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Objective:The coronavirus disease 2019 (COVID-19) vaccine may hold the key to ending the pandemic, but vaccine hesitancy is hindering the vaccination of healthcare personnel (HCP). We examined their perceptions of the COVID-19 vaccine and implemented an intervention to increase vaccination uptake.Design:Before-and-after trial.Participants and setting:Healthcare personnel at a 790-bed tertiary-care center in Tokyo, Japan.Interventions:A prevaccination questionnaire was administered to HCP to examine their perceptions of the COVID-19 vaccine. A multifaceted intervention was then implemented involving (1) distribution of informational leaflets to all HCP, (2) hospital-wide announcements encouraging vaccination, (3) a mandatory lecture, (4) an educational session about the vaccine for pregnant or breastfeeding HCP, and (5) allergy testing for HCP at risk of allergic reactions to the vaccine. A postvaccination survey was also performed.Results:Of 1,575 HCP eligible for enrollment, 1,224 (77.7%) responded to the questionnaire, 533 (43.5%) expressed willingness to be vaccinated, 593 (48.4%) were uncertain, and 98 (8.0%) expressed unwillingness to be vaccinated. The latter 2 groups were concerned about the vaccine’s safety rather than its efficacy. After the intervention, the overall vaccination rate reached 89.7% (1,413 of 1,575), and 88.9% (614 of 691) of the prevaccination survey respondents answered “unwilling” to or “unsure” about eventually receiving a vaccination. In the postvaccination questionnaire, factors contributing to increased COVID-19 vaccination included information and endorsement of vaccination at the medical center (274 of 1,037, 26.4%).Conclusions:This multifaceted intervention increased COVID-19 vaccinations among HCP at a Japanese hospital. Frequent support and provision of information were crucial for increasing the vaccination rate and may be applicable to the general population as well.

The frequent prescription of antimicrobials, such as at discharge from the emergency department, calls for optimizing this practice through modifying physicians’ prescribing behavior. A 1-year, multifaceted intervention implemented in an emergency department decreased the mean monthly antimicrobial prescription rate at discharge and increased the proportion of appropriate prescriptions.

The Ministry of Health, Labour and Welfare has published the Manual of Antimicrobial Stewardship (1st edition) in June 2017 to improve the prescribing practice of antimicrobials for immunocompetent adult and pediatric (both school-aged and older children) patients. Due to the increasing demand for further promoting outpatient antimicrobial stewardship, we conducted a literature and national guideline review to identify the area of need. The results of our review revealed a high antimicrobial prescription rate in the Japanese pediatric population. Furthermore, although the Japanese clinical guidelines/guidance covered the fields of almost all infectious diseases, no system exists to estimate the incidence and treatment patterns of important infectious diseases such as asymptomatic bacteriuria, skin and soft tissue infections, and dental practices in Japan. Therefore, addressing the issues of both establishing surveillance systems and the implementation of guidelines/guidance can be the next step to promote further outpatient antimicrobial stewardship.

A questionnaire was distributed to hospitals in Tokyo (N = 38) regarding their preparedness against and in-facility transmission of coronavirus disease 2019 (COVID-19). As of May 31, 2020, 284 HCP had contracted COVID-19, and in-facility COVID-19 transmission occurred at 13 hospitals, negatively impacting hospital functions and patient care.

Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP.This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis.Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029).The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

Background The present study assessed the impact of time-out on vancomycin use and compared the strategy’s efficacy when led by pharmacists versus infectious disease (ID) physicians at a tertiary care center. Methods Time-out, consisting of a telephone call to inpatient providers and documentation of vancomycin use >72 hours, was performed by ID physicians and clinical pharmacists in the Departments of Medicine and Surgery/Critical Care. Patients in the Department of Medicine were assigned to the clinical pharmacist-led arm, and patients in the Department of Surgery/Critical Care were assigned to the ID physician-led arm in the initial, 6-month phase and were switched in the second, 6-month phase. The primary outcome was the change in weekly days of therapy (DOT) per 1000 patient-days (PD), and vancomycin use was compared using interrupted time-series analysis. Results Of 587 patients receiving vancomycin, 132 participated, with 79 and 53 enrolled in the first and second phases, respectively. Overall, vancomycin use decreased, although the difference was statistically nonsignificant (change in slope, −0.25 weekly DOT per 1000 PD; 95% confidence interval [CI], −0.68 to 0.18; P = .24). The weekly vancomycin DOT per 1000 PD remained unchanged during phase 1 but decreased significantly in phase 2 (change in slope, −0.49; 95% CI, −0.84 to −0.14; P = .007). Antimicrobial use decreased significantly in the surgery/critical care patients in the pharmacist-led arm (change in slope, −0.77; 95% CI, −1.33 to −0.22; P = .007). Conclusions Vancomycin time-out was moderately effective, and clinical pharmacist-led time-out with surgery/critical care patients substantially reduced vancomycin use., The present study assessed the impact of time-out on vancomycin use and compared the strategy’s efficacy when led by pharmacists versus infectious disease physicians. Vancomycin time-out was moderately effective, and pharmacist-led time-out with surgery/critical care patients substantially reduced vancomycin use.

