Characteristics of antibiotic use in children

In antibiotic therapy of children bacteriological findings should be considered. The choice of antibiotic doses depends on the drug pharmacokinetics and damaging effect, the state of the excretory organs and some other factors. Antibiotic elimination in children during the postnatal period is limited: there is a relationship between the gestation term and intensity of drug elimination. Antibiotics penetrate through the placental barrier. They are detected in the mother milk. The damaging effect of antibiotics in many respects depends on their properties, dosage and administration route. Children are more sensitive to the direct toxic action of antibiotics as compared to adults. Development of dysbacteriosis in children is frequent. Allergic reactions with diverse clinical signs are possible in children. Combined antibiotic therapy with observation of definite requirements is more efficient. Still, because of the antibiotic damaging effect monotherapy is more preferable in all possible cases.     

儿童细菌性腹泻病的病原菌分布及耐药性分析

目的:调查本地区导致儿童细菌性腹泻病的病原菌分布及耐药趋势,为临床合理选用抗生素提供依据。方法:调阅2009年01月至2012年02月在我院诊断并治愈的细菌性腹泻病的患儿病历,统计分析患儿粪便中致病菌的鉴定、药物敏感性及超广谱β-内酰胺酶(ESBLs)检测结果。结果:期间共收治226例细菌性腹泻患儿,均获得痊愈,除经过经验性药物治疗治愈而未进行粪便培养的病例外,209例患儿进行便培养,192例培养出致病菌,培养阳性率91.9%,获取菌株337株,其中65例培养出超过两种以上细菌。培养出的细菌中:埃希菌属、志贺菌属、肠杆菌属及变形杆菌属4种致病菌占总分离菌株的78.6%;肠球菌属、克雷伯菌属、非发酵菌属、枸橼酸杆菌属及酵母样真菌等致病菌占总菌数的21.4%。常见的三种致病菌中,埃希菌属、志贺菌属、肠杆菌属三种细菌的耐药性均比较严重,对常见抗生素的耐药均处在较高比率。结论:儿童腹泻病致病菌谱的分布具有显著的地域性差异;部分致病菌具有较高的耐药性应引起临床重视;临床应用抗生素治疗儿童感染性腹泻病时应在确定致病菌及其耐药情况后有针对性地进行。     

The effect of benzylpenicillin on the activity of antioxidative enzymes in the erythrocytes and on methemoglobin formation in children

Activity of erythrocyte antioxidative enzymes and the content of methemoglobin were studied in 36 healthy children under preventive treatment with benzylpenicillin and in 65 healthy children of the control group. It was shown that there was relationship between the changes in the activity of superoxidodismutase and catalase and the antibiotic dose and duration of the use. After benzylpenicillin intramuscular administration for 3-4 days (the total dose of 80,000-3000000 units) the catalase activity decreased to 65.6 per cent while the activity of superoxidodismutase did not change. When the antibiotic was used for 1-2.5 weeks (the total dose of 3000000-6000,000 units) the activity of catalase and superoxidodismutase decreased to 53.6 and 82 per cent respectively. Beginning from the 3rd week of the antibiotic use the catalase activity increased to 71.6 per cent while the superoxidodismutase activity did not change and remained at the level of 84.9 per cent. The content of methemoglobin in the children treated with benzylpenicillin was about 3 times higher than that in the controls. The correlation between the activity of the antioxidative enzymes and the content of erythrocyte methemoglobin was inverse: the lower was the enzyme activity, the higher was the content of methemoglobin and vice versa. It was concluded that benzylpenicillin impaired definite balance between single electron reduction of oxygen and antioxidative protection resulting in the antibiotic adverse action i. e. increased methemoglobin formation. The effects of benzylpenicillin should be considered when it is used in combination with oxidants in treatment of children.     

Wheeze in preschool age is associated with pulmonary bacterial infection and resolves after antibiotic therapy

Background

Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children.

