Effect of interventions by an antimicrobial stewardship team on clinical course and economic outcome in patients with bloodstream infection.

BACKGROUND: Bloodstream infections (BSIs) represent one of the most severe and clinically important conditions in the hospital setting. We have organized an interdisciplinary antimicrobial stewardship team (AST) at our hospital and performed consultations focusing on BSI patients since 2013. This study aimed to evaluate the impact of AST interventions on the diagnosis, treatment, and clinical outcomes of BSI patients. METHODS: We conducted a retrospective quasi-experimental study of BSI patients at a single Japanese university hospital. AST provided recommendations to attending physicians regarding appropriate diagnosis, therapy, and management of BSI patients after reviewing medical charts. RESULTS: We identified a total of 308 cases of BSI from January to December, 2012 (pre-intervention group) and 324 cases of BSI from April, 2013 to March, 2014 (post-intervention group). No significant differences in the in-hospital mortality or 30-day mortality rates were observed between both the groups. Inappropriate therapy was initiated in a significantly lower proportion of patients in the post-intervention group (18.5% vs. 11.4%; P = 0.012). Multivariate analysis confirmed that inappropriate therapy was significantly associated with in-hospital mortality (odds ratio, 2.62; 95% confidence interval, 1.42-4.82; P = 0.002). CONCLUSIONS: An interdisciplinary AST intervention approach decreases the use of inappropriate therapy and may improve clinical outcomes in BSI patients.

Evaluation of the initial timing of infection control pharmacist-driven audit and monitoring of vancomycin therapy in patients with infectious diseases: A retrospective observational study.

BACKGROUND: Early monitoring and feedback on the treatment of infectious diseases are some of the methods for optimising antimicrobial treatment throughout the treatment period. Prospective audits and feedback interventions have also been shown to improve antimicrobial use and reduce antimicrobial resistance. We examined the appropriate use of antimicrobials by focusing on the initial timing for audits and feedback intervention of antimicrobial prescription by Infection Control Team pharmacists. METHODS: We conducted a retrospective observational study in a university hospital in Tokyo, Japan from 1 January 2019 to 31 May 2021. We retrospectively enrolled patients with infections and those patients suspected of having an infection, who were administered vancomycin and assessed at our hospital. The definition of primary outcome was the maintenance of target vancomycin trough blood concentrations of 10-20 µg/ml during treatment. Multivariable logistic regression and multivariate linear regression analyses were performed to test the effectiveness of the initial timing of the intervention by Infection Control Team pharmacists as the explanatory variable. RESULTS: A total of 638 patients were included in this study, with a median age of 69 years (interquartile range: 54-78 years). Multivariable logistic regression revealed that the maintenance of target vancomycin trough concentrations was not associated with the timing of the audit and the initiation of monitoring by Infection Control Team pharmacists (adjusted odds ratio: 0.99, 95% confidence interval: 0.99-1.00, p = 0.990). Multivariate linear regression revealed that the duration of vancomycin administration was significantly correlated with the timing of initiation of monitoring by Infection Control Team pharmacists (adjusted estimate: 0.0227, standard error: 0.0051, p = 0.012). CONCLUSIONS: Our study showed that early initiation of a comprehensive audit and monitoring by Infection Control Team pharmacists did not affect the maintenance of the target vancomycin trough blood concentration. However, it reduced the duration of vancomycin administration.

MAOA, MTHFR, and TNF-ß genes polymorphisms and personality traits in the pathogenesis of migraine.

Migraine is a multifactorial disease with various factors, such as genetic polymorphisms and personality traits, but the contribution of those factors is not clear. To clarify the pathogenesis of migraine, the contributions of genetic polymorphisms and personality traits were simultaneously investigated using multivariate analysis. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms analysis and NEO-FFI personality test were performed. At first, the univariate analysis was performed to extract the contributing factors to pathogenesis of migraine. We then extracted the factors that independently contributed to the pathogenesis of migraine using multivariate stepwise logistic regression analysis. Using the multivariate analysis, three gene polymorphisms including monoamine oxidase A (MAOA) T941G, methylenetetrahydrofolate reductase (MTHFR) C677T, and tumor necrosis factor beta (TNF-ß) G252Α, and the neuroticism and conscientiousness scores in NEO-FFI were selected as significant factors that independently contributed to the pathogenesis of migraine. Their odds ratios were 1.099 (per point of neuroticism score), 1.080 (per point of conscientiousness score), 2.272 (T and T/T or T/G vs G and G/G genotype of MAOA), 1.939 (C/T or T/T vs C/C genotype of MTHFR), and 2.748 (G/A or A/A vs G/G genotype of TNF-ß), respectively. We suggested that multiple factors, such as gene polymorphisms and personality traits, contribute to the pathogenesis of migraine. The contribution of polymorphisms, such as MAOA T941G, MTHFR C677T, and TNF-ß G252A, were more important than personality traits in the pathogenesis of migraine, a multifactorial disorder.