Objectives In Japan, most cases of tuberculosis (TB) occur among individuals aged 65 years or older. However, data on in-hospital adverse events (AEs) associated with TB management, especially in high-income nations with an ageing population, are scarce. The present study aimed to scrutinize the current TB unit practices, incidence of in-hospital AEs and predictors of in-hospital mortality. Methods This retrospective cohort study was conducted at a tertiary care centre in Tokyo, Japan from 2012 to 2017. Inpatients with the diagnosis of TB and aged >18 years were included. Quality of in-hospital care and factors associated with in-hospital mortality were investigated using multivariate logistic regression analysis. Results In total, 448 patients were enrolled. The in-hospital mortality rate was 16.7% (75/448). Miliary/disseminated TB was common (59/448, 13.2%), especially in those who died (17/75, 22.7%). Factors independently associated with in-hospital mortality were a low Karnofsky performance status score on admission (score: 40-10, adjusted odds ratio (aOR) 25.65, 95% CI 5.63–116.92 and score: 70-50, aOR 9.47, 95% CI 2.07–43.3), age over 89 years (aOR 3.68, 95% CI 1.08–12.46), Charlson Co-morbidity Index >5 (aOR 3.56, 95% CI 1.37–9.21), development of any health-care-associated infection (aOR 2.95, 95% CI 1.35–6.41), and development of any drug-related AE leading to discontinuation of anti-TB agents (seven patients were unable to resume treatment with anti-TB agents before death) (aOR 2.29, 95% CI 1.02–5.11). Conclusions In-hospital AEs (i.e. health-care-associated infection and drug-related AEs), as well as patient-related variables, were associated with in-hospital mortality among TB patients.

SummaryBackgroundElevated proinflammatory cytokines have been associated with 2019 coronavirus disease (COVID-19) severity. We assessed efficacy and safety of sarilumab, an interleukin-6 receptor inhibitor, in severe (requiring supplemental oxygen by nasal canula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19.MethodsThis was a 60-day, randomised, double-blind, placebo-controlled, multinational trial in patients hospitalised with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomised 2:2:1 to intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. The primary endpoint was time to ≥2-point clinical improvement (7-point scale; range: 1 [death] to 7 [not hospitalised]). The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This trial is registered withClinicalTrials.gov(NCT04327388).FindingsBetween March 28 and July 3, 2020, 420 patients were randomised; 416 received treatment (placebo, n=84; sarilumab 200 mg, n=159; sarilumab 400 mg, n=173). At day 29, there were no significant differences in median (95% CI) time to ≥2-point improvement between placebo (12·0 [9·0–15·0] days) and sarilumab groups (200 mg: 10·0 [9·0–12·0] days, p=0.96, log-rank test; 400 mg: 10·0 [9·0–13·0] days, p=0.34) or in proportions of patients alive (placebo, 91·7%; sarilumab 200 mg, 89·9%, p=0·63; sarilumab 400 mg, 91·9%, p=0·85). At day 29, there were numerical, nonsignificant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +9%, 95% CI −7·7 to 25·5, p=0·25) for critical patients. There were no unexpected safety signals.InterpretationThis trial did not demonstrate efficacy of sarilumab in patients hospitalised with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19.FundingSanofi and Regeneron Pharmaceuticals, Inc.

Introduction Clusters of novel coronavirus infectious disease of 2019 (COVID-19) have spread to become a global pandemic imposing a significant burden on healthcare systems. The lack of an effective treatment and the emergence of varied and complicated clinical courses in certain populations have rendered treatment of patients hospitalized for COVID-19 difficult. Methods Tokyo Metropolitan Tama Medical Center, a public tertiary acute care center located in Tokyo, the epicenter of COVID-19 in Japan, has been admitting patients with COVID-19 since February 2020. The present, retrospective, case-series study aimed to investigate the clinical course and outcomes of patients with COVID-19 hospitalized at the study institution. Results In total, 101 patients with COVID-19 were admitted to our hospital to receive inpatient care. Eleven patients (10.9%) received ECMO, and nine patients (8.9%) died during hospitalization after COVID-19 was diagnosed. A history of smoking and obesity were most commonly encountered among patients with a complicated clinical course. Most patients who died requested to be transferred to advanced palliative care in the early course of their hospitalization. Conclusions Our experience of caring for these patients demonstrated a relatively lower mortality rate and higher survival rate in those with extracorporeal membrane oxygenation placement than previous reports from other countries and underscored the importance of proactive, advanced care planning in the early course of hospitalization.

The coronavirus disease 2019 (COVID-19) pandemic has influenced current infection control practices in the healthcare setting. We surveyed 74 hospitals in Japan regarding changes in their infection control practices or policies between 2020 and the present. We found that the current hospital infection control practices for COVID-19 are adequate.

Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.

Pasteurella multocida, a zoonotic infectious pathogen, is a rare cause of mycotic aneurysms in human hosts. A 61-year-old male patient with myelodysplastic syndromes (MDS) was admitted due to fever, chills, and malaise. He had been frequently licked by his pet dog. Soon after admission, a bloodstream infection due to P. multocida was found, and he received two weeks of antimicrobial therapy. However, the bloodstream infection recurred at short intervals. Computed tomography revealed a mycotic aneurysm for which he underwent aortic graft placement. Mycotic aneurysms should be considered in patients with recurrent bloodstream infections due to Pasteurella, especially if they recur at short intervals in patients with a preexisting immunocompromised state.

An outbreak of metallo-β-lactamase (MBL) producingKlebsiella pneumoniaeoccurred at a children’s hospital in Japan. MBL-producingK. pneumoniaewas detected in tea dispenser in the hospital, the use of which was associated with the acquisition of the MBL-producing Enterobacteriaceae. The outbreak ceased after use of the tea dispenser was banned.

