization protocols, identification and treatment of household carriers, and sometimes long-term suppressive antibiotic therapy under close medical supervision.

The Impact of MRSA Nasal Infections on Public Health

MRSA nasal infections pose significant challenges to public health due to their potential for spread and antibiotic resistance. Healthcare facilities have implemented strict infection control measures to prevent the transmission of MRSA, including:

• Screening high-risk patients for MRSA colonization
• Isolating MRSA-positive patients
• Implementing rigorous hand hygiene protocols
• Educating healthcare workers and the public about MRSA prevention

These efforts have helped reduce the incidence of healthcare-associated MRSA infections, but community-acquired MRSA remains a concern.

Emerging Research and Future Directions in MRSA Management

Ongoing research into MRSA is focusing on several promising areas:

1. Development of new antibiotics effective against resistant strains
2. Exploration of alternative therapies, such as bacteriophages
3. Investigation of nasal microbiome manipulation to prevent MRSA colonization
4. Improvement of rapid diagnostic techniques for faster identification of MRSA

These research directions hold potential for improving the prevention, diagnosis, and treatment of MRSA nasal infections in the future.

The Role of Patient Education in MRSA Prevention

Educating patients about MRSA is crucial for prevention and early detection. Key points to emphasize include:

• Recognizing the signs and symptoms of MRSA infections
• Understanding the importance of completing prescribed antibiotic courses
• Implementing proper hygiene practices at home
• Knowing when to seek medical attention for potential infections

Patient education empowers individuals to take an active role in preventing the spread of MRSA and managing their own health effectively.

MRSA in Special Populations: Considerations and Challenges

Certain populations are at higher risk for MRSA nasal infections and may require special considerations:

• Healthcare workers
• Athletes in contact sports
• Individuals in correctional facilities
• Military personnel
• Patients with chronic medical conditions

These groups may benefit from targeted screening, education, and prevention strategies to reduce their risk of MRSA colonization and infection.

The Economic Burden of MRSA Nasal Infections

MRSA infections, including those in the nasal passages, contribute significantly to healthcare costs. Factors contributing to this economic burden include:

• Extended hospital stays
• Specialized antibiotic treatments
• Infection control measures
• Lost productivity due to illness

Addressing MRSA effectively not only improves patient outcomes but also has the potential to reduce healthcare expenditures associated with these infections.

Global Perspectives on MRSA Nasal Infections

The prevalence and management of MRSA nasal infections vary globally. Factors influencing these differences include:

• Antibiotic use policies
• Healthcare system structures
• Population density and living conditions
• Climate and environmental factors

Understanding these global variations is crucial for developing effective international strategies to combat MRSA.

The Psychological Impact of MRSA Nasal Infections

Living with MRSA colonization or recurrent infections can have psychological effects on patients, including:

• Anxiety about potential spread to family members
• Social stigma associated with MRSA
• Stress related to ongoing medical treatments
• Concerns about future health implications

Addressing these psychological aspects is an important part of comprehensive care for individuals affected by MRSA nasal infections.

Integrating MRSA Management into Primary Care

Primary care providers play a crucial role in managing MRSA nasal infections. Key aspects of this integration include:

• Educating patients about MRSA prevention
• Conducting risk assessments for MRSA colonization
• Providing appropriate screening and treatment
• Coordinating care with specialists when necessary

Effective management of MRSA at the primary care level can significantly impact overall infection rates and patient outcomes.

The Role of Environmental Factors in MRSA Transmission

Understanding the environmental factors that contribute to MRSA transmission is crucial for effective prevention. Key considerations include:

• Survival of MRSA on various surfaces
• Impact of humidity and temperature on bacterial growth
• Effectiveness of different cleaning and disinfection methods
• Role of air quality in MRSA spread

Implementing evidence-based environmental control measures can significantly reduce the risk of MRSA transmission in both healthcare and community settings.

Ethical Considerations in MRSA Management

Managing MRSA infections raises several ethical considerations, including:

• Balancing individual privacy with public health needs in MRSA reporting
• Addressing potential discrimination against MRSA carriers
• Ensuring equitable access to MRSA screening and treatment
• Managing antibiotic stewardship in the face of resistant infections

Navigating these ethical issues is essential for developing fair and effective MRSA management policies.

