Pyelonephritis with bacteremia caused by Salmonella Choleraesuis in a Japanese patient with carcinoma of unknown primary origin: A case report.

Salmonella enterica subspecies enterica serovar Choleraesuis (S. Choleraesuis) is a nontyphoidal Salmonella pathogen that causes swine paratyphoids. S. Choleraesuis is a zoonotic pathogen transmitted to humans via contaminated food and causes sepsis. Here, we report a rare case of pyelonephritis caused by S. Choleraesuis in a Japanese patient with a carcinoma of unknown primary origin. On the day of admission, the patient was diagnosed with pyelonephritis associated with ureteral stent obstruction. He had no history of raw pork consumption or gastrointestinal symptoms. Gram-negative rods were isolated from urine and blood cultures, identified as Salmonella enterica subsp. enterica using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The serological typing results were O7: -: 1 and 5; however, the serotypes could not be determined. The isolate was identified as S. Choleraesuis using multilocus sequence typing, nucleotide sequence analysis of the fliC gene, and biochemical examination. Four days after a 14-day course of intravenous piperacillin-tazobactam (9 g/day), the patient showed relapse of the condition. Subsequently, the patient was treated with intravenous ceftriaxone (2 g/day) and oral amoxicillin (1000 mg/day) for 14 days each; recurrence was not observed. This novel case of pyelonephritis with bacteremia was caused by S. Choleraesuis in Japan. Conventional testing methods could not identify the serotypes; however, the case highlights the importance of adopting advanced diagnostic techniques based on molecular biology to ensure accurate pathogen identification.

Pediatric Invasive Pneumococcal Disease (IPD) in Yogyakarta, Indonesia: A Case Series.

Given the fact that invasive pneumococcal disease (IPD) has a high clinical burden, particularly among children in developing countries, data on its occurrence and clinical profile in Indonesia is still insufficient. We presented 3 cases of IPD in children who were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia between 2016 and 2019. While our first 2 patients had milder course of disease, our third patient who presented with meningoencephalitis had poor outcome. Risk factors shown in our cases were young age and malignancy history. Multiple antibiotic resistance was observed in our isolates. The fact that none of our patients have received pneumococcal vaccination marks the necessity of this vaccine especially for at-risk children.

Immunogenicity and safety of routine 13-valent pneumococcal conjugate vaccination outside recommended age range in patients with hematological malignancies and solid tumors.

Hematological malignancy and solid tumor are major risks for invasive pneumococcal disease. Thirteen-valent pneumococcal conjugate vaccine (PCV13) is recommended for immunocompromised patients aged 6 years and older and adults who had not received the vaccine previously. However, vaccination for these individuals is not publicly subsidized in Japan. We measured pneumococcal serotype-specific IgGs (Pn-IgGs) and opsonophagocytic activities (Pn-OPAs) against PCV13 serotypes (1, 3, 5, 6A, 7F, and 19A) in patients with hematological malignancies and solid tumors who were outside the recommended age range for routine vaccination at baseline and at 1 and 6 months after the first dose of PCV13. Pneumococcal serotype-specific memory B cells (Pn-MBCs) against serotype 3 were measured from a portion of the study samples. Thirty-seven patients (30 in the young patient group and 7 in the adult patient group) completed the study. Pn-IgGs were significantly elevated at 1 month post-vaccination and persisted in protection level for 6 months after the first vaccination against all six serotypes measured except serotype 3. Pn-OPAs were significantly elevated and persisted as well against all six serotypes. Pn-MBCs were measured in 10 patients, and 90% of them had at least one detectable Pn-MBC, and 70% of them showed an increased frequency of Pn-MBCs against serotype 3. No serious adverse events were observed up to 1 month after vaccination. PCV13 is thus safe and immunogenic, including against serotype 3, in patients with hematological malignancies and solid tumors outside the recommended age range for routine vaccination.

Genetic system underlying responses of Cryptococcus neoformans to cadmium.

