Detection of Variants With Reduced Baloxavir Marboxil and Oseltamivir Susceptibility in Children With Influenza A During the 2019-2020 Influenza Season.

BACKGROUND: We aimed to detect influenza variants with reduced susceptibility to baloxavir marboxil (baloxavir) and oseltamivir and identify differences in the clinical course between children with and without these variants after antiviral treatment. METHODS: During the 2019-2020 influenza season, we enrolled children with confirmed influenza A (20 treated with baloxavir and 16 with oseltamivir). We analyzed patients' sequential viral RNA loads and infectious virus titers, the drug susceptibilities of clinical isolates, and amino acid substitutions in the viral polymerase acidic protein subunits or neuraminidase. We assessed patients' clinical information using questionnaires. RESULTS: All viral RNA loads and virus titers were significantly decreased after treatment, but we detected baloxavir-resistant and oseltamivir-resistant variants in 5 of 20 and 3 of 16 patients, respectively. The duration of fever was similar between patients with and without the variants, but infectious viral shedding lasted 3 days longer in patients with baloxavir-resistant variants. In addition, the duration to improvement of clinical symptoms was longer in these patients (75.0 vs 29.5 hours; P = .106). CONCLUSIONS: After antiviral treatment, the emergence of baloxavir-resistant variants may affect the patients' clinical course, but oseltamivir-resistant variants had no clinical impact.

Detection of Variants With Reduced Baloxavir Marboxil Susceptibility After Treatment of Children With Influenza A During the 2018-2019 Influenza Season.

During the 2018-2019 influenza seasons, we detected reduced baloxavir marboxil (baloxavir) susceptible variants with I38S or I38T amino acid substitutions on the PA subunit of influenza virus ribonucleic acid polymerase in 7 of 18 baloxavi-treated children and found that virus titer rebounded in some of these children with variants. We also found fever durations to be similar between patients with or without the variants, but the patients with variants shed the virus 3 days longer and took longer to improve clinical symptoms than those without variants. The emergence of these variants should be monitored during future influenza seasons.

Clinical and epidemiologic factors related to subsequent wheezing after virus-induced lower respiratory tract infections in hospitalized pediatric patients younger than 3 years.

UNLABELLED: Most wheezing episodes in infants are caused and exacerbated by virus-induced lower respiratory tract infections. However, there are few reports of epidemiologic and clinical virus-specific research with a focus on virus-induced wheezing. The purpose of the current study was to characterize the clinical presentation of virus-induced wheezing in pediatric patients <3 years of age who were hospitalized with lower respiratory tract infections. Of the 412 patients in the study, 216 were followed for 3 years. Nasopharyngeal aspirates collected from the patients at the time of admission were examined for the presence of respiratory syncytial virus (RSV), rhinovirus (RV), parainfluenza-3 virus (PIV-3), human metapneumovirus (hMPV), and influenza virus (Flu) using reverse-transcription polymerase chain reaction and rapid diagnostic tests. Clinical signs were assessed using a severity scoring system. In patients with wheezing at the time of admission, RSV, RV, RSV+RV, Flu, PIV-3, and hMPV were detected in 33, 14, 8, 8, 5, and 3 % of samples, respectively. There were no differences in age and severity scores between patients harboring more prevalent viruses (RSV and RV) and those with less common infections. Patients with wheezing and RV-positive aspirates at the time of admission were more likely to develop subsequent wheezing during the following 3 years. CONCLUSION: RSV and RV infections are factors in the development and exacerbation of wheezing after virus-induced lower respiratory tract infections. Moreover, RV-induced wheezing may be associated with subsequent recurrent wheezing and the development of asthma.

Launch of Board Certification in Pediatric Infectious Diseases in Japan.

