A Fatal Case of Disseminated Infection Caused by Community-Associated Methicillin-Resistant Staphylococcus aureus USA300 Clone.

Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is a representative community-associated MRSA (CA-MRSA) clone worldwide. Herein, we report the case of a patient with USA300 clone infection who could not be salvaged. A 25-year-old man who had sex with men presented with symptoms including fever persisting for one week and skin lesions located on the buttocks. Computed tomography imaging showed multiple nodules and consolidations, especially in the peripheral lung fields, right iliac vein thrombosis, and pyogenic myositis of medial thighs bilaterally. Blood cultures revealed MRSA bacteremia. The patient's condition deteriorated rapidly, complicated by acute respiratory distress syndrome and infective endocarditis. Despite the intubation on the 6th hospital day, he died on the 9th day. Multilocus sequence typing of this patient's MRSA strain revealed sequence type 8 with a staphylococcal cassette chromosome of mec type IVa, Panton-Valentine leukocidin gene, and the arginine catabolic mobile element, indicating presence of the USA300 clone. Patients with CA-MRSA skin lesions presenting with furuncles or carbuncles on the lower body are at a higher risk of severe disease. The patient's background, appearance, and location of skin lesions are critical for the early diagnosis of severe CA-MRSA infection.

Waning of Anti-SARS-CoV-2 Spike Antibody Levels 100 to 200 Days after the Second Dose of the BNT162b2 Vaccine.

Anti-SARS-CoV-2 antibodies of 444 vaccinated hospital employees in Japan were measured 94-109 days and 199-212 days after receiving the second BNT162b2 vaccine dose to evaluate the intensity and duration of antibody response in our own cohort. Among uninfected participants, anti-S antibody levels were greatly decreased 199-212 days after the second vaccination compared to the levels measured 94-109 days after the second vaccination (median levels: 830 AU/mL and 2425 AU/mL, respectively; p < 0.001). The rate of decrease between the two testing periods was lower in infected participants than in uninfected participants (median: 47.7% and 33.9%, respectively; p < 0.001). Anti-S antibody levels were significantly higher in females (median: females, 2546 AU/mL; males, 2041 AU/mL; p = 0.002 during the first test period). The peak body temperature after vaccination was higher in females than in males (median: females, 37.4 °C; males: 37.1 °C; p = 0.044). Older males tended to have lower antibody levels. In conclusion, the duration of the anti-S antibody response to the BNT162b2 vaccine was short-lived, particularly in males. Anti-S antibody levels of 1000 AU/mL or lower according to SARS-CoV-2 IgG II Quant (Abbott) might indicate insufficient prevention against the delta variant, and the majority of participants appeared to have lost their protection 200 days after vaccination.

Development of an efficient one-step real-time reverse transcription polymerase chain reaction method for severe acute respiratory syndrome-coronavirus-2 detection.

The general methods to detect the RNA of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in clinical diagnostic testing involve reverse transcriptases and thermostable DNA polymerases. In this study, we compared the detection of SARS-CoV-2 by a one-step real-time RT-PCR method using a heat-resistant reverse transcriptase variant MM4 from Moloney murine leukemia virus, two thermostable DNA polymerase variants with reverse transcriptase activity from Thermotoga petrophila K4 and Thermococcus kodakarensis KOD1, or a wild-type DNA polymerase from Thermus thermophilus M1. The highest performance was achieved by combining MM4 with the thermostable DNA polymerase from T. thermophilus M1. These enzymes efficiently amplified specific RNA using uracil-DNA glycosylase (UNG) to remove contamination and human RNase P RNA amplification as an internal control. The standard curve was obtained from 5 to 105 copies of synthetic RNA. The one-step real-time RT-PCR method's sensitivity and specificity were 99.44% and 100%, respectively (n = 213), compared to those of a commercially available diagnostic kit. Therefore, our method will be useful for the accurate detection and quantification of SARS-CoV-2.

Radioligand Assay-Based Detection of Antibodies against SARS-CoV-2 in Hospital Workers Treating Patients with Severe COVID-19 in Japan.