Background The optimal timing of preoperative surgical antimicrobial prophylaxis (SAP) remains uncertain. This study aimed to evaluate the impact of changing the timing of SAP on the incidence of surgical site infection (SSI) in laparoscopic surgery. Methods We performed a before-after study from August 2014 through June 2017 to assess the impact of changes in the timing of SAP on the incidence of SSI at a 790-bed tertiary care center in Japan. The intervention was the administration of SAP immediately after the study patients entered the operating room for laparoscopic surgery. Results In total, 1397 patients who met the inclusion criteria were analyzed. After the intervention, the median time between the time of SAP completion and the time of surgical incision changed from 8 min to 26 min (p

A 90-year-old female patient with diabetes mellitus presented with newly developed anorexia and oral pain during hospitalisation. She was admitted for severe COVID-19 about 6 weeks earlier. For COVID-19 treatment, she received oral dexamethasone 6 mg/day for 10 days. One week after the completion

Background An antimicrobial stewardship program (ASP) is one of the core elements needed to optimize antimicrobial use. Although collaboration at the national level to address the importance of ASPs and antimicrobial resistance has occurred in the Asia Pacific region, hospital-level ASP implementation in this region has not been comprehensively evaluated. Methods We conducted a systematic review and meta-analysis to assess the efficacy of ASPs in inpatient settings in the Asia Pacific region from January 2005 through March 2016. The impact of ASPs on various outcomes, including patient clinical outcomes, antimicrobial prescription outcomes, microbiological outcomes, and expenditure were assessed. Results Forty-six studies were included for a systematic review and meta-analysis. The pooled risk ratio for mortality from ASP before-after trials and 2-group comparative studies were 1.03 (95% confidence interval [CI], .88-1.19) and 0.69 (95% CI, .56-.86), respectively. The pooled effect size for change in overall antimicrobial and carbapenem consumption (% difference) was -9.74% (95% CI, -18.93% to -.99%) and -10.56% (95% CI, -19.99% to -3.03%), respectively. Trends toward decreases in the incidence of multidrug-resistant organisms and antimicrobial expenditure (range, 9.7%-58.1% reduction in cost in the intervention period/arm) were also observed. Conclusions ASPs in inpatient settings in the Asia Pacific region appear to be safe and effective to reduce antimicrobial consumption and improve outcomes. However, given the significant variations in assessing the efficacy of ASPs, high-quality studies using standardized surveillance methodology for antimicrobial consumption and similar metrics for outcome measurement are needed to further promote antimicrobial stewardship in this region.

The shortage of antimicrobials poses a global health threat. In Japan, for instance, the current, critical shortage of cefazolin, a first-line agent for the treatment of common infectious diseases and surgical antimicrobial prophylaxis, has had a substantial impact on inpatient care. A shortage of essential antimicrobial agents like cefazolin leads to increased consumption of alternative antimicrobial agents with broad-spectrum activity, with the unintended consequence of militating against antimicrobial stewardship efforts in inpatient settings and potentially promoting antimicrobial resistance. Although there is global awareness of the shortage of crucial antimicrobials, action to resolve this problem, especially with a view to preventing antimicrobial resistance and promoting antimicrobial stewardship, has been slow, possibly due to the failure to appreciate the urgency of the dilemma. A comprehensive plan for stabilizing antimicrobial access and international collaboration to secure a continuous supply of essential antimicrobials are urgently needed.

Human adenoviruses cause a wide spectrum of illnesses, including invasive infections, in immunocompromised hosts. We report a case of disseminated adenovirus infection following unrelated cord–blood transplantation in a 46-year-old male with a lymphoma. A review of the literature on disseminated adenovirus infections in adult patients with hematopoietic stem cell transplantation has also been included. Despite antiviral therapy, the mortality rate in hematopoietic stem cell transplantation recipients with a disseminated adenovirus infection is as high as 72%, and estimating the risk of human adenovirus infection in a timely manner is crucial to improving outcomes., Lay abstract Human adenoviruses are common viruses that cause a range of illness such as bronchitis, gastroenteritis and conjunctivitis. We recently experienced a case of disseminated adenovirus infection following hematopoietic stem cell transplantation in a patient with a lymphoma who received chemotherapy. Although disseminated adenovirus infection is not a rare disease in immunocompromised patients, it is noteworthy that its mortality remains high and it may not frequently occur. Therefore, this work provides a case presentation and a review of disseminated adenovirus infection in patients with hematopoietic stem cell transplantation in order to aid our understanding of the nature of illness of human adenovirus infections in immunocompromised patients.

Our goal was to evaluate the 5-year sustainability of a multimodal intervention that included a prize to the hospital with the highest overall hand hygiene adherence rates among health care workers.We conducted an observational study in 3 Japanese tertiary care hospitals using unobtrusive direct observation of physician and nurse hand hygiene adherence. Observations were performed by a trained observer on inpatient medical, surgical, intensive care, and emergency units. The primary outcome was hand hygiene adherence rates before patient contact. Secondary outcomes were health care worker survey responses to a World Health Organization (WHO) questionnaire on hand hygiene practices.Hand hygiene adherence rates had improved significantly after the introduction of a multimodal intervention (based on principles recommend by the WHO) in 2012 and 2013 (from 18.0% pre-intervention to 32.7% 6 months post-intervention; P.001). No significant changes were found in hand hygiene adherence in these hospitals 5 years after the original intervention (31.9% 5 years after intervention; P = .53); however, substantial variability in hand hygiene adherence by unit and health care worker type was noted.A multimodal hand hygiene initiative achieved sustained improvement in hand hygiene adherence in 3 Japanese hospitals 5 years after the original intervention.

