Method for treating postoperational purulent-inflammatory complications induced by cross infection
FIELD: medicine, surgery, urology.
SUBSTANCE: one should apply bactisporin probiotic preparation introduced per os at 1-10 x 109 microbial cells twice or thrice for 10-20 d in combination with staphylo-proteic-pyocyanic adsorbed (SPPA) vaccine; moreover, the mentioned combination of preparation should be applied, also, for instillation of wounds, serous cavities, cavities of urinary and biliary ducts at the quantity of 1-5 x 109 microbial cells in isotonic sodium chloride solution. The present innovation provides better humoral and cellular immunity to already developed infectious process, moreover, combined application of SPPA vaccine and bactisporin leads to increased body immune response to antigens of associated vaccine at the background of secondary immunodeficient state induced by infectious process.
EFFECT: higher efficiency of therapy.
1 cl, 5 ex, 3 tbl
The invention relates to medicine, in particular to surgery and urology, and can be used for the prevention and treatment of purulent-septic complications after surgical interventions on the organs of the abdominal cavity, chest, retroperitoneum, soft tissues, bones and joints.
The existing scheme for the prevention and treatment of purulent-inflammatory complications is the use of broad-spectrum antibacterial drugs. The main ones are: β-lactam antibiotics, cephalosporins, aminoglycosides, fluoroquinolones, macrolides, nitrofurans, sulfonamides .
Prevention of antibiotic therapy is administered in preparation for surgery, intraoperative, early postoperative period, however, its effectiveness is far from desirable. The difficulty of prevention and treatment is associated with a fairly rapid development of pathogens of nosocomial infection resistance to the main groups used antimicrobial drugs, the development of cross-resistance of pathogens in the hospital environment, as well as with secondary immunodeficiency condition of patients in the postoperative period . On the other hand, antibiotics have a number of side effects: inhibit the immune system, have a toxic effect on the liver and kidneys, cause Allergy the definition of the reaction, lead to the development of dysbiosis, reducing the body's resistance to nosocomial infections .
Known application for etiotropic therapy of nosocomial infections in the postoperative period polyvalent bacteriophages. Bacteriophages are highly specific, harmless, does not inhibit normalor . However, stamosishot bacteriophages makes their application difficult, as it requires before assigning pre-commercial adaptation of the drug to the selected serotypes specific microbial epitope that makes inefficient use of bacteriophages for the prevention of septic infection (GSE). In the treatment of nosocomial infection, the phage therapy is used as a tool allowance, because inefficient or inadequate application is the rapid emergence of favoritestest strains.
Known way to prevent septic complications by creating a patients specific immunity to the pathogens of nosocomial infection. To do this, in the preoperative period immunization coverage of various mono - and poliovaccine containing antigens of the most common opportunistic pathogens .
The known method of prevention of inflammatory complications accidental traumatic and surgical wounds . The method is local in operationem introduction stafilo-proteaceae-Pseudomonas aeruginosa (SPSA) vaccine in the wound in the amount of 0.3 to 1.0 ml.
Closest to the claimed method is a method of prevention of inflammatory complications in patients with injuries of the musculoskeletal and joint injuries by introducing traditional antibacterial scheme parenteral immunization stafilo-proteaceae-Pseudomonas vaccine . Immunization was performed within the first 72 hours after admission to hospital introduction subcutaneously in the region of the inferior angle of the scapula 0.5 ml once and 0.5-1.0 ml of SPSA vaccine with an interval of 14 days in a double vaccination.
SPSA vaccine as protective antigens contains toxoids aureus and Pseudomonas aeruginosa, cytoplasmic antigen of Staphylococcus and soluble antigens of 6 strains of Proteus .
However, vaccination of SPSA-vaccine generates specific immunity against certain pathogens, not excluding the possibility of infection and the development of septic infection due to other members of the hospital flora. The use of vaccination involves the combination of it with antibiotics and antibacterial drugs that in terms of the multiple antibiotic resistance of nosocomial strains often do not give the expected results. On the other hand, systemic immunization with protective titers of specific antibodies is achieved only after 10-14 days of polivaktsiny, that does not provide adequate prevention of inflammatory complications when performing surgical interventions for urgent and emergency.