Cryptococcus neoformans, basidiomycetous pathogenic yeast, is basically an environmental fungus and, therefore, challenged by ever changing environments. In this study, we focused on how C. neoformans responds to stress caused by cadmium that is one of high-risk pollutants. By tracking phenotypes of the resistance or sensitivity to cadmium, we undertook forward and reverse genetic studies to identify genes involved in cadmium metabolism in C. neoformans. We found that the main route of Cd2+ influx is through Mn2+ ion transporter, Smf1, which is an ortholog of Nramp (natural resistance-associated macrophage protein 1) of mouse. We found that serotype A strains are generally more resistant to cadmium than serotype D strains and that cadmium resistance of H99, a representative of serotype A strains, was found to be due to a partial defect in SMF1. We found that calcium channel has a subsidiary role for cadmium uptake. We also showed that Pca1 (P-type-ATPase) functions as an extrusion pump for cadmium. We examined the effects of some metals on cadmium toxicity and suggested (i) that Ca2+ and Zn2+ could exert their protective function against Cd2+ via restoring cadmium-inhibited cellular processes and (ii) that Mg2+ and Mn2+ could have antagonistic roles in an unknown Smf1-independent Cd2+ uptake system. We proposed a model for Cd2+-response of C. neoformans, which will serve as a platform for understanding how this organism copes with the toxic metal.

Recombinant thrombomodulin attenuates hyper-inflammation and glycocalyx damage in a murine model of Streptococcus pneumoniae-induced sepsis.

PURPOSE: The anticoagulant agent recombinant thrombomodulin (rTM) activates protein C to prevent excessive coagulation and also possibly regulates hyper-inflammation via neutralization of high-mobility-group B1 (HMG-B1). The glycocalyx layer in endothelial cells also plays a pivotal role in preventing septic shock-associated hyperpermeability. The present study examined the effect of rTM in a murine model of Streptococcus pneumoniae-induced sepsis. METHODS: Male C57BL/6N mice were injected intratracheally via midline cervical incision with 2 × 107 CFU of S. pneumoniae (capsular subtype 19A). Control mice were sham-treated identically but injected with saline. rTM (10 mg/kg) was injected intraperitoneally 3 h after septic insult. Blood concentrations of soluble inflammatory mediators (interleukin [IL]-1ß, IL-6, IL-10, and tumor necrosis factor [TNF]-α) were determined using a microarray immunoassay. Serum concentrations of HMG-B1 and syndecan-1, as a parameter of glycocalyx damage, were determined by enzyme-linked immunosorbent assay. The glycocalyx was also evaluated with electron microscopy. The lungs were removed, and digested to cells, which were then stained with a mixture of fluorophore-conjugated antibodies. Anti-mouse primary antibodies included PE-Cy7-conjugated anti-CD31, AlexaFluor 700-conjugated anti-CD45, PerCP-Cy5.5-conjugated anti-CD326, APC-conjugated anti-TNF-α, PE-conjugated anti-IL-6, and PE-conjugated anti-IL-10. A total of 1 × 106 cells per sample were analyzed, and 2 × 105 events were recorded by flow cytometry, and parameters were compared with/without rTM treatment. RESULTS: The blood concentration of TNF-α was significantly reduced 24 h after intratracheal injection in S. pneumoniae-challenged mice treated with rTM (P = 0.016). Levels of IL-10 in the lung endothelium of rTM-treated S. pneumoniae-challenged mice increased significantly 12 h after intratracheal injection (P = 0.03). Intriguingly, serum HMGB-1 and syndecan-1 levels decreased significantly (P = 0.010 and 0.015, respectively) in rTM-treated mice 24 h after intratracheal injection of S. pneumoniae. Electron microscopy indicated that rTM treatment preserved the morphology of the glycocalyx layer in septic mice. CONCLUSIONS: These data suggest that rTM modulates local inflammation in the lung endothelium, thus diminishing systemic inflammation, i.e., hypercytokinemia. Furthermore, rTM treatment reduced serum syndecan-1 levels, thus preventing glycocalyx damage. The use of rTM to treat sepsis caused by bacterial pneumonia could therefore help prevent both excessive inflammation and glycocalyx injury in the lung endothelium.

Pediatric Parapneumonic Effusion/Pleural Empyema in Japan: A Nationwide Survey.

