[Burkholderia cepacia persistence in patients with mucoviscidosis].

AIM: Study features of persistence of Burkholderia cepacia in mucoviscidosis patients. MATERIALS AND METHODS: In the period from 2008 to 2009, 56 B. cepacia strains isolated from children with mucoviscidosis were obtained. 114 medical histories of children with mucoviscidosis from various age groups were analyzed. The developed algorithm for identification and typing including phenotype and molecular biology methods was used to identify B. cepacia bacteria. Strain genotyping was carried out by RAPD-PCR with random oligonucleotide primer as well as pulse-electrophoresis. RESULTS: Persistence of associations ofmicroogranisms in 59.4% of cases was established to be the feature of persistent infection in mucoviscidosis. The feature of persistence of B. cepacia strains in patients with diagnosis ofmuco-viscidosis mixed form, severe course is persistence in association with Pseudomonas aeruginosa. B. cepacia bacteria that can persist in mucoviscidosis patients are characterized by resistance to many antibiotics. A prolonged (up to 1 year and 5 months) persistence of B. cepacia strains isolated from 1 patient was proven by using microflora monitoring of lower respiratory tract. CONCLUSION: B. cepacia bacteria may colonize lower respiratory tract of mucoviscidosis patients, persist for a long time and be transmitted between patients.

[Microbial population of lower respiratory tract in children from different age groups with cystic fibrosis].

AIM: To study microflora of lower respiratory tract of children from different age groups with cystic fibrosis during follow-up for determination of its variability and possible sources of infectious complications. MATERIALS AND METHODS: One hundred forty-one medical histories of patients from different age groups with cystic fibrosis living in various regions of Russian Federation were analyzed. Eighty-four children with cystic fibrosis living in Moscow and Moscow region treated as outpatients and inpatients were prospectively followed. For identification and characterization of microorganisms, microbiological, molecular biological, and statistical methods were used. RESULTS: It was demonstrated that chronic pseudomonas, staphylococcal or mixed infection was already diagnosed in 25% of children aged 1-4 years, and identified in 80% of patients to the age of 18 years. In two-thirds of cases association of microorganisms was identified, and in hospitalized patients these associations were comprised by 3-5 microorganisms in 60% of cases. Aside from main agents in associations (Pseudomonas aeruginosa and Staphylococcus aureus), representatives of Gram-negative nonfermentative microorganisms (Burkholderia cepacia, Stenotrophomonas maltophilia, Acinetobacter baumanii) were often identified that possibly determined by tropism of these species to lung tissue. CONCLUSION: Chronic mixed infection is characteristic for patients with cystic fibrosis. Identification of possible mechanisms of lung infection in patients with cystic fibrosis will allow to develop evidence-based system of prevention of infectious complications in these patients.

[Clinical and bacteriological efficacy and tolerability of meropenem in the treatment of bronchopulmonary affections in children with mucoviscidosis].

Meropenem (in combination with amikacin) was used in the treatment of children and adolescents with mucoviscidosis and severe exacerbation of bronchopulmonary affections. The drug showed satisfactory clinical and moderate bacteriological effects (48.3%) as dependent on the severity and duration of the disease and the microbial flora. Meropenem was well tolerated: no side effects were observed during the treatment, whereas it was used in high doses (60-105 mg/kg daily).

[Efficacy and safety of cefepime in the treatment of bronchopulmonary disease exacerbation in pediatric patients with mucoviscidosis].

Clinicobacteriological effect of cefepime (in combination with amikacin) was studies in 25 pediatric patients of the age of 7 to 17 years with a mixed form of mucoviscidosis at the stage of the bronchopulmonary infection exacerbation. The basic pathogens isolated from the sputum were: Pseudomonas aeruginosa sm., P. aeruginosa muc. (67.5%) and Staphylococcus aureus (29.1%). The 2-week treatment course resulted in a marked clinical effect with improvement of the lung functional indices and eradication of the majority of the S. aureus strains (81.2%) and half of the P. aeruginosa strains (49.6%). The only side effect was moderate diarrhea not requiring discontinuation of the drug use.

[Efficacy and safety of cefoperazone/sulbactam in the treatment of children with mucoviscidosis during exacerbation of the bronchopulmonary process]. / Effektivnost' i bezopasnost' tsefoperazona/sul'baktama pri lechenii obostrenii bronkholegochnogo protsessa u detei s mukovistsidozom.

The use of cefoperazone/sulbactam in combination with amikacin in the treatment of 20 patients with mucoviscidosis and exacerbation of bronchopulmonary pathological process resulted in marked positive dynamics of the clinical and functional indices of the lungs state. The bacteriological effect with respect to the main pathogens in the cases of mucoviscidosis was strain-dependent: eradication of 10 (83.4%) out of 12 Staphylococcus aureus strains and only 3 (15.8%) out of 19 Pseudomonas aeruginosa strains. The most frequent adverse reaction was diarrhea (5 children) successfully corrigated by loperamide. Discontinuation of the drug use was required in 3 patients because of macrohematuria (1 child) and allergic eruption.

