Evolution and Transmission of Cefiderocol-Resistant Acinetobacter baumannii During an Outbreak in the Burn Intensive Care Unit.

We report on 11 critically ill burn patients treated with cefiderocol for carbapenem-resistant Acinetobacter baumannii infections. Clinical success was achieved in 36% and complicated by treatment-emergent resistance and interpatient transmission of cefiderocol-resistant A. baumannii. Resistant isolates harbored disrupted pirA and piuA genes that were not disrupted among susceptible isolates.

Real-world evaluation of the impact of two anti-SARS-CoV-2 monoclonal antibody regimens on COVID-19 hospitalizations in older adults.

Evidence from clinical trials suggest anti-SARS-CoV-2 monoclonal antibodies (mABs) may reduce coronavirus disease 2019 (COVID-19)-related hospitalizations. The purpose of this study was to assess the real-world impact of mAB administration on COVID-19 hospitalization among patients 65 years or older. This was a retrospective, propensity-matched cohort study that included patients aged 65 years and older who presented to the emergency department (ED) within 10 days of symptom onset of mild to moderate COVID-19 infection. Outcomes were compared between those who did and did not receive mAB therapy. The primary endpoint was the rate of hospitalization for COVID-19 within 30 days of index ED visit. A total of 137 patients receiving mABs were matched to 137 controls. Hospitalization occurred in 2.9% of mAB-treated patients compared to 14.6% of patients of the standard of care (SOC) arm (odds ratio: 0.20 [95% CI: 0.07-0.59]). There were zero intubations and zero deaths compared to 3 (2.2%) and 2 (1.5%) in the SOC group. Among the 223 patients receiving mAB in the overall cohort, adverse drug events occurred in 10 (4.5%). Treatment with mAB therapy for mild to moderate COVID-19 was associated with a substantially reduced risk of hospitalization among patients at least 65 years of age.

The DOOR to Antibiotic Stewardship: Refining Assessments of Interventions With Desirability of Outcome Ranking.

BACKGROUND: Limited sample size and disparate outcome measures can hinder the ability of antimicrobial stewardship programs to assess the utility of their quality improvement interventions. Desirability of outcome ranking (DOOR) is a novel methodology that incorporates multiple outcomes into a single value to more comprehensively compare therapeutic strategies. The objective of this study was to apply DOOR to a single center antibiotic stewardship intervention. METHODS: A pre- and post-interventional study was conducted evaluating the impact of prospective pharmacist review of rapid molecular diagnostic testing (RDT) of blood cultures on antibiotic optimization. Outcomes included the percentage of patients who were switched to appropriate therapy, the time to appropriate therapy, and the percentage of patients who had missed de-escalation opportunities. RESULTS: A total of 19 and 29 patients were included in the final analysis. The percentage of patients reaching appropriate therapy was 84% (16/19) and 97% ([28/29], p = 0.16) in the pre-intervention and post-intervention groups respectively. Median time to appropriate therapy was 26 hours and 36 minutes (IQR 13:05-50:45) and 22:40 (IQR 3:42-48:23, p = 0.32), respectively. One missed de-escalation opportunity was identified in the post-intervention group (0% vs 3%, p = 1.00). DOOR analysis indicated that the probability of a better outcome for the post-intervention group than the pre-intervention group was 58% (95% CI 54-62). CONCLUSION: In this analysis, DOOR revealed a benefit that would not have been apparent with traditional outcomes assessments. Antimicrobial stewardship programs conducting quality improvement studies should consider incorporating DOOR into their methodology.

Save the Quinolones! Impact of a Non-Restrictive Fluoroquinolone Reduction Initiative on Antibiotic Use and Resistance at an Urban Teaching Hospital.

