Evaluation of MALDI-TOF mass spectrometry coupled with ClinProTools as a rapid tool for toxin-producing Clostridioides difficile.

INTRODUCTION: The performance of MALDI-TOF MS combined with analysis platform for identification of toxin-producing Clostridiodes difficile is yet to be known. METHODS: Between August 2018 and September 2020, 61 isolates from stool specimens of patients with C. difficile-associated diarrhea were analyzed using the MALDI Biotyper system. A C. difficile toxin-producer detection model was developed using ClinProTools. The model was validated using 28 known strains that differed from the isolates used to develop the model. RESULTS: The sensitivity and specificity of the Genetic Algorithm (GA) model using isolates grown on Brucella with hemin and vitamin K (BHK) agar plates were 91.7% and 44.4%, respectively. When isolates grown on cycloserine-cefoxitin mannitol agar were analyzed by the model, sensitivity and specificity were 6.3% and 100%, respectively. The GA model using BHK medium showed the highest discriminatory performance in detection of toxin-producing C. difficile. However, a discrepancy in detection of toxin-producing C. difficile was observed in the results generated when the model was being developed and when the model was validated which suggests that incubation conditions may have affected the results. CONCLUSION: MALDI-TOF analysis using ClinProTools has a potential to be a cost-effective tool for rapid diagnosis and contribute to antimicrobial stewardship by differentiating toxin-producing C. difficile from non-producers.

Immunogenicity and safety of two doses of SARS-CoV-2 mRNA vaccine in kidney transplant recipients with low-dose rituximab.

OBJECTIVES: We evaluated whether the treatment history of low-dose rituximab affected safety profiles, and humoral and cellular responses induced by severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine in healthy controls and kidney transplant recipients. METHODS: We enrolled 10 healthcare workers as controls, 22 kidney transplant recipients with rituximab, and 36 kidney transplant recipients without rituximab without history of coronavirus disease 2019 who received two doses of vaccine. We assessed anti-severe acute respiratory syndrome coronavirus 2 spike antibody and the antigen-specific T cells using enzyme-linked immunospot against spike protein at baseline and after two doses of vaccine. RESULTS: All controls showed anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion and enzyme-linked immunospot positivity. Only 19/58 (33%) kidney transplant recipients experienced anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion and 31/58 (53%) kidney transplant recipients developed enzyme-linked immunospot assay positivity after vaccination. The anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion rate and enzyme-linked immunospot assay positivity rate after vaccination were not significantly different between kidney transplant recipients with or without rituximab. Multivariate regression analysis demonstrated rituximab was not associated with a lack of humoral and cellular responses to the vaccine. CONCLUSIONS: Low-dose rituximab in kidney transplant recipients did not affect humoral or cellular responses to the severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine without severe systemic adverse events including the deterioration of kidney function.

Change in antimicrobial susceptibility of pathogens isolated from surgical site infections over the past decade in Japanese nation-wide surveillance study.

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014-2015 surveillance studies. Although the rate of detection of extended-spectrum ß-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014-2015, the incidence decreased to 8.7% in 2018-2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 µg/mL). By contrast, relatively low geometric mean MICs (0.397 µg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018-2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014-2015, and 38.9% in 2018-2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group.

Clinical and microbiological effect of pulsed xenon ultraviolet disinfection to reduce multidrug-resistant organisms in the intensive care unit in a Japanese hospital: a before-after study.

BACKGROUND: No-touch environmental disinfection using ultraviolet devices has been highlighted in the past several years to control the transmission of multidrug-resistant organisms (MDROs). However, its effectiveness in non-US healthcare settings is yet to be examined. This study aimed to evaluate the effectiveness of disinfection by portable pulsed xenon ultraviolet (PX-UV) devices in controlling transmission of MDROs in a non-US healthcare setting. METHODS: All patients admitted in the intensive care unit in a 629-bed tertiary referral hospital in Japan from August 2016 to February 2019 were enrolled. During the study period, PX-UV disinfection was added to manual terminal cleaning after every patient transfer/discharge. For microbiological evaluation, surfaces were selected for sampling by contact plates before/after manual cleaning and after PX-UV. After overnight incubation, colonies on the plates were counted. RESULTS: The incidence of newly acquired methicillin-resistant Staphylococcus aureus (MRSA) declined significantly (13.8 to 9.9 per 10,000 patient days, incidence rate ratio 0.71, p = 0.002), as well as that of newly acquired drug-resistant Acinetobacter (48.5 to 18.1, 0.37, p < 0.001). The percent reduction of the microbiological burden by manual cleaning was 81%, but a further 59% reduction was achieved by PX-UV. CONCLUSIONS: PX-UV is effective in further reducing the microbial burden and controlling MDROs in a non-US healthcare setting.