The Future of MRSA Prevention and Treatment

Looking ahead, several promising developments may shape the future of MRSA prevention and treatment:

• Development of MRSA vaccines
• Advancements in rapid, point-of-care diagnostic tools
• Novel antimicrobial agents targeting resistant strains
• Innovative approaches to modulating the nasal microbiome

These advancements hold the potential to revolutionize our approach to managing MRSA nasal infections and reduce their impact on public health.

Symptoms, Causes, Diagnosis, and Treatment

A staph infection is a bacterial infection that’s caused by Staphylococcus bacteria, which are fairly common in the environment.

An infection with staph bacteria can cause a variety of skin conditions, including:

• cellulitis
• boils
• impetigo
• folliculitis
• scalded skin syndrome

These skin conditions aren’t contagious, but the bacteria that cause them are. The bacteria spreads through either person-to-person contact or touching a contaminated object, such as a doorknob.

Staph bacteria tend to hang out in your nasal passages, so your nose is a common site for a staph infection.

Common types of nasal staph infections include:

• Nasal vestibulitis. This is an infection of the front area of your nasal cavity. It may cause crusts and bleeding.
• Folliculitis. This is an infection of one or more hair follicles.
• Boils. Also called furuncles, a boil is a deeper infection around a hair follicle or oil gland that can drain pus if it breaks open.

Read on to learn more about staph infections in your nose, including common symptoms and how to treat them.

Potential symptoms of a staph infection in your nose include:

• swelling
• redness
• crusting
• light bleeding
• lesions that ooze pus or fluid
• pain or soreness
• fever

You probably come into contact with staph bacteria on a daily basis, but it doesn’t always cause an infection. If you have a break in your skin, though, such as a cut, scrape, or burn, the bacteria can enter your body and cause an infection.

There are several things that can cause a a break in the delicate skin inside your nose, including:

• excessive nose blowing
• picking your nose
• plucking or tweezing your nose hairs
• having a nose piercing

To confirm you have a nasal staph infection, it’s best to see your primary care provider. They’ll examine your nose and ask about your symptoms. They may collect a sample of tissue or nasal secretions to test in a laboratory to check for bacteria.

Testing can help check if the infection is caused by methicillin-resistant Staphylococcus aureus (MRSA). MRSA is a type of staph bacteria that’s resistant to many types of antibiotics, so it requires careful treatment.

Mild staph infections often heal on their own without any treatment.

However, some staph infections can quickly become serious and cause certain complications, such as:

• Cellulitis. An infection occurs in the deeper layers of your skin.
• Cavernous sinus thrombosis. This rare but serious complication of nasal or facial infections involves the formation of a blood clot at the base of your brain.
• Sepsis. Potentially life-threatening, this condition is your body’s extreme response to an infection.

Staph bacteria are commonly present in our nasal cavity and on our skin. Usually, these bacteria are harmless. But they can cause an infection if they enter your body through a break in your skin.

If you notice an area in your nose that’s red or irritated, keep an eye on it. If it becomes painful or forms a pus- or fluid-filled bump or lesion, seek medical treatment to avoid a more serious infection.

Symptoms, Causes, Diagnosis, and Treatment

A staph infection is a bacterial infection that’s caused by Staphylococcus bacteria, which are fairly common in the environment.

An infection with staph bacteria can cause a variety of skin conditions, including:

• cellulitis
• boils
• impetigo
• folliculitis
• scalded skin syndrome

These skin conditions aren’t contagious, but the bacteria that cause them are. The bacteria spreads through either person-to-person contact or touching a contaminated object, such as a doorknob.

Staph bacteria tend to hang out in your nasal passages, so your nose is a common site for a staph infection.

Common types of nasal staph infections include:

• Nasal vestibulitis. This is an infection of the front area of your nasal cavity. It may cause crusts and bleeding.
• Folliculitis. This is an infection of one or more hair follicles.
• Boils. Also called furuncles, a boil is a deeper infection around a hair follicle or oil gland that can drain pus if it breaks open.

Read on to learn more about staph infections in your nose, including common symptoms and how to treat them.

