Difficult-to-treat resistance, not carbapenem non-susceptibility, is associated with 30-day mortality in respiratory gram-negative bacilli: a 12-year surveillance cohort.
Antimicrobial resistance in respiratory gram-negative bacilli (GNB) is rising in Saudi Arabia, yet the clinical impact of difficult-to-treat resistance (DTR) remains poorly defined. We characterized temporal trends in organism distribution, non-susceptibility phenotypes, and their association with 30-day in-hospital mortality.
Retrospective cohort of hospitalized patients aged ≥12 years with culture-positive respiratory GNB at a referral hospital in southern Saudi Arabia (January 2013-August 2024). Non-susceptibility phenotypes were fluoroquinolone (FQ-NS), extended-spectrum cephalosporin (ESC-NS), carbapenem non-susceptibility, and DTR. Trends were assessed with segmented binomial regression, mortality with modified Poisson regression.
Among 6,999 isolate-episodes from 3,808 patients, Enterobacterales (57.2%) increased while non-fermenting GNB declined (AAPC, -2.5%). Carbapenem non-susceptibility rose among Enterobacterales (AAPC, + 5.4%), driven by Klebsiella pneumoniae. DTR was 37.6%, rising in Enterobacterales (AAPC, + 12.1%) but declining in Acinetobacter baumannii. Thirty-day mortality was 27.9%. DTR was associated with mortality in Enterobacterales (aRR, 1.34; 95% CI, 1.16-1.55) and non-fermenting GNB (aRR, 1.28; 95% CI, 1.12-1.46); carbapenem non-susceptibility without DTR was not. Mortality rose as active first-line agents decreased (P-trend<.001).
Respiratory GNB epidemiology is shifting toward Enterobacterales with rising resistance. DTR, not carbapenem non-susceptibility alone, was consistently associated with 30-day mortality and provides a meaningful framework for risk stratification and resistance-centered surveillance.
Retrospective cohort of hospitalized patients aged ≥12 years with culture-positive respiratory GNB at a referral hospital in southern Saudi Arabia (January 2013-August 2024). Non-susceptibility phenotypes were fluoroquinolone (FQ-NS), extended-spectrum cephalosporin (ESC-NS), carbapenem non-susceptibility, and DTR. Trends were assessed with segmented binomial regression, mortality with modified Poisson regression.
Among 6,999 isolate-episodes from 3,808 patients, Enterobacterales (57.2%) increased while non-fermenting GNB declined (AAPC, -2.5%). Carbapenem non-susceptibility rose among Enterobacterales (AAPC, + 5.4%), driven by Klebsiella pneumoniae. DTR was 37.6%, rising in Enterobacterales (AAPC, + 12.1%) but declining in Acinetobacter baumannii. Thirty-day mortality was 27.9%. DTR was associated with mortality in Enterobacterales (aRR, 1.34; 95% CI, 1.16-1.55) and non-fermenting GNB (aRR, 1.28; 95% CI, 1.12-1.46); carbapenem non-susceptibility without DTR was not. Mortality rose as active first-line agents decreased (P-trend<.001).
Respiratory GNB epidemiology is shifting toward Enterobacterales with rising resistance. DTR, not carbapenem non-susceptibility alone, was consistently associated with 30-day mortality and provides a meaningful framework for risk stratification and resistance-centered surveillance.
Authors
Shabi Shabi, Alwadei Alwadei, Alshahrani Alshahrani, Somily Somily, Binkhamis Binkhamis, Asiri Asiri, Mohamed Mohamed, Bawazeer Bawazeer, Al Oudhah Al Oudhah, Alqahtani Alqahtani, Alhamlan Alhamlan, Salem Salem, Al Ghamdi Al Ghamdi, Habtar Habtar, Alqahtani Alqahtani, Asiri Asiri, Jali Jali, Almahdi Almahdi, Alahmari Alahmari
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