Japan Nosocomial Infections Surveillance Research Articles

Antimicrobial use and combination of resistance phenotypes in bacteraemic Escherichia coli in primary care: a study based on Japanese national data in 2018.

Antimicrobial use (AMU) in primary care is a contributing factor to the emergence of antimicrobial-resistant bacteria. We assessed the potential effects of AMU on the prevalence of a combination of resistance phenotypes in bacteraemic Escherichia coli in outpatient care settings between primary care facilities ('clinics') and hospitals. Population-weighted total AMU calculated from the national database was expressed as DDDs per 1000 inhabitants per day (DID). National data for all routine microbiological test results were exported from the databases of a major commercial clinical laboratory, including 16 484 clinics, and the Japan Nosocomial Infections Surveillance, including 1947 hospitals. AMU and the prevalence of combinations of resistance phenotypes in bacteraemic E. coli isolates were compared between clinics and hospitals. The five most common bacteria isolated from patients with bacteraemia were the same in clinics, outpatient settings and inpatient settings in hospitals, with E. coli as the most frequent. Oral third-generation cephalosporins and fluoroquinolones were the top two AMU outpatient drugs, except for macrolides, and resulted in at least three times higher AMU in clinics than in hospitals. The percentage of E. coli isolates resistant to both drugs in clinics (18.7%) was 5.6% higher than that in hospitals (13.1%) (P < 10-8). Significant AMU, specifically of oral third-generation cephalosporins and fluoroquinolones, in clinics is associated with a higher prevalence of E. coli isolates resistant to both drugs. This study provides a basis for national interventions to reduce inappropriate AMU in primary care settings.

Distribution, Trends, and Antimicrobial Susceptibility of Bacteroides, Clostridium, Fusobacterium, and Prevotella Species Causing Bacteremia in Japan During 2011-2020: A Retrospective Observational Study Based on National Surveillance Data.

The increasing prevalence of anaerobic bacteremia is a major concern worldwide and requires longitudinal monitoring. We present one of the largest and longest longitudinal studies on the prevalence and antimicrobial resistance of Bacteroides, Clostridium, Fusobacterium, and Prevotella spp. isolated from blood culture samples using national comprehensive surveillance data in Japan during 2011-2020 as part of the Japan Nosocomial Infections Surveillance. Data for 41 949 Bacteroides spp., 40 603 Clostridium spp., 7013 Fusobacterium spp., and 5428 Prevotella spp. isolates were obtained. The incidences of bacteremia caused by Bacteroides fragilis, Clostridium perfringens, and Fusobacterium nucleatum significantly increased during the period (P < .0001). Among the 20 species analyzed, 18 showed no significant changes in susceptibility over time, including B. fragilis, C perfringens, and F. nucleatum. However, resistance to clindamycin increased in B. thetaiotaomicron (P = .0312), and resistance to ampicillin increased in B. ovatus (P = .0008). Our comprehensive national surveillance data analysis demonstrated a continuous increase in the incidence of anaerobic bacteremia, particularly in B. fragilis, C. perfringens, and F. nucleatum. This may be linked to the increasing number of colorectal cancer cases or advancing methods for species identification and susceptibility testing, requiring cautious interpretation. The discovery of an upsurge in anaerobic bacteremia and potential alterations in susceptibility highlights the necessity for more extensive studies in this field.

Current Prevalence of Antimicrobial Resistance in Okayama from a National Database between 2018 and 2021.