This study aimed to clarify whether infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent among the staff of a hospital providing treatment to patients with severe coronavirus disease 2019 (COVID-19) using radioligand assay (RLA). One thousand samples from the staff of a general hospital providing treatment to patients with severe COVID-19 were assayed for SARS-CoV-2 nucleocapsid protein (N) IgG using RLA. Nine patients with COVID-19 who had been treated in inpatient settings and had already recovered were used as control subjects, and 186 blood donor samples obtained more than 10 years ago were used as negative controls. Four of the 1000 samples showed apparently positive results, and approximately 10 or more samples showed slightly high counts. Interestingly, a few among the blood donor samples also showed slightly high values. To validate the results, antibody examinations using ELISA and neutralizing antibody tests were performed on 21 samples, and chemiluminescence immunoassay (CLIA) was performed on 201 samples, both resulting in a very high correlation. One blood donor sample showed slightly positive results in both RLA and CLIA, suggesting a cross-reaction. This study showed that five months after the pandemic began in Japan, the staff of a general hospital with a tertiary emergency medical facility had an extremely low seroprevalence of the antibodies against SARS-CoV-2. Further investigation will be needed to determine whether the slightly high results were due to cross-reactions or a low titer of anti-SARS-CoV-2 antibodies. The quantitative RLA was considered sensitive enough to detect low titers of antibodies.

First case report of prosthetic valve endocarditis caused by Mycobacterium wolinskyi.

To date, only 26 cases of Mycobacterium wolinskyi infections have been reported in humans. We herein report a first case of prosthetic valve endocarditis due to this organism after cardiovascular surgery. An 82-year-old man presented with repeat episodes of syncope and fever after aortic valve replacement, mitral valve replacement, left atrial appendage closure, and pulmonary vein isolation. Blood cultures maintained in aerobic bottles were repeatedly positive after 90-100 hours, and Gallium scan revealed abnormal accumulations in the sternum and left testis. While colonies formed by culturing the fluid of the parasternal area and blood cultures revealed gram-positive rods, we could not analyze the colony using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF). M. wolinskyi was finally identified on 16S rRNA, hsp65, and rpoB gene sequencing. We treated the patient with multiple antimycobacterial drugs, i.e., amikacin, imipenem, and clarithromycin for 6 weeks, which was changed to oral ciprofloxacin and minocycline for 12 months. This case highlights the need to consider rapidly growing mycobacteria, including M. wolinskyi, if chronic fever persists from weeks to months after surgery, the blood culture is positive, and the organism is not identified. In addition, sequencing the 16S rRNA, hsp65, and rpoB genes is essential for diagnosis.

Shortening antibiotic duration in the treatment of acute cholangitis: rationale and study protocol for an open-label randomized controlled trial.

BACKGROUND: Antimicrobial therapy with appropriate biliary drainage is considered the standard of care for acute cholangitis, but the optimal duration of antimicrobial therapy remains unknown. Seven to 10 days of antimicrobial therapy are common for the treatment of acute cholangitis, but a recent retrospective cohort study suggested a shorter duration might be effective. A shorter duration of antimicrobial therapy can be beneficial in decreasing the length of hospital stay, improving patients' quality of life, decreasing adverse effects, and even contributing to a decrease in the occurrence of antimicrobial resistance. METHODS/DESIGN: We will conduct a multi-centre, open-label, randomized, non-inferiority trial to compare short-course therapy (SCT) with conventional long-course therapy (LCT) in treating patients with acute cholangitis. SCT consists of 5-day intravenous antimicrobial therapy if the patients had clinical improvement, while at least 7 days of intravenous antibiotics will be provided to the LCT group. The primary outcome is clinical cure at 30 days after onset. Patients will be randomly assigned in an open-label fashion. A total sample size of 150 was estimated to provide a power of 80% with a one-sided α level of 2.5% and a non-inferiority margin of 10%. DISCUSSION: This trial is expected to reveal whether SCT is non-inferior to conventional LCT or not, and may provide evidence that one can shorten the treatment duration for acute cholangitis for the benefit of patients. TRIAL REGISTRATION: University Hospital Medical Information Network, UMIN000028382. Registered on 30 August 2017.

Ancylostoma ceylanicum, novel etiological agent for traveler's diarrhea-report of four Japanese patients who returned from Southeast Asia and Papua New Guinea.

