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Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults

Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults
Author:
Michael Klompas, MD, MPH
Section Editor:
Thomas M File, Jr, MD
Deputy Editor:
Milana Bogorodskaya, MD
Literature review current through: Apr 2025. | This topic last updated: Mar 20, 2025.

INTRODUCTION — 

Hospital-acquired (or nosocomial) pneumonia (HAP) and ventilator-associated pneumonia (VAP) are important causes of morbidity and mortality despite improved antimicrobial therapy, supportive care, and prevention. The risk factors and prevention of HAP and VAP will be reviewed here.

The clinical presentation, diagnosis, epidemiology, pathogenesis, microbiology, and treatment of HAP and VAP are discussed separately. (See "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia" and "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults" and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults".)

DEFINITIONS

Pneumonia types — Pneumonia is frequently categorized based on site of acquisition (table 1).

●Hospital-acquired (or nosocomial) pneumonia (HAP) is pneumonia that occurs 48 hours or more after admission to the hospital and did not appear to be incubating at the time of admission.

●Ventilator-associated pneumonia (VAP) is a type of HAP that develops in intubated patients on mechanical ventilation for more than 48 hours. VAP also includes HAP that occurs within 48 hours of extubation.

●Non-ventilator-associated HAP (NV-HAP) refers to HAP that develops in hospitalized patients who are not on mechanical ventilation nor underwent extubation within 48 hours before pneumonia developed. NV-HAP can be divided into patients that ultimately require mechanical ventilation (VHAP) due to the pneumonia versus those that do not. VHAP is associated with particularly poor clinical outcomes [1].

Healthcare-associated pneumonia (HCAP) is no longer recognized as a separate category of pneumonia and was purposefully not included in the 2016 and 2019 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) HAP [2] and community-acquired pneumonia (CAP) [3] guidelines or the combined 2017 European and Latin American HAP guidelines [4]. Historically, HCAP referred to pneumonia acquired in health care facilities such as nursing homes, hemodialysis centers, and outpatient clinics, or pneumonia acquired within three months following a hospitalization [5]. This category was used to identify patients at risk for infection with multidrug-resistant (MDR) pathogens. However, the majority of patients identified by this categorization did not have MDR pathogens and so the HCAP classification may have led to increased, inappropriate broad antibiotic use. Although patients with recent contact with health care facilities are at increased risk for infection with MDR pathogens, this risk is small for most patients and the overall incidence of MDR pathogens in this population is low. Other risk factors such as recent antibiotic exposures and a prior history of MDR infection or colonization are much more potent predictors of MDR infections [6-12].

We manage patients who would have been previously classified as having HCAP in a similar way to those with CAP, deciding whether to include therapy targeting MDR pathogens on a case-by-case basis depending upon each patient's specific risk factors and severity of illness [3]. Specific risk factors for resistance that should be assessed include known colonization with MDR pathogens, recent receipt of antimicrobials, comorbidities, functional status, and severity of illness [13,14]. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting" and "Treatment of community-acquired pneumonia in adults who require hospitalization".)

Antimicrobial resistance — The United States Centers for Disease Control and Prevention (CDC) and the European Centre for Disease Prevention and Control (EDCD) have developed standard terminology for antimicrobial-resistant gram-negative bacilli, which are important causes of HAP and VAP [15]:

●MDR refers to acquired nonsusceptibility to at least one agent in three different antimicrobial classes.

●Extensively drug resistant refers to nonsusceptibility to at least one agent in all but two antimicrobial classes.

●Pandrug resistant refers to nonsusceptibility to all antimicrobial agents that can be used for treatment.

Awareness of local resistance patterns is critical for decisions regarding empiric therapy for HAP and VAP [16]. All hospitals should regularly create and disseminate a local antibiogram, ideally one that is specific to the different units in the hospital (although small numbers of cases per unit may preclude this) [2].

RISK FACTORS

Intubation — The most significant risk factor for HAP is intubation. Prolonged intubation, reintubation, and frequent ventilator circuit changes also increase the risk of developing HAP [17-25]. As an example, in a multicenter survey of over 230,000 patients across Europe, HAP was much more likely to occur in intubated patients compared with non-intubated patients (15 versus 1 percent; OR 18.0, 95% CI 17-20) [25]. (See "The decision to intubate" and "Initial weaning strategy in mechanically ventilated adults" and "Extubation management in the adult intensive care unit" and "The ventilator circuit".)

Other risk factors — Other risk factors, which have emerged from multivariate analyses, include [17-19,26-37]:

●Older age [31,38].

●Chronic lung disease [29].

●Depressed consciousness [39].

●Aspiration [29].

●Chest or upper abdominal surgery [19,29,39].

●Previous antibiotic exposure, especially broad spectrum [18,20,40].

