RU2137483C1 - Method of treatment of patients with urogenital chlamydium, ureaplasma and mycoplasma infection - Google Patents

Abstract

FIELD: medicine, gynecology. SUBSTANCE: method involves carrying out two successive treatment courses for 10 days each. Course involves the use of antibiotics, proteolytic enzymes and preparation improving microcirculation. Immunomodulating therapy is carried out between 7-days break and involves the use of preparations of thymus, interferon, blood cytokins. After termination of the second course the immunomodulation therapy is carried out for 30 days. EFFECT: enhanced effectiveness of treatment. 4 ex

Description

 The invention relates to medicine, namely to gynecology, andrology, urology, venereology, and can be used in the treatment of inflammatory processes and infertility caused by these pathogens.

 Chlamydial and mycoplasma infections are currently the most common cause of inflammatory processes in the urogenital system of men and women and a factor causing infertility even with asymptomatic carriage (WHO, 1994). At the same time, there are no optimal treatment regimens for these infections. When using conventional methods of therapy, improvement is observed in 40% with chlamydial and 85% with mycoplasma infection, and complete cure is observed only in 23-30% of cases [1, p. 231, p. 258]. This is explained, firstly, by the biology of these pathogens, which are facultative intracellular parasites, which makes it difficult for drugs to penetrate, and secondly, by the specifics of the action of antibiotics: penicillins, cephalosporins, aminoglycosides do not act on these microorganisms due to the lack of a cell wall, tetracyclines, macrolides and azalides are bacteriostatic and only prevent their reproduction, rifampicins and sulfonamides are not specific enough, fluoroquinolones do not penetrate into ureaplas mu because of the lipophilicity of its shell. The number of strains resistant to each of the antibiotic groups is increasing, which requires their combined use in the form of several courses in combination with vascular, enzymatic and antihistamines, local and physiotherapeutic procedures [2].

 The closest to the proposed method is essentially a method of treating these infections with a combination of antibiotics with tactivin (6-10 injections per course), human leukocyte interferon and IVF interferonogen in the form of vaginal balls (1-2 times a day for 2-4 weeks). and / or interferon 500 thousand ME in the form of injections (daily 2 weeks) [1]. Positive treatment results were obtained in this case in 83.4-93.8% of patients, depending on various combinations of pathogens. The disadvantage of this method is the relatively low efficiency, since the authors did not take into account the individual characteristics of patient immunity and the appointment of immunomodulators was performed blindly, focusing only on the clinical picture of the disease "in severe and neglected (complicated) cases" [1, p. 288], and cure control was performed in within one month after completion of treatment, while in many patients relapse can be detected only after 1-1.5 months. after completion of the course of therapy [2, p. 31].

 The objective of the present invention is to increase the effectiveness of treatment and reduce course doses of antibiotics and immunomodulators based on the individual characteristics of the state of immunity of patients.

 This problem is solved by conducting two ten-day courses of antibiotics in combination with proteolytic enzymes, immunomodulators, drugs that improve microcirculation, in a 7-day break between which a human leukocyte interferon drug is administered at a dose of 10,000 IU / day, and after completing the second course of antibiotics, a thirty-day course of immunomodulating therapy, including thymic polypeptide preparations, such as tactivin or thymalin, human interferons and cytokines, such as le ykinferon and viferon.

 The therapeutic effect of such a complex is based, on the one hand, on the synergistic action of enzyme preparations and vasodilators with antibiotics, on the other hand, it is ensured by the activation of immunity between and after antibiotic therapy, which allows the intracellular pathogens and host cells to be destroyed or to wait for their natural elimination from the mucous membranes, while blocking the reproduction and expansion of microorganisms.

 The effectiveness of the method is shown in the treatment of 72 men aged 19 to 53 years and 80 women aged 19 to 42 years, who came for inflammatory processes and / or infertile marriage in SC A, D and P of the RAMS, in which smears from the urethra chlamydia, mycoplasma and / or ureaplasma have been detected in the cervical canal or prostate juice. These pathogens were detected by DNA probes and polymerase chain reaction (PCR), allowing to detect specific for each pathogen DNA. To detect chlamydia, in addition, a specific antigen was detected by indirect fluorescence method with Chlamyzet MAT and the detection of antichlamydial antibodies in the blood using the ELISA micrometric method. At the same time, the number and ratio of various subpopulations of T and B cells were evaluated by flow cytometry, the nephelometric method was used to determine the concentration of IgA, IgM, IgG immunoglobulins in the blood, the method of luminol-dependent chemoluminescence, the determination of spontaneous and induced peroxide-producing activity of phagocytes, according to the Kembel method, determination of the natural and induced production of interferons alpha, beta and gamma. In men, sperm morphology, the concentration of fructose in it and the presence of antispermal autoantibodies (MAR) were examined, and if necessary, bacteriosis was performed; in women, a cytological and microbiological examination of a vaginal smear.

