Efficacy of educational intervention on reducing the inappropriate use of oral third-generation cephalosporins.

PURPOSE: This study aimed to evaluate the efficacy of an educational intervention on reducing the inappropriate use of oral third-generation cephalosporins, the prevalence of resistant bacteria, and clinical outcomes. METHODS: A before-after study was conducted to compare the data for 1 year before and after intervention at a Japanese university hospital. Educational intervention included lectures for all medical staff on oral antibiotics and educational meetings with each medical department. The primary outcome was the use of oral third-generation cephalosporins in inpatients as measured by the monthly median days of therapy (DOTs) per 1000 patient days. Secondary outcomes included the use of each oral antibiotic in inpatients and outpatients, proportion of ß-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (BLNAR), penicillin-resistant Streptococcus pneumoniae (PRSP) and extended-spectrum ß-lactamase producing Escherichia coli (ESBLEC), the incidence of hospital-acquired Clostridioides difficile infection (HA-CDI), and hospital mortality. RESULTS: The use of oral third-generation cephalosporins in inpatients was significantly decreased after intervention [DOTs (interquartile range): 24.2 (23.5-25.1) vs. 3.7 (0.0-7.1), P < 0.001], and the value in outpatients was also decreased significantly. The use of fluoroquinolones and macrolides did not increase after intervention. The proportion of BLNAR, PRSP and ESBLEC did not change significantly during the study period. The incidence of HA-CDI was significantly decreased, and hospital mortality did not change after intervention. CONCLUSION: Educational intervention was effective in reducing the use of oral third-generation cephalosporins without increasing the use of broad-spectrum antibiotics and worsening clinical outcome. The prevalence of resistant bacteria did not change during the study period.

Long-term efficacy of comprehensive multidisciplinary antibiotic stewardship programs centered on weekly prospective audit and feedback.

OBJECTIVE: To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes. DESIGN: Before-after study. SETTING: National university hospital with 934 beds. INTERVENTION: Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration. METHODS: The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia. RESULTS: The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend). CONCLUSION: The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.

Mycotic aneurysm caused by Edwardsiella tarda successfully treated with stenting and suppressive antibiotic therapy: a case report and systematic review.

BACKGROUND: Mycotic aneurysm is an uncommon disease which could be fatal without appropriate treatment. Although standard therapy for mycotic aneurysms consists of resection of the infected aorta and in situ graft replacement, some treat with endovascular stent-grafting because patients may not tolerate graft replacement due to underlying diseases. There are 6 more reported cases of mycotic aneurysm caused by Edwardsiella tarda. With the exception of our case, all underwent resection and debridement of the infected aorta or vascular prosthesis. Herein we report the first case ever of mycotic aneurysm caused by E. tarda, successfully treated with stenting and suppressive antibiotic therapy without resection of the infected aorta. CASE PRESENTATION: A 65-year-old Japanese woman with cirrhosis and hepatocellular carcinoma complained of fatigue. Her work up revealed a ruptured aneurysm of the descending aorta. She went through endovascular stent-graft placement. Edwardsiella tarda grew from blood cultures, which led to the diagnosis of mycotic aneurysm. Edwardsiella tarda is a Gram negative bacillus which rarely causes infections in humans. In the case of bacteremia, its mortality is reported to be very high and all reported cases with mycotic aneurysm caused by E. tarda ended up with resection of the infected aorta. CONCLUSION: Our case shows that in the case of mycotic aneurysm caused by E. tarda, endovascular stent-graft placement could be an alternative to in situ graft replacement.

Evaluation of the drug-drug interactions management system for appropriate use of nirmatrelvir/ritonavir: a retrospective observational study.

PURPOSE: While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r. METHODS: A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality. RESULTS: This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1-3.1]. CONCLUSIONS: Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.

Sustained Improvements in Antimicrobial Therapy and Clinical Outcomes following a Pharmacist-Led Antimicrobial Stewardship Intervention: Uncontrolled Before-After Study.

