Nationwide surveillance of bacterial pathogens isolated from children conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2017: General overview of pathogenic antimicrobial susceptibility.

A nationwide surveillance of the antimicrobial susceptibility of pediatric patients to bacterial pathogens was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in Japan in 2017. The isolates were collected from 18 medical facilities between March 2017 and May 2018 by the three societies. Antimicrobial susceptibility testing was conducted at the central laboratory (Infection Control Research Center, Kitasato University, Tokyo) according to the methods recommended by the Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 926 strains (331 Streptococcus pneumoniae, 360 Haemophilus influenzae, 216 Moraxella catarrhalis, 5 Streptococcus agalactiae, and 14 Escherichia coli). The ratio of penicillin-resistant S. pneumoniae was 0% based on CLSI M100-ED29 criteria. However, three meropenem or tosufloxacin resistant S. pneumoniae isolates were obtained. Among H. influenzae, 13.1% of them were found to be ß-lactamase-producing ampicillin resistant strains, while 20.8% were ß-lactamase non-producing ampicillin-resistant strains. No capsular type b strains were detected. In M. catarrhalis, 99.5% of the isolates were ß-lactamase-producing strains. All S. agalactiae and E. coli strains were isolated from sterile body sites (blood or cerebrospinal fluid). The ratio of penicillin-resistant S. agalactiae was 0%, while that of extended spectrum ß-lactamase-producing E. coli was 14.3%.

Recent trends in pediatric bacterial meningitis in Japan, 2016-2018 - S. agalactiae has been the most common pathogen.

BACKGROUND: Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan. The overall incidence of bacterial meningitis decreased thereafter. Streptococcus agalactiae has become the main organism. OBJECTIVES: The purpose of the present study was to investigate the incidence rate per 1000 admissions of bacterial meningitis and the change in causative organisms in subsequent years. METHODS: A cross-sectional, multicenter, non-interventional retrospective study regarding pediatric bacterial meningitis was conducted in Japan in 2019. We analyzed the epidemiological and clinical data for 2016-2018, and compared the information obtained in our previous nationwide survey database. We also investigated the risk factors for disease outcome. RESULTS: In the 2016-2018 surveys, 197 patients from 153 hospitals from all prefectures were evaluated. S. agalactiae (0-3 months, 39%), Streptococcus pneumoniae (2-112 months, 20%), and E. coli (0-136 months, 13%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.00 to 1.68 in 2000-2010 to 0.38 in 2013-2015, bu remained stable thereafter (0.35-0.40 in 2016-2018). Only one case with Neisseria meningitidis was reported. Nine cases with death were reported, including four cases with S. agalactiae. Risk factors for death and sequelae were consciousness disturbance, duration of convulsion, low CSF glucose levels, and disuse of dexamethasone (p < 0.05). CONCLUSIONS: The incidence in pediatric bacterial meningitis remained low, and S. agalactiae remains the most common cause of bacterial meningitis in Japan since 2012. S. pneumoniae is the most common cause after 3 months of age.

Surveillance on susceptibility of strains isolated from pediatric infections.

During the period from January to December 2015, 104 Streptococcus pneumoniae strains, 129 Haemophilus influenzae strains and 54 Moraxella catarrhalis strains isolated from clinical specimens of pediatric infections in the national 16 institutions, studied susceptibilities of total 28 antibiotics, the capsular serotype for S. pneumoniae, the capsular b type and ß-lactamase production capability for H. influenzae, and the ß-lactamase production capability for M. catarrhalis were measured. In S. pneumoniae, the results showed that 68 strains (65.4%) were PSSP, 32 (30.8%) were PISP, and 4 (3.8%) were PRSP. The susceptibilities of TBPM and GRNX among oral antibiotics, and PAPM among injectable antibiotics demonstrated the lowest value with MIC90 ≤ 0.06 µg/mL. The most frequent distribution of S. pneumoniae serotypes was seen in 15B, followed by 19A, and 35B. Serotype strains contained in 13-valent pneumococcal conjugate vaccine (PCV13) were 19 strains (18.3%). In H. influenzae, the results showed that BLNAS accounted for 40 strains (31.0%), BLNAI for 28 strains (21.7%), BLNAR for 47 strains (36.4%), ß-lactamase producing for 14 strains (10.8%). The susceptibilities of quinolones demonstrated the lowest outcome among oral antibiotics with MIC90 ≤ 0.06 µg/mL, and CTRX and TAZ/PIPC (TAZ4 fixed) among injectable antibiotics with MIC of 0.25 µg/mL. There was no detection of capsular type b strains. In M. catarrhalis, all the isolates were ß-lactamase producing strains. The susceptibilities of TBPM, CPFX, TFLX and GRNX among oral antibiotics, and TAZ/PIPC (TAZ4 fixed), PAPM, MEPM and DRPM among injectable antibiotics demonstrated the lowest outcome with MIC of ≤0.06 µg/mL.

