Method of treatment of bacterial purulent meningitis in children

FIELD: medicine.

SUBSTANCE: during acute period of purulent meningitis (BPM) additionally, Wobenzyme is prescribed in daily dose 1 tablet per 6 kg of body weight 3 times a day within 10 days simultaneously with antibacterial therapy. Treatment of meningococcal and pneumococcal meningitis is ensured with prescribed benzylpenicillin in daily dosage 300 thousand units/kg. Haemophilic meningitis is treated by prescribed Ceftriaxone in daily dose 100 mg/kg.

EFFECT: higher efficiency of BPM specific therapy due to Wobenzyme ability to improve antibiotic penetration through blood-brain barrier and transport to inflammatory tissue and autointoxication reduction.

3 cl, 2 tbl, 4 ex

 

This invention relates to the field of medicine, more specifically to the CNS, and is intended for the treatment of children with purulent bacterial meningitis (HMD), and can be used in clinical practice.

HMD - acute bacterial polietiologic inflammation of the membranes of the brain, characterized by intoxication syndrome, meningeal syndrome, syndrome, encephalitis, inflammatory changes in the cerebrospinal fluid (CSF), and in complicated cases - by edema and brain swelling, and multiorgan failure. The urgency of the problem HMD in children due to mortality (25%), high incidence of complications (30%), the presence of residual neurological effects from 15-30%. The widespread prevalence of the tendency to increase of the frequency of prolonged and chronic and high frequency of lethal and incapacitating outcomes determine the urgency of the problem HMD in children.

Known methods of treatment HMD, including causal (antibiotics) and pathogenic (holding detoxification, dehydration therapy, the use of antihypoxants and nootropics) therapy. Etiotropic therapy aimed at eliminating direct etiological causes of the disease, the success of which depends on: the type of pathogen, the degree of permeability is hematoencephalic barrier (BBB) for drug dose of antibiotic, route of administration, etc. However, the use of different antibiotics in the maximum doses in the HMD in children leads to the development of dysbacteriosis, signs of toxic effects of the drug in 60% of patients, which lengthens the presence of the patient in the hospital (Lobzin J.V. Selected questions of the treatment of infectious patients / physicians Manual / St. Petersburg: Folio, 2005).

There are also known methods of treatment HMD using antibacterial products, aimed at the elimination of the pathogen, with different dosages (Meronem - 120 mg / kg body weight / day, rifampin 20 mg per kg of body weight a day, a course of 10 to 20 days each). The increase of antibiotic resistance in the last two decades, the emergence of protracted forms of HMD in children cause a 25% change etiotropic drugs during treatment HMD, and a 40% increase in the duration of antibiotic therapy, which leads to a longer stay of the patient in hospital and increased frequency of complications (Yakovlev V.P. Rational antimicrobial therapy. M: Littera, 2003).

Closest to the proposed method is the use of antibiotic therapy in combination with vascular and nootropic drugs, on the background of the prolonged infusion therapy (5-7 days), which helps reduce intoxicat and and duration of inflammation in the CSF, to improve the rheological properties of blood. From the funds etiotropic therapy is most often used are the following drugs: chloramphenicol dose of 70-100 mg per kg of body weight, benzylpenicillin in a daily dose of from 250 thousand to 500 thousand units unit rate from 10 to 20 days, Ceftriaxone at a daily dose of 50 to 200 mg rate from 10 to 20 days. However, this therapy does not need to change antibiotic in 25% of cases, leading to protracted course of the disease and the presence of dysbacteriosis in 90% of cases. The use of vascular and nootropic drugs prescribed in addition to antibacterial, admittedly non-specific, mediated by improving microcirculation, aiming at enhancing the action of the antibiotic, which does not contribute to reduction of treatment time and reduce side effects.

The technical result achieved by the invention is the reduction of treatment time, reducing the severity of disease, number of complications. This is achieved by improving the transport of antibiotic in the inflammation, reduce toxicity and side effects of antibiotics.

