Effect of probiotics on mother-to-neonate vertical transmission of group B streptococci: A prospective open-label randomized study.

BACKGROUND: Group B Streptococci (GBS) are common vaginal bacteria found in 20-30% of pregnant women and a significant cause of invasive infections in newborns. Recently, attention has been focused on the efficacy of probiotics during the perinatal period. However, the effect of probiotic intake on the mother-to-child transmission (MTCT) of GBS remains unknown. METHODS: Pregnant women with positive GBS results from vaginal and rectal swab cultures at 35-37 weeks of gestation were randomly assigned to the probiotic group or the control group in an open-label manner at the Department of Obstetrics and Gynecology, San-ikukai Hospital, Tokyo, Japan. The probiotic group received Lactobacillus reuteri during antenatal checkups from 35 to 37-week gestation to 1 month after delivery. Rectal swabs were obtained from the newborns at 5 days and at 1 month of age. Whole-genome sequencing was performed to test for GBS strains in the mother, whose newborn carried GBS at the 1-month checkup. Multi-locus sequence typing and single nucleotide polymorphism analyses were performed to identify MTCT. RESULTS: Overall, 67 mother-infant pairs were included, with 31 in the probiotic group and 36 in the control group. The positivity rate of GBS in newborns at 1 month of age was 10% (n = 3) in the probiotic group and 28% (n = 10) in the control group. In newborns carrying GBS at 1 month of age, genetic analysis revealed that the MTCT rate was 6% in the probiotic group and 22% in the control group, although the difference was not statistically significant (p = 0.0927). CONCLUSION: No statistically significant difference was found; however, the consumption of L. reuteri by women with GBS-positive pregnancies may inhibit the MTCT of GBS.

Characteristics and antimicrobial choice of pediatric bacterial enteritis in the Kanto region of Japan: A multicenter retrospective observational study.

INTRODUCTION: There are few reports on the causative microorganisms of bacterial enteritis in children in Japan in recent years. The distribution of causative microorganisms is important for estimating pathogens and making decisions regarding the treatment plan, as antimicrobial agents are not required for mild bacterial enteritis cases but are used for severe cases or immunocompromised patients. METHODS: We retrospectively surveyed pediatric patients who underwent stool culture at eight hospitals in the Kanto region of Japan from 2014 to 2019 for patient characteristics, causative microorganisms, and prescribed antimicrobial agents. RESULTS: A total of 4,475 stool cultures were submitted, and the positivity rate for bacterial enteritis was 11%. The causative microorganisms were Campylobacter spp. in 338 cases (67.3%), Salmonella spp. in 85 cases (16.9%), enterohemorrhagic Escherichia coli O157 in 23 cases (4.6%), and Yersinia spp. in 45 cases (9.0%). Hospitals with pediatric infectious disease physicians had a lower rate of antimicrobial therapy for Campylobacter enteritis than hospitals without pediatric infectious disease physicians. CONCLUSIONS: Campylobacter spp. are the most common causative agent for bacterial enteritis in this study, and the presence of pediatric infectious disease physicians may promote the appropriate use of antimicrobial agents.

Amoxicillin effect on bacterial load in group A streptococcal pharyngitis: comparison of single and multiple daily dosage regimens.

BACKGROUND: Culture tests have demonstrated that once-daily administration of amoxicillin may be effective in the treatment of group A streptococcal (GAS) pharyngitis. However, culture methods do not allow accurate assessments of bacterial load changes because of the suppressive effect of the antibiotic on bacterial growth. In this study, we used real-time PCR to compare the effectiveness of once-daily and multiple-daily amoxicillin treatment for pediatric patients with GAS pharyngitis. METHODS: The subjects were children (≧3 years of age) diagnosed with GAS pharyngitis. Amoxicillin was administered at a dose of 40-50 mg/kg/day, divided into one (QD), two (BID), or three (TID) daily doses, for 10 days. Throat swabs were collected before treatment (visit 1), 1 to 3 days after treatment (visit 2), and 9 to 11 days after treatment (visit 3), and GAS copies were quantified by real-time PCR. The main compared parameters were the rate of negative PCR results and the number of GAS determined by PCR in throat swabs between each regimen. RESULTS: Samples were collected from 34 patients (QD, 12; BID, 15; TID, 7) at visit 1, 32 patients (QD, 11; BID, 14; TID, 7) at visit 2, and 25 patients (QD, 7; BID, 11; TID, 7) at visit 3. The rates of negative PCR result for QD, BID, and TID regimens were 18.2, 0, and 14.3% at visit 2, and 85.7, 72.7, and 85.7% at visit 3, respectively. The median values of bacterial load for QD, BID, and TID groups at visit 1 were 1.4 × 106, 8.2 × 105, and 5.4 × 105 copies/µL. At visit 2, they comprised 3.8 × 103, 1.1 × 103, and 2.8 × 103 copies/µL, respectively, whereas at visit 3, GAS copies were mostly undetectable. There was no statistical difference in the negative results and median value of GAS copies between regimens at any stage. CONCLUSIONS: Our results obtained by a molecular biology approach indicated that the QD regimen was as effective in eradicating GAS infection as BID or TID. TRIAL REGISTRATION: UMIN000036083 / March 12, 2019.