Antimicrobial resistance is an emerging global threat that must be addressed using a multidisciplinary approach. This study aimed to raise awareness of high-level antimicrobial-resistant (AMR) pathogens in Japan by comparing their recent prevalences among prefectures, particularly Okayama. Data for the isolation proportions of meropenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae, and levofloxacin-resistant E. coli and K. pneumoniae were collected from the Japan Nosocomial Infections Surveillance, a national database sponsored by the Japanese Ministry of Health, Labour, and Welfare, between 2018 and 2021. The average isolated proportions of the seven AMR pathogens were higher in Okayama compared to other prefectures: the worst (19.9%) was meropenem-resistant P. aeruginosa, the sixth worst (57.2%) was methicillin-resistant S. aureus, the eighth worst (3.3%) was vancomycin-resistant E. faecium, the second (37.8%) and fifth worst (17.6%) were cefotaxime-resistant E. coli and K. pneumoniae, respectively, and the fourth (49.9%) and third worst (8.7%) were levofloxacin-resistant E. coli and K. pneumoniae, respectively. Our study highlights the notably high prevalences of representative AMR pathogens in Okayama, suggesting the need for fundamental infection prevention and control by healthcare professionals, promoting antimicrobial stewardship, and educating undergraduates and postgraduates in Okayama.

Effect of participation in a surgical site infection surveillance programme on hospital performance in Japan: a retrospective study

The effect of hospital participation in the Japan Nosocomial Infection Surveillance (JANIS) programme on surgical site infection (SSI) prevention is unknown. To determine if participation in the JANIS programme improved hospital performance in SSI prevention. This retrospective before-after study analysed Japanese acute care hospitals that joined the SSI component of the JANIS programme in 2013 or 2014. The study participants comprised patients who had undergone surgeries targeted for SSI surveillance at JANIS hospitals between 2012 and 2017. Exposure was defined as the receipt of an annual feedback report 1 year after participation in the JANIS programme. The changes in standardized infection ratio (SIR) from 1 year before to 3 years after exposure were calculated for 12 operative procedures: appendectomy, liver resection, cardiac surgery, cholecystectomy, colon surgery, caesarean section, spinal fusion, open reduction of long bone fracture, distal gastrectomy, total gastrectomy, rectal surgery, and small bowel surgery. Logistic regression models were used to analyse the association of each post-exposure year with the occurrence of SSI. In total, 157,343 surgeries at 319 hospitals were analysed. SIR values declined after participation in the JANIS programme for procedures such as liver resection and cardiac surgery. Participation in the JANIS programme was significantly associated with reduced SIR for several procedures, especially after 3 years. The odds ratios in the third post-exposure year (reference: pre-exposure year) were 0.86 [95% confidence interval (CI) 0.79-0.84] for colon surgery, 0.72 (95% CI 0.56-0.92) for distal gastrectomy, and 0.77 (95% CI 0.59-0.99) for total gastrectomy. Participation in the JANIS programme was associated with improved SSI prevention performance in several procedures in Japanese hospitals after 3 years.

Baseline and seasonal trends of Bacillus cereus and Bacillus subtilis from clinical samples in Japan

Outbreaks of Bacillus cereus bloodstream infections (BSIs) are a concern in Japanese medical settings. This study determined baseline values for B.cereus detection in clinical samples that are useful as reference values for hospitals when assessing the need for intervention. A retrospective analysis of B.cereus detection in the Japan Nosocomial Infections Surveillance data from 2008 to 2014 was performed; it included 950 individual hospitals across the country. Bacillus spp. were detected in 0.54% of the clinical specimens submitted for bacteriological testing. Specimens positive for Bacillus spp. were mainly blood (24.6%), stool (26.5%), and respiratory specimens (23.3%). Identification of Bacillus spp. at the species level (i.e., B.cereus or B.subtilis) was reported in 55.3%, 14.7%, and 15.4% of cases, of which 88.9%, 48.3%, and 33.1% were B.cereus in blood, stool, and respiratory specimens, respectively. Of the 4105 hospital-years, 75.7% had blood specimens with Bacillus spp., with a median of 0.85 blood specimens/100 beds annually (interquartile range, 0.17-2.10). The B.cereus detection showed significant summer seasonality, regardless of specimen type or geographic distribution. The B.subtilis detection did not show seasonality, and its detection remained constant throughout the year. The seasonality of Bacillus spp. reflects the high proportion of B.cereus. The increased detection rate of Bacillus spp. during summer should be interpreted as a risk factor for B.cereus BSIs. A post-summer decrease in Bacillus spp. should not be interpreted as an effect of interventions.

