MALDI-TOF with AST intervention decreased time to organism identification and time to effective and optimal antibiotic therapy.

Abstract Background Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is approved treatment. Methods We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). Results 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.58 (0.36, 0.94)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. Staphylococcus aureus accounted for ~50% of bacterial pneumonia. Conclusions In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.

Background Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. Methods We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). Findings 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. Interpretation In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings.

No abstract

A comprehensive candidemia care bundle directed by our institution's AST improved the management of patients with candidemia. We encourage further exploration into the use of care bundles by ASTs as part of their multifaceted approach to promoting appropriate antimicrobial utilization and optimizing the management of patients with infectious diseases.

Studies evaluating rapid diagnostic testing plus stewardship intervention have consistently demonstrated improved clinical outcomes for patients with bloodstream infections. However, the cost of implementing new rapid diagnostic testing can be significant, and such testing usually does not generate additional revenue. There are minimal data evaluating the impact of adding matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for rapid organism identification and dedicating pharmacy stewardship personnel time on the total hospital costs. A cost analysis was performed utilizing patient data generated from the hospital cost accounting system and included additional costs of MALDI-TOF equipment, supplies and personnel, and dedicated pharmacist time for blood culture review and of making interventions to antimicrobial therapy. The cost analysis was performed from a hospital perspective for 3-month blocks before and after implementation of MALDI-TOF plus stewardship intervention. A total of 480 patients with bloodstream infections were included in the analysis: 247 in the preintervention group and 233 in the intervention group. Thirty-day mortality was significantly improved in the intervention group (12% versus 21%, P Ͻ 0.01), and the mean length of stay was reduced, although the difference was not statistically significant (13.0 Ϯ 16.5 days versus 14.2 Ϯ 16.7 days, P ϭ 0.44). The total hospital cost per bloodstream infection was lower in the intervention group ($42,580 versus $45,019). Intensive care unit cost per bloodstream infection accounted for the largest share of the total costs in each group and was also lower in the intervention group ($10,833 versus $13,727). Implementing MALDI-TOF plus stewardship review and intervention decreased mortality for patients with bloodstream infections. Despite the additional costs of implementing MALDI-TOF and of dedicating pharmacy stewardship personnel time to interventions, the total hospital costs decreased by $2,439 per bloodstream infection, for an approximate annual cost savings of $2.34 million.

SUMMARYWhat is known and objective: Obesity is a significant burden on the healthcare system in the United States, and determining the appropriate antimicrobial dosing regimen in morbidly obese patients is challenging. Morbidly obese patients have documented differences in pharmacokinetic and pharmacodynamic properties compared to normal-weight patients, which impact antibiotic efficacy and toxicity. The Food and Drug Administration does not recognize obesity as a special population and does not require pharmaceutical companies to perform studies specific to obese patients. However, there are an increasing number of post-approval studies in obese patients, and this manuscript reviews available clinical and pharmacokinetic literature regarding weight-based antimicrobial agents. Additionally, we describe a single-centre approach to optimize dosing in morbidly obese patients. Methods: A comprehensive literature search was performed on 15 weight-based antimicrobials in the setting of obesity: acyclovir, aminoglycosides, amphotericin B, cidofovir, colistimethate, daptomycin, flucytosine, foscarnet, ganciclovir, quinupristin/ dalfopristin, trimethoprim/sulfamethoxazole, vancomycin and voriconazole. A weight-based antimicrobial dosing guideline for morbidly obese patients was developed. An analysis of guideline compliance and cost analysis were performed following guideline implementation. Results and discussion: This review describes the pharmacokinetic changes that occur in obese patients, including increased volume of distribution, altered hepatic metabolism, renal excretion and changes in protein binding. The majority of weightbased antimicrobials result in increased serum concentrations in morbidly obese patients compared to normal-weight patients when the calculated dose is based on actual body weight. What is new and conclusion: This review demonstrates different antibiotic pharmacokinetic properties are altered in obese patients that could impact efficacy and toxicity. A single-centre guideline for weight-based antimicrobial dosing in obesity was developed and provides recommendations for using ideal body weight, adjusted body weight or actual body weight when calculating antimicrobial doses. However, more research is needed to better elucidate optimal dosing of weight-based antimicrobials in obesity, with particular focus on efficacy and toxicity. WHAT IS KNOWN AND OBJECTIVEObesity is a major issue in the United States, with 78 million US adults and 12Á5 million children and adolescents classified as obese [body mass index (BMI) greater than or equal to 30].1 This equates to an obesity rate of 35% and 16Á9% in adults and children in the United States, respectively.1 Physiological changes in obesity can alter immunological pathways and increase the risk of central line infection, post-operative surgical site infections, intensive care unit length of stay and risk for severe pneumonia and influenza. [2][3][4][5] Additionally, changes in antimicrobial pharmacokinetic and pharmacodynamic properties are well docume...

No abstract