Vancomycin-Induced Neutropenia With Subsequent Perioperative Readministration: A Case Report.

Vancomycin (VCM), an essential antibiotic for antimicrobial-resistant Gram-positive cocci, can lead to complications such as neutropenia. Here, we present a case of a 25-year-old male with noncommunicating hydrocephalus due to an intraventricular tumor who developed neutropenia during VCM therapy. Despite the suspected VCM-induced neutropenia, short-term readministration was deemed necessary for perioperative infection prophylaxis. This patient was readministered without neutropenia. A review of the literature revealed an earlier onset of VCM-induced neutropenia than that previously reported, emphasizing the importance of vigilant monitoring. Although readministration of VCM in patients with neutropenia is uncommon, it may be feasible with careful risk assessment, particularly in cases of mild neutropenia and short-term therapy. However, the mechanisms underlying VCM-induced neutropenia remain unclear, necessitating further research on the optimal management strategies.

Evaluation of long-term pharmacist-led prospective audit and feedback in antimicrobial stewardship: An 8-year study.

BACKGROUND: Limited research has evaluated the long-term outcomes of prospective audit and feedback (PAF) led by pharmacists. We assessed pharmacist-led PAF processes and outcome measures over 8 years. METHODS: This study was conducted at a single public hospital in Japan. Between 2014 and 2021, pharmacists conducted weekday PAFs for hospitalized patients and annually evaluated the process and outcome measures. The endpoints included detection of drug-resistant bacteria, drug susceptibility rates, duration of antimicrobial therapy, and proportion of long-term administration. RESULTS: Among inpatients, methicillin-resistant Staphylococcus aureus significantly decreased from 50.9% in 2014 to 32.8% in 2021 (P < .001). The susceptibility rate of Pseudomonas aeruginosa to meropenem significantly increased from 91.2% in 2014 to 94.4% in 2021 (P < .001) and levofloxacin increased from 84.9% in 2014 to 89.3% in 2021 (P < .001). Antimicrobial therapy duration did not differ significantly between 2014 and 2016, but decreased significantly from 2017 onwards (P < .001), except in 2018. The number of patients receiving intravenous antimicrobials for >10 days decreased significantly between 2014 and 2021 (P < .001). CONCLUSIONS: Long-term continuous PAF interventions by pharmacists contribute to improving and maintaining process and outcome indicators and prevent the spread of drug-resistant bacteria.

Analysis of pharmacological interventions among hospitalised patients with COVID­19: A focus on severe cases.

Existing recommendations regarding pharmaceutical interventions for patients with coronavirus disease 2019 (COVID-19) focus on outpatient, inpatient and post-discharge care. However, there are no studies examining the actual activities of pharmacists in relation to hospitalised patients. The present study aimed to identify pharmacists' roles by analysing cases of pharmaceutical interventions, particularly for patients admitted to high-care units. Pharmacological interventions were provided to patients with severe COVID-19 or patients at high risk of severe disease in 2021. These pharmaceutical interventions were analysed and evaluated. Pharmacists also developed a COVID-19 drug compatibility chart for use by care team members. In the present study, 54 patients were included, of which 33 were severe cases. A total of 28 patients (52%) received pharmacological interventions and 25 of them were severe cases. Out of 68 pharmacological interventions, interventions for antimicrobial agents were the most common (28 interventions), followed by nutrition and anti-COVID-19 drug-related interventions. In addition, the need for interventions relating to drug compatibility was reduced by ~43% after the drug compatibility chart was implemented. In conclusion, pharmacists have a responsibility to improve the quality of pharmacotherapy for patients with COVID-19. They should focus on creating specific pharmacotherapy tools for patients with COVID-19 and supporting appropriate antimicrobial use for secondary bacterial infections.

Impact of continuous pharmacist intervention for injectable antimicrobials on the treatment of patients with Escherichia coli bacteremia.

BACKGROUND: A prospective audit with intervention and feedback (PAF) by pharmacists is important for the appropriate use of antimicrobials. Clinically, Escherichia coli (E. coli) bacteremia is a common condition, but only few researchers have examined the role of PAF in its appropriate use of antimicrobials. METHODS: We started PAF by pharmacists in 2017 for all injectable antibiotics. This study included cases of E. coli bacteremia that resulted in hospitalization over a 4 year period from 2016 to 2019. Patients were grouped by year (Period 0-3), and clinical outcomes were examined. RESULTS: The pharmacists had 12 and 54 suggestions in Periods 0 and 3, respectively. The most common suggestion was de-escalation. The median duration of antimicrobial use was 12 (interquartile range: 8-15) days in Periods 0-2. The duration of antimicrobial use was significantly reduced to 9 (7-12) days in Period 3. In Period 3, the duration of antimicrobial use was reduced by 29%, while anti-pseudomonal drug use was reduced by 42% compared with that in period 0. The 30 day mortality rates were not significantly different between the groups. CONCLUSIONS: PAF by pharmacists promotes the appropriate use of antimicrobials in patients with E. coli bacteremia; it is important to continue the program for several years.