Our antimicrobial pharmacist-led intervention included: (a) a structured review of antibiotic prescriptions; (b) educating prescribers on antimicrobial therapy; (c) monthly reporting of department-level rates of blood sampling for culture. Daily review began in May 2018 and was discontinued after 10 months; however, the other interventions were conducted throughout the study period. This study aimed to evaluate the sustained impact of pharmacist's interventions on antimicrobial therapy and clinical outcomes between the baseline (May-December 2017), intervention (May-December 2018), and post-intervention (May-December 2019) periods. The rate of blood culture collections before starting antipseudomonal agent therapy was significantly increased from the baseline to post-intervention periods (71% vs. 85%, p < 0.001). Antipseudomonal agent therapy was more frequently de-escalated in the post-intervention period than in the baseline period (73% vs. 54%, p = 0.038). Total use of antipseudomonal agents was reduced from the baseline to intervention periods and persisted during the post-intervention period (50.5 vs. 41.8 and 42.6 DDD per 1000 patient-days, p = 0.016 and p = 0.022, respectively). During the study period, there were significant reductions in the incidence of hospital-acquired Clostridioides difficile infection (1.12, 0.54, and 0.51 per 10,000 patient-days, respectively, p = 0.031) and 30-day mortality with bacteremia (19%, 18%, and 12%, respectively, p = 0.005). Our pharmacist-led interventions sustainably achieved appropriate antimicrobial therapy and improved clinical outcomes.

Impact of Infectious Disease Consultation on Management and Outcomes of Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) is associated with significant morbidity and mortality, and successful management requires expertise in both cardiac surgery and infectious disease (ID). However, the impact of ID consultation on the clinical outcomes of IE is not clear. METHODS: The present study was a quasi-experimental, interrupted time series analysis of the clinical outcomes of patients with IE before (April 1998-April 2008) and after (May 2008-March 2019) the establishment of an ID department at a tertiary care hospital in Japan. The primary outcome was clinical failure within 90 days, defined as a composite of all-cause mortality, unplanned cardiac operation, new-onset embolic events, and relapse of bacteremia caused by the original pathogen. RESULTS: Of 238 IE patients, 59 (25%) were treated in the preintervention period, and 179 (75%) were treated in the postintervention period. Establishment of an ID department was associated with a 54% reduction in clinical failure (relative risk, 0.46; 95% confidence interval, 0.21-1.02; P = .054) and a 79% reduction in new-onset embolic events (relative risk, 0.21; 95% confidence interval, 0.07-0.71; P = .01). In addition, the rate of inappropriate IE management significantly decreased (relative risk, 0.06; 95% confidence interval, 0.02-0.22; P < .01). CONCLUSIONS: Establishment of an ID department at a tertiary care hospital was associated with improved management, better clinical outcomes, and reduced embolic events in patients with IE admitted to the hospital.

Serum Cytokine Profiles of Rapid Recovery Patients with COVID-19: Series of 6 Cases.

COVID-19 patients reveal various clinical manifestations; however, the specific mechanisms and factors contributing to rapid recovery remain unclear. We performed serum cytokine profiling using a bead-based immunoassay in six COVID-19 patients with mild symptoms who experienced rapid recovery. All patients had fever that resolved within 4 days. During the study, the interferon gamma-related protein 10 (IP-10) level rapidly increased initially, and then rapidly decreased in all six patients. Similarly, the interferon (IFN)-λ 2/3 levels rapidly increased initially, and then decreased in five of the six patients. IP-10 and IFN-λ2/3 may play a key role in the rapid recovery of mild COVID-19.

Massive surge of mRNA expression of clonal B-cell receptor in patients with COVID-19.

