RU2171676C1 - Method of treatment of patients with rickettsiosis - Google Patents

Abstract

FIELD: medicine, infectious diseases. SUBSTANCE: method involves administration of immunomodulating preparation tamerit in a single dose 400 mg and daily dose 800 mg up to arresting intoxication symptoms and then in the dose 50-100 mg per a day to temperature value normalization. EFFECT: accelerated recovery, decreased expression of clinical symptoms. 6 tbl

Description

 The invention relates to medicine, in particular, to the treatment of acute febrile infectious diseases, accompanied by a violation of the immune status.

 There is a method of treating rickettsioses, for example, Astrakhan rickettsial fever, including taking antipyretics (aspirin), as well as glucocorticosteroids (prednisone), antibiotics (levomycetin or rifampicin). In addition, the treatment includes detoxification by infusion of hemodesis (400.0, 3 days), 5% glucose solution (800.0, 3 days), and drinking the solution will oralit 1.5-2.5 liters per day (5 days) (see , for example, Kh. M. Galimzyanov et al. "Astrakhan rickettsial fever", Astrakhan, 1999, p. 53).

 With this treatment, the temperature of the patients, lytically decreasing from the 9th day, returned to normal on the 11th day of the illness, by the 17th day the pain syndrome gradually decreased, and by the 22nd day the rash was finally extinguished.

 There is a method of treating rickettsioses, for example, tick-borne typhus (see, for example, K.M. Loban "The most important human rickettsioses", L., Medicine, 1980, p. 270), based on taking antibiotics (chloramphenicol and (or) tetracycline group), as well as taking in moderate doses of cardiac and vascular agents, in severe cases - additional intravenous administration of 5% glucose solution. In some cases, cardiac glucosyls and hormones are prescribed.

 This method requires long-term treatment, in which recovery usually occurs after 3-4 weeks.

 There is a method of treating rickettsioses, for example, Ku fever (See, for example, K.M. Loban "The most important human rickettsioses", L., Medicine, 1980, pp. 364-366), including taking tetracycline antibiotics in combination with chloramphenicol (0.3 g 3 times a day tetracycline or tetramycin and 0.5 g 3 times a day levomycetin). In the absence of noticeable improvements in the condition, glucocorticoid preparations, for example, prednisone, are prescribed at a dose of 30-60 mg per day, and with the development of the myocardium, cardiac (glycosites) and vasopressor drugs, as well as detoxification drugs in the form of 5% glucose or saline intravenously.

 With this method of treatment, its duration is about 15 days.

 An analogue of the prototype method for treating rickettsioses is complex therapy (see, for example, N.M. Gracheva and N.I. Schetinin, "Clinical Chemotherapy for Infectious Diseases", L., Medicine, 1980, p. 150), including a combination of tetracycline antibiotics a number (tetracycline, terramycin, oletetrin or doxycycline) with drugs aimed at increasing the body's defense mechanisms (immunomodulating drugs).

 However, no effective means of targeted immunotherapy for the treatment of rickettsioses has been proposed.

 The essence of the invention lies in the fact that in the method of treatment of rickettsiosis based on the use of an antibiotic in combination with an immunomodulating drug, Tamerite is used as an immunomodulating drug, while it is administered in a single dose of up to 400 mg and a daily dose of up to 800 mg, before the symptoms of intoxication are stopped and then, until the temperature normalizes, at a dose of 50-100 mg per day.

 The proposed method for the treatment of rickettsioses provides less severe clinical symptoms and faster recovery.

 Clinical studies performed in the treatment of patients with rickettsioses (Astrakhan fever, tick-borne typhus, Q fever) have confirmed the feasibility of using the Tamerite immunomodulating drug in the treatment process and the correct dosage of this drug, which includes higher, in comparison with the known, single and daily doses in the acute stage of the disease and usually recommended (maintenance) doses in the recovery phase.

 The drug Tamerite, presented here as an immunomodulating drug, is a phthalhydrazide derivative (5 aminophthalhydrazide) in chemical composition and is approved for use in accordance with the registration certificate of the Ministry of Health of the Russian Federation dated 03.04.2000 No. 2000/113/5.

 Studies have shown that this drug has bifunctional properties (a dose-dependent effect), that is, it is able to selectively inhibit the synthesis of hyperactivity by macrophages of certain key cytokines: interleukin-1, tumor necrosis factor and reactive radicals.

 At the same time, the inhibition time determines the frequency of drug administration into the patient’s body, and the dose dependence is determined by the severity of the toxic-toxic syndrome.

 Tamarit acts on neutrophilic granulocytes, stimulating their microbicidal system and enhancing the phagocytosis of pathogens, and is also able to reversibly inhibit the function of excess activated macrophages. Its effect opens the pathogenetic chain and in most cases leads to a relief of the pathological process, regardless of its etiology.

 The statistics of clinical trials in the treatment of astrakhan rickettsial fever (ARL) are shown in table 1.

 Seventy-five ARL patients were monitored, of which 30 comprised the control group and tetracycline antibiotics (Doxycycline), while the remaining patients were additionally injected with the Tamerit drug according to the above procedure.

 The main clinical symptoms and their duration for the above patients were distributed as follows (see table. 1).

 Moreover, the incubation period for all groups averaged 9 days, and the primary affect was 71%.

