INTRODUCTION

Background

Ventilator-associated pneumonia (VAP) remains one of the most consequential healthcare-associated infections in intensive care units (ICUs), affecting up to 27% of patients on mechanical ventilation, with mortality rates ranging from 20% to 50%. A comprehensive systematic review of randomized preventive studies showed that VAP is associated with significantly increased mortality, particularly in surgical patients [1]. Surveillance of ventilator-associated events has recently been standardized with a three-tiered algorithm encompassing ventilator-associated conditions (VAC), infection-related VAC (IVAC), and VAP, which facilitates earlier detection and intervention [2]. Although many preventive measures for VAP have been proposed, effective prevention generally requires a multifaceted strategy rather than reliance on a single intervention [3].

The prophylactic use of inhaled antibiotics remains a subject of debate within the critical care community. Aerosolized amikacin can be effectively distributed to both the airways and alveoli, demonstrating particular utility in patients with extensive lung parenchymal injury, such as those with trauma, where systemic antimicrobial therapy may fail to achieve minimum inhibitory concentrations [4]. Ongoing research continues to explore the potential role of aerosolized amikacin in VAP prevention [5,6]. The proposed mechanism involves reducing bacterial colonization of the respiratory tract [7,8]. Despite this rationale, evidence supporting its efficacy remains limited. The recent large multicenter AMIKINHAL randomized controlled trial provided encouraging findings, showing that prophylactic inhaled amikacin significantly reduced IVAC incidence compared with placebo (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.50–0.89) in patients on mechanical ventilation [9]. However, these results have generated substantial debate [10]. A subsequent meta-analysis indicated that although inhaled amikacin reduced VAP occurrence, it failed to improve key clinical outcomes, including mortality, mechanical ventilation duration, and ICU or hospital length of stay [11]. Thus, the clinical efficacy of prophylactic inhaled amikacin has not reached consensus and is not included in current VAP prevention guidelines. Importantly, the effect of prophylactic inhaled amikacin has never been examined specifically in mechanically ventilated trauma patients, who face increased VAP risk due to rib fractures, pulmonary contusions, failed prehospital intubations, and prolonged ventilation requirements [12].

In light of the potential benefits reported in earlier studies, our institution implemented a standardized inhaled amikacin protocol in September 2024 for trauma patients requiring mechanical ventilation for more than 72 hours who were considered at high risk for VAP.

Objectives

We hypothesized that prophylactic administration of inhaled amikacin would prevent VAP development in the trauma ICU setting. This retrospective cohort study analyzed our institutional experience by comparing VAP incidence between trauma patients who received prophylactic inhaled amikacin and those who did not. The primary objective was to assess the effectiveness of this preventive approach in mechanically ventilated trauma patients.

METHODS

Ethics statement

This study was approved by the Institutional Review Board of National Medical Center (No. 2025-02-029). The requirement for informed consent was waived due to the use of deidentified electronic medical record (EMR) data and the retrospective observational nature of the study. All data were anonymized before extraction and transferred to the research team for analysis. All study procedures were performed in accordance with the principles of the Declaration of Helsinki.

Study design and setting

After the introduction of an inhaled amikacin protocol for VAP prevention in September 2024, we conducted a retrospective cohort study comparing equal time periods before and after protocol initiation. Data were collected from patients who received mechanical ventilation following traumatic injury in the trauma ICU of our tertiary care institution between May 2024 and December 2024. A total of 187 patients were initially screened for eligibility.

Participants

Exclusion criteria were as follows: mechanical ventilation for <72 hours, percutaneous tracheostomy prior to admission, receipt of systemic aminoglycosides during the ICU stay, or ICU admission for mechanical ventilation due to nontraumatic causes. After applying these criteria, 66 patients were included in the final analysis, with 28 in the prophylaxis group and 38 in the control group (Fig. 1). In the control group, 30 of 38 participants were male, whereas in the prophylaxis group, 20 of 28 participants were male.

Data collection

Data were obtained by reviewing the EMR of enrolled patients. Inclusion criteria were mechanically ventilated patients admitted to the trauma ICU with traumatic injury who required ventilation for >72 hours. Investigators reviewed each EMR for evidence of pulmonary infection.