BACKGROUND: Countries in the Southeast Asia region have a high prevalence of soil-transmitted helminth, such as roundworm, whipworm, and hookworms [Ancylostoma duodenale, Necator americanus, Ancylostoma ceylanicum]. Recent molecular-based surveys have revealed that A. ceylanicum, a zoonotic hookworm, is likely the second most prevalent hookworm species infecting humans in that part of the world, while others have noted that this infection is an emerging public health risk not only for indigenous people but also for visitors from other countries. CASE PRESENTATION: We recently encountered four cases of A. ceylanicum infection in Japanese individuals who returned from Southeast Asia and Papua New Guinea. Case 1 was a 25-year-old male who stayed in a rainforest in Malaysia for 4 weeks, where he developed abdominal pain and diarrhea in the third week. Eleven adult worms (five males, six females) were expelled after treatment with pyrantel pamoate and identified as A. ceylanicum based on morphological characteristics and DNA sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Case 2 was a 26-year-old male who spent 2 years as an overseas cooperation volunteer for agriculture in Papua New Guinea. He did not note any symptoms at that time, though eggs were detected in feces samples at a medical check-up examination after returning. Although collection of adult worms was unsuccessful, DNA analysis of the eggs for cox1 and the ribosomal internal transcribed spacer (ITS)-1 and ITS-2 genes demonstrated that they were A. ceylanicum. Case 3 was a 47-year-old male who spent 1 month in a rural village in Lao People's Democratic Republic and began suffering from watery diarrhea from the third week. A total of nine adult worms (three males, six females) were collected by endoscopic procedures and following treatment with pyrantel pamoate. Morphological examination and molecular analyses of the cox1 gene showed that they were A. ceylanicum. Case 4 was a 27-year-old male who participated in group travel to India for 5 days. Three weeks after returning, he developed abdominal pain and diarrhea. Hookworm eggs were found in feces samples and developed into larvae in culture, which were identified as A. ceylanicum based on molecular analysis of the cox1 gene. Eosinophilia was observed in all of the cases prior to treatment. CONCLUSIONS: A. ceylanicum should be recognized as an important etiologic pathogen of hookworm diseases in travelers to countries in the Southeast Asia and West Pacific Ocean regions.

Longitudinal nosocomial outbreak of Pseudomonas fluorescens bloodstream infection of 2 years' duration in a coronary care unit.

BACKGROUND: Outbreaks of bloodstream infections (BSI) of nonfermenting bacteria are a critical issue and often associated with hospital environments. We experienced a long-lasting outbreak of Pseudomonas fluorescens BSI limited to a coronary care unit (CCU). METHODS: We conducted a retrospective epidemiologic investigation and a case-control study for Pseudomonas fluorescens BSI from April 2011-July 2014. Environmental sample culture was conducted to detect the specific environmental source of transmission. RESULTS: Hospital-wide microbiology data from the term identified 13 case patients with P fluorescens BSI and 32 control patients with BSI due to organisms other than P fluorescens in the CCU. The case-control study revealed that the case group had significantly higher odds of exposure to only cardiac output (CO) measurement with thermodilution method (odds ratio, 22.0; 95% confidence interval, 2.4-202.3). The organism was identified only from an ice bath used for CO measurement. The susceptibility patterns were identical among all strains derived from the cases and the environment. CONCLUSIONS: The nosocomial outbreak of P fluorescens BSI in our CCU over 2 years was associated with a contaminated ice bath used for CO measurement within the unit. Detection and elimination of the specific source was essential to stop the outbreak.

Prolonged varicella-zoster virus reinfection in an adult after unrelated cord blood transplantation.

Most varicella-zoster virus (VZV) infections after cord blood transplantation (CBT) present as localized herpes zoster. Here, we report a case of VZV reinfection in an adult patient after CBT that appeared clinically to be varicella. A 50-year-old Japanese man underwent CBT for the management of acute lymphoblastic leukemia. Seventeen months later, he developed a small number of vesicles with umbilicated centers. A skin biopsy showed an intraepidermal blister containing degenerated balloon cells. Subsequently, the skin eruption developed over his entire body. The patient was treated with intravenous acyclovir for 5 days, followed by oral valacyclovir for 9 days. It took more than 3 weeks for most of the skin lesions to scab. Serum levels of anti-VZV IgG on days 3 and 33 after the onset of the skin eruption were negative and 260 mIU/ml, respectively. Serum anti-VZV IgM on days 3 and 33 was not detected. Our patient was diagnosed with VZV reinfection.

Hospital-acquired pneumonia in Japan may have a better mortality profile than HAP in the United States: a retrospective study.