Direct comparison of prognostic ability of cardiac biomarkers for cardiogenic stroke and clinical outcome in patients with stroke.

Despite many recent advances in medicine, cardiogenic stroke is still a health problem with a high mortality rate. Cardiac biomarkers have been reported to be useful indicators for cardiogenic stroke and subsequent cerebrovascular events. However, there are no data directly comparing the cardiac biomarkers in stroke patients. We measured atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) levels and performed transthoracic and transesophageal echocardiography in 282 stroke patients. There were 108 cases of cardiogenic stroke and 47 cases of major adverse cardiovascular and cerebrovascular events (MACCE) during the follow-up period. Association with left atrial function and left atrial appendage function appeared somewhat stronger for BNP and NT-proBNP than ANP and hsTnT. Multivariate logistic analysis demonstrated that cardiac biomarkers excluding ANP were significantly associated with cardiogenic stroke in stroke patients, multivariate Cox's proportional hazards regression analysis demonstrated that all biomarkers were significantly associated with MACCE after adjustment for confounding risk factors. Receiver operating characteristic curve analysis showed that the C indices of BNP and NT-proBNP for cardiogenic stroke and MACCE were almost equal, but significantly greater than those of ANP and hsTnT. Both BNP and NT-proBNP levels are useful predictors of cardiogenic stroke and subsequent MACCE superior to ANP and hsTnT in stroke patients.

Epidemiology and risk factors associated with surgical site infection after different types of hepatobiliary and pancreatic surgery.

PURPOSE: Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs); however, SSI after hepatobiliary and pancreatic surgery (HBPS) has not been well investigated in a large cohort of patients. This study analyzed the factors associated with SSI following HBPS in Japan, using a Japanese national database. METHODS: Data on HBPS performed between 2012 and 2014 were extracted from a national monitoring system for HAI: The Japan Nosocomial Infections Surveillance. Using multivariate logistic regression, I assessed the factors associated with SSI. RESULTS: The cumulative incidence of SSI following HBPS was 15.6% (2873/18,398). The incidence of SSI after pancreatoduodenectomy was 28.0%, which was significantly higher than that after liver resection and other types of HBPS (8.8 and 15.5%, respectively). Among the four traditional risk factors, the American Society of Anesthesiologists score was ineffective for predicting SSI in the final model of all three types of surgery. Additional risk factors were identified, including age and male gender. CONCLUSIONS: The incidence of and factors associated with SSI after the three types of HBPS analyzed differed significantly. To accurately compare hospital performance in relation to SSI following HBPS, the operative procedure category in the surveillance system must be divided into three types.

[Risk Factor Analysis of Pneumonia after Cardiovascular Surgery].

Pneumonia is a major and life-threatening complication after cardiovascular surgery. The objective of our study was to describe epidemiology, clinical characteristics, and risk factors of pneumonia after cardiovascular surgery. From January 2007 to December 2011, 511 consecutive patients (age 67.3±11.9;336 men, 175 women) were enrolled in this study. Pneumonia was diagnosed according to Centers of Disease Control and Prevention surveillance criteria for healthcare associated infection. Data collection included preoperative, intraoperative, and post-operative variables. The overall incidence of pneumonia was 72 cases(14.0%). The mortality in pneumonia group was significantly higher than that in non-pneumonia group (16.6% vs 4.3%, Odds ratio 4.4 p<0.001). Multi-logistic analysis revealed that elderly patient, preoperative congestive heart failure, preoperative hemodialysis, and operation of the thoracic aorta were independent risk factors for pneumonia after cardiovascular surgery.

[Issues Associated with the Management of Clinical Laboratories and Their Future: What is the Problem in Our Laboratory?--Chairmen's Introductory Remarks].

The management of clinical laboratories in hospitals has to be changed in accordance with the trends in the healthcare-providing system. In this symposium, six presenters talked about various issues associated with their laboratories. The issues raised included conflict between specialty and generality, phlebotomy as a duty of laboratory technologists, management of the phlebotomy section, imbalance of numbers between retirees and newcomers, and cooperation with the division of clinical research. Presenters, chairmen, and the audience were able to understand that we are now facing these issues, and we could identify some of their solutions.

