RU2348406C1 - Method of treatment of bacterial purulent meningitis in children - Google Patents

Abstract

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

Description

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

BGM is an acute bacterial polyetiological inflammation of the membranes of the brain, characterized by intoxication syndrome, meningeal syndrome, encephalitis syndrome, inflammatory changes in cerebrospinal fluid (CSF), and in complicated cases, by edema and swelling of the brain and multiple organ failure. The urgency of the problem of BGM in children is due to mortality (up to 25%), a high incidence of complications (30%), and the presence of residual neurological consequences in 15-30%. The widespread prevalence, the tendency to increase the frequency of prolonged and chronic course, and the high frequency of lethal and disabling outcomes determine the relevance of the problem of BGM in children.

Known methods of treating BGM, including etiotropic (prescribing antibiotics) and pathogenetic (detoxification, dehydration therapy, the use of antihypoxants and nootropics) therapy. Etiotropic therapy is aimed at eliminating the immediate etiological cause of the disease, the success of which depends on: the type of pathogen, the degree of permeability of the blood-brain barrier (BBB) for the drug, the dose of the antibiotic, route of administration, etc. However, the use of various antibiotics at maximum doses for children with hypertension in children inevitably leads to the development of dysbiotic disorders, the appearance of signs of toxic effects of the drug in 60% of patients, which lengthens the patient's stay in the hospital (Lobzin Yu.V. Selected issues of treatment of infectious patients / Guide for doctors / - St. Petersburg: Tome, 2005).

There are also known methods of treating BGM using antibacterial drugs aimed at eliminating the pathogen, with various dosages (Meronem - 120 mg per kg of body weight per day, rifampicin - 20 mg per kg of body weight per day, course from 10 to 20 days each). An increase in antibiotic resistance in the last two decades, the emergence of protracted forms of BGM in children cause a 25% change in etiotropic drugs during treatment of BGM, and in 40% of cases, an increase in the duration of the course of antibiotic therapy, which leads to a longer stay of the patient in the hospital and an increase in the frequency of complications (Yakovlev V.P. Rational Antimicrobial Therapy (Moscow: Litterra, 2003).

Closest to the proposed method is the use of antibiotic therapy in combination with vascular and nootropic drugs, against the background of prolonged infusion therapy (5-7 days), which helps to reduce intoxication and the duration of inflammation in CSF, improve the rheological properties of blood. The following drugs are most often used from the means of etiotropic therapy: chloramphenicol at a dose of 70-100 mg per kg of body weight, benzylpenicillin in a daily dose of 250 thousand units. up to 500 thousand units in a course of 10 to 20 days, ceftriaxone in a daily dose of 50 to 200 mg in a course of 10 to 20 days. However, such therapy does not avoid the need to change the antibacterial drug in 25% of cases, which leads to a protracted course of the disease and the presence of dysbiotic disorders in 90% of cases. The use of vascular and nootropic drugs prescribed in addition to antibacterial drugs should be recognized as nonspecific, mediated by improved microcirculation, not aimed at enhancing the effect of the antibiotic, which does not help to reduce treatment time and reduce side effects.

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

The essence of the invention is to achieve the specified technical result in a method of treating BGM in children by using benzylpenicillin and ceftriaxone, and according to the invention in the acute period, additionally, simultaneously with antibiotic therapy, wobenzym is administered orally in a daily dose of 1 tablet of the drug per 6 kg of body weight, 3 times per day for 10 days.

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

3. The method according to claim 1, characterized in that with hemophilic meningitis, ceftriaxone is prescribed in a daily dose of 100 mg / kg per day.

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

The authors first discovered the feasibility and effectiveness of the simultaneous use of wobenzym and antibacterial drugs benzylpenicillin and ceftriaxone in hypertension. The authors established the doses and duration of the combined use of antibacterial drugs with systemic enzymes in children with hypertension. It was established that the simultaneous administration of two drugs contributes to better penetration of antibacterial agents through the blood-brain barrier, which, according to the authors, is extremely necessary, given the intrathecal localization of the inflammatory process. The authors showed not only the ability of Wobenzym to potentiate the effects of antibacterial drugs in hypertension, but also to reduce endogenous intoxication. This property was found in the study of substances of low and medium molecular weight (VNSSM) plasma and red blood cells in patients with BHM (table 1).

