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The Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures in participating medical institutions nationwide and is intended to be used for promotion of AMR measures in participating facilities and their communities. This multicenter study aimed to determine the usefulness of the J-SIPHE system for evaluating the correlation between antibiotic use and antibiotic resistance in Hokkaido, Japan.Data on antibiotic use and detection rate of major resistant Gram-negative bacteria at 19 hospitals in 2020 were collected from the J-SIPHE system, and data correlations were analyzed using JMP Pro.The detection rate of carbapenem-resistant Pseudomonas aeruginosa was significantly positively correlated with carbapenem use (Spearman's ρ = 0.551; P = .015). There were significant positive correlations between the detection rate of fluoroquinolone-resistant Escherichia coli and the use of piperacillin/tazobactam, carbapenems, and quinolones [ρ = 0.518 (P = .023), ρ = 0.76 (P.001), and ρ = 0.502 (P = .029), respectively].This is the first multicenter study to investigate the correlation between antibiotic use and antibiotic resistance using the J-SIPHE system. The results suggest that using this system may be beneficial for promoting AMR measures.

Background The number of spinal infections has been increasing in developed countries due to the increase of aged or immunosuppressed patients. Spondylitis caused by multidrug-resistant (MDR) bacterial infection often become intractable and require long-term antibiotic therapy and multiple surgeries. Therefore, it is of great importance to understand risk factors for MDR spinal infections. The aim of this study was to elucidate the risk factors for MDR bacterial spondylitis. Methods A total of 122 patients (82 men, 40 women; average age: 63.8 y) with thoracic/lumbar spondylitis who underwent posterolateral full-endoscopic debridement and irrigation were included. The organisms detected by this endoscopic procedure were investigated, and the incidence and risk factors for MDR bacterial infection were retrospectively analyzed. Results Cultures of specimens obtained by endoscopic procedures were positive in 78 patients (63.9%). Among 68 isolated bacteria, MDR bacteria accounted for 47.1%. Multivariate analysis showed that significant risk factors for MDR bacterial infection included autoimmune connective tissue disease (P = 0.03) and central venous catheter (P = 0.02). The incidence of MDR bacteria in patients who were administered a broad-spectrum antibiotic for more than 1 month preoperatively was 64.0%, which was significantly higher than in patients who were administered a broad-spectrum antibiotic for less than 1 month and patients who were administered a narrow-spectrum antibiotic (P Conclusions The significant risk factors for MDR bacterial spondylitis included immunosuppressed conditions, such as autoimmune connective tissue disease, presence of central venous catheter, and longer administration periods of a broad-spectrum antibiotic. In patients with pyogenic spondylitis who could not be controlled with previous antibiotics and whose result of culture was negative, administration of anti-MRSA antibiotics would be considered when they have the risk factors identified in this study.

Background: There are no reports on the effects of interventions, such as discontinuation and change and/or deescalation of carbapenems and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics by an antimicrobial stewardship team focusing on detailed patient outcomes. This study aimed to evaluate these effects. Methods: This retrospective cohort study was conducted at a tertiary care hospital from December 2018 to November 2019. Results: Favorable clinical responses were obtained in 165 of 184 cases (89.7%) in the intervention-accepted group, higher than those in the not accepted group (14/19 cases, 73.7%; P = .056). All-cause 30 day mortality was lower in the accepted group than in the not accepted group (1.1% and 10.5%, respectively; P = .045). The microbiological outcomes were similar between the two groups. Duration of carbapenem and anti-MRSA antibiotic use in the accepted group was significantly lower than that in the not accepted group (median [interquartile range]: 8 days [5-13] versus 14 days [8-15], respectively, P = .026 for carbapenem; 10 days [5.3-15] vs 15.5 days [13.8-45.3], respectively, P = .014 for anti-MRSA antibiotic). Conclusions: This is the first study to investigate the effects of interventions such as discontinuation and change and/ or de-escalation of antibiotics on detailed outcomes. Our intervention could reduce the duration of carbapenem and anti-MRSA antibiotic use without worsening clinical and microbiological outcomes. (c) 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Objectives Mycoplasma pneumoniae is one of the common causative pathogens of community-acquired respiratory tract infections mainly in children and young adults. Rapid and accurate diagnostic techniques for identifying the causative pathogen would be useful for initiating treatment with an appropriate antibiotic. The purpose of the present study was to evaluate the sensitivity and specificity of a novel immunochromatographic assay using silver amplification technology using FUJI DRI-CHEM IMMUNO AG2 and FUJI DRI-CHEM IMMUNO AG cartridge Myco (FUJIFILM Co., Tokyo, Japan) for detection of M. pneumoniae. Methods Throat swab samples were collected from 170 pediatric patients who were diagnosed with bronchitis or pneumonia. The silver amplification immunochromatographic (SAI) assay was performed using these samples and the results were compared with those of real-time PCR. The time required for the SAI assay is approximately 20 min (5 min for sample preparation and 15 min for waiting time after starting the assay). Results The sensitivity and specificity of the SAI assay for detection of M. pneumoniae were 85.2 and 99.1%, respectively, and the assay showed positive and negative predictive values of 98.1 and 92.3%, respectively, compared with the results of real-time PCR. The diagnostic accuracy was 94.1%. Conclusions FUJI DRI-CHEM IMMUNO AG2 and FUJI DRI-CHEM IMMUNO AG cartridge Myco are appropriate for clinical use. The optimal timing of this assay is five days or more after the onset of M. pneumoniae infection. However, PCR or other molecular methods are superior, especially with regard to sensitivity and negative predictive value.

