Impact of a 20 mg/kg vancomycin loading dose on early AUC target attainment.

This retrospective chart review evaluated whether 20 mg/kg vancomycin loading doses increase early area under the curve (AUC) target attainment within 48 hours in comparison to non-loading dose regimens. There were no differences between groups for the primary outcome (46 % vs. 50 %; P = 0.58).

Antibiotic de-escalation in pneumonia with pharmacist education and ordering of methicillin-resistant Staphylococcus aureus nasal swabs.

INTRODUCTION: When methicillin-resistant Staphylococcus aureus (MRSA) is the causative pathogen in pneumonia, in-hospital mortality rate is approximately 31.2%. However, the occurrence of MRSA pneumonia is uncommon, with a reported incidence of approximately 4.2%. Vancomycin is often empirically used for MRSA pneumonia coverage, but can lead to serious harm. The purpose of this study was to measure the impact of a pharmacy-driven MRSA nares testing protocol on vancomycin and linezolid prescribing patterns and clinical outcomes in patients diagnosed with pneumonia after removal of immediate educational intervention. METHODS: This single-centre, quasi-experimental study evaluated the use of a MRSA nasal swab on patients diagnosed with community-acquired pneumonia, hospital-acquired pneumonia and ventilator-associated pneumonia. This study consisted of three phases, the preimplementation phase, the active/educational phase and the postimplementation phase. The primary outcome was intravenous anti-MRSA antibiotic duration of therapy. Secondary outcomes included the occurrence of acute kidney injury, duration of hospital stay, number of vancomycin levels obtained, the number of MRSA nares swabs ordered and time points in the MRSA nares collection process. RESULTS: The preimplementation phase (n=39), the active phase (n=45) and the postimplementation phase (n=26) demonstrated similar baseline characteristics. The primary outcome for duration of anti-MRSA therapy 0-72 hours was 61.5% vs 77.8% vs 76.9% (p=0.19). Acute kidney injury was decreased throughout the study at 25.6%, 24.4% and 16.7% (p=0.32). The number of MRSA nares swabs ordered were 23.1%, 60% and 30.8% in each of the phases, respectively (p=0.49). DISCUSSION: Our novel approach to measuring the impact of pharmacist education and ordering of MRSA nasal swabs has demonstrated benefits that were sustained for a short period after the intervention was removed. Additional study is required to determine the long-term impact. CONCLUSION: The implementation of a hospital-wide anti-MRSA protocol in patients with confirmed or suspected pneumonia indicated sustained changes for at least 3 months after direct intervention.

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.

Risk Factors and Clinical Outcomes of Candidemia Associated With Severe COVID-19.

COVID-19 can cause serious illness requiring multimodal treatment and is associated with secondary infections. Studies have suggested an increased risk of fungal infections, including candidemia following severe COVID-19 though understanding of risk factors and clinical outcomes remains unclear. OBJECTIVES: To describe clinical characteristics, outcomes and risk factors of candidemia among patients hospitalized with severe COVID-19. DESIGN SETTING AND PARTICIPANTS: A multicenter, case-control study of patients with severe COVID-19 was conducted to evaluate risk factors and clinical outcomes in patients who developed candidemia between August 2020 and August 2021. MAIN OUTCOMES AND MEASURES: Chart review evaluating institutional and patient demographics, clinical and mycological characteristics, concomitant interventions (antibiotics, immunosuppressive agents, parenteral nutrition, degree of oxygen support, mechanical ventilation, surgery), treatment regimens, and outcomes (length of stay and discharge disposition). RESULTS: A total of 275 patients were enrolled in the study, including 91 patients with severe COVID-19 and subsequent candidemia and 184 with severe COVID-19 without candidemia. Most patients received antibiotics prior to candidemia episode (93%), while approximately one-quarter of patients received biologic for COVID-19. In-hospital mortality was significantly higher in the cases compared with the controls (68% vs 40%; p < 0.01). Candida albicans was the most common (53%), followed by C. glabrata (19%). Use of central lines, biologic, and paralytics were independent risk factors for candidemia. CONCLUSIONS AND RELEVANCE: Candidemia following COVID-19 infection is a concern that requires clinical consideration and patient monitoring. Risk factors for the development of candidemia in the setting of COVID-19 infection are largely consistent with traditional risk factors for candidemia in hospitalized patients.

A Post-Neurosurgical Infection due to KPC-Producing Klebsiella pneumoniae Treated with Meropenem-Vaborbactam: A Case Report.

This case report describes a patient with post-neurosurgical infection and bacteremia caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae. There is limited evidence to guide antibiotic treatment decisions for such infections. The patient was treated with meropenem-vaborbactam (MEV). MEV monotherapy was associated with bacteremia clearance.

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.

Selective antibiotic susceptibility reporting and broad-spectrum intravenous antibiotic use: A multicentre ecological study.

Recent estimates of inpatient antibiotic use in the USA suggest that broad-spectrum antibiotic use has increased significantly. The objective of this study was to assess the impact of a selective antibiotic susceptibility reporting intervention on broad-spectrum intravenous (i.v.) antibiotic use in seven hospitals of a health system in New Jersey. This was a retrospective pre- and post-intervention ecological study. Standardised selective antibiotic susceptibility reporting rules were developed and implemented between January 2016 and June 2017. The 8 months before and after each individual hospital's implementation constituted the pre- and post-intervention study periods. The primary outcome was the rate of broad-spectrum i.v. antibiotic use for hospital-onset/multidrug-resistant infections (broad MDR). Secondary outcome measures were the use rates of non-glycopeptide anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agents, carbapenems, non-carbapenem antipseudomonal ß-lactams, third-generation cephalosporins, first/second-generation cephalosporins, fluoroquinolones and narrow-spectrum penicillins. Antibiotic use data were collected as inpatient i.v. antibiotic days of therapy per 1000 patient days (DOT/1000-PD). Interrupted time series analysis with segmented regression was used to compare outcomes. There was no significant change in the use of broad MDR agents (slope change, +0.54 DOT/1000-PD per month, 95% confidence interval -1.78 to 2.87) or other antibiotic classes. Whilst the implementation of selective antibiotic susceptibility reporting across seven hospitals had no impact on overall broad-spectrum i.v. antibiotic use, further study is needed to determine the long-term impact of this intervention.