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.

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.

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.

Evaluation of hypokalemia and potassium supplementation during administration of liposomal-amphotericin B.

Patients prescribed liposomal-amphotericin B (L-AMB) frequently require supplemental potassium to prevent hypokalemia. The aim of this retrospective study was to examine the appropriate potassium supplementation conditions to treat hypokalemia induced by L-AMB. The subjects were 100 hematological patients who received L-AMB for the first time between April 2012 and March 2013. A total of seven patients were excluded. Of the remaining 93 patients, 48 (51.6%) were assigned to the group receiving supplemental potassium (supplementation group), and 45 (48.4%) were assigned to the group without potassium supplementation (non-supplementation group). Hypokalemia greater than grade 3 was exhibited by 50 of the 93 (53.8%) patients. Multivariate analysis revealed that the minimum serum potassium levels during L-AMB administration (≤2.98 mEq/l) were an independent factor significantly contributing to the effectiveness of potassium supplementation [odds ratio (OR), 3.62; 95% confidence interval (CI), 1.44-9.59; P<0.01]. In addition, multivariate analysis revealed that the serum potassium levels (≥2.83 mEq/l) prior to the potassium supplementation were an independent factor significantly contributing to the development of proper potassium supplementation (OR, 14.21; 95% CI, 1.95-310.72; P=0.02), and no significant difference was observed in the dosage of the potassium supplementation administered to the patients who recovered from hypokalemia and those who did not. In conclusion, it is necessary to begin potassium supplementation prior to the reduction of the serum potassium levels to <2.83 mEq/l. Potassium supplementation at an early stage of L-AMB treatment is important to prevent severe electrolyte abnormalities.

[Continuation of chemotherapy with bevacizumab for advanced and recurrent colorectal cancer].

We evaluated the association between the number of treatment courses with the concomitant use of bevacizumab(BV) and the reasons for discontinuation of the regimen in patients who received FOLFOX with or without BV as first-line chemotherapy and FOLFIRI with or without BV as second-line chemotherapy for advanced and recurrent colorectal cancer. In first-line treatment, 12 (2-46) and 10 (2-60) treatment courses were administered with and without BV, respectively, and this difference was not significant (p=0.60). In second-line treatment after first-line treatment with the concomitant use of BV, 11 (1-23) and 3 (1-12) treatment courses were administered with and without BV, respectively, and this difference was significant (p<0.01). Discontinuation due to adverse reactions was more frequent for first-line treatment (34.9%) than for second-line treatment (6.2%; p<0.01). The reasons for discontinuation due to adverse reactions during first-line treatment with BV were often associated with BV, and those during first-line treatment without BV were most often associated with peripheral neuropathy. Therefore, we conclude that early detection and prevention of adverse reactions are important in first-line treatment and that pharmacists as well should be involved in the monitoring and management of adverse reactions, although continued administration of BV even during second-line treatment after first-line treatment with BV is recommended.

[Induction of allergic reactions by anticancer drugs in outpatient chemotherapy].

We must understand the conditions during the onset of allergic reactions induced by anticancer drugs in order to respond with an appropriate treatment. We have therefore conducted this study, focusing on allergic reactions induced by each anticancer drug used in outpatient chemotherapy. Allergic reactions occurred in a total of 3.9% (76 cases), most of which were induced by platinum and taxane anticancer drugs. The number of administrations at symptom onset and the times of onset for platinums and taxanes were 11. 7±1. 3 times and 43. 3±4. 8 minutes for platinum; and 2. 3±0. 5 times and 18. 1± 3. 6 minutes for taxanes, respectively. This demonstrated a significant difference between these two drugs(both were p< 0. 01). In terms of re-administration following the onset of allergic reactions, 21 cases(72. 4%)out of 29 cases(38. 2%) were able to continue the administration of suspected drugs. We studied various factors surrounding the possibility of continued administration to two groups which were or were not able to continue receiving treatment. No significant differences were observed between the groups. For continuous safe treatment, it is necessary to understand the characteristics of allergic reactions induced by each anticancer drug. It is also advisable to consider possible precautions(by introducing prevention regimens)and appropriate measures at the time of re-administration, following the onset of allergic reactions.

[Appearance of skin and nail toxicity in patients with breast cancer who underwent trastuzumab-containing chemotherapy].