[Pefloxacin in the treatment of patients with mucoviscidosis]. / Mesto pefloksatsina v lechenii bol'nykh mukovistsidozom.

It was shown that microbial flora isolated from the bronchial secretion of 39 patients with mucoviscidosis in 1999-2001 consisted in one third (32.8%) of S. aureus strains. Evaluation of pefloxacin efficacy in the case of monoinfection and pathogens association revealed potent antistaphylococcal effect of the drug. Positive result was demonstrated in 82.3% cases by the 7th day. Among the side effects dominated arthropathy which disappeared at the period from 3 days to 3 months after drug administration was stopped.

[On fluoroquinolones treatment safety in children (clinical, morphological and catamnesis data)]. / O bezopasnosti primeneniia ftorkhinolonov u detei (kliniko-morfologicheskie i katamnesticheskie dannye).

Results of prospective comparative investigation of monofluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin) arthropathy are presented. The trial was performed at 144 children with mucoviscidosis (aged 0.5-16) and at 37 children with aplastic anemia (aged 1.75-15). Two groups differ by necessary antibacterials regimes and hence by different abilities for arthropathy development: patients with mucoviscidosis were treated with fluoroquinolones followed by repeated short courses in combination with other antibacterials; patients with aplastic anemia--were treated permanently for a long time with low doses as monotherapy for autoinfection prophylaxis. Analysis was performed on the base of catamnesis, year growth rate, postmortal morphological investigation of the right knee joint. It was shown that quinolone arthropathy development didn't depend on treatment duration, as it developed during the first three weeks of the fluoroquinolone use, but depended on the drug, patient age and nosology. Arthropathy has favourable prognosis and was fully resolved at the period from 7 days to 3 month according to the arthropathy form (arthrologic, arthritic). Quinolones arthropathy at the children has specific features, the main one is absence of cartilage damage confirmed by morphological analysis.

[Antibiotic therapy of cystic fibrosis in children]. / Antibiotikoterapiia pri muskovistsidoze u detei.

It is postulated that P. aeruginosa in monoculture or in association with Staphylococcus aureus keeps its leading position in chronic bacterial inflammatory broncho-pulmonary processes in children with cystic fibrosis. Antibiotic resistant strains of Burkholderia cepacia, Stenotrophomonas maltophila, Alcaligenes xylosoxidans were revealed (7.1% of the strains). P. aeruginosa strains were susceptible to aminoglycosides, ciprofloxacin, and polymixin B. Susceptibility of smooth and mucoid forms of P. aeruginosa to ceftazidime stayed at the level of 49.6-57.1%. Such microbial associations as P. aeruginosa sm. + S. aureus, P. aeruginosa sm. + P. aeruginosa muc. + S. aureus were mainly susceptible to ciprofloxacin, aminoglycosides and resistant to ceftasidime. Meropenem, cefepim and ciprofloxacin are highly effective antibiotics for the treatment of broncho-pulmonary processes exacerbations at children with chronic P. aeruginosa cystic fibrosis. Intravenous use of antibiotics out of hospital for the treatment of the children with cystic fibrosis is clinically effective, and is economically and psychologically reasonable. It should be used more widely in medical practice.

[Evaluation of tolerance and efficacy of pefloxacin in the treatment and prevention of severe infections in children with mucoviscidosis and aplastic anemia]. / Otsenka éffektivnosti i perenosimosti pefloksatsina pri lechenii i profilaktike tiazhelykh infektsii u detei s mukovistsidozom i aplasticheskoi anemiei.

Pefloxacin (Abaktal) efficacy and safety were investigated at 21 children (7-16 years old) randomized in 2 groups: children with mucoviscidosis and children with aplastic anemia. The drug was used at the dose 15-20 mg/kg per day bid for 14-28 days. Pefloxacin was used in combination with ceftazidime and amikacin. Combined therapy demonstrated good clinical efficacy. Bacteriological efficacy was not uniform: staphylococci were not isolated from sputum since the 7th day of treatment, but pseudomonads were cultured even on the 14th day of the treatment (the sensitivity to pefloxacin remained). The only but frequent side-effect was arthropathy. The background and some peculiarities of arthropathy development were analyzed. This phenomenon is called quinolone-induced synovitis. The risk group for quinolone-induced synovitis was estimated--children elder than 10 years with allergic anamnesis. Good clinical efficacy and tolerability of pefloxacin at the children with mucoviscidosis or aplastic anemia is a reason and base to cancel the limits to its use in pediatrics.

[The efficacy and safety of ciprofloxacin in treating children with mucoviscidosis]. / Effektivnost' i bezopasnost' tsiprofloksatsina pri lechenii detei s mukovistsidozom.