Groups of patients with varying severity of brain inflammation Number of patients VNSSM plasma (c.u.) CRP (mg / L) Acute period 3-5 days of illness Acute period Reconvalescence Benzylpenicillin + Wobenzym 25 18.43 ± 4.12 ^x 11.65 ± 3.41 ° 47.8 ± 3.6 ^x 7.65 ± 4.9 ° Ceftriaxone + Wobenzym 24 17.64 ± 5.63 ^x 10.34 ± 2.65 ^x 54.6 ± 5.6 ^x 4.3 ± 3.6 ^x Benzylpenicillin 25 16.43 ± 4.12 ^x 15.65 ± 2.33 44.8 ± 3.6 ^x 8.65 ± 6.9 ° Ceftriaxone 24 16.46 ± 4.50 ^x 14.34 ± 2.65 ^x 54.6 ± 5.6 ^x 10.3 ± 2.6 ^x The control 10 8.65 ± 3.41 ° ^* 8.65 ± 3.41 ° 5.6 ± 3.40 ^x 7.6 ± 4.4 ° x - differences are significant compared with the control ° - the differences are significant compared with the comparison group * - the differences are significant compared with the antibiotic + wobenzym group

The authors developed the dose, duration and frequency of administration of Wobenzym in case of BGM in children. The authors proved that wobenzym reduces the severity of side effects of etiotropic drugs, reduces their toxicity, which can significantly improve the outcome of the disease, reduce the length of the patient in the hospital (table 2).

Patient groups Number of patients The degree of pleocytosis (× 10 ⁶ / l) Symptom Duration Headache Meningeal syndrome Fever Focal symptoms Dysbacteriosis Bed days Benzylpenicillin + Wobenzym 25 10000 ± 320 1.4 ± 0.6 ° 2.3 ± 0.6 ° 2.9 ± 1.8 ° 0 ° 0.4 ± 0.2 ° 10.3 ± 1.9 ° Ceftriaxone + Wobenzym 24 11200 ± 240 2.1 ± 0.2 ° 3.3 ± 1.62 ° 3.2 ± 0.62 ° 1.7 ± 0.7 ° 2.2 ± 0.6 ° 13.4 ± 3.4 ° Benzylpenicillin 10 12300 ± 340 3.9 ± 0.9 ^* 4 ± 1.82 ^* 3.8 ± 0.9 3.4 ± 1.2 ^* 3.9 ± 2.2 ^* 13.8 ± 4.6 ^* Ceftriaxone 24 14000 ± 360 5.1 ± 0.9 ^* 3.9 ± 1.6 ^* 4.9 ± 0.6 ^* 2.7 ± 0.7 ^* 5.4 ± 3.3 ^* 15.2 ± 2.8 ^* ° - the differences are significant compared with the antibiotic group ^* - the differences are significant compared with the antibiotic + wobenzym group

The authors for the first time obtained a positive result of the administration of Wobenzym in the protracted (with prolonged rehabilitation of the cerebrospinal fluid) types of BGM course, when negative clinical and laboratory dynamics were noted against the background of repeated changes in antibiotic therapy. The use of wobenzym allowed to achieve a positive effect without resorting to intrathecal administration of an antibiotic. The resulting positive effect and the absence of complications allowed the use of wobenzym as a drug of pathogenetic therapy in combination with etiotropic drugs (example 4).

The authors proved that such a combination of ongoing therapy with established dosages provides the effect that leads to the best outcomes for HDM. In the literature available to us, such methods for treating BGM are not described. The choice and dosage of antibacterial drugs is based on our monitoring of antibiotic sensitivity, taking into account the least pronounced side effects. It should be noted that 95% of bacterial purulent meningitis in children is caused by meningococcus, pneumococcus and haemophilus influenzae, the most effective drug in the treatment of meningococcal and pneumococcal meningitis is 300 thousand units of benzylpenicillin. per kg of body weight per day, according to our data, such a dose of the drug is effective, does not give a toxic effect, is sufficient to illuminate the pathogen. Ceftriaxone is an antibacterial drug from the group of third generation cephalosporins, highly effective against hemophilic bacillus and at a dose of 100 mg per kg of body weight per day, as shown by our studies, is effective with the used dosage.