●Total opioid exposure [41].

●Alcohol use disorder [42].

●Multiple trauma [20,21].

●Paralysis and deep sedation [21].

●Number of central venous catheter placements and surgeries [22].

●Use of muscle relaxants or glucocorticoids [22].

●The presence of an intracranial pressure monitor [26].

●Malnutrition, chronic renal failure, anemia, Charlson Comorbidity Index, previous hospitalization [39].

●Poor oral hygiene [43,44].

●Increased gastric pH – observational studies have suggested an association between gastric acid suppression and an increased risk for HAP [45-49] but large, randomized trials of proton pump inhibitors (the agents most commonly used for gastric acid suppression) versus placebo have not reported any impact on HAP rates [50,51].

PREVENTION

Essential practices — The Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) issues updated practice recommendations to reduce the risk of VAP and NV-HAP in 2022 (table 2) [52]. Essential practices that are recommended by SHEA/IDSA for preventing VAP and NV-HAP in all acute care hospitals include avoiding intubation and preventing reintubation when possible (eg, using noninvasive ventilation or high-flow oxygen by nasal cannula instead), maintaining and improving physical conditioning, elevating the head of the bed, and providing oral care with toothbrushing but without chlorhexidine. For ventilated patients, additional essential practices include minimizing sedation through the use of sedative protocols, implementing ventilator liberation protocols, and changing ventilator circuits only if visibly soiled or malfunctioning. Although evidence supporting the use of bundles is mixed, combining a core set of prevention measures into a bundle can be a practical way to enhance care [53-60]. (See 'HAP prevention bundles' below.)

The following discussion will review some of the modalities that have been evaluated for preventing VAP and NV-HAP.

Most prevention trial data is focused on prevention of VAP. The data on preventing NV-HAP are limited to observational studies, retrospective analyses of quality improvement initiatives, and a handful of randomized trials [61-64].

General issues related to prevention of infections in the intensive care unit (ICU) and infection control are discussed separately. (See "Nosocomial infections in the intensive care unit: Epidemiology and prevention" and "Infection prevention: Precautions for preventing transmission of infection".)

Minimize time intubated — The biggest risk factor for VAP is the time spent intubated. Thus, preventing intubation and reintubation and facilitating early extubation are essential practices to reduce the risk of ventilator-associated pneumonia. Additionally, we avoid changing the ventilator circuit unless it is visibly soiled, malfunctioning, or if periodic changes are recommended by the circuit manufacturer.

The approach to mechanical ventilation, noninvasive ventilation, maintenance of the ventilator circuit, and sedation is discussed separately. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit" and "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients", section on 'Suctioning and oral care' and "The ventilator circuit" and "Sedative-analgesia in ventilated adults: Management strategies, agent selection, monitoring, and withdrawal".)

Prevent aspiration — Aspiration is a major predisposing mechanism for both NV-HAP and VAP. Elevating the head of the bed, minimizing sedation, draining subglottic secretions in ventilated patients, maintaining endotracheal tube airway cuff pressure (20 to 30 cm H2O), applying positive end-expiratory pressure, and taking dysphagia precautions are measures that have been proposed to minimize aspiration [34,65-68]. (See "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients", section on 'Maintain optimal cuff pressure' and "Positive end-expiratory pressure (PEEP)".)

Elevate the head — The head of the bed should be elevated to 30 to 45° [53]. Supine positioning appears to predispose to aspiration and the development of HAP, particularly in patients receiving enteral nutrition [60]. In a meta-analysis of eight randomized trials evaluating over 750 mechanically ventilated adults, semirecumbent positioning (≥30 to 60°) appeared to reduce rates of clinically suspected VAP when compared with supine positioning but showed no impact on duration of mechanical ventilation, ICU length of stay, or mortality [69]. One randomized trial evaluated the impact of placing patients in the lateral Trendelenburg position in order to preferentially drain oral secretions away from the lungs [70]. VAP rates were lower in patients randomized to the lateral Trendelenburg position compared with the semirecumbent position (relative risk [RR] 0.13, 95% CI 0.02-1.03), but the trial was stopped early due to increased adverse events among patients placed in lateral Trendelenburg (eg, transient oxygen desaturation and hemodynamic instability). While no effect of positioning on duration of mechanical ventilation or mortality has been demonstrated, it seems prudent to preferentially place intubated patients in the semirecumbent position unless contraindicated [58,71].

Minimize sedation — Minimizing sedation may help prevent delirium, deconditioning, atelectasis, and aspiration, and therefore VAP [72,73]. In a systematic review and meta-analysis of 45 randomized trials including 5493 participants, daily sedation interruption greatly reduced VAP rates (RR 0.57, 95% CI 0.43-0.77) [72]. In one of the randomized trials included in the meta-analysis, a nurse-implemented protocol for minimizing sedation was associated with a lower incidence of VAP (6 versus 15 percent; HR 0.81, 95% CI 0.62-0.95) and shorter duration of mechanical ventilation (4 versus 8 days) [73].