Surgical site infections in thyroid and parathyroid surgery in Japan: An analysis of the Japan Nosocomial Infections Surveillance database from 2013 to 2020.

Surgical site infections (SSIs) after thyroid surgery are rare complications, with incidence rates of 0.3%-1.6%. Using a Japanese database, we conducted exploratory analyses on the incidence of SSIs, investigated the incidence of SSIs by the National Nosocomial Infections Surveillance risk index, and identified the causative bacteria of SSIs. SSIs occurred in 50 (0.7%) of 7388 thyroid surgery cases. Risk index-0 patients had the lowest incidence rate of SSIs (0.41%). The incidence of SSIs in risk index-1 patients was 3.05 times the incidence of SSIs in risk index-0 patients. The rate of SSI occurrence for risk index-2 patients was 4.22 times the rate of SSI occurrence for risk index-0 patients. Thirty-one bacterial species were identified as the cause of SSIs in thyroid surgery cases, of which 12 (38.7%) SSIs were caused by Staphylococcus aureus and Staphylococcus epidermidis. Of the nine SSIs caused by Staphylococcus aureus, 55.6% (five cases) were attributed to methicillin-resistant Staphylococcus aureus. Therefore, routine prophylactic antibiotic administration should be avoided, while the target for administration should be narrowed, according to the SSI risk. Administration of prophylactic antibiotics, such as 2 g piperacillin or 1 g cefazolin, is considered appropriate.

Distribution, trends, and antifungal susceptibility of Candida species causing candidemia in Japan, 2010-2019: A retrospective observational study based on national surveillance data.

The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are required. Here, we provide one of the largest longitudinal overviews of the trends in the prevalence of Candida species using national data of 57 001 candidemia isolates obtained from > 2000 hospitals for the 2010–2019 period in the Japan Nosocomial Infections Surveillance database. The proportion of Candida species, except Candida krusei and Candida guilliermondii, was almost the same during the study period. The proportion of C. guilliermondii surpassed that of C. krusei in 2014. The incidence of candidemia due to C. albicans (P < 0.0001), C. parapsilosis (P = 0.0002), and C. tropicalis (P < 0.0001) have decreased significantly over this period. Azole susceptibility of C. tropicalis was low, with 17.8% of isolates resistant to fluconazole and 13.5% resistant to voriconazole. The micafungin susceptibility of C. glabrata was low, with 8.0% of isolates showing resistance. The resistance rate of C. krusei toward amphotericin B fluctuated considerably (between 3.2% and 35.7%) over this period. The incidence rate of candidemia caused by C. parapsilosis and C. guilliermondii in hospitals responsible for bone marrow transplantation was significantly higher than that in other hospitals. Overall, our study suggests that in Japan, the species distribution of Candida was almost the same in this period and similar to that reported in North America and Europe. A relatively high resistance to azoles and micafungin was observed in C. glabrata, C. tropicalis, and C. krusei isolates, which require continued surveillance.

Surveillance of multi-drug resistance phenotypes in Staphylococcus aureus in Japan and correlation with whole-genome sequence findings

Antimicrobial resistance in Staphylococcus aureus imposes a high disease burden. Both phenotypic and genotypic monitoring are key to understanding and containing emerging resistant strains. Phenotypic monitoring of emerging resistance in S.aureus and correlation of priority strain phenotypes with whole-genome sequencing (WGS) findings. Antimicrobial susceptibility test results of >40,000 isolates from 213 participating hospitals from 2011 to 2019 were exported from the national Japan Nosocomial Infections Surveillance (JANIS) database. Longitudinal and geographic distribution and prevalence of distinct multi-drug resistance phenotypes ('resistance profiles') of S.aureus were examined among hospitals and prefectures. We further conducted a genome sequence analysis of strains with specific resistance profiles of concern. The overall prevalence of meticillin-resistant S.aureus (MRSA) decreased from 40.3% to 35.1% from 2011 to 2019. However, among dozens of S.aureus resistance profiles, only one profile of a type of MRSA, exhibited a statistically significant increase in inpatient frequency, exceeding 10% during the nine years. This MRSA profile showed resistance to oxacillin, erythromycin and levofloxacin. Analysis of WGS results of S.aureus isolates with this phenotype revealed that most belonged to clonal complex 8, and all carried SCCmec IV, typical of community-acquired MRSA. Tracking distinct resistance profiles deepened our understanding of the overall decrease in MRSA and led to recognition of the emergence of a new resistance phenotype. This study provides a model for future epidemiological research on antimicrobial resistance correlating multi-drug resistance phenotypes with selective genome sequencing, which can be applied to other bacterial species.

