Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2022.

The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements.

[Antimicrobial Susceptibility of Streptococcus pneumoniae Isolated from 8 Hospitals in Chiba Prefecture Following the Introduction of 7-valent Pneumococcal Conjugate Vaccine].

We investigated the susceptibility of Streptococcus pneumoniae isolated from 8 hospitals in Chiba prefecture during 2012-2013. We further checked the serotype of S. pneumoniae derived from invasive pneumococcal disease (IPD). We tested for antimicrobial susceptibility in 256 clinical isolates (137 isolates from children, 119 isolates from adults) for 25 drugs. In MIC50 and MIC90, there were very little differences between children and adults, but there were 3 isolates from adults which were resistant to levofloxacin. The most major serotypes were 15A and 3 in IPD. Additionally there was no isolation of the type contained in the 7-valent pneumococcal conjugate vaccine in children, so it seems that the vaccination is very effective for children. Furthermore, in contrast with our preceding report, a decreasing was seen in PCG resistant proportion of S. pneumoniae. The maximum PCG-MIC was 2 µg/mL.

[Comparison of the clinical effectiveness of three neuraminidase inhibitors for Japanese pediatric patients with influenza in the 2013/2014 season].

We investigated the clinical symptoms of 206 pediatric patients with influenza virus infection and compared them among oseltamivir-treated, zanamivir-treated, and laninamivir-treated groups in 2013/2014 influenza season. The drug compliance of each neuraminidase inhibitor was good in all three groups. Although the duration of fever after administration of the first dose of each neuraminidase inhibitor were significantly prolonged in the patient with influenza B infection than in the patient with influenza A infection, no statistically significant difference in the clinical efficacy and the side effect among three groups were found. The number of biphasic fever episodes in patients treated with neuraminidase inhibitor was rare (two episodes of oseltamivir-treated group and one episode of zanamivir-treated group). In conclusion, under the good drug compliance, the efficacy of all three neuraminidase inhibitor was the same for the treatment of influenza virus infection in children.

Comparison of clinical efficacy between 3-day combined clavulanate/amoxicillin preparation treatment and 10-day amoxicillin treatment in children with pharyngolaryngitis or tonsillitis.

The efficacy of 3-day treatment with a combined clavulanate/amoxicillin preparation (Clavamox combination dry syrup for pediatric cases) and 10-day treatment with amoxicillin against pediatric pharyngolaryngitis and tonsillitis caused by Group A ß-hemolytic Streptococcus was compared. Among the patients included in the efficacy evaluation (54 from the clavulanate/amoxicillin group and 43 from the amoxicillin group), the clinical response rate on completion of treatment was 98.1 % in the clavulanate/amoxicillin group and 92.9 % in the amoxicillin group, thus supporting the equivalent efficacy of these two therapies. The Group A ß-hemolytic Streptococcus eradication rate at approximately 1-2 weeks after completion/discontinuation of treatment was 65.4 % in the clavulanate/amoxicillin group and 85.4 % in the amoxicillin group. Even in cases from which the pathogen continued to be isolated, relapse/recurrence of clinical symptoms was seldom seen. Urinalysis, conducted to assess the presence or absence of acute glomerulonephritis, revealed no abnormality in any patient. These results suggest that 3-day treatment with this clavulanate/amoxicillin preparation is expected to provide a valid means of treating pediatric pharyngolaryngitis and tonsillitis caused by Group A ß-hemolytic Streptococcus.

Complications of adenotonsillectomy: a case report of meningitis due to dual infection with nontypeable Haemophilus influenzae and Streptococcus pneumoniae, and a prospective study of the rate of postoperative bacteremia.

CASE REPORT: Bacterial meningitis is a rare complication of adenotonsillectomy. We present a case of meningitis due to nontypeable Haemophilus influenzae and Streptococcus pneumoniae after adenotonsillectomy. Pulsed-field gel electrophoresis patterns indicated that the oral cavity was the source of H. influenzae and S. pneumoniae isolated from the cerebrospinal fluid. BLOOD CULTURE STUDY: As bacteremia is thought to be one of the etiologies of meningitis, we prospectively investigated the rate of bacteremia as a complication of adenotonsillectomy. Of the 46 patients included in the study, mean age of five years old, 11 (24%) had positive blood cultures during the operation. H. influenzae was the commonest organism grown (seven cultures), three of seven produced beta-lactamase, followed by S. pneumoniae (one culture), H. parainfluenzae (one culture), Peptostreptococcus micros (one culture), and Veillonella spp. (one culture). The bacteria were composed of tonsil or adenoid surface cultures in eight of 11 patients (73%). CONCLUSIONS: We present a rare case of meningitis complicating a adenotonsillectomy procedure, in a three years old boy. Meningitis is a rare complication of adenotonsillectomy, but bacteremia which may lead to meningitis occurs frequently, as the results.