Pediatric bacterial meningitis in Japan, 2013-2015 - 3-5 years after the wide use of Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines.

BACKGROUND: Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan when both vaccines were supported by the regional governments, and they were covered as routine recommended vaccines in 2013. The incidence of bacterial meningitis due to these organisms decreased in 2011 and 2012, but meningitis due to Streptococcus agalactiae and Escherichia coli remained unchanged. OBJECTIVES: We planned to confirm whether the incidence also decreased in subsequent years. METHODS: We analyzed the epidemiological and clinical data for 2013-2015, and compared the information obtained in the previous nationwide survey database and our previous reports. We also investigated the risk factors for disease outcome. RESULTS: In the 2013-2015 surveys, 407 patients from 366 hospitals from all prefectures were evaluated. S. agalactiae (33%), Streptococcus pneumoniae (25%), and E. coli (10%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.19 in 2009-2010 to 0.37 in 2013-2015 (p < 0.001). The incidence of H. influenzae and S. pneumoniae meningitis significantly decreased from 0.66 in 2009-2010 to 0.01 in 2013-2015, and from 0.30 to 0.09, respectively (p < 0.001). Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2015. The fatality rates for H. influenzae, S. pneumoniae, S. agalactiae, and E. coli in 2013-2015 were 0.0, 4.1, 3.1, and 2.6%, respectively. Risk factors for death and sequelae were consciousness disturbance, convulsion, low CSF glucose, and Staphylococcus sp. as a causative organism (p < 0.01). CONCLUSIONS: Hib vaccine and PCV have decreased the rate of bacterial meningitis. S. agalactiae has subsequently become the most common cause of bacterial meningitis in Japan.

Is It Necessary to Achieve a Complete Box Isolation in the Case of Frequent Esophageal Temperature Rises? Feasibility of Shifting to a Partial Box Isolation Strategy for Patients With Non-Paroxysmal Atrial Fibrillation.

INTRODUCTION: There are some cases with frequent luminal esophageal temperature (LET) rises despite titrating the radiofrequency energy while creating a linear lesion for the Box isolation of atrial fibrillation (AF). Little is known about the feasibility of redesigning the ablation lines for a modified Box isolation strategy to prevent fatal esophageal injury in those cases. METHODS AND RESULTS: Two hundred and seventeen patients who underwent a Box isolation of non-paroxysmal AF were evaluated. We divided them into 2 groups, patients in whom a box lesion set of the entire posterior left atrium had been achieved (complete Box isolation [CBI]; n = 157) and those in whom 2 additional peri-esophageal vertical lines were created at both the right and left ends of the esophagus, and those areas were left with an incomplete isolation when frequent rapid LET rises above 39.0 °C were observed while creating the floor line (partial Box isolation [PBI]; n = 60). During 20.1 ± 13.9 months of follow-up, the arrhythmia-free rates were 54.1% in the CBI group versus 48.3% in the PBI group (P = 0.62). In the second session, a complete Box isolation was highly achieved even in the PBI group (94.3% vs. 83.3%, respectively; P = 0.17) and after 2 procedures, the arrhythmia-free rates increased to 75.2% vs. 68.3%, respectively (P = 0.34). There was no symptomatic esophageal injury in the PBI group. CONCLUSION: In the case of frequent LET rises while creating the linear lesions for the Box isolation strategy for non-paroxysmal AF, shifting to the PBI strategy was feasible.

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan.

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case-control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE.

Long-Term Results of Radiofrequency Hot Balloon Ablation in Patients With Paroxysmal Atrial Fibrillation: Safety and Rhythm Outcomes.