Increasing rates of laparoscopic gastrointestinal surgery and decreasing rates of surgical site infections: an observational study in Japan from 2012\u20132017

BackgroundSurgical site infections (SSI) are the most common healthcare-associated infection, and gastrointestinal surgery is frequently followed by a high incidence of SSI. Epidemiological analysis of the temporal trends in SSI following gastrointestinal surgery has yet to be performed in Japan. Our purpose was to descriptively investigate these trends.MethodsExtracting national surveillance data from the Japan Nosocomial Infections Surveillance (JANIS) system, we analyzed the frequency of SSI events following gastrointestinal surgery, which consisted of seven surgical procedures, from 2012–2017. We calculated the standardized infection ratio to compute risk-adjusted SSI frequency, and used the trend test to detect time-dependent changes.ResultsThe frequency of SSI events, except for those associated with surgery of the upper gastrointestinal tract, revealed a decreasing time-dependent trend. The use of laparoscopic surgery increased dramatically over time (p < 0.01 for the six applicable surgical sites), while the frequency of SSI events during laparoscopic surgery remained unchanged.ConclusionsThe increasing use of laparoscopic surgery was identified, and the observation coincided with the decreasing trend in SSI, especially in lower gastrointestinal tract surgery. If the relationship is causal, the overall SSI incidence among previously healthy individuals is expected to decrease, because the use of laparoscopic surgery has large growth potential in Japan.

A View on 20 Years of Antimicrobial Resistance in Japan by Two National Surveillance Systems: The National Epidemiological Surveillance of Infectious Diseases and Japan Nosocomial Infections Surveillance.

The Ministry of Health, Labour and Welfare (MHLW) of Japan has conducted two national surveillance systems for approximately 20 years to monitor antimicrobial resistance (AMR) in bacteria: the National Epidemiological Surveillance of Infectious Diseases (NESID) and the Japan Nosocomial Infections Surveillance (JANIS). Data accumulated for 20 years by these two surveillance systems have helped depict the epidemiology of the representative AMR bacteria in Japan chronologically. The epidemiology of methicillin-resistant Staphylococcus aureus teaches us that once AMR bacteria have established their high endemicity, controlling such AMR bacteria requires time and is challenging. On the other hand, the epidemiology that multidrug-resistant Acinetobacter sp. exhibits when a strict containment policy for AMR bacteria was introduced in the early phase of its emergence and spread reveals that it is possible to control it. Detailed epidemiology provided by these two different national surveillance systems in Japan enabled us to set up the goal for controlling each AMR bacteria at the hospital level to the prefecture/national level. It is the public health authorities’ responsibility to maintain a good surveillance system for AMR bacteria and share the data and findings with healthcare professionals and academicians.