The invention consists in the achievement of the technical result in the treatment HMD in children through the use of penicillin and Ceftriaxone, and according to the SNO invention in the acute period, additionally, simultaneously with antibacterial therapy is prescribed Wobenzym orally in a daily dose of 1 tablet of the drug for 6 kg of body weight, 3 times a day for 10 days.

2. The method according to claim 1, characterized in that when meningococcal and pneumococcal meningitis appoint benzylpenicillin in a daily dose of 300 thousand units/kg per day.

3. The method according to claim 1, characterized in that when Haemophilus influenzae meningitis prescribe Ceftriaxone in a daily dose of 100 mg/kg per day.

Wobenzym - drug systemic enzyme therapy, increases the permeability of membranes. It is used as a booster therapy (therapy amplification) in children with infectious diseases of the upper respiratory tract, urogenital system. It is quite safe, compatible with traditional means of treatment of bacterial diseases. In the treatment of HMD in children have not been applied.

The authors first discovered the feasibility and efficacy of the simultaneous use of Wobenzym and antibiotics penicillin and Ceftriaxone with HMD. The authors found a dose and duration combined use of antibacterial drugs with systemic enzymes with HMD in children. Found that simultaneous administration of the two drugs promotes better penetration of antibacterial agents through the blood-brain barrier, which is, according to the authors, the Rheine needed given intrathecal localization of the inflammatory process. The authors showed not only the ability of Wobenzym to potentiate the action of antibacterial drugs in HMD, but also to contribute to the reduction of endogenous intoxication. This property was discovered in the study of substances of low and medium molecular weight (VNSM) plasma and red blood cells when HMD in children (table 1).

Groups of patients with different severity of inflammation of the brainThe number of patientsVNSM plasma ($)CRP (mg/l)
Acute3-5 day diseasesAcuteReconvalescent
Benzylpenicillin + Wobenzym2518,43±4,12x11,65±3,41°47,8±3,6x7,65±4,9°
Ceftriaxone + Wobenzym2417,64±5,63x10,34±2,65x54,6±5,6x4,3±3,6x
Penicillin2516,43±4,12x15,65±2,3344,8±3,6x8,65±6,9°
Ceftriaxone24 16,46±4,50x14,34±2,65x54,6±5,6x10,3±2,6x
Control108,65±3,41°*8,65±3,41°5,6±3,40x7,6±4,4°
x - the difference is significant compared to the control
° - the difference is significant compared to the comparison group
* - the difference is significant compared with the group of antibiotic + Wobenzym

The authors have developed dose, duration, and frequency assignment of Wobenzym with HMD in children. The authors proved that Wobenzym reduces the severity of side effects etiotropic drugs reduces their toxicity that can significantly improve outcomes, reduce the duration of a patient's hospitalization (table 2).

The group of patientsThe number of patientsThe degree of pleocytosis (×106/l)The duration of symptoms of
HeadacheMeningeal syndromeFeverFocal symptomsDysbacteriosisBed-days
benzilpenicillin + Wobenzym 2510000±3201,4±0,6°2,3±0,6°2,9±1,8°0,4±0,2°10,3±1,9°
Ceftriaxone + Wobenzym2411200±2402,1±0,2°3,3±1,62°3,2±0,62°1,7±0,7°2,2±0,6°13,4±3,4°
Penicillin1012300±3403,9±0,9*4±1,82*3,8±0,93,4±1,2*3,9±2,2*13,8±4,6*
Ceftriaxone2414000±3605,1±0,9*3,9±1,6*4,9±0,6*2,7±0,7*5,4±3,3*15,2±2,8*
° - the difference is significant compared with group antibiotic
*- the difference is significant compared with the group of antibiotic + Wobenzym

The authors first got the positive result of the appointment of Wobenzym in protracted (long readjustment CSF) flow types HMD, when the background neodeck atoi change of antibiotic therapy was negative clinical and laboratory dynamics. The use of Wobenzym helped to achieve a positive effect, without resorting to the intrathecal injection of antibiotic. The positive effect and no complications were allowed to use Wobenzym as drug pathogenetic therapy in combination with etiotropic drugs (example 4).