Background The efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli have been poorly investigated in Japanese patients. This study was performed to investigate the efficacy and safety of colistin in Japanese patients by analyzing a considerable number of cases. Furthermore, we evaluated the relationship between the plasma concentration and efficacy and safety of colistin in some cases. Methods A retrospective cohort study was conducted at Hokkaido University Hospital, analyzing patients treated with colistin (colistimethate sodium) during the period from January 2007 to December 2019. Results Overall, 42 cases were enrolled. Favorable clinical response was observed in 25 cases (59.5%), with an all-cause 30-day mortality of 33.3% (14/42 cases). Microbiological eradication was achieved in 18 cases (42.9%). Nephrotoxicity was observed in 20 cases (47.6%) and was mild and reversible in all cases. Plasma trough concentrations of colistin determined in nine patients correlated with changes in serum creatinine concentration (⊿) and creatinine clearance (%). The cutoff value of colistin trough concentration for nephrotoxicity was 2.02 μg/mL. Conclusion Our results showed approximately 60% clinical efficacy of colistin therapy against infections caused by multidrug-resistant gram-negative bacilli in the patients. Further studies with larger populations are needed to elucidate the efficacy and safety of colistin in Japanese patients.

Daptomycin, a cyclic lipopeptide antibiotic, has bactericidal activity against Gram-positive organisms and is especially effective against methicillin-resistant Staphylococcus aureus. Although daptomycin causes unique adverse drug reactions such as elevation of creatine phosphokinase or rhabdomyolysis, the detailed mechanisms underlying these adverse drug reactions in skeletal muscle are unclear. This study aimed to elucidate whether daptomycin causes direct skeletal muscle cell toxicity and investigate the relationship between daptomycin exposure and musculoskeletal toxicity. First, we evaluated the relationship between daptomycin exposure and skeletal muscle toxicity. Of the 38 patients who received daptomycin intravenously, an elevation in creatine phosphokinase levels was observed in five. The median plasma trough concentration of daptomycin in patients with elevated creatine phosphokinase levels was significantly higher than that in patients whose creatine phosphokinase levels were within the normal range, suggesting that increased exposure to daptomycin is related to elevation in creatine phosphokinase levels. In an in vitro study using human rhabdomyosarcoma cells, daptomycin reduced cell viability and increased membrane damage. These effects were more marked under hypoxic conditions. A necroptotic pathway seemed to be involved because phosphorylated mixed lineage kinase domain-like protein expression was enhanced following daptomycin exposure, which was significantly enhanced under hypoxic conditions. These findings indicate that daptomycin elicits cytotoxic effects against skeletal muscle cells via the necroptotic pathway, and the extent of toxicity is enhanced under hypoxic conditions.

Background The aim of this study was to determine the sensitivity and specificity of a novel immunochromatographic (IC) assay (APD1806) using monoclonal antibodies against the matrix (M) protein of human metapneumovirus (hMPV) for detection of hMPV from nasopharyngeal swab samples based on the results of real-time RT-PCR. Methods Nasopharyngeal swab samples taken from 189 patients aged 0 - 5 years who were suspected of having respiratory tract infections associated with hMPV were used in this study. The samples were tested both by the IC assay and by real-time RT-PCR for detection of hMPV. Results The sensitivity and specificity of the IC assay for detection of hMPV were 88.8% (95/107) and 92.7% (76/82), respectively. Conclusions The IC assay using monoclonal antibodies against the M protein of hMPV is an accurate and fast assay that is suitable as a diagnostic tool for hMPV infection. The optimal timing of the IC assay is 12 hours or more after the onset of fever due to hMPV infection.