Impact of the COVID-19 pandemic on the surveillance of antimicrobial resistance

BackgroundThe impact of the coronavirus disease (COVID-19) pandemic on antimicrobial resistance (AMR) is a major concern.AimTo compare the number of patients and isolation rate of antimicrobial-resistant bacteria before and after the beginning of the COVID-19 pandemic using the comprehensive national surveillance data.MethodsWe utilized comprehensive surveillance data, collected in the Japan Nosocomial Infections Surveillance programme, which included a total of 16.7 million samples of 5.9 million tested patients from >1300 hospitals. We compared the number of patients and isolation rate of five bacteria between 2019 and 2020, including antimicrobial-susceptible and -resistant bacteria of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.FindingsThe number of patients and isolation rate of S. aureus and meticillin-resistant S. aureus decreased slightly; those of S. pneumoniae and penicillin-resistant S. pneumoniae decreased by 60%; and those of third-generation cephalosporin-resistant K. pneumoniae increased. The isolation rate of the remaining bacteria apparently increased, although the number of patients decreased. This was due to a substantial decrease in the total number of tested patients (the denominator of the isolation rate), which was larger than that of the number of patients (the numerator of the isolation rate). Consistent results were obtained when the same data were re-aggregated using the procedure of the World Health Organization Global Antimicrobial Resistance Surveillance System, demonstrating the general importance of this problem.ConclusionSurveillance data during the COVID-19 pandemic must be carefully interpreted based on examination of the numerator, denominator and background factors that affect the denominator.

Length of stay, hospitalisation costs and in-hospital mortality of methicillin-susceptible and methicillin-resistant Staphylococcus aureus bacteremia in Japan

ObjectivesTo examine the length of stay, hospitalisation costs and case fatality of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA) bacteremia in Japan. Study designRetrospective cohort study. Patients with a diagnosis of S. aureus bacteremia who were admitted to a tertiary care hospital (the National Centre for Global Health and Medicine [NCGM]) in Tokyo, Japan, between 1st January 2016 and 31st December 2020 were included in the study. MethodsWe combined Japan Nosocomial Infections Surveillance data and Diagnosis Procedure Combination data at NCGM from 2016 to 2020. The data were stratified into MSSA and MRSA groups. Length of stay (LoS), LoS after submission of a blood culture specimen (LoS-after), hospitalisation cost, hospitalisation costs per day and clinical outcome were compared after propensity score matching. ResultsMedian LoS was 46 (interquartile range [IQR] 28.5–64.5) days in the MSSA group and 66 (IQR 40–91) days in the MRSA group (P = 0.020). Median LoS-after was 38 (IQR 25–62.5) days and 45 (IQR 24–63) days (P = 0.691) in the MSSA and MRSA groups, respectively. Median hospitalisation cost was significantly higher in the MRSA group (26,035 [IQR 18,154–47,362] USD) than in the MSSA group (19,823 [IQR 13,764–32,042] USD) (P = 0.036), but cost per day was not (MRSA: 528.9 [IQR 374.9–647.4] USD; MSSA: 455.6 [IQR 359.2–701.7] USD; P = 0.990). Case fatality rate was higher in the MRSA group than in the MSSA group (22/60 vs 9/60, P = 0.012). ConclusionsPatients with MRSA bacteremia had longer LoS and higher costs than those with MSSA bacteremia. However, LoS-after and hospitalisation costs per day were not different. The longer LoS of patients in Japan compared with other countries might contribute to the higher disease burden of S. aureus bacteremia in Japan.

Surgical Site Infection(SSI)in Neurosurgery

Although surgical site infections(SSIs)are usually controllable, their occasional occurrence is unavoidable. SSIs in neurosurgery comprise surgical-wound infections and surgical-organ/space infections. Data from the Japan Nosocomial Infections Surveillance revealed an overall infection rate of 1.1% during the first half of 2020. Responses to two questionnaire-based surveys on SSI prevention and complications related to cranial implant/artificial bone revealed the real world situation in neurosurgery. In 2020, neurosurgical information was added to the practical guidelines concerning the proper use of prophylactic antibacterial drug for SSIs. COVID-19 hygiene control protocols may have reduced the incidence of SSIs. It may be prudent to continue this stringent hygiene control after the COVID-19 pandemic has abated. Information of medical material on SSI is presented in this article, including the Plus suture®, DuraGen®, DuraSeal®, Adherus®, ultra-high-molecular-weight polyethylene(SKULPIO®, CRANIOFIT-PE®), Bioglide® and Bactiseal® shunt systems, and olanexidine. Minimizing SSIs requires proper knowledge on infection control, taking care while performing neurosurgical procedures, and compassion for the patients. In addition, information and material must be updated over time.