The characteristics of hospital-acquired pneumonia (HAP) are not well documented. In the present study we investigated the severity and mortality, microbiological profile, and the value of Gram staining in culture-confirmed HAP in a Japanese hospital by retrospective review conducted at a Japanese university hospital. Only culture-confirmed cases with good specimen quality were included in the analysis. The clinical characteristics of HAP, as well as the causative organisms, were investigated. Furthermore, the prognostic ability of existing prediction rules were evaluated for prediction of overall mortality. Forty-two cases were enrolled in this analysis. The majority of patients were admitted to the ICU (61.9 %), and 40.5 % had ventilator-associated pneumonia (VAP). The 30-day mortality was 23.8 %, which is less than that reported in the United States. Factors commonly known to be associated with worse outcome in the USA did not appear to influence the mortality from HAP in Japan. The most frequent causative organisms were methicillin-resistant Staphylococcus aureus (MRSA), followed by Pseudomonas spp. Sensitivity and negative predictive value of Gram staining were 89.4 and 85.7 %, respectively. SMART-COP predicted 30-day mortality with an area under the ROC curve (AUC) >0.7. The characteristics of HAP in Japan differ from HAP reported in the USA. In addition to lower mortality, we found both fewer ICU cases and VAP. Gram staining of good-quality specimens demonstrated promising sensitivity to predict the causative organisms. SMART-COP predicted mortality with appropriate ROC curve (AUC).

How were the high-fever consultation center perceived by the officers who provided it in Kobe City, during swine-origin influenza A (H1N1) outbreak? A qualitative study utilizing SCQRM.

BACKGROUND: For the preparation of pandemic influenza, Japan's government requested to set up a high-fever consultation center at each prefectural and city government. During the initial period of pandemic influenza A (H1N1) outbreak in Japan, high-fever consultation centers received a great number of calls. The effectiveness of this system, however, has not been fully evaluated. This study reports the result of a qualitative study, which explored officers who provided the high-fever consultation center during influenza outbreak. METHODS: A qualitative study, using semi-structured interviews (n=3), was conducted to the officers of a major city government in Japan, who provided the service. Theory construction was conducted with a use of structure construction qualitative research method. RESULTS: The officers expressed many difficulties during the outbreak. The uncertainty of the disease characteristics, rapidly changing situation, fear of bad outcome of patients due to wrong triage, and miscommunications among health care workers were among the difficulties extracted. While inefficiency was among the problems extracted, lessening anxiety of callers was one of the achievements they felt the high-fever consultation center provided. Development of practical manual made their provision of the service easier.

Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis.

INTRODUCTION: Sivelestat is neutrophil elastase inhibitor, which is widely used in Japan for the treatment of acute lung injury. However, the clinical efficacy of the medication has not been convincingly demonstrated. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials on sivelestat for the treatment of acute lung injury and acute respiratory distress syndrome. Studies were identified using MEDLINE, EMBASE, Cochrane library, conference proceedings, and references of included studies. Authors were contacted if necessary. ICHUSHI, the Japanese database for medical literature and conference proceedings was also used for the search, since many studies on sivelestat were published in Japanese language and not registered in major databases such as MEDLINE. The primary outcome was mortality within 28-30 days after randomization. Relative risks were pooled with the random effect model. RESULTS: 8 trials were included in the analysis. There was no difference in mortality within 28-30 days after randomization (relative risk 0.95, 95% confidence interval 0.72 to 1.26). Subgroup analysis conducted only on studies conducted in Japan showed the same result (0.59, 0.28 to 1.28). There was no difference in mechanical ventilation days (standardized mean difference -0.43, -1.12 to 0.27), but sivelestat was associated with a better short term PaO(2)/FiO(2) ratio (0.30, 0.05 to 0.56). Heterogeneity was not significant for the main analysis and funnel plot did not suggest publication bias. CONCLUSION: Sivelestat was not associated with decreased mortality, even when including studies published in Japanese language.

[Multidisciplinary strategy for lung cancer patients with bone metastasis].

The fall of QOL by bone metastasis poses a problem with the increase in lung cancer. The examples of long-term survival of lung cancer are also increasing by progress of chemotherapy or molecular-targeted therapy. Now, in addition to the conventional radiotherapy, the multidisciplinary treatment including a newer bisphosphonates or an orthopedic operation has been needed to bone metastasis of lung cancer. We presented the lung cancer case who showed the symptoms in transcervical pathologic fracture and whose QOL was improved by orthopedic surgery, radiotherapy to bone metastasis, chemotherapy, gamma knife surgery, and treatment with zoledronic acid and gefitinib.