A multicenter evaluation of antibacterial use in hospitalized patients through the SARS-Cov-2 pandemic waves.

BACKGROUND: Excessive use of antibiotics has been reported during the SARS-CoV-2 pandemic. We evaluated trends in antibiotic use and culture positive Gram-negative (GN)/Gram-positive (GP) pathogens in US hospitalized patients before and during the SARS-CoV-2 pandemic. METHODS: This multicenter, retrospective study included patients from 271 US facilities with > 1-day inpatient admission with discharge or death between July 1, 2019, and October 30, 2021, in the BD Insights Research Database. We evaluated microbiological testing data, antibacterial use, defined as antibacterial use ≥ 24 h in admitted patients, and duration of antibacterial therapy. RESULTS: Of 5,518,744 patients included in the analysis, 3,729,295 (67.6%) patients were hospitalized during the pandemic with 2,087,774 (56.0%) tested for SARS-CoV-2 and 189,115 (9.1%) testing positive for SARS-CoV-2. During the pre-pandemic period, 36.2% were prescribed antibacterial therapy and 9.3% tested positive for select GN/GP pathogens. During the SARS-CoV-2 pandemic, antibacterial therapy (57.8%) and positive GN/GP culture (11.9%) were highest in SARS-CoV-2-positive patients followed by SARS-CoV-2-negative patients (antibacterial therapy, 40.1%; GN/GP, pathogens 11.0%), and SARS-CoV-2 not tested (antibacterial therapy 30.4%; GN/GP pathogens 7.2%). Multivariate results showed significant decreases in antibacterial therapy and positive GN/GP cultures for both SARS-CoV-2-positive and negative patients during the pandemic, but no significant overall changes from the pre-pandemic period to the pandemic period. CONCLUSIONS: There was a decline in both antibacterial use and positive GN/GP pathogens in patients testing positive for SARS-CoV-2. However, overall antibiotic use was similar prior to and during the pandemic. These data may inform future efforts to optimize antimicrobial stewardship and prescribing.

Morbidity and mortality of hospitalised patients with candidemia during the various severe acute respiratory syndrome coronavirus 2 pandemic waves: A multicentre evaluation of 248 US hospitals.

BACKGROUND: Studies evaluating outcomes of COVID-19 patients with candidemia are limited and have only evaluated a single timepoint during the pandemic. OBJECTIVES: To compare the prevalence and outcomes associated with candidemia in patients based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status and through the various pandemic waves (1 March 2020-5 March 2022). PATIENTS/METHODS: Multicentre, retrospective cohort analysis of data from 248 US medical facilities using the BD Insights Research Database (Becton, Dickinson and Company, Franklin Lakes, New Jersey, USA). Eligible patients were adults aged ≥18 years who were hospitalised for >1 day, had a SARS-CoV-2 test and a positive blood culture for Candida spp. RESULTS: During the study time frame, there were 2,402,879 hospital admissions; 234,903 (9.7%) and 2,167,976 (90.3%) patients were SARS-CoV-2 positive and negative, respectively. A significantly higher rate of candidemia/1000 admissions was observed in SARS-CoV-2-positive patients compared to SARS-CoV-2-negative patients (3.18 vs. 0.99; p < .001). The highest candidemia rate for SARS-CoV-2-positive patients was observed during the Alpha SARS-CoV-2 wave (June 2020-August 2020) with the lowest candidemia rate during the Omicron wave. Hospital mortality was significantly higher in SARS-CoV-2-positive patients compared to SARS-CoV-2-negative patients with candidemia (59.6% vs. 30.8%; p < .001). When evaluating the mortality rate through the various pandemic waves, the rate for the overall population did not change. CONCLUSIONS: Our study indicates high morbidity and mortality for hospitalised patients with COVID-19 and candidemia which was consistent throughout the pandemic. Patients with COVID-19 are at an increased risk for candidemia; importantly, the magnitude of which may differ based on the circulating variant.

Hospital-onset bacteremia and fungemia: An evaluation of predictors and feasibility of benchmarking comparing two risk-adjusted models among 267 hospitals.