No Association Observed Between the Number of Infectious Disease Experts and Prevalence of Antimicrobial-Resistant Pathogens in Japan.

Introduction: The global spread of emerging infections has increased the demand for infectious disease (ID) experts. There is no established method to evaluate the sufficiency of professionals on a regional basis. We aimed to determine the correlation of the number of ID doctors and certified nurses in infection control (CNIC) with the prevalence of representative antimicrobial-resistant (AMR) pathogens across the 47 prefectures in Japan using publicly available databases.Methods: We determined the number of ID doctors and CNIC registered in each prefecture based on the Japanese Association for Infectious Diseases and the Japanese Nursing Association websites and calculated their numbers per 100,000 population. Data on representative AMR pathogens were extracted from the Japan Nosocomial Infections Surveillance database. Spearman’s correlation coefficient was used to measure statistical associations.Results: There was no epidemiologically applicable correlation between the deployment of ID doctors and CNIC and the isolation rates of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime- or levofloxacin-resistant Escherichia coli and Klebsiella pneumoinae, and meropenem-resistant Pseudomonas aeruginosa. Solely, the isolation rate of levofloxacin-resistant K. pneumoinae and the number of CNIC were statistically correlated (correlation coefficient = −0.33; p = 0.02), while the isolation rate of cefotaxime-resistant E. coli was paradoxically correlated with the number of ID doctors (correlation coefficient = 0.33; p = 0.02).Conclusions: Our macroscopic analysis using the open database was not a reliable method to evaluate the sufficiency of ID experts across the prefectures in Japan. A scheme to assess the appropriate distribution of ID experts should be developed.

Deployment of Infectious Disease Experts and Prevalence of Antimicrobial Resistance in Okayama: A Call for Training of Specialists.

ObjectiveDuring the ongoing global pandemic of novel coronavirus disease 2019 (COVID-19), an emerging infectious disease, the implementation and execution of infection prevention and control (IPC) is of paramount importance. In this study, we aimed to assess the current deployment of infection control medical personnel in Okayama prefecture, who are supposed to play an essential role to prevent the outbreak of infectious diseases, and the current prevalence of antimicrobial-resistant (AMR) bacteria isolated in Okayama.Materials and methodsThis was a descriptive study using publicly available data. The numbers of infectious disease (ID)-doctors and the certified nurses in infection control (CNIC) per 100,000 population in 47 prefectures in Japan were calculated. We then compared the detected proportions of AMR pathogens among the prefectures in 2019 to be employed as a comparative parameter, which was obtained from Japan Nosocomial Infections Surveillance (JANIS) data.ResultsThe number of ID-doctors was the 11th highest in Japan; however, they were unevenly distributed in southern Okayama, particularly at three tertiary hospitals. While the deployment of CNIC was geographically less uneven in the prefecture, their number was lower than the domestic average. According to the JANIS data, isolation rates of AMR pathogens were high in Okayama compared to other prefectures in Japan: vancomycin-resistant Enterococcus faecium (the third-worst); cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae (the third-worst and the second-worst, respectively); and meropenem-resistant Pseudomonas aeruginosa (the worst).ConclusionsOur assessment provides underlying data and reinforces the need for educating multi-professional experts in the field of infectious diseases to prevent future public health threats in Okayama.

An alternative index for evaluating AMU and anti-methicillin-resistant Staphylococcus aureus agent use: A study based on the National Database of Health Insurance Claims and Specific Health Checkups data of Japan