The objective of the invention is to develop a method for the prevention and treatment of purulent-inflammatory complications, combining immunization of SPSA-vaccine leading hospital agents with the drug active against antibiotic-resistant nosocomial strains.
The technical result consists in increasing the effectiveness of prevention and treatment of postoperative septic complications caused by hospital flora, preventing chronicity of the inflammatory process.
The problem is solved by the combined use of immunization of patients in preparation for surgery stafilo-proteaceae-Pseudomonas vaccine (SPSA-vaccine) at a dose of 0.5-1.0 ml with the probiotic Bactoprenol per os no 1-10×109microbial cells 2-3 times within 10-20 days. The proposed method of treatment does not exclude the use of antibiotics or antibacterial drugs. With contraindications to systemic immunization (polyvalent Allergy, pregnancy, etc.) vaccine can be used topically by application to mucous membranes of internal organs and cavities, as well as on the wound surface to the activation of m is local immunity. If you have an open wound surfaces and drainage systems and catheters, backspin additionally applied topically injected into the wound and drained bodies in a dose of 1-5×109microbial cells, diluted with sterile isotonic solution of sodium chloride in the amount of 5-20 ml If it is impossible enteral intake of probiotic (paresis of the intestine and so on). Backspin applies only locally.
Preparation of Backspin is a lyophilized live bacteria Bacillus subtilis strain MN. The bacteria Bacillus subtilis strain MN secrete antibacterial substance, broad-spectrum, the vast development of pathogenic and conditionally pathogenic microorganisms, including with antibiotic resistance, have no toxic or allergic side effects . It is known the use of bactisporin for the treatment of diseases of the gastrointestinal tract, disbacteriosis, enzyme deficiency of the digestive system, purulent infections, food allergies, for surgical treatment of soft tissue infections, for prevention of surgical infections trauma and surgical interventions .
Preparations on the basis of the bacteria Bacillus subtilis possess nonspecific immunomodulatory effects on different parts of the immune system, stimulates the anti-infective immunity and restore and munny status . Their intermittent reception period of vaccination, for example, of DTP vaccine increases the titer of specific antibodies in 2-3 times .
It is known that bacteria Bacillus subtilis oral application in the bacterial translocation into the blood, lymph, accumulate in the spleen, lymph nodes, tissue lesions and inflammation. In inflammation of the bacteria secrete biologically active substances (antibiotics, proteolytic and charolaise enzymes, immunomodulators, and other) and can have a pronounced therapeutic effect. Depending on the type of tissue the bacteria Bacillus subtilis remain viable from an hour to several days [13, 14].
The proposed scheme unlike the prototype has a broad antimicrobial spectrum against hospital flora due to the antagonism of B. subtilis relatively persistent flora, and also affects the main pathogenetic mechanisms of purulent-inflammatory complications in patients.
The method is as follows.
Example 1. In preparation for the planned intervention for 7-21 days before the operation is carried out immunization of SPSA-vaccine according to standard methods (0.5 ml subcutaneously with booster is not earlier than 14 days at a dose of 1.0 ml) or a single dose of 0.5 ml subcutaneously. When emergency interfering is listach vaccination of SPSA-vaccine can be carried out directly during the preoperative dose of 0.5 ml subcutaneously. If necessary, after 14 days it is possible booster dose of 1 ml
In the early postoperative period (first 3-5 days after surgery) is assigned probiotic, Backspin oral 2×109-10×109microbial cells (1-2 doses) 2-3 times a day for 10-20 days.
Patient, 24 years of age he entered the urology Department with a diagnosis of Chronic pyelonephritis, the active phase. Status post excision of carbuncle right kidney. Diabetes mellitus, type 1.
Complained of weakness, malaise, low-grade fever in the evening, stupid recurrent pain in region of right kidney, persistent inflammatory changes in the urine. This state continues for one month after discharge from hospital.