Underestimating antimicrobial use based on days of therapy (DOT) is recognized for certain antimicrobial agents. We investigated the difference between DOT and therapeutic drug monitoring (TDM)–based exposure days in estimating vancomycin use and demonstrated that DOT may underestimate vancomycin exposure by ∼10%.

We conducted a restrospective cohort study of patients discharged from the emergency department at a tertiary care center with an antimicrobial prescription. More than half of the prescribed antimicrobials were misused and frequently inappropriate for various infectious diseases. In this study, we analyzed the physician-related and environment-related factors predicting misuse.

Background: Shortages of essential medicines, a long-standing issue in healthcare, apply equally to antimicrobial agents, a group of essential drugs necessary for sustainable healthcare. The WHO categorized essential medicines into the access, watch, and reserve groups. Older antimicrobials, in particular, were categorized into the access group, meaning that these drugs are in theory widely available at an affordable cost. The shortage of essential antimicrobial agents like cefazolin leads to increased consumption of alternative antimicrobial agents with broad-spectrum activity, which often has the undesirable consequence of defeating antimicrobial stewardship efforts in inpatient settings and potentially promoting antimicrobial resistance. In Japan, cefazolin has been in critically short supply since March 2019. Cefazolin is a first-line agent against common infectious diseases and in surgical antimicrobial prophylaxis, and its shortage has substantially impacted inpatient care. The aim of the present study was to investigate changes in antimicrobial practice at a tertiary-care center in Japan following the emergence of the national cefazolin shortage in March 2019. Methods: Data on each antimicrobial use are logged as days of therapy (DOT) per 1,000 patient days (PD) for antimicrobial stewardship purposes at the study institution. We extracted weekly data from September 2018 to September 2019 to evaluate the impact of the national cefazolin shortage on antimicrobial use at our tertiary-care center. Changes in weekly antimicrobial use and the weekly incidence of Clostridium difficile infections were analyzed by interrupted time series analysis. We also investigated changes in antimicrobial practice at selected situations. Results: As weekly cefazolin use significantly declined after the emergence of the national shortage, use of third-generation cephalosporin (+18.9 DOT per 1,000 PD for intercept [P < .001] and +0.65 DOT per 1,000 PD per week for trend [P = .037]) and clindamycin (18 DOT per 1,000 PD for intercept [P = .008] and 0.12 DOT per 1,000 PD per week for trend [P = .003]) significantly increased. Significant changes in antimicrobial practice were also observed in surgical antimicrobial prophylaxis: third-generation cephalosporin use increased from 1.0% (31 of 3,032) to 62.9% (2,237 of 3,554) (P < .001). However, no significant change in the incidence of Clostridium difficile infection was observed during the study period: +1.72 per 10,000 PD for intercept (P = .12) and 0.12 per 10,000 PD per week for the trend (P = .09). Conclusions: The national cefazolin shortage had a significantly negative impact on patient care and led to increased use of alternative, broader-spectrum antimicrobials, which are not ideal choices either for prophylaxis or treatment.Funding: NoneDisclosures: None

BackgroundAn inpatient antimicrobial stewardship program is vital for judicious antimicrobial use. We began a hospital-wide, postprescription review with feedback (PPRF) in 2014; the present study evaluated its impact on antimicrobial consumption and clinical outcomes over 4 years.MethodsOnce-weekly PPRF for carbapenems and piperacillin/tazobactam was implemented. We tracked the data on each antimicrobial use as days of therapy (DOT) per 1000 patient-days (PD). Changes in the incidence of drug-resistant organisms, in-hospital mortality, and length of hospital stay per month were analyzed by an interrupted time series.ResultsCarbapenem use continued to decline in the preintervention and intervention periods (−0.73 and −0.003 DOT/1000 PD, respectively), and although monthly average use remained low in the intervention period (8.3 DOT/1000 PD), more importantly, the postintervention change in the slope diminished significantly. Piperacillin/tazobactam use showed a steeper decline in the intervention period, but the change in the slope was not statistically significant (change in slope: −0.20 DOT/1000 PD per month [P = .16]). Postintervention use of narrower-spectrum antimicrobials including ampicillin/sulbactam (change in slope: +0.58 DOT/1000 PD per month [P < .001]) increased. The antimicrobial cost and the monthly average length of hospital stay also declined (−37.4 USD/1000 PD per month [P < .001] and −0.04 days per month [P < .001], respectively), whereas few postintervention changes in the incidence of drug-resistant organisms were observed.ConclusionsIn our study, the 4-year PPRF for broad-spectrum antimicrobials coincided with a reduction in the use of targeted antimicrobials and resulted in an improvement in 1 patient-centered outcome, thus conferring the additional benefit of reducing expenditures for antimicrobials.

