Vikas Gupta

Rapid pathogen identification, resistance detection, and susceptibility profiling improve antimicrobial prescribing and associated outcomes, but fragmented workflows lead to inefficiencies and are costly. We evaluated a research-use-only (RUO) approach using ASTar remnant bacterial suspension from routine antimicrobial susceptibility testing (AST) for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) pathogen identification and lateral flow assay (LFA)-based detection of targeted resistance mechanisms. Gram-negative bacterial strains from reference and curated resistance collections (CDC1, ARLG2, and ATCC3) ( n = 129) were contrived into blood culture bottles and processed in the ASTar System using the ASTar BC G- Kit (Q-linea AB, Sweden). Under RUO conditions, remnant bacterial suspensions were collected ~1–2 h after ASTar run initiation and analyzed using NG Test CTX-M Multi, NG Test CARBA-5, NG Test Acineto-5 RUO, and MALDI-TOF MS. Mean (±SD) remnant suspension volume was 2,722 μL (±300 µL). All samples yielded high-confidence MALDI-TOF MS scores (>2.0), with five initially scoring blaCTX-M positive/negative (32/32) and with 60 or 61 target carbapenemase-positive/negative isolates. Testing of a subset of samples to mimic reflex workflows with ASTar phenotypic results did not affect LFA performance ( n = 35; 23 Enterobacterales, 3 Pseudomonas aeruginosa , and 9 Acinetobacter baumannii ). Cost savings can be realized versus commercial multiplex PCR. This integrated approach of ~6 h rapid phenotypic AST with same-run identification and resistance detection (1–2 h from instrument start) or reflex testing upon availability of ASTar results may support earlier susceptibility results and offer cost savings to current workflows. IMPORTANCE: Rapid, integrated diagnostic workflows are recommended and essential for improving patient outcomes in bloodstream infections, where delays in pathogen identification and resistance detection can compromise timely antimicrobial therapy. Current workflows often rely on multiple platforms, increasing turnaround time and laboratory burden. Additionally, the clinical impact of rapid diagnostic results is dependent on timely interpretation and implementation within antimicrobial stewardship frameworks, which may involve complex decision algorithms. This study demonstrates that remnant bacterial suspensions generated during routine antimicrobial susceptibility testing (AST) using the ASTar System can be recovered and utilized for rapid matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and lateral flow assay-based resistance detection. By enabling pathogen identification and/or resistance detection within ~1–2 h of AST initiation or resistance detection via reflex testing, this approach reduces duplicate sample testing and may enable earlier access to rapid microbiological results.

Introduction Urinary tract infections (UTIs) caused by antimicrobial-resistant Enterobacterales are a global health threat. There are limited surveillance data available to characterize the prevalence of antimicrobial resistance among outpatients in the United States (US). Methods This retrospective cohort (database) study investigated co-resistance among Escherichia coli and Klebsiella pneumoniae urinary isolates from US female outpatients aged ≥ 12 years with presumed uncomplicated UTI (uUTI), ≥ 3 months of data (2011–2019), and antimicrobial susceptibility testing results. Eligible isolates were the first urinary E. coli or K. pneumoniae isolate per patient collected within 30 days; classified as not susceptible (NS) if antimicrobial susceptibility testing results were intermediate or resistant to each antibiotic tested. Four resistance phenotypes were identified: NS to fluoroquinolones (FQ), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NTF), and extended-spectrum β-lactamase+/third-generation cephalosporin (ESBL+/3GC NS). Co-resistance phenotypes included all possible combinations of resistance to ≥ 2 drug classes. Results Of 1,513,882 E. coli isolates and 250,719 K. pneumoniae isolates, 856,918 and 187,459 isolates with ≥ 1 resistance phenotype were included in the analysis, respectively. The most common resistance phenotypes were SXT NS for the E. coli isolates (44.8%) and NTF NS for the K. pneumoniae isolates (75.5%), while ESBL+/3GC NS comprised 11.2 and 5.9%, respectively. Among ESBL+/3GC NS E. coli isolates, 72.4, 56.7, and 46.6% were co-resistant to FQ, SXT, and FQ + SXT, respectively. For ESBL+/3GC NS K. pneumoniae isolates, 65.7 and 45.7% were co-resistant to SXT and FQ + SXT. Conclusion Both species exhibited high rates of co-resistance, emphasizing the need to raise awareness of co-resistance and of the unmet need for effective treatment options for uUTI.