Methodology/Principal Findings

Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2–16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥10⁴ colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination.

Conclusions/Significance

Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy.     

Improvement of the Management of Infants,Children and Adults with a Molecular Diagnosis of Enterovirus Meningitis during Two Observational Study Periods

Enteroviruses (EVs) are a major cause of aseptic meningitis, and RNA detection using molecular assay is the gold standard diagnostic test. The aim of this study was to assess the impact of an EV positive diagnosis on the clinical management of patients admitted for meningitis over the course of two observational study periods (2005 and 2008–09) in the same clinical departments. We further investigated in multivariate analysis various factors possibly associated with hospital length of stay (LOS) in all age groups (infants, children, and adults). The results showed an overall improvement in the management of patients (n = 142) between the study periods, resulting in a significantly shorter hospital LOS for adults and children, and a shorter duration of antibiotic use for adults and infants. In multivariate analysis, we observed that the time from molecular test results to discharge of patients and the median duration of antibiotic treatment were associated with an increase in LOS in all age groups. In addition, among adults, the turnaround time of the molecular assay was significantly correlated with LOS. The use of CT scan in children and hospital admission outside the peak of EV prevalence in infants tended to increase LOS. In conclusion, the shorter length of stay of patients with meningitis in this study was due to various factors including the rapidity of the EV molecular test (particularly in adults), greater physician responsiveness after a positive result (in adults and children), and greater experience on the part of physicians in handling EV meningitis, as evidenced by the shorter duration of antibiotic use in adults and infants.     

Value of determining the spectrum of blood serum fatty acids in evaluating increasing the effectiveness of antibiotic therapy of dysentery in children with prodigiozan and ephedrine

One hundred and ninety one children with acute Sonne and Flexner dysentery were observed with respect to the disease process, immunity indices and blood serum fatty acid spectrum. 104 children were treated with monomycin alone and 87 children were treated with the antibiotic in combination with prodigiozan and ephedrine as immunostimulators. It was shown that the recovery terms in the patients treated with the use of the immunostimulators decreased as compared to the patients treated with the antibiotic alone. The fatty acid spectrum in the children treated with the use of the immunostimulators differed from that in the children treated without them by low levels of fatty acids of the C12:0 to C18:1 composition.     

Reducing Antibiotic Use for Young Children with Intussusception following Successful Air Enema Reduction

China introduced a new policy regarding the management of antibiotic use. We evaluated the reasonableness of antibiotic use among children suffering from intussusception before and after policy. A retrospective study was conducted involving 234 young children with intussusception who were treated between January 1, 2011 and December 30, 2013. Demographics and detailed antibiotics regimens were collected. χ ² test was used to evaluate differences between the phase I (preintervention, n = 68) and phase II (postintervention, n = 166). We determined that the overall antibiotic use rate following successful air enema reduction was 41% (97/234), which decreased from 99% (67/68) in phase I to 18% (30/166) in phase II. In phase I, prophylactic antibiotic usage reached up to 84% (56/67). The quantity of aztreonam for injection accounted for 63% (45/71), and cefamandole nafate for injection accounted for 25% (18/71). In phases II, prophylactic antibiotic usage were reduced to 13% (4/30). The quantity of aztreonam for injection was decreased to 12% (4/33) and cefamandole nafate for injection was 3% (1/33). Antibiotics'' options were more diverse. In conclusion, policy intervention was effective in addressing some aspects of antibacterial drug usage among young children with intussusception. However, excessive drug use remains a public health problem. The guidelines for the antibiotic management of intussusception for children must be established in China.     

Etiology and treatment of pneumonia in children]

The most widespread pathogens of pneumonia in children i.e. Streptococcus pneumoniae and Haemophilus influenzae and their antibiotic susceptibility are described. The ways of selecting starting antibacterial drugs for the treatment of community-acquired and hospital pneumonia are recommended proceeding from the original findings and some literature data. Oral drugs for the treatment of uncomplicated pneumonia are shown to be preferential. In the treatment of nosocomial or hospital pneumonia the starting regimen should allow for the previous antibacterial therapy.     