Following the US Centers for Disease Control and Prevention (CDC)’s ventilator-associated event surveillance protocol [2], IVAC was defined as the new onset of pulmonary infiltrates on chest radiography (x-ray or computed tomography) accompanied by fever and elevated inflammatory markers, including white blood cell count, C-reactive protein, and procalcitonin. VAP was diagnosed when IVAC criteria were met along with microbiological confirmation from pulmonary secretion cultures.

Baseline characteristics, such as age, sex, and anthropometric data (including body weight and height), as well as medical data, including the severity of patient’s conditions as represented by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and comorbidities, were analyzed to assess patients’ medical conditions at the time of IVAC or VAP identification.

Because this was a retrospective study, IVAC was assumed to precede VAP in the clinical course. Upon suspicion of IVAC, appropriate management, including active lung care and antimicrobial therapy, was implemented to prevent progression to VAP. Each suspected IVAC or VAP case was reviewed and discussed with the attending clinician for diagnostic confirmation.

The primary outcomes were the incidence of IVAC and VAP, measured from 48 hours to 28 days after ICU admission in both prophylaxis and control groups. Secondary outcomes included 30-day mortality, duration of mechanical ventilation (including post-tracheostomy ventilation), duration of endotracheal intubation (defined as ventilation via an endotracheal tube), ICU length of stay, hospital length of stay, and duration of antimicrobial therapy.

Statistical analysis

Continuous variables were expressed as mean±standard deviation and compared using the Student t-test or Wilcoxon test, depending on normality as assessed with the Shapiro-Wilk test. Variance homogeneity was evaluated with equality of variance tests, and the Welch t-test was applied if assumptions of equal variance were violated. Categorical variables were reported as frequencies or proportions and compared using the chi-square test or Fisher exact test, depending on expected frequencies. Kaplan-Meier curves were constructed to illustrate the cumulative incidence of IVAC and VAP in the prophylaxis and control groups, with comparisons performed using log-rank tests.

Baseline variables showing significant between-group differences (APACHE II score and proton pump inhibitor [PPI] use) were included in multivariable analyses to adjust for confounding. Restricted cubic spline functions with knots at the 25th, 50th, and 75th percentiles of APACHE II scores were used to model potential nonlinear associations between APACHE II scores and IVAC/VAP incidence, confirming APACHE II score as a confounder. Models were adjusted for inhaled amikacin and PPI use.

To minimize selection bias and control for confounding, propensity score matching was performed using logistic regression with a caliper width of 0.25 standard deviation and 1:1 nearest-neighbor matching without replacement. Propensity scores were calculated based on APACHE II scores and PPI use. Between-group balance was assessed using standardized mean differences (SMDs), with SMD of <0.1 considered indicative of good balance. Post–propensity score matching analyses included multivariable binary logistic regression to identify risk factors for IVAC and VAP, and multivariable Cox proportional hazards regression to confirm independent predictors, with results expressed as HRs and 95% CIs.

Statistical significance was defined as P<0.05. All analyses were conducted using R ver. 4.4.2 (R Foundation for Statistical Computing).

RESULTS

Study population and the inhaled amikacin protocol

Among the 66 enrolled patients, 28 (42.42%) received prophylactic inhaled amikacin according to the implemented protocol (prophylaxis group), and 38 patients (57.58%), most of whom were admitted before September 2024, served as the control group. Indications for inhaled amikacin were age >18 years and mechanical ventilation via endotracheal tube for >72 but <96 hours. Contraindications included tracheostomy, pregnancy or lactation, and systemic aminoglycoside therapy. The prescribed dose was 20 mg/kg of body weight, with a maximum of 2 g, diluted to a concentration of 1 g/8 mL and up to 2 g/16 mL. Inhaled amikacin was administered once daily for 3 consecutive days beginning 72 hours after mechanical ventilation (Table S1). The proportion of patients who received antibiotics was similar between the two groups (52.63% vs. 60.71%, P=0.69). The duration of antibiotic therapy was also comparable (7.5±4.09 days vs. 10.7±7.85 days, P=0.24). Patients receiving antibiotics had clinical conditions requiring treatment, such as open fractures, contaminated wounds, or bowel perforation.