To cultivate specialists in pediatric infectious diseases (ID) in Japan, the Japanese Society for Pediatric Infectious Diseases initiated board certification for pediatric ID in 2017. Previously, in 2014, we had formed a committee for board certification in pediatric ID and discussed the fundamentals of the board certification system, including the goals, requirements for designated training institutions, provisional certification of pediatric ID specialists and eligibility for and content of the board certification examination. After approval from 31 programs, the pediatric ID programs started in 2017 with 8 fellows in 7 programs. The first 6 graduates received board certification in 2020. To date, 61 pediatricians have been board certified as pediatric ID specialists. In parallel, we introduced board certification for pediatricians who work mainly in primary care settings and have a special interest in pediatric ID. This system has certified 338 pediatricians. During and after the development of the programs, we achieved substantial progress in highlighting the pivotal role of pediatric ID specialists, including the establishment and maintenance of antimicrobial stewardship programs, pediatric ID consultations and introduction of viral diagnosis by polymerase chain reaction at institutions. However, several issues need to be addressed, including the establishment of independent pediatric ID departments in institutions, payment of consultation fees, program site visits, maintenance of certification and cultivation of physician-scientists. These challenges will be the focus of future efforts.

Clinical and Virologic Impacts of Respiratory Viral Co-infections in Children With Influenza.

BACKGROUND: Advances in multiplex polymerase chain reaction (PCR) methods have enabled the simultaneous detection of multiple respiratory viruses. We aimed to estimate the clinical and virologic impacts of influenza and other respiratory virus co-infection in children. METHODS: We enrolled 38 and 35 children diagnosed with influenza and treated with baloxavir marboxil (baloxavir) and oseltamivir, respectively. We performed quantitative reverse transcription-PCR to detect and measure the levels of noninfluenza viruses from 3 nasopharyngeal swab samples collected before and on days 3 and 5 after the initial antiviral dose. We assessed patients' clinical information using questionnaires. RESULTS: One or more respiratory viruses other than influenza virus were detected in 26 (35.6%) of 73 children before antiviral treatment. The influenza virus load and clinical characteristics on the day of influenza onset were similar between children with and without virus co-infections. Of the 26 and 32 children without the emergence of the reduced baloxavir and oseltamivir susceptible variants after treatment, 8 (30.8%) and 7 (21.9%) children were dually co-infected with human rhinovirus only, respectively. The level of human rhinovirus RNA on day 0 in these children was less than -3 log 10 that of influenza virus RNA, and the human rhinovirus co-infection had no impact on the disease course either clinically or virologically. CONCLUSIONS: When multiple respiratory viruses are detected in the same patient, it is necessary to assess clinical symptoms as well as the levels of detected viruses to determine which virus contributes to the development of illness.

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis.

BACKGROUND: The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. METHODS: We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. FINDINGS: We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. INTERPRETATION: Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. FUNDING: WHO; Bill & Melinda Gates Foundation.

Rhinovirus load and disease severity in children with lower respiratory tract infections.

It has not been clarified if there is a correlation between rhinovirus (RV) load and disease severity in the lower respiratory tract infections of hospitalized children. This study was undertaken to elucidate the contribution of the viral load to the development of disease severity in 412 children ≤3 years of age who were hospitalized with lower respiratory tract infections. The RV load in nasopharyngeal aspirates obtained from the patients at the time of admission was measured by real-time quantitative reverse-transcription polymerase chain reaction (PCR), and the clinical symptoms of the patients were assessed using a severity scoring system. Of the 412 patients, 43 (10.4%) were diagnosed with RV infections only, and 15 were determined to have high severity scores. When all patients infected with RV were assessed, there was no correlation between the viral load and the disease severity. However, there was a significant negative correlation between the disease severity and age among children <11 months of age (n = 15, ρ = -0.677, P = 0.006) and a significant positive correlation between the viral load and the disease severity among children ≥11 months of age (n = 28, ρ = 0.407, P = 0.032). Among the patients infected with RV <11 months of age, the disease severity may be associated with an immature immune response and the small diameter of their airways rather than viral load. By contrast, in the patients ≥11 months of age, viral load may contribute to the development of disease severity.

Uteroglobulin-related protein 1 and severity of respiratory syncytial virus infection in children admitted to hospital.