[Strategies to Cope with the Shortage of Technologists: Facing the Mass-Retirement of the 'Baby-Boomer' Generation].

In Japan, the primary 'baby-boomer' generation, born between 1947 and 1949, is now in its retirement. This has caused a marked shortage of human resources nationwide. Clinical laboratory technologists are no exception, and many clinical laboratories in Japanese healthcare facilities are struggling with management because the number of new graduates, i.e., newly licensed technologists, is mostly fixed and, therefore, their recruitment is becoming more and more competitive. Our laboratory is now facing a wave of mass-retirement associated with our history. In addition, in the early 2000s, there was almost no position for new graduates replacing those retiring because of the change in the social healthcare system as well as our hospital's policy. This resulted in uneven numbers of technologists in generations, and it seemed to be getting worse. Fortunately, five years ago, the direction of social health care was changed and lots of positions became available as a result. We have been trying to recruit new graduates and experienced technologists as well, and were able to hire 18 people. Among them, 8 were non-freshmen. The generation gap has been mostly resolved. We will continue to make our laboratory more attractive not just to new graduates but also to experienced technologists, especially those who wish to return to work after a several-year absence to raise their children. We believe that this will energize our laboratory.

[Clinical characteristics of biliary tract infection and acalculous cholecystitis after cardiovascular surgery].

Biliary tract infection (BTI) including acalculous cholecystitis is a rare but life-threatening complication after cardiovascular surgery. The objective of our study was to describe epidemiology, clinical characteristics, and risk factors of BTI after cardiovascular surgery. From January 2007 to December 2011, 586 consecutive patients(age68±11;397 men,189 women)were enrolled in this study. BTI was diagnosed according to Centers for Disease Control and Prevention (CDC) surveillance criteria for healthcare associated infection. Data collection included preoperative, intraoperative, and post-operative variables. The overall incidence of BTI was 3.9%. The mortality in BTI group was significantly higher than that in non-BTI group (17.1% vs 5.5%, p<0.05). Multi-logistic analysis revealed that operation of the thoracic aorta( p<0.05) and massive transfusion(p<0.01) were independent risk factors for BTI after cardiovascular surgery.

[Procalcitonin as a marker of the postoperative infection in cardiovascular surgery].

BACKGROUND: Procalcitonin( PCT) is a new diagnostic marker of severe bacterial infection and sepsis. PURPOSE: To evaluate the usefulness of PCT in patients with suspicion of bacterial infection after cardiovascular surgery. METHODS: From January 2012 to December 2012, 150 consecutive patients after cardiovascular surgery were studied retrospectively. Postoperative infection was diagnosed under Centers for Disease Control and Prevention (CDC) guideline for healthcare associated infection, and biomarker levels and microbiological specimen were evaluated. RESULTS: Only blood stream infection group revealed higher PCT levels( median 5.0 ng/ml) than non blood stream infection group( median 0.1 ng/ml)[p<0.01]. CONCLUSION: PCT is the best biomarker available for the clinical diagnosis of blood stream infection after cardiovascular surgery.

Development of a Machine Learning-Based Model for Predicting the Incidence of Peripheral Intravenous Catheter-Associated Phlebitis.

Introduction: Early and accurate identification of high-risk patients with peripheral intravascular catheter (PIVC)-related phlebitis is vital to prevent medical device-related complications. Aim of the study: This study aimed to develop and validate a machine learning-based model for predicting the incidence of PIVC-related phlebitis in critically ill patients. Materials and methods: Four machine learning models were created using data from patients ≥ 18 years with a newly inserted PIVC during intensive care unit admission. Models were developed and validated using a 7:3 split. Random survival forest (RSF) was used to create predictive models for time-to-event outcomes. Logistic regression with least absolute reduction and selection operator (LASSO), random forest (RF), and gradient boosting decision tree were used to develop predictive models that treat outcome as a binary variable. Cox proportional hazards (COX) and logistic regression (LR) were used as comparators for time-to-event and binary outcomes, respectively. Results: The final cohort had 3429 PIVCs, which were divided into the development cohort (2400 PIVCs) and validation cohort (1029 PIVCs). The c-statistic (95% confidence interval) of the models in the validation cohort for discrimination were as follows: RSF, 0.689 (0.627-0.750); LASSO, 0.664 (0.610-0.717); RF, 0.699 (0.645-0.753); gradient boosting tree, 0.699 (0.647-0.750); COX, 0.516 (0.454-0.578); and LR, 0.633 (0.575-0.691). No significant difference was observed among the c-statistic of the four models for binary outcome. However, RSF had a higher c-statistic than COX. The important predictive factors in RSF included inserted site, catheter material, age, and nicardipine, whereas those in RF included catheter dwell duration, nicardipine, and age. Conclusions: The RSF model for the survival time analysis of phlebitis occurrence showed relatively high prediction performance compared with the COX model. No significant differences in prediction performance were observed among the models with phlebitis occurrence as the binary outcome.