Japanese Guidelines for the Management of Respiratory Infectious Diseases in Children 2007 with focus on pneumonia.

Members of the Japanese Society of Pediatric Pulmonology and the Japanese Society for Pediatric Infectious Diseases developed the Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating the appropriate diagnosis and treatment of childhood respiratory infections. To date, a first edition (2004) and a revised edition (2007) have been issued. Many problems complicate the diagnosis of the pathogens responsible for bronchopulmonary infections in children. The Guidelines were the first pediatric guidelines in the world to recommend treatment with antimicrobials suited to causative pathogens as identified from cultures of sputum and other clinical specimens collected from infection sites and satisfying assessment criteria. The major causative microorganisms for pneumonia in infants and children were revealed to be Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae. This manuscript describes the Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2007, with a focus on pneumonia.

Intravenous immune globulin plus corticosteroids in refractory Kawasaki disease.

BACKGROUND: The aim of the present study was to investigate the efficacy of i.v. immune globulin (IVIG) therapy combined with corticosteroids for additional treatment of acute Kawasaki disease (KD) unresponsive to initial IVIG treatment. METHODS: In 50 prospective KD patients, six IVIG non-responders without clinical improvement within 24-48 h after completion of initial IVIG, received 2 g/kg IVIG concurrently with 2 mg/kg i.v. prednisolone sodium succinate (PSL) until normalization of C-reactive protein level. Treatment was then changed to oral PSL, which was tapered over time. Clinical and coronary artery lesion (CAL) outcomes were compared with those of 13 IVIG non-responders who received additional heterogeneous therapies in 125 retrospective KD patients. In addition, the scoring system of Kobayashi et al. for prediction of non-responsiveness to initial IVIG treatment was retrospectively verified in 175 KD subjects, consisting of 50 prospective and 125 retrospective patients in order to evaluate the efficacy of the re-treatment regimen. RESULTS: Incidence of CAL in the study patients was lower than in the control patients, although differences were not significant both in the acute stage (within 1 month: 1/6, 16.7% vs 7/13, 53.8%; P= 0.177) and in the convalescent stage (after 1 month: 0/6, 0.0% vs 4/13, 30.8%; P= 0.255). According to the non-responder prediction system, the scores of six study and 13 control patients before initial IVIG treatment were similar (7.2 ± 1.9 vs 5.3 ± 3.1; P= 0.200). No serious adverse effects related to each treatment were noted in patients of either group. CONCLUSIONS: Additional IVIG combined with concurrent PSL appears to be safe and worth evaluation for the treatment of acute KD unresponsive to initial IVIG treatment.

[Incidence of community-acquired pneumonia and pneumococcal pneumonia, among children in Chiba City, Japan].

Population-based studies on community-acquired pneumonia (CAP) are rare in Japan. Among 984 Chiba City children admitted with CAP to 19 local hospitals in 2005, 854 were younger than 5 years old. The annual CAP incidence among children < 5 years old was 19.7 per 1,000. Five, 4 of whom were under 5 years old, had pneumococcus isolated from blood. The incidence of CAP with pneumococcal bacteremia was 9.21 per 100,000 among those < 5 years old.

The incidence of pediatric invasive pneumococcal disease in Chiba prefecture, Japan (2003-2005).