There are several reports suggesting that genetic factors contribute to the severity of infection with the respiratory syncytial virus (RSV). Infants hospitalized with lower respiratory tract infection (LRTI) due to RSV are at a significantly increased risk for both recurrent wheezing and childhood asthma. Uteroglobin-related protein 1 (UGRP1) is a secretory protein expressed in the airways, and speculated to have anti-inflammatory activity. The presence of the -112G/A polymorphism in the UGRP1 promoter was found to have a significant correlation with asthma phenotype. Also plasma UGRP1 levels were shown to be associated both with this polymorphism and the severity of asthma. The study population consisted of 62 previously healthy infants, ≤12 months of age, who were hospitalized with RSV LRTI, and a control group of 99 healthy adults. Genotyping was performed by restriction fragment length polymorphism. UGRP1 serum levels were determined using ELISA. There were no significant differences in the overall distribution of UGRP1 -112G/A polymorphism genotypes or alleles between the hospitalized infants and healthy adults. A comparison of serum UGRP1 concentration measured at the time of admission and discharge between patients with and without the -112A allele revealed that there was no relation between the presence of the -112A allele and serum UGRP1 in hospitalized infants with RSV infection. Furthermore, there was no relationship between severity of RSV infection and genotype or serum UGRP1 concentration. These results suggest that UGRP1 does not have a major role in the development of severe RSV infection.

Clinical course and background of nasopharyngeal antibiotic-resistant bacteria carriers among preschool children hospitalized for lower respiratory tract infection.

AbstractWe investigated the nasopharyngeal microbiota in preschool patients hospitalized with lower respiratory tract infection to clarify the relationships between culturable nasopharyngeal bacteria and prognosis. From 2016 to 2018, nasopharyngeal culture was performed on inpatients under 6 years of age with a lower respiratory tract infection. Among the 1,056 study patients, 1,046 provided nasopharyngeal samples that yielded positive cultures, yielding 1,676 isolated strains. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, were isolated in 25%, 27%, and 31% of the samples, respectively, and were the major causes of respiratory tract infection in these children. The only factor associated with the isolation of antibiotic-resistant strains from the nasopharynx was daycare attendance, which did not affect clinical severity, such as duration of fever and hospitalization. This study demonstrated that resistant bacteria in the nasopharynx did not affect the severity of lower respiratory tract infection and supports the use of narrow-spectrum antimicrobial agents in accordance with published guidelines when initiating therapy for pediatric patients with community-acquired pneumonia.

The trend of drug-resistant Streptococcus pneumoniae from nasopharynx of children.

We investigated the trend of the carriage of drug-resistant Streptococcus pneumoniae in nasopharynx of children. The 202 isolates from pediatric outpatients and their previous antibiotic use was investigated from 2004 to 2006. The total rate of patients medicated with antibiotics was 47.5%, a 6.9% decrease compared with our previous study performed from 2001 to 2003. There were 56 (27.7%) penicillin-susceptible, 83 (41.1%) penicillin-intermediate, and 63 (31.2%) penicillin-resistant strains by the susceptibility breakpoints used during the previous study period. There were 196 (97%) susceptible, 5 (2.5%) intermediate, and 1 (0.5%) resistant strains by breakpoints in this study, which were introduced in 2008 by the Clinical Laboratory and Standards Institute. The rate of strains with a single altered pbp gene was 21.8% (44), with 2 altered pbp genes was 21.8% (31), and with 3 altered pbp genes was 53.5% (108). The total rate of strains with altered pbp gene(s) was 90.1% (183). We found the emergence of strains with pbp1a and 2b and the higher rate of strains with pbp2x. There was obvious association between amoxicillin use and the carriage of altered pbp gene(s). These results might suggest that amoxicillin was not a safe alternative to prevent the emergence of resistant strains. We need to reassess a beneficial approach for the treatment of pediatric outpatients.

[Trend of drug-resistant Haemophilus influenzae from the pediatric nasopharynx].

The influence of amoxicillin (AMPC) on drug-resistant Haemophilus influenzae gene must be carefully considered in using antibiotics to treat children with respiratory infections. We studied 197 isolates from pediatric outpatients and their previous antibiotic use in northern Japan from 2004 to 2006. We found that the population treated with antibiotics was 45%-11% decrease from the previous 2001-2003 study. Those treated with AMPC increased by 15% and those treated with cephalosporins decreased by 18%. Susceptibility testing showed that strains resistant to ampicillin (ABPC) increased from 31% to 49%. Strains with altered pbp gene(s) in ABPC-susceptible strains also increased. AMPC use was clearly associated with strains with resistant gene(s) such as beta-lactamase-nonproducing ampicillin-resistant H. influenzae (low-BLNAR), BLNAR, beta-lactamase-producing ampicillin-resistant H. influenzae (BLPAR) beta-lactamase-producing amoxicillin/clavulanic acid-resistant H. influenzae (BLPACR).