Maintain oral care and toothbrushing — Maintaining oral care with toothbrushing (but not with chlorhexidine) has demonstrated to be effective in reducing risk of HAP. In a systematic review and meta-analysis of 15 randomized controlled trials with an effective population size of 2786 hospitalized patients (most of whom were on mechanical ventilation), daily toothbrushing was associated with lower risk for HAP (133 versus 207 HAP episodes; RR 0.68, 95% CI 0.57-0.82) and ICU mortality (187 versus 230 deaths; RR 0.81, 95% CI 0.69-0.95) [43]. When analysis was limited to only non-ventilated patients, there was a similar trend toward lower risk of NV-HAP but it did not reach statistical significance, most likely due to a smaller number of events (1 versus 4 HAP episodes; RR 0.32, 95% CI 0.05-2.02).

Chlorhexidine use in oral care is no longer recommended due to lack of clear evidence that chlorhexidine reduces pulmonary infections and a possible increase in mortality [52]. (See 'Practices that are not recommended' below.)

Enteral nutrition — If oral intake is not possible, we prefer providing enteral nutrition over parenteral nutrition. Early (within 48 hours of ICU admission) enteral nutrition is associated with reduced infectious complications, including HAP. In a meta-analysis of six randomized trials including over 5000 patients in the ICU, early enteral nutrition was associated with reduced incidence of infectious complications compared with early parenteral nutrition (RR 0.75, 95% CI 0.57, 0.98) [74].

Maintain physical conditioning — Early exercise and mobilization programs may help reduce the risk of HAP in ICU patients. Therefore, we engage physical therapy as early and as frequently as reasonably possible to maintain (and increase) the patient's physical conditioning. In a meta-analysis of 15 randomized controlled trial including 1941 patients in the ICU, early mobilization reduced the risk of VAP (RR 0.26, 95% CI 0.11-0.63) but did not reduce mortality rates [75]. Other meta-analyses of randomized controlled trials had similar findings [76-78]. All these studies focused on physical conditioning and rehabilitation in the ICU setting and the incidence of VAP rates. Smaller, less comprehensive studies suggest that physical conditioning may also reduce NV-HAP rates [62,79,80].

Practices that may be of benefit — These practices may decrease the risk of HAP but may be associated with other adverse events or may only be beneficial in a specific setting or patient population.

●Selective decontamination of the oropharynx and digestive tract – Decontamination of the oropharynx and/or digestive tract may reduce the incidence of pneumonia in critically ill patients by decreasing pathogen burden in the upper respiratory and gastrointestinal tract. Potential methods used include antiseptics (eg, chlorhexidine) in the oropharynx, selective decontamination of the oropharyngeal tract (SOD) with nonabsorbable antibiotics applied in the oropharynx, and selective decontamination of the digestive tract (SDD) with nonabsorbable antibiotics administered orally, with or without four days of intravenous antibiotics. Examples of antimicrobials included in oral and gastric tube regimens include colistin, tobramycin, and nystatin. The intravenous agent is typically a third-generation cephalosporin or a quinolone.

These strategies have demonstrated efficacy in reducing pneumonia risk in regions with low baseline antimicrobial resistance rates, but concern for promoting antimicrobial resistance limits the use of these strategies. Because of the concern for promoting antimicrobial resistance, the practice has not been routinely adopted in North America [5,53,81-83]; the Society for Healthcare Epidemiology of America guidelines and combined European and Latin American HAP and VAP guidelines recommend against SDD in settings with high baseline rates of antimicrobial utilization and antimicrobial resistance [4,52].

Meta-analyses have shown that SDD reduces the risk of VAP and HAP [84-87], particularly when the SDD regimen includes an intravenous component [88]. Both SOD and SDD have shown mortality benefits in trials of ICU patients performed mainly in regions with low baseline antimicrobial resistance rates [89,90]. The applicability of the studies showing benefit to other settings has been questioned since low rates of antibiotic resistance were present at the institutions included in the key trials [83,91].

In a multicenter randomized trial performed in European ICUs with high baseline antimicrobial resistance rates, no difference in 28-day mortality was detected with SOD, SDD, or 1 percent chlorhexidine oral care when compared with standard practice [92]. Because standard practice included oral care with 0.12 or 0.20 percent in most centers, the effect of chlorhexidine versus placebo on mortality could not be determined from this trial. The effect of these interventions on VAP was not reported. Of note, the SDD regimen in this trial did not include an intravenous component.