Baseline characteristics did not differ significantly between the prophylaxis and control groups, except for the APACHE II score and the use of PPI and histamine-2 blockers (Table 1). Inhaled amikacin was delivered via vibrating mesh nebulizers integrated into mechanical ventilators. Administration time varied with body weight–based dosing (20 mg/kg). The dose was determined according to the inhaled amikacin protocol used in the AMIKINHAL randomized controlled trial. Because this study was retrospective, drug delivery times were not recorded, and analysis of delivery duration was not part of the initial protocol. However, interviews with nurses at our institution indicated that administration typically required approximately 1 hour. Inhaled amikacin was administered to patients meeting the same inclusion criteria used in the AMIKINHAL randomized controlled trial. Thus, 72 hours after admission to the trauma ICU, inhaled amikacin therapy was initiated and continued for the following 72 hours.

VAP and IVAC

VAP occurred more frequently in the prophylaxis group compared with the control group (78.6% vs. 44.7%, P=0.01). Similarly, the incidence of IVAC was higher in the prophylaxis group (85.7% vs. 55.3%, P=0.02). Although the time to VAP onset was slightly longer in the prophylaxis group, the difference was not statistically significant (13.7±6.7 days vs. 11.9±3.0 days, P=0.28). The time to IVAC onset was also similar (5.9±2.9 days vs. 5.7±2.8 days, P=0.46) (Table 2).

During the 28-day follow-up after initiation of mechanical ventilation, Kaplan-Meier analysis showed a higher cumulative incidence of IVAC in the prophylaxis group, though this did not reach statistical significance (P=0.09). The cumulative incidence of VAP was not significantly different between groups (Fig. 2).

After adjustment for APACHE II score with or without PPI use, APACHE II score remained significantly associated with increased risk of both VAP (odds ratio [OR], 1.09; 95% CI, 1.01–1.17; P=0.03) and IVAC (OR, 1.09; 95% CI, 1.01–1.19; P=0.04). In contrast, inhaled amikacin lost statistical significance, suggesting that the higher incidence in the prophylaxis group may be explained by APACHE II score differences (Table 3). Restricted cubic spline regression confirmed the confounding effect of APACHE II score on logistic regression–derived ORs (Fig. S1).

Propensity score matching was applied to balance APACHE II scores and PPI use between groups. SMDs were calculated as the mean difference divided by the pooled standard deviation. After matching, the SMD for APACHE II scores decreased from 0.736 to 0.107, with no statistically significant between-group differences (P=0.43), indicating adequate covariate balance (Table S2). Baseline characteristics after propensity score matching showed no significant differences between groups (Table 1).

Multivariate logistic regression adjusted for APACHE II scores and PPI use indicated that inhaled amikacin was associated with higher odds of both VAP (OR, 3.00; 95% CI, 0.80–12.81; P=0.11) and IVAC (OR, 3.10; 95% CI, 0.71–18.43; P=0.15), though neither association reached statistical significance (Fig. 3). In the Cox proportional hazards model, inhaled amikacin showed neither a significant risk-enhancing nor protective effect for IVAC (HR, 1.68; 95% CI, 0.78–3.59; P=0.18) or VAP (HR, 1.10; 95% CI, 0.47–2.58; P=0.82) (Fig. 4).

Secondary clinical outcomes

Although 30-day mortality was lower in the prophylaxis group, the difference was not statistically significant. The overall duration of mechanical ventilation was similar between the groups; however, the duration of endotracheal intubation was significantly longer in the prophylaxis group (P=0.03), which may reflect the higher incidence of VAP in this cohort. No significant between-group differences were observed for ICU length of stay, hospital length of stay, or duration of antibiotic use. The comparison of acute kidney injury incidence was limited by the low frequency of events (<10% in both groups). These nonsignificant differences remained unchanged after propensity score matching (Table S3). Rates of acute kidney injury and the number of patients requiring reintubation were also comparable between the two groups, with no statistically significant differences.

DISCUSSION

The efficacy of inhaled antibiotics for pulmonary infections has been widely investigated. Systematic reviews have shown that inhaled antibiotics can improve clinical cure rates with minimal renal toxicity, though no mortality benefit has been demonstrated. However, their use is limited by a higher incidence of bronchospasm [13,14]. Current guidelines provide only weak recommendations. The clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society Guidelines endorse inhaled antibiotics primarily for treating multidrug-resistant VAP in situations where systemic options are restricted [15], whereas the European Society of Clinical Microbiology and Infectious Diseases Study Group for Infections in Critically Ill Patients advises against their routine use [16]. Although meta-analyses have suggested potential preventive benefits, particularly in reducing colonization by multidrug-resistant pathogens, robust evidence supporting prophylactic use remains lacking [17].

