Identification and validation of robust hospital-acquired pneumonia subphenotypes associated with all-cause mortality: a multi-cohort derivation and validation

Martin, FP; Poulain, C; Mulier, JH; Motos, A; Gourain, V; Ogan, I; Montassier, E; Launey, Y; Lasocki, S; Cinotti, R; Dahyot Fizelier, C; Ranzani, O; Reyes, LF; Martin-Loeches, I; Derde, L; Torres, A; Cremer, O; Roquilly, A

doi:10.1007/s00134-025-07884-3

Sepsis & infection

Identification and validation of robust hospital-acquired pneumonia subphenotypes associated with all-cause mortality: a multi-cohort derivation and validation

Intensive Care MedPublished 22 Apr 2025Multi-cohort derivation and validation study

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Authors' conclusion

We identified two robust clinical subphenotypes by extensively analyzing HAP data sets.

Study context

Population: Critically ill patients with hospital-acquired pneumonia (HAP) in France, Netherlands and Europe-South America cohorts4 derivation cohorts + VITAL n = 726

Comparison: HAP subphenotype 2 vs subphenotype 1
Outcome: Association of subphenotypes with all-cause mortality
Follow-up: 28 days

Methodological detailsunsupervised clustering, machine learning-based classification model, independent replication data set

Unsupervised clustering
Machine learning-based classification model
Independent replication data set

Performance

As reported in the abstract

28-day mortality

Prevalence of subphenotype 2 across derivation cohorts

26.9 to 66.9%

Further findings

Treatment failure with tedizolid vs linezolid (VITAL trial)

	← Lower risk ←→ Higher risk →	RR (95% CI)
Subphenotype 1Tedizolid · statistically significant tedizolid effect modification	0.512	1.52 (1.12–2.06)
	0.512Relative risk (log scale)

Outcome	← Lower risk with subphenotype 2 ←→ Higher risk with subphenotype 2 →	RR (95% CI)
Treatment failure with tedizolid vs linezolid (VITAL trial)Subphenotype 2 vs Subphenotype 1 · tedizolid · statistically significant tedizolid effect modification	0.512	0.98 (0.7–1.38)
	0.512Relative risk (log scale)

Treatment failure at test-of-cure

Consistently differed between subphenotypes (p < 0.01 for all comparisons)

Respiratory microbiome and cytokines (ATLANREA subgroup)

Subphenotype 2 associated with greater respiratory microbiome dysbiosis and higher proinflammatory cytokines

Original publication

Identification and validation of robust hospital-acquired pneumonia subphenotypes associated with all-cause mortality: a multi-cohort derivation and validation. Intensive Care Med. Published 22 April 2025. doi:10.1007/s00134-025-07884-3

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