Trastuzumab is used for patients with metastatic breast cancer of HER2 over expression and adjuvant chemotherapy. Trastuzumab is recognized as a medicine with few adverse effects, although infusion reaction at its first dosage appears in high frequency as a main adverse effect. However, because we realized that there were many patients who appeared to have skin toxicity or nail toxicity, the adverse effects of trastuzumab were investigated retrospectively. Of 51 cases who underwent trastuzumab-containing chemotherapy, 25 cases(49. 0%)had skin toxicity, 14 cases(27. 5%) had nail toxicity, and 12 cases(23. 5%)had both toxicities. Skin toxicity and nail toxicity appeared in 14 of 25 cases(56. 0%) and 6 of 14 cases(42. 9%)respectively, within 6 months after the first medication dosage. Symptoms of skin toxicity were eruptions on the face and body(14 cases; 27. 5%), skin detachment or thinning on hands and feet(9 cases; 17. 6%), itching (8 cases; 15. 7%), skin drying(7 cases; 13. 7%)and so on. On the other hand, symptoms of nail toxicity were softening, thinning, or loss(13 cases; 25. 5%), paronychia(4 cases; 7. 8%), and discoloration(2 cases; 3. 9%). Our present findings suggest that skin toxicity and nail toxicity are highly frequent adverse events for those taking trastuzumab, although the drug is considered to be a molecular target drug with few adverse effects.

[The frequency and risk factor of herpes zoster infection in non-Hodgkin's lymphoma patients].

The chemotherapy treatment of non-Hodgkin's lymphoma(NHL)is associated with an increased risk of infection because of the intensity of the treatment. We examined the frequency of herpes zoster infections in 170 non-Hodgkin's lymphoma patients who had completed a chemotherapy course. Furthermore, we examined the risk factors contributing to these infections. This study took place in the Department of Hematology at Ogaki Municipal Hospital. Of the 170 patients treated in our facility, 25 developed herpes zoster(14. 7%), 19 of whom developed symptoms within 30 days of starting the chemotherapy treatment. Significant risk factors for the development of herpes zoster were post-autologous peripheral blood stem cell transplantation, relapsing patients, ten or more total treatments and the use of two or more regimens. In these cases the average interval of the treatments had to be extended from 6. 6 days to 14. 2 days due to the infection(comparing post - infection to pre-infection). We recommend the prophylactic use of low-dose acyclovir in patients with a higher risk of herpes zoster infection. We also recommend further monitoring of other opportunistic infections associated with chemotherapy usage.

[Clinical evaluation of calculating carboplatin doses using modification of diet in renal disease (MDRD) estimate and adverse events].

A modified diet in renal disease (MDRD), a formula to estimate glomerular filtration rate (GFR), was proposed by Levey in 2006. In this study, we compared the dosage of carboplatin (CBDCA) calculated using MDRD with that calculated by conservative creatinine clearance (Ccr), and investigated the actual dosage given and the incidence of its adverse effects. In the 101 patients undergoing chemotherapy including CBDCA, the dosage calculated from the estimated GFR was 16% lower than that based on the estimated Ccr. This difference was greater in those under 65 years, women and those with a body mass index (BMI) > or =25. The most prominent incidence of adverse effects was thrombocytopenia in patients with lung cancer. In men, a serum creatinine level of > or =0. 6 mg/dL, GFR of <50 mL/min/1. 73 m(2) and a combined use of gemcitabine were cited as the factors responsible for the development of thrombocytopenia. It was concluded that the MDRD formula is an effective tool for evaluating patients with impaired renal function. It was suggested, on the other hand, that the dosage for medication should be decided by giving due consideration to factors other than renal functions.

Inhibition of alpha-glucosidase and alpha-amylase by flavonoids.

The inhibitory activity of six groups of flavonoids against yeast and rat small intestinal alpha-glucosidases and porcine pancreatic alpha-amylase was compared, and chemical structures of flavonoids responsible for the inhibitory activity were evaluated. Yeast alpha-glucosidase was potently inhibited by the anthocyanidin, isoflavone and flavonol groups with the IC50 values less than 15 microM. The following structures enhanced the inhibitory activity: the unsaturated C ring, 3-OH, 4-CO, the linkage of the B ring at the 3 position, and the hydroxyl substitution on the B ring. Rat small intestinal alpha-glucosidase was weakly inhibited by many flavonoids, and slightly by the anthocyanidin and isoflavone groups. 3-OH and the hydroxyl substitution on the B ring increased the inhibitory activity. In porcine pancreatic alpha-amylase, luteolin, myricetin and quercetin were potent inhibitors with the IC50 values less than 500 microM. The 2,3-double bond, 5-OH, the linkage of the B ring at the 3 position, and the hydroxyl substitution on the B ring enhanced the inhibitory activity, while 3-OH reduced it.

[Management of the system to allow the terminal cancer patients and their families to choose from in-hospital care, outpatient care and home care at Matsuyama Bethel hospital].

Hospice ward at Matsuyama Bethel Hospital opened in April 2000. The hospice care has been provided for inpatients and outpatients. We considered a system that should be established to allow patients and their families to choose from in-hospital care, outpatient care and home care. The hospice consultation for outpatients opened in April 2004. The terminal cancer patients who are within 6 months of remaining days were hospitalized to the hospice ward. After making the hospice consultation for outpatients, hospice care services have been provided for terminal cancer patients including those with more than 6 months of remaining days under the coordination of palliative care for outpatients and inpatients.