Search

Background: Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years., Methods: We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region., Findings: Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type., Interpretation: Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved., Funding: The Centers for Disease Control and Prevention., Competing Interests: Declaration of interests NPK reports support for other work from Sanofi Pasteur, Merck, Pfizer, Seqirus, and GSK, unpaid expert panel membership for a planned hepatitis E phase 2 vaccine clinical trial among pregnant women in Pakistan, and unpaid membership on the Western States COVID-19 Scientific Safety Review Workgroup, Board on Population Health and Public Health Practice, National Academies of Science, Engineering, and Medicine, and National Vaccine Advisory Committee Safety Subcommittee. SJG reports funding from the National Institutes of Health's National Center for Advancing Translation Sciences and National Institute of Mental Health. TCO reports consulting fees from Regenstrief Institute as a domain expert in patient matching in global health informatics, travel support from Regenstrief Institute and Patient-Centered Outcomes Research institute, and holds a patent (patent number PCT/US2018/047961). MBD, BED, and WFF report an additional CDC contract for the Vaccine Safety Datalink. TS reports unpaid participation as a member of the Advisory Committee on the Immunization Practices Influenza Vaccine Work Group, is chief of the Utah Adult Immunization Coalition, and is a member of the Utah Department of Health and Human Services Scientific Advisory Committee on Vaccines. OZ reports funding from the National Institute of Allergy and Infectious Diseases (grant number R01AI168373). NPK, JT, and KG report a CDC contract for VISION (contract number 75D30123C17595). SR reports funding from Biofire and GSK. MB reports speaker bureau participation for Innoviva Specialty Therapeutics. CEM reports funding from AstraZeneca, GSK, National Institutes of Health, US Department of Defense, and Patient-Centered Outcomes Research Institute, payment or honoraria for a lecture from Pri-Med, and leadership on the American Lung Association of Minnesota board, the Minnesota Department of Health Long COVID Advisory Committee, and on the Minnesota Department of Health Asthma Care Advisory Committee. JAW, PKM, SWB, SER, and EAKR report a CDC contract for VISION (contract number 75D30121D12779). KD, SAI, SJG, TCO, MBD, KN, BED, WFF, CR, KSA, and CEM report payments made to their institution by CDC via Westat. All other authors declare no competing interests., (Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

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., (© 2024. GSK.)

Objective: This paper examines question-response sequences, in which clinicians asked questions to child patients who appear to interact using means other than the verbal mode of communication., Methods: Conversation Analysis methods were used to study questions in 46 paediatric palliative care consultations. These questions were directed towards children who observably used vocalisations and embodied modes of communication (e.g., gaze, gesture and facial expressions) but did not appear to use the verbal mode., Results: Most questions asked children either about their willingness and preferences for a proposed next activity, or their current feelings, experiences or intentions. Questions involved children by foregrounding their preferences and feelings. These questions occasioned contexts where the child's vocal or embodied conduct could be treated as a relevant response., Conclusion: This paper demonstrates how questions are used to involve children in consultations about their own healthcare, and how their views come to be understood by clinicians and family members, even when children interact using means other than the verbal mode of communication., Practice Implications: Questions can be asked of both children who do and do not verbally communicate. When asking questions, clinicians should be mindful of the modes of communication an individual child uses to consider how the child might meaningfully respond., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Author AH was a participant in the study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

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., (© 2023 Wiley-VCH GmbH.)

Background: Antimicrobial resistance (AMR) poses a significant challenge for treating pneumococcal disease. This study assessed AMR trends in Streptococcus pneumoniae from US children., Methods: We evaluated antibiotic resistance, defined as facility antimicrobial susceptibility reports of intermediate/resistant, in 30-day nonduplicate S pneumoniae isolates from children (<18 years of age) with invasive (blood or cerebrospinal fluid/neurological) or noninvasive (respiratory or ear/nose/throat) isolates at 219 US hospital inpatient/outpatient settings in the BD Insights Research Database (January 2011-February 2020). We used descriptive statistics to characterize the percentage of antimicrobial-resistant isolates and generalized estimating equations to assess variations in resistance over time., Results: Of 7605 S pneumoniae isolates analyzed, 6641 (87.3%) were from noninvasive sources. Resistance rates were higher in noninvasive 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%)., Conclusions: 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., Competing Interests: Potential conflicts of interest. S. M. and K. F. are employees of MSD and may own stock/stock options in Merck & Co, Inc. J. A. W., K. C. Y., and V. G. are employees of BD, which was contracted by MSD to conduct the study. K. C. Y. and V. G. also own stock in BD., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., (© 2023. The Author(s).)