INTRODUCTION: Isolation of pulmonary veins (PVs) and the posterior left atrium (LA) can be safely performed by radiofrequency hot balloon (RHB)-based box isolation. However, data on long-term effects for the treatment of atrial fibrillation (AF) by the use of this method remain limited. METHODS AND RESULTS: We treated 238 patients with paroxysmal AF (194 male; age. 62.6 ± 9.4 years) by RHB ablation. During 6.2-year (75 months) follow-up, 154 (64.7%) patients were free from atrial tachyarrhythmias (ATAs) without antiarrhythmic-drugs (AADs). We performed re-ablation in 69 of 84 patients with ATA recurrence (average 1.3 ± 0.6; median 1, total 91 procedures) using a 3D-mapping system and a conventional catheter. The sites of reconnection were observed at the PV in 61 of 69 (88.4%) patients and at the posterior LA in 58 of 69 (84.1%) patients. Finally, during mean follow-up of 4.6 ± 1.6 years, no-ATA episodes were detected in 201 (84.5%) patients without AADs. Independent predictors of ATA recurrence following a single procedure were heart failure with preserved ejection fraction (HR: 2.67, 95%CI: 1.40-5.10, P = 0.003) and low estimated glomerular filtration rate (HR: 1.81, 95%CI: 1.11-2.93, P = 0.03; cut-off of 62.0 mL/min/1.73 m(2)). During the follow-up period, there were 4 (1.7%) patients with PV stenosis (>70% reduction in PV diameter); however, none of these cases required intervention. Phrenic nerve palsy was detected in 8 patients (3.4%), but resolved during 3 months in all cases. CONCLUSION: RHB ablation can be effective during a long-term follow-up for patients with paroxysmal AF. Safety outcomes were within an acceptable range.

Prevalence of esophageal ulceration after atrial fibrillation ablation with the hot balloon ablation catheter: what is the value of esophageal cooling?

BACKGROUND: Little is known about luminal esophageal temperature (LET) monitoring during catheter ablation for atrial fibrillation (AF) using the radiofrequency hot balloon (RHB) technology. OBJECTIVE: The aim of this study is to investigate the impact of the use of a unique esophageal cooling method during RHB ablation. METHODS AND RESULTS: In this observational study, 318 consecutive patients (231 men; mean age, 63 ± 9 years) with symptomatic, drug-refractory, paroxysmal (n = 183) or persistent (n = 135) AF underwent RHB ablation with LET monitoring followed by a postprocedural, nonsymptom-driven esophageal endoscopy within 3 days of the ablation procedure. The patients have been divided into 3 groups. The first 22 patients treated are in Group A (n = 22) and had only LET monitoring without cooling of the esophagus. In Groups B (n = 128) and C (n = 168), patients had LET monitoring with cooling of the esophagus when the LET exceeded 43 °C and 39 °C, by infusion of cooled saline mixed with Gastrographin or Iopamidol, respectively. Group A had a higher risk of esophageal ulceration among the 3 groups (P < 0.0001). Saline infusion cooling initiated when the LET exceeded 43 °C (Group B) was not as safe as saline infusion cooling initiated when the LET exceeded 39 °C (Group C), demonstrated by the Group C minimum ulceration score and LET measurements while ablating the left superior pulmonary vein (LSPV) and left inferior pulmonary vein (LIPV) (P < 0.0001). CONCLUSION: Cooling the esophagus by a mix of Iopamidol and saline infusion when the LET exceeds 39 °C during RHB ablation may decrease the incidence and severity of esophageal thermal injury.

Antibiotic susceptibility survey of blood-borne MRSA isolates in Japan from 2008 through 2011.

We conducted an antibiotic susceptibility survey of 830 blood-borne methicillin resistant Staphylococcus aureus collected from nationwide hospitals in Japan over a three-year period from January 2008 through May 2011. Antibiotic susceptibility was judged according to the criteria recommended by the Clinical Laboratory Standard Institute. Over 99% of the MRSA showed to be susceptible to teicoplanin, linezolid, sulfamethoxazole/trimethoprim and vancomycin, and over 97% of them were susceptible to daptomycin, arbekacin and rifampin. The majority of the MRSA strains showed resistant to minocycline, meropenem, imipenem, clindamycin, ciprofloxacin, cefoxitin, and oxacillin in the rates of 56.6, 72.9, 73.7, 78.7, 89.0, 99.5, and 99.9%, respectively. Among the MRSA strains, 72 showed reduced susceptibility to vancomycin, including 8 strains (0.96%) of vancomycin-intermediate S. aureus (VISA), 54 (6.51%) of heterogeneous vancomycin-intermediate S. aureus (hVISA), and 55 (5.63%) of ß-lactam antibiotics-induced vancomycin resistant S. aureus (BIVR). Unexpectedly, among the 54 hVISA and 55 BIVR, 45 isolates (83.3% and 81.8%, respectively) showed both hVISA and BIVR phenotypes. A new trend of vancomycin resistance found in this study was that VISA strains were still prevalent among the bacteremic specimens. The high rates of the hVISA/BIVR two-phenotypic vancomycin resistance, and the prevalence of VISA in the bloodborne MRSA call attention in the MRSA epidemiology in Japan.