Our retrospective analysis of early institutional experience with inhaled amikacin yielded findings that diverged from the anticipated protective effect. Contrary to its theoretical benefit, inhaled amikacin was associated with a higher incidence of VAP in unadjusted analyses. However, this association was weakened after adjustment for established VAP risk factors, most notably APACHE II score [18], which differed significantly between groups. After propensity score matching to control for confounders, especially APACHE II score, which emerged as a significant predictor of VAP in multivariate regression, the association between inhaled amikacin and increased VAP risk was no longer statistically significant. Cox proportional hazards regression further confirmed that inhaled amikacin did not act as either a protective or risk factor for VAP development.

These results contrast with the preventive effect reported in the AMIKINHAL randomized controlled trial [9]. Notably, criticism of the AMIKINHAL trial questioned the justification for prophylactic inhaled amikacin, highlighting methodological concerns such as the possibility that reduced bacterial burden from amikacin exposure could lead to underdiagnosis of VAP in the treatment group [10]. The same critics also argued against using VAP as a primary endpoint, pointing out diagnostic uncertainty, procedural variability, and the limited sensitivity and specificity of detection methods [19]. Our institutional findings align with these criticisms, as implementation of a prophylactic inhaled amikacin protocol did not demonstrate clinical benefit. Although our study did not quantify bacterial burden and therefore could not assess diagnostic bias directly, the consistent results across both VAP and IVAC outcomes suggest that underdetection of pulmonary infection alone is unlikely to explain our observations. Large, multicenter, prospective studies remain necessary to establish the true efficacy and safety profile of prophylactic inhaled amikacin. Such trials should employ standardized diagnostic criteria and incorporate microbiological quantification to overcome the limitations noted in earlier studies.

Despite the lack of statistical significance in the final results, the prophylaxis group still demonstrated a trend toward worse pulmonary outcomes after adjustment for confounding factors. Beyond drug efficacy, the nebulization process itself warrants consideration as a potential contributor to adverse effects. Aerosol delivery equipment is classified as a semicritical device under the CDC guidelines, requiring strict disinfection, sterilization, and protection against microbial colonization to prevent it from becoming a source of infection [20]. Furthermore, aerosolization may alter the microenvironment of the bronchial and alveolar spaces by increasing humidity, thereby promoting microbial proliferation [21]. Maintaining optimal hygienic and technical conditions for aerosol devices is essential to avoid iatrogenic infection. The administration of a prophylactic intervention without validated efficacy could therefore increase infection risk, in contrast to the established safety of conventional nebulized agents such as ipratropium bromide (a short-acting antimuscarinic agent) or N-acetyl-L-cysteine (a mucolytic agent).

A notable finding was the marked difference in nebulization parameters between amikacin therapy and conventional treatments. Standard nebulized medications typically require 1 to 3 mL and approximately 15 minutes for administration, whereas amikacin nebulization requires substantially larger volumes and extended administration times exceeding one hour. Although this protocol mirrored the AMIKINHAL trial methodology, the prolonged exposure and increased solution volume may have independently contributed to infection risk. The higher incidence of IVAC and VAP in the prophylaxis group may also reflect the absence of placebo inhalation in the control group, unlike previous studies such as the AMIKINHAL trial, in which a saline placebo at comparable volumes was administered. Currently, there is no consensus on the optimal dilution volume for inhaled amikacin. Pharmacokinetic studies suggest that conventional dosing may exceed what is necessary to achieve therapeutic targets [1]. This implies that lower doses could be sufficient for clinical efficacy, particularly in a preventive setting. If our dosing protocol delivered supratherapeutic levels, it is possible that patients received overly potent therapy while simultaneously being exposed to conditions favorable for infection through the nebulization process itself. Future studies should evaluate whether increased solution volume and extended nebulization duration independently worsen pulmonary outcomes and identify dosing strategies that balance therapeutic efficacy with minimal risk.

