Abstract
Background
Despite preventive measures, ventilator-associated pneumonia (VAP) persists as the most frequent healthcare-associated infection in intensive care units (ICUs),1 with high incidence and mortality rates.2,3 Here, we wanted to study the incidence of VAP in 192 Italian ICUs in the last decade. Secondly, we wanted to describe the clinical and microbiological characteristics. Finally, we wanted to assess the variables associated with their intra-ICU mortality.
Methods
In this multicentric observational study, data from 192 Italian ICUs were retrieved from the PROSAFE project, a prospective international research network (2014–2023).4 Bootstrap sampling estimated the incidence rate (IR), while comparisons between VAP versus non-VAP patients were tested with the Kruskall-Wallis and Chi-Square tests. Finally, a multivariable logistic regression identified intra-ICU mortality risk-factors.
Results
Among 402 085 ICU admissions, a total of 11 978 VAPs were identified. The IR was 10.5 cases per 1000 MV-days (CI:10.3–10.7), median MV exposure before VAP was 7 days (IQR: 4–12 days), and 68% of episodes were classified as late-onset VAP. Patients with VAP had prolonged median intra-ICU LOS (23 versus 2 days, P < 0.001) and higher intra-ICU mortality (30.0% versus 14.9%, P < 0.001) (Table 1). Notably, ventilator-free days were significantly lower (7 ± 10 days versus 9 ± 10 days, P < 0.01) in the subgroup of multidrug-resistant organisms (MDROs) VAP patients.
Klebsiella spp. (22.2%), Pseudomonas spp. (22.4%), and Staphylococcus aureus (22.7%) were the predominant pathogens, but Acinetobacter spp. showed the highest resistant profile, with 85% of the strains resistant to carbapenems. Concomitant bloodstream infections occurred in 20.7% of VAP cases. Finally, older age, chronic liver and kidney diseases (ORs 1.4, 1.9, and 2.5, respectively, P < 0.01), longer intra-ICU LOS before VAP occurrence (OR 2.6 after 4 ICU days, P = 0.02), MDROs (OR 1.3, P < 0.01) and Acinetobacter spp. (OR 1.9, P < 0.01) aetiology were associated with increased intra-ICU mortality.
Discussion
These findings underscore the high intra-ICU mortality of patients with VAP, and might help to target high-risk groups of patients with the hope to improve outcomes and reduce the burden of VAP.
Table 1.
Demographic and clinical characteristic of patients admitted to the ICU (2014–2023)
| Total (N = 402 085) |
Patients without VAP (N = 390 107) |
Patients with VAP (N = 11 978) |
P value | |
|---|---|---|---|---|
| Age > 65 years (n, %) | 251 341 (62.5%) | 245 044 (62.8%) | 6297 (52.6%) | <0.001 |
| Sex Male (n, %) | 244 618 (61.0%) | 236 033 (60.7%) | 8585 (71.8%) | <0.001 |
| Ward of origin (n, %) | <0.001 | |||
| Medical | 54 863 (13.7%) | 52 550 (13.5%) | 2313 (19.4%) | |
| Surgical | 195 681 (48.9%) | 193 748 (49.9%) | 1933 (16.2%) | |
| Emergency room | 117 197 (29.3%) | 111 581 (28.7%) | 5616 (47.1%) | |
| Other ICU | 22 415 (5.6%) | 21 015 (5.4%) | 1400 (11.7%) | |
| High Intensity Wards | 10 347 (2.6%) | 9682 (2.5%) | 665 (5.6%) | |
| Admission indication (n, %) | <0.001 | |||
| Monitoring and weaning from ICU support | 183 410 (45.6%) | 182 935 (46.9%) | 475 (4.0%) | |
| Medical intensive care | 125 522 (31.2%) | 119 333 (30.6%) | 6189 (51.7%) | |
| Surgical and post-operative care | 67 947 (16.9%) | 65 425 (16.8%) | 2522 (21.1%) | |
| Trauma and emergency critical care | 25 206 (6.3%) | 22 414 (5.7%) | 2792 (23.3%) | |
| BMI (n, %) | <0.001 | |||
| Underweight | 21 157 (5.3%) | 20 740 (5.4%) | 417 (3.5%) | |
| Obese | 75 051 (18.9%) | 72 705 (18.8%) | 2346 (19.8%) | |
| Comorbidities (n, %) | ||||
| Respiratory disease | 89 029 (22.1%) | 86 766 (22.2%) | 2263 (18.9%) | <0.001 |
| Neurologic disease | 61 971 (15.4%) | 60 265 (15.4%) | 1706 (14.2%) | <0.001 |
| Cardiovascular disease | 266 855 (66.4%) | 259 808 (66.6%) | 7047 (58.8%) | <0.001 |
| Hypertension | 220 935 (54.9%) | 214 995 (55.1%) | 5940 (49.6%) | <0.001 |
| Liver disease | 19 191 (4.8%) | 18 709 (4.8%) | 482 (4.0%) | <0.001 |
| Renal disease | 42 635 (10.6%) | 41 751 (10.7%) | 884 (7.4%) | <0.001 |
| Diabetes | 82 303 (20.5%) | 80 111 (20.5%) | 2192 (18.3%) | <0.001 |
| Autoimmune disease | 12 401 (3.1%) | 12 063 (3.1%) | 338 (2.8%) | 0.092 |
| Immunosuppression | 79 893 (19.9%) | 78 565 (20.1%) | 1328 (11.1%) | <0.001 |
| ICU-related procedures (n, %) | ||||
| Tracheostomy at admission | 11 135 (2.8%) | 10 642 (2.8%) | 493 (4.1%) | <0.001 |