Amplitude-integrated EEG revealed nonconvulsive status epilepticus in children with non-accidental head injury.

OBJECTIVE: We describe the clinical course and amplitude-integrated EEG findings in three children with non-accidental head injury and discuss on the importance of continuous aEEG monitoring in infants. METHODS: NCSE was defined as a continuous 30-min seizure or briefer seizures occurring consecutively comprising at least 30 min of any 1-h period. Non-accidental head injury was diagnosed on the basis of neuroimaging findings such as subdural hemorrhage. Antiepileptic treatment was performed with continuous amplitude-integrated EEG monitoring. RESULTS: The age of the patients ranged from 48 days to nine months. All of them had loss of consciousness and seizures on presentation. Nonconvulsive status epilepticus without clinical symptoms were recognized in all patients. Vigorous antiepileptic treatment against nonconvulsive status epilepticus was made in two patients, whereas nonconvulsive status epilepticus disappeared within one hour without additional treatment in one. CONCLUSIONS: Our experience indicates that nonconvulsive status epilepticus were not uncommon in children with non-accidental head injury. Continuous amplitude-integrated EEG monitoring will be one of the useful methods in encephalopathic children in order to estimate seizure burden objectively and to treat seizures appropriately.

Intestinal carriage of methicillin-resistant Staphylococcus aureus in nasal MRSA carriers hospitalized in the neonatal intensive care unit.

BACKGROUND: The current data regarding the correlation between the methicillin-resistant Staphylococcus aureus (MRSA) clones carried in the nasal cavity and digestive tract are inadequate. METHODS: MRSA strains were isolated from both the feces and nasal swabs of 21 nasal-MRSA carriers ranging from 10 to 104 days of age treated at the neonatal intensive care units of two hospitals. The molecular epidemiological characteristics of the isolates were determined: multilocus sequence types, spa-types, staphylococcal cassette chromosome mec (SCCmec) types, carriage of four exotoxin genes, and genes contained in commercially available kit. RESULTS: The feces of all nasal carriers contained MRSA at levels ranging from 4.0 × 10(2) to 2.8 × 10(8) colony forming units/g feces. The MRSA clones isolated from the feces and the nasal swabs of each patient were the same. Four MRSA clones, clonal complex (CC) 8-SCCmec IVl, CC8-SCCmec IVb, CC1-SCCmec IVa and CC5-SCCmec IIa were identified from 21 patients. All CC8-SCCmec IVl strains and one of three CC5-SCCmec IIa strains carried the toxic shock syndrome toxin gene. CONCLUSIONS: The feces of tested MRSA carriers contained the same MRSA clones as the nasal isolates in considerable amounts, suggesting that more careful attention should be paid for the handling of excrement in the case of newborn babies or infants than that of adults.

The clinical utility of a near patient care rapid microarray-based diagnostic test for influenza and respiratory syncytial virus infections in the pediatric setting.

We evaluated the potential clinical utility of an automated near patient molecular assay Verigene Respiratory Virus Plus (RV+) and rapid immunochromatographic antigen tests (RIAT) in the pediatric setting for diagnosis of influenza and respiratory syncytial virus infections when testing was performed by the pediatrician seeing the patient. Overall, with respect to influenza virus, sensitivity and specificity for RIAT were 70.8% and 100%, respectively, compared to 100% and 96.2%, respectively, for RV+. For respiratory syncytial virus, sensitivity and specificity for RIAT were 78.9% and 100%, respectively, compared to 100% and 100%, respectively, for RV+. When RIAT and RV+ sensitivity for influenza virus was compared based on the time the patient presented after onset of fever, the sensitivity of RIAT at 6 hours was 37.5% compared to 100% for RV+. At 12 hours, RIAT improved to 60.9%. This study confirms the clinical utility of RV+ in the pediatric setting.