Prevalence of Tetracyclines in Children's Teeth—Study II: Resurvey after Five Years

The capacity of the tetracyclines to discolour teeth has been widely recognized for over 10 years. This survey examined recent trends in tetracycline usage as shown by deposits of the antibiotic in primary molars extracted from 505 children aged from 3 to 5 years.It was found that 70% of the children had been given the antibiotic during their first three years of life, each having received on average 2·4 courses. This represented an increase of 12% in tetracycline usage in children of this age as compared with a similar series five years ago. There was no evidence of increasing preference by prescribers for oxytetracycline (the analogue least likely to cause dental discoloration). Staining of the permanent incisor teeth frequently occurs if tetracyclines are given to children under 6 years of age and it is predicted that some degree of staining will occur in about 23% of the children in this series.All things considered, there appears to be a strong case for stopping the manufacture of paediatric preparations of tetracycline except for those comprised of oxytetracycline for use in exceptional cases.     

Meta-analysis of trials of prophylactic antibiotics for children with measles: inadequate evidence.

OBJECTIVE: To assess whether antibiotics should be given to all children with measles in communities with a high case fatality rate. DESIGN: Meta-analysis of randomised controlled trials that compared routine antibiotic prophylaxis with no antibiotic treatment or selective treatment of pneumonia or sepsis. SUBJECTS: Six trials of children admitted to hospital with measles: five in Glasgow, London, or New York between 1939 and 1954; and one in India in 1967. MAIN OUTCOME MEASURES: Incidence of pneumonia or sepsis, and mortality. RESULTS: All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia or sepsis in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia or sepsis was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls (exact odds ratio 4.0, mid-P corrected 95% confidence interval 0.5 to 101.6). CONCLUSION: The quality of the trials reviewed was poor, and they provide weak evidence for giving antibiotics to all children with measles. Available evidence suggests that, when mortality from measles is high, all children with measles should be treated with vitamin A but antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.     

双歧杆菌三联活菌散治疗儿童抗生素相关性腹泻的疗效及安全性观察

目的探讨双歧杆菌三联活菌散治疗儿童抗生素相关性腹泻的疗效及安全性观察。方法选取抗生素相关性腹泻的患儿86例,采用随机数字表将纳入患者分为观察组（n=43例）和对照组（n=43例）。两组患儿均予以调整饮食、口服或静脉补液及口服蒙脱石散等常规治疗。观察组患儿加用双歧杆菌三联活菌散1.0 g/次,3次/d,溶解于温水中口服。对照组患儿除不使用双歧杆菌三联活菌散外余治疗同观察组。观察并记录两组患儿治疗后大便次数恢复时间和性状改变时间,并比较其临床疗效及不良反应。结果观察组患儿大便次数恢复时间和性状改变时间明显短于对照组（P〈0.05）;治疗72 h后,观察组患儿的临床总有效率为明显优于对照组（95.35%vs.81.40%）（χ^2=4.07,P〈0.05）,两组患儿治疗中均未出现明显的不良反应。结论双歧杆菌三联活菌散治疗抗生素相关性腹泻具有较好效果及安全性,能明显减少患儿腹泻次数及程度,改善患儿大便性状,较快缓解患儿的病情。     

Longitudinal Nasopharyngeal Carriage and Antibiotic Resistance of Respiratory Bacteria in Indigenous Australian and Alaska Native Children with Bronchiectasis

Background

Indigenous children in Australia and Alaska have very high rates of chronic suppurative lung disease (CSLD)/bronchiectasis. Antibiotics, including frequent or long-term azithromycin in Australia and short-term beta-lactam therapy in both countries, are often prescribed to treat these patients. In the Bronchiectasis Observational Study we examined over several years the nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in these two PCV7-vaccinated populations.