Potential symptoms of a staph infection in your nose include:

• swelling
• redness
• crusting
• light bleeding
• lesions that ooze pus or fluid
• pain or soreness
• fever

You probably come into contact with staph bacteria on a daily basis, but it doesn’t always cause an infection. If you have a break in your skin, though, such as a cut, scrape, or burn, the bacteria can enter your body and cause an infection.

There are several things that can cause a a break in the delicate skin inside your nose, including:

• excessive nose blowing
• picking your nose
• plucking or tweezing your nose hairs
• having a nose piercing

To confirm you have a nasal staph infection, it’s best to see your primary care provider. They’ll examine your nose and ask about your symptoms. They may collect a sample of tissue or nasal secretions to test in a laboratory to check for bacteria.

Testing can help check if the infection is caused by methicillin-resistant Staphylococcus aureus (MRSA). MRSA is a type of staph bacteria that’s resistant to many types of antibiotics, so it requires careful treatment.

Mild staph infections often heal on their own without any treatment.

However, some staph infections can quickly become serious and cause certain complications, such as:

• Cellulitis. An infection occurs in the deeper layers of your skin.
• Cavernous sinus thrombosis. This rare but serious complication of nasal or facial infections involves the formation of a blood clot at the base of your brain.
• Sepsis. Potentially life-threatening, this condition is your body’s extreme response to an infection.

Staph bacteria are commonly present in our nasal cavity and on our skin. Usually, these bacteria are harmless. But they can cause an infection if they enter your body through a break in your skin.

If you notice an area in your nose that’s red or irritated, keep an eye on it. If it becomes painful or forms a pus- or fluid-filled bump or lesion, seek medical treatment to avoid a more serious infection.

Sore throat. Crossroads of problems and search for solutions | Radtsig E.Yu., Gurov A.V.

Introduction

Sore throat, which develops as a result of infectious inflammation of the upper respiratory tract, is one of the most common reasons for patients of all ages to seek outpatient care, including otorhinolaryngological, therapeutic, pediatric services, as well as family doctors and general practitioners. Most often, this symptom occurs in acute respiratory infections (ARVI, acute respiratory infections, nasopharyngitis, laryngopharyngitis), as well as against the background of an isolated lesion of the pharynx (pharyngitis, tonsillitis, tonsillopharyngitis) [1–3].

The relevance of the problem of treating conditions accompanied by sore throat, in addition to the significant prevalence of the diseases themselves, is determined by a number of aspects (see figure). So, despite the peculiarities of the etiology, which will be briefly discussed below, sore throat for many decades has been one of the most common reasons for prescribing systemic antibacterial drugs as basic therapy [4-6]. In turn, the high frequency of use of systemic antibacterial drugs for the treatment of sore throat largely contributes to the further growth of antibiotic resistance [6, 7]. Finally, in recent years, considerable attention has been paid to the effect of antibiotic therapy on the qualitative and quantitative composition of the microbiota [8].

Etiology of infectious diseases accompanied by sore throat

Among the etiological factors of infectious diseases accompanied by sore throat, regardless of the age of patients, respiratory viruses dominate (adenovirus, Epstein-Barr virus, influenza B and parainfluenza viruses, respiratory syncytial virus, rhinovirus, bocavirus, metapneumovirus). In children younger than 3 years, the frequency of inflammatory diseases of the pharynx of viral etiology can reach 80–90%, but as they grow older, the proportion of the “bacterial” genesis of this disease increases (24% at preschool age versus 52% at senior school age) [7, 9, 10]. According to the results of studies conducted during the COVID-19 pandemic, the SARS-CoV-2 virus (delta and omicron strains) can also cause sore throat against a mild infection [11].

Despite the fact that, according to the literature, among bacterial pathogens (especially in children from 3 years old and adolescents up to 15 years old), Streptococcus pyogenes (group A β-hemolytic streptococcus (GABHS)) plays the leading role in frequency and clinical significance [2, 7, 9], there are works in which researchers demonstrate the lesser significance of this pathogen in the genesis of acute tonsillopharyngitis in pediatric patients [10, 12].

According to the results of studies aimed at identifying the etiological significance of other pathogens, the possible etiological role of hemolytic streptococci of groups C and G, Fusobacterium necrophorum, Arcanobacterium haemolyticum, Mycoplasma pneumoniae, Chlamydophila pneumoniae is discussed [9, 13, 14].

