Background Antibacterials may be initiated out of concern for bacterial co-infection in patients with COVID-19. We determined prevalence and predictors of empiric antibacterial therapy and community-onset bacterial co-infections in hospitalized patients with COVID-19. Methods Randomly sampled cohort of 1705 patients hospitalized with COVID-19 in 38 Michigan hospitals between 3/13/2020-6/18/2020. Data were collected on early (prescribed within 2 days of hospitalization) empiric antibacterial therapy and community-onset bacterial co-infections (positive culture or diagnostic test within 3 days). Poisson generalized estimating equation models were used to assess predictors of empiric antibacterial use. Results Of 1705 patients with COVID-19, 56.6% were prescribed early empiric antibacterial therapy; 3.5% (59/1705) had a confirmed community-onset bacterial infection. Across hospitals, early empiric antibacterial use varied from 27%-84%. Patients were more likely to receive early empiric antibacterial therapy if they were older (adjusted rate ratio [ARR]: 1.04 [1.00-1.08] per 10 years), had a lower body mass index (ARR: 0.99 [0.99-1.00] per kg/m 2), had more severe illness (e.g., severe sepsis, ARR: 1.16 [1.07-1.27]), had a lobar infiltrate (ARR: 1.21 [1.04-1.42]), or were admitted to a for-profit hospital (ARR: 1.30 [1.15-1.47]). Over time, COVID-19 test turnaround time (returned ≤1 day in March [54.2%, 461/850] vs. in April [85.2%, 628/737], P<.001) and empiric antibacterial use (ARR: 0.71 [0.63-0.81] April vs. March) decreased. Conclusion The prevalence of confirmed community-onset bacterial co-infections was low. Despite this, half of patients received early empiric antibacterial therapy. Antibacterial use varied widely by hospital. Reducing COVID-19 test turnaround time and supporting stewardship could improve antibacterial use.

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.

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