Bacteriophage Therapy in Tonsillitis

Bacteriophage Therapy in Acute Tonsillitis

The patients received bacteriophage therapy with a liquid piobacteriophage complex (liquid pyobacteriophage complex - PCL). PСL was administered via nebulizer inhalation to irrigate the tonsil mucosa. A total of 5 ml of PCL was inhaled for 10 minutes every 5 days. The drug causes the lysis of certain bacteria, including staphylococcus, enterococcus, streptococcus, enteropathogenic E. coli, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae and Klebsiella oxytoca. The choice of this drug was based on bacteriological studies.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Tonsillitis
• Intervention / Treatment: Drug: Nebulizer inhalation irrigation of the mucous membranes of the tonsils with a bacteriophage.

Detailed Description

Comprehensive outpatient treatment was based on standard clinical guidelines, and symptomatic treatment was performed. On the first day of diagnosis, patients were prescribed complex antibacterial therapy on the basis of possible causative agents. Subsequently, antibiotic therapy was adjusted based on the results of the bacteriological examinations. A total of 67 patients received bacteriophage therapy using a liquid complex of pyobacteriophages (pyobacteriophage complex liquid - PСL). PСL was administered via nebulizer inhalation to irrigate the mucous membranes of the tonsils. In total, 5 ml of PCL was inhaled for up to 10 minutes once every 5 days.

The drug causes lysis of specific bacteria including Staphylococcus, Enterococcus, Streptococcus, enteropathogenic Escherichia coli, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Klebsiella oxytoca. The drug is recommended for use for diseases of the ear, throat, nose, respiratory tract and lungs; inflammation of the sinuses and middle ear; tonsillitis; pharyngitis; laryngitis; tracheitis; bronchitis; pneumonia, pleurisy; and other inflammatory diseases. The choice of this drug was based on bacteriological studies.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 3

Contacts and Locations

Study Locations

• Uzbekistan
  • Tashkent, Uzbekistan, 100140
    • Tashkent Pediatric Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• children from 3 to 14 years old.
• children with sore throat.
• children diagnosed with acute tonsillitis.
• children diagnosed with acute respiratory infection (rhinitis, sinusitis, nasopharyngitis).
• children with the opportunity to visit the outpatient clinic.
• children with the ability to receive inhalation therapy.
• children from parents (or guardians) who have given written permission to conduct clinical and laboratory research.

Exclusion Criteria:

• children under 3 years old and over 14 years old.
• children receiving hospital treatment.
• children with acute respiratory tract diseases (bronchitis, pneumonia, pleurisy).
• children with сhronic respiratory tract diseases (bronchitis, pneumonia).
• children who are allergic to antibiotics.
• children with cancer, immunological and hematological diseases.
• children with severe psychological illnesses (schizophrenia, mental retardation, etc.)
• children with cancer, immunological and hematological diseases.
• children with tuberculosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nebulizer inhalation bacteriophage therapy; To study the effects of bacteriophage therapy on acute tonsillitis in children and adolescents in an outpatient setting.

Drug: Nebulizer inhalation irrigation of the mucous membranes of the tonsils with a bacteriophage.; Bacteriophage therapy using a liquid complex of pyobacteriophages (pyobacteriophage complex liquid - PСL). PСL was administered via nebulizer inhalation to irrigate the mucous membranes of the tonsils. In total, 5 ml of PCL was inhaled for up to 10 minutes once every 5 days.; Other Names: Bacteriophage therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical observation of sick children.	Children with clinically diagnosed acute tonsillitis are examined. The clinical study will be carried out on an outpatient basis in cooperation with the clinic of the Tashkent Pediatric Medical Institute. Prior to the study, written permission will be obtained from the parents or guardians of the children to participate in the study. Investigated: anamnesis of the child, the course of the disease, complaints of parents about the child's condition, body temperature in dynamics, visually - the state of the nasopharynx, the manifestation of clinical symptoms (sore throat, headaches, difficulty swallowing food, aphonia, and other signs) in dynamics, the functional state of internal organs (percussion, palpation and auscultation).	study of one patient - 4 weeks
Laboratory research methods.	All examined children will undergo general clinical examination and pharyngoscopy. Additionally, all patients will have tonsil swabs for bacteriological examination (bacteriological culture, n x 10⁴/mL ) according to the standard technique. Also, swabs from the nasopharynx will be taken for viral lesions by the standard method - PCR (polymerase chain reaction). The research will be carried out in specialized laboratories.	study of one patient - 2 weeks
Experimental clinical stage. Bacteriophage therapy.	Comprehensive outpatient treatment will be based on standard clinical guidelines. Patients will be prescribed antibiotic therapy based on possible pathogens. Patients will receive bacteriophage therapy using a liquid pyobacteriophage complex (liquid pyobacteriophage complex - PCL), through nebulizer inhalation to irrigate the mucous membranes of the tonsils. Just 5 ml PCL for 10 minutes once every 5 days. Efficacy will be studied based on immunological studies.A study of cellular (class of T-lymphocytes, Inflammatory cytokines (e.g., IL-1,2,4,5,6,11,13 - U/ml) and TNF-α) and humoral ( IgA / IgM / IgG -IU/mL) immunity in children will be carried out, using (Enzyme Linked Immunosorbent Assay) ELISA which is an immunoassay, suited to the determination of antibodies in the field of infectious serology.	study of one patient - 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The second stage of the study (statistical).	The results will be analyzed using a statistical program based on Excel 2017 (Microsoft Office 2017). Clinical signs will be calculated as a percentage (%) incidence. We will calculate the chi-square (χ2) test or Fisher's exact test (for expected values <5) to assess if certain pairs of microbes are more common than expected by chance in bacteriological examination. In addition, we will use the Kruskal-Wallis test to compare the average delay between disease onset and sample collection between samples containing one or more organisms. When evaluating immunological analyzes, characterizing the statistical significance of differences, the Student's t-test will be used with the definition of the confidence interval. The X-square test will be used to assess the frequency of identifying qualitative features. In all analyzes, P ≤ 0.05 was considered significant.	4 weeks

Collaborators and Investigators

• Sponsor: Tashkent State Medical University (Tashkent Pediatric Medical Institute), Uzbekistan
• Investigators: Study Director: Shokhida T. Turdieva, MD, Tashkent State Medical University (Tashkent Pediatric Medical Institute), Uzbekistan

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2020
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 19, 2020
• First Posted (Actual): December 24, 2020

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 16, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: children; immunity; bacteriophage; acute tonsillitis; ambulatory treatment
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Suppuration; Pharyngeal Diseases; Pharyngitis; Abscess; Tonsillitis; Peritonsillar Abscess
• Other Study ID Numbers: TashkentPediatricMI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are planning to create a joint project to research the treatment of bacterial infection in children with respiratory diseases by COVED-19.
• IPD Sharing Time Frame: 2021-2024
• IPD Sharing Access Criteria: Children 0-17 years old, after being diagnosed with COVID-19, with a bacterial infection of the upper respiratory tract. We will work together with children's hospitals and research centers.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No