Characteristics of needlestick and sharps injuries of the hands in the operating room among orthopedic surgeons in Japan.

Among the reports on needlestick and sharps injuries (NSIs), many are orthopedic-related due to the frequent use of sharp devices such as pins and wires. This study aimed to identify high-risk instruments, the most common injury sites for each instrument, and the circumstances of NSIs of the hand during orthopedic surgeries in Japan. Incidents of exposure to blood or bodily fluids among physicians during orthopedic surgeries reported to the Japan-EPINet between 2000 and 2015 were included in this study. The four most common devices were identified and the associations among years of experience, equipment users, and injured sites were analyzed. We identified 666 cases of NSIs affecting orthopedic surgeons in the operating room. The instrument most frequently responsible for NSIs was suture needles, which were involved in 265 cases (39.7%). The second most common instrument was pins/wires, which was involved in 111 cases (16.6%). NSIs of the hands of orthopedic surgeons were frequently caused by suture needles used in all surgeries, but relatively often caused by orthopedic devices. Orthopedic surgeons must be aware that they are at risk of NSIs and must take appropriate measures and always be cautious when performing surgery, regardless of their years of experience.

Impact of the failure of initial insertion of a peripheral intravascular catheter on the development of adverse events in patients admitted to the intensive care unit from the emergency room: A post hoc analysis of the AMOR-VENUS study.

Aim: To investigate an association between failure of initial peripheral intravascular catheter (PIVC) insertion and adverse events in patients admitted to the intensive care unit (ICU) from the emergency room (ER). Methods: This study was a post hoc analysis of the AMOR-VENUS study, a multicenter cohort study that included 22 institutions and 23 ICUs in Japan between January and March of 2018. Study participants included consecutive adult patients admitted to the ICU with PIVCs inserted in ICU during the study period exclusively from the ER. The primary outcome was adverse events. Adverse events were composite of arterial puncture, hematoma, extravasation, nerve injury, tendon injury, compartment syndrome, pain, redness, bad location, and effusion. Multivariate logistic regression analyses were performed to assess the association between adverse events and the failure of initial PIVC insertion. Results: In total, 363 patients and 1121 PIVCs were analyzed. Moreover, 199 catheters failed to insert properly, and 36 patients and 107 catheters experienced adverse events. After performing multivariate logistic regression analysis, there were statistically significant associations in the odds ratio (OR) and 95% confidence interval (CI) for the failure of initial insertion (OR, 1.66 [1.02-2.71]; p = 0.04). Conclusion: Failure of initial insertion may be a risk factor for adverse events. We could potentially provide various interventions to avoid failure of initial PIVC insertion. For example, PIVC insertion could be performed by experienced practitioners.

T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis.

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

Infection control in healthcare settings in Japan.

In Japan, the practice of infection control in healthcare settings has a short history of less than 3 decades. Before that, infection control practices were far from perfect and even ignored. This review summarizes changes in infection control in Japan since the 1980s and offers some comparisons with practices in foreign countries, especially the United States. Infection control is far better now than 25 years ago, but there remain fundamental issues that limit the development of better infection control practices. These problems include insufficient funding and human resources due to the socialized healthcare insurance system in Japan and the lack of interest in infection control research.

[Management of infectious diseases and the role of Infection Control Team(ICT) in the cancer treatment].