[Retrospective Observational Study on Predictors of Body Weight and BNP Teduction in Cases of Tolvaptan Induction for Heart Failure].

Tolvaptan (TLV) carries the risk of serious side effects, and its introduction requires hospitalization. Therefore, it is important from the viewpoints of safety and medical economics to predict in advance, the patients for whom it will be effective and introduce it. The purpose of this study was to investigate the noninvasive and simple predictors for identifying TLV responders. We conducted a retrospective observational study of patients with heart failure who had TLV introduced at our hospital from January 1, 2017, to December 31, 2018. By using the body weight and BNP reduction as the effect indices, predictors of body weight and BNP reduction were extracted by logistic analysis. The sensitivity and specificity at the cutoff value obtained by ROC analysis were also examined. Among 85 subjects, urine sodium concentration >63 mEq/L [odds ratio (OR): 6.11, 95% confidence interval (CI): 1.36-27.4] was detected as a predictor of body weight reduction. The sensitivity at this cutoff value was 81%, and the specificity was 70%. Serum osmolarity>291 mOsm/L (OR: 3.76, 95% CI: 1.00-14.2), urine potassium concentration<21 mEq/L (OR: 4.45, 95% CI: 1.09-18.2), and urine sodium concentration>71 mEq/L (OR: 7.38, 95% CI: 2.05-26.6) were detected as predictors of BNP reduction. The sensitivities were 62%, 53%, and 73%, and the specificities were 58%, 68%, and 68%, respectively. Therefore, it was suggested that urine sodium concentration may be useful as a predictor of body weight and BNP decrease after TLV induction.

Evaluation and Comparison of Daiokanzoto and Lubiprostone for Constipation: A Retrospective Cohort Study.

Daiokanzoto (DKT) and lubiprostone (LPS) are drugs used for constipation, but few studies have compared them. This study examined the effectiveness, adverse events, and medical economic efficiency of DKT and LPS for constipation. Patients who received DKT (DKT group) and those who received LPS (LPS group) during admission to Ogaki Municipal Hospital between November 2012 and May 2016 were enrolled. Drug efficacy was evaluated based on the median value of bowel movement frequency over 1 week before and after drug administration, and their safety was evaluated by the presence or absence of diarrhea, abdominal pain, nausea, and vomiting. To assess medical economic efficiency, drug costs for constipation per week were calculated. The median values (quartile ranges) of bowel movement frequency at 1 week after drug administration were 8.5 (6.0-12.0) in the DKT group and 5 (3.0-7.0) in the LPS group, which was significantly different (p < 0.01). Diarrhea occurred significantly less often in the DKT group (4 cases) than in the LPS group (17 cases) (p < 0.01). The median cost of drugs administered for constipation for 1 week was significantly lower in the DKT group (631 [quartile range, 513-653] yen) than in the LPS group (1431 [1135-2344] yen) (p < 0.01). DKT had a higher immediate effect on constipation and was associated with more frequent bowel movement and fewer adverse events of diarrhea than LPS, suggesting that it may be effective and safe for treating constipation, and DKT is inexpensive.

Single-centre retrospective observational study comparing trough blood concentration and safety of teicoplanin formulations.

Teicoplanin formulations are marketed as antibiotic mixtures with several compounds that share the same core structure. Recent studies conducted in vitro have reported differences in the composition ratio of different teicoplanin products. In this retrospective study, we examined the trough blood concentration of the originator brand and a generic teicoplanin product. Target patients were retrospectively assigned to the originator (Targocid) or generic group. The groups were matched 1:1 using propensity scores. The initial trough blood concentration analysis identified 44 matches. In both groups, the median dosing day for the first measurements was 4, respectively. The initial trough blood concentration of the originator group was significantly higher (mean ± SD, 16.3 ± 4.5 mg/L) than that of the generic group (12.8 ± 4.7 mg/L; 95% CI, -5.4 to -1.6). A significant difference was observed in the frequency of serum creatinine elevation in the study of the frequency of adverse events using Common Terminology Criteria for Adverse Events (originator group, 41.9% vs generic group, 20.9%). In cases where discontinuation was necessary due to side effects, there were three patients in the originator group and one patient in the generic group. This study found that trough blood concentration differed between formulations. Therefore, correction might be necessary while monitoring drug concentration in the blood. Trough blood concentrations are used as surrogate markers for efficacy and safety, so further studies on differences in efficacy and safety between formulations are required.