Effectiveness of inactivated influenza and COVID-19 vaccines in hospitalized children in 2022/23 season in Japan - The first season of co-circulation of influenza and COVID-19.

We have analyzed the inactivated vaccine effectiveness (VE)for preventing influenza hospitalization by test-negative design in the 2022/23 season. This is the first season of co-circulation of influenza and COVID-19, and a unique period because all inpatients received COVID-19 screening. Among 536 children hospitalized with fever, none were positive for both influenza and SARS-CoV-2. The adjusted VE for preventing influenza A for all children, the 6-12-year-old group, and those with underlying diseases was 34 % (95 ％CI, -16 %-61 %, n = 474), 76 % (95 ％ CI, 21 %-92 %, n = 81), and 92 % (95 ％ CI, 30 %-99 %, n = 86), respectively. Only 1 out of 35 hospitalized cases with COVID-19, and 42 out of 429 controls, had been immunized with COVID-19 vaccine. This is the first report showing influenza VE by age group in children in this limited season. We still recommend the inactivated influenza vaccine for children based on the significant VE in subgroup analysis.

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.

Serum and cerebrospinal fluid S100B, neuron-specific enolase, and total tau protein in acute encephalopathy with biphasic seizures and late reduced diffusion: a diagnostic validity.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized clinically by biphasic seizures and late magnetic resonance imaging abnormalities, such as reduced subcortical diffusion from day 3 onwards, often accompanied with some neurological sequelae. In the early stages of the disease, AESD closely resembles its far more prevalent and relatively benign counterpart, febrile seizure (FS). METHODS: We measured and compared the serum or cerebrospinal fluid (CSF) levels of S100B, neuron-specific enolase (NSE), and total tau protein in 43 patients with FS and 18 patients with AESD, at any point during the disease. To assess early diagnostic validity, we compared these biomarkers in 43 FS and eight AESD patients, with whom the day 0-2 samples were available. We used the receiver-operator characteristic curve to evaluate the diagnostic values of these markers. RESULTS: The levels of all biomarkers were significantly higher in AESD than FS patients. When only day 0-2 samples from AESD patients were used, the levels of all the measured biomarkers, except serum NSE, were still significantly higher in patients with AESD than in FS, suggesting that AESD could damage astrocytes, neurons, and axons, even in the early stages of the disease. According to the receiver-operator characteristic curve analyses, CSF S100B (cut-off value, 100 pg/mL) and CSF total tau protein (cut-off value, 100 pg/mL) were better predictors of AESD than other biomarkers. CONCLUSION: The combination of CSF S100B and CSF total tau protein resulted in a positive predictive value of AESD 83.3%, which could be helpful for early diagnosis, facilitating early therapeutic interventions.

Trends in effectiveness of inactivated influenza vaccine in children by age groups in seven seasons immediately before the COVID-19 era.

BACKGROUND: We have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6-11 months) and older (6-15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups. METHODS: The overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6-11 months, 1-2, 3-5, 6-12, and 13-15 years old) with adjustments including influenza seasons. RESULTS: A total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% [95% confidence interval (CI), 41-47], 63% [95 %CI, 51-72], and 37% [95 %CI, 32-42], respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% [95 %CI, 55-65] and 52% [95 %CI, 41-61], respectively). Analysis for the 2020/21 season was not performed because no cases were reported. CONCLUSIONS: This is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.

Transcatheter aortic valve implantation in rheumatic aortic stenosis with a functioning mitral prosthesis.