Modern approaches to the diagnosis and treatment of diseases accompanied by sore throat

In accordance with modern domestic and international clinical guidelines, GABHS infections require treatment with systemic antibacterial drugs in order to prevent the development of metatonsillar and systemic complications. Currently, the “gold standard” for confirming the streptococcal etiology of the disease are rapid tests based on the detection of antigens or DNA of the pathogen, although the use of clinical scales (Centor score, McIsaac score, FeverPain) is also allowed. It should be emphasized that rapid tests are not recommended in age categories for which GABHS etiology is not predominant (children under 3 years old, patients over 50 years old). In children over 3–5 years of age and adolescents in doubtful cases (with discrepancy between the results of express diagnostics and clinical scales), as well as in risk groups for the development of complications, it is recommended to conduct a classical bacteriological method of research [7, 9, 15].

Given the continued high sensitivity of GABHS to β-lactam antibiotics, penicillins are the first-line therapy (preferably amoxicillin). In cases of allergy to penicillin preparations, cephalosporins are prescribed, and in case of intolerance to the entire β-lactam group, macrolides are prescribed. However, it should be taken into account that over the past decade there has been a significant increase in GABHS resistance to drugs of this group, as well as to lincosamides. In all other cases, the vast majority of clinical guidelines recommend only symptomatic therapy aimed at relieving pain and other associated complaints [2, 7, 9, 15]. The use of topical drugs with anti-inflammatory properties, as well as anesthetics and antiseptics is discussed [16, 17].

Among the reasons for refusing to use systemic antibiotics, there are risks of resistance formation, the development of systemic adverse events and a negative impact on the microbiota of the macroorganism. To reduce the use of systemic antibacterial drugs, strict adherence to clinical guidelines (careful, consistent clinical and laboratory diagnostics) is recommended – the so-called “smart” choice of therapy, the tactic of delayed prescribing of drugs. In addition, a number of reviews note that even untreated cases of GABHS pharyngitis are prone to self-healing, and given the low incidence of delayed complications, the possibility of not using systemic antibacterial drugs in immunocompetent patients is discussed [15].

Despite extensive efforts, including the development of clinical guidelines, various educational projects, and monitoring of prescriptions, the medical community is experiencing significant difficulties in implementing strategies to reduce the frequency of use of systemic antimicrobials among practitioners in various countries, including countries in Europe and America with highly developed health systems. [2, 4, 6, 18].

According to the results of studies, infectious and inflammatory diseases accompanied by sore throat significantly reduce the quality of life of patients. Most of those who seek medical help associate more severe pain precisely with the developed infection, which largely determines the choice of a doctor in favor of etiotropic therapy [19].].

A more thorough study of the etiological profile with simultaneous detection of viral and bacterial pathogens often reveals viral-bacterial associations [3, 10, 11, 20]. However, the authors failed to find publications of the results of studies in which, along with the identification of viral and / or bacterial pathogens, a comprehensive study of their etiological significance would be simultaneously carried out using classical serological methods. At the same time, in clinical practice, when discussing etiotropic therapy, the classical thesis is not taken into account: viruses open the gates of the inflammation focus for the expansion of bacteria, as well as the fact that in reality both viral and bacterial pathogens are simultaneously present on the oropharyngeal mucosa. It is in relation to the pathogenesis of acute pharyngitis/tonsillopharyngitis that it is logical to assume a gradual, not immediately indicated by clinical markers, the transition of the predominant etiological role from viruses to bacteria, which may be reflected by research data that simultaneously reveal viral and bacterial presence [10, 20, 21].

Finally, the authors draw attention to the combination of two important trends. On the one hand, the desire to get away from the widespread use of broad-spectrum systemic antibacterial drugs in order to reduce the pressure on microorganisms in general and, first of all, reduce the aggressive impact on regional biotopes and the patient’s microbiome. It should be noted that even in countries with the highest level of health care, the use of narrowly targeted antibiotics will require a significant set of diagnostic measures in a mode approaching real time, which is currently a difficult strategy [8]. The second important trend is the active use of drugs that have the ability to overcome the main mechanisms of formation of microbial resistance, which can also reduce the threat of the spread of antibiotic resistance [22].