The method is as follows: upon admission of a patient with BGM, after carrying out infusion therapy, with meningococcal and pneumococcal BGM, in addition to the appointment of benzylpenicillin in a daily dose of 300 thousand units / kg per day in the acute period of the disease, orally administered wobenzym in a daily dose of 1 tablet of the drug per 6 kg of body weight, 3 times a day for 10 days, with hemophilic BGM, in addition to the appointment of ceftriaxone in a daily dose of 100 mg / kg per day, Wobenzym is prescribed in a daily dose of 1 tablet per 6 kg of weight body, 3 times a day for 10 days. The diagnosis was confirmed by examination of cerebrospinal fluid with the release of the pathogen or its antigen.

The developed method for the treatment of hypertension has been clinically tested in the treatment of 25 children aged 2 years to 17 years in the clinic of neuroinfection NIIDI. Of these, 20 children (80%) had a meningococcal etiology of the disease, pneumococcus was isolated in 2 patients (8%), and hemophilic bacillus in 3 children (12%). Depending on the duration of the increase in 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 therapy. The comparison group was comparable by sex, age and nature of the disease. All patients underwent clinical and laboratory monitoring and follow-up for 1 year. As a result, it was found that the use of the treatment method proposed by the authors made it possible to improve outcomes and reduce the length of hospital stay (by 15%) of patients of the first group in the clinic, as well as reduce the frequency of residual deficiency (by 20%), dysbiotic disorders (in 60% cases). Both in the main group and in the comparison group, a moderate course of HMF was observed, however, in the main group of children, the duration of antibiotic therapy was 7.4 ± 2.8, and in the comparison group it was significantly longer and amounted to 10.1 ± 6.2%. Moreover, if in the main group the need for the use of broad-spectrum antibiotics was noted in only one patient, in the comparison group the need to change the antibiotic arose in 22% of cases. The effectiveness of this treatment method can be confirmed by the following examples.

Example 1. Patient D., 13 years old. Case history No. 1478, the diagnosis is a generalized form of meningococcal infection, meningococcemia, purulent meningitis. He became acutely ill, there was a sharp rise in temperature to 39.5 degrees, a headache, a hemorrhagic rash appeared. Hospitalized in NIIDI on the first day of the disease. Upon receipt, the condition is serious. At a neurological examination - moderate severity of shell symptoms (stiff neck (++), Kernig symptom (+),) focal neurological symptoms in the form of asymmetry of the palpebral fissures. Analysis of cerebrospinal fluid (CSF) - cytosis 4398 × 10 ⁶ / l, total protein 0.46 g / l. The data of a quantitative study of the content of VNSSMM (low and medium molecular weight substances) in plasma is 26.23 conventional units (cu). The level of C-reactive protein (CRP) is 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 admission, the child received benzylpenicillin at a 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. Against the background of the therapy, the condition improved, the shell syndrome stopped on the third day. Repeated lumbar puncture was performed on the 6th day: protein - 0.3 g / l, cytosis - 18 × 10 ⁶ / l, VNSMM - 8 c.u., CRP - 3 mg / l, which corresponds to an almost normal level of endogenous intoxication, absence signs of an inflammatory process. Thus, in this case, against the background of the therapy, a favorable course of the disease was noted, the child was discharged on the 8th day without complications, there was no need to increase the dose of the antibiotic or to use broad-spectrum drugs.

Example 2. Patient L., 4 years 7 months. Case history No. 4832, the diagnosis is a generalized form of hemophilic infection, purulent meningitis. He fell ill acutely, fever up to 39 degrees, 9 times vomiting, restlessness, trembling, a hemorrhagic rash appeared on his left thigh. Hospitalized in NIIDI on the first day of the disease. Upon admission, the condition is serious, consciousness at the level of stupor. Focal neurological symptoms are absent, pronounced shell symptoms are noted: stiff neck (+++), Kernig symptom (+++). In the analysis of CSF: cytosis - 5547 × 10 ⁶ / l, protein - 2.13 g / l. The content of VNSSM plasma is 25.46 cu, the CRH is 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, wobenzym was added at a dose of 1 tablet per 6 kg of weight. The time spent in the intensive care unit is 24 hours. Studies in dynamics (on the 10th day) revealed positive changes in the composition of the cerebrospinal fluid: cytosis - 24 × 10 ⁶ / l, protein - 0.44 g / l, VNSMM - 9.45 cu, CRP - 5 mg / l. Shell syndrome stopped on the third day. The patient was discharged without residual consequences. Thus, against the background of the therapy, there was a rapid regression of neurological symptoms and normalization of laboratory data. The patient was discharged without complications on the 9th day of illness.