Transcatheter aortic valve implantation (TAVI) for patients with rheumatic aortic stenosis (AS) is not well-known. We herein report a case of TAVI in rheumatic AS without significant calcification and prior mitral valve replacement. An 80-year-old woman underwent TAVI for severe AS. Preoperative computed tomography revealed tricuspid aortic valve leaflets with commissural fusion, minimal calcification, and a minimal distance between the aortic annulus and mechanical mitral valve. TAVI was performed through a transfemoral approach under general anesthesia. After predilatation of the aortic valve with a 20-mm balloon, a 23-mm SAPIEN 3 valve was successfully deployed via slow inflation. Valve embolization did not occur, and the valve did not interfere with the prosthetic mitral leaflets. This report shows that TAVI can be safe, feasible, and effective in patients with rheumatic AS without significant calcification and prior mitral valve replacement. .

Influenza vaccine effectiveness against influenza A in children based on the results of various rapid influenza tests in the 2018/19 season.

During influenza epidemics, Japanese clinicians routinely conduct rapid influenza diagnostic tests (RIDTs) in patients with influenza-like illness, and patients with positive test results are treated with anti-influenza drugs within 48 h after the onset of illness. We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children (6 months-15 years old, N = 4243), using a test-negative case-control design based on the results of RIDTs in the 2018/19 season. The VE against influenza A(H1N1)pdm and A(H3N2) was analyzed separately using an RIDT kit specifically for detecting A(H1N1)pdm09. The adjusted VE against combined influenza A (H1N1pdm and H3N2) and against A(H1N1)pdm09 was 39% (95% confidence interval [CI], 30%-46%) and 74% (95% CI, 39%-89%), respectively. By contrast, the VE against non-A(H1N1)pdm09 influenza A (presumed to be H3N2) was very low at 7%. The adjusted VE for preventing hospitalization was 56% (95% CI, 16%-77%) against influenza A. The VE against A(H1N1)pdm09 was consistently high in our studies. By contrast, the VE against A(H3N2) was low not only in adults but also in children in the 2018/19 season.

Long-term effects of box isolation on sympathovagal balance in atrial fibrillation.

BACKGROUND: Complete isolation of the posterior left atrium, including all pulmonary veins (box isolation), is a feasible and safe atrial fibrillation (AF) treatment method. Data on long-term effects of box isolation on autonomic function, however, remain limited. METHODS AND RESULTS: A total of 92 patients (paroxysmal AF, n=76; persistent AF, n=16) undergoing box isolation with non-contact mapping were studied. Twenty-four-hours ambulatory electrocardiograms and transthoracic echocardiography were done at baseline and after 2 days, and at 3, 6 and 12 months. Autonomic functions were evaluated by means of heart rate variability (HRV). During a mean follow up of 16+/-5 months, no AF episodes were detected in 76 patients while AF recurred in 16. Significant long-term HRV attenuations were observed in all patients without AF recurrence, but not in those with AF recurrence. In patients without AF recurrence, the natural logarithm (Ln) high-frequency (HF) decreased significantly from 5.5+/-1.3 ms(2) (before) to 4.2+/-0.9 ms(2) (after 12 months, P<0.001) and the ratio of the low-frequency to HF power increased significantly from 2.4+/-2.0 (before) to 3.4+/-2.3 (after 12 months, P=0.05). LnHF was significantly lower in patients without than in those with AF recurrence during the 12-month period after ablation. Cardiac function improved significantly in patients without AF recurrence after box isolation. CONCLUSIONS: Changes in the sympathovagal balance with box isolation may contribute to AF prevention.

Characterization of beta-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR) in a patient with septicemia during long-term vancomycin administration.