BACKGROUND: Antibody production is one of the primary mechanisms for recovery from coronavirus disease 2019 (COVID-19). It is speculated that massive clonal expansion of B cells, which can produce clinically meaningful neutralizing antibodies, occurs in patients who recover on the timing of acquiring adaptive immunity. METHODS: To evaluate fluctuations in clonal B cells and the size of the clones, we chronologically assessed the B-cell receptor (BCR) repertoire in three patients with COVID-19 who recovered around 10 days after symptom onset. RESULTS: We focused on the three dominant clonotypes (top 3) in each individual. The percentage frequencies of the top 3 clonotypes increased rapidly and accounted for 27.8 % on day 9 in patient 1, 10.4 % on day 12 in patient 2, and 10.8 % on day 11 in patient 3, respectively. The frequencies of these top 3 clonotypes rapidly decreased as the patients' clinical symptoms improved. Furthermore, BCR network analysis revealed that accumulation of clusters composed of similar complementarity-determining region 3 (CDR3) sequences were rapidly formed, grew, and reached their maximum size around 10 days after symptom onset. CONCLUSIONS: BCR repertoire analysis revealed that a massive surge of some unique BCRs occurs during the acquisition of adaptive immunity and recovery. The peaks were more prominent than expected. These results provide insight into the important role of BCRs in the recovery from COVID-19 and raise the possibility of developing neutralizing antibodies as COVID-19 immunotherapy.

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

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

Late diagnosis: a case of rapidly progressive extranodal NK/T cell lymphoma, nasal type.

Extranodal natural killer (NK)/T cell lymphoma, nasal type is a condition that has poor prognosis. Accurate diagnosis of lymphoma is made by pathological findings. We report a case of extranodal NK/T cell lymphoma, nasal type affecting the lung and liver and which was difficult to diagnose because of negative biopsy results from multiple sites. A 39-year-old man who had dry cough and fever for 1 month was referred to our hospital. He had pancytopenia and elevated serum levels of lactate dehydrogenase and soluble interleukin-2 receptor. Hepatosplenomegaly and multiple lung nodules were found on imaging study. Specimens of bronchoscopic lung, percutaneous liver, bone marrow and random skin biopsies were all negative. Open lung biopsy was not definitive. Unfortunately, disease progression was rapid and fatal before results of pleural fluid cytology and a second liver biopsy showed extranodal NK/T cell lymphoma, nasal type. This report focused on diagnostic planning for rapidly progressive extranodal NK/T-cell lymphoma, nasal type.

Cluster of diffuse alveolar hemorrhage cases after the 2011 Tohoku Region Pacific Coast Earthquake.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a clinical syndrome that presents with progressively hemorrhagic bronchoalveolar lavage fluid (BALF) in serial samples and generally has a poor prognosis. The South Miyagi Medical Center, located on the inland side of southern Miyagi Prefecture, documented an increase in the number of patients with DAH after the 2011 Tohoku Region Pacific Coast Earthquake. METHODS: We describe the clinical features of post-earthquake DAH in comparison to pre-earthquake DAH. We analyzed the data of the DAH patients we have been able to follow for at least 6 months since we started performing bronchoscopy and bronchoalveolar lavage (BAL) for all patients with interstitial lung disease in August 2009 until September 2011, and separated these patients into pre- and post-earthquake groups according to the earthquake date of March 11, 2011. RESULTS: Post-earthquake DAH patients tended to test positive for infectious agents and showed higher serum IgE titers, with BALF that exhibited a tendency to higher silica concentrations. Post-earthquake DAH generally had a better prognosis than pre-earthquake DAH. CONCLUSIONS: In describing the clinical features of post-earthquake cases of DAH, this report documents the possibility of an infection- and/or dust-induced, partially allergic, and relatively benign form of DAH.

Combined Legionella and Escherichia coli lung infection after a tsunami disaster.

Pulmonary infection after a tsunami is often polymicrobial and tends to form chronic pyogenic lung disease, necrotizing pneumonia, and empyemas. We report a combined pulmonary infection of Legionella and multiple antibiotic-resistant Escherichia coli in a previously well 75-year-old woman following immersion in tsunami waters 1 km inland from the Pacific coastline following the Tohoku Region Pacific Coast Earthquake of 2011. She needed drainage several times and the long-term use of multiple antibiotics according to the type of bacteria found and antibiotic susceptibility. We should be mindful of infections caused by multiple pathogens in the environment in Japan as a consequence of a tsunami disaster.