OBJECTIVES: The purpose of the study is to evaluate the incidence, spectrum of clinical manifestations and outcome of invasive pneumococcal disease (IPD) in children in Chiba prefecture, Japan. METHODS: To determine the precise incidence of IPD in Chiba prefecture, we implemented a retrospective survey of the period from 2003 to 2005. A written questionnaire was sent to 45 hospitals that have pediatric wards, and information was obtained from all hospitals. The questionnaire included the clinical diagnosis, patient's age, underlying disease, prognosis and antimicrobial susceptibility of the isolated strains. RESULTS: During the 3 study years, 130 patients were diagnosed with IPD. The mean annual incidence rates of IPD among children <2 and <5 years were 19.5-23.8 and 12.6-13.8 per 100,000, respectively. Among 130 patients with systemic infection, 66 patients had bacteremia, 39 had pneumonia and 16 had meningitis. Five patients had neurological sequelae and 2 patients died. Seventy-four out of 115 isolates (64.3%) exhibited resistance to penicillin G. CONCLUSIONS: The annual incidence of pediatric IPD has remained constant during the study period. Two-third of isolated strains were at least partially resistant to penicillin G. Establishment of appropriate antibiotic therapy against IPD due to penicillin-resistant strains and the introduction of pneumococcal conjugate vaccines are emergent issues in Japan.

[Studies of treatment for Haemophilus influenzae type b meningitis in children].

We summarize 41 cases of bacterial meningitis in the last 11 years caused by Haemophilus influenzae. All isolates were serotype b strain (Hib). Initial chemotherapy was started with ceftriaxone (CTRX) in 22 cases, ampicillin plus cefotaxime (CTX) in 9, CTRX plus panipenem/betamipron in 5, and CTX in 2. Some 31 cases were treated mainly with CTRX. Although therapeutic antibiotics showed good susceptibility for isolates, 8 complicated cases (19.5%) occurred. Sequalae were observed in 7 (17.1%) but none were fatal. Five strains with elevated MIC of CTX (0.12 to 1 microg/mL) recovered after 2001, and 3 of 5 strains also showed elevated MIC of CTRX (0.12 to 0.5 microg/mL), but all were cured completely with CTRX. At present, no treatment failures due to antibiotic resistance have been observed, and CTRX remains suitable as initial therapy for Hib meningitis. A decline in susceptibility for third-generation cephalosporin against beta-lactamase-nonproducing ampicillin-resistant H. influenzae is emerging, however, so it will be necessary to consider combination therapy with CTRX given the foreseeable trend in MICs.

[Epidemiological survey of pneumococcus serotypes in pediatric patients with acute suppurative otitis media].

To determine the distribution of Streptococcus pneumoniae serotypes isolated from patients under 6 years of age with acute suppurative otitis media, to calculate the serotype coverage of 7-valent pneumococcal conjugate vaccine, and to clarify trends in PCG-resistant Streptococcus pneumoniae, we conducted a one-year prospective study from April 2005 to March 2006 at 10 medical institutions in Hokkaido, Miyagi, Chiba, Tokyo, Kanagawa, and Mie, Japan. Specimens collected by tympanotomy or myringotomy numbered 856, and 691 strains were isolated from 599 specimens. Of these, 219 isolates (31.7%) were identified as Streptococcus pneumoniae and 201 met study requirements. The most common serotype was 19F (52 isolates, 25.9%), followed by 6B (30 isolates, 14.9%) and 23F (24 isolates, 11.9%). Seven-valent vaccine serotype coverage was 62.7%. The percentage of PSSP was 40.3%, PISP 42.8%, and PRSP 16.9%, resistant strains (PISP and PRSP) combined accounted for 59.7%. Seven-valent vaccine serotype coverage for PISP was 80.2% and PRSP 82.4%. PBP gene mutation was observed in 175 isolates (87.1%), including 70 of gPISP (34.8%) and 105 of gPRSP (52.2%). Gene mutation induced by macrolides was found in 176 isolates (87.6%).

[Annual changes in antimicrobial susceptibility and macrolide resistance of Streptococcus pyogenes from 1995 through 2004].

This aim of this study was to reveal annual changes in antibiotic susceptibility, especially the macrolide susceptibility of Streptococcus pyogenes. A total of 755 strains of S. pyogenes were clinicaly isolated from throat swabs of children from 1995 through 2004 in Chiba Municipal Kaihin Hospital. All isolates were fully susceptible to benzylpenicillin, cefotaxim and cefaclor. The rate of resistance to erythromycin (EM) was over 10% every year after 2001 and 19% in 2004, and the rate of high resistance (MIC > or =16 microg/mL) has been increasing. A significant increase in EM resistance was observed over a 10-year period. There were 118 strains (15.6%) that persisted after treatment with beta-lactams. In the past few years it has been discovered that some S. pyogenes can be internalized by human cells of respiratory tract origin and survive within them. Since beta-lactams do not reach high intracellular concentrations, this ability of S. pyogenes may be related to treatment failure. Since macrolides can enter eukaryotic cells and remain active in intracellular compartments, they will be effective for these S. pyogenes. In case of pharyngitis which againist treatment with beta-lactams, there is a possibility macrolides are effective. Macrolides may be effective in pharyngitis resistant to treatment with beta-lactams. However, macrolide resistance is not rare, susceptibility must be tested.