Without going into a detailed description of the mechanisms of realization of bacterial resistance to the action of antimicrobial agents, we note that two fundamentally important directions can be distinguished at the basis of their development: mutations in their own genome and the acquisition of resistance genes through horizontal transfer, including through plasmids. Two other important aspects of the resistance of microorganisms to the action of antimicrobials are the reduction of their metabolic activity, in particular the transition to the state of persisters, and the formation of biofilms. Assessing the prospects for overcoming resistance and tolerance, it should be recognized that from an evolutionary point of view, the creation of drugs that act on the infectious agent in the complete absence of the risk of resistance formation is extremely unlikely. A more realistic approach is the development of drugs that act simultaneously on several targets in a bacterial cell [23].

These drugs include antimicrobial peptides, in particular, the most thoroughly studied and long-term use of antimicrobial polypeptides (AMPs) of microbial origin [24]. The topical use of AMPs, due to direct entry into the inflammation site in an adequate and safe concentration, makes it possible, to a greater extent than the systemic administration of antibacterial drugs, to achieve rapid and complete eradication of the pathogen, relief of inflammation and pain. Unlike classical antibacterial drugs, AMPs act simultaneously on several targets, the main of which is the cytoplasmic membrane of a bacterial cell. The death of microorganisms (achieving a rapid bactericidal effect) occurs in a very short time, which leads to a significantly lower risk of developing pathogen resistance.

In focus — AMP

Gramicidin C

Given the above, AMPs of microbial origin have recently been considered as promising means of treating infectious diseases in conditions of a high risk of developing antibiotic resistance to systemic drugs [25]. Thus, the US Food and Drug Administration (FDA) included substances from the gramicidin group in the list approved for use against infections caused by gram-positive and gram-negative bacteria [24].

In contrast to the linear gramicidins discovered by Rene Dubos as part of antimicrobial polypeptides (tyrothricin) produced by the bacterium Aneurinibacillus migulanus (formerly Bacillus brevis) in 1939 [26], the cyclic decapeptide gramicidin C (Soviet gramicidin, GS) was isolated by G. F. Gause and M.G. Brazhnikova and described in the 40s of the XX century. [27].

The HS molecule is a rigid ring, has amphiphilic properties due to the presence of positively charged (cationic) and hydrophobic parts. Among other amino acids, the composition of the GS molecule synthesized by the nonribosomal route includes L-ornithine, which is extremely rare in the composition of natural proteins and peptides. The high stability of the molecule, combined with the presence of a non-canonical amino acid in the composition, allows GS to retain its bactericidal effect in a wide pH range and avoid proteolytic degradation by common proteases of microorganisms [28].

Due to its properties, GS is characterized by a pronounced multipurpose bactericidal action against a wide range of gram-positive and gram-negative bacteria and some yeast fungi. GS is active against both planktonic forms of microorganisms, including persister cells, and against biofilms [28–30]. According to studies conducted as part of the search for promising drugs against SARS-CoV-2, the ability of GS to significantly reduce the viral load in Vero cells infected with SARS-CoV-2 was revealed at an effective concentration of 1.57 μg/ml, while maintaining maximum efficiency up to 24 h. In addition, proteomic analysis showed that in infected cells against the background of the use of GS, the regulation and synthesis of proteins associated with virus reproduction in cells in vitro were disturbed [31].

The main way to implement the bactericidal action of GS is to disrupt the structure and function of the lipid bilayer of the plasma membrane of bacteria, up to the formation of significant defects in high concentrations. Due to the low molecular weight and structural features of the molecule, GS, unlike other antimicrobial peptides, has a higher permeability and quickly enters the cells of gram-positive and gram-negative microorganisms. In addition, GS disrupts the processes of cellular respiration and cell division of a wide range of pathogenic bacteria [28, 32, 33].

Additionally, it was shown that (p)ppGpp molecules (stress signaling molecules that initiate and regulate the formation of biofilms, the transition of cells to a persistent state, and a number of other adaptive reactions) can be one of the key targets of GS. This activity obviously underlies the ability of GS to effectively inhibit the bacterial stress response and prevent the formation of biofilms, as well as cause the killing of persister cells [28].