At admission the patient is vaccinated, SPSA-vaccine dose of 0.5 ml of n/K. Scheduled preventive antibacterial therapy drug Amikacin 1,0×2 times a day, and advanced probiotic, Backspin 2 doses 2 times a day per os the course of 10 days. Bacteriological examination of urine selected antibiotic-resistant strain of Proteus vulgaris 105CFU/ml during therapy on the 3rd day of normalized thermal response after 5 days started to grow at the rate of hemoglobin, decreased leukocytosis, ESR. After 10 days the patient's condition will satisfy the lnoe, in the control crops urine bacteria growth is not detected, the main indicators of urine and blood within normal limits. 14 day level antiprotein antibodies increased 2.5 times, enticingly 2 times, antistaphylococcal - 3 times.
Example 2. The treatment is identical to example 1, only in the presence of drainage systems advanced therapeutic purposes, backspin injected into the serous cavities, cavity system the urinary, biliary tract, wounds in the amount of 1-5×109microbial cells (1 dose), diluted with sterile isotonic sodium chloride solution, once daily in the amount of 5-20 ml
Patient K., aged 47 about bladder cancer underwent radical cystectomy with excretion of both ureters on the skin. In preparation for the second stage - the formation of the bladder from a loop of the small intestine by Studer conducted a survey in which from the urine inoculated Ps. aeruginosa 105CFU/ml, not sensitive to 30 of the tested antibiotics. 15 days before entering the hospital produced by immunization of SPSA-vaccine dose of 0.5 ml s/C, 14 days held a booster dose of 1.0 ml Before the operation level antiprotein antibodies increased in 3 times, enticingly 2 times, antistaphylococcal - 2.5 times. But in spite of combination therapy completely arrest the inflammatory percent of the SS and to eliminate Pseudomonas aeruginosa failed.
In the early postoperative period after resolution of paresis of the intestine drug therapy supplemented with a biological product, Backspin orally 2 doses 2 times a day and once daily 1 dose of bactisporin in 20-30 ml of isotonic sodium chloride was injected into the cavity intestinal transplant. The course of treatment was 10 days. Operating the wound healed by first intention. The reaction of the urine changed from alkaline to neutral, reduce the amount of mucus, leukocyturia decreased to 10-15 cells per field. In the blood normalized leukocyte count decreased ESR. After 10 days from the urine inoculated Pantoea agglomerans, which itself was eliminated after removal of the urethral catheter. Pyo-inflammatory complications in the postoperative period were observed. The patient recovered self urination. Discharged within 28 days of recovery.
Example 3. Immunization of SPSA-vaccine, but the drug Backspin is applied only locally to instalatii RAS, serous cavities, cavities, organs, urinary and biliary tract in the amount of 1-5×109microbial cells (1 dose).
Patient B., 68 years old, was admitted to the urology Department for planned surgical treatment with a diagnosis of Benign prostatic hyperplasia (adenoma) 2 tbsp. Secondary cystitis. Diabetes Tip. When examining the growth of bacteria in the urine not detected. Given the high risk of inflammatory complications in the postoperative period for 5 days prior to surgery the patient were immunized, SPSA-vaccine dose of 0.5 ml After performing crespuzyrna adenomectomy patient assigned to antibacterial therapy drug Amikacin 1,0×2 times a day. On the 7th day after the operation on the background drained lower urinary tract developed acute cystitis. From the urine allocated Enterobacter agglomerans (106CFU/ml), resistant to broad spectrum antibiotics. For relief of the inflammatory process in the scheme was further introduced backspin, which was used locally by introducing into the cavity of the bladder through cystostomy in quantities of 1 dose of 20 ml isotonic sodium chloride. The exposure time of the drug in the bladder was not less than 15 minutes. After 3 days growth was positive, the patient has decreased tenesmus, urine was clear. After 7 days of acute inflammatory process in the urinary bladder were stopped on the 10th day the growth of bacteria in the urine was not determined. Cystoscopically drainage deleted, restored self urination.