Background Children with influenza virus infections are prone to complications and are common sources of influenza transmission. Baloxavir marboxil inhibits cap-dependent endonuclease and was approved for influenza treatment in adolescent, adult, and pediatric patients in Japan. The miniSTONE-2 study included pediatric patients with influenza (1 to Methods This is a multicenter, open-label, randomized, active-controlled trial in which 200 Japanese subjects aged 6 to Discussion No comparative studies have been conducted to confirm the efficacy and safety of baloxavir versus a comparator in pediatric patients with influenza infection in Japan. The outcomes from this trial will provide evidence on the efficacy and safety of baloxavir as an antiviral treatment option for Japanese pediatric patients with influenza infection. Trial registration Japan Registry of Clinical Trials: jRCTs011200011. Registered November 2020. (https://rctportal.niph.go.jp/en/).

We characterized 515 Mycoplasma pneumoniae specimens in Hokkaido. In 2013 and 2014, the p1 gene type 1 strain, mostly macrolide-resistant, was dominant and the prevalence of macrolide resistance was over 50 %. After 2017, the p1 gene type 2 lineage, mostly macrolide-sensitive, increased and the prevalence of macrolide resistance became 31.0 % in 2017, 5.3 % in 2018 and 16.3 % in 2019.

WHAT IS KNOWN AND OBJECTIVE Haematological toxicities such as neutropaenia are a common side effect of ganciclovir (GCV); however, risk factors for GCV-induced neutropaenia have not been well established. Decision tree (DT) analysis is a typical technique of data mining consisting of a flow chart-like framework that shows various outcomes from a series of decisions. By following the flow chart, users can estimate combinations of risk factors that may increase the probability of certain events. In our previous study, we demonstrated the usefulness of this approach in the evaluation of adverse drug reactions. Therefore, we aimed to construct a risk prediction model of GCV-induced neutropaenia including severity grade. METHODS We performed a retrospective study at the Hokkaido University Hospital and enrolled patients who received GCV between April 2008 and March 2018. Neutropaenia was defined as an absolute neutrophil count (ANC)

Antecedentes: Hasta ahora, la prevalencia de infecciones por Mycoplasma pneumoniae (MP) resistente a los macrólidos entre pacientes adultos ha sido baja, y los reportes de neumonía grave por MP debida a una cepa resistente a los macrólidos han sido escasos. En este trabajo describimos un caso raro de neumonía grave y potencialmente mortal en un adulto debido a una cepa de MP resistente a macrólidos, que finalmente se trató con fluoroquinolona y tetraciclina luego de un fracaso terapéutico con macrólido y corticosteroide. Presentación del caso: Una mujer de 39 años, aparentemente saludable, refirió fiebre y tos productiva. Tres días después del inicio de los síntomas se le ingresó en un hospital general local. Al momento de su admisión sus signos vitales eran estables, excepto por una fiebre elevada. Imágenes de rayos X y tomografía computada del pecho de la paciente revelaron una consolidación subtegumentaria en el lóbulo inferior derecho. Se inició tratamiento con ampicilina/sulbactam y azitromicina, con diagnóstico de neumonía adquirida en la comunidad. La fiebre no cedió con el tratamiento y la lesión pulmonar se extendió a todo el lóbulo inferior. Así, se administró prednisolona en pulsos a partir del día 7. Sin embargo, ni los síntomas ni la lesión pulmonar mejoraron, y se le transfirió a nuestro hospital para su examen y tratamiento. En la admisión (día 14 de progresión clínica), el título de hemaglutinación indirecta para MP se elevó hasta 1:2560, y el examen del fluido broncoalveolar dio resultados positivos para el antígeno de micoplasma. Con base en estos hallazgos clínicos, confirmamos un caso de neumonía grave y potencialmente mortal por MP. Puesto que la condición respiratoria de la paciente era extremadamente grave, iniciamos tratamiento con levofloxacina y tetraciclina. Dos días después (día 16 de progresión clínica) se resolvieron la fiebre, el malestar y la hipoxia, y las lesiones pulmonares mejoraron significativamente. Análisis moleculares identificaron el DNA de MP en el fluido broncoalveolar, y se reveló la mutación A2063G en el gen 23S rRNA. Con base en estos resultados y en la progresión clínica, confirmamos que nuestro caso se debió a neumonía grave por MP debido a una cepa resistente a macrólidos. Conclusión: Se requiere mayor sensibilización ante la emergencia de infecciones por MP resistente a los macrólidos en adultos, puesto que la infección puede agravarse a pesar del tratamiento inicial con macrólidos y esteroide, la terapia estándar para MP.