The authors proved that the combination therapy with exhaust dosage provides the effect, which leads to better outcomes in HMD. In the available literature such treatments HMD is not described. The choice and dosage of antimicrobial drugs based on our monitoring of antibiotic susceptibility with regard to the least side effects. It should be noted that 95% of bacterial purulent meningitis in children are caused by meningococcus, pneumococcus and Haemophilus influenzae, the most effective drug in the treatment of meningococcal and pneumococcal meningitis is penicillin at a dose of 300 thousand units per kg of body weight per day, according to our records this dose is effective, does not produce toxic effects, sufficient for illumination of the pathogen. Ceftriaxone - antibiotic from the group of cephalosporins of the third generation, highly effective against Haemophilus influenzae Bacillus, and in a dose of 100 mg per kg of body weight per day, as shown by the ASHI research is effective with a proven dosage.

The method is as follows: when entering a patient with HMD, after conducting infusion therapy, meningococcal and pneumococcal HMD in addition to the purpose of benzylpenicillin in a daily dose of 300 thousand units/kg / day in the acute period of the disease is for oral administration Wobenzym in a daily dose of 1 tablet of the drug for 6 kg of body weight, 3 times a day for 10 days, with Haemophilus HMD in addition to the purpose of Ceftriaxone in a daily dose of 100 mg/kg / day appointed Wobenzym in a daily dose of 1 tablet of the drug for 6 kg of body weight, 3 times a day for 10 days. The diagnosis was confirmed by examination of the cerebrospinal fluid with the release of the pathogen or antigen.

A method of treating HMD passed clinical trials in the treatment of 25 children aged from 2 years to 17 years in the clinic of the CNS NEEDY. Of these 20 children (80 per cent) was established meningococcal etiology of the disease, 2 patients (8%) - selected pneumoniae, have 3 children (12%) - Haemophilus influenzae. Depending on the duration of the slew of neurological symptoms all patients were divided into groups. All patients in this group received therapy according to the claimed method.

The comparison group consisted of 24 children who received standard etiotropic terap the Y. The comparison group was matched by sex, age and nature of the disease. All patients underwent clinical and laboratory monitoring for monitoring and follow-up within 1 year. In the result, it was found that the use proposed by the authors of this method of treatment has allowed to improve outcomes and reduce length of stay in hospital (15%) patients of the first group in the clinic, as well as to reduce the frequency of residual deficit (20%), dysbiotic disorders (60% of cases). As in the main group and the comparison group were observed moderate for HMD, but in the main group of children duration of antibiotic therapy was 7.4±2,8, and in the comparison group significantly longer and amounted to 10.1±6.2 percent. If the main group of the need to use broad-spectrum antibiotics was observed only in one patient in the comparison group the need for change of antibiotic occurred in 22% of cases. The effectiveness of this treatment method can be confirmed by the following examples.

Example 1. Patient D., aged 13. Case history No. 1478, a diagnosis of generalized form of meningococcal infection, meningococcemia, purulent meningitis. Ill acutely, there was a sharp rise of temperature up to 39.5 degrees, headache, appeared hemorrhagic rash. Hospitalized in NEEDY in PE is the first day of the disease. When entering a serious condition. In the neurological examination - moderate severity meningeal symptoms (stiff neck (++), symptom, Cernica (+),) focal neurological symptoms in the form of the asymmetry of the eye slits. Analysis of cerebrospinal fluid (CSF) lymphocytosis 4398×106/l, total protein and 0.46 g/l Data quantitative research content VNSM (substances of low and medium molecular weight) plasma - 26,23 conventional units (cu). C-reactive protein (CRP) - 54 mg/l, which corresponds to a pronounced degree of endogenous intoxication and inflammation. The first day the child was in the intensive care unit. Immediately after receiving the child received benzylpenicillin dose of 300 thousand per kg of body weight 6 times a day and Wobenzym at the rate of 1 tablet per 6 kg of body weight three times a day. On the background of therapy condition has improved, meningeal syndrome were stopped on the third day. Repeated lumbar puncture performed on the 6th day: protein - 0.3 g/l, lymphocytosis - 18×106/l VNSM - $ 8, CRP - 3 mg/l, which corresponds to almost the normal level of endogenous intoxication, no signs of inflammation. Thus, in this case, the background of therapy was observed favorable course of the disease, the child was discharged on the 8th day without complications, having increased the I-dose antibiotic or drug use broad-spectrum was not.