[Clinical effects of piperacillin and tazobactam/piperacillin on Haemophilus influenzae lower respiratory tract infection in pediatric patients].

OBJECTIVE: The prevalence of beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae (H. influenzae) has been increasing in recent years. Piperacillin (PIPC) is one of a few beta-lactams possessing good activity against BLNAR H. influenzae. We studied clinical efficacy of piperacillin and its beta-lactamase inhibitor, tazobactam/piperacillin (TAZ/PIPC) in children with lower respiratory tract infection caused by H. influenzae including resistance strains. METHODS: Subjects were 20 children with lower respiratory tract infection caused by H. influenzae treated with PIPC 100mg/kg/day (7 cases) or TAZ/PIPC 125mg/kg/day (13 cases). We selected cases from which resistant H. influenzae strains might be detected. Patients received prior antimicrobial therapy within two weeks before admission, or with underlying diseases. We examined patient profiles, clinical efficacy, susceptibilities for 6 beta-lactam antibiotics [PIPC, TAZ/PIPC, ampicillin (ABPC), cefotaxime (CTX), ceftriaxone (CTRX), and meropenem (MEPM)] and analyzed 6 genotype patterns of beta-lactam resistant genes by PCR. RESULTS: Efficacy was 7/7 in patients in PIPC group and 12/13 in patients in TAZ/PIPC group. Diminished efficacy was seen in only one case complicated with severe RSV infection. The susceptibility of all strains but one beta-lactamase producing, ABPC resistant (BLP) strain to PIPC and of all to TAZ/ PIPC was below 0.25 microg/mL. The genotype of the 15 strains isolated from the sputum on administration was as follows; beta-lactamase nonproducing, ABPC-susceptible (gBLNAS) strains were 4, gBLP strain was 1, beta-lactamase nonproducing, and ABPC-resistant (gLow-BLNAR) strains were 2, beta-lactamase nonproducing, ABPC resistant (gBLNAR) strains were 8. CONCLUSION: PIPC and TAZ/PIPC were useful against lower respiratory tract infection caused by H. influenzae including BLNAR in children.

Efficacy of intravenous immune globulin therapy combined with dexamethasone for the initial treatment of acute Kawasaki disease.

UNLABELLED: We studied the effects of a new regimen consisting of intravenous immune globulin (IVIG) combined with dexamethasone (DEX) on clinical outcome and serum levels of vascular endothelial growth factor (VEGF) in the initial treatment of Kawasaki disease (KD). A total of 46 KD patients received 0.3 mg/kg per day DEX plus heparin i.v. for 3 consecutive days, together with 2 g/kg IVIG over 4 to 5 days (DEX group). Low-dose acetylsalicylic acid was started after completion of DEX therapy. The control group consisted of 46 KD patients retrospectively treated earlier with 2 g/kg IVIG over 4 to 5 days plus higher dose acetylsalicylic acid (CONTROL group). No serious adverse effect was noted in either group. There were no differences in baseline and post-treatment laboratory data except for C-reactive protein between the groups. Post-treatment C-reactive protein in the DEX group (median 0.9 mg/dl, range 0.0 to 24.7 mg/dl) was lower than that (1.2 mg/dl, range 0.2 to 19.5 mg/dl) in the CONTROL group ( P=0.033 by Mann-Whitney U test). In addition, the mean duration of fever after the first IVIG infusion was 2.2 days (median 1 day, range 1 to 12 days) in the DEX group and 2.8 days (2 days, 1 to 16 days) in the CONTROL group ( P=0.015 by Mann-Whitney U test). The new regimen did not reduce VEGF levels. Two patients in each group developed small- or medium-sized coronary artery aneurysms. CONCLUSION: Although this regimen did not affect coronary outcome, intravenous immune globulin therapy combined with dexamethasone for the initial treatment of Kawasaki disease was safe and may accelerate the resolution of systemic inflammation.