S. maltophilia Pneumonia Linked to Higher ICU Treatment Failure
Key Takeaways
- Among critically ill adults with clinically significant S. maltophilia respiratory infection in Madrid ICUs, therapeutic failure was more frequent with VAP/HAP than VAT.
- ICU mortality was numerically higher with pneumonia than tracheobronchitis, without a statistically significant between-group difference.
- Exploratory laboratory-reported active therapy was associated with lower failure, whereas empirical therapy at treatment initiation was not.
Investigators retrospectively assessed consecutive eligible adults in two tertiary intensive care units (ICUs) in Madrid, Spain, from August 2021 through December 2025. The 67 adults contributed 90 clinically significant episodes; their 67 first episodes entered the primary analysis, including 35 ventilator-associated tracheobronchitis (VAT) and 32 ventilator-associated pneumonia (VAP) or hospital-acquired pneumonia (HAP) episodes. Later episodes were examined separately and exploratorily. Independent adjudication applied predefined clinical, imaging and microbiologic criteria, excluding colonization, more plausible alternative diagnoses and unclassifiable episodes. VAT followed mechanical ventilation without a new or progressive infiltrate; VAP followed intubation and HAP followed hospitalization, both with an infiltrate. Therapeutic failure meant persistent or worsening infection during treatment, a change for documented inadequate clinical response, or infection-related death. Follow-up continued to discharge or death. A prespecified Firth model adjusted for Acute Physiology and Chronic Health Evaluation II (APACHE II) score and prior carbapenem exposure.
Therapeutic failure occurred in 13 of 32 (40.6%) VAP/HAP index episodes versus 5 of 35 (14.3%) VAT episodes, an absolute difference of 26.3 percentage points (95% confidence interval (CI), 5.0–45.2; p = 0.026). Sensitivity analyses adjusting for Sequential Organ Failure Assessment (SOFA) score or restricting pneumonia to VAP pointed in the same direction. ICU mortality was numerically higher with pneumonia but did not differ significantly between groups.
The prespecified adjusted model associated VAP/HAP with greater odds of failure than VAT (adjusted odds ratio, 4.06; 95% CI, 1.32–14.25); those odds are not an absolute risk difference. An exploratory model associated laboratory-reported active therapy with lower odds of failure (adjusted odds ratio, 0.19; 95% CI, 0.05–0.72). Active therapy required administration before failure and was not a baseline treatment assignment. In contrast, failure with empirical anti-S. maltophilia therapy defined at treatment initiation was 4 of 15 (26.7%) versus 14 of 52 (26.9%) without it, with no demonstrated reduction.
Only 18 index episodes ended in failure, leaving broad confidence bounds. Baseline imbalance, residual confounding and possible misclassification along the colonization–VAT–pneumonia continuum limit the observational comparison. Cultures were predominantly semiquantitative tracheal aspirates without a fixed quantitative threshold, and retrospective failure assessment was unblinded. Patients who failed early had less opportunity to receive laboratory-reported active therapy; reverse causation, selective and heterogeneous susceptibility testing, and clinician-chosen regimens further limit that exploratory association. The empirical comparison neither establishes benefit nor rules it out, and the syndrome association does not establish causation. Repeated exploratory observations and selective testing cannot establish population-wide susceptibility, drug equivalence or agent-specific effects.
The investigators concluded that therapeutic failure differed by syndrome in this cohort from two Madrid hospitals. They called for confirmation of the exploratory active-therapy association and could not infer comparative effectiveness for specific antimicrobial agents.
Clinician Questions
Can therapeutic failure in S. maltophilia respiratory infection be followed by clinical cure?
Yes. Among critically ill adults with clinically significant S. maltophilia lower respiratory infection, failure of the initial regimen could be followed by clinical cure after treatment was modified. Investigators assessed initial failure and eventual cure separately, so the outcomes were not mutually exclusive.
What limits interpretation of cefiderocol susceptibility results in S. maltophilia ICU respiratory infections?
For S. maltophilia respiratory isolates in the two Madrid ICUs, cefiderocol testing was selective and used local non-reference disk or gradient diffusion methods. The authors noted that EUCAST provides no clinical susceptible/intermediate/resistant breakpoints for this organism–agent pairing; local interpretations therefore cannot be treated as population-wide susceptibility categories.