A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting γ-aminobutyric acid degradation. We describe here a boy with a severe phenotype of SSADH deficiency. He was referred because of a developmental delay at 4 months of age. At the age of 8 months, severe seizures developed. The diagnosis of SSADH deficiency was confirmed by an increase in 4-hydroxybutyric acid and heteroallelic mutation in the ALDH5A1 gene. His seizures were successfully treated with high-dose phenobarbital, and the electroencephalogram (EEG) abnormalities were ameliorated. However, the patient showed a degenerative clinical course with severe neurological deficits. A magnetic resonance imaging (MRI) scan revealed abnormal high intensities in the putamina and caudate nuclei on T2-weighted images, followed by marked atrophic changes. The clinical manifestation of our patient indicates the wide variety of SSADH deficiency phenotypes.

Dissemination of multiple MRSA clones among community-associated methicillin-resistant Staphylococcus aureus infections from Japanese children with impetigo.

The proportion of MRSA strains that cause skin and soft infections has recently increased. In 3 months we have characterized 17 MRSA strains isolated from children with impetigo at a Japanese hospital. Seventeen MRSA strains belonged to 7 clones defined by clonal complex (CC) in MLST genotype and type of SCCmec, which were rarely identified among healthcare-associated MRSA: CC 91-SCCmecIIb (4 strains); CC91-SCCmecIIn (2 strains); CC91-SCCmecIVa (2 strains); CC91-SCCmecV (4 strains); CC88-SCCmecIVg (3 strains); CC1-SCCmecIVc (1 strain); and CC5-SCCmecIVn (1 strain). Although one strain belonged to CC5, which has been commonly identified in healthcare-associated MRSA, it did not carry type II SCCmec, but carried type IV SCCmec. Fourteen of the 17 strains carried exfoliative toxin a or b gene, and none carried Panton-Valentine leukocidine gene. Furthermore, we determined the entire nucleotide sequences of two type V SCCmec elements carried by strains JCSC5952, a CC91 strain, and TSGH17, a Taiwanese CC59 strain. The structure of SCCmecJCSC5952 was more than 99% homologous in nucleotide identity with those of Taiwanese PVL-positive ST59 MRSA strains TSGH17 and PM1, which were designated as type V (5C2&5). Identification of multiple MRSA clones distinct from those disseminating at the hospital suggests that MRSA strains might be emerging in the community from MSSA strains by acquiring SCCmec elements on various occasions. Carriage of the similar type V(5C2&5) SCCmec element by strains of distinct genetic backgrounds, CC91 and CC59, suggested horizontal transfer of the SCCmec element.

Clinical trial of minimal treatment for clustering seizures in cases of convulsions with mild gastroenteritis.

UNLABELLED: The aim of this study was to identify means of shortening the treatment period for clustering seizures in patients with convulsions with mild gastroenteritis (CwG). METHODS: Sixty-two episodes in 61 patients who presented with CwG managed with carbamazepine (CBZ) or Lidocaine (Lidocaine tape (LDT) or intravenous infusion (Lid-iv)) between November 2005 and October 2008 were studied. The subjects were divided into the following groups: 33 episodes treated with CBZ-1 (5mg/kg/day, 1 day), 7 with CBZ-3 (5mg/kg/day, 3 days), 11 with LDT-1 (LDT 2 sheets in 24h), 4 with LDT-2 (LDT 2 sheets in 48 h), and 7 with Lid-iv (1mg/kg/h, continuous infusion). RESULTS: One to seven seizures were recognized before starting CBZ or Lidocaine therapy, followed by complete cessation in 57 episodes and one or two recurrent seizures in five. Efficacy rates were 97% for CBZ-1, 100% for CBZ-3, 72.7% for LDT-1, 75% for LID-2, and 100% for Lid-iv. Efficacy was significantly higher in the CBZ groups than the Lidocaine groups (p=0.019), while the differences between treatment periods (CBZ-1 vs. CBZ-3, and Lid-1 vs. Lid-2) did not reach statistical significance (p>0.999). CONCLUSIONS: CBZ and Lidocaine were effective for treating clustering seizures of CwG. We confirmed that the treatment period can be shortened without loss of efficacy. Therefore, we consider 1 day therapy with CBZ or Lidocaine to be sufficient.