 Patients who were found to have gonorrhea, trichomoniasis or gardnerelosis were excluded from the group.

 Among men, 15% (11 people) had complaints of more or less pronounced subjective sensations: itching, pain in the urethra, redness and sticking of her lips, frequent urination, slight discharge from the urethra, pain in the perineum, anus, in the lumbar region. In several cases, there were violations of sexual intercourse: worsening erection, shortening the time of intromission. 85% of men (61 people) had no complaints about the genitourinary system. Despite this, the majority of men (81%) showed a decrease in the quality of the ejaculate: oligo-, astheno-, teratozoospermia in various combinations with a predominance of asthenozoospermia, in 11% - pyospermia.

 Of the 80 women examined, complaints of itching and burning in the external genital area were in 27 women (33%); for itching in the anus - in 5 women (6%); 12 women (15%) complained of pain in the knee joints, worse in the evening, tearing and burning eyes. 36 women had no complaints about the genitourinary system. Despite this, cervicitis was revealed in 11 women (13%).

 All men and women received treatment according to the proposed method. The course of immunomodulating therapy depended on the initial immune status and was carried out under the control of an immunogram.

 Control studies were performed after 2 weeks, 2 and 6 months. after completion of complex antibiotic therapy.

 It was shown that in all men with subjective and laboratory signs of the inflammatory process, clinical improvement was observed. Only two men had complaints of mucous discharge in the form of a morning drop and burning in the urethra after provocation with alcohol, one had pyospermia, but the severity of these phenomena was significantly lower than before treatment. An etiological cure (the absence of pathogens in a smear from the urethra and prostate juice) was shown with ureaplasmosis in 84% of cases, with chlamydia - 89%, with mycoplasmosis - 100%. Of 44 women with clinical manifestations of urogenital chlamydia, cure occurred in 40 women (91%), improvement in 3 women (7%), and no effect in 1 woman (2%). An etiological cure was observed with ureaplasmosis - in 81%, with chlamydia - 87%, with mycoplasmosis - in 100%.

 The effectiveness of the method is illustrated by examples.

 Example 1. Patient S., barren marriage 4 years. A history of gonorrhea urethritis, chronic chlamydial prostatitis. Previously, he twice took courses of anti-chlamydial therapy with doxycycline (21 days) and sumamed (7 days), repeated courses of prostate massage. Complaints are not periodic burning in the urethra, discharge in the form of a morning drop, pain in the perineum, radiating to the inner thighs, shortening of sexual intercourse. On examination: hyperemia, adhesion of the lips of the urethra, prostate slightly enlarged, elastic consistency. The interlobar groove is somewhat smoothed, the boundaries are clear, with palpation moderately painful. Ultrasound: prostate 3.3-4.6 cm in size, volume 26 ml, echogenicity is heterogeneous. Chlamydia trachomatis was found in a smear from the urethra and prostate juice, specific antibodies in the blood - 1/32. Ejaculate: volume 2.2 ml, concentration - 14 mln / ml, category A motility - 8%, pathological forms - 53%, fructose - 150 mg%, MAR - 10%. Immune status: blood leukocytes - 6.40 million / ml, lymphocytes - 3.53 million / ml, incl. T-lymphocytes - 1.08 mln / ml, T-helpers - 0.95 mln / ml, T-suppressors - 0.39 mln / ml, normal killers - 1.60 mln / ml, B-lymphocytes - 0.11 mln / ml, IgG - 1200 mg%, IgM - 95 mg%, IgA - 320 mg%. Phagocytic activity of peripheral blood leukocytes: spontaneous - 4.6 cu, induced - 4.6 cu; activity index - 1.0. Interferon status: alpha / beta interferon in serum - 8 units / ml: spontaneous activity - 4 units / ml, alpha / beta-virus-induced activity less than 4 units; gamma-mitogen-induced - less than 4 units. Diagnosis: chlamydial prostatitis; oligoastenoteratozoospermia with an autoimmune component; moderate T-link immunodeficiency, phagocyte hyperfunction in the absence of reserve capacity, overproduction of serum alpha-IFN and a significantly reduced response to all inducers.