Objectives Macrolides are generally considered to be the drugs of choice for treatment of patients with Mycoplasma pneumoniae infection. However, macrolide-resistant M. pneumoniae has been emerging since about 2000. The Smart Gene® system (MIZUHO MEDY Co., Ltd., Tosu, Japan) is a novel fully automated system for detection of pathogens using the method of quantitative polymerase chain reaction (qPCR) with QProbe (QProbe PCR). The entire procedure is completed within 50 min and the size of the instrument is small (15 x 34 x 30 cm). The purpose of this study was to evaluate the usefulness of the Smart Gene® system for detection of M. pneumoniae and detection of a point mutation at domain V of the 23S rRNA gene of M. pneumoniae. Materials Pharyngeal swab samples were collected from 154 patients who were suspected of having respiratory tract infections associated with M. pneumoniae. Results Compared with the results of qPCR, the sensitivity and specificity of the Smart Gene® system were 98.7% (78/79) and 100.0% (75/75), respectively. A point mutation at domain V of the 23S rRNA gene was detected from 7 (9.0%) of 78 M. pneumoniae-positive samples by the Smart Gene® system and these results were confirmed by direct sequencing. The minimum inhibitory concentrations of clarithromycin among the 5 isolates of M. pneumoniae with a point mutation at domain V of the 23S rRNA gene were >64 μg/ml and those among the 33 isolates without a mutation in the 23S rRNA gene were Conclusion The Smart Gene® system is a rapid and accurate assay for detection of the existence of M. pneumoniae and a point mutation at domain V of the 23S rRNA gene of M. pneumoniae at the same time. The Smart Gene® system is suitable for point-of-care testing in both hospital and outpatient settings.

The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014-2015 to 2016-2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1.06 per 1 year of age, p < 0.001) and that the duration of fever after administration of the first dose of the NAI was shorter in patients with influenza A infection than in patients with influenza B infection (hazard ratio = 2.21, p < 0.001). A logistic regression model showed that the number of biphasic fever episodes was 2.99-times greater for influenza B-infected patients than for influenza A-infected patients (p < 0.001). The number of biphasic fever episodes in influenza A-or B-infected patients aged 0-4 years was 2.89-times greater than that in patients aged 10-18 years (p = 0.010), and the number of episodes in influenza A-or B-infected patients aged 5-9 years was 2.13times greater than that in patients aged 10-18 years (p = 0.012).

Bacteremia is one of the most serious infectious illness resulting from nosocomial infection. Therefore, appropriate antimicrobial chemotherapy should be provided as soon as possible to patients exhibiting symptoms of infectious disease and having positive blood culture results. Antimicrobial stewardship (AS) guidelines were recently released by the Infectious Diseases Society of America. The guidelines recommend "proactive intervention and feedback" as one of the core strategies for implementing optimal antimicrobial drug use to improve patient outcomes in clinical settings. We began using the AS program for optimizing antimicrobial chemotherapy in patients with positive blood culture results. The results of blood cultures and antimicrobial prescriptions for the corresponding patients were daily reviewed by a pharmacist and a physician, members of the infection control team (ICT). If the antimicrobial agents selected were inappropriate, ICT made a recommendation to the attending physicians who prescribed the antibiotics. To evaluate the outcomes of this program, we conducted a single-center, retrospective investigation for near a hundred of patients who underwent intervention by infection-control physician and pharmacist. Resolution of bacteremia (determined by blood culture results) was 96.3% in the group that accepted intervention, whereas only 16.7% of the cases resolved in the group that did not accept intervention. These results strongly suggest the importance of the infection disease-specialist team intervention. This program could become an important method for improving clinical outcomes in patients with bacteremia.

Inpatients who had been in close contact with patients with influenza were given oseltamivir [75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children] for three days as postexposure prophylaxis (PEP). The index patients with influenza were prescribed a neuraminidase inhibitor and were discharged immediately or transferred to isolation rooms. The protective efficacy of oseltamivir for three days was 93% overall [95% confidence interval (CI) 53-99%; P = 0.023] and 94% for influenza A (95% CI 61-99%; P = 0.017), which is comparable to that of seven- to 10-day regimens of oseltamivir as PEP.

Recently, macrolide-resistant (MR) Mycoplasma pneumonia appeared, and prevalence of macrolide resistance among M. pneumoniae infections varies by country. However, reports on regional differences in the prevalence of MR M. pneumonia within a country are scarce. In this study, 617 nasopharyngeal swab samples were collected from 617 pediatric patients, and DNA of M. pneumoniae was identified in 95 samples. In 51 of the 95 M. pneumonia positive samples, we detected the presence of mutation A2063G mutation (conferring macrolide resistance) in the 23S rRNA gene. The overall macrolide resistance rate was 53.7%, but there were regional differences: 0.0% in Muroran, 5.3% in Asahikawa, 55.3% in Sapporo, and 100.0% in Kushiro. Statistically significant pairwise differences in the prevalence of MR M. pneumoniae were observed among these cities except for the pair of Muroran and Asahikawa. After exclusion (in order to avoid the influence of macrolides) of patients who were prescribed macrolides before collection of nasopharyngeal swab samples, statistically significant differences persisted: 0.0% in Muroran, 5.6% in Asahikawa, 38.5% in Sapporo, and 100.0% in Kushiro.