Growing evidence indicates antimicrobial resistance disproportionately affects individuals living in socially vulnerable areas. This study evaluated the association between the CDC/ATSDR Social Vulnerability Index (SVI) and Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) in the United States. Adult patients ≥18 years with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011 to December 2022 with zip codes of residence were evaluated across 177 facilities in the BD Insights Research Database. Isolates were identified as SP AMR if they were non-susceptible to ≥1 antibiotic class (macrolide, tetracycline, extended-spectrum cephalosporins, or penicillin). Associations between SP AMR and SVI score (overall and themes) were evaluated using generalized estimating equations with repeated measurements within county to account for within-cluster correlations. Of 8008 unique SP isolates from 574 US counties across 39 states, the overall proportion of AMR was 49.9%. A significant association between socioeconomic status (SES) theme and SP AMR was detected with higher SES theme SVI score (indicating greater social vulnerability) associated with greater risk of AMR. On average, a decile increase of SES, indicating greater vulnerability, was associated with a 1.28% increased risk of AMR (95% confidence interval [CI], .61%, 1.95%; P = .0002). A decile increase of household characteristic score was associated with a 0.81% increased risk in SP AMR (95% CI, .13%, 1.49%; P = .0197). There was no association between racial/ethnic minority status, housing type and transportation theme, or overall SVI score and SP AMR. SES and household characteristics were the SVI themes most associated with SP AMR.

New antibiotics have been developed to combat antibiotic-resistant Gram-negative pathogens, which are difficult to treat and associated with poor clinical outcomes. We conducted a multicenter evaluation of real-world testing practices and susceptibility to newer antibiotics. Our study included 71 facilities in the BD Insights Research Database (2018–2022) and involved adult patients with a positive culture for Enterobacterales or Pseudomonas aeruginosa and facility-reported antibiotic susceptibility data for cefiderocol (FDC), ceftazidime–avibactam (CZA), ceftolozane–tazobactam (C/T), eravacycline (ERV), imipenem–relabactam (I-R), or meropenem–vaborbactam (MVB). A total of 27,531 susceptibility results were available, including 22,111 (80.3%) Enterobacterales and 5,420 (19.7%) P . aeruginosa. Escherichia coli (11,882 [43.2%]) was the most frequently tested potential pathogen, and CZA (13,567 [49.3%]) and C/T (13,299 [48.3%]) had the greatest numbers of susceptibility results. For the other four antibiotics, susceptibility data were available for fewer than 2% of isolates. Susceptibility comparisons should be considered with caution. Among isolates tested, CZA had the highest susceptibility rates for total Enterobacterales (98.7%) and multidrug-resistant (92.9%) and carbapenem-non-susceptible (85.0%) isolates. For P. aeruginosa , FDC had the highest susceptibility rates for total (95.6%) and carbapenem-non-susceptible (93.3%) isolates. The susceptibility of carbapenem-non-susceptible Enterobacterales to CZA and C/T decreased modestly from 2020 to 2022, but carbapenem-non-susceptible P. aeruginosa susceptibility rates increased. We conclude that Gram-negative pathogens have high real-world susceptibility rates to newer antibiotics but may show important differences across resistance profiles. Newer antibiotics are a valuable option for the management of resistant Enterobacterales and P. aeruginosa . Additional effort may be required to integrate these agents into routine clinical care. IMPORTANCE: Newer antibiotics against Gram-negative pathogens provide important treatment options, especially for antibiotic-resistant bacteria, but little is known about their use during routine clinical care. To use these agents appropriately, clinicians need to have access to timely susceptibility data. We evaluated 27,531 facility-reported susceptibility results from the BD Insights Research Database to gain a better understanding of real-world testing practices and susceptibility rates for six newer antibiotics. Escherichia coli was the most frequently tested potential pathogen, and ceftazidime–avibactam and ceftolozane–tazobactam had the greatest numbers of susceptibility results. For cefiderocol, eravacycline, imipenem–relabactam, and meropenem–vaborbactam, susceptibility data were available for fewer than 2% of isolates. Susceptibility comparisons should be considered with caution. Ceftazidime–avibactam had the highest susceptibility rates for Enterobacterales while cefiderocol had the highest susceptibility rates for Pseudomonas aeruginosa . New antibiotics have the potential to improve the management of Gram-negative infections, but their use may be hampered by the absence of susceptibility data.