Example 2. Patient L., 4 years 7 months. Case history No. 4832, diagnosed with generalized form of Haemophilus influenzae infection, purulent meningitis. Ill acutely, fever up to 39 degrees, 9 times vomiting, anxiety, tremors, on the left hip appeared hemorrhagic rash. Hospitalized in NEEDY in the first days of the disease. When entering a serious condition, consciousness at the level of the spoor. Focal neurological symptoms absent, marked meningeal symptoms: stiff neck (+++), a symptom of Cernica (+++). In the analysis of CSF: lymphocytosis - 5547×106/l, protein - 2,13 g/l Content VNSM plasma - $ 25,46, CRH - 48 mg/l, which corresponds to a pronounced degree of endogenous intoxication and inflammation. The patient received Ceftriaxone at a dose of 100 thousand per kg 4 times a day, in addition to etiotropic therapy was added Wobenzym in the dose of 1 tablet per 6 kg mass. The time spent in the intensive care unit for 24 hours. Studies in the dynamics (10 day) showed positive shifts in the composition of the liquor: lymphocytosis - 24×106/l, protein - 0,44 g/l, VNSM - 9,45$, CRP - 5 mg/L. Meningeal syndrome were stopped on the third day. The patient was discharged without residual effects. Thus, on the background of therapy has been a rapid regression of neurological symptoms and normalization of laboratory data. Balnaves without complications on the 9th day of illness.

Example 3. Patient C., 1 year. Case history No. 1242, diagnosed with generalized form of meningococcal infection, purulent meningitis. Enrolled in the intensive care unit of NEEDY in the first days of the disease. Ill acutely, there was an increase of body temperature up to 38 degrees, three times vomiting. When entering a serious condition: consciousness is not impaired, expressed meningeal symptoms, focal symptoms are not identified. The study CSF: lymphocytosis - 3386×106/l, total protein - 1,94 g/l, VNSM - $ 16,23, SLO - 36 mg/l, which corresponds to a pronounced degree of endogenous intoxication and inflammation. Etiotropic treatment included the appointment of benzylpenicillin dose of 300 thousand per kg per day. However, on the background of therapy remained meningeal symptoms, the child continued fever, on the 7th day from diseases produced by lumbar puncture: lymphocytosis - 2674×106/l, total protein - 1,03 g/l, VNSM plasma -18,32 c.u., SLO - 28 mg/l was changed antibacterial therapy rifampicin at a dose of 20 mg/kg. the Child was discharged at 38 days after the onset of the disease with severe asthenia, fronto-cerebellar ataxia.

Example 4. Patient C., 1 year 1 month. Case history No. 1368, a diagnosis of generalized form of meningococcal infection, purulent meningitis. He entered NEEDY on the second day of the disease. Ill acutely, promoted the eating of body temperature up to 40 degrees, was once vomiting, drowsiness. When entering a serious condition: consciousness is not impaired, expressed meningeal symptoms, focal symptoms were not. The study CSF: lymphocytosis - 4531×106/l, total protein - 0.84 g/l, VNSM - $ 18,23, SLO - 48 mg/l, which corresponds to a pronounced degree of endogenous intoxication and inflammation. The drug of choice was benzylpenicillin dose of 300 thousand per kg per day. The patient was conducted infusion therapy. On the background of therapy was noted positive dynamics of clinical symptoms, but the patient with 13 days of hospital stay was trouble appeared frequent liquid stool, on the 13th day from diseases produced by lumbar puncture: lymphocytosis - 3629×106/l, total protein 0.9 g/l, VNSM plasma - $ 18,32, SLO - 64 mg/l was changed antibacterial therapy first darifenacin at a dose of 20 mg/kg, positive dynamics was not received, then numeronym at a dose of 120 mg per kg of body weight per day. The state has remained severe, the child continued fever. In therapy with 25 days of hospital stay in addition to the antibiotic was appointed Wobenzym, at a dose of 1 tablet per 6 kg of body weight per day, the child has no fever for 3 days from receiving the drug. Duration of use of Wobenzym was 10 days. During the control study CSF was noted but militaria cellular and protein composition. The child was discharged without complications.