IntroductionAnti-methicillin-resistant Staphylococcus aureus (MRSA) agents have different doses and administration periods. Thus, it is difficult to evaluate antimicrobial use (AMU) of anti-MRSA agents using defined daily doses per 1000 inhabitants per day (DID) or days of therapy per 1000 inhabitants per day (DOTID). This study aimed to evaluate the relationship between anti-MRSA agent use and resistant bacteria using the number of patients per 1000 inhabitants per day (PID) as an alternative index of AMU. MethodsAMU data for anti-MRSA agents were collected from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) in 2016. The relationship between PID and DID or DOTID was evaluated. The number of patients with MRSA isolated was obtained from Japan Nosocomial Infections Surveillance, and their correlation with PID was analyzed. The rate of anti-MRSA agent use in each prefecture was investigated. ResultsPID showed a significant linear relationship with both DID and DOTID (all p < 0.0001). PID was significantly correlated with the number of patients with MRSA isolated. Additionally, the rate of anti-MRSA agent use was markedly different in each region. ConclusionsPID is not affected by doses and administration periods, and thus may be an alternative index for the selective pressure of antibiotics. Evaluating AMU using PID based on NDB data will help in the development of effective antimicrobial resistance measures.

593. Additional medical expenditures attributable to pneumococcal disease in Japan

BackgroundJapan requires a reexamination of its current vaccination policies to reduce the prevalence of pneumococcal disease (PD). Although the decision-making process for vaccination programs must be informed by cost-effectiveness analyses, the lack of cost data from Japan precludes such investigations. This study was therefore performed to quantify the medical expenditures attributable to PD in Japan.MethodsThe study was conducted using surveillance data from the Japan Nosocomial Infections Surveillance (JANIS) program’s Clinical Laboratory Division and insurance claims data under the Diagnosis Procedure Combination (DPC) system. Data from April 2015 to September 2017 were obtained from 145 hospitals throughout Japan. As the analysis focused on community-acquired infections, the medical expenditures incurred during the PD hospitalization episodes directly represented the additional expenditures attributable to these infections. The descriptive statistics of the medical expenditures (mean, standard deviation, median, and interquartile range) incurred by the PD cases were calculated from the linked JANIS data and DPC data. In addition, these descriptive statistics were also generated according to the presence/absence of IPD and age groups.ResultsThe study sample comprised 1,689 PD cases from 29 hospitals during the study period. Of these, 77 were IPD cases and 1,612 were non-IPD cases. The mean medical expenditures (standard deviation) for all PD cases, IPD cases, and non-IPD cases were estimated to be 1,016,801 yen (1,704,067 yen), 1,660,477 yen (2,078,667 yen), and 986,055 yen (1,678,705 yen), respectively. In addition, the medical expenditures associated with patients aged 60–64 years (1,646,739 yen) and 65 years or older (1,646,286 yen) were substantially higher than those of younger patients aged 5–59 years (1,424,105 yen).ConclusionThese estimates have applications in cost-effectiveness analyses of PD preventive measures, which can subsequently inform and guide national vaccination policies.Disclosures Haruhisa Fukuda, n/a, Pfizer Japan Inc. (Scientific Research Study Investigator)

233. Improved Penicillin Susceptibility of Streptococcus pneumoniae and Increased Penicillin Consumption in Japan, 2013–18

BackgroundPenicillin is often recommended as the first choice for Streptococcus pneumoniae infection due to its effectiveness and narrow spectrum. However, it is not clear whether increased penicillin consumption at the population level induces penicillin resistance in S. pneumoniae. The main objective of this study was to examine the association between penicillin susceptibility of S. pneumoniae and penicillin consumption in Japan.MethodsWe used Japan Nosocomial Infection Surveillance data, which comprehensively collected all routine microbiological test results from approximately 2,000 out of 8,000 hospitals across Japan that voluntarily participated in the surveillance. on susceptibility of S. pneumoniae, and sales data obtained from IQVIA Services Japan on national penicillin and cephalosporin consumption from January 2013 to December 2018. Clinical and Laboratory Standards Institute minimum inhibitory concentration breakpoints for meningitis were used as indicators of susceptibility. We analysed both sets of data by decomposing them into seasonality components and chronological trend components. The cross-correlation function was checked using Spearman’s rank correlation coefficient to examine for correlation between susceptibility and consumption.ResultsAfter adjusting for the influence of seasonality, the susceptibility of S. pneumoniae to penicillin gradually improved from 0.53 in January 2013 to 0.61 in December 2018 and penicillin consumption increased in the same period from 0.67 defined daily doses per 1,000 inhabitants per day (DID) in January 2013 to 1.23 DID in December 2018, thus showing positive cross-correlation (coefficient = 0.801, p < 0.001). Conversely, cephalosporin consumption decreased from 3.80 DID in January 2013 to 3.33 DID in December 2018, showing negative cross-correlation with penicillin susceptibility of S. pneumoniae (coefficient = -0.981, p < 0.001).Figure 1. Trend of penicillin-susceptibility of Streptococcus pneumoniae in Japan, 2013–2018 (based on non-meningitis MICs) Figure 2. Sales amount of penicillins in Japan, 2013–2018 Figure 3. Sales amount of cephalosporins in Japan, 2013–2018 ConclusionThe rate of penicillin-resistant S. pneumoniae isolate was not positively correlated with penicillin consumption at the population level. Increased penicillin consumption might not induce penicillin resistance of S. pneumoniae.Disclosures All Authors: No reported disclosures