Background The aim of this study was to determine the sensitivity and specificity of a novel immunochromatographic assay (ICA) kit, ALSONIC® Adeno (Alfresa Pharma Co., Osaka, Japan), for the detection of human adenovirus (HAdV) from throat swab samples based on the results of real-time PCR. The incubation time required for the novel assay kit (5 minutes) is shorter than that required for other ICA kits that are available in Japan. Methods Throat swab samples were taken from 151 patients aged 6 months to 15 years who were suspected of having respiratory tract infections caused by HAdV. Results The sensitivity and specificity of the ICA for detection of HAdV were 92.2% (83/90) and 95.1% (58/61), respectively, and the assay showed positive and negative predictive values of 96.5% (83/86) and 89.2% (58/65), respectively. Conclusions ALSONIC® Adeno is suitable as a diagnostic tool in the acute phase of HAdV infection.

Only minimal information exists regarding the treatment outcomes of patients suffering from methicillin-resistant Staphylococcus aureus (MRSA) bacteremia treated with teicoplanin (TEIC) when the TEIC minimum inhibitory concentration (MIC) is close to the upper limit of the "susceptibility range" according to the Clinical Laboratory Standards Institute (CLSI) . We investigated the outcome of TEIC-treated patients in MRSA bacteremia, focusing on TEIC MIC against MRSA. A retrospective cohort study was conducted on patients with MRSA bacteremia. TEIC treatment failure was defined as any of the following: (1) all-cause 60-day mortality, (2) persistent bacteremia until the end of TEIC treatment, or (3) 30-day recurrence of MRSA bacteremia. Nineteen patients were enrolled, of whom 15 exhibited TEIC MICs 2 mu g/mL. The rate of treatment failure and all-cause 60-day mortality in patients with MIC >2 mu g/mL were significantly higher than those in patients with MIC 2 mu g/mL had persistent bacteremia, which was quantitatively higher than in patients with MIC 2 mu g/mL may be related to poor treatment outcome in MRSA bacteremia, and that TEIC should not be used in this case.

Background Until now, the prevalence of macrolide-resistant Mycoplasma pneumoniae (MP) infection among adult patients has been low, and severe MP pneumonia due to a macrolide-resistant strain has seldom been reported. Here, we describe a rare case of severe life-threatening MP pneumonia due to a macrolide-resistant strain in an adult, which was finally treated with fluoroquinolone and tetracycline after failed treatment with macrolide and corticosteroid. Case presentation A 39-year-old apparently healthy woman complained of fever and productive cough. Three days after onset, she was admitted to a local general hospital. On admission, her vital signs were stable except for high-grade fever. The patient’s chest X-ray and chest computed tomography images revealed subsegmental consolidation in her right lower lobe. Treatment with ampicillin/sulbactam, and azithromycin were initiated under a clinical diagnosis of community-acquired pneumonia. After treatment initiation, her fever had not subsided, and the pulmonary lesion had extended to the entire lower lobe. Thus, treatment with prednisolone as steroid pulse therapy was initiated from clinical day 7. However, neither her symptoms nor her pulmonary lesion improved; therefore, she was transferred to our hospital for further examination and treatment. On admission (clinical day 14), her indirect hemagglutination titer for MP was elevated at 1:2560, and bronchoalveolar fluid examination yielded positive results for the mycoplasma antigen. Based on these clinical findings, we confirmed a case of severe life-threatening MP pneumonia. Since her respiratory condition was extremely severe, we initiated levofloxacin and tetracycline. Two days later (clinical day 16), her fever, malaise, and hypoxia resolved, and her pulmonary lesions had significantly improved. Further molecular identification yielded the DNA of MP from her bronchoalveolar fluid, and mutation of A2063G in the 23S rRNA gene was revealed. Based on these results and the clinical course, we confirmed our case as severe MP pneumonia due to a macrolide-resistant strain. Conclusion More awareness is needed on the emergence of macrolide-resistant MP infection in adults, because severe infection could develop despite initial treatment with macrolide and steroid therapy, which are generally considered as standard therapy for MP.