OBJECTIVES: To evaluate the prevalence of hospital-onset bacteremia and fungemia (HOB), identify hospital-level predictors, and to evaluate the feasibility of an HOB metric. METHODS: We analyzed 9,202,650 admissions from 267 hospitals during 2015-2020. An HOB event was defined as the first positive blood-culture pathogen on day 3 of admission or later. We used the generalized linear model method via negative binomial regression to identify variables and risk markers for HOB. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables plus additional measures of blood-culture testing practices. Performance of each model was compared against the unadjusted rate of HOB. RESULTS: Overall median rate of HOB per 100 admissions was 0.124 (interquartile range, 0.00-0.22). Facility-level predictors included bed size, sex, ICU admissions, community-onset (CO) blood culture testing intensity, and hospital-onset (HO) testing intensity, and prevalence (all P < .001). In the complex model, CO bacteremia prevalence, HO testing intensity, and HO testing prevalence were the predictors most associated with HOB. The complex model demonstrated better model performance; 55% of hospitals that ranked in the highest quartile based on their raw rate shifted to a lower quartile when the SIR from the complex model was applied. CONCLUSIONS: Hospital descriptors, aggregate patient characteristics, community bacteremia and/or fungemia burden, and clinical blood-culture testing practices influence rates of HOB. Benchmarking an HOB metric is feasible and should endeavor to include both facility and clinical variables.

A Multicenter Comparison of Prevalence and Predictors of Antimicrobial Resistance in Hospitalized Patients Before and During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

Background: Antibacterial therapy is frequently used in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without evidence of bacterial infection, prompting concerns about increased antimicrobial resistance (AMR). We evaluated trends in AMR before and during the SARS-CoV-2 pandemic. Methods: This multicenter, retrospective cohort analysis included hospitalized adults aged ≥18 years with >1-day inpatient admission and a record of discharge or death from 271 US facilities in the BD Insights Research Database. We evaluated rates of AMR events, defined as positive cultures for select gram-negative and gram-positive pathogens from any source, with nonsusceptibility reported by commercial panels before (1 July 2019-29 February 2020) and during (1 March 2020-30 October 2021) the SARS-CoV-2 pandemic. Results: Of 5 518 666 admissions evaluated, AMR rates per 1000 admissions were 35.4 for the prepandemic period and 34.7 for the pandemic period (P ≤ .0001). In the pandemic period, AMR rates per 1000 admissions were 49.2 for SARS-CoV-2-positive admissions, 41.1 for SARS-CoV-2-negative admissions, and 25.7 for patients untested (P ≤ .0001). AMR rates per 1000 admissions among community-onset infections during the pandemic were lower versus prepandemic levels (26.1 vs 27.6; P < .0001), whereas AMR rates for hospital-onset infections were higher (8.6 vs 7.7; P < .0001), driven largely by SARS-CoV-2-positive admissions (21.8). AMR rates were associated with overall antimicrobial use, rates of positive cultures, and higher use of inadequate empiric therapy. Conclusions: Although overall AMR rates did not substantially increase from prepandemic levels, patients tested for SARS-CoV-2 infection had a significantly higher rate of AMR and hospital-onset infections. Antimicrobial and diagnostic stewardship is key to identifying this high-risk AMR population.

Epidemiology and outcomes of culture-positive bloodstream pathogens prior to and during the SARS-CoV-2 pandemic: a multicenter evaluation.

BACKGROUND: Bloodstream infections (BSIs) are an important cause of morbidity and mortality in hospitalized patients. We evaluate incidence of community- and hospital-onset BSI rates and outcomes before and during the SARS-CoV-2 pandemic. METHODS: We conducted a retrospective cohort study evaluating patients who were hospitalized for ≥ 1 day with discharge or death between June 1, 2019, and September 4, 2021, across 271 US health care facilities. Community- and hospital-onset BSI and related outcomes before and during the SARS-CoV-2 pandemic, including intensive care admission rates, and overall and ICU-specific length of stay (LOS) was evaluated. Bivariate correlations were calculated between the pre-pandemic and pandemic periods overall and by SARS-CoV-2 testing status. RESULTS: Of 5,239,692 patient admissions, there were 20,113 community-onset BSIs before the pandemic (11.2/1000 admissions) and 39,740 (11.5/1000 admissions) during the pandemic (P ≤ 0.0062). Corresponding rates of hospital-onset BSI were 2,771 (1.6/1000 admissions) and 6,864 (2.0/1000 admissions; P < 0.0062). Compared to the pre-pandemic period, rates of community-onset BSI were higher in patients who tested negative for SARS-CoV-2 (15.8/1000 admissions), compared with 9.6/1000 BSI admissions among SARS-CoV-2-positive patients. Compared with patients in the pre-pandemic period, SARS-CoV-2-positive patients with community-onset BSI experienced greater ICU admission rates (36.6% vs 32.8%; P < 0.01), greater ventilator use (10.7% vs 4.7%; P < 0.001), and longer LOS (12.2 d vs 9.1 d; P < 0.001). Rates of hospital-onset BSI were higher in the pandemic vs the pre-pandemic period (2.0 vs 1.5/1000; P < 0.001), with rates as high a 7.3/1000 admissions among SARS-CoV-2-positive patients. Compared to the pre-pandemic period, SARS-CoV-2-positive patients with hospital-onset BSI had higher rates of ICU admission (72.9% vs 55.4%; P < 0.001), LOS (34.8 d vs 25.5 d; P < 0.001), and ventilator use (52.9% vs 21.5%; P < 0.001). Enterococcus species, Staphylococcus aureus, Klebsiella pneumoniae, and Candida albicans were more frequently detected in the pandemic period. CONCLUSIONS AND RELEVANCE: This nationally representative study found an increased risk of both community-onset and hospital-onset BSI during the SARS-CoV-2 pandemic period, with the largest increased risk in hospital-onset BSI among SARS-CoV-2-positive patients. SARS-CoV-2 positivity was associated with worse outcomes.