Background Bloodstream infections are responsible for a large proportion of deaths among geriatric patients. Japan is a rapidly aging society; however, little is known about the epidemiology of bloodstream infections in geriatric patients in Japanese institutions. Methods We conducted a retrospective cohort study of patients aged ≥65 years old with a bloodstream infection in a Japanese tertiary care hospital in 2013. We defined inadequate empiric antimicrobial therapy as either antimicrobial treatment that was ineffective against subsequently isolated organisms or treatment initiated after notification of a positive culture. Predictors of inadequate antimicrobial therapy and 30-day mortality among geriatric patients with bloodstream infections were evaluated. Results We identified 275 patients with a bloodstream infection, of which 42.2% of cases (116/275) were healthcare-associated, hospital-onset. The most common source of bloodstream infection was hepatobiliary (28.0%). Inadequate empiric antimicrobial therapy occurred in 29.8% of the patients. Factors associated with inadequate empiric therapy included a history of surgery prior to bloodstream infection during index hospitalization (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.18–9.12). In 275 patients, 38 (13.8%) died within 30 days after the first positive blood culture. Predictors of 30-day mortality was Pitt bacteremia score >6 (aOR 9.80; 95% CI 4.72–20.36). Conclusion Inadequate empiric antimicrobial therapy occurred in approximately one-third of episodes of bloodstream infection in geriatric patients. Severity at the time of bloodstream infection was likely to have contributed to mortality. The initiation of adequate empiric antimicrobial therapy may have important implications for antimicrobial stewardship even in the elderly population.

Department of Rheumatology, Tokyo Metropolitan TamaMedical Center, Fuchu City, Tokyo, Japan; Division of Infectious Diseases, Tokyo Metropolitan TamaMedical Center, FuchuCity, Tokyo, Japan; Division of Rheumatology, NagoyaMedical Center, Nagoya, Japan; University of California, San Francisco, San Francisco, CA, USA; Faculte de Medecine, Unite des Rickettsies, Marseille, France; Japan Community Healthcare Organization, Tokyo, Japan.

Summary Background Differences in the risk factors for surgical site infection (SSI) following open heart surgery and coronary artery bypass graft surgery are not well described. Aim To identify and compare risk factors for SSI following open heart surgery and coronary artery bypass graft surgery. Methods SSI surveillance data on open heart surgery (CARD) and coronary artery bypass graft surgery (CBGB) submitted to the Japan Nosocomial Infection Surveillance (JANIS) system between 2008 and 2010 were analysed. Factors associated with SSI were analysed using univariate modelling analysis followed by multi-variate logistic regression analysis. Non-binary variables were analysed initially to determine the most appropriate category. Findings The cumulative incidence rates of SSI for CARD and CBGB were 2.6% (151/5895) and 4.1% (160/3884), respectively. In both groups, the duration of the operation and a high American Society of Anesthesiologists' (ASA) score were significant in predicting SSI risk in the model. Wound class was independently associated with SSI in CARD but not in CBGB. Implants, multiple procedures and emergency operations predicted SSI in CARD, but none of these factors predicted SSI in CBGB. Conclusions There was a remarkable difference in the prediction of risk for SSI between the two types of cardiac surgery. Risk stratification in CARD could be improved by incorporating variables currently available in the existing surveillance systems. Risk index stratification in CBGB could be enhanced by collecting additional variables, because only two of the current variables were found to be significant for the prediction of SSI.

BACKGROUNDRapidly growing nontuberculous mycobacteria (RGM) are considered rare pathogens, causing central line–associated bloodstream infection. We identified an outbreak of central line–associated bloodstream infection due to RGM at a hematology-oncology ward during a 5-month period.DESIGNOutbreak investigation and literature review.SETTINGA Japanese tertiary care center.PATIENTSAdults who were hospitalized at the hematology-oncology ward from October 15, 2011, through February 17, 2012.RESULTSA total of 5 patients with a bloodstream infection due to RGM (4 cases ofMycobacterium mucogenicumand 1 case ofMycobacterium canariasenseinfection) were identified; of these, 3 patients had acute myeloid leukemia, 1 had acute lymphocytic leukemia, and 1 had aplastic anemia. Four of the 5 patients received cord blood transplantation prior to developing the bloodstream infection. All central venous catheters in patients with a bloodstream infection were removed. These patients promptly defervesced after catheter removal and their care was successfully managed without antimicrobial therapy. Surveillance cultures from the environment and water detectedM. mucogenicumandM. canariasensein the water supply of the hematology-oncology ward. The isolates from the bloodstream infection and water sources were identical on the basis of 16S-rRNA gene sequencing.CONCLUSIONSThe source of RGM in the outbreak of bloodstream infections likely was the ward tap water supply. Awareness of catheter-related bloodstream infections due to nontuberculous mycobacteria should be emphasized, especially where immunocompromised patients are at risk. Also, using antimicrobials after catheter removal to treat central line–associated bloodstream infection due to RGM may not be necessary.Infect Control Hosp Epidemiol 2015;36(1): 76–80

Background Bacterial meningitis is an emergent disease requiring prompt diagnosis and treatment with appropriate antimicrobials. Although the lumbar puncture is widely used as a diagnostic tool for bacterial meningitis, it remains unclear which value in cerebrospinal fluid (CSF) analysis in emergency laboratory tests precisely predicts the presence of bacterial meningitis. Methods This is a single-center, retrospective review of medical records to determine which emergency laboratory CSF test results are useful for predicting bacterial meningitis. The diagnosis of meningitis is made when the white blood cell count in CSF exceeds 5 cells/ μ L, while the diagnosis of bacterial meningitis additionally requires the growth of a pathogen from a CSF culture or the identification of a pathogen in Gram staining of CSF specimen. Results We identified 15 patients with bacterial meningitis and 129 patients with aseptic meningitis. While neutrophil-predominant pleocytosis and a decreased glucose level in CSF can predict the presence of bacterial meningitis, the CSF/blood glucose ratio is more precise (optimal cut-off=0.36, sensitivity=92.9%, specificity=92.9%, area under the curve=.97) even after administration of antimicrobials prior to examination in the emergency department. Conclusion This study suggests that the CSF/blood glucose ratio may be a better single indicator for bacterial meningitis. Since the CSF glucose and blood glucose values are promptly and easily obtained from a lumbar puncture, the CSF/blood glucose ratio should be considered as a timely diagnostic indicator of bacterial meningitis. It may also help exclude the diagnosis of bacterial meningitis especially in cases in which no microorganisms can be cultured.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6–7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9–75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018”/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018” isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.

