Showing papers by "Natasha N Pettit published in 2021"

Late onset infectious complications and safety of tocilizumab in the management of COVID-19.

Abstract: BACKGROUND: Tocilizumab (TCZ) has been used in the management of COVID-19-related cytokine release syndrome (CRS). Concerns exist regarding the risk of infections and drug-related toxicities. We sought to evaluate the incidence of these TCZ complications among COVID-19 patients. METHODS: All adult inpatients with COVID-19 between 1 March and 25 April 2020 that received TCZ were included. We compared the rate of late-onset infections (>48 hours following admission) to a control group matched according to intensive care unit admission and mechanical ventilation requirement. Post-TCZ toxicities evaluated included: elevated liver function tests (LFTs), GI perforation, diverticulitis, neutropenia, hypertension, allergic reactions, and infusion-related reactions. RESULTS: Seventy-four patients were included in each group. Seventeen infections in the TCZ group (23%) and 6 (8%) infections in the control group occurred >48 hours after admission (P = .013). Most infections were bacterial with pneumonia being the most common manifestation. Among patients receiving TCZ, LFT elevations were observed in 51%, neutropenia in 1.4%, and hypertension in 8%. The mortality rate among those that received TCZ was greater than the control (39% versus 23%, P = .03). CONCLUSION: Late onset infections were significantly more common among those receiving TCZ. Combining infections and TCZ-related toxicities, 61% of patients had a possible post-TCZ complication. While awaiting clinical trial results to establish the efficacy of TCZ for COVID-19 related CRS, the potential for infections and TCZ related toxicities should be carefully weighed when considering use.

COVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia.

Abstract: Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the mortality of coronavirus disease 2019 (COVID-19). The IL-6 receptor-blocking monoclonal antibody tocilizumab has been repurposed for COVID-19, but prospective trials and dose-finding studies in COVID-19 have not yet fully reported. We conducted a single-arm phase II trial of low-dose tocilizumab in nonintubated hospitalized adult patients with COVID-19, radiographic pulmonary infiltrate, fever, and C-reactive protein (CRP) ≥ 40 mg/L. We hypothesized that doses significantly lower than the emerging standards of 400 mg or 8 mg/kg would resolve clinical and laboratory indicators of hyperinflammation. A dose range from 40 to 200 mg was evaluated, with allowance for one repeat dose at 24 to 48 hours. The primary objective was to assess the relationship of dose to fever resolution and CRP response. Thirty-two patients received low-dose tocilizumab, with the majority experiencing fever resolution (75%) and CRP decline consistent with IL-6 pathway abrogation (86%) in the 24-48 hours following drug administration. There was no evidence of a relationship between dose and fever resolution or CRP decline over the dose range of 40-200 mg. Within the 28-day follow-up, 5 (16%) patients died. For patients who recovered, median time to clinical recovery was 3 days (interquartile range, 2-5). Clinically presumed and/or cultured bacterial superinfections were reported in 5 (16%) patients. Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with COVID-19. Results of this trial provide rationale for a randomized, controlled trial of low-dose tocilizumab in COVID-19.

Reducing the use of empiric antibiotic therapy in COVID-19 on hospital admission.

Abstract: Empiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19. This was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics > 48 h following admission or if another source of infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics. A total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n = 76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n = 170), p < 0.001. The median DOT in the post-intervention group was 1.3 days shorter (p < 0.001) than the pre-intervention group, and antibiotics directed at atypical bacteria DOT was reduced by 2.8 days (p < 0.001). More patients in the post-intervention group were initiated on antibiotics based on criteria consistent with our guideline (68% versus 87%, p = 0.001). There were no differences between groups in terms of clinical outcomes. Following the implementation of a guideline outlining recommendations for initiating and discontinuing antibiotics for CABP among COVID-19 inpatients, we observed a reduction in antibiotic prescribing and DOT. The guideline also resulted in a significant increase in the rate of guideline-congruent empiric antibiotic initiation.

The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock.