Acute kidney injury and reintubation events were comparable between the groups, suggesting that nephrotoxicity from amikacin and pulmonary complications such as bronchospasm, previously reported adverse effects of inhaled antibiotics, may not have been significantly induced by inhaled amikacin in this cohort. Nonetheless, given the small sample size and the limited number of patients with such events, our institutional experience is insufficient to definitively establish the safety of inhaled amikacin.

Limitations

This study has several limitations. First, the retrospective observational design may have hindered the optimal recognition and management of VAP and IVAC, since these conditions were identified retrospectively and may not have been consistently detected during clinical care. Second, important confounders, including PPI use and APACHE II scores, were unevenly distributed between groups. Third, additional variables such as sedation depth, use of neuromuscular blockers (e.g., vecuronium bromide), and ventilator or humidifier settings were not evaluated, though they may influence pulmonary outcomes. Fourth, the single-center design limits the generalizability of these results to other institutions. Fifth, the retrospective identification of IVAC and VAP from chart review and clinician input may have introduced detection bias. Finally, amikacin was used off-label as an inhaled antibiotic, which could have contributed to unintended adverse effects.

The incidence of IVAC and VAP in this study was higher than in prior reports. This may be explained by several limitations, including possible selection bias introduced by the attending clinicians who managed each case. Furthermore, treatment of patients with severe traumatic injuries may differ from that in other studies. In our population, extensive pain, aggressive volume resuscitation, and risk factors such as ventilator-induced lung injury from patient-ventilator asynchrony or volume overload were likely present but could not be assessed because relevant records were not consistently available in this retrospective analysis.

Conclusions

The implementation of an inhaled amikacin protocol for IVAC and VAP prevention in mechanically ventilated trauma patients did not demonstrate significant prophylactic benefit in our institution. The effectiveness of inhaled antimicrobial therapy may be lower than initially hypothesized and appears influenced by factors such as dilution volume requirements to achieve pulmonary parenchymal concentrations and prolonged nebulization times. Future studies should specifically address these confounding factors while also exploring the pharmacokinetic feasibility of lower antibiotic doses. Given the retrospective, single-center design of this study, the findings should be interpreted cautiously and may not be generalizable. Further large-scale research with careful attention to confounding factors is required to clarify the precise role of inhaled amikacin in VAP prevention.

ARTICLE INFORMATION

Author contributions

Conceptualization: Youngwoong Kim; Data curation: Youngwoong Kim, SHY, Younghwan Kim, MK, JJ, GH; Funding acquisition: Youngwoong Kim, SHY, Younghwan Kim; Investigation: OK; Methodology: OK, Youngwoong Kim, NL; Project administration: Youngwoong Kim, NL; Resources: Youngwoong Kim, SHY, Younghwan Kim, MK, JJ, GH; Software: OK, Youngwoong Kim, NL; Supervision: Youngwoong Kim; Validation: OK, GH; Visualization: OK; Writing–original draft: OK; Writing–review & editing: Youngwoong Kim, NL, SHY, Younghwan Kim, MK, JJ, GH. All authors read and approved the final manuscript.

Conflicts of interest

The authors have no conflicts of interest to declare.

Funding

This study was supported by the publication fee support from the Researcher Support Project of the Public Health and Medical Research Institute, National Medical Center of Korea.

Acknowledgments

The authors thank Mijeong Kim and Himchan Lee (Seoul Regional Trauma Center, National Medical Center) for their assistance with data collection. The authors also thank Sooyeon Min (Department of Neuropsychiatry, Seoul National University Hospital) for consultation on statistical validation methodology.

Data availability

Data analyzed in this study are available from the corresponding author upon reasonable request.

Supplementary materials

Fig. 1.

Study process flowchart.

Fig. 2.

Kaplan-Meier curves illustrating the cumulative incidence of (A) ventilator-associated pneumonia (VAP) and (B) infection-related ventilator-associated conditions (IVAC).

Fig. 3.

Binary logistic regression analysis of the odds ratio (OR) for (A) ventilator-associated pneumonia and (B) infection-related ventilator-associated conditions after propensity score matching. APACHE, Acute Physiology and Chronic Health Evaluation; PPI, proton pump inhibitor; CI, confidence interval.

Fig. 4.

