Difficult-to-treat resistance, not carbapenem non-susceptibility, is associated with 30-day mortality in respiratory gram-negative bacilli: a 12-year surveillance cohort.

OBJECTIVES

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.