Introduction
This post-hoc analysis of a multinational ICU study assessed and compared the clinical profiles, microbiological findings, and outcomes of immunosuppressed versus non-immunosuppressed patients with nosocomial lower respiratory tract infections (nLRTIs). Using data from 1,060 ICU patients, 24.9% were identified as immunosuppressed—mostly due to oncological conditions. Pseudomonas aeruginosa was the most common pathogen, especially among immunosuppressed patients. The study found that immunosuppressed patients had significantly lower 28-day survival, with the severity of illness (SAPS II score) and specific immunosuppressive conditions like hematological malignancies or recent chemotherapy strongly linked to higher mortality.
nLRTIs remain the most frequent and costly infections in ICUs, particularly among ventilated patients. Immunosuppressed individuals—such as those with cancer, on immunosuppressive therapy, or post-transplant—are especially vulnerable, often presenting with severe disease and higher fatality rates. Despite medical advances, these patients face prolonged hospital stays, increased costs, and worse outcomes. This study emphasizes the need for targeted strategies and improved understanding of how immunosuppression affects the clinical course of nLRTIs to reduce complications and enhance survival in this high-risk group.
Methods
This study analyzed data from the ENIRRI cohort, a prospective, multicenter study including 1,060 critically ill adult patients with nosocomial lower respiratory tract infections (nLRTIs) admitted to 28 ICUs across 13 countries (2016–2019). Patients were included if they were ≥18 years and diagnosed with nLRTIs per international guidelines. Clinical, microbiological, and outcome data were collected and anonymized. Immunosuppressed patients were identified based on active neoplasia, AIDS, recent transplants, or use of immunosuppressive medications. Patients were stratified into immunosuppressed and non-immunosuppressed groups for analysis.
Statistical analyses involved descriptive comparisons, Kaplan–Meier survival curves, and multivariable Cox regression models adjusted for disease severity and relevant clinical variables. Missing data were addressed using multiple imputation. Subgroup analyses assessed the impact of specific immunosuppressive conditions on 28-day mortality. Variables were grouped by clinical relevance, and hazard ratios were calculated with 95% confidence intervals using Stata 17 and RStudio 2024.
Results
A total of 1,060 patients admitted to the ICU were included in the present study, with 25% (264/1060) classified in the immunosuppressed group, primarily due to non-metastatic solid tumors and autoimmune diseases (Fig. 1)
Figure 1. Flowchart of included patients diagnosed with ICU-related respiratory infections and clinical outcomes.
Ventilator-associated pneumonia (VAP) was the most common form of nosocomial LRTI in both groups, representing 53% of all cases and 49% of infections in immunosuppressed patients. The leading causes of immunosuppression were solid tumors (56%), autoimmune diseases (22%), chemotherapy (19%), and chronic steroid use (16%). Chronic lung (27%) and heart diseases (23%) were the most frequent comorbidities in the immunosuppressed group. These patients had longer hospital stays (median 42 vs. 36.5 days; p=0.018) and higher mortality (43% vs. 36%; p=0.042) compared to non-immunosuppressed patients.
Microbiological identification was achieved in 74% of immunosuppressed and 79% of non-immunosuppressed patients (p=0.002). Pseudomonas aeruginosa was the predominant pathogen overall and especially in immunosuppressed VAP cases (37%), followed by Klebsiella spp. and Acinetobacter baumannii. As shown in Fig. 2, P. aeruginosa was significantly more common in immunosuppressed patients (25% vs. 17%; p=0.032). Immunosuppressed patients also underwent more respiratory virus testing (p=0.002) and pleural fluid cultures (p<0.001), while other diagnostic methods showed no major group differences.
Figure 2. Identified microorganisms in A the Immunosuppressed and B the Non-Immunosuppressed group. Distribution of identified microorganisms in both immunosuppressed and non-immunosuppressed patients diagnosed with ICU-related respiratory infections.
Piperacillin-tazobactam was the most commonly used antibiotic in both groups, with no significant difference in use. However, meropenem/imipenem was prescribed more often to immunosuppressed patients (22.3% vs. 15.3%; p=0.009), while amoxicillin-clavulanate and levofloxacin were used less frequently in this group. Overall, antibiotic use patterns were largely similar between groups, aside from these few differences.
Survival analysis revealed that patients with immunosuppression had significantly lower survival, as illustrated in Fig. 3 (Kaplan–Meier curve). Higher SAPS II scores were strongly associated with increased 28-day mortality, while factors like polytrauma, altered consciousness, and postoperative status were linked to lower mortality. Among immunosuppressed patients, those with hematologic malignancies, recent chemotherapy, or bone marrow transplants had the highest risk of death. Immunosuppression increased overall in-hospital mortality risk (OR 1.70; p=0.016), particularly in VAP cases, though this effect was not observed in other nLRTI subtypes.
Figure 3. Kaplan–Meier Survival Curve at 28 days, Adjusted for Disease Severity Using SAPS II Score. Kaplan–Meier survival analysis comparing 28-day survival between immunosuppressed and non-immunosuppressed patients, adjusted for disease severity based on SAPS II scores
Conclusion
In conclusion, our study provides insights into the epidemiology and clinical outcomes of nLRTIs among immunosuppressed patients in the ICU. Immunosuppressed patients had a lower adjusted survival probability compared to non-immunosuppressed patients. The high prevalence of P. aeruginosa in this population highlights the challenges in when deciding empiric antimicrobial treatment in these patients, emphasizing the need for targeted treatment strategies. These findings underscore the importance of continued research to optimize the prevention and management of nosocomial infections in immunosuppressed critically ill patients.
