Casirivimab-imdevimab neutralizing SARS-CoV-2: post-infusion clinical events and their risk factors.

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.

Interprofessional Antimicrobial Stewardship Influencing Clostridioides difficile Infection: An 8-Year Study Using Antimicrobial Use Density.

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.

Does antimicrobial use density at the ward level influence monthly central line-associated bloodstream infection rates?

The aim of this study was to elucidate risk factors, including ward antimicrobial use density (AUD), for central line-associated bloodstream infection (CLABSI) as defined by the Centers for Disease Control and Prevention in a 430-bed community hospital using central venous lines with closed-hub systems. We calculated AUD as (total dose)/(defined daily dose × patient days) ×1,000 for a total of 20 drugs, nine wards, and 24 months. Into each line day data, we inputed AUD and device utilization ratios, number of central line days, and CLABSI. The ratio of susceptible strains in isolates were subjected to correlation analysis with AUD. Of a total of 9,997 line days over 24 months, CLABSI was present in 33 cases (3.3 ‰), 14 (42.4%) of which were on surgical wards out of nine wards. Of a total of 43 strains isolated, eight (18.6%) were methicillin-resistant Staphylococcus aureus (MRSA); none of the MRSA-positive patients had received cefotiam before the onset of infection. Receiver-operating characteristic analysis showed that central line day 7 had the highest accuracy. Logistic regression analysis showed the central line day showed an odds ratio of 5.511 with a 95% confidence interval of 1.936-15.690 as did AUD of cefotiam showing an odds ratio of 0.220 with 95% confidence interval of 0.00527-0.922 (P=0.038). Susceptible strains ratio and AUD showed a negative correlation (R (2)=0.1897). Thus, CLABSI could be prevented by making the number of central line days as short as possible. The preventative role of AUD remains to be investigated.

Is Clostridium difficile infection influenced by antimicrobial use density in wards?

This study was performed to elucidate the relationship between antimicrobial use density (AUD) and Clostridium difficile infection (CDI) manifesting as antimicrobial-associated diarrhea (AAD) in hospital wards during a 4-year period. Case definition of CDI was an adult exhibiting AAD with a daily stool frequency of three or more, arising at least 48 hours after ward admission, and fecal samples testing positive for toxin (A and/or B). Metronidazole or vancomycin was orally administered as treatment. AUDs were calculated for a total of 21 antimicrobials in a span of 48 months and nine wards. We included the average value of AUDs, representing two succeeding months of sample submission into the sample information. We also entered data on the 2-year division and intensified contact precaution for statistical analysis. Of a total of 463 cases, 95 (20.5%) were CDI-positive. Multivariate regression analysis showed odds ratios [OR] of 1.739 (95% confidence interval [CI] of 1.050 - 2.881, P = 0.032) and 1.598 (95% CI of 1.006 -2.539, P = 0.047) for clindamycin and piperacillin, respectively in AUD. Thus increased ward AUDs of clindamycin and piperacillin may run the risk of CDI.

Central line-associated bloodstream infection: is the hospital epidemiology of methicillin-resistant Staphylococcus aureus relevant?

We aimed to evaluate the risk factors, including the hospital epidemiology of methicillin-resistant Staphylococcus aureus (MRSA), for central venous line-associated and laboratory-confirmed bloodstream infections (CLA-BSI and LC-BSI, respectively). The risk factors examined included the age and sex of patients, whether or not they were in the surgery service, the number of days of central line (CL) placement, the monthly number of inpatients and those positive for MRSA, and whether the standard or maximal barrier precautions were observed at CL insertion. As the outcome factors, we selected CLA-BSI and LC-BSI, while precluding repeated isolation within 28 days. Of a total of 22,723 device days in 927 patients with CL placement, we observed 81 CLA-BSIs and 40 LC-BSIs, rates of 3.56 and 1.76 (/1000 device-days), respectively. Logistic regression analysis revealed a single significant factor, CL placement of more than 30 days, with odds ratios of 3.038 [95% confidence interval (CI) 1.733-5.326; P < 0.001] for CLA-BSI and 3.227 (95% CI 1.427-7.299; P = 0.005) for LC-BSI. Both BSIs included MRSA in seven events without temporal clusters. We conclude that the factor of long CL placement outweighs other risk factors, including the hospital epidemiology of MRSA.