Example 4. Stafilo-proteaceae-Pseudomonas vaccine is applied topically at a dose of 0.5 ml by application to mucous membranes of internal organs (kidneys, the bladder, alchemipedia path, the trachea, bronchi, genitals) serous cavities, the wound surface during operation to produce secretory immunity caused by the synthesis of specific Ig and migration in mucosal lymphocyte precursors. Local immunization after the operation can be carried out by administration of the vaccine through the drains or in the endoscopic manipulation. Local application of the vaccine is combined with the administration in the early postoperative period of drug Backspin per os 1-10×109microbial cells 2-3 times within 10-20 days.
Patient K., aged 26, after suffering a year ago operation on the bladder about ureterocele suffer from chronic recurrent cystitis. Exacerbations occur 1-2 times per month. The patient has to take antibiotics and rosatti, the effect of which is short in nature. If the urine culture is highlighted Pseudomonas aeruginosa and Enterococcus, both of the pathogen resistant to antibiotics. With the purpose of specific immunotherapy through the catheter into the cavity of the bladder entered SPSA vaccine in the amount of 0.5 ml at 4 hours after administration of the vaccine is marked exacerbation of the inflammatory process in the urinary bladder characterized by the appearance dysuric phenomena. Simultaneously with the local immunization together with the RMCS is political therapy (nolitsin 400 mg× 2 times a day) appointed the preparation of Backspin orally 2 doses 2 times a day. In 3 days after receiving bactisporin produced crops urine specific for .subtilis environment (potato agar). Of urine planted .subtilis at a concentration of 104CFU/ml treatment bactoprenol amounted to 10 days. The results of the control urine culture growth was not given. The period of observation the patient was 3 months, during which acute cystitis was not observed.
Example 5. The method corresponds to claim 4, only backspin additionally used for instalatii RAS, serous cavities, cavities, organs, urinary and biliary tract in the amount of 1-5×109ál diluted with sterile isotonic solution of sodium chloride and entering the drainage system 1 once a day in amounts of 5-20 ml
Patient R., 72 years, with a diagnosis of Benign prostatic hyperplasia (adenoma), suprapubic rocheposay fistula, secondary cystitis entered the urology Department at the second stage of adenomectomy. When surveyed in the urine planted Proteus vulgaris 106CFU/ml in combination with Enterococcus 105CFU/ml. Of antibiotic sensitivity are saved only to the Tienam. The alkaline reaction of urine, leukocytes entirely, salt, phosphates and tripolyphosphate ++++, turbid urine with a foul smell.
For the purpose of renovation of the urinary tract to prepare for peratively treatment in the cavity of the bladder after rinsing it with saline solution introduced in 0.5 ml CPSA vaccine. Assigned backspin orally 2 doses 2 times a day and once daily one dose was injected into the cavity of the bladder, dissolved in 20 ml of sterile isotonic solution of sodium chloride. Acute inflammatory process in the urinary bladder was arrested within 7 days. Urine became transparent, the reaction of the urine is slightly acidic, leukocyturia 10-15 in the field of view, the growth of bacteria in the urine is not defined. The patient made Rasputina adenomectomy. Postoperative period was unremarkable. The wound healed by first intention. After closing cystostomy the growth of bacteria in the urine not detected. Recovered self urination. Discharged on the 14th day after the operation.
The proposed method is tested on 32 patients with urological pathology, the treatment of which required surgical intervention. In table 1 presents the comparative results of the effectiveness of methods of prevention and treatment of postoperative inflammatory complications.