Thanks to the use proposed by the authors of complex therapy HMD children were able to improve the outcomes of the disease, significantly increasing the percentage of children fully recovered without neurological abnormalities, to reduce the duration of hospital stay due to a more rapid reorganization of the liquor. This method can find a wide primeneniia in clinical practice in the treatment of children with severe generalized bacterial infection. Using this technique will strengthen the action of antibacterial drugs without frequent change of antibiotic without increasing the dosage.

1. A method of treatment of purulent bacterial meningitis in children, including the use of penicillin and Ceftriaxone, characterized in that in the acute period advanced, simultaneously with antibacterial therapy is prescribed Wobenzym in a daily dose of 1 tablet of the drug for 6 kg of body weight 3 times a day for 10 days.

2. The method according to claim 1, characterized in that when meningococcal and pneumococcal meningitis appoint benzylpenicillin in a daily dose of 300 production/kg per day.

3. The method according to claim 1, characterized in that when Haemophilus influenzae meningitis prescribe Ceftriaxone in a daily dose of 100 mg/kg per day.



 

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37 cl, 2 ex, 11 tbl

FIELD: medicine, urology.

SUBSTANCE: susceptibility of pathogenic organism to antiprotozoan drugs is determined. At the preliminary stage sporobacterin, sulodexide, methadoxil, and vobenzyme are injected; the prostate is affected by ultrasound exposure. After that at the etiotropic treatment stage, the blood is taken and separated in plasma, erythrocyte suspension, and leukocyte suspension fractions by sequential centrifuging at 800 rpm and 1800 rpm speed and temperature +4°C. The plasma is eliminated and replaced by crystalloid solution. The erythrocyte suspension is injected intravenously to the patient. The leukocyte suspension, with 0.5 ml ATP added, is affected by semiconductor laser radiation exposure at λ=0.70 mcm, then 0.75 g of metronidazol in solution is added and, after incubation at +37°C, injected to the patient. Simultaneously nifuratel is administered perorally in 200 mg dose twice a day. The procedure is repeated during 8 days. At the rehabilitation therapy stage during 10 days trilact is administered by 2 doses twice a day, as well as polyvitamin mix "Alpha-Vit". The method provides directed metronidazol transport into infection focuses, activates autoblood cells metabolism and phagocytic, adhesive, and migration leukocyte activities, stimulates resorption of fibrotic degenerated chronic inflammation niduses in urino-genital tract, decreases manifestation of side effects.

EFFECT: increase in treatment effectiveness.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, surgery, and can be used for X-ray diagnostics of esophagus perforations. For this purpose X-ray contrast composition is introduced. X-ray contrast composition contains water-soluble iodinated contrast and water solution of antiseptic or antibiotic of wide spectrum action in standard dilution with ratio 1:1. Carrying out such diagnostics allows to achieve the most full contrasting of perforation opening and leaks in cellular tissue of mediastenum, and at the same time sanitise pyoinflammatory nidus of perforated esophagus, eliminating source of development of acute mediastenitis, and stop pain syndrome without additional use of analgetics.

EFFECT: ensuring possibility of sanitising pyoinflammatory nidus of perforated esophagus, eliminating source of development of acute mediastenitis, and stopping pain syndrome without additional use of analgetics.

1 ex

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