Non-antibiotic treatment for pediatric outpatients with common cold inhibits the emergence of drug resistant pneumococci.

The occurrence of drug resistant Streptococcus pneurmoniae (S. pneumoniae) is very high in Japan. Unnecessary use of antibiotics had been thought to cause this problem but previous studies had not clearly showed that the decreasing rate of antibiotic use had been related to the reduction of the prevalence of resistant strains. In this study, we tried to prove that non-antibiotic treatment for common cold would reduce the antibiotic resistant S. pneumoniae in nasopharynx in children. Forty-five children with the common cold were randomly selected from pediatric patients who had taken antibiotics within the past three months. We collected nasopharyngeal swabs from all of the participants and once again after a period of 2 to 3 months without using any antibiotics. Twenty-four of these patients had the S. pneumoniae strains isolated. Then these strains were undergone a susceptibility test and drug-resistant gene detection. The susceptibility test reveled that patients with penicillin-resistant strains decreased from 17 to 7 (p < 0.01). The test also reveled that the decreased number of patients had strains that were resistant to cefditren. The gene detection revealed that none of the patients acquired a higher resistance to penicillin. Our study suggests that the treatment without antibiotics reduces the drug-resistant S. pneumoniae. Controlled antibiotic use in children might prevent children from carrying the antibiotic resistant S. pneumoniae.

Serum KL-6 levels as a biomarker of lung injury in respiratory syncytial virus bronchiolitis.

To evaluate whether KL-6 concentration is a useful biomarker of the severity of respiratory syncytial virus (RSV) bronchiolitis, we determined KL-6 concentrations in patients with RSV bronchiolitis with or without chronic heart disease (CHD). We enrolled 52 patients who had been diagnosed with RSV bronchiolitis and required admission to the hospital at the Department of Pediatrics of Fukushima Medical University School of Medicine from 2004 to 2005. These patients were divided into two groups: Group 1 consisted of patients without any underlying disease, and Group 2 consisted of patients with CHD. These patients were assigned to three categories. Stage A consisted of patients without oxygen dosage, stage B of patients who required oxygen dosage, and stage C of patients required artificial respiration. We evaluated baseline characteristics, clinical features, and serum KL-6 concentration in Group 1, Group 2, and a control group (healthy infants without infection). Mean serum KL-6 concentrations in patients with RSV bronchiolitis were higher than those in the control group (471.8 +/- 236.9 and 127.1 +/- 69.1 U/ml, respectively). Mean serum KL-6 concentration was higher in Group 2 than in Group 1 (692.8 +/- 313.1 and 390.4 +/- 132.7 U/ml, respectively). Mean serum KL-6 concentrations were higher in stage C than in stages A and B, and mean serum KL-6 concentrations were higher in stage B than in stage A. These findings suggest that serum KL-6 is associated with the severity of RSV bronchiolitis and that it may be a useful biomarker for the severity of RSV bronchiolitis.

Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children.

Prostaglandin I(2) (PGI(2)) protects against RSV-induced illness in mice. A variable-number tandem repeat (VNTR) polymorphism has been detected in the promoter region of the PGI(2) synthase (PGIS) gene. We sought to determine if PGI(2) concentrations or polymorphisms of the PGIS gene correlate with severity of RSV lower respiratory tract infections (LRTI) in human infants. VNTR polymorphisms were studied in 81 previously healthy children between birth and 12 months of age who were hospitalized for LRTI due to RSV and 98 healthy adult control subjects. The severity of RSV infection was quantified using a clinical scoring system, and infant urine samples were collected during the acute illness for measurement of the urinary metabolite of PGI(2). There were no significant differences in the overall distribution of alleles and genotypes between infants with RSV LRTI and the control subjects. The severity of RSV infection significantly inversely correlated with urinary PGI(2) metabolite concentrations. The urinary PGI(2) metabolite concentration correlated with the number of VNTR. The presence of a genotype with a low number VNTR repeats significantly correlated with the most severe RSV LRTI, and genotypes with the highest number of VNTR correlated with the least severe RSV LRTI. A functional polymorphism in the promoter region of the PGIS gene is associated with both significant differences in urinary PGI(2) concentrations during RSV LRTI, and severity of RSV infection in previously healthy infants.

