Highlights
– In 50 Brazilian adult ICUs (Sept 2019–Dec 2021), VAP incidence was 6.03/1,000 MV-days and CLABSI 1.63/1,000 CVC-days among at-risk patients.
– Hospital-level measures (structure and processes) explained ~40–45% of between-hospital variability in infection rates; hospital random-effects showed large heterogeneity (median rate ratios 4.39 for VAP, 3.53 for CLABSI).
– Protective institutional factors included formal prevention protocols, hand hygiene training, flexible family visitation, higher nursing staffing ratios, single-use gowns, alcohol availability, nurse-led sedation titration, respiratory-therapist-led weaning, and dentist availability.
– Findings strengthen the case for investing in basic infection prevention infrastructure and workforce in LMIC ICUs.
Background
Healthcare-associated infections (HAIs) in intensive care units — notably ventilator-associated pneumonia (VAP) and central line-associated bloodstream infection (CLABSI) — cause excess morbidity, mortality, length of stay, and cost. The burden is disproportionately high in low- and middle-income countries (LMICs) where constrained resources, variable staffing, and limited infection-prevention infrastructure reduce the ability to reliably deliver evidence-based care bundles. Prior systematic reviews estimate a substantially higher prevalence of HAIs in developing countries compared with high-income settings (Allegranzi et al., Lancet Infect Dis 2011). Landmark quality-improvement efforts in high-income countries (for example, Pronovost et al., NEJM 2006) demonstrate that structured bundles, training, and systems change can dramatically reduce device-associated infection rates. However, robust, multicenter patient-level evidence linking specific institutional structure and process measures to device-associated HAI rates in LMIC ICUs has been limited.
Study design
This nested cohort analysis used prospectively collected patient-level data from the IMPACTO‑MR platform, a multicenter research platform in Brazil, and cross-sectional baseline hospital-level data. Fifty adult ICUs participated. All patients admitted between September 2019 and December 2021 who were exposed to at least 48 hours of invasive mechanical ventilation (MV) or central venous catheter (CVC) were included in the respective at-risk cohorts. VAP and CLABSI were reported according to Brazilian regulatory agency guidance. Investigators used negative binomial or Poisson multivariable regression models to identify associations between hospital-level factors and infection incidence, adjusting for individual-level covariates, and including hospital random-effects to quantify between-hospital variability. The design is observational and hypothesis-generating rather than interventional.
Key findings
Population and crude rates: Among 75,164 ICU admissions, 19,108 patients were at risk for VAP (≥48 hr of MV) contributing 244,059 MV-days. The VAP incidence rate was 6.03 per 1,000 MV-days (95% CI, 5.73–6.35). For CLABSI, 26,560 patients contributed 375,078 CVC-days with an incidence of 1.63 per 1,000 CVC-days (95% CI, 1.51–1.77).
Between-hospital variability: Hospital-level random-effects were large. The median rate ratio (MRR) for hospitals was 4.39 (95% CI, 2.72–6.06) for VAP and 3.53 (95% CI, 2.30–4.76) for CLABSI — indicating that a typical patient’s risk could differ several-fold between two randomly selected hospitals, after accounting for measured individual covariates.
Explanatory power of hospital measures: Hospital-level fixed effects (capturing structure and process variables measured at baseline) explained 39.9% (95% CI, 33.6–46.1%) of between-hospital variability for VAP and 44.7% (95% CI, 35.0–54.5%) for CLABSI. In other words, roughly four in ten differences between hospitals’ infection rates were attributable to measurable institutional characteristics.
Institutional factors associated with lower HAI rates: Several modifiable measures were independently associated with lower infection rates after multivariable adjustment.
– Prevention protocols (formalized care bundles and written policies) were associated with reduced rates of both VAP and CLABSI.
– Hand hygiene training was associated with lower VAP and CLABSI incidence, consistent with the central role of hand hygiene in infection prevention.
– Flexible family visitation policies correlated with reduced rates — a finding that may reflect beneficial effects on patient-oriented processes (e.g., mobilization, delirium prevention) rather than a direct microbiologic mechanism.
– For CLABSI specifically, higher nurse-to-patient staffing ratios, availability of single-use gowns, and ready access to alcohol-based hand rubs were associated with lower rates.
– For VAP, nurse-led sedation titration, respiratory-therapist-led weaning protocols, and on-site dentist availability (supporting oral care) were associated with reduced VAP incidence.
Effect sizes: The paper reports incidence-rate ratios from multivariable models (exact numeric IRRs for each factor were presented by the authors). The large MRR values underscore clinically meaningful differences that may be narrowed by targeted investments and process changes.