It was reported that some methicillin-resistant Staphylococcus aureus (MRSA) show resistance to vancomycin (VCM) and beta-lactam antibiotics; thus, they are termed beta-lactam antibiotic-induced VCM-resistant MRSA (BIVR). The VCM resistance of MRSA is induced by the administration of beta-lactam antibiotics, but this phenomenon can be difficult to detect in the clinical laboratory. We detected the BIVR strain in a 64-year-old man who had had a ventilator tube inserted directly into the windpipe during long-term VCM therapy. The patient was diagnosed with MRSA pneumonia and septicemia on July 5, 2007, and sulbactam/ampicillin (SBT/ABPC) was administered for 5 days. However, the fever recurred, and administration of VCM was resumed for 7 days from July 19. Fever developed again, and VCM was administered again for 14 days from September 30. BIVR and VCM-low-sensitive MRSA were isolated from blood on October 18 and 22, although the VCM trough concentration was 10.2 microg/ml. On October 27, we changed to a combination of fosfomycin (FOM) and arbekacin (ABK), and thereafter the fever quickly decreased and the clinical symptoms abated. We isolated five MRSA strains from the blood of the patient, three strains of VCM-sensitive MRSA, one strain of BIVR, and one strain of a VCM-low-sensitive MRSA. The DNA band patterns determined by pulsed-field gel electrophoresis were completely identical except for the VCM-low-sensitive MRSA, which was missing one band. Furthermore, the VCM-low-sensitive MRSA became sensitive to beta-lactam antibiotics. Our results indicate the possibility that long-term VCM therapy is one of the factors that allow BIVR or VCM-low-sensitive MRSA to emerge, and this allows VCM therapy for MRSA to fail.

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013-18.

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses. METHODS: VE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed. RESULTS: In the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505-0.621], 0.550 [95% CI, 0.516-0.586]), 0.549 [95% CI, 0.517-0.583], and 1.014 [95% CI, 0.907-1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1-12 years, especially among those aged 1-5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A. CONCLUSIONS: Both one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.

Three-season effectiveness of inactivated influenza vaccine in preventing influenza illness and hospitalization in children in Japan, 2013-2016.

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age in 2015/16 season. In addition, based on the data obtained during the three seasons from 2013 to 2016, we estimated the three-season VE in preventing influenza illness and hospitalization. METHODS: Our study was conducted according to a test-negative case-control design (TNCC) and as a case-control study based on influenza rapid diagnostic test results. RESULTS: During 2015/16 season, the quadrivalent IIV was first used in Japan. The adjusted VE in preventing influenza illness was 49% (95% confidence interval [CI]: 42-55%) against any type of influenza, 57% (95% CI: 50-63%) against influenza A and 34% (95% CI: 23-44%) against influenza B. The 3-season adjusted VE was 45% (95% CI: 41-49%) against influenza virus infection overall (N = 12,888), 51% (95% CI: 47-55%) against influenza A (N = 10,410), and 32% (95% CI: 24-38%) against influenza B (N = 9232). An analysis by age groups showed low or no significant VE in infants or adolescents. By contrast, VE was highest in the young group (1-5 years old) and declined with age thereafter. The 3-season adjusted VE in preventing hospitalization as determined in a case-control study was 52% (95% CI: 42-60%) for influenza A and 28% (95% CI: 4-46%) for influenza B, and by TNCC design, it was 54% (95% CI: 41-65%) for influenza A and 34% (95% CI: 6-54%) for influenza B. CONCLUSION: We demonstrated not only VE in preventing illness, but also VE in preventing hospitalization based on much larger numbers of children than previous studies.

Inactivated influenza vaccine effectiveness and an analysis of repeated vaccination for children during the 2016/17 season.

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age during the 2016/17 season. In addition, we estimated the impact of repeated vaccination in children on VE. METHODS: Our study for VEs in preventing influenza and admission due to influenza were conducted according to a test-negative case-control design (TNCC) based on influenza rapid diagnostic test results. We also analyzed the VE by vaccine status in the current and previous seasons for the impact of repeated vaccination. RESULTS: During the 2016/17 season, the quadrivalent IIV was used in Japan. The adjusted VE in preventing influenza illness was 38% (95% CI, 29-46) against influenza A and 39% (95% CI, 18-54) against influenza B. Infants showed no significant VE. The VE in preventing hospitalization was not demonstrated. For the analysis of repeated vaccination, the vaccine was effective only when immunization occurred in the current season. The children who were immunized in two consecutive seasons were more likely to develop influenza compared to those immunized in the current season only (odds ratio, 1.58 [95% CI, 1.05-2.38], adjusted odds ratio, 1.53 [95% CI, 0.99-2.35]). However, the odds ratio of repeated vaccination was not significant when the analysis excluded those who developed influenza in the previous season. CONCLUSIONS: VE in children in the 2016/17 season was similar to values previously reported. Repeated vaccination interfered with the VE against any influenza infection in the 2016/17 season. The results of our study suggest that decreased VE by repeat vaccination phenomenon was associated with immunity by influenza infection in the previous season. However, the influenza vaccine should be recommended every season for children.