Along with increasing titers of specific antibodies the use of the claimed scheme in the early postoperative period promoted the activation of nonspecific factors antibacterial defenses. A study of indicators of immunity 10-14 days after surgery revealed in comparison with the initial level of activation of the synthesis of them is noglobulin G and M (Ig G from 12.4±1.2 to of 14.25±1,4; Ig M 1.45±0.1-2.0±0.3 g/l), phagocytic index (PI from 46.8±3.4% to 56,37±4,2%); phagocytic number (FC from 3.8±0.4-5,14±0,34). Patients revealed no signs of dysbiosis on a background of antibacterial therapy that prevented the possibility of endogenous infection. The proposed scheme unlike the prototype had a broad antimicrobial spectrum against hospital flora (table 2). The best result was achieved in the group where the appointment of bactisporin inside combined with the local introduction of it into the cavity drained body (example 2). Colonization of catheters and drains by hospital strains did not lead to an acute inflammatory process in the kidney, and was manifested as asymptomatic bacteriuria. Local reactions to the vaccine did not exceed the permissible norms. Systemic pathological reactions in the application of the scheme have not been recorded.
As can be seen from the presented data (table 3) application schema, including vaccination, SPSA-vaccine, backspin, has significantly reduced the level of inflammatory complications in the postoperative period (9,4%) compared with patients receiving conventional treatment (46%), and a group of patients immunized before surgery (33%).
1. Briskin BS, Khachatryan N. Nosocomial infections and their prevention: in glad surgeon // CONSILIUM MEDICUM - 2002. - V. 4, No. 6. - S-311.
2. Stratchounski PS Status of antimicrobial resistance in Russia. The wedge. pharmacology and therapeutics. - 2000. - 9. No. 2. - P.6-9.
3. On The Main Page. Drugs in Russia: a Handbook. M: Attraversare, 2000 1504 S.
4. Pushkarev A. M. Etiotropic therapy of nosocomial urinary tract infections in the postoperative period polyvalent bacteriophages. Abstract. Diss. Kida. the honey. Sciences. - Ufa, 2000.
5. Madunice NV Vaccinology. - M., “Triada-X”, 1999, 272 S.
6. The sibagatullin N., Mikhailova N.A. Method of prevention of inflammatory complications accidental traumatic and surgical wounds // Patent RF №2193890, class a 61 K 39/116, 24.07.2000,
7. Cunagin O.V., Mikhailova N.A., Grabar, Y.M. and other Stafilo-proteaceae-Pseudomonas vaccine - a new drug for the prevention of purulent-septic diseases and complications // materials of the international. the Symposium. “The role of vaccines in modern medicine” - Ufa, 1995, - part 1. With 131-138.
8. Mikhailova N.A., Cunagin O.V., Grabar, Y.M. and other Method of obtaining the associated vaccine for the prevention of infections caused by opportunistic bacteria // Patent No. 2035189, class a 61 K 39/116, publ. 02.01.96, BI No. 14.
9. RF patent №2130316, class a 61 K 35/74, 20.05.1999,
10. Instructions for use of bactisporin dry. Approved 20.05.97.
11. Kudryavtsev V.A., Safronov L.A., Osadchaya AII other The effects of live cultures of Bacillus subtilis on nonspecific resistance of the organism // Microbiol. W. - 1996 - T.58. N2. - P.46-53.
12. Lopatin AS, MS (manuscript); Nikolaenko, VLADIMIR. and other Immunomodulatory effects of eubiotics in various types of pathological conditions involving dysbacteriosis. All-Russian scientific-practical conference dedicated to the 100th anniversary of the founding of mniam them. Hingamisega. Proc. Dokl. M, March 26-28, 1996. - P.21.
13. Smirnov V.V., Reznik S.R., Sorokulova IB, Kunicka VA Controversial issues of the creation and application of bacterial preparations for correction of microflora of warm-blooded // Microbiol. W. - 1992. - T, N 6. - S-92.
14. V.I. Nikitenko, Borodin A.V., M.V. Nikitenko Some new data on the mechanism of action of spore-forming probiotics /Topical questions of military and practical medicine. Sat. proceedings of the scientific-practical conference of physicians of the Volga military district. Orenburg, 2000 - http:esculapus.hl.ru.