BACKGROUND: Pediatric parapneumonic effusion/ pleural empyema (PPE/PE) is a severe infectious condition, and its management should be guided by local epidemiology and the patient's medical history. This survey aimed to determine the clinical and bacteriologic features of PPE/PE in Japan. METHODS: A nationwide retrospective questionnaire survey was conducted, targeting 159 pediatric specialist training medical facilities for inpatients ≤18 years of age who were admitted for PPE/PE between January 2007 and December 2016. RESULTS: Valid responses were obtained from 122 facilities, and 96 patients were identified from 38 facilities. The median age (interquartile range) was 2.7 (0.8-7.8) years. Overall, 60 (63 %) patients were men and 49 (51%) had comorbidities. The causative bacteria were identified in 59% of patients by culture except in one case identified using PCR. Streptococcus pyogenes (16%), Staphylococcus aureus (14%) and Streptococcus pneumoniae (13%) were the major pathogens. Carbapenems were administered to 34% of patients without comorbidities. Chest tube drainage was performed in 71%, intrapleural fibrinolytic therapy in 9.4%, surgery in 25% and mechanical ventilation in 29% of the patients. Five patients (5.2%) had complications and one (1.1%) had sequelae, but all patients (100%) survived. CONCLUSIONS: This is first report of a nationwide survey pertaining to pediatric PPE/PE in Japan. We found that the etiology showed a different trend from that reported in other countries. It is worrisome that molecular methods were rarely used for pathogenic diagnosis and carbapenems were overused. Thus, it is imperative to establish clinical guidelines for PPE/PE in Japan.

Haemophilus influenzae type b capsular polysaccharide antibody levels in Japanese young patients with hematological malignancies and asplenia.

Individuals with immunosuppressive condition have a high risk of invasive Haemophilus influenzae type b (Hib) infection. In Japan, routine Hib vaccination program for children under 5 years old was introduced in December 2008. However, the national policy does not make provision for individuals aged ≥5 years who have medical conditions associated with a high risk of invasive Hib disease to receive Hib vaccine. We measured serum anti-polyribosylribitol phosphate specific (anti-PRP) antibodies to Hib in patients aged ≥5 years with hematological malignancies and asplenia and evaluated their levels of anti-PRP antibodies in post administration of Hib vaccine era. A total of 65 patients (48 with hematological malignancies, and 17 with asplenia) were included in this study, of which 84% had not received Hib vaccine. In addition, 95.4% had short-term protective levels of anti-PRP antibodies (defined as ≥0.15 µg/mL) and 41.5% had long-term protective levels of anti-PRP antibodies (defined as ≥1.0 µg/mL). Five patients had low anti-PRP antibody levels despite a history of Hib vaccination. Our results suggest that young patients with underlying diseases such as hematological malignancies and asplenia may be at risk of invasive Hib disease. Hence, we recommend they should receive Hib vaccines even if they are over the age limit for routine Hib vaccination program.

The effects of health education on health science teachers' intention to recommend adolescent HPV vaccine for female students in Japan.

The Japanese government suspended proactive recommendation of human papillomavirus (HPV) vaccination due to several reports of adverse events related to it in 2013. After that, the immunization rate of HPV vaccine quickly declined in Japan. Health science teachers (HSTs) are qualified and licensed teachers in charge of health care and health education for students in Japanese schools. HSTs have not recommended HPV vaccination to female students, since active governmental recommendation for HPV vaccination was halted for 5 y. We conducted a primary survey targeting HSTs (N = 39) and university students taking the HST training course (N = 123). In each group, awareness regarding HPV vaccine and disease burden was evaluated and factors related to and barriers to HPV vaccine recommendation were identified. The primary survey found that many HSTs and university students recognized their insufficient knowledge regarding the HPV vaccine. Based on the primary survey's results, infectious disease specialists, collaborating with Japanese HSTs, developed educational slide sets on HPV vaccine. A secondary survey was conducted before and after the lecture with HSTs (N = 162), where we evaluated their intelligibility and intention to recommend HPV vaccination for female students. In the post-lecture, secondary survey, the number of HSTs who recommended the HPV vaccine to their students had statistically increased from 76 before the lecture, to 103 (p < .05). An educational lecture using appropriate materials improved HSTs' vaccine confidence and intention to recommend the HPV vaccine to their students, verifying the study's hypothesis.