Additional detail on SDD is discussed separately. (See "Nosocomial infections in the intensive care unit: Epidemiology and prevention", section on 'Digestive and oropharyngeal decontamination'.)

●Subglottic drainage – Drainage of subglottic secretions that pool above the endotracheal tube cuff may lessen the risk of aspiration of secretions around the cuff and thereby decrease the incidence of VAP. Specially designed endotracheal tubes have been developed to provide continuous or intermittent aspiration of subglottic secretions (figure 1) [93-95]. However, these devices cost more than standard endotracheal tubes and have a large external diameter which may increase airway trauma. When available, they should be used for patients expected to require >48 or 72 hours of mechanical ventilation [53].

In a meta-analysis of 20 randomized trials evaluating 3684 patients, subglottic secretion drainage reduced the risk of VAP from 23 to 14 percent (RR 0.56, 95% CI 0.48-0.63) but there were no significant differences in duration of mechanical ventilation, ICU length of stay, or mortality [96,97].

●Postpyloric feeding – Postpyloric feeding may be beneficial in preventing HAP in patients with high risk of aspiration. As an example, in a meta-analysis of 19 randomized trials with over 1300 patients in the ICU, postpyloric feeding was associated with reduced pneumonia risk compared to gastric feeding (RR 0.70, 95% CI 0.55-0.90) [98]. However, there was no difference in duration of mechanical ventilation and mortality. Other meta-analyses demonstrated similar outcomes [74,99].

●Avoiding prolonged intubation with a tracheostomy – Early tracheostomy (within 7 days of intubation) has been shown to decrease the rate of VAP compared to late tracheostomy. In a meta-analysis of 17 randomized trials including over 3000 patients, early tracheostomy resulted in lower VAP rates (OR 0.59, 95% CI 0.35-0.99) and more ventilator-free days (mean difference 1.74, 95% CI 0.48-3.00) compared with late tracheostomy [100,101]. Another meta-analysis restricted to patients without neurological injury did not find significant impact of early tracheostomy on VAP rates [101], thus raising the question of whether early tracheostomy is best prioritized for patients with neurological injury.

●Systemic antibiotics – The efficacy of systemic antibiotics for the prevention of HAP is uncertain. In a meta-analysis of seven randomized trials including over 800 patients with acute brain injury (including hypoxemic brain injury from cardiac arrest) who received invasive mechanical intubation in an intensive care unit (ICU), administration of a short course of intravenous (IV) antibiotics reduced the incidence of VAP but did not reduce the duration of mechanical ventilation, ICU length of stay, nor in-hospital mortality [102]. As an example, in one of the randomized trials included in the meta-analysis, administration of ampicillin-sulbactam for two days reduced early-onset VAP (within the first seven days of ICU stay) but did not reduce late-onset VAP, duration of mechanical ventilation, ICU length of stay, nor 28-day mortality [103]. In contrast, another trial included in the meta-analysis that randomized 345 patients with traumatic brain injury or stroke to one dose of ceftriaxone versus placebo; those who received ceftriaxone not only had lower rates of early VAP but also more ventilator-free days (nine versus five days) and lower 28-day mortality (15 versus 25 percent) [104]. Although the data of the latter trial are compelling, the small number of events and participants in the trial, the lack of similar results in prior studies, and the concern for increased antibiotic resistance among respiratory bacterial flora preclude us from routinely using systemic antibiotics for the prevention of VAP [105].

Evidence evaluating the effect of prophylactic systemic antibiotics on rates of NV-HAP is limited. Although there are some trials conducted in patients with acute stroke [106-108], results have been mixed and these studies have not been generalized to the rest of the general population with NV-HAP. (See "Complications of stroke: An overview", section on 'Pneumonia'.)

●Inhaled antibiotics – The efficacy of inhaled antibiotics for the prevention of VAP is uncertain. In a double-blinded randomized study of 850 patients on mechanical ventilation for 72 to 96 hours, receipt of daily inhaled amikacin for the next three days reduced the incidence of VAP within the next 28 days compared with placebo (15 versus 22 percent, p = 0.004) [109]. In two network meta-analyses of randomized trials that both included over 1000 patients on mechanical ventilation, inhaled antibiotics also reduced the occurrence of VAP compared to placebo [110,111]. However, none of these studies demonstrated a difference in duration of mechanical ventilation, days of antibiotic utilization, or mortality between the two groups as would be expected if incidence of VAP decreased with the intervention. Additionally, there remains concern that widespread use of prophylactic inhaled antibiotics may select for colonization with multidrug resistant bacteria.

Practices that are not recommended — The following practices either have evidence suggesting possible harm or insufficient evidence to demonstrate benefit for preventing HAP.