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., (© 2022. The Author(s).)

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., Competing Interests: Potential conflicts of interest. K. A. B., L. A. P., and P. A. M. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, and are shareholders in Merck & Co, Inc. L. A. P. was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, and a shareholder in Merck & Co, Inc, at the time of the study. K. C. Y., J. A. W., C. A., and V. G. are employees of Becton, Dickinson & Company, which was contracted by Merck to conduct the study. K. C. Y. and V. G. also own stock in Becton, Dickinson & Company. All other authors report no potential conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Management of pneumococcal disease is complicated by high rates of antimicrobial resistance (AMR). This study assessed AMR trends for Streptococcus pneumoniae isolates from adults with pneumococcal disease., Methods: From January 2011 to February 2020, we evaluated 30-day nonduplicate S. pneumoniae isolates from 290 US hospitals (BD Insights Research Database) from adults (≥18 years) in inpatient and outpatient settings. Isolates were required to have ≥1 AMR result for invasive (blood, cerebrospinal fluid/neurologic) or noninvasive (respiratory or ear/nose/throat) pneumococcal disease samples. Determination of AMR was based on facility reports of intermediate or resistant. Descriptive statistics and generalized estimated equations were used to assess variations over time., Results: Over the study period, 34 039 S. pneumoniae isolates were analyzed (20 749 [61%] from noninvasive sources and 13 290 [39%] from invasive sources). Almost half (46.6%) of the isolates were resistant to ≥1 drug, and noninvasive isolates had higher rates of AMR than invasive isolates. Total S. pneumoniae isolates had high rates of resistance to macrolides (37.7%), penicillin (22.1%), and tetracyclines (16.1%). Multivariate modeling identified a significant increasing trend in resistance to macrolides (+1.8%/year; P  < .001). Significant decreasing trends were observed for penicillin (-1.6%/year; P  < .001), extended-spectrum cephalosporins (ESCs; -0.35%/year; P  < .001), and ≥3 drugs (-0.5%/year; P  < .001)., Conclusions: Despite decreasing trends for penicillin, ESCs, and resistance to ≥3 drugs, AMR rates are persistently high in S. pneumoniae isolates among US adults. Increasing macrolide resistance suggests that efforts to address AMR in S. pneumoniae may require antimicrobial stewardship efforts and higher-valent pneumococcal conjugate vaccines., Competing Interests: Potential conflicts of interest. S.M. and K.D.J. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Inc. J.A.W., K.C.Y., and V.G. are employees of Becton, Dickinson & Company, which was contracted by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, to conduct the study. K.C.Y. and V.G. also own stock in Becton, Dickinson & Company., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Outpatient antibiotic use increases during winter months, but information on temporal changes in inpatient antibiotic use in US hospitals is limited. The use of certain inpatient antibiotics, including extended-spectrum cephalosporins, macrolides, and tetracyclines, was strongly associated with influenza activity during the 2015-2019 viral respiratory seasons., (© The Author(s) 2022.)