Usefulness of Gastric Aspirate Culture for Diagnosing Congenital Immunodeficiency in an Infant with Fungal Pneumonia Caused by Rasamsonia piperina.

Chronic granulomatous disease (CGD) is a type of primary immunodeficiency disease, which increases susceptibility to recurrent bacterial and fungal infections. Sputum and bronchoalveolar lavage fluid are often obtained using bronchoscopy from adult patients for pathogenic diagnosis, although this approach is much more invasive for infants. We report the case of a 2-month-old boy with CGD, in which gastric aspirate culture was used to diagnose fungal pneumonia. Rasamsonia piperina was isolated from the gastric aspirate, and the patient was successfully treated with micafungin based on the drug susceptibility test results for the fungal isolate. The acid tolerance test revealed that R. piperina could grow at pH 2, indicating high acid resistance. Although we can only report our experience with a single case, gastric aspirate culture may be a useful tool for detecting fungal respiratory pathogens in children with primary immunodeficiency. Detecting these pathogens may help improve outcomes, as early diagnosis and appropriate treatment are extremely important for immunocompromised patients with respiratory infections.

Two pediatric cases of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction of gastric lavage.

Detecting Pneumocystis jirovecii by bronchoalveolar lavage or lung biopsy is the gold standard for diagnosis of P. jirovecii pneumonia (PJP); however, these techniques are not always applicable in children because of their high invasiveness. We report two pediatric cases of PJP diagnosed by polymerase chain reaction (PCR) of gastric lavage that were successfully treated. To date, there are no reported cases of using PCR of gastric lavage to diagnose PJP. On the day of PJP onset, both the infants required respiratory support and infiltrative shadows were observed in both lung fields on chest radiography. Furthermore, their (1 â†’ 3)-ß-D glucan levels were elevated. P. jirovecii was detected by PCR of gastric lavage and trimethoprim-sulfamethoxazole was administered for 3 weeks, following which their condition improved. They were long-term steroid users, but without any prophylaxis. PCR of gastric lavage in cases of suspected PJP may help in confirming the diagnosis in children who have mild to moderate airway symptoms, or have difficulty with invasive examination like bronchoscopy.

Novel biosynthetic pathway for sulfur amino acids in Cryptococcus neoformans.

We elucidated a unique feature of sulfur metabolism in Cryptococcus neoformans. C. neoformans produces cysteine solely by the O-acetylserine pathway that consists of serine-O-acetyl transferase and cysteine synthase. We designated the gene encoding the former enzyme CYS2 (locus tag CNE02740) and the latter enzyme CYS1 (locus tag CNL05880). The cys1Δmutant strain was found to be avirulent in a murine infection model. Methionine practically does not support growth of the cys1Δ strain, and cysteine does not serve as a methionine source, indicating that the transsulfuration pathway does not contribute to sulfur amino acid synthesis in C. neoformans. Among the genes encoding enzymes catalyzing the reactions from homoserine to methionine, the gene corresponding to the Saccharomyces cerevisiae MET17 encoding O-acetylhomoserine sulfhydrylase (Met17p) had remained to be identified in C. neoformans. By genetic analysis of Met- mutants obtained by Agrobacterium tumefaciens-mediated mutagenesis, we concluded that Cnc01220, most similar to Str2p (36% identity), cystathionine-γ-synthase, in the Saccharomyces genome, is the C. neoformans version of O-acetylhomoserine sulfhydrylase. We designated CNC01220 as MET17. The C. neoformans met3Δ mutant defective in the first step of the sulfate assimilation pathway, sulfate adenylyltransferase, barely uses methionine as a sulfur source, whereas it uses cysteine efficiently. The poor utilization of methionine by the met3Δ mutant is most probably due to the absence of the transsulfuration pathway, causing an incapability of C. neoformans to produce cysteine and hydrogen sulfide from methionine. When cysteine is used as a sulfur source, methionine is likely produced de novo by using hydrogen sulfide derived from cysteine via an unidentified pathway. Altogether, the unique features of sulfur amino acid metabolism in C. neoformans will make this fungus a valuable experimental system to develop anti-fungal agents and to investigate physiology of hydrogen sulfide.

Molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B.