Methods

Indigenous children aged 0.5–8.9 years with CSLD/bronchiectasis from remote Australia (n = 79) and Alaska (n = 41) were enrolled in a prospective cohort study during 2004–8. At scheduled study visits until 2010 antibiotic use in the preceding 2-weeks was recorded and nasopharyngeal swabs collected for culture and antimicrobial susceptibility testing. Analysis of respiratory bacterial carriage and antibiotic resistance was by baseline and final swabs, and total swabs by year.

Results

Streptococcus pneumoniae carriage changed little over time. In contrast, carriage of Haemophilus influenzae declined and Staphylococcus aureus increased (from 0% in 2005–6 to 23% in 2010 in Alaskan children); these changes were associated with increasing age. Moraxella catarrhalis carriage declined significantly in Australian, but not Alaskan, children (from 64% in 2004–6 to 11% in 2010). While beta-lactam antibiotic use was similar in the two cohorts, Australian children received more azithromycin. Macrolide resistance was significantly higher in Australian compared to Alaskan children, while H. influenzae beta-lactam resistance was higher in Alaskan children. Azithromycin use coincided significantly with reduced carriage of S. pneumoniae, H. influenzae and M. catarrhalis, but increased carriage of S. aureus and macrolide-resistant strains of S. pneumoniae and S. aureus (proportion of carriers and all swabs), in a ‘cumulative dose-response’ relationship.

Conclusions

Over time, similar (possibly age-related) changes in nasopharyngeal bacterial carriage were observed in Australian and Alaskan children with CSLD/bronchiectasis. However, there were also significant frequency-dependent differences in carriage and antibiotic resistance that coincided with azithromycin use.     

The effect of immunotherapy with the VP-4 multicomponent vaccine in children with frequent acute respiratory diseases and obstructive bronchitis

The results of prolonged observations on children with frequent acute respiratory diseases (ARD), subject to immunoprophylaxis with the use of polycomponent vaccine (VP-4), prepared from the antigens of opportunistic microorganisms, are presented. The vaccine was introduced to 30 children in 3 intranasal administrations and 6-8 oral administrations. The morbidity rate of the children was registered and their clinical status was evaluated for a year after the introduction of vaccine VP-4. As revealed in these observations, the frequency of ARD cases among the immunized children decreased 3 times or more in comparison with that among the same children, registered during a year prior to the introduction of the vaccine. In addition to a decrease in the frequency of ARD cases, a decrease in their duration and in the number of antibiotic administrations, as well as in the necessity of hospitalization, were also registered.     

The epidemiology of pneumococcal infection in children in the developing world.

Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio-economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing countries. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide-protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.     

New approaches towards the identification of antibiotic and vaccine targets in Streptococcus pneumoniae

Streptococcus pneumoniae causes more than one million deaths every year, mostly of young children in developing countries, due to pneumonia, bacteremia and meningitis. The emergence and dissemination of drug-resistant pneumococcal strains, coupled to changing patterns of virulence and the inadequacy of available vaccines, calls for an aggressive search for novel targets for antibiotic and vaccine development. Microbial genomics techniques allow genetic and biochemical tools to be employed to tackle discovery, design and development of new anti-infective agents based on the identification of hundreds of new targets. In this review, novel approaches employed to identify potential antibiotic and vaccine targets in S. pneumoniae are highlighted. Recently identified virulence factors, as well as molecules essential for bacterial viability, cell wall integrity and infectivity, are discussed.     

Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children

The composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured for S. pneumoniae, and real-time PCR was used to identify S. pneumoniae, H. influenzae, and M. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization by S. pneumoniae, H. influenzae, and M. catarrhalis was associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, including Lactococcus and Propionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance of Streptococcus and Haemophilus, and a high abundance of Corynebacterium and Dolosigranulum were less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies.     

The efficacy and safety of ciprofloxacin in treating children with mucoviscidosis]

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.