●Chlorhexidine – The SHEA/IDSA guidelines recommends against the use of chlorhexidine for oral care due to the lack of clear evidence that chlorhexidine reduces pulmonary infections and the possibility that it may increase mortality [52].

Chlorhexidine use is controversial because of its uncertain efficacy and possible association with increased mortality [58,112-116]. The mechanism by which chlorhexidine might increase mortality is unclear. One hypothesis is that aspiration of chlorhexidine may precipitate acute respiratory distress syndrome in a small fraction of patients.

An increase in mortality with chlorhexidine use was detected in a single meta-analysis of 11 trials evaluating 2618 ICU patients when compared with placebo (28.5 versus 24.5 percent; odds ratio [OR] 1.25, 95% CI 1.05-1.50) [114]. In a subsequent retrospective review of 5539 mechanically ventilated patients, chlorhexidine was associated with an increased risk for ventilator mortality (hazard ratio [HR] 1.63, 95% CI 1.15-2.31) [58]. Other observational studies have raised the same concern for non-ventilated patients [117].

Several meta-analyses of randomized trials have reported an association between chlorhexidine and lower VAP rates [112-114,116,118]. One meta-analysis reported that oral care with chlorhexidine was associated with an RR for VAP of 0.67 (95% CI 0.47-0.97) based on review of 13 randomized trial including >1200 patients [118]. However, this finding should be interpreted with caution because the diagnostic criteria used for VAP were subjective and nonspecific, and multiple open-label trials were included in the analysis, introducing risk of bias.

Another meta-analysis of 16 trials evaluating 3630 critically ill patients showed a strong trend toward decreased VAP rates among open-label trials (RR 0.61, 95% CI 0.35-1.04) but a much weaker, non-significant effect amongst blinded trials (RR 0.88, 95% CI 0.66-1.16) [116]. None of the meta-analyses have found differences between chlorhexidine versus placebo in duration of mechanical ventilation, ICU length of stay, or hospital length of stay.

A cluster randomized trial of chlorhexidine discontinuation versus usual care conducted amongst 3260 patients in six ICUs in Canada reported that discontinuing chlorhexidine had no impact on infection-related ventilator-associated complications (a proxy for VAP; 4.8 versus 2.5 percent, OR 1.06, 95% CI 0.44-2.57), time to extubation (median 2 days versus 2 days, OR 1.03, 95% CI 0.83-1.23), or ICU mortality (23.5 versus 21.2 percent, OR 1.13, 95% CI 0.82-1.54) [119]. Oral health scores, however, were better amongst patients randomized to chlorhexidine de-adoption. De-adoption of chlorhexidine was accompanied by a multicomponent oral care bundle that included twice-daily oral assessment and toothbrushing, mouth moisturization, and lip moisturization with additional secretion removal every four hours.

●Probiotics – Probiotics are defined as live microorganisms of human origin that are able to tolerate the hostile gastrointestinal environment such that they persist in the lower alimentary tract to confer a health benefit to the host [120,121]. Available results do not provide sufficient evidence to draw conclusions regarding the efficacy or safety of probiotics for the prevention of HAP. Therefore, we do not use probiotics for the prevention of HAP.

In a meta-analysis of 13 randomized trials comparing a probiotic (eg, Lactobacillus spp) with a control, probiotic use was associated with reduced incidence of VAP (OR 0.62, 95% CI 0.45-0.85) [122]. However, when the meta-analysis was limited to the six trials that were double-blinded, the reduction in VAP incidence did not reach statistical significance. A subsequent multicenter randomized controlled trial of 2650 patients in the ICU randomized patients to Lactobacillus rhamnosus probiotic twice daily versus placebo and found a similar incidence of VAP in both groups (21.9 versus 21.3 percent) [123]. Twelve patients in the probiotic group with adverse events had the probiotic Lactobacillus strain isolated from a sterile body site. An updated meta-analysis that included this trial and focused on studies with low risk of bias also reported no association between probiotics and VAP, HAP, or hospital length of stay [124].

●Silver-coated endotracheal tubes – We do not use silver-coated endotracheal tubes (ETTs). Silver-coated ETTs may reduce the incidence of VAP but have no clear impact on other important outcomes [125-128]. As an example, in a meta-analysis of seven randomized trials, noble meta-coated ETTs resulted in a lower incidence of VAP compared to non-coated ETTs (9 versus 12 percent) but with no difference in mortality rates (29 versus 28 percent), duration of mechanical ventilation, or ICU stay [127].