The emergence of drug-resistant Streptococcus pneumoniae and host risk factors for carriage of drug-resistant genes in northeastern Japan.

Our 2-year study includes research into the occurrence, molecular characteristics, and host risk factors for the carriage of drug-resistant strains of Streptococcus pneumoniae as a continuation of our previous report. From September 2001 to June 2003, strains of S. pneumoniae were isolated from the nasopharynx of children with respiratory tract infection in Soma General Hospital. Of the total of 949 strains, 761 (81%) had a decreased susceptibility to penicillin (MIC > 0.12 microg/ml), while 818 (86%) were resistant to erythromycin (MIC > 1 microg/ml) and 789 (83%) were resistant to clarithromycin (MIC > 1 microg/ml). More than half of the strains had decreased susceptibility to meropenem. Gene analysis of 226 randomly selected strains showed that 200 strains (88.5%) had one or more altered pbp genes and 191 strains (84.5%) had mef(A) and/or erm(B) genes. We reviewed the patient backgrounds for previous antibiotic use, age, daycare attendance, and siblings. Previous use of oral beta-lactams has shown a strong relationship with the carriage of altered pbp genes (P value < 0.01), and previous oral macrolide use has been related to the carriage of macrolide-resistant genes (P value < 0.01). The controlled use of antibiotics might be an important factor in preventing the emergence of S. pneumoniae with antibiotic-resistant genes.

[Host risk factors for acquirement of antimicromial resistant gene in Haemophilus influenzae].

The present study investigated the host risk factors for carriage of Haemophilus influenzae (H. influenzae) with resistant gene (s) against antibiotics. From September 2001 to January 2004, 174 strains of H. influenzae were isolated from the nasopharynx of children with respiratory tract infections. We classified these strains on the basis of the MIC to Ampicillin and the presence of resistant gene (s) for antibiotics resistance (gene for beta-lactams and altered pbp gene (s)). The patients' background such as previous antibiotic usage, age, daycare attendance, siblings and underlying diseases was investigated. The risk factor for carriage of strains with altered pbp gene (s) was the usage of beta-lactams within the last 3 months. Controlled usage of oral beta-lactams might be an important issue for preventing the spread of resistant H. influenzae strains such as beta-lactamase non-producing ampicillin resistant H. influenzae. We have to reconsider a therapeutic approach for the treatment of young children with respiratory tract infection.

Correlation between serum interleukin 6 and C-reactive protein concentrations in patients with adenoviral respiratory infection.

OBJECTIVE: To characterize adenoviral respiratory infection, we evaluated clinical features, laboratory findings and serum cytokine concentrations in patients with adenoviral infection and compared them with those in patients with influenza virus and respiratory syncytial virus (RSV) infections. METHODS: We enrolled 106 patients who had been diagnosed with acute viral respiratory infection caused by adeno-, influenza and respiratory syncytial viruses from January, 1995, through December, 1998. Forty-nine patients had adenovirus infection, 19 patients had influenza virus infection and 38 patients had RSV infection. Etiologic diagnosis was made based on the antigen detection by enzyme immunoassay (influenza virus, RSV), and viral isolation was done by tissue culture (adenovirus, influenza virus) from nasopharyngeal specimens. We evaluated clinical manifestations, laboratory findings (white blood cell count, C-reactive protein, erythrocyte sedimentation rate) and serum cytokine [interleukin (IL)-1-beta, IL-6, IL-8, interferon gamma and tumor necrosis factor alpha] concentrations. RESULTS: We observed prolonged fever, strong inflammatory response such as leukocytosis with neutrophilia and high C-reactive protein values in patients with adenoviral respiratory infection compared with those in patients with influenza virus and RSV infections. Serum IL-6 concentrations in patients with adenoviral respiratory infection were higher than those in patients with influenza virus and RSV infections. Other cytokine (IL-1-beta, IL-2, interferon gamma and tumor necrosis factor alpha) values did not differ among adenovirus, influenza virus and RSV infections. CONCLUSIONS: Patients with adenoviral respiratory infection have high grade and prolonged fever, strong inflammatory response and higher serum IL-6 than in influenza and RSV infection.

Application of polymerase chain reaction and subsequent phylogenetic analysis to the diagnosis of enteroviral infection in the central nervous system.