Clinical outcome of pharmacist-led prospective audit with intervention and feedback after expansion from patients using specific antibiotics to those using whole injectable antibiotics.

Prospective audit with intervention and feedback (PAF) and preauthorisation of antimicrobials are core strategies for antimicrobial stewardship (AS). PAF participants were expanded from patients using specific antibiotics to those using whole injectable antibiotics to evaluate clinical outcome. From January 2016 to December 2016, PAF was performed in patients using specific antibiotics (period 1) and from January 2017 to December 2017, PAF was performed in patients using whole injectable antibiotics (period 2). PAF was implemented for 5 days every week by pharmacists involved in infectious diseases chemotherapy. In total, 11,571 and 11,103 patients used antibiotic injections during periods 1 and 2, respectively. No significant difference in mortality within 30 days from the initial use of injection antibiotics was observed. The average duration of hospitalisation was significantly shorter during period 2 among patients using antibiotics; however, this was not significantly different from that of patients not receiving antibiotics. The average duration of therapy for intravenous antibiotics was significantly shorter during period 2 than during period 1. The ratio of methicillin-resistant Staphylococcus aureus (MRSA) to S. aureus was significantly low during period 2. The duration of intravenous antibiotic therapy for Escherichia coli bacteraemia during period 2 decreased significantly. De-escalation and appropriate antimicrobial treatment rates at specific doses during period 2 increased significantly. Expansion of patients eligible for PAF from patients using specific antibiotics to patients using whole injectable antibiotics shortened hospital stays, suppressed drug resistance, and promoted the appropriate use of antibiotics.

Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects.

BACKGROUND: Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. PATIENTS AND METHODS: Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. RESULTS: Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases (P < 0.01). One case (3%) of watery stool, one case of loose stools (3%), and no cases of abdominal pain (0%) were observed. Median defaecation frequencies in the high-dose group (7 and 9) were significantly higher than those in the low-dose group (4 and 3) in the first (P = 0.0133) and second (P = 0.0101) weeks, respectively. There was no significant change in clinical laboratory values. CONCLUSION: We suggest that DKT increases defaecation frequency and is safe for treating constipation.

Evaluation of treatment outcomes of patients with MRSA bacteremia following antimicrobial stewardship programs with pharmacist intervention.

BACKGROUND: Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) is associated with high mortality and implementing an appropriate antimicrobial stewardship (AS) program with treatment intervention is essential. The aim of this study was to evaluate the impact of AS with pharmacist intervention on patients with MRSA-B. METHODS: Patients who were diagnosed with MRSA-B between January 2012 and April 2013 were defined as the pre-intervention group, while those diagnosed between May 2013 and December 2015 were defined as the intervention group (ie, AS with pharmacist intervention). The factors affecting bundle compliance rates and mortality were analysed. RESULT: The pre-intervention group comprised 43 patients and the intervention group comprised 51 patients. Bundle compliance rates were estimated as follows in the intervention group: an increase was observed in the appropriate duration of therapy (from 44.8% to 72.1%, P = .027), incidences of the early use of anti-MRSA drugs (from 62.3% to 82.4%, P = .038), and the number of negative follow-up blood cultures (from 40.0% to 80.0%, P < .001), and a decrease was observed for 30-day mortality (from 41.8% to 21.6%, P = .044) and hospital mortality (from 58.1% to 27.5%, P = .003). In multivariate analysis, the intervention group was independent of 30-day mortality and hospital mortality risk reduction factors (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.12-0.86, and OR, 0.20; 95% CI, 0.07-0.53). CONCLUSIONS: AS programs with pharmacist intervention improve mortality in patients with MRSA-B.

Effectiveness of a Computer-facilitated, Pharmacist-driven Antimicrobial Stewardship Program for Infection Management.