Background The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. Methods A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6–7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. Results Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018”, and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. Conclusion The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.

Background The emergency department (ED) is one of the most important settings where antimicrobials are frequently prescribed in developed countries, and at least 30% of antimicrobials prescribed at the ED are inappropriate. Some studies revealed that various factors, especially the physician-related factors were associated with inappropriate antimicrobial use. Implementing effective strategies to modify prescribing practice is needed to optimize antimicrobial therapy at the ED. Methods We implemented a multifaceted intervention to patients discharged with oral antimicrobial agents in the ED at a Japanese tertiary care center from October 2018 to March 2019. The intervention included (1) an educational didactic session to physicians, (2) an evidence-based tool book regarding antimicrobial use for common diagnoses, (3) antimicrobial order sets for common diagnoses, (4) monthly reports of the appropriateness of antimicrobial use, and (5) post-prescription review and feedback by an infectious diseases physician. The proportion of appropriate discharge antimicrobial prescription at ED, and changes in the prescription density, measured as the number of prescription per 1,000 patient visits between pre- and post-intervention were evaluated. Results The total number of patient visits at the ED during the study period was 52,274. With the intervention, the mean monthly discharge antimicrobial prescription decreased from 42.7 to 34.2 per 1,000 visits (proportional reduction 0.20; P < 0.01). Overall, appropriate prescription rate significantly increased from 47.7% (742/1,555) to 77.4% (421/544) (P < 0.01). The rate of unnecessary and inappropriate discharge antimicrobial prescription accounted from 27.5% (428/1,555) and 21.7% (337/1,555) to 8.5% (46/544) and 10.7% (58/544), respectively. A substantial improvement in discharge antimicrobial prescription against intra-abdominal infections and odontogenic infections during the intervention period was observed (changes in the proportion of appropriate prescription was 0.37 [P < 0.01] and 0.51 [P < 0.01], respectively. Conclusion An evidence-based, multifaceted intervention led to decreasing unnecessary prescription and optimizing physicians’ antimicrobial prescriptions at the ED. Disclosures All authors: No reported disclosures.

Objective.Although mandatory vaccination programs have been effective in improving the vaccination rate among healthcare workers, implementing this type of program can be challenging because of varied reasons for vaccine refusal. The purpose of our study is to measure improvement in the influenza vaccination rate from a multifaceted intervention at a Japanese tertiary care center where implementing a mandatory vaccination program is difficult.Design.Before-and-after trial.Participants and Setting.Healthcare workers at a 550-bed, tertiary care, academic medical center in Sapporo, Japan.Interventions.We performed a multifaceted intervention including (1) use of a declination form, (2) free vaccination, (3) hospital-wide announcements during the vaccination period, (4) prospective audit and real-time telephone interview for healthcare workers who did not receive the vaccine, (5) medical interview with the hospital executive for noncompliant (no vaccine, no declination form) healthcare workers during the vaccination period, and (6) mandatory submission of a vaccination document if vaccinated outside of the study institution.Results.With the new multifaceted intervention, the vaccination rate in the 2012-2013 season increased substantially, up to 97%. This rate is similar to that reported in studies with a mandatory vaccination program. Improved vaccination acceptance, particularly among physicians, likely contributed to the overall increase in the vaccination rate reported in the study.Conclusions.Implementation of comprehensive strategies with strong leadership can lead to substantial improvements in vaccine uptake among healthcare workers even without a mandatory vaccination policy. The concept is especially important for institutions where implementing mandatory vaccination programs is challenging.

Objectives Acute cholangitis is a common cause of bacteraemia resulting in severe sepsis or septic shock. The impact of the appropriate initial antimicrobial therapy on short-term mortality in bacteraemic cholangitis has not been well investigated. Methods We conducted a retrospective cohort study of patients with bacteraemic cholangitis at two large tertiary care centres in Tokyo, Japan between 2009 and 2015. We determined the factors associated with 30-day all-cause mortality from the date of drawing the first positive blood culture, using a multivariate logistic regression analysis. Results We identified 573 patients with bacteraemic cholangitis (median age, 77 years; male, 58.3%). The 30-day all-cause mortality rate was 6.6% (38/573). Inadequate initial antimicrobial therapy occurred in 133 (23.2%) patients. Factors associated with 30-day all-cause mortality included the Charlson co-morbidity index score >3 (adjusted odds ratio (aOR) 4.12; 95% CI 1.18–14.38), jaundice (total bilirubin >2.5 mg/dL) (aOR 3.39; 95% CI 1.46–7.89), septic shock within 48 h of the first positive blood culture (aOR 3.34; 95% CI 1.42–7.89), biliary obstruction due to hepatobiliary malignancy (aOR 8.00; 95% CI 2.92–21.97), and inadequate initial antimicrobial therapy (aOR 2.78; 95% CI 1.27–6.11). Conclusions Inadequate initial antimicrobial therapy was an important, modifiable determinant of survival.

