Comparative effectiveness of cefmetazole versus carbapenems and piperacillin/tazobactam as initial therapy for bacteremic acute cholangitis: A retrospective study.

INTRODUCTION: Carbapenems and piperacillin/tazobactam (PIPC/TAZ) are commonly used as the initial therapy to treat extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales in acute cholangitis. However, the overuse of these antibiotics contributes to the spread of antimicrobial resistance. Cefmetazole (CMZ) is stable to hydrolysis by ESBLs, so it may be an alternative to carbapenems and PIPC/TAZ. However, the effectiveness of CMZ compared with that of carbapenems and PIPC/TAZ as the initial therapy for acute cholangitis is unknown. METHODS: We conducted a retrospective cohort study at a university hospital between April 1, 2014, and December 31, 2022. Patients with bacteremic acute cholangitis who received CMZ, carbapenems, or PIPC/TAZ as the initial therapy were included. The patients were divided into a CMZ group and a carbapenems or PIPC/TAZ (CP) group to compare patient outcomes. RESULTS: A total of 99 patients (54 in the CMZ group and 45 in the CP group) were analyzed. The baseline characteristics of the patients were similar and 30-day mortality did not differ between groups (4% vs. 7%, P = 0.66). However, the CMZ group had a shorter length of stay (LOS) (8 days vs. 15 days, P < 0.001) and lower mean antibiotic cost (98.92 USD vs. 269.49 USD, P < 0.001) than the CP group. CONCLUSIONS: In bacteremic acute cholangitis, initial therapy with CMZ may contribute to a shorter LOS and lower antibiotic costs than treatment with carbapenems and PIPC/TAZ, without worsening patient outcomes.

Risk Factors for Infusion Reactions in Patients with Breast Cancer Administered Trastuzumab Therapy.

Trastuzumab is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) that is indicated for the treatment of HER2-positive breast cancer. The administration of biologics, such as trastuzumab, frequently causes infusion reactions (IRs) with fever and chills. This study aimed to clarify the risk factors for IRs in trastuzumab therapy. Between March 2013 and July 2022, 227 patients with breast cancer who started trastuzumab therapy were included in this study. The severity of IRs was graded according to the Common Terminology Criteria for Adverse Events, Version 5.0. The incidence of IRs in trastuzumab therapy was 27.3% (62/227). Dexamethasone administration was significantly different between the IR and non-IR groups in patients receiving trastuzumab therapy (univariate analysis, p < 0.001; multivariate analysis, p = 0.0002). Without dexamethasone, the severity of IRs in the pertuzumab combination group (Grade 1, 8/65; Grade 2, 23/65) was significantly higher than that in the non-pertuzumab group (Grade 1, 9/37; Grade 2, 3/37; p < 0.05). Our findings suggest that the risk of IRs is significantly higher in patients not premedicated with dexamethasone in trastuzumab therapy and that the concomitant use of pertuzumab without dexamethasone increases the severity of IRs caused by trastuzumab.

Incidence and risk factors of infusion reactions in patients with breast cancer administered trastuzumab plus pertuzumab-based regimen.

PURPOSE: Pertuzumab (Per) is a humanized monoclonal antibody used in combination with trastuzumab (Tra) in the treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer. The administration of biologics, such as Tra and Per, frequently causes infusion reactions (IRs) with fever and chills. This study aimed to clarify the characteristics of and risk factors for IRs in Tra + Per combination therapy. METHODS: Between March 2013 and December 2019, 64 patients with breast cancer who started Tra + Per combination therapy were included in the study. The severity of IRs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: The incidence of IRs in the Tra + Per combination therapy was 48.4% (31/64). The severity of IRs in the Tra + Per combination therapy was Grade 1 (9 patients) and Grade 2 (22 patients). Lymphocyte counts were significantly different between the IR and non-IR groups in patients receiving Tra + Per combination therapy (univariate analysis, p = 0.006; multivariate analysis, p = 0.050). ROC curve analysis found the cutoff value of lymphocyte counts were 1.60 (× 103/µL). The incidence of IRs in the lymphocyte counts ≥ 1.60 group was significantly higher than that in the lymphocyte counts < 1.60 group (p < 0.001). CONCLUSION: Our study indicates that the severity of IRs in most patients is moderate or less and the risk of IRs is higher in patients with higher lymphocyte counts (≥ 1.60 × 103/µL).

Biomarker repurposing: Therapeutic drug monitoring of serum theophylline offers a potential diagnostic biomarker of Parkinson's disease.

Caffeine has been considered a neuroprotective agent against Parkinson's disease (PD). Recent metabolomic analysis showed that levels of caffeine and its metabolites were decreased in sera from patients with PD compared with those from healthy controls. We focused on theophylline, which is one of the primary caffeine metabolites, as a candidate biomarker of PD because: (1) its serum level can be measured in hospital laboratories by standardized immunoassay kits for therapeutic drug monitoring and (2) because it is less markedly affected by caffeine intake. This was a pilot study to measure the levels of theophylline in sera of 31 patients with PD and 33 age-matched disease controls using an immunoassay kit. We confirmed the previous finding of significantly lower levels of serum theophylline in the PD group compared with control group (PD: 0.07±0.09 µg/mL, control: 0.18±0.24 µg/mL, p<0.05). Using such an approach of applying known medical biomarkers for neurodegenerative diseases may allow us to skip the process from the discovery phase to clinical application, and subsequently shorten the period of time necessary for biomarker development.

Predictive factors in patients eligible for pegfilgrastim prophylaxis focusing on RDI using ordered logistic regression analysis.

Although pegfilgrastim prophylaxis is expected to maintain the relative dose intensity (RDI) of chemotherapy and improve safety, information is limited. However, the optimal selection of patients eligible for pegfilgrastim prophylaxis is an important issue from a medical economics viewpoint. Therefore, this retrospective study identified factors that could predict these eligible patients to maintain the RDI. The participants included 166 cancer patients undergoing pegfilgrastim prophylaxis combined with chemotherapy in our outpatient chemotherapy center between March 2015 and April 2017. Variables were extracted from clinical records for regression analysis of factors related to maintenance of the RDI. RDI was classified into four categories: 100% = 0, 85% or < 100% = 1, 60% or < 85% = 2, and < 60% = 3. Multivariate ordered logistic regression analysis was performed to identify predictive factors in patients eligible for pegfilgrastim prophylaxis to maintain the RDI. Threshold measures were examined using a receiver operating characteristic (ROC) analysis curve. Age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04-1.11; P < 0.0001], anemia (grade) (OR 1.77, 95% CI 1.10-2.84; P = 0.0184), and administration 24-72 h after chemotherapy (OR 0.44, 95% CI 0.22-0.89; P = 0.0224) were factors that significantly correlated with RDI maintenance. ROC curve analysis of the group that failed to maintain the RDI indicated that the threshold for age was 70 years and above, with a sensitivity of 60.0% and specificity of 80.2% (area under the curve: 0.74). In conclusion, younger age, anemia (less), and administration of pegfilgrastim 24-72 h after chemotherapy were significant factors for RDI maintenance.