Antimicrobial resistance in Enterobacterales has made empiric therapy for hospitalized patients with urinary tract infections (UTIs) more challenging. We analyzed the antibiotic susceptibility of nonduplicate Enterobacterales isolates from urine cultures tested at US hospitals in the BD Insights Research Database (2011-2020). Multivariable generalized estimating equation models were used to assess resistance trends over time. A total of 322 US hospitals provided data on 876,507 urinary Enterobacterales isolates (62.4% Escherichia coli). Enterobacterales antibiotic resistance rates were 64.6%, 29.3%, 27.6%, and 26.3% for beta-lactams, fluoroquinolones, nitrofurantoin, and trimethoprim/sulfamethoxazole, respectively, and 12.4% had an extended-spectrum beta-lactamase (ESBL) phenotype. In multivariable models, rates of ESBL isolates and isolates resistant to ≥3 drug classes increased significantly between 2011 and 2020, while other categories of resistance generally decreased. We conclude that antimicrobial resistance is common in urinary Enterobacterales isolates. Management of UTIs should be guided by urine culture data and may benefit from new therapies., Competing Interests: Declaration of competing interest SIA is an employee of Iterum Therapeutics and MWD was previously employed by Iterum Therapeutics. KCY, JAW, and VG are employees of Becton, Dickinson & Company, which was contracted by Iterum Therapeutics to conduct the study. KCY and VG also own stock in Becton, Dickinson & Company., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Adoption of revised antimicrobial susceptibility breakpoints is often slow, potentially leading to underreporting of antimicrobial resistance. We compared facility-reported rates of carbapenem nonsusceptibility (NS; intermediate or resistant) with NS rates based on current Clinical and Laboratory Standards Institute (CLSI) breakpoints for Enterobacterales or Pseudomonas aeruginosa isolates in ambulatory and inpatient adults in the BD Insights Research Database (US) from 2016 to 2020. Overall, 77.4% (937,926/1,211,845) and 90.6% (2,157,785/2,381,824) of nonduplicate Enterobacterales isolates with facility-reported susceptibility results had MIC data for ertapenem (ETP) and imipenem/meropenem/doripenem (IPM/MEM/DOR), respectively; 86.9% (255,844/294,426) of P. aeruginosa isolates had MIC data for IPM/MEM/DOR. Facility-reported susceptibility and susceptibility based on CLSI criteria resulted in comparable carbapenem susceptibility rates (99.3% versus 99.1% for ETP-susceptible Enterobacterales, 98.9% versus 98.4% for IPM/MEM/DOR-susceptible Enterobacterales, and 84.9% versus 83.3% for IPM/MEM/DOR-susceptible P. aeruginosa). However, compared with CLSI criteria, facilities underreported Enterobacterales- and IPM/MEM/DOR-NS isolates by 18.8% and 26.5%, respectively, and P. aeruginosa IPM/MEM/DOR-NS isolates by 9.8%. Underreporting was observed for both intermediate and resistant isolates. Our data suggest that delayed adoption of revised breakpoints has a small but potentially important impact on reported rates of antimicrobial resistance. Facilities should be aware of local epidemiology, evaluate potential underreporting of resistance, and assess the related clinical impact. IMPORTANCE Clinicians often base antimicrobial therapeutic decisions on laboratory determinations of pathogen susceptibility to an antibiotic based on MIC breakpoints. MIC breakpoints evolve over time based on new information; between 2010 and 2012 the CLSI lowered carbapenem breakpoints for Enterobacterales and Pseudomonas aeruginosa, and these were subsequently adopted by the US Food and Drug Administration. Carbapenems are important therapeutic options for these difficult-to-treat pathogens, so understanding resistance rates is critically important. However, laboratories can be slow to adopt updated breakpoints. We used MIC data to evaluate whether reports received by hospitals for carbapenem susceptibility were consistent with updated CLSI breakpoints. Although overall susceptibility rates were similar between hospital reports and susceptibility based on updated CLSI criteria, the percentages of carbapenem-resistant isolates were significantly underreported by hospital reports. Delayed adoption of MIC breakpoints may impact epidemiological understanding of resistance and contribute to the spread of resistant pathogens.

