COMPARATIVE ANALYSIS OF THE EFFECTIVENESS OF «BACTERIOPHAGE SALMONELLA POLYVALENT» - “MEDIPHAG” AND CIPROFLOXACIN IN CLINICAL TRIALS

ABSTRACT

In this study, the «Bacteriophage salmonella polyvalent» - “MediPhag” produced by “ASIA IMMUNOPREPARAT” LLC was studied by comparing the results of the use of the drug in liquid and capsule form and the antibiotic ciprofloxacin in the treatment of acute intestinal inflammation in clinical trials.

АННОТАЦИЯ

В данном исследовании был изучен производства “ASIA IMMUNOPREPARAT” ООО «Bacteriophage salmonella polyvalent» - “MediPhag”  путем сравнения результатов применения препарата в жидкой и капсульной форме и антибиотика ципрофлоксацина при лечении острого воспаления кишечника в клинических испытаниях.

Keywords: «Bacteriophage salmonella polyvalent» - “MediPhag” , Ciprofloxacin, Salmonella, Bacteriophage

Ключевые слова: «Bacteriophage salmonella polyvalent» - “MediPhag”, ципрофлоксацина, Salmonella, Бактериофаг

Introduction. Salmonellosis is an infectious disease caused by numerous serotypes of more than 2200 bacteria of the genus Salmonella [7]. They are characterized by a variety of clinical manifestations from asymptomatic carriage and mild forms of gastroenteritis to severe generalized forms of the disease occurring with pronounced intoxication and prolonged fever (typhoid-like septicopyemiemic form) [3]. The high resistance of Salmonella to antibiotics to the main means of etiotropic therapy of patients with this pathology, the emergence of multidrug-resistant variants of the pathogen poses the problem of finding new medicinal antimicrobial agents created on the basis of modern biotechnologies [6].

One of the directions in solving this complex problem is the use of therapeutic and prophylactic preparations of bacteriophages that provide a specific lytic effect on the pathogen and do not have adverse toxic and allergic reactions to the human body [8]. In conditions of increasing resistance of microorganisms to antibiotics, bacteriophages are increasingly being used in clinical practice [1]. Anti-Salmonella bacteriophages of groups A, B, C, D, E (Bacteriophage Salmonellae gr. A B C D E) appeared on the market, for example from Microgen FSUE NPO Russia.

In Uzbekistan, the company AZIYA IMMUNOPREPARAT LLC began to produce the anti-salmonella drug «Bacteriophage salmonella polyvalent» - “MediPhag” in the dosage form of capsules and liquids in 20 ml vials for oral use. It is a sterile purified filtrate of phagolysates of salmonellosis bacteria S. typhimurium, S. newport, S. enteritidis, S. moscow, S. paratyphi B, S. agama and S. yava with a phage titer of at least 1*10⁶ PFU/ml. The aim of the study was to study the clinical tolerability of the drug «Bacteriophage salmonella polyvalent» - “MediPhag” for oral and rectal use in comparison with the drug Ciprofloxacin.

Material and methods. Patients over 18 years of age with acute diarrhea of identified salmonella serovars (S. typhimurium, S. newport, S. enteritidis, S. moscow, S. paratyphi B, S. agama, S. yava) were selected for the study. The patients were divided into 2 groups of 30 people. For the distribution of subjects into groups the method of simple randomization was used. The initial table of distribution of patients by groups was formed on the basis of random numbers obtained using the Graffad Prism (ANOVA) random number generation function. There were 13 women and 17 men in the study group receiving «Bacteriophage salmonella polyvalent» - “MediPhag”, and in the control group receiving Ciprofloxacin there were 8 women and 22 men. The average age in the main group was 29.7±2.0; and in the comparison group 34.1±2.5 (p≥0.05).

Patients of the study group were divided into 2 subgroups of 15 people. The first subgroup was prescribed «Bacteriophage salmonella polyvalent» - “MediPhag” in capsules, 3 capsules 3 times a day, an hour before meals for 5 days. The capsules were taken orally. The second subgroup was prescribed «Bacteriophage salmonella polyvalent» - “MediPhag” liquid 20 ml 3 times a day one hour before meals for 5 days. In both cases, the drug «Bacteriophage salmonella polyvalent» - “MediPhag” was taken against the background of basic therapy (analgesics, antispasmodics and rehydration therapy).

Patients in the control group (30 people) received standard therapy: ciprofloxacin tablets (500 mg) were taken orally 2 times a day, after meals with a small amount of water, for 5 days against the background of basic therapy. After the end of taking the drugs (day 5), all patients were examined according to the following scheme. Clinical examination: assessment of the general condition (nausea, vomiting, diarrhea, abdominal pain, headache, dry skin), heart rate, blood pressure, pulse, temperature. Clinical tests: complete blood count, urine, general analysis of feces. Biochemical analyzes: hemoglobin, erythrocytes, leukocytes and erythrocyte sedimentation rate. Special types of examination: microbiological examination of feces [4, 11, 9].