A 56-year-old woman with systemic lupus erythematosus had bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDRP). She was initially treated with imipenem-cilastatin, tobramycin, and aztreonam; however, MDRP was still detected intermittently in her plasma. Multidrug-susceptibility tests demonstrated that MDRP was susceptible only to colistin. Therefore, in addition to these antibiotics, the administration of intravenous colistin methanesulfonate, a prodrug formula of colistin, was started at a daily dose of 2.5 mg/kg (as colistin base activity). The initial dose setting was based on the patient's renal function (baseline creatinine clearance=32.7 mL/min). After initiating colistin, the patient's C-reactive protein levels gradually decreased. Blood cultures showed no evidence of MDRP on days 8, 14, and 22 after colistin initiation. However, the patient's renal function went from bad to worse owing to septic shock induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. A few days later, the trough plasma levels of colistin were 7.88 mg/L, which appeared to be higher than expected. After decreasing the colistin dose, the patient's renal function gradually improved. On the final day of colistin treatment, the plasma levels decreased to 0.60 mg/L. MDRP could not be detected in blood culture after colistin treatment. Therefore, we successfully treated a case of bloodstream infection due to MDRP by therapeutic drug monitoring (TDM) of colistin. It is suggested that the monitoring of blood colistin levels by liquid chromatography-tandem mass spectrometry can contribute to safer, more effective antimicrobial therapy of MDRP because TDM facilitates quick decisions on dose adjustments.

Based on the predictive performance in our previous study, we switched the therapeutic drug monitoring (TDM) analysis software for dose setting of vancomycin (VCM) from "Vancomycin MEEK TDM analysis software Ver2.0" (MEEK) to "SHIONOGI-VCM-TDM ver.2009" (VCM-TDM) in January 2015. In the present study, our aim was to validate the effectiveness of the changing VCM TDM analysis software in initial dose setting of VCM. The enrolled patients were divided into two groups, each having 162 patients in total, who received VCM with the initial dose set using MEEK (MEEK group) or VCM-TDM (VCM-TDM group). We compared the rates of attaining the therapeutic range (trough value; 10-20 μg/mL) of serum VCM concentration between the groups. Multivariate logistic regression analysis was performed to confirm that changing the VCM TDM analysis software was an independent factor related to attaining the therapeutic range. Switching the VCM TDM analysis software from MEEK to VCM-TDM improved the rate of attaining the therapeutic range by 21.6% (MEEK group: 42.6% vs. VCM-TDM group: 64.2%, p

Background Hematogenous vertebral osteomyelitis (HVO) has a generally favorable prognosis if appropriate treatment is initiated in its early phase; however, some intractable cases with HVO can develop neurological impairment as well as spinal deformity during the course of treatment and these sequelae may lead to impaired quality of life (QOL). In this study, we aimed to evaluate the long-term relapse rate, mortality, and QOL of patients with HVO. Methods In this retrospective case series study, medical records of 60 patients with HVO with a mean follow-up period of 8 years (5–23 years) were reviewed to assess demographic data, details of infection, and clinical course. Mortality rate was assessed using a Kaplan–Meier plot. QOL was measured using the EuroQol 5 Dimension (EQ-5D) questionnaire and residual pain using a numeric rating scale (NRS). Results HVO relapsed in 4 of 60 patients (7%). Overall 5-year survival rate in 60 patients with HVO was 85%. The factors associated with increased mortality were malignant tumor, diabetes mellitus, chronic use of glucocorticoids, and drug-resistant strains of staphylococcus. Female-to-male ratio, NRS, prevalence of neurological impairment were significantly higher in patients with low EQ-5D score (poor health) compared to those with high EQ-5D score (good health). Conclusions Patients with HVO have shorter life expectancy if they have malignancy, diabetes mellitus, chronic use of glucocorticoids, and a history of drug-resistant strains of staphylococcus infection. Female gender, residual neurological defects and persistent back pain are associated with impaired QOL in patients with HVO.

Objective: To clarify therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia and against macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia in pediatric patients. Methods: A prospective, multicenter observational study was conducted from July 2013 to August 2015. The therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin were evaluated in 59 patients with pneumonia caused by MRMP and in 50 patients with pneumonia caused by MSMP. In vitro activities of antimicrobial agents against isolates of Mycoplasma pneumoniae were also measured. Results: Mean durations of fever following commencement of treatment in patients infected with MRMP and MSMP were 5.2 and 1.9 days, respectively (log-rank test, P < 0.0001). Among patients infected with MRMP, mean durations of fever were 4.6, 5.5, 1.0 and 7.5 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P < 0.0001). Among patients infected with MSMP, mean durations of fever were 2.5, 1.7, 0.9 and 4.3 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P = 0.0162). The MIC90s of azithromycin and clarithromycin among the 27 isolates of MRMP were 64 and 256 μg/ml, respectively, and those among the 23 isolates of MSMP were

Polyomaviruses KI (KIPyV) and WU (WUPyV) were detected from 7 (3.0%) and 38 (16.4%) of 232 children with respiratory tract infections by real-time PCR. The rates of infection by KIPyV and WUPyV alone were 3 of 7 (42.9%) and 20 of 38 (52.6%), respectively. In the other samples, various viruses (human respiratory syncytial virus, human metapneumovirus, human rhinovirus, parainfluenza virus 1 and human bocavirus) were detected simultaneously. One case was positive for KIPyV, WUPyV and hMPV. There was no obvious difference in clinical symptoms between KIPyV-positive and WUPyV-positive patients with or without coinfection. KIPyV was detected in one of 30 specimens of lung tissue (3.3%). Neither of the viruses was detected in 30 samples of lung adenocarcinoma tissue.