Antimicrobial resistance (AMR) can complicate effective management of urinary tract infections. We conducted a retrospective study of AMR in Enterobacterales urine isolates from ambulatory and hospitalized adult patients from 2018-2020 (BD Insights Research Database) to evaluate regional differences in isolates with an extended-spectrum beta-lactamase-producing phenotype and those not susceptible to beta-lactams, fluoroquinolone (FQ), nitrofurantoin (NFT), trimethoprim/sulfamethoxazole (TMP/SMX), or multiple antibiotic classes (≥ 2 or ≥ 3). Our analyses included 349,741 Enterobacterales urine isolates from 321 inpatient facilities and 980,354 isolates from 338 ambulatory care facilities. In multivariable analyses, the highest rate of resistance was to beta-lactams (60.8% and 55.8% for inpatient and ambulatory settings, respectively), followed by FQ (27.5%), NFT (27.0%), and TMP/SMX (25.4%) for inpatients and by TMP/SMX (22.4%), FQ (21.6%), and NFT (21.6%) for ambulatory patients. Isolates with an extended-spectrum beta-lactamase-producing phenotype (13.2% and 8.6% for inpatient and ambulatory settings, respectively) and multidrug resistance (inpatient and ambulatory rates of 23.4% and 17.7% for ≥ 2 drugs; 9.9% and 6.4% for ≥ 3 drugs) were also prevalent. Statistically significant differences by geographic region (P ≤ 0.005) were observed for AMR classes in both inpatient and ambulatory settings, but the rates remained above the thresholds recommended for empiric urinary tract infection therapy across most regions., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Urinary tract infections (UTIs), which are usually caused by bacteria in the Enterobacterales family, are a common reason for outpatient visits. Appropriate empiric therapy for UTIs requires an understanding of antibiotic resistance in the community. In this nationwide study, we examined trends in antibiotic resistance in urinary Enterobacterales isolates from ambulatory patients in the United States (US)., Methods: We analyzed the antimicrobial susceptibility profiles (extended-spectrum beta-lactamase [ESBL]-producing phenotype and not susceptible [NS] to beta-lactams, trimethoprim/sulfamethoxazole [TMP/SMX], fluoroquinolones [FQ], or nitrofurantoin [NFT]) of 30-day non-duplicate Enterobacterales isolates from urine cultures tested at ambulatory centers in the BD Insights Research Database (2011-2020). The outcome of interest was the percentage of resistant isolates by pathogen and year. Multi-variable generalized estimating equation models were used to assess trends in resistance over time and by additional covariates., Results: A total of 338 US facilities provided data for > 2.2 million urinary Enterobacterales isolates during the 10-year study. Almost three-quarters (72.8%) of Enterobacterales isolates were Escherichia coli. Overall unadjusted resistance rates in Enterobacterales isolates were 57.5%, 23.1%, 20.6%, and 20.2% for beta-lactams, TMP/SMX, FQ, and NFT, respectively, and 6.9% had an ESBL-producing phenotype. Resistance to two or more antibiotic classes occurred in 16.4% of isolates and 5.5% were resistant to three or more classes. Among isolates with an ESBL-producing phenotype, 70.1%, 59.9%, and 33.5% were NS to FQ, TMP/SMX, and NFT, respectively. In multivariable models, ESBL-producing and NFT NS Enterobacterales isolates increased significantly (both P < 0.001), while other categories of resistance decreased. High rates (≥ 50%) of beta-lactam and NFT resistance were observed in Klebsiella isolates and in non-E. coli, non-Klebsiella Enterobacterales isolates., Conclusions: Antimicrobial resistance was common in urinary Enterobacterales isolates. Isolates with an ESBL-producing phenotype increased by about 30% between 2011 and 2020, and significant increases were also observed in NFT NS Enterobacterales isolates. Resistance rates for all four antibiotic classes were higher than thresholds recommended for use as empiric therapy. Non-E. coli Enterobacterales isolates showed high levels of resistance to commonly used empiric antibiotics, including NFT. These data may help inform empiric therapy choices for outpatients with UTIs., (© 2022. The Author(s).)