BACKGROUND: Enteroviral infections of the central nervous system (CNS) are often difficult to diagnose, even if consistent conventional laboratory methodologies are used. OBJECTIVES: To clarify the efficiency of two polymerase chain reaction (PCR) methods for the sensitive detection of enteroviruses and for the identification of enteroviral genotypes based on phylogenetic analysis of the amplified genome sequences, and to facilitate the diagnosis of enteroviral infection in CNS. STUDY DESIGN: Cerebrospinal fluid (CSF), throat swab, rectal swab, and/or serum samples were collected from 171 patients with aseptic meningitis and 67 patients with febrile seizures. The samples were tested for the presence of enteroviruses by cell culture and PCR methods for the detection and identification of enteroviruses. RESULTS: In 111 (64.9%) of 171 patients with aseptic meningitis, enteroviruses were isolated by cell cultures from any site. In 143 (83.6%) patients, including 110 of 111 patients with aseptic meningitis, the enteroviral genome was detected in CSF by PCR. No enterovirus was isolated from any site for the 67 patients with febrile seizures. PCR detected the enteroviral genome in CSF samples from 13 (61.9%) of 21 patients who developed febrile seizures in the summer (June-August). Phylogenetic analysis of amplified genome sequences showed that the major pathogens of febrile seizures in summer were group A coxsackieviruses, which are usually difficult to isolate by cell culture. CONCLUSION: PCR methods for the detection and identification of enteroviruses were useful for the diagnosis of enteroviral infection in CNS.

[Antimicrobial resistance in Streptococcus pneumoniae and Haemophilus influenzae isolated from nasopharynx in children].

The aims of this study are to investigate the antimicrobial susceptibility of bacteria isolated from children and clarify the risk factors for the carriage of the resistant strains. We examined the minimum inhibitory concentrations (MICs) of antimicrobial agents against 949 strains of Streptococcus pneumoniae (S. pneumoniae) and 791 strains of Haemophilus influenzae (H. influenzae) isolated at our department between September, 2001 and May, 2003. Of those, 226 S. pneumoniae strains and 115 H. influenzae strains were analysed for the resistance genes. Also we retrospectively reviewed the profiles of 1,359 patients with either S. pneumoniae, H. influenzae, or both in nasopharynx. From the view point of MICs, PSSP strains were 185 (19%), PISP strains were 443 (47%), and PRSP strains were 321 (34%) in 949 S. pneumoniae strains, and BLNAS strains were 545 (69%), low-BLNAR strains were 104 (13%), BLNAR strains were 81 (11%), and BLPAR strains were 61 (8%) in 791 H. influenzae strains. The results of gene analysis showed that all resistant strains by MICs such as PISP, PRSP, BLNAR, and BLPAR had resistant genes and that 55% of and 21% of susceptible strains of S. pneumoniae (PSSP) and H. influenzae (BLNAS), respectively, had resistant genes. From the investigation for profiles of 1,359 patients, age less than 3 years old, day nursery, and use of antimicrobial agents in last 3 month, seemed to be the risk factors for carriage of resistant strains. To prevent the resistant bacteria from disseminating we should re-consider how to use the antimicobial agents and nurse the young children.

[The study on efficacy of oseltamivir for influenza A in children].

From January 2001 to July 2002, we investigated the duration of fever, the duration of hospitalization, the frequency of antipyretic use, and other clinical symptoms of 162 inpatients with influenza A virus infection, and compared them with oseltamivir-treated, amantadine-treated, and untreated groups. The duration of fever and the duration of hospitalization treated were significantly shortened in the oseltamivir-treated group than in the amantadine-treated group and untreated group. There was no difference in the duration of fever between patients treated by oseltamivir at 2 mg/kg/day and those at 4 mg/kg/day. The frequency of antipyretic use was lower in the oseltamivir-treated group than in the other group. No difference was observed in the duration of fever and the frequency of antipyretic use between patients treated by oseltamivir with antibiotics and those by oseltamivir alone. The complications such as vomiting, abdominal pain, irritability were observed in 9% of patients treated by oseltamivir. But those symptoms were not serious, and the rate of complications in the oseltamivir-treated group was lower than that in untreated group. In conclusion, oseltamivir is safe and effective in the treatment of influenza virus infection in children, and it may reduce the amount of antibiotics and antipyretic use.