Immunofluorescence assays (IFAs) for detection of human bocavirus (HBoV) proteins (VP1, VP2, NP-1, and NS1) were developed. The VP1 IFA was the most sensitive for detection of IgG antibody and suitable for screening. IgG antibodies in convalescent-phase sera from HBoV-positive patients were detected by VP1 and VP2 IFAs. Sensitivities of NP-1 and NS1 IFAs were low.

A lateral-flow immunochromatography (IC) assay for the detection of human metapneumovirus (hMPV) has been developed by using two mouse monoclonal antibodies to the nucleocapsid protein of hMPV. The purpose of this study was to compare the virus detection rate in nasopharyngeal secretions by the IC assay with that by real-time reverse transcription-PCR (RT-PCR). We collected nasopharyngeal swab samples from 247 children with respiratory symptoms in Sapporo, Japan, during the period from April to July 2007. Sixty-eight of the 247 children were positive for hMPV by real-time RT-PCR. When the real-time RT-PCR was used as the reference standard, the IC assay results were positive for 48 of the 68 real-time RT-PCR-positive children (70.6% sensitivity) and 8 of the 179 real-time RT-PCR-negative children (95.5% specificity). Although the sensitivity of the IC assay is lower than that of real-time RT-PCR, the IC assay is a rapid and useful test for the diagnosis of hMPV infections in children.

A new human virus, provisionally named human bocavirus (HBoV), was discovered by Swedish researchers in 2005. A new immunofluorescence assay using Trichoplusia ni insect cells infected with a recombinant baculovirus expressing the VP1 protein of HBoV was developed, and the levels of immunoglobulin G antibody to the VP1 protein of HBoV in serum samples were measured. The overall seroprevalence rate of antibodies against the VP1 protein of HBoV in a Japanese population aged from 0 months to 41 years was 71.1% (145 of 204). The seropositive rate was lowest in the age group of 6 to 8 months and gradually increased with age. All of the children had been exposed to HBoV by the age of 6 years. A rise in titers of antibody against the VP1 protein of HBoV during the convalescent phase was observed for four patients with lower respiratory tract infections, and HBoV DNA was detected in nasopharyngeal swab and serum samples from all four patients. These results suggest that HBoV is a ubiquitous virus acquired early in life and that HBoV might play a role in the course of lower respiratory tract infections.

Human metapneumovirus (hMPV) nucleocapsid (N) protein is a major structural protein that encapsidates the RNA genome and is essential for replication and transcription of the hMPV genome. We developed two mouse monoclonal antibodies (MAbs), designated 3D1 and 5B10, against N protein of hMPV and characterized them by an immunofluorescence assay and an immunoprecipitation assay using Trichoplusia ni (Tn5) insect cells infected with a recombinant baculovirus-expressing hMPV N protein. Both MAbs were found to be reactive to two groups of hMPV by an immunofluorescence assay using two groups of hMPV-infected cells. A chromatographic immunoassay (lateral flow assay) was developed using the MAbs. The assay is a sandwich immunoassay that uses a paper membrane with a gold colloid-conjugated MAb (5B10) in a liquid phase and an MAb (3D1) in a solid phase. We preliminarily examined the sensitivity and specificity using hMPV-infected cells, Tn5 insect cells infected with a recombinant baculovirus-expressing hMPV N protein, hMPV, and purified N protein. The assay had good specificity and sufficient sensitivity to detect hMPV. Therefore, the assay may be a rapid and useful test for diagnosis of hMPV infections.

The aim of this study was to determine the sensitivity and specificity of a loop-mediated isothermal amplification (LAMP) assay kit for the detection of Mycoplasma pneumonia (Eiken Chemical Co., Ltd, Tokyo, Japan) from nasopharyngeal swab samples compared with those of real-time PCR.Nasopharyngeal swab samples taken from 223 patients aged 3 - 18 years who were suspected of having respiratory tract infections associated with Mycoplasma pneumonia were used in this study. The samples were tested both by the LAMP assay and by real-time PCR for detection of Mycoplasma pneumonia.The sensitivity and specificity of the LAMP assay for the detection of Mycoplasma pneumonia were 99.1% (105/106) and 100.0% (117/117), respectively.The LAMP assay for the detection of Mycoplasma pneumonia is an accurate and fast assay that is suitable as a diagnostic tool in the acute phase of Mycoplasma pneumonia infection.