[Impact of the Antimicrobial Stewardship Team Intervention Focusing on Changes in Prescribing Trends and the Rate of Carbapenem-resistant P. aeruginosa].

Antimicrobial stewardship (AS) intervention strategy is a critical process in promoting appropriate antibiotic use, thus preventing unnecessarily prolonged therapy and reducing antimicrobial resistance (AMR). Although limiting unnecessary carbapenem use by AS intervention is speculated to reduce AMR, there is a lack of specific data on the efficacy of AS team (AST) intervention regarding carbapenem-resistant Pseudomonas aeruginosa (CRPA). Consequently, this study aimed to evaluate the impact of our AS strategy on carbapenem use and CRPA. The AS intervention strategy was launched in July 2017 and consisted of daily audits and feedback on carbapenem use. We evaluated the 4-year prescription trend, including the rate of switching to other antimicrobials, and the rate of CRPA and the days of therapy required prior to and after the beginning of the AST intervention. The rate of switching to narrow-spectrum antibiotics and the discontinuation of carbapenem treatment were significantly higher in the pre-intervention period compared with the post-intervention period. (7.0% vs. 14.5%; p<0.001; 54.1% vs. 50.9%; p=0.027). However, there were no significant differences in the rate of CRPA prior to and after the beginning of the AST intervention. Furthermore, there was no correlation found between consumption and resistance rate (Pearson's r=0.123). Our results suggest that it is extremely important for AST to promote de-escalation and reduce unnecessary use, while the combination of process and outcome indicators other than antimicrobial consumption and resistance rate are required for the evaluation of the AS programs.

Days of Antibiotic Spectrum Coverage Trends and Assessment in Patients with Bloodstream Infections: A Japanese University Hospital Pilot Study.

The antibiotic spectrum is not reflected in conventional antimicrobial metrics. Days of antibiotic spectrum coverage (DASC) is a novel quantitative metric for antimicrobial consumption developed with consideration of the antibiotic spectrum. However, there were no data regarding disease and pathogen-specific DASC. Thus, this study aimed to evaluate the DASC trend in patients with bloodstream infections (BSIs). DASC and days of therapy (DOT) of in-patients with positive blood culture results during a 2-year interval were evaluated. Data were aggregated to calculate the DASC, DOT, and DASC/DOT per patient stratified by pathogens. During the 2-year study period, 1443 positive blood culture cases were identified, including 265 suspected cases of contamination. The overall DASC, DASC/patient, DOT, DOT/patient, and DASC/DOT metrics were 226,626; 157.1; 28,778; 19.9; and 7.9, respectively. A strong correlation was observed between DASC and DOT, as well as DASC/patient and DOT/patient. Conversely, DASC/DOT had no correlation with other metrics. The combination of DASC and DOT would be a useful benchmark for the overuse and misuse evaluation of antimicrobial therapy in BSIs. Notably, DASC/DOT would be a robust metric to evaluate the antibiotic spectrum that was selected for patients with BSIs.

Association of the A-1438G polymorphism in serotonin 2A receptor in migraine with aura among Japanese patients.

We investigated the possible association of serotonin (5-HT) 2A receptor gene A-1438G polymorphism in Japanese patients with migraine. Genotyping of 5-HT(2A) A-1438G polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism in patients with migraine (male 17 : 3 with aura and 14 without aura, female 65 : 17 with aura and 48 without aura) and controls (male 31, female 84). The distribution of 5-HT(2A) A-1438G genotype frequency between migraine patients and controls did not differ. These results suggest that the A-1438G polymorphism of the 5-HT(2A) receptor gene is not a direct risk factor for migraine; however, the incidence of the A/A genotype between migraine with aura (MA) and without aura (MO) was significantly different. The 5-HT(2A) A-1438G polymorphism may be involved in determining the subtypes of migraine in Japanese.