According to the mechanism of action in a number of aspects – the effect on the biosynthesis and integrity of the cell membrane, changes in the membrane potential, delocalization of the MinD-GFP protein, activation of rapid potassium loss, induction of membrane stress marker proteins LiaH and TrmB – GS is similar to nisin (bacteriocin produced by streptococci group N, such as Lactobacillus lactis), as well as with a number of bacteriocins I and II of the normobiota of the oral cavity, in particular, with class 1B cyclic bacteriocin produced by Lactobacillus acidophilus [34, 35]. Due to such functional similarity, GS can positively interact not only with the normal microflora of the oropharynx, but also with factors of local nonspecific protection [36].

Extremely high proteolytic stability, as well as multiple mechanisms of bactericidal action, including pronounced membranotropy, may cause the practical absence of cases of detection of acquired resistance to GS in microorganisms in clinical practice up to the present time [24, 28, 37].

Obtained under in vitro conditions during a targeted experiment using artificial induction, laboratory strains of Staphylococcus aureus 209P with reduced sensitivity to GS remained sensitive to other antibacterial drugs, but had a 30% lower respiratory activity and viability [38]. In contrast to GS, other antimicrobial peptides used in OTC sore throat preparations (linear gramicidin A, bacitracin, and tyrothricin) have been shown in resistance experiments to show a persistent increase in the minimum inhibitory concentration after cessation of the peptides ( IPC) against a number of microorganisms. Simultaneously with the emergence of resistance to these peptides, bacteria developed acquired cross-resistance to classical antimicrobials (ciprofloxacin, fusidic acid, gentamicin, cefpodoxime, amoxicillin/clavulanic acid, and cefotaxime) [39], which raises the question of revising the prospects of these peptides in topical etiotropic therapy.

According to data published over the past 40 years, high bactericidal activity of GS against gram-negative bacteria, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, etc., has been shown, with MICs in the range of 4–64 µg/ml. GS is more active against gram-positive pathogens. For example, MICs for Staphylococcus aureus, including methicillin-resistant strains (MRSA), starting at 1981 g is stable at a level not exceeding 8 µg/ml [40–42]. According to S. Derbal et al. [43], GS at a concentration of <10 μg/ml inhibits the growth of streptococci (GABSA strain 5448 and a number of other streptococci).

In a study conducted with the participation of one of the authors in October-December 2021, the MIC of HS against Staphylococcus aureus did not exceed 8 μg / ml, including in clinical isolates characterized by multiple resistance to several groups of classical antimicrobials for systemic action (groups β-lactams, macrolides, respiratory fluoroquinolones, tetracyclines, aminoglycosides, etc. ), which once again allows us to conclude that this pathogen does not have resistance to HS [44]. The level of MIC HC in relation to all test pathogens did not exceed the concentration contained in drugs widely used in clinical practice (Grammidin 9 line0066 ® (URL: https://grls.rosminzdrav.ru/grls.aspx?s=%D0%B3%D1%80%D0%B0%D0%BC%D0%BC%D0%B8%D0%B4 %D0%B8%D0%BD&m=tn)…. MIC of HS against Streptococcus pneumoniae, including strain resistant to oxacillin and erythromycin, did not exceed 16 μg/ml.

The study showed that the difference between the MIC and the minimum bactericidal concentration (MBC, the concentration that causes the complete death of bacterial cells) of GS in relation to the studied clinical isolates of pathogens did not exceed 8 times, which also reflects the high potential of bactericidal action.

Additionally, an experiment was carried out with the aim of modeling the course effect of GS, close to the use of a substance in the composition of drugs in clinical practice (7-day use in a single dose of 1600-3200 mcg 3-4 times a day according to the instructions for medical use of the Grammidin ^{line of drugs ®} ). In this experiment, we studied the effect of GS on test pathogens in suppressive and sub-inhibitory concentrations (concentrations less than the MIC reflect the real concentrations created during clinical use in the oral cavity, and are also used in experiments on the targeted formation of resistance of microorganisms to antimicrobial agents in laboratory conditions) on dense and liquid media. The results of the experiment showed that with repeated daily exposure of the GS to the studied microorganisms, the characteristics of the antimicrobial activity of the GS (MIC and MBC) did not increase throughout the experiment (7 passages in solid and liquid media). Thus, the results of the study demonstrated the high bactericidal activity of GS against the leading pathogens of respiratory infections, and during the repeated exposure of GS to pathogens, including those with resistance to widely used systemic antibiotics and antimicrobials, no signs of resistance formation were revealed [44].