●Gastric volume monitoring – It has long been standard clinical practice to monitor patients' gastric residual volume at regular intervals and/or prior to increasing the infusion rate of gastric tube feeding, with the hope of minimizing the risk of unrecognized gastric fluid accumulation and vomiting resulting in pneumonia. However, several studies have shown that measurement of gastric residuals correlates poorly with aspiration risk and is associated with a decrease in calorie delivery [129-131]. Furthermore, a randomized trial did not find lower VAP rates with monitoring of gastric residuals [132]. Based on these findings, we do not routinely check gastric residual volumes in asymptomatic patients receiving tube feedings. This is discussed in greater detail separately. (See "Nutrition support in critically ill adult patients: Enteral nutrition", section on 'Monitoring and management of complications'.)

HAP prevention bundles — HAP prevention bundles involve the integrated implementation of a combination of measures aimed at reducing the incidence of HAP among patients at risk. Bundling multiple measures together is hypothesized to provide synergistic protection against HAP. Typical bundle components include educational programs, technical measures, surveillance, and feedback [133]. Many studies have shown that prevention bundles can be effective in preventing VAP and NV-HAP and developing HAP prevention bundles is a practical way to enhance care. However, there is no consensus about which care processes to include in bundles [53,134].

Accurately assessing the impact of VAP bundles is challenging because of the subjectivity and lack of specificity of VAP diagnostic criteria. For example, it is difficult to determine whether observed decreases in HAP incidence represent true declines or stricter application of subjective criteria. This is of particular concern because hospitals and quality improvement advocates have an interest in being able to report lower HAP rates, and bundle implementations by nature are implemented in an open-label fashion.

●VAP prevention bundles

•Efficacy of bundles reducing HAP incidence – Many studies have shown that prevention bundles can be effective in preventing VAP and non-ventilator-associated HAP (nvHAP). In a prospective surveillance study conducted in 181 Spanish ICUs (the Pneumonia Zero project), VAP incidence declined from 9.8 to 4.3 episodes per 1000 ventilator days with institution of a prevention bundle that included seven mandatory measures including education and training in airway management, strict hand hygiene before airway management, control and maintenance of cuff pressure, oral care with chlorhexidine, semirecumbent positioning, protocols for minimizing sedation, and avoiding elective changes of ventilator circuits, humidifiers, and endotracheal tubes [135]. Other cohort studies have shown similar findings [133,136].

•Efficacy of VAP bundles reducing mortality – A meta-analysis of 13 observational studies evaluating the effect of VAP bundles on mortality reported a 10 percent decrease in mortality following bundle implementation (OR 0.90, 95% CI 0.84-0.97) [137]. These results should be interpreted with caution, however, due to the observational nature of the included studies, variations in bundle components, and lack of correlation between bundle adherence rates and mortality.

•Most efficacious components of VAP bundles – One retrospective cohort study sought to determine which components of VAP prevention bundles are efficacious [58]. In evaluation of 5539 mechanically ventilated patients, the following interventions were found to be beneficial:

-Semirecumbent positioning

-Sedation interruptions

-Spontaneous breathing trials, and

-Deep vein thrombosis prophylaxis (see 'Essential practices' above)

By contrast, stress ulcer prophylaxis was associated with an increased risk of VAP (HR 7.69, 95% CI 1.44-41.1) (see 'Other risk factors' above), and oral chlorhexidine was associated with increased mortality (HR 1.63, 95% CI 1.15-2.31). While the latter association is concerning, whether chlorhexidine is a causal factor is not clear. (See 'Practices that are not recommended' above.)

●Efficacy of NV-HAP prevention bundles – In a randomized trial of 123 hospitalized patients aged ≥65 years of age, 1-year hospitalization rate due to a respiratory infection were lower in the group that received a multi-intervention HAP prevention bundle [138]. The bundle consisted of reverse Trendelenburg position, dysphagia screening, oral care (toothbrushing/denture cleansing and oral chlorhexidine), and vaccination against respiratory pathogens. Although pneumonia rates during the initial admission were lower in the intervention group, it was not statistically significant (1 versus 3 HAP episodes). In a prospective intervention study conducted in 21 hospitals, NV-HAP incidence declined from 5.9 to 1.8 episodes per 1000 admissions with initiation of a prevention bundle that included mobilization, upright feeding, swallowing evaluation, sedation restrictions, elevation of head of bed, oral hygiene care, and gastrointestinal tube care [139]. Other cohort studies have shown similar findings [61,140].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hospital-acquired pneumonia and ventilator-associated pneumonia in adults".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Hospital-acquired pneumonia (The Basics)")

SUMMARY

●Definitions – The following types of nosocomial pneumonia have been defined (table 1):

•Hospital-acquired (or nosocomial) pneumonia (HAP) is pneumonia that occurs 48 hours or more after admission to the hospital and did not appear to be incubating at the time of admission.

•Ventilator-associated pneumonia (VAP) is a type of HAP that develops in intubated patients on mechanical ventilation for more than 48 hours. VAP also includes HAP that occurs within 48 hours of extubation.