In this study, we examined the molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B (HRSV-B). First, we performed time-scale evolution analyses using the Bayesian Markov chain Monte Carlo (MCMC) method. Next, we performed genetic distance, linear B-cell epitope prediction, N-glycosylation, positive/negative selection site, and Bayesian skyline plot analyses. We also constructed a structural model of the F protein and mapped the amino acid substitutions and the predicted B-cell epitopes. The MCMC-constructed phylogenetic tree indicated that the HRSV F gene diverged from the bovine respiratory syncytial virus gene approximately 580years ago and had a relatively low evolutionary rate (7.14×10-4substitutions/site/year). Furthermore, a common ancestor of HRSV-A and -B diverged approximately 290years ago, while HRSV-B diverged into three clusters for approximately 60years. The genetic similarity of the present strains was very high. Although a maximum of 11 amino acid substitutions were observed in the structural model of the F protein, only one strain possessed an amino acid substitution located within the palivizumab epitope. Four epitopes were predicted, although these did not correspond to the neutralization sites of the F protein including the palivizumab epitope. In addition, five N-glycosylation sites of the present HRSV-B strains were inferred. No positive selection sites were identified; however, many sites were found to be under negative selection. The effective population size of the gene has remained almost constant. On the basis of these results, it can be concluded that the HRSV-B F gene is highly conserved, as is the F protein of HRSV-A. Moreover, our prediction of B-cell epitopes does not show that the palivizumab reaction site may be recognized as an epitope during naturally occurring infections.

Quality control in QuantiFERON-TB gold in-tube for screening latent tuberculosis infection in health care workers.

QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube.

Clinical and bacteriological analyses of bacteremia due to Corynebacterium striatum.

BACKGROUND: Corynebacterium striatum was recently recognized as a potential pathogen of various infectious diseases. However, the clinical entity of this microorganism has not been clearly identified. Therefore, we analyzed C. striatum isolates from blood culture and explored their clinical determinants. METHODS: We reviewed the medical records of all patients from whom C. striatum isolates were recovered from blood culture for analysis of the patients' backgrounds and clinical course including response to antimicrobial therapy and prognosis. RESULTS: During the 5-year study period (January 2010 to December 2014), 24 C. striatum strains were isolated from blood samples, and the frequency of C. striatum bacteremia increased. The majority of the strains were multidrug resistant. All of the tested strains were susceptible to only vancomycin. The age at onset of C. striatum bacteremia encompassed all adult age groups, and at least one underlying condition was documented in all patients. Thirteen of the 24 patients were cured using appropriate antibiotics (true infection group); however, 11 of the 24 patients were cured using inappropriate antibiotic therapy or no antibiotics (contamination group). Malignancy and neutropenia significantly increased the odds of true C. striatum bloodstream infection. CONCLUSIONS: The Corynebacterium species is often considered a contaminant when isolated in culture. Instead, particularly when the strain is isolated from blood, the species should be considered clinically relevant and identified to the species level; in addition, antimicrobial susceptibility testing is recommended.

The First Case of Invasive Mixed-Mold Infections Due to Emericella nidulans var. echinulata and Rasamsonia piperina in a Patient with Chronic Granulomatous Disease.

A 16-year-old boy with chronic granulomatous disease presented with pneumonia and rib osteomyelitis. Emericella nidulans var. echinulata was isolated from his sputum. After starting voriconazole, Rasamsonia piperina was isolated from the rib swelling. A combination therapy of voriconazole and micafungin effectively eradicated this invasive mixed-mold infection. In immunocompromised patients, a precise pathogenic diagnosis is clinically useful for administration of an appropriate treatment regimen.

Linezolid-resistant Staphylococcus epidermidis associated with long-term, repeated linezolid use in a pediatric patient.

We report an 8-year-old patient with catheter-related bacteremia caused by linezolid-resistant Staphylococcus epidermidis that was isolated after the long-term, repeated use of linezolid. Three S. epidermidis strains isolated from this patient were bacteriologically analyzed. While the strain isolated prior to linezolid initiation was susceptible to linezolid, two strains after linezolid therapy displayed low-level linezolid susceptibility (MIC, 4 mg/L) and linezolid resistance (MIC, 16 mg/L). T2500A mutation in two copies and G2575T mutations in three copies of 23S rRNA were detected in the low-susceptible strain and the resistant strain, respectively. Linezolid-resistant S. epidermidis infection is rare, but may occur with the long-term administration of linezolid.