BACKGROUNDSurgical site infection (SSI) following gastric surgery has not been well documented.OBJECTIVETo describe and assess factors associated with SSI following gastric surgery in Japan using a Japanese national database for healthcare-associated infections.DESIGNA retrospective nationwide surveillance-based study.SETTINGJapanese healthcare facilities.METHODSData on gastric surgeries performed between 2012 and 2014 were extracted from the Japan Nosocomial Infections Surveillance. Gastric surgery was divided into 3 types of procedures: total gastrectomy (GAST-T), distal gastrectomy (GAST-D), and other types of gastric surgery (GAST-O). The incidence of and factors associated with SSI following gastric surgery were assessed by the 3 types of procedures.RESULTSThe cumulative incidence of SSI following gastric surgery was 8.8% (3,156/36,052). The incidence of SSI following GAST-T (12.4%) was significantly higher than that following GAST-D (7.01%) or GAST-O (7.84%). Besides the 4 conventional risk factors for predicting SSI, additional risk factors were identified. Male sex was significantly associated with SSI following all types of gastric surgery, but the effect of the association was substantially different (adjusted odds ratio, 1.52, 1.47, and 1.28 for GAST-T, GAST-D, and GAST-O, respectively). The effect of an emergency operation was similar. Age was also identified as a risk factor, but the most suitable modification of age as a variable differed.CONCLUSIONSThe incidence and factors associated with SSI following 3 types of gastric surgery differed. To accurately compare hospital performance in SSI prevention following gastric surgery, dividing surgical procedures in the surveillance system into 3 types should be considered.Infect Control Hosp Epidemiol 2016;1–6

Personal protective equipment (PPE) protects healthcare workers (HCWs) from infection by highly virulent pathogens via exposure to body fluids and respiratory droplets. Given the recent outbreaks of contagious infectious diseases worldwide, including Ebola virus and Middle Eastern respiratory syndrome, there is urgent need for further research to determine optimal PPE use in high-risk settings. This review intends to provide a general understanding of PPE and to provide guidelines for appropriate use based on current evidence.Although previous studies have focused on the efficacy of PPE in preventing transmission of pathogens, recent studies have examined the dangers to HCWs during removal of PPE when risk of contamination is highest. Access to adequate PPE supplies is crucial to preventing transmission of pathogens, especially in resource-limited settings. Adherence to appropriate PPE use is a challenge due to inadequate education on its usage, technical difficulties, and tolerability of PPE in the workplace. Future projects aim at ameliorating this situation, including redesigning PPE which is crucial to improving the safety of HCWs.PPE remains the most important strategy for protecting HCW from potentially fatal pathogens. Further research into optimal PPE design and use to improve the safety of HCWs is urgently needed.

Background Antimicrobials are commonly prescribed in the emergency department despite the fact that a large proportion of these drugs are misused. However, comprehensive studies of factors leading to the misuse of antimicrobials in the emergency department (ED) are few. Understanding current practice of antimicrobial use in the ED is important for developing an effective antimicrobial stewardship program for this setting. Methods We performed a 1-year cohort study of patients discharged from the ED in a tertiary care center with a prescription for oral antimicrobial agents. A retrospective audit of the appropriateness of antimicrobial prescription using prespecified criteria was performed by two infectious disease physicians. Patterns in antimicrobial prescription and the physician-, patient-, and environment-related factors predicting unnecessary/inappropriate antimicrobial prescription were evaluated. Results Of the 36,308 annual visits to the ED, 1,555 patients (4.3% of visit) received oral antimicrobial prescriptions upon discharge. Pneumonia (18.2% [283/1,555]) was the most common indication for antimicrobial prescription. Of the 1,555 antimicrobial prescriptions issued, 852 (52.9%) were considered inappropriate. Factors significantly associated with unnecessary/inappropriate antimicrobial prescription included the lack of comorbidities (adjusted odds ratio [aOR]: 1.39; 95% confidence interval [CI]: 1.03–1.87), late-night visit (aOR: 1.48 95%; CI: 1.05–2.09), the spring-summer season (aOR: 1.13 95%; CI: 1.03–1.25), higher postgraduate year (>10 years) (aOR: 1.77 95%; CI: 1.24–2.52), and physicians in surgical subspecialties (aOR: 4.51 95%; CI: 3.34–6.09). Conclusion More than half of oral antimicrobial prescriptions in the ED were inappropriate. Unnecessary or inappropriate antimicrobial prescriptions were frequently issued during the late-night shift, and by older physicians and physicians in surgical subspecialties. Disclosures All authors: No reported disclosures.