As mentioned above, in cases where there are no indications for systemic administration of antimicrobials, local therapy is widely used in clinical practice, which is reflected in current clinical guidelines [9]. The purpose of prescribing local drugs is to suppress the activity of infectious agents, quickly achieve anti-inflammatory and analgesic effects, as well as prevent secondary infection of the damaged pharyngeal mucosa with a favorable safety profile of the drug [9]. At the same time, the clinical guidelines note the presence of undesirable effects and the risk of developing allergic reactions inherent in some of these drugs, for example, those containing chlorhexidine and iodine compounds [9]. In addition, not all local antimicrobial and antiseptic agents understand the degree and nature of their effect on the normal microbiota, which is an important aspect at the present time [9].

Taking into account all the aspects discussed above (the breadth of the spectrum of action, the severity of the therapeutic effect of antimicrobial drugs, overcoming the risks of developing antibiotic resistance, as well as the impact on local protective factors, including the normal microbiota of the oropharynx), the greatest efficiency in the use of topical drugs can be achieved due to the combined effect of several synergistically active components [45]. So, in addition to the topical use of antimicrobial peptides, topical use of drugs with antiseptic properties can be considered promising, which will provide a more stable effect on a wide range of pathogens [9].

Cetylpyridinium chloride

Antiseptics approved for topical use in children and adults include cetylpyridinium chloride (CPC), a quaternary ammonium compound that has been widely known since 1946 [46]. In vitro and in vivo studies have demonstrated the safety and efficacy of CPC in the oral cavity and pharynx [35, 47]. The mechanism of action of CPC is based on the disintegration of lipid membranes of gram-positive and gram-negative pathogenic and opportunistic oral bacteria, such as Staphylococcus aureus, including MRSA, Streptococcus sanguinis, Pseudomonas aeruginosa, as well as fungi Candida albicans and Aspergillus niger. In addition, CPC prevents the formation of biofilms of pathogenic microbiota in the oral cavity and pharynx and is highly active against multimicrobial biofilms [48]. Laboratory studies of the effect of antiseptics on the microbiota showed that CPC had the most gentle effect on indigenous microorganisms (representatives of the normal microbiota) [49]. Clinical study by Prof. J.R. Radford et al. [50] demonstrated the absence of disturbances in the normobiota of the oral cavity when using a 0.05% solution of CPC 2 times a day for 6 weeks. in healthy volunteers. In addition, according to studies published over the past 10 years, CPC exhibits antiviral activity against respiratory viruses (influenza A and B viruses, parainfluenza, respiratory syncytial virus, coronaviruses SARS-COV-2, MERS-CoV, MHV-A59 and HCoV-NL63) [47, 51, 52].

The combination of gramicidin C and CPC is widely used in clinical practice in two dosage forms for the topical treatment of sore throat (the Grammidin® product line). The efficacy and safety of drugs in the form of a spray has been confirmed in adults and children over the age of 3 years [35, 53] and in the form of lozenges in children aged 4 years and older [54, 55].

It is known that viruses that have a tropism for the epithelium of the mucous membrane of the nasopharynx and oropharynx, as well as bacterial pathogens and viral-bacterial associations in the process of developing infectious inflammation lead to pronounced changes in the normobiota – one of the most important physiological barriers and links of nonspecific resistance of the human body in the upper sections. respiratory and digestive tracts [56].

Returning to one of the very important aspects touched upon in the article, it should be noted that the composition and functional activity of the normal microbiota play a key role in the functioning of the local resistance system. Violation of the colonization resistance of the mucous membrane of the respiratory tract as a result of exposure to viral and bacterial pathogens of respiratory infections leads to an easier development of these infections, a pronounced long-term and recurrent nature of their course [57]. In this regard, when choosing drugs for topical etiotropic therapy of infectious and inflammatory diseases of the upper respiratory tract, it is advisable to use the biocenosis-preserving therapy scenario [58, 59].

Conclusion

The problem of adequate treatment of acute infectious and inflammatory diseases of the upper respiratory tract, accompanied by sore throat, remains relevant, despite numerous studies, available authoritative clinical guidelines and algorithms for diagnosis and therapy.