Abstract: Background Early antibiotics are fundamental to sepsis management. Second-dose antibiotic delays were associated with increased mortality in a recent study. Study objectives include: 1) determine factors associated with delays in second-dose antibiotic administration; 2) evaluate if delays influence clinical outcomes. Methods ED-treated adults (≥18 years; n = 1075) with severe sepsis or septic shock receiving ≥2 doses of intravenous antibiotics were assessed, retrospectively, for second-dose antibiotic delays (dose time > 25% of recommended interval). Predictors of delay and impact on outcomes were determined, controlling for MEDS score, 30 mL/kg fluids and antibiotics within three hours of sepsis onset, lactate, and renal failure, among others. Results In total, 335 (31.2%) patients had delayed second-dose antibiotics. A total of 1864 second-dose antibiotics were included, with 354 (19.0%) delays identified by interval (delayed/total doses): 6-h (36/67) = 53.7%; 8-h (165/544) = 30.3%; 12-h (114/436) = 26.1%; 24-h (21/190) = 8.2%; 48-h (0/16) = 0%. In-hospital mortality in the timely group was 15.5% (shock-17.6%) and 13.7% in the delayed group (shock-16.9%). Increased odds of delay were observed for ED boarding (OR 2.54, 95% 1.81–3.55), shorter dosing intervals (6/8-h- OR 2.99, 95% CI 1.95–4.57; 12-h- OR 2.46, 95% CI 1.72–3.51), receiving 30 mL/kg fluids by three hours (OR 1.42, 95% CI 1.06–1.90), and renal failure (OR 2.57, 95% CI 1.50–4.39). Delays were not associated with increased mortality (OR 0.87, 95% CI 0.58–1.29) or other outcomes. Conclusions Factors associated with delayed second-dose antibiotics include ED boarding, antibiotics requiring more frequent dosing, receiving 30 mL/kg fluid, and renal failure. Delays in second-dose administration were not associated with mortality or other outcomes.

Investigating the impact of a β-lactam allergy label on preoperative antibiotic prophylaxis administration

Abstract: Objective: Surgical site infection (SSI) is a common postprocedure complication that may be prevented by adhering to established recommendations, including administration of preoperative antibiotic prophylaxis. Patients with a β-lactam allergy (BLA) label have an increased risk of SSI. We sought to evaluate the appropriateness of preoperative antibiotic prophylaxis in patients labeled with a BLA compared those without a BLA. Methods: This was a single-center, retrospective, matched cohort study of adult patients who underwent a clean or clean-contaminated knee replacement, abdominal hysterectomy, colorectal surgery, or coronary artery bypass graft (CABG). Patients with a BLA label were matched to patients without a BLA label based on procedure, age, and body mass index (BMI). The primary end point was the rate of appropriate preoperative antibiotic prophylaxis, including antibiotic selection and timing prior to incision. Results: In total, 260 patients were included. Knee replacement (38%) was the most common procedure, followed by abdominal hysterectomy (25%), colorectal surgery (18%), and CABG (18%). Appropriate preoperative antibiotic prophylaxis was higher among patients without a BLA (76% vs 37%; P < .001). Among patients with a mild-to-moderate reaction or intolerance, 29 (53%) received antibiotics that would have been appropriate only if the patient had had a severe BLA. Patients with a BLA were more likely to have had an antibiotic omitted from the prophylactic regimen (44% vs 4%; P < .001). Conclusion: Patients with a BLA were more likely to receive inappropriate preoperative antibiotic prophylaxis, attributed to misinterpretation of BLA labels and antibiotic omissions. Optimizing antibiotic prophylaxis among patients with BLAs remains an area of opportunity to prevent SSIs.

Impact of a structured interview on beta-lactam reaction documentation quality

Abstract: Incomplete documentation of β-lactam reactions often leads to inappropriate antibiotic prescribing. The objective of this study was to evaluate the impact of a structured interview on the quality of β-lactam reaction documentation. After 203 interviews, documentation of the core components of a β-lactam reaction improved (48% vs 1%; P < .001).