Background Antimicrobials are frequently administered to patients with an advanced stage of illnesses. Understanding current practice of antimicrobial use at the end of life and factors influencing physicians’ prescribing behavior is necessary to provide an effective antimicrobial stewardship program and the best end-of-life care in terminally ill patients. Methods The current study was a 1-year retrospective cohort study of patients with an advanced stage of illnesses and was conducted at a 790-bed, public, tertiary care center in Japan. Patterns in current antimicrobial use in the last 14 days of the life of terminally ill patients and the factors influencing physicians’ prescribing behaviors were analyzed. Results Of the 260 patients, 192 (73.8%) had an advanced stage malignancy, 136 (52.3%) received antimicrobial therapy in the last 14 days of their life, of whom 60 (44.1%) received antimicrobials for symptom relief. Overall antimicrobial use in the last 14 days of their life was 421.9 days of therapy per 1,000 patient-days. Factors associated with antimicrobial use in this period included a history of antimicrobial use prior to the last 14 days of life during index hospitalization (adjusted odds ratio [aOR]: 4.86; 95% confidence interval [CI]: 2.67–8.84), antipyretic use in the last 14 days of life (aOR: 4.19 95%; CI: 2.01–8.71), and the Charlson comorbidity index ≤ 5 (aOR: 2.18 95%; CI: 1.06–4.53). Conclusion Approximately half of the patients hospitalized with an advanced stage of illnesses received antimicrobials in the last 14 days of their life. Antimicrobials were commonly prescribed and their overall consumption was significant despite their limited efficacy. The factors associated with antimicrobial use at the end-of-life in this study are likely to explain physicians’ prescribing behaviors. In the era of robust antimicrobial stewardship, reconsidering antimicrobial use in terminally ill patients is necessary. Disclosures All authors: No reported disclosures.

Staphylococcus aureus bacteremia results in substantial mortality. Infectious diseases specialist consultation can improve adherence to evidence-based management of S. aureus bacteremia, but its effect on mortality is unclear.A 2-year prospective cohort study of patients with S. aureus bacteremia was performed at a large tertiary care hospital. Patients who died within 2 days of diagnosis were excluded. Independent risk factors for 28-day mortality were determined.Among 341 patients with S. aureus bacteremia, 189 (55%) were male, 196 (58%) were Caucasian, 185 (54%) had methicillin-resistant S. aureus, 108 (32%) had nosocomial bacteremia, and 231 (68%) had a central venous catheter at the time of diagnosis. The median age was 56 years (range 22-95 years). A total of 111 patients (33%) had an infectious diseases consultation. Fifty-four patients (16%) died within 28 days after diagnosis. Factors associated with mortality were intensive care unit admission 48 hours or less after the first positive blood culture (adjusted hazard ratio, 4.65; 95% confidence interval [CI], 2.65-8.18), cirrhosis (adjusted hazard ratio, 4.44; 95% CI, 2.40-8.20), and advanced age (adjusted hazard ratio, 1.27 per every 10 years of age; 95% CI, 1.08-1.50). Infectious diseases consultation was associated with a 56% reduction in 28-day mortality (adjusted hazard ratio, 0.44; 95% CI, 0.22-0.89).Only one third of patients with S. aureus bacteremia in this cohort had an infectious diseases specialist consultation. Infectious diseases consultation was independently associated with a reduction in 28-day mortality. Routine infectious diseases consultation should be considered for patients with S. aureus bacteremia, especially those with greater severity of illness or multiple comorbidities.

Previous studies have suggested that preventive health care measures may be improved by proactive patient-reminder systems and use of electronic medical databases.Our objective was to use Kaiser Permanente's (KP's) electronic medical databases to improve the preventive health care delivered to KP patients in Honolulu, HI.Patients not seen by their primary care physician in more than one year ("low-utilizing patients") and overdue for preventive health care services were identified using KP's electronic medical databases. These patients were then sent letters requesting that they obtain these services. Response rates and results of their screening tests were tracked.Of 309 letters sent, 84 (27.2%) patients responded. Of the 260 patients who were reminded of overdue immunizations (tetanus, pneumonia, influenza, or a combination of these), 51 (19.6%) came in to obtain them. Ten of the 37 (27.0%) women overdue for breast cancer screening came in for mammograms. Eleven of the 109 (10.1%) patients overdue for colorectal cancer screening completed fecal occult blood testing.Outreach letters that target low-utilizing patients identified by an electronic medical database may be an efficient and cost-effective way of improving patient use rates of preventive health care.

Despite advances in antimicrobial and antiviral therapy, meningitis and brain abscess are infections that result in significant morbidity and mortality. A multidisciplinary approach, including intensive care, is often required in the treatment of these infections. Meningitis is defined by the presence of the inflammation of the meninges, with characteristic changes in cerebrospinal fluid. Brain abscess is a focal infection of the brain parenchyma, commonly caused by bacterial, fungal, and parasitic pathogens. This article reviews the common infectious etiologies of central nervous system infections, especially bacterial meningitis and brain abscess, and their subsequent management in the intensive care unit.

In this paper we discuss two techniques to reduce the size of the acoustic model while maintaining or improving the accuracy of the recognition engine. The first technique, demiphone modeling, tries to reduce the redundancy existing in a context dependent state-clustered Hidden Markov Model (HMM). Three-state demiphones optimally designed from the triphone decision tree are introduced to drastically reduce the phone space of the acoustic model and to improve system accuracy. The second redundancy elimination technique is a more classical approach based on parameter tying. Similar vectors of variances in each HMM cluster are tied together to reduce the number of parameters. The closeness between the vectors of variances is measured using a Vector Quantizer (VQ) to maintain the information provided by the variances parameters. The paper also reports speech recognition improvements using assignment of variable number Gaussians per cluster and gender-based HMMs. The main motivation behind these techniques is to improve the acoustic model and at the same time lower its memory usage. These techniques may help in reducing memory and improving accuracy of an embedded Large Vocabulary Continuous Speech Recognition (LVCSR) application.