 The treatment was prescribed by the proposed method: Wobenzym from 9 tab / day to 15 tab / day in 60 days; from the 5th day, minocycline 0.1 g in the morning and evening for 9 days; at the same time tiberal, nystatin, koplamin in usual dosages; from 15 to 20 days, leukinferon 1 ampoule (10000 ME) every other day B / M (N = 3); from the 21st day, ciprofloxacin 0.5 g in the morning and evening in combination with nystatin, komplamin.

 After the end of the course of antibiotics, carlsil and lactobacterin in usual doses. Immunomodulating course: Tactivin 1 ml of 0.01% solution (1 vial) in the first week every other day, then once a week (N = 6); leukinferon - the second week for 1 ampoule (10000 ME) every other day (N = 3), viferon (candles) from the third week every day for 1 pc. rectally at night (N = 20).

 The results of treatment 2 weeks after completion of the course (8 weeks after taking antibiotics): the clinical effect is the disappearance of burning, secretions, pain, improved erections and overall well-being; with ultrasound prostate size 3.0-4.0 cm, a volume of 20 ml, painless on palpation. Chlamydia in a smear from the urethra and juice of the prostate and antibodies in the blood were not found. Ejaculate: volume 3.4 ml, concentration - 37 million / ml; category A mobility - 26%; pathological forms - 42%, fructose-270 mg%. Immune status: white blood cells - 4.90 million / ml; lymphocytes -1.90 million / ml; T-lymphocytes - 1.50 million / ml; T-helpers - 0.84 million / ml; T-suppressors - 0.31 million / ml; normal killers - 0.24 million / ml; B-lymphocytes - 0.20 million / ml; IgG-1200, IgM-190, IgA-95 mg /%; phagocyte activity: spontaneous - 0.9, induced - 3.31, activation index - 3.4; interferon status: IFN in serum less than 4 units / ml; virus-induced IFN alpha / beta - 64 units / ml: mitogen-induced IFN gamma - 16 units / ml.

 These results correspond to normozoospermia and the normal state of cellular, humoral immunity and the system of interferons. Thus, after treating a patient with the proposed method, there are clinical and etiological cures for chlamydia, normalization of spermogram and immune status, an improvement in well-being and potency is observed.

 Example 2. Patient M., 29 years old, came in April 1994. Barren marriage 5 years. History of two honey. abortion, after the last abortion within 5 years of pregnancy was not; conjunctivitis - treated by an optometrist. The diagnosis was first made: chlamydia, was made in 1993, the patient (with her husband) was treated with doxycycline 21 days. Complaints about the absence of pregnancy, burning and itching in the external genital area, mucopurulent discharge from the vagina, aggravating before the upcoming menstruation.

 On examination: the cervix is hyperemic, the body of the uterus is not enlarged, dense, painless. Appendages on both sides in commissures, painful on examination. The discharge is mucopurulent. Chlamydia is found in a smear from the cervical canal (twice PCR, twice DNA probe).

 General blood test: white blood cells - 8.80 million / ml; erythrocytes - 4.26 million / ml; hemoglobin - 131.0; lymphocytes - 2.90 million / ml, including: T-lymphocytes - 0.90 million / ml; T-helpers - 0.50 million / ml; T-suppressors - 0.44 million / ml; normal killers - 0.20 million / ml; B - lymphocytes -0.14 million / ml; IgG-1120; IgM -125 (mg%). Interferon status: alpha-interferon in blood serum - less than 4 units / ml; spontaneous activity - 8 units / ml; alpha virus-induced - less than 4; gamma-mitogen-induced - less than 4. (Production of interferon formation is sharply reduced, spontaneous activity is increased). Diagnosis: Infertility II. Urogenital chlamydia.