Background: Viral infections are often treated with empiric antibiotics due to suspected bacterial coinfections, leading to antibiotic overuse. We aimed to describe antibiotic resistance (ABR) trends and their association with the influenza season in ambulatory and inpatient settings in the United States., Methods: We used the BD Insights Research Database to evaluate antibiotic susceptibility profiles in 30-day nonduplicate bacterial isolates collected from patients >17 years old at 257 US healthcare institutions from 2011 to 2019. We investigated ABR in Gram-positive ( Staphylococcus aureus and Streptococcus pneumoniae ) and Gram-negative (Enterobacterales [ENT], Pseudomonas aeruginosa [PSA], and Acinetobacter baumannii spp [ACB]) bacteria expressed as the proportion of isolates not susceptible ([NS], intermediate or resistant) and resistance per 100 admissions (inpatients only). Antibiotics included carbapenems (Carb), fluoroquinolones (FQ), macrolides, penicillin, extended-spectrum cephalosporins (ESC), and methicillin. Generalized estimating equations models were used to evaluate monthly trends in ABR outcomes and associations with community influenza rates., Results: We identified 8 250 860 nonduplicate pathogens, including 154 841 Gram-negative Carb-NS, 1 502 796 Gram-negative FQ-NS, 498 012 methicillin-resistant S aureus (MRSA), and 44 131 NS S pneumoniae . All S pneumoniae rates per 100 admissions (macrolide-, penicillin-, and ESC-NS) were associated with influenza rates. Respiratory, but not nonrespiratory, MRSA was also associated with influenza. For Gram-negative pathogens, influenza rates were associated with the percentage of FQ-NS ENT, FQ-NS PSA, and Carb-NS ACB., Conclusions: Our study showed expected increases in rates of ABR Gram-positive and identified small but surprising increases in ABR Gram-negative pathogens associated with influenza activity. These insights may help inform antimicrobial stewardship initiatives., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Ambulatory esophageal pH monitoring is, currently, the recommended diagnostic exam for gastroesophageal reflux disease. Data are currently available for African-American (AA) and non-Hispanic white (nHw) volunteers among United States ethnic groups. The purpose of this study was to obtain normal values of 24-h esophageal pH by monitoring healthy adult Hispanic American (HA) volunteers and to compare these with values obtained from healthy AA and nHw volunteers to determine if ethnic variation exists in 24-h esophageal pH., Methods: 24-h Dual esophageal pH monitoring was performed for healthy AA, HA, and nHw. Values for total number of reflux episodes, episodes longer than 5 min, total reflux time, and longest reflux episode in the proximal and/or distal esophagus were obtained for all groups. Differences between groups were considered significant if p<0.05., Results: One-hundred and thirty-six subjects volunteered and completed 24-h pH testing. Fifty-three were AA, 25 HA, and 58 nHw, with males accounting for 52, 47, and 47%, respectively, of each group. AA were older than nHw only and nHw had a lower body mass index than both AA and HA. Shorter study duration was observed for HA than for AA and nHw. No difference was observed between ethnic groups for any measured pH data in the proximal or distal esophagus., Conclusions: No difference exists in values obtained during esophageal pH monitoring among healthy AA, HA, and nHw. This indicates that currently accepted normal values of ambulatory esophageal pH monitoring can be used for all major United States ethnic groups without compromising diagnostic accuracy.

Background: Oesophageal manometry is the standard for diagnosis of oesophageal motor disorders. Minimal data exist assessing the effect of gender on normal oesophageal manometry values., Aim: Evaluate the impact of gender on normal oesophageal manometry values., Methods: Healthy volunteers were recruited from the Jacksonville metropolitan area. Exclusion criteria were symptoms suggestive of oesophageal disease, medication use or concurrent illness that could affect oesophageal manometry. All underwent oesophageal manometry using a solid-state system with wet swallows., Results: Sixty-three males and 66 females were enrolled. All completed oesophageal manometry without difficulty. Resting lower oesophageal sphincter pressure, distal oesophageal contraction duration and distal oesophageal body contraction amplitude values were significantly higher in females while distal oesophageal body contraction velocity was significantly lower in females (p<0.05). No differences were seen in other oesophageal manometry parameters., Conclusion: Significant gender differences exist in normal oesophageal manometry. Gender-specific reference values for oesophageal manometry are needed for accurate diagnosis of oesophageal motility disorders., ((c) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)