•Non-ventilator-associated HAP (NV-HAP) refers to HAP that develops in hospitalized patients who are not on mechanical ventilation nor underwent extubation within 48 hours before pneumonia developed. NV-HAP can be divided into patients that ultimately require mechanical ventilation (VHAP) due to the pneumonia versus those that do not. VHAP is associated with particularly poor clinical outcomes. (See 'Pneumonia types' above.)

●Risk factors – The most significant risk factor for HAP is intubation for mechanical ventilation; other risk factors include older age, chronic lung disease, depressed consciousness, and aspiration, among others. (See 'Risk factors' above.)

●Prevention practices – Practices that are recommended for preventing VAP include avoiding intubation when possible, minimizing sedation, instituting ventilator liberation protocols, maintaining and improving physical conditioning, providing regular oral care with toothbrushing, elevating the head of the bed, and changing ventilator circuits only when visibly soiled or damaged (table 2). (See 'Essential practices' above.)

Although evidence supporting VAP prevention bundles is heterogenous, combining a core set of prevention measures into a bundle is a practical way to enhance care. (See 'HAP prevention bundles' above.)

ACKNOWLEDGMENT — 

UpToDate gratefully acknowledges John G Bartlett, MD, who contributed on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.

  1. Zilberberg MD, Nathanson BH, Puzniak LA, Shorr AF. Descriptive Epidemiology and Outcomes of Nonventilated Hospital-Acquired, Ventilated Hospital-Acquired, and Ventilator-Associated Bacterial Pneumonia in the United States, 2012-2019. Crit Care Med 2022; 50:460.
  2. 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.
  3. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019; 200:e45.
  4. Torres A, Niederman MS, Chastre J, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J 2017; 50.
  5. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388.
  6. Kollef MH. Health care-associated pneumonia: perception versus reality. Clin Infect Dis 2009; 49:1875.
  7. Murri R, De Pascale G. The challenge of identifying resistant-organism pneumonia in the emergency department: still navigating on the erie canal? Clin Infect Dis 2012; 54:199.
  8. Ewig S, Welte T, Torres A. Is healthcare-associated pneumonia a distinct entity needing specific therapy? Curr Opin Infect Dis 2012; 25:166.
  9. Chalmers JD, Taylor JK, Singanayagam A, et al. Epidemiology, antibiotic therapy, and clinical outcomes in health care-associated pneumonia: a UK cohort study. Clin Infect Dis 2011; 53:107.
  10. Yap V, Datta D, Metersky ML. Is the present definition of health care-associated pneumonia the best way to define risk of infection with antibiotic-resistant pathogens? Infect Dis Clin North Am 2013; 27:1.
  11. Ma HM, Wah JL, Woo J. Should nursing home-acquired pneumonia be treated as nosocomial pneumonia? J Am Med Dir Assoc 2012; 13:727.
  12. Chalmers JD, Rother C, Salih W, Ewig S. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis 2014; 58:330.
  13. Shorr AF, Zilberberg MD, Reichley R, et al. Validation of a clinical score for assessing the risk of resistant pathogens in patients with pneumonia presenting to the emergency department. Clin Infect Dis 2012; 54:193.
  14. Webb BJ, Dascomb K, Stenehjem E, et al. Derivation and Multicenter Validation of the Drug Resistance in Pneumonia Clinical Prediction Score. Antimicrob Agents Chemother 2016; 60:2652.
  15. Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268.
  16. Beardsley JR, Williamson JC, Johnson JW, et al. Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia. Chest 2006; 130:787.
  17. Torres A, Gatell JM, Aznar E, et al. Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med 1995; 152:137.
  18. Chastre J, Trouillet JL, Vuagnat A, et al. Nosocomial pneumonia in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 1998; 157:1165.
  19. Hortal J, Giannella M, Pérez MJ, et al. Incidence and risk factors for ventilator-associated pneumonia after major heart surgery. Intensive Care Med 2009; 35:1518.
  20. Ranjan N, Chaudhary U, Chaudhry D, Ranjan KP. Ventilator-associated pneumonia in a tertiary care intensive care unit: Analysis of incidence, risk factors and mortality. Indian J Crit Care Med 2014; 18:200.
  21. Wałaszek M, Kosiarska A, Gniadek A, et al. The risk factors for hospital-acquired pneumonia in the Intensive Care Unit. Przegl Epidemiol 2016; 70:15.