 The treatment was prescribed by the proposed method: vobeizim from 9 tablets per day to 15 tablets per day for 60 days, from 5 days to vibramycin 100 mg after 12 hours, ultra-levur in usual doses, from 15 to 20 days leukinferon every other day for 1 amp. (10000 ME) v / m, from the 21st day, tarid is 0.2 g in the morning and evening in combination with ultra-levure, locally polygynax. After the end of the course of antibiotic treatment - lactobacterin and bifidumbacterin, bactisubtil in usual doses.

 Immunomodulating course: tactivin 1 fl. (10 mcg) in the first week every other day, then once a week (N = 6), leukinferon in the second week, 1 amp. every other day (N = 3), viferon (candles) from week III daily, 1 pc. rectally at night (n = 20).

 The results of treatment 1 month (4 weeks) after the end of the full course of treatment, 7 weeks after the end of antibiotic therapy: the clinical effect is the absence of complaints of itching and burning. When viewed per vaginum: no features. Chlamydia in smears from the cervical canal by two methods (twice PCR; twice DIC probe) was not detected. General blood test: white blood cells - 8.8 million / ml; erythrocytes - 4.54 billion / ml; hemoglobin 140.0; lymphocytes - 26%; ESR - 5. Immune status: T - lymphocytes - 1.5 million / ml; T-helpers -1.2 million / ml; T-helpers - 1.2 million / ml; T - suppressors - 0.5 million / ml; normal killers - 0.2 million / ml; B-lymphocytes - 0.2 million / ml. Interferon status: alpha-interferon in blood serum - less than 4 units / ml; spontaneous activity - less than 4 units / ml; IFN alpha virus-induced - 256; gamma mitogen-induced - 64.

 These results correspond to the normal state of cellular, humoral immunity and the system of interferons. Thus, after treatment of the patient with this method, there is a clinical and etiological cure for chlamydia, there is an improvement in well-being. 6 months after the end of the entire course of treatment, the patient became pregnant (at the moment - 01.07.95, the patient has a gestational age of 28 weeks).

 Example 3. Patient B., 33 L, complained of mucous discharge from the urethra and itching when urinating. A history of recurrent herpetic eruptions on the foreskin every 2-3 months. The last few years, chlamydia a year ago, about which he took a course of antibiotic therapy with his wife. Married 5 years, wife three miscarriages, last 2 months. back, after curettage - acute endometritis. Both underwent a course of antibacterial therapy: doxycycline, trichopolum, nystatin 10 days. My wife currently has no complaints. Recently, sex with a condom.

 Inspection: the penis and scrotum organs are developed normally, hyperemia of the lips of the urethra, no lymphadenitis.

 Research results: Ureaplasma urealytinum and HSV were detected in a smear by PCR, ejaculate - asthenozoospermia; blood leukocytes - 6.8 million / ml, including lymphocytes - 2.1 million / ml, of which T-lymphocytes - 0.77 million / ml, T-helpers - 0.50 million / ml, T- suppressors - 0.53 million / ml, NK - 0.96 million / ml, B-lymphocytes - 0.26 million / ml, IgG immunoglobulins - 1362, IgA - 220, IgM - 385 mg%, phagocyte activity - 11.7 units, activation index - 0.6, interferon alpha / beta serum - 16 U / ml, alpha / beta virus-induced - 8 U / ml, gamma-mitogen-induced - 4 U / ml. The diagnosis was made: ureaplasmosis, recurrent herpes, a violation of the ratio of immunoregulatory cells by type of suppression of helper activity, hyperactivity of phagocytes and interferon systems with a decrease in the reserve capacity of cells.

 The treatment was prescribed according to the proposed method: maxaquin 0.4 g / day in the first, sumamed - 0.5 g / day in the second ten-day course, simultaneously with nystatin of 1500 thousand units / day and wobenzym of 15 tab / day; 10 mcg of tactivin on days 11, 13, 16, 23, 30 of treatment (N = 5), 10,000 IU of leukinferon on days 12, 14, 17.31, 33 of treatment (N = 5).

 2 weeks after completion of treatment: a smear on ureaplasma is negative, HSV is weakly positive, ejaculate is normozoospermia, blood leukocytes - 6.50 million / ml, including lymphocytes - 2.90 million / ml, of which T-lymphocytes - 2.00 million / ml, T-helpers - 1.50 mln / ml, T-suppressors - 0.64 mln / ml, NK - 0.80 mln / ml, B-lymphocytes - 0.60 mln / ml, IgG - 940, IgA - 240, IgM - 175, peroxid phagocyte activity is 3.1, activation index is 1.6, serum interferon alpha / beta is 4 U / ml, virus-induced is 32 U / ml, gamma-mitogen-induced is 16 U / ml.