Improved penicillin susceptibility of Streptococcus pneumoniae and increased penicillin consumption in Japan, 2013-18.

To examine the association between penicillin susceptibility of Streptococcus pneumoniae and penicillin consumption in Japan. We used Japan Nosocomial Infection Surveillance data on the susceptibility of S. pneumoniae and sales data obtained from IQVIA Services Japan K.K. for penicillin consumption. We analysed both sets of data by decomposing them into seasonality and chronological trend components. The cross-correlation function was checked using Spearman's rank correlation coefficient to examine the correlation between susceptibility and consumption. After adjusting for seasonality, the susceptibility of S. pneumoniae to penicillins gradually improved (55.7% in 2013 and 60.6% in 2018, respectively) and penicillin consumption increased during the same period (0.76 defined daily doses per 1,000 inhabitants per day [DID] in 2013, and 0.89 DID in 2018). The results showed positive cross-correlation (coefficient 0.801, p-value < 0.001). In contrast, cephalosporin consumption decreased (3.91 DID in 2013 and 3.19 DID in 2018) and showed negative cross-correlation with susceptibility of S. pneumoniae to penicillins (coefficient -0.981, p-value < 0.001). The rates of penicillin-susceptible S. pneumoniae isolates did not negatively correlate with penicillin consumption at the population level. Increased penicillin consumption might not impair the penicillin susceptibility of S. pneumoniae.

National trend of blood-stream infection attributable deaths caused by Staphylococcus aureus and Escherichia coli in Japan

There has been scarce evidence about deaths due to blood stream infection (BSI) in Japan so far. The main objective of this study is to understand the epidemiological trend of deaths caused by BSIs due to Staphylococcus aureus and Escherichia coli including Methicillin-resistant S. aureus (MRSA) and fluoroquinolone-resistant E. coli (FQREC) at national level. We annually estimated the number of BSI caused by S. aureus and E. coli between 2011 and 2017 across Japan using comprehensive data of bacterial culturing and drug susceptibilities collected in Japan Nosocomial Infection Surveillance (JANIS). The number of death was estimated by using BSI mortality obtained from previous studies in Japan. The number of BSI death attributable to S. aureus was estimated to 17,412 in 2011 and 17,157 in 2017, respectively, out of the whole population (126.8 million) in Japan. Among them, cases attributed to MRSA accounted for 5924 (34.0%) in 2011, and decreased to 4224 (24.6%) cases in 2017. On the other hand, the number of BSI death attributable to E. coli was estimated to 9044 in 2011 and increased to 14,016 in 2017. Among them, cases attributed to FQREC accounted for 2045 (22.6%) in 2011 and increased to 3915 (27.9%) cases in 2017. The number of BSI death attributable to MRSA has been decreasing and that attributable to FQREC has been increasing. This study provides the first annual estimate of disease burden of BSI caused by antimicrobial resistant (AMR) bacteria in Japan, and basis for formulating health policy to deal with AMR.