Background The aim of this study was to determine the sensitivity and specificity of a loop-mediated isothermal amplification (LAMP) assay kit for the detection of Mycoplasma pneumonia (Eiken Chemical Co., Ltd, Tokyo, Japan) from nasopharyngeal swab samples compared with those of real-time PCR. Methods Nasopharyngeal swab samples taken from 223 patients aged 3 - 18 years who were suspected of having respiratory tract infections associated with Mycoplasma pneumonia were used in this study. The samples were tested both by the LAMP assay and by real-time PCR for detection of Mycoplasma pneumonia. Results The sensitivity and specificity of the LAMP assay for the detection of Mycoplasma pneumonia were 99.1% (105/106) and 100.0% (117/117), respectively. Conclusions The LAMP assay for the detection of Mycoplasma pneumonia is an accurate and fast assay that is suitable as a diagnostic tool in the acute phase of Mycoplasma pneumonia infection.

Detection of antibodies against individual proteins of human metapneumovirus (hMPV) is important in the analysis of immune responses to hMPV. Specific antibodies against nucleocapsid (N) and matrix (M) proteins in 97 serum samples were tested by Western blot using recombinant N and M proteins of hMPV expressed in Escherichia coli. The results were compared with those of immunofluorescence assays (IFAs) based on hMPV-infected LLC-MK2 cells, which expressed the whole hMPV proteins. Thirty (61.2%) and 31 (63.3%) of 49 serum samples with titers of >/=1:160 by IFA reacted with N and M proteins, respectively. Only 2 (4.2%) of 11 serum samples with titers of 1:80 by IFA reacted with N and M proteins. Antibodies against N and M proteins were not detected in 37 serum samples with titers of

Human metapneumovirus (hMPV) F protein promotes fusion of viral and cell membranes, and is thought to be a major antigenic determinant that mediates effective neutralization and protection against hMPV infection. In this paper, the development of two mouse monoclonal antibodies (MAbs) by immunization with hMPVinfected cells is described. Immunofluorescence assay (IFA) using hMPV F protein-expressing cells indicated that two MAbs, designated 1G3 and 9B10, recognized hMPV F protein. Both MAbs were found to be reactive to two groups of hMPV by an IFA using two groups of hMPV-infected cells. The 9B10 mAb had strong neutralizing activity against both groups of hMPV, while the 1G3 MAb had only weak neutralization activity. These results indicate that the hMPV F protein is a major antigenic determinant that mediates extensive cross-lineage neutralization and protection. Production of MAbs to the hMPV F protein is critical for development of diagnostic techniques, vaccine research, and studies on viral pathogenesis.

S100 family proteins are calcium-binding proteins, some of which have been shown to have intracellular and extracellular functions associated with inflammation. The serum concentration of S100A12 has been reported to increase in the acute phase of Kawasaki disease. The purpose of this study was to evaluate leukocyte gene expressions of S100 family proteins in the acute phase of Kawasaki disease. Ten paired blood samples were obtained from ten patients with Kawasaki disease in the acute phase and in the convalescent phase. We examined leukocyte expression levels of 18 S100 genes in the acute phase compared with those in the convalescent phase by using quantitative real-time polymerase chain reaction. Significantly elevated expression of seven S100 genes (S100A6, A8, A9, A11, A12, S100P, and S100Z) was observed in the acute phase. Conclusion:Of the upregulated S100 genes, calgranulin members of S100 genes (S100A8, S100A9, and S100A12) were most highly expressed in the acute phase. Only one S100 gene, the S100A13 gene, exhibited a significantly decreased expression level in the acute phase.

Human metapneumovirus (hMPV) is a recently discovered pathogen associated with respiratory tract infections, primarily in young children, immunocompromised individuals, and elderly individuals. Reverse transcription-PCR (RT-PCR) has been reported to be a more sensitive method for the diagnosis of hMPV infections than virus isolation by culture and serological study. However, there has been no report on rapid methods, such as an immunofluorescent-antibody test or an enzyme-linked immunosorbent assay, for the detection of hMPV antigens in nasopharyngeal secretions. In this study, we compared an indirect immunofluorescent-antibody test (IFA) with a monoclonal antibody with RT-PCR for detection of hMPV in nasal secretions from 48 hospitalized children with respiratory tract infections. Fifteen of the 48 children were positive for hMPV by RT-PCR. IFA results were positive for 11 of the 15 RT-PCR-positive children (sensitivity, 73.3%) and 1 of the 33 RT-PCR-negative children (specificity, 97.0%). Although the sensitivity of IFA is lower than that of RT-PCR, IFA is a rapid and useful test for the diagnosis of hMPV infections in children.