Evidence map›Paper›PMID 41903557›Full record

ArticleThe Lancet. Infectious diseases2026

Survival trends in patients with difficult-to-treat, antibiotic-resistant, Gram-negative infections in the era of next-generation antibiotics in the USA: a retrospective cohort study.

Morgan K Walker, Christina Yek, Sadia Sarzynski, Sarah Warner, Anthony D Harris, Jonathan D Baghdadi, Katherine E Goodman, John H Powers, Michael Klompas, Chanu Rhee and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Morgan K WalkerClinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA; University of Maryland Institute for Health Computing, North Bethesda, MD, USA.
Christina YekClinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA; International Center of Excellence in Research Cambodia, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia.
Sadia SarzynskiClinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
Sarah WarnerClinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA; University of Maryland Institute for Health Computing, North Bethesda, MD, USA.
Anthony D HarrisUniversity of Maryland Institute for Health Computing, North Bethesda, MD, USA; Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Jonathan D BaghdadiUniversity of Maryland Institute for Health Computing, North Bethesda, MD, USA; Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Katherine E GoodmanUniversity of Maryland Institute for Health Computing, North Bethesda, MD, USA; Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
John H PowersNational Institute of Allergy and Infectious Diseases, Bethesda, MD, USA; Clinical Medicine, George Washington University School of Medicine, Washington, DC, USA; Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Michael KlompasDepartment of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Chanu RheeDepartment of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Bruce SwihartClinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
Sameer S KadriClinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA; University of Maryland Institute for Health Computing, North Bethesda, MD, USA. Electronic address: sameer.kadri@nih.gov.
NIH Antimicrobial Resistance Outcomes Research Initiative (NIH-ARORI)

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Big Data - Epidemiology of Critical Illness and SepsisZIACL090045 · CLC · CLINICAL CENTER · PI KADRI, SAMEER · 2017 to 2025
$0k
Big Data- Epidemiology of Antimicrobial ResistanceZIACL090046 · CLC · CLINICAL CENTER · PI KADRI, SAMEER · 2017 to 2025
$0k
Intramural NIH HHS ZIA CL090045Intramural NIH HHS ZIA CL090046NIH HHS 75N91019D00024
6 · The paper itself

Abstract

backgroundDifficult-to-treat resistant (DTR) Gram-negative infections show resistance to all first-line antibiotics (ie, β-lactams and fluoroquinolones) and have a 40% greater mortality rate than susceptible infections. New antibiotics are now available with improved safety and efficacy and with in-vitro activity against DTR infections; however, their influence on the outcomes of patients with DTR infections remains unclear. We aimed to evaluate whether and why mortality in patients with DTR infections has changed since the introduction of these newer antibiotics in the USA.

methodsIn this retrospective cohort study in the USA, adult patients (aged ≥18 years) with a DTR Gram-negative infection, defined as microbiological evidence of DTR Enterobacterales, Pseudomonas aeruginosa, or Acinetobacter baumannii and receipt of at least 3 consecutive days of any antibiotic therapy, were identified from hospitals reporting microbiology data in the PINC-AI Healthcare Database. We characterised the proportion of inpatient encounters receiving newer DTR-active antibiotics, traditional DTR-active antibiotics, and non-DTR-active antibiotics. We used a generalised linear mixed model with marginal predictions to examine changes in in-hospital mortality, defined as death or discharge to hospice, over the study period when adjusting for patient-related and treatment-related factors (including receipt of a new antibiotic and receipt of in-vitro discordant initial therapy), hospital-related factors (including the availability of newer antibiotics and corresponding susceptibility testing), and COVID-19 pandemic-related factors. A three-way interaction term for time (year), pathogen, and infection site (ie, bloodstream and non-bloodstream) was included given the expected differences in mortality.

findingsBetween Jan 1, 2016, and Aug 31, 2023, 8 319 398 adult inpatient encounters with available microbiology data were recorded from 471 hospitals, of which 9384 (0·11%) encounters had microbiological evidence of an eligible DTR organism. 5065 (54·0%) of these 9384 encounters, from 262 hospitals, met the inclusion criteria for DTR Gram-negative infections and were included in the study. Among this cohort, the prescription of newer antibiotics, as well as the availability of newer antibiotics and their corresponding susceptibility tests, increased substantially from 2016 to 2023. Although the proportion of encounters in which the patient received a newer antibiotic as initial therapy increased from 4% (21 of 589) in 2016 to 15% (34 of 234) in 2023, in most cases (196 [84%] of 234) patients continued to receive in-vitro discordant initial antibiotic therapy, even in 2023. We observed no change in the average marginal effect (the average percentage change per year) for adjusted mortality between 2016 and 2023 for Enterobacterales (0·1% [95% CI -1·1 to 1·4]), P aeruginosa (-0·7% [-1·7 to 0·3]), or A baumannii (-0·4% [-1·8 to 0·9]) infections. When dichotomised into bloodstream and non-bloodstream infections, the marginal effect for adjusted mortality remained unchanged over time for most pathogen and site combinations, with the exception of P aeruginosa bloodstream infections, for which a decrease was observed (-4·5% [-8·2 to -0·60]).

interpretationDespite the availability of newer antibiotic agents, the estimated mortality and ongoing use of in-vitro discordant initial antibiotics remains unacceptably high among patients with DTR infections in US hospitals. Prompt recognition of both the pathogen and resistance phenotype could be a crucial component in reducing mortality. Although notable, the decrease over time in adjusted mortality for P aeruginosa bloodstream infections should be considered hypothesis-generating because the cohort of patients with such infections was small.

fundingUS National Institutes of Health (NIH) Clinical Center; US National Cancer Institute; the Intramural Research Program of the US National Heart, Lung, and Blood Institute; the US National Institute of Allergy and Infectious Diseases; and the US Food and Drug Administration.

Indexed as

Anti-Bacterial AgentsDrug Resistance, BacterialGram-Negative Bacterial InfectionsAcinetobacter baumanniiAdultAgedAged, 80 and overFemaleGram-Negative BacteriaHumansMaleMiddle AgedPseudomonas aeruginosaRetrospective StudiesUnited StatesAnti-Bacterial Agents

Identifiers

PMID41903557
PMCPMC13268009

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.