[Role of pharmacists in a community pharmacy for self-medication of patients with headache].

Pharmacists in a community pharmacy may recommend an over-the-counter (OTC) drug to patients with headache. However, it is not clear how pharmacists should distinguish the symptoms of patients and facilitate appropriate self-medication. Here, we investigated the role of pharmacists in a community pharmacy in recommending OTC drugs for self-medication by patients with headache and elucidated their future needs using a questionnaire intended for doctors and pharmacists. More than half of the pharmacists surveyed did not have any experience with recommending OTC drugs for patients with headache. To distinguish between patients for whom pharmacists should "recommend OTC drugs" and patients who should be encouraged "to consult a hospital or clinic," doctors thought that pharmacists should use an "assistance tool to diagnosis headache, such as a screener for migraine" and "guidelines for chronic headache." However, few pharmacists used these tools. About 68% of doctors indicated that it would be "meaningful" for pharmacists to distinguish patients with headache. Moreover, both doctors and pharmacists thought that pharmacists should provide patients not only with "instruction on the use of drugs" but also suggest "when to consult a hospital or clinic." However, 32% of doctors indicated that it is "meaningless" for pharmacists to attempt to distinguish patients with headache and expressed concern about the increase of patients who overuse headache medication. These findings provide useful information to guide pharmacists in community pharmacy when recommending OTC drugs for self-medication by patients with headache.

[Need for collaboration between community pharmacies and hospitals or clinics in providing medical treatment for patients with headache].

It is often noted that the collaboration of hospital-to-hospital, hospital-to-clinic and clinic-to-clinic in medical care for patients with headache is important. However, the role of community pharmacies in the medical network for consultation of patients with headache is not clear. Here, we investigated the role of pharmacists in a community pharmacy in encouraging patients with headache to undergo medical examination and elucidated their future needs using a questionnaire intended for doctors and pharmacists. About 70% of pharmacists had experience with recommending that patients with headache consult a hospital. However, only 17% of doctors had experience with referral of patients with headache by pharmacists in a community pharmacy. About 22% of pharmacists had experiences in which the patient with headache refused to consult a hospital despite the recommendation, suggesting that many patients did not think that their headache symptoms were severe. In addition, 90% of doctors and 84% of pharmacists felt the need for collaboration between hospitals or clinics and community pharmacies. Doctors needed information from pharmacists on the "current state of drugs" taken by patients. However, pharmacists considered that they needed to provide not only "current state of drugs being taken" but also "symptoms of headache" to doctors. Although 67% of doctors considered the medication notebook to be useful for pharmacists to provide patient information to doctors, pharmacists preferred to provide the information by telephone. Moreover, 56% of pharmacists did not know how to search a website for medical specialists in headache. A medical network including not only hospitals or clinics but also community pharmacies might be useful for patients with headache.

Epidemiology and risk factors for mortality in bloodstream infections: A single-center retrospective study in Japan.

BACKGROUND: Few published data are available on the morbidity and mortality of bloodstream infections (BSIs) in Japan. We sought to investigate the epidemiology of BSIs, the involvement of antimicrobial resistance, and the factors that influence patient prognosis. METHODS: This single-center study retrospectively evaluated patients who were found to have positive blood cultures at a tertiary teaching hospital between January 2012 and December 2016. RESULTS: A total of 2,105 patients with BSIs were included; 1,786 survived and 319 died, and the 30-day mortality rate was 15.2% over the 5-year study period. BSIs caused by yeasts were independently associated with 30-day mortality. The 30-day mortality rate of BSIs caused by extended-spectrum beta lactamase-producing gram-negative bacteria was significantly higher than that of BSIs caused by nonproducing bacteria. DISCUSSION: The differences in mortality may be caused by differences in the distribution of pathogens and in the delivery of health care. CONCLUSIONS: This study reported epidemiology and antimicrobial resistance data of BSIs in Japan and identified several risk factors associated with 30-day mortality. National surveillance of BSIs is required in Japan for comparison with other countries.