In recent years, hospitals have routinely implemented antimicrobial stewardship (AS) programs, and it is important that these programs are effective. Consequently, we utilized a customized computer system to support infection management and implemented a pharmacist-driven AS program in our hospital. Using this computer system, a pharmacist monitored the daily usage of carbapenems and agents against anti-methicillin-resistant Staphylococcus aureus and generated a patient database. With the use of this computer system, we found that the patient database entry time significantly decreased from 24 to 12 min (p<0.01). Subsequently, we were also able to monitor tazobactam/piperacillin usage owing to the increased efficiency of our AS program. As a result, the average number of monitored patients significantly increased from 51 to 72 per month (p<0.01) and the number of proposed prescriptions increased from 189 to 238 per year. Additionally, the usage of carbapenems and tazobactam/piperacillin significantly decreased (p<0.01) after implementation of this computer support system. In summary, we recommend that pharmacists utilize computer systems to implement AS programs because they increase the efficiency of interventions and monitoring of patients and promote appropriate antibiotic use.

Efficacy of daiokanzoto in chronic constipation refractory to first-line laxatives.

There are only a few treatment options for constipation and limited evidence of suitable treatments. Daiokanzoto (DKT) is a Kampo medicine often used clincally to treat constipation. DKT is a laxative used predominantly in Japan; however, clinical data on its efficacy and safety is lacking. Patients who used DKT, but were intolerant to either magnesium oxide (MgO; MgO group; n=16) or senna extract (Senna group; n=26) were included in the present study. The frequencies of their bowel movements were compared during the 1 week prior to and following DKT administration. Within 24 hours after DKT administration, 93.8% of the patients in the MgO group evacuated their bowels. The median bowel movement frequency 1 week prior to DKT administration was 2.5 and 1 week after DKT administration was significantly increased to 7.5. In the Senna group, within 24 h of DKT administration, 80.8% of the patients evacuated their bowels. The median bowel movement frequency 1 week prior to the DKT treatment was 2.0, which significantly increased to 8.5 1 week after the administration of DKT. The adverse events from DKT treatment were mild and controllable.

Potential drug interaction between paclitaxel and clopidogrel.

Paclitaxel is mainly inactivated in vivo by cytochrome P5402C8 (CYP2C8). In recent years, the clopidogrel metabolite has been reported to potently inhibit CYP2C8. However, clinical information regarding the interaction between these two drugs is limited. To the best of our knowledge, this is the first retrospective study investigating the potential for the drug interaction between paclitaxel and clopidogrel. A total of 8 cases in which clopidogrel and paclitaxel were used in combination were examined. The incidence of adverse events and discontinuation rate in these cases were assessed. Neutrophil counts were compared in patients prior and subsequent to the combined administration of clopidogrel and paclitaxel. Grade 3 neutropenia occurred in all cases of combination therapy and grade 4 occurred in 7 cases (88%). In addition, 4 cases (50%) showed febrile neutropenia. Four cases (50%) involved a severe adverse event requiring discontinuation of drug administration. In 1 case involving 6 courses of paclitaxel and nedaplatin therapy prior and subsequent to clopidogrel, there was a significant reduction in the average neutrophil count after 8 days of combination treatment (1,240±395 counts/mm3 without clopidogrel; 370±148 counts/mm3 with clopidogrel; mean ± standard deviation, P<0.01). Drug interactions during co-administration of clopidogrel and paclitaxel may cause severe neutropenia. To avoid these interactions, alternative medications should be considered. If these two drugs are used in combination, it may be necessary to monitor for adverse events more carefully.

Daily Review of Antimicrobial Use Facilitates the Early Optimization of Antimicrobial Therapy and Improves Clinical Outcomes of Patients with Bloodstream Infections.

Insufficient information is available to confirm the beneficial effects of implementing an antimicrobial stewardship program in reducing mortality of patients with bloodstream infections. A single institutional cohort study was conducted to evaluate clinical outcomes after implementation of a daily review of antimicrobials used to treat patients with bloodstream infections. Subjects were allocated to groups receiving either intervention or nonintervention. After implementation of an antimicrobial stewardship program, the day from the onset of infection required to administer effective intravenous antimicrobial treatment was significantly shortened (p=0.022), and the rate of de-escalation was significantly elevated (p<0.001) compared with the nonintervention group. Further, the rate of 30-d death associated with bloodstream infection was siginificantly reduced from 11.4 to 5.4% (p=0.030) compared with the nonintervention group. The incidence of adverse events was significantly lower in the intervention group than in the nonintervention group (7.7 vs. 28.0%, p<0.001). Our present findings suggest that daily review of the use of antimicrobials was highly effective for optimizing early antimicrobial therapy and improved clinical outcomes of patients with bloodstream infections.