Background: Antibiotic usage and antibiotic resistance (ABR) patterns changed during the COVID-19 pandemic. Inadequate empiric antibiotic therapy (IET) is a significant public health problem and contributes to ABR. We evaluated factors associated with IET before and during the COVID-19 pandemic to determine the impact of the pandemic on antibiotic management. Methods: This multicenter, retrospective cohort analysis included hospitalized US adults who had a positive bacterial culture (specified gram-positive or gram-negative bacteria) from July 2019 to October 2021 in the BD Insights Research Database. IET was defined as antibacterial therapy within 48 h that was not active against the bacteria. ABR results were based on susceptibility testing and reports from local facilities. Multivariate analysis was used to identify risk factors associated with IET in patients with any positive bacterial culture and ABR-positive cultures, including multidrug-resistant (MDR) bacteria. Results: Of 278,344 eligible patients in 269 hospitals, 56,733 (20.4%) received IET; rates were higher in patients with ABR-positive (n = 93,252) or MDR-positive (n = 39,000) cultures (34.9% and 45.0%, respectively). Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients had significantly higher rates of IET (25.9%) compared with SARS-CoV-2-negative (20.3%) or not tested (19.7%) patients overall and in the ABR and MDR subgroups. Patients with ABR- or MDR-positive cultures had more days of therapy and longer lengths of stay. In multivariate analyses, ABR, MDR, SARS-CoV-2-positive status, respiratory source, and prior admissions were identified as key IET risk factors. Conclusions: IET remained a persistent problem during the COVID-19 pandemic and occurred at higher rates in patients with ABR/MDR bacteria or a co-SARS-CoV-2 infection.

Objectives: To evaluate the incidence of a candidate definition of healthcare facility-onset, treated Clostridioides difficile (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data.Methods: We analyzed 9,134,276 admissions from 265 hospitals during 2015–2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug. The generalized linear model method via negative binomial regression was used to identify predictors. 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 and CD testing practices. The performance of each model was compared against cHT-CDI unadjusted rates.Results: The median rate of cHT-CDI events per 100 admissions was 0.134 (interquartile range, 0.023–0.243). Hospital variables associated with cHT-CDI included the following: higher community-onset CDI (CO-CDI) prevalence; highest-quartile length of stay; bed size; percentage of male patients; teaching hospitals; increased CD testing intensity; and CD testing prevalence. The complex model demonstrated better model performance and identified the most influential predictors: hospital-onset testing intensity and prevalence, CO-CDI rate, and community-onset testing intensity (negative correlation). Moreover, 78% of the hospitals ranked in the highest quartile based on raw rate shifted to lower percentiles when we applied the SIR from the complex model.Conclusions: Hospital descriptors, aggregate patient characteristics, CO-CDI burden, and clinical testing practices significantly influence incidence of cHT-CDI. Benchmarking a cHT-CDI metric is feasible and should include facility and clinical variables.

Antimicrobial resistance (AMR) poses a significant challenge for treating pneumococcal disease. This study assessed AMR trends in Streptococcus pneumoniae from US children. We evaluated antibiotic resistance, defined as facility antimicrobial susceptibility reports of intermediate/resistant, in 30-day non-duplicate S. pneumoniae isolates from children (S. pneumoniae isolates analyzed, 6,641 (87.3%) were from non-invasive sources. Resistance rates were higher in non-invasive versus invasive isolates. Isolates showed high observed rates of resistance to ≥1 drug class (56.8%), ≥2 drug classes (30.7%), macrolides (39.9%), and penicillin (39.6%) and significant annual increases in resistance to ≥1 drug class (+0.9%), ≥2 drug classes (+1.8%), and macrolides (+5.0%). Among US children over the last decade, S. pneumoniae isolates showed persistently high rates of resistance to antibiotics and significant increases in ≥1 drug class, ≥2 drug classes, and macrolide resistance rates. Efforts to address AMR in S. pneumoniae may require vaccines targeting resistant serotypes and antimicrobial stewardship efforts.

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. 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. 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. 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.