 Thus, there was a cure for ureaplasma infection, normalization of the ratio of immunocompetent cells, an increase in their absolute number, and restoration of functional activity.

 Example 4. Patient S., 32 g, was referred by a gynecologist for chronic salpingo-oophoritis in a wife. Complaints about shortening intercoitus to 1 min, dulling of an orgasm; erection is normal, itching, no discharge. Pregnancy is not planned. Examined: penis, scrotum organs without features, the prostate is slightly compacted, the groove is smooth, painless. Research results: chlamydia, urea and mycoplasma were detected in a smear by PCR, normozoospermia ejaculate, normal prostate juice, 4.70 million / ml blood leukocytes, including 1.13 million / ml lymphocytes, of T-lymphocytes - 0.80 million / ml, T-helpers - 0.50 million / ml, T-compressors - 0.19 million / ml, NK - 0.16 million / ml, B-lymphocytes - 0.05 million / ml, immunoglobulins IgG - 2145, IgA - 685, IgM - 126 mg /%, phagocyte activity spontaneous - 4.4, activation index - 1.1, interferon alpha / beta serum - 8 U / ml, alpha / beta virus induced - 4 U / ml, gamma-mitogen-induced - 4 U / ml. Diagnosis: urogenital chlamydia, ureaplasmosis, mycoplasmosis, immunodeficiency with a decrease in the number of T and B lymphocytes, a sharp decrease in the reserve functions of interferon production.

 The treatment was prescribed: vibramycin 200 mg / day., Tarivid 600 mg / day., Together with wobenzym, nizoral two consecutive courses of 10 days with a 7-day break, tactivin - 11, 13, 16, 27, 30, 35 days treatment (N = 6), leukinferon -12, 14, 17, 31, 34 days of treatment (N = 5).

 2 weeks after completion of the course: smear for the listed infections is negative, white blood cells - 5.20 million / ml, of which lymphocytes - 1.45 million / ml (28%), including T-lymphocytes - 0.90 mln / ml, T-helpers - 0.70 mln / ml, T-suppressors - 0.39 mln / ml, NK - 0.20 mln / ml, B-lymphocytes - 0.10 mln / ml, phagocyte activity - 3 , 0, activation index - 2.0, serum interferon - 4 U / ml, alpha / beta virus-induced -16 U / ml, gamma-mitogen-induced - 16 U / ml.

 Thus, there was a cure for mixed urogenital infection, accompanied by the restoration of most of the basic parameters of immunity. The duration of sexual intercourse increased to 3-5 minutes. There are no complaints of the genitourinary apparatus.

 The proposed method allows for inflammatory processes of chlamydial, ureaplasma and mycoplasma etiology in 98% of cases to obtain clinical improvement and in 84-100% to achieve etiological cure with remote control up to 6 months, while reducing the number and spectrum of necessary immunomodulating drugs 1.5-2 times, reducing single doses of interferon up to 5 times and does not require local, including physiotherapeutic procedures. The results obtained allow us to consider the proposed method as more effective than the prototype.

Sources of information taken into account
1. Kozlova V.I., Pukhner A.F. Viral, chlamydial and mycoplasma diseases of the genitals. - M.: Avicena, 1995.- c.229, 230, 236, 287-289.

 2. Ilyin I.I. et al. Reflections on the treatment of urogenital chlamydia // Bulletin of dermatol. and Venus. - 1994.-N1.- c. 30-33.

Claims (1)

 A method of treating urogenital chlamydial, ureaplasma and mycoplasma infections, including the use of antibiotics, proteolytic enzymes, immunomodulators, drugs that improve microcirculation, characterized in that in a 7-day break between two consecutive ten-day courses of various antibiotics, a human leukocyte 10-interferon drug is introduced into the body 000 IU / day, and after completing the second course of antibiotics, a thirty-day course of immunomodulating therapy is carried out, including thymus polypeptide drugs such as timalin, taktivin, interferon, and human blood cytokines such as leukinferon, viferon.