Amplitude-integrated electroencephalography in patients with acute encephalopathy with refractory, repetitive partial seizures.

We report amplitude-integrated EEG findings in two children with acute encephalopathy with refractory, repetitive partial seizures. Both patients had a febrile illness one week before the onset of seizure. They had reduction of consciousness and repetitive seizures refractory to first-line antiepileptic drugs. Seizure frequency rapidly increased and evolved into status epilepticus. Continuous seizure monitoring with amplitude-integrated EEG revealed frequent subclinical seizures which were missed by direct observation. In addition, the site of origin of seizures was multifocal, and seizure foci shifted from one hemisphere to the other. Their seizures were controlled after an administration of high-dose phenobarbital. Continuous seizure monitoring with amplitude-integrated EEG will contribute to correct estimation of seizure burden and efficacy of antiepileptic drugs in children with acute encephalopathy with refractory, repetitive partial seizures.

Efficacy of bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR for detecting neonatal sepsis: a case control study.

BACKGROUND: Neonatal sepsis is difficult to diagnose and pathogens cannot be detected from blood cultures in many cases. Development of a rapid and accurate method for detecting pathogens is thus essential. The main purpose of this study was to identify etiological agents in clinically diagnosed neonatal sepsis using bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR (BrRNA-RT-qPCR) and to conduct comparisons with the results of conventional blood culture. Since BrRNA-RT-qPCR targets bacterial ribosomal RNA, detection rates using this approach may exceed those using conventional PCR. METHODS: Subjects comprised 36 patients with 39 episodes of suspected neonatal sepsis who underwent BrRNA-RT-qPCR and conventional blood culture to diagnose sepsis. Blood samples were collected aseptically for BrRNA-RT-qPCR and blood culture at the time of initial sepsis evaluation by arterial puncture. BrRNA-RT-qPCR and blood culture were undertaken using identical blood samples, and BrRNA-RT-qPCR was performed using 12 primer sets. RESULTS: Positive rate was significantly higher for BrRNA-RT-qPCR (15/39, 38.5%) than for blood culture (6/39, 15.4%; p = 0.0039). BrRNA-RT-qPCR was able to identify all pathogens detected by blood culture. Furthermore, this method detected pathogens from neonates with clinical sepsis in whom pathogens was not detected by culture methods. CONCLUSIONS: This RT-PCR technique is useful for sensitive detection of pathogens causing neonatal sepsis, even in cases with negative results by blood culture.

Clustered subclinical seizures in a patient with acute encephalopathy with biphasic seizures and late reduced diffusion.

Using single-channel amplitude-integrated electroencephalography (aEEG), we monitored clustered seizures in a 12-month-old boy suffering from acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). He was admitted to our hospital after losing consciousness and experiencing repeated seizures in association with fever. Although the patient's state of consciousness improved the next day, it declined on the fifth day of illness, and clinical seizures were observed. Diffusion-weighted images revealed abnormal high intensities in the frontal area bilaterally. On the same day, aEEG monitoring revealed an unexpected cluster of subclinical seizures. Attending pediatricians, nurses, and other caregivers did not recognize the presence of these frequent subclinical seizures. The efficacy of antiepileptic drugs could also be objectively assessed from aEEG findings. aEEG is useful for continuous monitoring in children with acute encephalopathy, may disclose subclinical seizures, and can contribute to an objective evaluation of the efficacy of antiepileptic drugs.

Use of a sensitive chemiluminescence-based assay to evaluate the metabolic suppression activity of linezolid on methicillin-resistant Staphylococcus aureus showing reduced susceptibility to vancomycin.

Recently, strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (VCM) have been clinically isolated. The antibacterial activity of a new drug, linezolid (LZD), in such a strain was evaluated by measuring bacterial metabolic activity. A total of 73 MRSA strains having various susceptibilities to VCM were subjected to a novel and highly sensitive chemiluminescence-based assay. LZD MIC in the tested strains, measured by the microbroth dilution method, was within the range 1-4 mg/l (mostly

Usefulness of single-channel amplitude-integrated electroencephalography for continuous seizure monitoring in infancy: a case report.