Patients with malignancy undergoing treatment for the disease have an elevated risk of infectious diseases. Due to their immune status, bacterial translocation of normal flora from the intestine to the bloodstream and other events may occur, and are very difficult to prevent. However, infection from an external source can be prevented. This type of infection has been called nosocomial infection in recent years, or "healthcare-associated infection(HAI)". The strategies for preventing such infections are well-established, including transmission-based precautions and standard precautions, which are part of a comprehensive program established by the Centers for Disease Control and Prevention in the United States of America. It is very important at the hospital level to implement these programs for infection prevention, educating new employees and existing healthcare workers, encouraging them to perform sanitary and safe ? practices, and measuring HAIs in the hospital. To maintain this activity in Japan, teamwork is needed, because of the lack of human resources dedicated to HAI prevention. This is called an Infection Control Team(ICT). Activity proposed by the ICT is described in detail here.

Adverse reactions to BNT162b2 mRNA COVID-19 vaccine in medical staff with a history of allergy.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) vaccination is progressing globally. Several adverse reactions have been reported with vaccination against COVID-19. It is unknown whether adverse reactions to COVID-19 vaccination are severe in individuals with allergies. METHODS: We administered the COVID-19 vaccine to the medical staff at Yamagata University Hospital from March to August 2021. Subsequently, we conducted an online questionnaire-based survey to investigate the presence of allergy and adverse reactions after vaccination and examine the association between allergy and adverse reactions after immunization. RESULTS: Responses were collected from 1586 to 1306 participants after the first and second administration of the BNT162b2 mRNA COVID-19 vaccine, respectively. Adverse reactions included injection site pain, injection site swelling, fever, fatigue or malaise, headache, chills, nausea, muscle pain outside the injection site, and arthralgia. The frequency of some adverse reactions and their severity were higher, and the duration of symptoms was longer in participants with allergies than in those without allergies. Although several participants visited the emergency room for treatment after the first and second vaccinations, no participant was diagnosed with anaphylaxis. CONCLUSIONS: This study suggests that the frequency and severity of adverse reactions after injection of BNT162b2 mRNA COVID-19 vaccine were higher in individuals with allergy; however, no severe adverse reactions such as anaphylaxis or death were observed. These results indicate that individuals with allergic histories may tolerate the BNT162b2 mRNA COVID-19 vaccine.

Risk factors for peripheral venous catheter-related phlebitis stratified by body mass index in critically ill patients: A post-hoc analysis of the AMOR-VENUS study.

Introduction: Phlebitis is an important complication in patients with peripheral intravascular catheters (PIVCs). Although an association between body mass index (BMI) and phlebitis has been suggested, the risk of phlebitis according to BMI has not been well elucidated. Therefore, in this study, we analyzed the risk of phlebitis according to BMI in patients in the intensive care unit (ICU). Materials and methods: This study undertook a secondary analysis of the data from a prospective multicenter observational study assessing the epidemiology of phlebitis at 23 ICUs in Japan. Patients admitted into the ICU aged ≥18 years with a new PIVC inserted after ICU admission were consecutively enrolled and stratified into the following groups based on BMI: Underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 25.0 kg/m2), and overweight/obese (BMI ≥ 25.0 kg/m2). The primary outcome was phlebitis. The risk factors for phlebitis in each BMI-based group were investigated using a marginal Cox regression model. In addition, hazard ratios and 95% confidence intervals were calculated. Results: A total of 1,357 patients and 3,425 PIVCs were included in the analysis. The mean BMI for all included patients was 22.8 (standard deviation 4.3) kg/m2. Among the eligible PIVCs, 455; 2,041; and 929 were categorized as underweight, normal weight, and overweight/obese, respectively. In the underweight group, catheter size ≥ 18 G and amiodarone administration were independently associated with the incidence of phlebitis. Drug administration standardization was associated with the reduction of phlebitis. In the normal weight group, elective surgery as a reason for ICU admission, and nicardipine, noradrenaline, and levetiracetam administration were independently associated with the incidence of phlebitis. Heparin administration was associated with the reduction of phlebitis. In the overweight/obese group, the Charlson comorbidity index, catheter size ≥ 18 G, and levetiracetam administration were independently associated with the incidence of phlebitis. Catheters made from PEU-Vialon (polyetherurethane without leachable additives) and tetrafluoroethylene were associated with the reduction of phlebitis. Conclusion: We investigated the risk factors for peripheral phlebitis according to BMI in ICU and observed different risk factors in groups stratified by BMI. For example, in underweight or overweight patients, large size PIVCs could be avoided. Focusing on the various risk factors for phlebitis according to patients' BMIs may aid the prevention of phlebitis.