| Non-Invasive ventilation | 42 777 (10.9%) | 41 692 (11.0%) | 1085 (9.1%) | <0.001 |
| At least one surgical operation | 23 2961 (57.9%) | 227 672 (58.4%) | 5289 (44.2%) | <0.001 |
| Solid organ transplantation | 5165 (1.3%) | 5075 (1.3%) | 90 (0.8%) | <0.001 |
| Intra-ICU outcomes | ||||
| Intra-ICU LOS (median, IQR) | 2.0 (1.0, 6.0) | 2.0 (1.0, 6.0) | 23.0 (15.0, 36.0) | <0.001 |
| Intra-ICU mortality (n, %) | 61 630 (15.3%) | 58 038 (14.9%) | 3592 (30.0%) | <0.001 |
| Hospitalization outcomes | ||||
| Intra-hospital LOS(median, IQR) | 13.0 (7.0, 25.0) | 13.0 (7.0, 24.0) | 33.0 (20.0, 52.0) | <0.001 |
| Intra-hospital mortality (n, %) | 80 619 (20.2%) | 76 528 (19.8%) | 4091 (34.6%) | <0.001 |
| Transferred to another hospital, (n, %) | 37 646 (9.5%) | 35 540 (9.2%) | 2106 (17.8%) | |
| Transferred to another hospital regimen (n, %) | 75 052 (18.8%) | 70 978 (18.4%) | 4074 (34.4%) | |
| Home discharge (n, %) | 197 026 (49.5%) | 195 612 (50.6%) | 1414 (12.0%) | |
| VAP epidemiology | Total (N = 10 737) N (%) | MDROsa N (%) |
|---|---|---|
| Acinetobacter spp. | 1046 (9.7%) | 898 (85.9%) |
| Citrobacter spp. | 211 (2.0%) | 1 (0.5%) |
| Enterobacter spp. | 843 (7.9%) | 44 (5.2%) |
| Escherichia coli | 1042 (9.7%) | 19 (1.8%) |
| Klebsiella spp. | 2157 (20.1%) | 554 (25.7%) |
| S. pneumoniae | 171 (1.6%) | 12 (7.0%) |
| Proteus spp. | 288 (2.7%) | 7 (2.4%) |
| Pseudomonas spp. | 2258 (21.0%) | 513 (22.7%) |
| Serratia spp. | 553 (5.2%) | 6 (1.1%) |
| S. aureus | 2168 (20.2%) | 563 (26.0%) |
aMDROs: the multidrug-resistant organisms (MDROs) definition in this study included: carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Acinetobacter spp., carbapenem-resistant Enterobacterales (Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus spp., Serratia spp.), methicillin-resistant Stahpylococcus aureus (or MRSA), and penicillin-resistant Steptococcus pneumoniae.
Contributor Information
M Colaneri, Department of Infectious Diseases, Luigi Sacco Hospital Milan, Italy.
G Montrucchio, Department of Anesthesia, Intensive Care and Emergency, Città della Salute e della Scienza Hospital Turin, Italy.
G Scaglione, Department of Infectious Diseases, Luigi Sacco Hospital Milan, Italy.
M Offer, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan Milan, Italy.
G Tricella, Laboratory of Clinical Data Science, Department of Public Health, Mario Negri Institute for Pharmacological Research IRCCS Ranica, Italy.
C Genovese, Department of Infectious Diseases, Luigi Sacco Hospital Milan, Italy.
E Palomba, Department of Infectious Diseases, Luigi Sacco Hospital Milan, Italy.
F Agostini, Laboratory of Clinical Data Science, Department of Public Health, Mario Negri Institute for Pharmacological Research IRCCS Ranica, Italy.
F Dore, Laboratory of Clinical Data Science, Department of Public Health, Mario Negri Institute for Pharmacological Research IRCCS Ranica, Italy.
G Monti, Dipartimento di Anestesia e Rianimazione, ASST Grande Ospedale Metropolitano Niguarda Milan, Italy.
B Viaggi, Department of Anaesthesiology, Neuro-Intensive Care Unit, Careggi University Hospital Florence, Italy.
A Gori, Department of Infectious Diseases, Luigi Sacco Hospital Milan, Italy.
S Finazzi, Laboratory of Clinical Data Science, Department of Public Health, Mario Negri Institute for Pharmacological Research IRCCS Ranica, Italy.
References
- 1. Magill SS, O’Leary E, Janelle SJ et al. Changes in prevalence of health careassociated infections in U.S. hospitals. N Engl J Med 2018; 379: 1732–44. 10.1056/NEJMoa1801550 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Semet C. The ongoing challenge of ventilator-associated pneumonia: epidemiology, prevention, and risk factors for mortality in a secondary care hospital intensive care unit. Infect Prev Pract 2023; 5: 100320. 10.1016/j.infpip.2023.100320 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. European Centre for Disease Prevention and Control (ECDC) . Point Prevalence Survey of Healthcare-Associated Infections and Antimicrobial Use in European acute Care Hospitals Stockholm: ECDC. 2022. https://www.ecdc.europa.eu/sites/default/files/documents/antimicrobial-use-healthcare-associated-infections-point-prevalencesurvey-version6-1.pdf.
- 4. Finazzi S, Paci G, Antiga L et al. PROSAFE: a European endeavor to improve quality of critical care medicine in seven countries. Minerva Anestesiol 2020; 86: 1305–20. 10.23736/S0375-9393.20.14112-9 [DOI] [PubMed] [Google Scholar]