Example 3. Patient S., 1 year. Case history No. 1242, the diagnosis is a generalized form of meningococcal infection, purulent meningitis. He entered the intensive care unit of NIIDI on the first day of the disease. He fell ill acutely, there was an increase in body temperature up to 38 degrees, three times vomiting. Upon admission, the condition is serious: consciousness is not impaired, pronounced shell symptoms, focal symptoms not identified. CSF study: cytosis - 3386 × 10 ⁶ / l, total protein - 1.94 g / l, VNSSM - 16.23 cu, CRP - 36 mg / l, which corresponds to a pronounced degree of endogenous intoxication and inflammation. Etiotropic treatment included the appointment of benzylpenicillin at a dose of 300 thousand per kg per day. However, during the course of the therapy, she continued to have symptomatic symptoms, the child continued to have a fever, lumbar puncture was performed on the 7th day of the disease: cytosis - 2674 × 10 ⁶ / l, total protein - 1.03 g / l, VNSMM -18.32 cu ., CRP - 28 mg / l. A change in antibiotic therapy to rifampicin at a dose of 20 mg / kg was made. The child was discharged on the 38th day after the onset of the disease with severe asthenic syndrome, fronto-cerebellar ataxia.

Example 4. Patient C., 1 year 1 month. Case history No. 1368, the diagnosis is a generalized form of meningococcal infection, purulent meningitis. He entered NIIDI on the second day of the disease. He became acutely ill, with an increase in body temperature up to 40 degrees, there was a single vomiting, drowsiness. Upon admission, the condition is serious: consciousness is not impaired, expressed shell symptoms, there were no focal symptoms. CSF study: cytosis - 4531 × 10 ⁶ / l, total protein - 0.84 g / l, VNSSM - 18.23 cu, CRP - 48 mg / l, which corresponds to a pronounced degree of endogenous intoxication and inflammation. The drug of choice was benzylpenicillin at a dose of 300 thousand per kg per day. The patient was given infusion therapy. Against the background of the therapy, there was a positive dynamics of clinical symptoms, but the patient began to have a fever from 13 days in the hospital, frequent loose stools appeared, lumbar puncture was performed on the 13th day of the disease: cytosis - 3629 × 10 ⁶ / l, total protein - 0.9 g / l, VNSSM plasma - 18.32 cu, CRP - 64 mg / l. Antibacterial therapy was changed first to narifampicin at a dose of 20 mg / kg, no positive dynamics were obtained, then - we intend to use it at a dose of 120 mg per kg of body weight per day. The condition remained consistently severe, the child continued to have a fever. In addition to the antibiotic, Wobenzym was prescribed in therapy from the 25th day of hospitalization, at a dose of 1 tablet per 6 kg of body weight per day, the child stopped fever for 3 days from taking the drug. The duration of the use of Wobenzym was 10 days. In the control study of CSF normalization of the cellular and protein composition was noted. The child was discharged without complications.

Thanks to the use of the complex therapy of BGM proposed by the authors in children, it was possible to improve the outcome of the disease, significantly increasing the percentage of children who recovered completely without neurological abnormalities, to reduce the length of hospital stay due to faster rehabilitation of the cerebrospinal fluid. This method can be widely used in clinical practice in the treatment of children with severe generalized bacterial infection. The use of this method will enhance the effect of antibacterial drugs without resorting to a frequent change in antibiotic without increasing the dosage.

Claims (3)

1. A method of treating bacterial purulent meningitis in children, including the use of benzylpenicillin and ceftriaxone, characterized in that in the acute period, additionally, simultaneously with antibiotic therapy, Wobenzym is prescribed in a daily dose of 1 tablet per 6 kg of body weight 3 times a day for 10 days . 2. The method according to claim 1, characterized in that with meningococcal and pneumococcal meningitis, benzylpenicillin is prescribed in a daily dose of 300 thousand units / kg per day. 3. The method according to claim 1, characterized in that with hemophilic meningitis, ceftriaxone is prescribed in a daily dose of 100 mg / kg per day.