RESUMO
BACKGROUND: Casirivimab-imdevimab has been developed to neutralize SARS-CoV-2. The global clinical trials in outpatients documented several adverse effects (AE), which mandate caution in Japan where part of patients return home. To investigate post-infusion clinical events and their risk factors, we attempted a retrospective study. MAIN BODY: Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of casirivimab-imdevimab in our institute. The criteria for administration were in accordance with previous clinical trials, e.g., exclusion of patients necessitating oxygen supply. In Japan, however, SARS-CoV-2 vaccinees were eligible. Methods were review of background factors of status, imaging, and laboratory findings for the outcome of post-infusion events such as temperature increase (Temp+), pulse oximetry below 94%, and other events. Also, we documented the drug efficacy. Of a total of 96 patients with a median follow-up of 54 days, one (1.0%) died who alone was an exception demanding oxygen supply. Other 95 patients (99.0%) recovered from fever and hypoxia by Day 4 and later had no worsening of COVID-19. Median increase of body temperature was 1.0 degrees Celsius, which was used for computation of Temp+. Multivariate analysis showed that for Temp+ (n = 47), white blood cell counts more than 4.3 × 103/microliter (Odds Ratio [OR] 2.593, 95% Confidence Interval [CI] 1.060-6.338, P = 0.037) was at risk, whereas 2-time vaccination for SARS-CoV-2 (OR 0.128, 95% CI 0.026-0.636, P = 0.012) was a preventing factor. Likewise for lowered oximetry (n = 21), CT showing bilateral ground glass attenuation (OR 5.544, CI 1.599-19.228, P = 0.007) was a significant risk factor. Two patients (2.1%) showed bradycardia (asymptomatic, intervention not indicated) on Day 3 and recovery on Day 5. Limitations for this study included the difficulty distinguishing AE from worsening of COVID-19, thus we documented as clinical events. CONCLUSIONS: For 24 h after infusion of casirivimab-imdevimab, COVID-19 patients with increased white blood cell counts may be predisposed to temperature elevation more than 1.0 degrees centigrade, as may bilateral ground glass opacity to lowered oximetry. Thus, patients with leukocytosis and bilateral ground glass attenuation may need precaution for transient fever and hypoxia, respectively.
RESUMO
PURPOSE: To reduce Clostridioides difficile infection (CDI), we implemented interprofessional antimicrobial, infection control, and diagnostic stewardship (ipAS) conducted by physicians/pharmacists, infection control nurses, and medical technologists, respectively. As a numerical indicator for ipAS, we used antimicrobial use density (AUD) in an 8-year study to validate its efficacy in CDI reduction. PATIENTS AND METHODS: This was an observational study. CDI was defined as stool samples or C. difficile isolates containing toxin A and/or B from a patient with diarrhea occurring three or more times per day. From 2011-2018 at a 10-ward single site the subjects were in-patients with CDI, and the following data were collected: AUDs for 23 antibiotics, and antimicrobial test results. By 2015, we had established ipAS, consisting of culture submission before the administration of broad-spectrum antimicrobials, the promotion of point-of-care testing for diagnosis-based antimicrobials, perioperative prophylactic antibiotics, intervention at positive diagnosis of blood culture, team round for diarrhea, and inspection on contact precautions and disinfection in CDI cases. The study outcomes included annual numbers of CDI patients and blood culture sets. We compared annual AUDs between former (2011-14) and latter (2015-18) periods using Kruskal-Wallis tests and examined the correlation between AUDs and CDI numbers. RESULTS: Of a total 50,970 patients, 1,750 patients underwent C. difficile toxin tests, of whom 171 patients (9.8%) were positive for CDI. Between the former and latter periods, AUDs for flomoxef (11.96 to 2.71 by medians), panipenem/betamipron (0.30 to 0.00), and clindamycin (3.87 to 2.19) significantly decreased (P<0.05) as did numbers of CDIs (26.5 to 10) (P=0.043). The correlation analysis revealed a significant correlation between AUD for flomoxef and CDIs (P=0.004) and the AUD for piperacillin/tazobactam and CDIs (P=0.010) with a positive Pearson r. CONCLUSION: The integrated antimicrobial, diagnostic, and infection control approach used in ipAS may reduce CDIs.