 A review of the data in Table 1 shows that when Tamerit is used in the treatment complex, the time for manifestation of the main clinical symptoms of Astrakhan rickettsial fever is almost halved.

 Statistics of clinical trials in the treatment of tick-borne typhus are given in table 2.

 38 patients were monitored, of which 20 received only antibiotic (doxycycline) and detoxification therapy, and 18 patients were additionally injected with Tamerit. The diagnosis was confirmed on the basis of serological tests.

 A review of the data in Table 2 shows that additional injection of the drug Tamerit in the treatment of tick-borne typhus fever significantly reduces the time to stop the clinical syndromes of the disease.

 The statistics of clinical trials in the treatment of Q fever are given in table 3.

 There were 36 patients under observation, of whom 15 received therapy in accordance with the known method of treatment: antibiotics (doxycycline), detoxification therapy (reopolyglucene, crystalloids), and the rest were additionally injected with Tamerite intramuscularly.

 The diagnosis was confirmed by CSC with Burnet rickettsia with paired sera.

 A review of the data in Table 3 shows that, as in the above cases, the use of Tamerit in the treatment complex reduces the time of manifestation of the main clinical symptoms of the disease.

 At the same time, in clinical and laboratory studies of patients with rickettsioses in the immunograms, relative and absolute lymphopenia, T-cell insufficiency of various degrees, a decrease in the phagocytic activity of neutrophils, a lack of production, moderate hyperproduction were revealed.

 The invention is confirmed by examples.

 Example No. 1.

 Patient V., 40 years old.

 He fell ill on 05/20/99, was admitted to the infectious diseases hospital on 05/23/99, and was discharged on 06/06/99.

 The disease is associated with a tick bite (At the site of the bite in the ankle joint, primary affect is from 05/21/99).

Complaints: Weakness, nausea, myalgia, arthralgia, rash on the body and limbs (from 23.05.99), fever (temperature - 39.2 ^o C).

 On examination: The condition is closer to severe, on the body a spotty-papular rash of hemorrhagic nature, respiratory rate - 18 per minute, pulse 106 per minute, blood pressure - 110/60 mm Hg, liver +1.5 cm, pharynx hyperemic , language is overlaid.

 Diagnosis: Astrakhan rickettsial fever.

 Etiotropic therapy with doxycycline (an antibiotic of the tetracycline group) was prescribed at a dose of 0.1 g per day (pe 0), detoxification therapy - hemodesis 400 ml iv, and Tamerit - initially in a single dose of 350 mg per 5 ml of water for injection (up to relief of intoxication symptoms), and then at a dose of 100 mg per 1 ml of water for injection (until normalization of body temperature) intramuscularly once a day.

 Against the background of complex treatment, the fever stopped in 2 days, general weakness by the 4th day, headache and myalgia disappeared after 2 days, arthralgia after 3 days, and the rash regressed in 5 days. The phenomena of scleritis and erythema of the larynx were stopped in 7 days.

 Table 4 shows the data of laboratory studies of patient B.

Example N 2
Patient N., 48 years old.

 He fell ill on August 28, 1999, when he felt weakness, chills, headache, arthralgin and myalgia, was admitted to the infectious diseases hospital on September 5, 1999.

On admission: body temperature 38.6 ^o C, on the body and extremities a maculopapular rash, moderately enlarged cervical lymph nodes are palpated, the pharynx is hyperemic, the liver is +2 cm, the spleen is palpated.

 Diagnosis: Tick-borne typhus.

 Prescribed therapy with doxycycline at a dose of 0.1 g per day, detoxification agents, as well as intramuscularly Tamerit - to stop the infectious-toxic syndrome in a daily dose of 300 mg per 3 ml of water for injection, and then at a dose of 50 to 100 mg per 1 ml water for injection for 5 days.

 Discharged September 17, 1999

 When analyzing the clinical and laboratory data of patient examinations during treatment, rapid relief of the main infectious-toxic symptoms and regression of the rash, as well as the normalization of laboratory blood parameters, were noted.

 Table 5 shows the data of laboratory examinations of patient N.

 Example No. 3.

 Patient P., 36 years old.

 Sick since 06/26/99, was admitted to the infectious diseases hospital 06/28/99

 Complaints: General malaise, weakness, fever, dark color of urine.

 In the epid. history of drinking river water.

On examination: Body temperature - 38.8 ^o C, sclera is subacterial, moderate subacterial skin, hyperemia of the throat, a single rodeole rash on the body, pulse 96 min, blood pressure 120/65 mm Hg, liver +2.5 cm.

 Diagnosis: Q fever.

 Treatment: Doxycycline at a dose of 0.1 kg per day, detoxification therapy, IM Tamerite in a single dose of 400 mg per 4 ml of water for injection in a daily dose of 800 mg, after 3 days at a dose of 100 mg per 1 ml of water for injection.

 The temperature stopped after 72 hours. During the same time, the main symptoms of the disease regressed: headache, nausea, weakness, liver +1.5.

 Discharged on July 13, 1999.

 Table 6 shows the data of laboratory examinations of patient P.

Claims (1)

 A method of treating rickettsiosis based on the use of an antibiotic in combination with an immunomodulating drug, characterized in that Tamerit is used as an immunomodulating drug, in which case it is administered in a single dose of up to 400 mg and a daily dose of up to 800 mg, until the symptoms of intoxication are stopped, and then to normalize the temperature, in a dose of 50-100 mg per day.

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