Changes in the indices of non-specific mechanism of antibacterial protection 10-14 days of the postoperative period when different treatment regimens
|Protective factors||Initial level after surgery||Standard antibiotic regimen, n=26||+ immunization of SPSA-vaccine, n=12||+ immunization of SPSA-vaccine + .subtilis, n=32|
|IgG, M||oppression||does not activate||does not activate||normal|
|Phagocytosis||oppression||reduced||does not activate||normal|
Factors antibacterial protection under different regimens of hospital infections
|Factors antibacterial protection||Standard antibacterial scheme||+ immunization of SPSA-vaccine||+ immunization of SPSA-vaccine + .subtilis|
|Production of specific antibodies||+||+|
|Activation of phagocytic activity of leukocytes||+|
|The development of nonspecific humoral factors (IN the)||+|
|Elimination of dysbiosis||+|
|Note: + indicates a positive effect|
The frequency of inflammatory complications (miloc group) after emergency operations in the upper urinary tract
|The group of patients||The number of patients||The number of cases of miloc group|
|Comprehensive application of SPSA vaccines and .subtilis, including:||32||3||9,4|
|For example 1||10||1||10|
|For example 2||10||0||0|
|For example 3||10||2||20|
|In example 4||1||0||0|
|For example, 5||1||0||0|
1. A method for the treatment of postoperative inflammatory complications, including antibacterial therapy in combination with immunization stafilo-proteaceae-Pseudomonas adsorbed (SPSA) vaccine, characterized in that additionally used in probiotic drug, backspin that is administered per os 1-10·109microbial cells 2-3 times in 10-20 days, and/or used for instillation of the Russian Academy of Sciences, serous cavities, the cavities of organs of the urinary and biliary tract in the amount of 1-5·109microbial cells in isotonic sodium chloride.
2. The method according to claim 1, characterized in that SPSA the vaccine is administered parenterally at a dose of 0.5-1.0 ml single or double, or topically at a dose of 0.5 ml of mucous and serous membranes of internal organs and cavities.
FIELD: medicine, immunology, nucleic acids.
SUBSTANCE: invention relates to a method for stimulation of the immune response using nucleic acids-containing immunostimulating compositions, oligonucleotide-containing composition and to a method for treatment or prophylaxis of allergy or asthma. For stimulation of the immune response thymidine-enriched nucleic acid comprising poly-T sequences and/or comprising above 60% of thymidine-containing nucleotide residues is administrated. Invention provides the development of new method for stimulation of the immune response due to administration of the proposed immunostimulating nucleic acid.
EFFECT: valuable medicinal properties of nucleic acid.
27 cl, 12 dwg, 12 ex
FIELD: medicine, immunology.
SUBSTANCE: invention proposes an agent enhancing the immunogenic properties of tetanus anatoxin (adjuvant). Invention proposes the vegetable triterpenic compound miliacin as an agent enhancing immunogenic properties of tetanus anatoxin. Agent enhances the immune response value in its applying as a vaccine preparation of tetanus anatoxin. The agent miliacin elicits its stimulating effect for both the first and repeated administration of vaccine that allows suggesting its possible applying for prophylactic vaccinations with tetanus anatoxin. Taking into account the high tolerance of miliacin in the broad range of its doses it is suggested its practical applying as an agent promoting to the enhanced formation of vaccinal immunity in prophylactic vaccinations with tetanus anatoxin.
EFFECT: valuable medicinal properties of agent.
FIELD: biotechnology, medicinal microbiology.
SUBSTANCE: invention relates, in particular, to a method for preparing nutrient medium used for production of bacteriophages. Nutrient medium for production of bacteriophages contains acidic casein hydrolyzate as a base with hydrolysis degree 0.6-0.7 and vitamins: nicotinic acid, folic acid, calcium pantothenate, riboflavin, thiamine bromide and biotin, and distilled water. Also, invention relates to a method for preparing nutrient medium used for production of bacteriophages involving hydrolysis of natural casein mixed with water using hydrochloric acid under pressure 0.2 ± 0.05 MPa up to attainment of hydrolysis degree 0.6-0.7 being isoprecipitation and treatment with carbon are carried out simultaneously. Invention provide enhancing growth properties of medium and quality of bacteriophages produced and reducing the cost.
EFFECT: improved preparing method.
3 cl, 1 ex