Tolerability of drugs was assessed according to the following scale. On examination and lab. studies and dynamics do not reveal any pathological changes or clinically significant and the patient does not notice adverse reactions (4 points)

On examination and laboratory. studies and dynamics do not reveal minor changes that are transient and do not require a change in the treatment regimen with the study drugs, and the patient notes manifestations of minor adverse reactions that do not cause serious problems (3 points).

On examination and laboratory. studies and dynamics do not reveal significant changes that do not require additional measures and the patient notes manifestations of adverse reactions that have a negative impact on his condition but do not require discontinuation of the drug (2 points).

On examination and laboratory. studies and dynamics do not reveal significant changes and the patient notes manifestations of adverse reactions that have a negative impact on his condition and require discontinuation of the drug (1 point).

On examination and laboratory. studies and dynamics do not reveal significant changes and the patient notes manifestations of adverse reactions that require discontinuation of the drug and additional medical measures - 0 points [2, 5, 10].

Results and Discussion. The results of the examination of patients who took «Bacteriophage salmonella polyvalent» - “MediPhag” and ciprofloxacin are presented in Figure 1 - 3. When patients were given MediPhag and ciprofloxacin there was no significant difference between systolic and diastolic heartbeats and changes in body temperature. It was found that the number of systolic contractions of the heart before taking the drug «Bacteriophage salmonella polyvalent» - “MediPhag” in patients was 105, and the number of contractions after taking the drug increased to 110. It was found that the number of systolic contractions of the heart in patients before taking the drug ciprofloxacin was 109, and after taking the drug increased to 110.

An increase in the number of cardiac systolic contractions was observed after patients received MediFag and ciprofloxacin. The number of diastolic contractions of the heart in patients before and after taking the drug was also determined. The number of diastolic heartbeats in patients before taking MediFag was 68, while after taking the drug, an increase of 72 was observed.

Also, the number of diastolic contractions of the heart in patients before taking Ciprofloxacin was 67, and after taking the drug 71. Based on the clinical results obtained, the following conclusions can be drawn. Cardiac stress was not detected when patients were taking MediFag. The number of systolic and diastolic contractions was also normal, blood pressure was normal. Figure 1.

Symptoms such as nausea, vomiting, diarrhea, abdominal pain, headache, and dry skin were also reduced in patients receiving «Bacteriophage salmonella polyvalent» - “MediPhag” and Ciprofloxacin Table 1.

Table 1.

Points of change of symptoms in patients before and after treatment with MediFag and Ciprofloxacin

Remark: ^* - significant difference in indicators in the compared groups – p>0.05

Biochemical and clinical studies were conducted in patients treated with «Bacteriophage salmonella polyvalent» - “MediPhag” and ciprofloxacin. Differences in hemoglobin, erythrocytes, leukocytes and erythrocyte sedimentation rate before and after drug administration were revealed Figure 2 and 3.

The hemoglobin level was 115.2 g/l before taking «Bacteriophage salmonella polyvalent» - “MediPhag” and 117.6 g/l after taking the drug. The hemoglobin level of ciprofloxacin was 119.6 g/l before taking the drug and 117.6 g/l after taking the drug. The erythrocyte sedimentation rate was 11.4 mm/s before taking «Bacteriophage salmonella polyvalent» - “MediPhag” but decreased to 10.2 mm/s after taking the drug. When patients took ciprofloxacin, the erythrocyte sedimentation rate was 10.2 mm/s before the administration of the drug and 6.8 mm/s after the administration of the drug. Results were expressed as mean values ± standard deviations. GraphPad Prism 8.0.1 was used for statistical analysis. Twoway ANOVA with multiple comparisons was performed to determine differences between groups. A p-value less than 0.05 was considered statistically significant in all cases.

There were no significant changes in the number of erythrocytes and leukocytes before and after taking the drug. Thus, it can be summarized that treatment with «Salmonella polyvalent bacteriophage» - “MediPhag” was highly effective in 28 patients out of 30 (93.3%) of the main group, which can be estimated at 3 points in terms of efficiency. High efficiency from the use of the drug ciprofloxacin in the control group was also observed in 28 patients (93.3%), in whom the clinical symptoms of the disease stopped during therapy, and laboratory parameters improved. Coprogram analysis returned to normal in 93.3% of patients after treatment: only 2 (6.6%) patients had a small amount of leukocytes. Thus, the average efficiency score in the main and control groups was the same and amounted to 3.0±0.0 in both groups (p>0.05). The next objective of this clinical study was to study the comparative tolerability of the studied drugs.

Conclusion. As a result of the examination of the survey and laboratory studies of patients treated with the «Salmonella polyvalent bacteriophage» - “MediPhag” and Ciprofloxacin, no adverse events and adverse reactions were identified. Thus the tolerability of the drug «Salmonella polyvalent bacteriophage» - “MediPhag” in capsules and liquid in vials is assessment as good in all 100% of patients no side effects were detected.

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