Mortality Among US Patients Hospitalized With SARS-CoV-2 Infection in 2020.

Importance: Mortality is an important measure of the severity of a pandemic. This study aimed to understand how mortality by age of hospitalized patients who were tested for SARS-CoV-2 has changed over time. Objective: To evaluate trends in in-hospital mortality among patients who tested positive for SARS-CoV-2. Design, Setting, and Participants: This retrospective cohort study included patients who were hospitalized for at least 1 day at 1 of 209 US acute care hospitals of variable size, in urban and rural areas, between March 1 and November 21, 2020. Eligible patients had a SARS-CoV-2 polymerase chain reaction (PCR) or antigen test within 7 days of admission or during hospitalization, and a record of discharge or in-hospital death. Exposure: SARS-CoV-2 positivity. Main Outcomes and Measures: SARS-CoV-2 infection was defined as a positive SARS-CoV-2 PCR or antigen test within 7 days before admission or during hospitalization. Mortality was extracted from electronically available data. Results: Among 503 409 admitted patients, 42 604 (8.5%) had SARS-CoV-2-positive tests. Of those with SARS-CoV-2-positive tests, 21 592 (50.7%) were male patients. Hospital admissions among patients with SARS-CoV-2-positive tests were highest in the group aged 65 years or older (19 929 [46.8%]), followed by those aged 50 to 64 years (11 602 [27.2%]) and 18 to 49 years (10 619 [24.9%]). Hospital admissions among patients 18 to 49 years of age increased from 1099 of 5319 (20.7%) in April to 1266 of 4184 (30.3%) in June and 2156 of 7280 (29.6%) in July, briefly exceeding those in the group 50 to 64 years of age (June: 1194 of 4184 [28.5%]; 2039 of 7280 [28.0%]). Patients with SARS-CoV-2-positive tests had higher in-hospital mortality than patients with SARS-CoV-2-negative tests (4705 [11.0%] vs 11 707 of 460 805 [2.5%]; P < .001). In-hospital mortality rates increased with increasing age for both patients with SARS-CoV-2-negative tests and SARS-CoV-2-positive tests. In patients with SARS-CoV-2-negative tests, mortality increased from 45 of 11 255 (0.4%) in those younger than 18 years to 4812 of 107 394 (4.5%) in those older than 75 years. In patients with SARS-CoV-2-positive tests, mortality increased from 1 of 454 (0.2%) of those younger than 18 years to 2149 of 10 287 (20.9%) in those older than 75 years. In-hospital mortality rates among patients with SARS-CoV-2-negative tests were similar for male and female patients (6273 of 209 086 [3.0%] vs 5538 of 251 719 [2.2%]) but higher mortality was observed among male patients with SARS-CoV-2-positive tests (2700 of 21 592 [12.5%]) compared with female patients with SARS-CoV-2-positive tests (2016 of 21 012 [9.60%]). Overall, in-hospital mortality increased from March to April (63 of 597 [10.6%] to 1047 of 5319 [19.7%]), then decreased significantly to November (499 of 5350 [9.3%]; P = .04), with significant decreases in the oldest age groups (50-64 years: 197 of 1542 [12.8%] to 73 of 1341 [5.4%]; P = .02; 65-75 years: 269 of 1182 [22.8%] to 137 of 1332 [10.3%]; P = .006; >75 years: 535 of 1479 [36.2%] to 262 of 1505 [17.4%]; P = .03). Conclusions and Relevance: This nationally representative study supported the findings of smaller, regional studies and found that in-hospital mortality declined across all age groups during the period evaluated. Reductions were unlikely because of a higher proportion of younger patients with lower in-hospital mortality in the later period.

Effect of Inadequate Empiric Antibacterial Therapy on Hospital Outcomes in SARS-CoV-2-Positive and -Negative US Patients With a Positive Bacterial Culture: A Multicenter Evaluation From March to November 2020.