Ciprofloxacin clinical and bacteriological efficacies, as well as tolerability mainly with respect to chondrotoxicity were evaluated in the treatment of children with mucoviscidosis. The drug was shown to have high clinical and moderate bacteriological efficacies. As for its tolerability, adverse reactions chiefly associated with affection of the gastrointestinal tract, i.e. nausea, stomach pain, diarrhea, increased transaminase levels were recorded. The arthrotoxicity episode was single and transitory. The use of ciprofloxacin had no negative effect on the children growth. No chondrotoxic effect of ciprofloxacin in the treatment of children was observed which is explained in the paper. It is concluded that ciprofloxacin is in general an efficient and safe antibiotic useful for the treatment of children.

[Comparative morphological analysis of the articular cartilage, epiphyseal plate, spongy bone, and synovial membrane of the knee joint in children treated and not treated with ciprofloxacin]. / Sravnitel'nyi morfologicheskii analiz sostoianiia sustavnogo khriashcha, épifizarnoi plastinki, gubchatoi kosti i sinovial'noi obolochki kolennogo sustava u detei, poluchavshikh i ne poluchavshikh tsiprofloksatsin.

Comparative data on he postmortem morphological examination of the knee joint in children treated and not treated with ciprofloxacin while alive are presented. Nine children were ill with mucoviscidosis and 8 children were ill with aplastic anemia. The patients were ill with mucoviscidosis and 8 children were ill with aplastic anemia. The patients were treated with ciprofloxacin in a daily dose of 20 to 40 mg/kg body weight at the average for 148 days. The condition of the articular cartilage, growth area, spongy bone and synovial membrane of the knee joint was examined visually, histologically and morphologically. It was revealed that ciprofloxacin had no chondrotoxic effect. The structure affected in some cases by the ciprofloxacin treatment was the synovial membrane which developed subacute synovitis not clinically manifested (latent) in life. The phenomenon is explained.

[Fluorine level in the bone and cartilage in children treated with ciprofloxacin (data obtained from the femur distal part]. / Soderzhanie ftora v kosti i khriashche u detei, poluchavshikh tsiprofloksatsin (na modeli distal'nogo otdela bedrennoi kosti)

Comparative data on the content of fluorine in various sections of the left femur distal part, i.e. spongy bone, process zone and articular cartilage are presented. The examination was performed on postmortem sections from 10 pediatric cases (the average age of 9.5 years) with mucoviscidosis or aplastic anemia treated before the death for up to 12 months with ciprofloxacin in a dose of 20 to 40 mg/kg body weight. The control postmortem sections were from 10 practically healthy children (the average age of 10.4 years) killed in a car accident. The sections were subjected to 2-stage dry ashing with ionometric determination of the fluorine ions. The results were treated according to the V.Yu. Urbach procedure. It was shown that the content of fluorine in the sponge bone and process zone in both the groups did not significantly differ. A comparatively high content of fluorine was detected only in the postmortem sections of the articular cartilage from the children of the main group who however had no chondrotoxic symptoms while alive. That means that the difference is statistically and clinically insignificant.

[The safety of ofloxacin]. / K voprosu o bezopasnosti ofloksatsina.

The data on a comparative study of ofloxacin arthrotoxicity in pediatric and adult patients are presented. The tolerability of ofloxacin used in various doses and treatment terms (acute and cumulative effects) was investigated in children. The impact of the patient pubertal age, sex, ofloxacin concentrations (Cmax above 4 micrograms/ml) and arthrological diseases (in adult patients) on the risk of the quinolone arthropathy was evaluated. Good tolerability of the various ofloxacin dosing regimens in both the adult and pediatric patients was shown.

[Use of ciprofloxacin in children with mucoviscidosis]. / Primenenie tsiprofloksatsina u bol'nykh mukovistidozom detei.

The efficacy of ciprofloxacin was estimated for the last 3 years in the treatment of 139 children with mucoviscidosis. The drug was mainly used under hospital conditions. In 119 cases ciprofloxacin was administered orally in a daily dose of 25 to 50 mg/kg divided into 2 portions. The treatment course was 14-42 days. In 20 cases ciprofloxacin was used intravenously in a daily dose of 10 to 23 mg/kg injected twice a day with an interval of 12 hours. The treatment course was 14-18 days. Ciprofloxacin was used either alone (exclusively in outpatients) or in combination with the 2nd or 3rd generation cephalosporins or aminoglycosides. The positive effect was practically stated in all the patients in 10-14 days from the therapy start. The clinical remission at the background of the ciprofloxacin therapy in the inpatients was observed 3 days earlier than that in the inpatients treated without the use of ciprofloxacin. The remission period in the outpatients averaged 62 days while in the cases treated with gentamicin it was 35 days and in the cases treated with azlocillin it was 30 days. The adverse reactions were recorded in 8 per cent of the patients.