Interpretation
These findings align with existing evidence that relatively simple structural elements (adequate nursing staffing, alcohol-based hand rubs, single-use protective equipment) and process interventions (protocolized prevention bundles, staff training, dedicated roles for sedation/weaning and oral care) can materially reduce device-associated infections. Importantly, the study quantifies how much hospital-level action can explain between-hospital differences in a real-world LMIC setting — a critical input for policymakers prioritizing resource allocation.
Expert commentary
Strengths: This analysis leverages a large, prospective multicenter dataset with patient-level granularity and robust statistical modeling including hospital random-effects. Nesting within IMPACTO‑MR ensures standardized data infrastructure and enriched potential for future linked analyses (e.g., antimicrobial resistance outcomes). The timeframe captures pre‑ and intra‑COVID-19 pandemic care delivery, reflecting real-world operational challenges in ICUs.
Limitations and caveats: As an observational analysis, associations should not be interpreted as definitive causal effects. Hospital-level variables were measured cross-sectionally at baseline, which limits assessment of temporal relationships and may miss subsequent quality-improvement efforts. Residual confounding remains possible despite adjustment for individual covariates: ICUs with prevention protocols and better staffing may also differ in unmeasured ways (leadership, safety culture, diagnostics access). The definitions for VAP and CLABSI were according to Brazilian regulatory guidance; surveillance case definitions can vary internationally (e.g., NHSN definitions), which may affect direct comparisons with other cohorts. The study period partially overlaps the COVID-19 pandemic, a time of substantial system strain and altered infection dynamics; sensitivity analyses exploring pandemic vs non-pandemic periods would be informative but are not reported here. Lastly, the generalizability to other LMICs with different financing and health-system structures should be considered cautiously.
Mechanistic plausibility: The protective associations are biologically plausible. Hand hygiene and alcohol rub availability reduce cross-transmission. Adequate nurse staffing enables timely catheter care, early removal, mouth care, oral hygiene, mobilization, and adherence to ventilator bundles. Nurse-driven sedation management and respiratory-therapist-led weaning accelerate liberation from MV, reducing exposure time to the primary risk factor for VAP. Dentist availability likely improves oral health and reduces colonization burden, a recognized VAP risk modifier.
Implications for practice and policy
For clinicians and hospital leaders in LMICs, the study supports prioritizing foundational investments that are often overlooked but high-yield: ensuring access to alcohol‑based hand rubs, formalizing prevention bundles, implementing regular hand hygiene training, and staffing ICUs adequately. Empowering nurses and respiratory therapists with protocolized responsibilities (sedation titration, weaning algorithms) can be an effective, scalable strategy to reduce ventilator days and VAP risk. Policymakers should consider that measurable institutional changes can explain a substantial portion of inter-hospital variability in HAI rates — justifying financial and regulatory incentives to implement these measures across networks.
Research priorities
Key unanswered questions include: What is the causal impact of specific staffing thresholds for preventing CLABSI and VAP in LMIC ICUs? Can stepped-wedge or cluster-randomized trials of bundled interventions (staffing, training, equipment availability) demonstrate reductions in device-associated infections in resource-limited settings? What is the role of family presence interventions on physiologic and infection-related outcomes? Finally, linking institutional measures to antimicrobial resistance patterns and patient-centered outcomes (mortality, functional status) would help refine priorities.
Conclusion
The IMPACTO‑MR nested cohort provides robust, multicenter evidence that ICU structure and processes account for a substantial share of between-hospital variability in VAP and CLABSI rates in Brazilian ICUs. The associations are clinically meaningful and actionable: relatively low‑tech, high-impact interventions — prevention protocols, hand hygiene training, adequate nurse staffing, alcohol rubs and single-use gowns, and empowering clinical roles for sedation and weaning — are linked with lower infection burdens. For LMIC health systems striving to improve ICU quality, these findings offer an evidence-based roadmap for prioritizing interventions that are likely to yield measurable reductions in device-associated HAIs.
Funding and clinicaltrials.gov
Funding and registration details are reported in the original publication (Besen BAMP et al., Crit Care Med 2025). Readers should consult the primary article for the full funding statement and trial/platform registration information.
References
1. Besen BAMP, Dietrich C, Pinheiro CCG, et al; IMPACTO‑MR investigators and BRICNet. Institutional Risk Factors Associated With Healthcare-Associated Infections in Brazilian ICUs: A Nested Cohort Within the IMPACTO‑MR Platform. Crit Care Med. 2025 Dec 1;53(12):e2540-e2551. doi:10.1097/CCM.0000000000006881.
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