The relevance of this topic is determined not only by the high prevalence of this group of diseases among the population of almost all ages – the most important aspects are the choice of a therapeutic strategy taking into account the needs of patients, as well as the consequences of antimicrobial therapy in the form of an increase in antibiotic resistance and a decrease in colonization resistance of the mucous membrane with the development of dysbiotic changes.

Currently, on the one hand, there is an unreasonably widespread use of systemic antibacterial drugs by practitioners with the above consequences, on the other hand, there are distant prospects for the introduction of systemic narrowly targeted antimicrobial agents and the formation of an essentially new paradigm of antimicrobial therapy in general. At the same time, at the present time, there is a very real possibility of solving existing problems – the use of topical combined preparations, the components of which have a synergistic etiotropic effect and at the same time significantly reduce the risk of developing resistance of microorganisms while sparingly affecting the functioning of the normal microbiota of the oropharynx, which is a key link in the system. resistance of the human body.

Credits:

Radtsig Elena Yurievna — Doctor of Medical Sciences, Professor, Professor of the Department of Otorhinolaryngology, Faculty of Pediatrics, Russian National Research Medical University. N.I. Pirogov of the Ministry of Health of Russia; 117997, Russia, Moscow, st. Ostrovityanova, d. 1; ORCID iD 0000-0003-4613-922X.

Gurov Alexander Vladimirovich — Doctor of Medical Sciences, Professor of the Department of Otorhinolaryngology of the Faculty of Medicine, Professor of the Department of Microbiology and Virology of the Russian National Research Medical University. N.I. Pirogov of the Ministry of Health of Russia; 117997, Russia, Moscow, st. Ostrovityanova, d. 1; Senior Researcher, Department of Epidemiology, Clinical Research and Scientific Forecasting, GBUZ NIKIO named after A.I. L.I. Sverzhevsky DZM; 117152, Russia, Moscow, Zagorodnoye sh., 18a, building 2; ORCID iD 0000-0001-9811-8397.

Contact information: Radtsig Elena Yurievna, e-mail: [email protected].

Transparency of financial activities: none of the authors has a financial interest in the presented materials or methods.

Conflict of interest: A.V. Gurov announced that he had received a grant to conduct an independent expert analysis of the results of a preclinical study of the antimicrobial activity of gramicidin C in relation to the leading pathogens of respiratory infections, which, by order of JSC Valenta Pharm, as part of the current plan of scientific work of the company, was carried out by an independent research organization JSC NPO Dom Pharmacy”.

The article was received on 07/09/2022.

Received after peer review on 08/02/2022.

Accepted for publication on August 25, 2022.

About the authors:

Elena Yu. Radtsig-Dr. Sc. (Med.), Professor, Professor of the Department of Otorhinolaryngology, Pirogov Russian National Research Medical University; 1, Ostrovityanov str., Moscow, 117437, Russian Federation; ORCID iD 0000-0003-4613-922X.

Alexander V. Gurov Sc. (Med.), Professor of the Department of Otorhinolaryngology, Professor of the Department of Microbiology and Virology, Pirogov Russian National Research Medical University; 1, Ostrovityanov str., Moscow, 117437, Russian Federation; senior researcher of the Division of Epidemiology, Clinical Trials and Prognostic Research, L.I. Sverzhevskiy Research Clinical Institute of Otorhinolaryngology; 18A Build. 2, Zagorodnoe road, Moscow, 117152, Russian Federation; ORCID ID 0000-0001-9811-8397.

Contact information: Elena Yu. Radtsig, e-mail: [email protected].

Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.

Conflict of interests: A.V. Gurov informed that he has received a grant for performing an independent panel review of the results of the pre-clinical study of Gramycidin S antimicrobial activity against the most prevalent pathogens causing respiratory infections. The study was conducted upon request of AO Valenta Pharm within the implementation of the current plan of the company’s research activities by an independent research organization AO NPO “Home of Pharmacy”.

Received 07/09/2022.

Revised 08/02/2022.

Accepted 08/25/2022.

Review of abstracts on the topic “Pneumonia”, published in the proceedings of the XXIV Congress of the Russian Respiratory Society and the XXIV Congress of the European Respiratory Society | Shaimuratov

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