We continuously monitored clustered seizures using single-channel amplitude-integrated electroencephalography (aEEG) in a 6-month-old girl with probable benign partial epilepsy in infancy (BPEI). The patient was admitted with clustered seizures, and aEEG using three disposable electrodes was started by a non-expert pediatrician. During the recording, seven seizures were detected. The last seizure was nearly overlooked on clinical observation, but was later confirmed on the basis of aEEG findings. The efficacy of antiepileptic drugs could also be objectively assessed from aEEG findings. Our results show that aEEG is useful for the continuous monitoring of seizures even in older children.

The spectrum of acute encephalopathy with reduced diffusion in the unilateral hemisphere.

We describe the clinical, EEG, and MRI features of children with reduced diffusion in the unilateral hemispheres. Seven patients with reduced diffusion in the subcortical white matter of the unilateral hemisphere alone were identified. Their median age was 32 months. Human herpesvirus 6 infection was virologically proven in 2 patients and human herpesvirus 7 in 1. The initial neurological symptom was a prolonged seizure in 4, a brief seizure in 2, and delirious behavior in 1. Three patients had biphasic clinical course. Laboratory tests were unremarkable in most patients. MRI showed no abnormal findings during the acute phase, whereas reduced diffusivity in the unilateral hemisphere was seen during the subacute phase. EEG during the acute phase demonstrated marked slowing in the affected hemisphere in 1 patient, mild slowing in 4, and relatively low voltage in 1. No patients died, but 6 patients had various degrees of neurological sequelae. Acute encephalopathy with reduced diffusion in the unilateral hemisphere may be one of the representative phenotypes of acute encephalopathy.

Time-suppression test using a colorimetric probe (alamarBlue) that measures bacterial metabolic activity.

We developed a time-suppression test using alamarBlue, which will allow estimation of the cidal or static nature of antimicrobials very easily and quickly. As an example, the effects of vancomycin, linezolid, and daptomycin on a representative strain of Staphylococcus aureus were estimated.

Impact of reduced vancomycin susceptibility on the therapeutic outcome of MRSA bloodstream infections.

BACKGROUND: The aim of this study was to determine whether clinical outcome of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia was correlated with vancomycin susceptibility of the corresponding strains. METHODS: A retrospective study on MRSA bacteraemia was performed at a teaching hospital between January 1998 and October 2005 by linking vancomycin susceptibility profiles of patients' isolates with hospitalization data. RESULTS: A total of 20 out of 209 MRSA bacteraemia patients were treated with vancomycin for at least 5 days with adequate trough levels, and fulfilled the study's inclusion and exclusion criteria. Twenty-two S. aureus isolates from these patients' blood cultures were identified as MRSA, including two hetero-VISA from separate patients and two VISA with vancomycin MIC of 4 mg/L from one patient. Between patients who showed 'good' vancomycin response and patients who did not, there was a significant difference (p < 0.01) in their corresponding MRSAs' vancomycin susceptibility expressed by 'area under curve' (AUC) of population analysis. Significant correlations were found between AUC and initial vancomycin therapeutic response parameters of 'days till afebrile' (r = 0.828, p < 0.01) and 'days till CRP < or =30% of maximum' (r = 0.627, p < 0.01) CONCLUSION: Our study results caution healthcare personnel that early consideration should be given to cases with a poor vancomycin treatment response that could signify the involvement of MRSA with reduced susceptibility to vancomycin.

Rapid detection of Staphylococcus aureus strains having reduced susceptibility to vancomycin using a chemiluminescence-based drug-susceptibility test.

Current drug-susceptibility tests used routinely in clinical laboratories sometimes fail to identify strains of Staphylococcus aureus with reduced susceptibility to vancomycin. To solve this problem, we have developed a more sensitive and rapid method that measures bacterial metabolic activity by a chemiluminescence-based technique. This method is able to discriminate such strains from vancomycin-susceptible S. aureus with a sensitivity and specificity of > 95%. This rapid and reliable method appears to be promising for detection of vancomycin-intermediate S. aureus strains in clinical laboratories, and may supersede classical susceptibility testing.