Molecular evolution of the hypervariable region of the attachment glycoprotein gene in human respiratory syncytial virus subgroup B genotypes BA9 and BA10.

We studied the molecular evolution of the C-terminal 3rd hypervariable region in the attachment glycoprotein gene of human respiratory syncytial virus subgroup B (HRSV-B) genotypes BA9 and BA10. We performed time-scaled phylogenetic analyses using Bayesian Markov chain Monte Carlo methods. We also performed a genetic distance analysis (p-distance analysis), positive and negative selection analyses, and a Bayesian skyline plot (BSP) analysis. We found that genotype BA9 diverged from the common ancestor of genotypes BA7, BA8, and BA10, while genotype BA10 diverged from the ancestor of genotypes BA7 and BA8. Strains of both genotypes were distributed worldwide. BA9 and BA10 diverged between 1999 and 2001. Both BA9 and BA10 evolved rapidly (about 4.8×10(-3)substitutions/site/year) and formed three distinct lineages in a 10-year period. BA10 strains belonging to lineage 3 had large genetic distances (p-distance>0.07). Thus, it may be possible to classify these strains as a new genotype, BA11. No positive selection site was detected in either genotype. Phylodynamic analyses showed that the effective population size of BA10 decreased gradually since 2010 and BA9 slightly decreased since 2009. The results suggested that the recently prevalent HRSV-B genotypes BA9 and BA10 evolved uniquely, leading to epidemics of HRSV-B worldwide over a 15-year period.

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.

The effects of disodium cromoglycate on enhanced adherence of Haemophilus influenzae to A549 cells infected with respiratory syncytial virus.

Nontypeable Haemophilus influenzae (NTHi) secondary infection often complicates respiratory syncytial virus (RSV) infections. Previous studies have revealed that RSV infections enhance NTHi adherence to airway epithelial cells. In this study, we investigated the effects of disodium cromoglycate (DSCG) and corticosteroids, which are frequently used for the treatment of wheezing often related to RSV infections, on the adherence of NTHi to RSV-infected A549 cells. DSCG inhibited enhanced adherence of NTHi to RSV-infected A549 cells, whereas dexamethasone (Dex) and fluticasone propionate (Fp) did not. DSCG suppressed the expression of ICAM-1, which is one of the NTHi receptors. Furthermore, DSCG exhibited an inhibitory effect on RSV infections. It is suggested that DSCG exerts an anti-RSV effect, and consequently attenuates the expression of NTHi receptors.

Pneumococcal endocarditis in children: a nationwide survey in Japan.

BACKGROUND: Infective endocarditis (IE) due to Streptococcus pneumoniae (S. pneumoniae) carries a high mortality rate. However, little is known about pneumococcal IE in children and no optimal therapy has been established. Thus, we attempted to identify the clinical features of this disorder through a Japanese nationwide survey. METHODS: Members of the Japanese Society of Pediatrics Cardiology and Cardiac Surgery registered 170 pediatric patients with IE diagnosed during a 5-year period (1997-2001). Nine of these patients (5.3%) had pneumococcal IE. The clinical course, treatment and outcome of these 9 patients, aged 7 months to 4 years, were analyzed. RESULTS: Pneumococcal IE was associated with congenital heart disease in 7 patients and accompanied by other systemic infections including meningitis, pneumonia and otitis media, in 4 patients. Five of the 9 (55.6%) strains isolated by blood culture were penicillin-resistant S. pneumoniae strains. Seven patients were treated with carbapenem. Three underwent cardiac surgery due to cardiac failure and/or vegetation. One died due to septic shock on the first day of hospitalization. CONCLUSIONS: In children, pneumococcal endocarditis is often accompanied by severe systemic infections. The majority of pediatric cases are caused by penicillin-resistant S. pneumoniae strains. Carbapenem is an effective for IE caused by penicillin-resistant S. pneumoniae. This survey might be helpful to establish proper management strategies for pediatric pneumococcal IE.