BACKGROUND: Increased utilization of antimicrobial therapy has been observed during the coronavirus disease 2019 pandemic. We evaluated hospital outcomes based on the adequacy of antibacterial therapy for bacterial pathogens in US patients. METHODS: This multicenter retrospective study included patients with ≥24 hours of inpatient admission, ≥24 hours of antibiotic therapy, and discharge/death from March to November 2020 at 201 US hospitals in the BD Insights Research Database. Included patients had a test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a positive bacterial culture (gram-positive or gram-negative). We used generalized linear mixed models to evaluate the impact of inadequate empiric therapy (IET), defined as therapy not active against the identified bacteria or no antimicrobial therapy in the 48 hours following culture, on in-hospital mortality and hospital and intensive care unit length of stay (LOS). RESULTS: Of 438 888 SARS-CoV-2-tested patients, 39 203 (8.9%) had positive bacterial cultures. Among patients with positive cultures, 9.4% were SARS-CoV-2 positive, 74.4% had a gram-negative pathogen, 25.6% had a gram-positive pathogen, and 44.1% received IET for the bacterial infection. The odds of mortality were 21% higher for IET (odds ratio [OR], 1.21; 95% CI, 1.10-1.33; P < .001) compared with adequate empiric therapy. IET was also associated with increased hospital LOS (LOS, 16.1 days; 95% CI, 15.5-16.7 days; vs LOS, 14.5 days; 95% CI, 13.9-15.1 days; P < .001). Both mortality and hospital LOS findings remained consistent for SARS-CoV-2-positive and -negative patients. CONCLUSIONS: Bacterial pathogens continue to play an important role in hospital outcomes during the pandemic. Adequate and timely therapeutic management may help ensure better outcomes.

A multicenter analysis of the clinical microbiology and antimicrobial usage in hospitalized patients in the US with or without COVID-19.

BACKGROUND: Past respiratory viral epidemics suggest that bacterial infections impact clinical outcomes. There is minimal information on potential co-pathogens in patients with coronavirus disease-2019 (COVID-19) in the US. We analyzed pathogens, antimicrobial use, and healthcare utilization in hospitalized US patients with and without severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). METHODS: This multicenter retrospective study included patients with > 1 day of inpatient admission and discharge/death between March 1 and May 31, 2020 at 241 US acute care hospitals in the BD Insights Research Database. We assessed microbiological testing data, antimicrobial utilization in admitted patients with ≥24 h of antimicrobial therapy, and length of stay (LOS). RESULTS: A total of 141,621 patients were tested for SARS-CoV-2 (17,003 [12.0%] positive) and 449,339 patients were not tested. Most (> 90%) patients tested for SARS-CoV-2 had additional microbiologic testing performed compared with 41.9% of SARS-CoV-2-untested patients. Non-SARS-CoV-2 pathogen rates were 20.9% for SARS-CoV-2-positive patients compared with 21.3 and 27.9% for SARS-CoV-2-negative and -untested patients, respectively. Gram-negative bacteria were the most common pathogens (45.5, 44.1, and 43.5% for SARS-CoV-2-positive, -negative, and -untested patients). SARS-CoV-2-positive patients had higher rates of hospital-onset (versus admission-onset) non-SARS-CoV-2 pathogens compared with SARS-CoV-2-negative or -untested patients (42.4, 22.2, and 19.5%, respectively), more antimicrobial usage (68.0, 45.2, and 25.1% of patients), and longer hospital LOS (mean [standard deviation (SD)] of 8.6 [11.4], 5.1 [8.9], and 4.2 [8.0] days) and intensive care unit (ICU) LOS (mean [SD] of 7.8 [8.5], 3.6 [6.2], and 3.6 [5.9] days). For all groups, the presence of a non-SARS-CoV-2 pathogen was associated with increased hospital LOS (mean [SD] days for patients with versus without a non-SARS-CoV-2 pathogen: 13.7 [15.7] vs 7.3 [9.6] days for SARS-CoV-2-positive patients, 8.2 [11.5] vs 4.3 [7.9] days for SARS-CoV-2-negative patients, and 7.1 [11.0] vs 3.9 [7.4] days for SARS-CoV-2-untested patients). CONCLUSIONS: Despite similar rates of non-SARS-CoV-2 pathogens in SARS-CoV-2-positive, -negative, and -untested patients, SARS-CoV-2 was associated with higher rates of hospital-onset infections, greater antimicrobial usage, and extended hospital and ICU LOS. This finding highlights the heavy burden of the COVID-19 pandemic on healthcare systems and suggests possible opportunities for diagnostic and antimicrobial stewardship.