Cox proportional hazards regression analysis of the hazard ratio (HR) for (A) ventilator-associated pneumonia and (B) infection-related ventilator-associated conditions after propensity score matching. PPI, proton pump inhibitor; APACHE, Acute Physiology and Chronic Health Evaluation; CI, confidence interval.

REFERENCES

• 1. Melsen WG, Rovers MM, Groenwold RH, et al. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013;13:665–71.ArticlePubMed
• 2. Klompas M. Complications of mechanical ventilation: the CDC's new surveillance paradigm. N Engl J Med 2013;368:1472–5.ArticlePubMed
• 3. Morrow LE, Kollef MH. Recognition and prevention of nosocomial pneumonia in the intensive care unit and infection control in mechanical ventilation. Crit Care Med 2010;38:S352–62.ArticlePubMed
• 4. Ehrmann S, Chastre J, Diot P, Lu Q. Nebulized antibiotics in mechanically ventilated patients: a challenge for translational research from technology to clinical care. Ann Intensive Care 2017;7:78.ArticlePubMedPMCPDF
• 5. Palmer LB, Smaldone GC, Chen JJ, et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit Care Med 2008;36:2008–13.ArticlePubMed
• 6. Zha S, Niu J, He Z, et al. Prophylactic antibiotics for preventing ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis. Eur J Med Res 2023;28:348.ArticlePubMedPMCPDF
• 7. Kollef MH. The prevention of ventilator-associated pneumonia. N Engl J Med 1999;340:627–34.ArticlePubMed
• 8. Rello J, Kollef M, Diaz E, et al. Reduced burden of bacterial airway colonization with a novel silver-coated endotracheal tube in a randomized multiple-center feasibility study. Crit Care Med 2006;34:2766–72.ArticlePubMed
• 9. Ehrmann S, Barbier F, Demiselle J, et al. Inhaled amikacin to prevent ventilator-associated pneumonia. N Engl J Med 2023;389:2052–62.ArticlePubMed
• 10. Ehrmann S, Gregoire N, Tavernier E. Inhaled amikacin to prevent ventilator-associated pneumonia. Reply. N Engl J Med 2024;390:770.ArticlePubMed
• 11. Hsu WH, Wu JY, Shiau BW, et al. The preventive effect of inhaled antibiotic against ventilator-associated pneumonia: a systematic review and meta-analysis. Int J Antimicrob Agents 2024;64:107324.ArticlePubMed
• 12. Mangram AJ, Sohn J, Zhou N, et al. Trauma-associated pneumonia: time to redefine ventilator-associated pneumonia in trauma patients. Am J Surg 2015;210:1056–61.ArticlePubMed
• 13. Sweeney DA, Kalil AC. Why don't we have more inhaled antibiotics to treat ventilator-associated pneumonia? Clin Microbiol Infect 2019;25:1195–9.ArticlePubMed
• 14. Tang R, Luo R, Wu B, Wang F, Song H, Chen X. Effectiveness and safety of adjunctive inhaled antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials. J Crit Care 2021;65:133–9.ArticlePubMed
• 15. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:e61–111.ArticlePubMedPMC
• 16. Rello J, Solé-Lleonart C, Rouby JJ, et al. Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases. Clin Microbiol Infect 2017;23:629–39.ArticlePubMed
• 17. Póvoa FC, Cardinal-Fernandez P, Maia IS, Reboredo MM, Pinheiro BV. Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis. J Crit Care 2018;43:240–5.ArticlePubMed
• 18. Li W, Cai J, Ding L, Chen Y, Wang X, Xu H. Incidence and risk factors of ventilator-associated pneumonia in the intensive care unit: a systematic review and meta-analysis. J Thorac Dis 2024;16:5518–28.ArticlePubMedPMC
• 19. Young PJ, Delaney A, Hills T. Ventilator-associated pneumonia: a problematic outcome for clinical trials. Crit Care Resusc 2023;25:159–60.ArticlePubMedPMC
• 20. Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R. Guidelines for preventing health-care–associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep 2004;53:1–36.
• 21. O'Malley CA. Device cleaning and infection control in aerosol therapy. Respir Care 2015;60:917–27.ArticlePubMed

Figure & Data

References

Citations

Citations to this article as recorded by