BACKGROUND: Many antibiotic stewardship programs have sought to reduce fluoroquinolone use due to their association with a myriad of negative consequences. In hospital settings with fewer resources, initiatives that are less labor intensive may offer a more feasible approach to addressing fluoroquinolone use and improving patient care. OBJECTIVE: This study assessed the impact of a non-restrictive fluoroquinolone reduction initiative on antibiotic use and resistance. METHODS: This was a retrospective pre- and post-interventional ecological study conducted from 2016 to 2017. The fluoroquinolone reduction initiative consisted of education on risks and alternatives. Buttons promoting "Save the Quinolones" were also worn to increase visibility. Outcome measures were the rate of fluoroquinolone use and antibiotic resistance in Staphylococcus aureus, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Pseudomonas aeruginosa before and after the intervention. RESULTS: Overall, fluoroquinolone use decreased throughout the study, but there was a significantly greater rate of decrease in the post-intervention period (monthly decrease of 3.3% (1.3, 5.1) v. 7.4% (5, 9.8) p = 0.043). S. aureus susceptibility to oxacillin increased from 47.2% to 55.2% (difference 8.0, 95%CI 1.2 to 14.7). P. aeruginosa susceptibility to levofloxacin increased from 60% to 70.7% (difference 10.7, 95%CI 0.8 to 20.6). No differences in susceptibility rates of E. coli, P. mirabilis or K. pneumoniae were detected. CONCLUSION: This non-restrictive fluoroquinolone reduction initiative led to a significant decrease in fluoroquinolone use that was associated with decreased antibiotic resistance in S. aureus and P. aeruginosa.

Medication safety in a pandemic: A multicentre point prevalence study of QTc monitoring of hydroxychloroquine for COVID-19.

WHAT IS KNOWN AND OBJECTIVE: A pandemic can strain all aspects of the healthcare system, including the ability to monitor the safety of medication use. Reviewing the adequacy of medication safety practices during the COVID-19 pandemic is critical to informing responses to future pandemics. The purpose of this study was to evaluate medication safety practices at a height of both COVID-19 cases and hydroxychloroquine use. METHODS: This was a multicentre observational point prevalence study. Adult inpatients receiving hydroxychloroquine for COVID-19 between March 22 and 28, 2020 were included. The primary outcome was the percentage of patients receiving appropriate QTc monitoring. Secondary outcomes included QTc prolongation, early discontinuation of hydroxychloroquine and ventricular arrhythmias. RESULTS AND DISCUSSION: A total of 59% (167/284) of patients treated with hydroxychloroquine received appropriate QTc monitoring. QTc prolongation occurred in 25%. Hydroxychloroquine was prematurely discontinued in 1.4% of patients, all due to QTc prolongation. Ventricular arrhythmia occurred in 1.1%. WHAT IS NEW AND CONCLUSION: Medication safety practices were suboptimal with regard to hydroxychloroquine monitoring at the height of the COVID-19 pandemic. Preparation for future pandemics should devote considerable attention to medication safety.

Early clinical outcomes with tocilizumab for severe COVID-19: a two-centre retrospective study.

Severe COVID-19 (coronavirus disease 2019) is associated with elevated inflammatory markers, consistent with cytokine release syndrome (CRS). Tocilizumab is an interleukin-6 (IL-6) inhibitor effective in treating CRS secondary to chimeric antigen receptor T-cell (CAR T-cell) therapy. The efficacy of tocilizumab in treating COVID-19 is unknown. This was a retrospective cohort study conducted at two hospitals in northern New Jersey (USA). All patients treated with tocilizumab for confirmed or suspected COVID-19 between 10 March 2020 and 9 April 2020 at the study sites were included. The primary endpoint was clinical improvement on Day 7 after treatment as assessed by respiratory status. Univariate analysis compared data between those who improved and those who did not. A total of 45 severe and critically ill patients treated with tocilizumab for COVID-19 were evaluated. Of the 45 patients, 11 (24.4%), 22 (48.9%) and 12 (26.7%) patients improved, had no change or worsened by Day 7 after treatment, respectively. Lower white blood cell count and lactate dehydrogenase at the time of drug administration as well as shorter time from supplemental oxygen initiation to dosing were significantly associated with clinical improvement in the univariate analysis. In conclusion, tocilizumab administration was associated with a low rate of clinical improvement within 7 days in this cohort of severe and critically ill patients with COVID-19.