  22. Nakaviroj S, Cherdrungsi R, Chaiwat O. Incidence and risk factors for ventilator-associated pneumonia in the surgical intensive care unit, Siriraj Hospital. J Med Assoc Thai 2014; 97 Suppl 1:S61.
  23. Markowicz P, Wolff M, Djedaïni K, et al. Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome. Incidence, prognosis, and risk factors. ARDS Study Group. Am J Respir Crit Care Med 2000; 161:1942.
  24. Magill SS, O'Leary E, Janelle SJ, et al. Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals. N Engl J Med 2018; 379:1732.
  25. Walter J, Haller S, Quinten C, et al. Healthcare-associated pneumonia in acute care hospitals in European Union/European Economic Area countries: an analysis of data from a point prevalence survey, 2011 to 2012. Euro Surveill 2018; 23.
  26. Craven DE, Kunches LM, Kilinsky V, et al. Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am Rev Respir Dis 1986; 133:792.
  27. Kollef MH. Prevention of hospital-associated pneumonia and ventilator-associated pneumonia. Crit Care Med 2004; 32:1396.
  28. Bornstain C, Azoulay E, De Lassence A, et al. Sedation, sucralfate, and antibiotic use are potential means for protection against early-onset ventilator-associated pneumonia. Clin Infect Dis 2004; 38:1401.
  29. Celis R, Torres A, Gatell JM, et al. Nosocomial pneumonia. A multivariate analysis of risk and prognosis. Chest 1988; 93:318.
  30. Kollef MH, Von Harz B, Prentice D, et al. Patient transport from intensive care increases the risk of developing ventilator-associated pneumonia. Chest 1997; 112:765.
  31. Kollef MH. Ventilator-associated pneumonia. A multivariate analysis. JAMA 1993; 270:1965.
  32. Kollef MH, Vlasnik J, Sharpless L, et al. Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med 1997; 156:1040.
  33. Coffin SE, Klompas M, Classen D, et al. Strategies to prevent ventilator-associated pneumonia in acute care hospitals. Infect Control Hosp Epidemiol 2008; 29 Suppl 1:S31.
  34. Lukasewicz Ferreira SA, Hubner Dalmora C, Anziliero F, et al. Factors predicting non-ventilated hospital-acquired pneumonia: systematic review and meta-analysis. J Hosp Infect 2022; 119:64.
  35. Bergin SP, Coles A, Calvert SB, et al. PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the ICU. Chest 2020; 158:2370.
  36. Dananché C, Vanhems P, Machut A, et al. Trends of Incidence and Risk Factors of Ventilator-Associated Pneumonia in Elderly Patients Admitted to French ICUs Between 2007 and 2014. Crit Care Med 2018; 46:869.
  37. van der Kooi TII, Boshuizen H, Wille JC, et al. Using flexible methods to determine risk factors for ventilator-associated pneumonia in the Netherlands. PLoS One 2019; 14:e0218372.
  38. Tejerina E, Frutos-Vivar F, Restrepo MI, et al. Incidence, risk factors, and outcome of ventilator-associated pneumonia. J Crit Care 2006; 21:56.
  39. Sopena N, Heras E, Casas I, et al. Risk factors for hospital-acquired pneumonia outside the intensive care unit: a case-control study. Am J Infect Control 2014; 42:38.
  40. Charles MP, Kali A, Easow JM, et al. Ventilator-associated pneumonia. Australas Med J 2014; 7:334.
  41. Lewis SC, Li L, Murphy MV, et al. Risk factors for ventilator-associated events: a case-control multivariable analysis. Crit Care Med 2014; 42:1839.
  42. Sophonsri A, Lou M, Ny P, et al. Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection. Front Med (Lausanne) 2023; 10:1268488.
  43. Ehrenzeller S, Klompas M. Association Between Daily Toothbrushing and Hospital-Acquired Pneumonia: A Systematic Review and Meta-Analysis. JAMA Intern Med 2024; 184:131.
  44. Baker D, Giuliano KK, Thakkar-Samtani M, et al. The association between accessing dental services and nonventilator hospital-acquired pneumonia among 2019 Medicaid beneficiaries. Infect Control Hosp Epidemiol 2023; 44:959.
  45. Huang HB, Jiang W, Wang CY, et al. Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: a systematic review and meta-analysis. Crit Care 2018; 22:20.
  46. Alhazzani W, Alshamsi F, Belley-Cote E, et al. Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med 2018; 44:1.
  47. Barbateskovic M, Marker S, Granholm A, et al. Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 2019; 45:143.
  48. Sasabuchi Y, Matsui H, Lefor AK, et al. Risks and Benefits of Stress Ulcer Prophylaxis for Patients With Severe Sepsis. Crit Care Med 2016; 44:e464.
  49. Alquraini M, Alshamsi F, Møller MH, et al. Sucralfate versus histamine 2 receptor antagonists for stress ulcer prophylaxis in adult critically ill patients: A meta-analysis and trial sequential analysis of randomized trials. J Crit Care 2017; 40:21.
  50. Krag M, Marker S, Perner A, et al. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. N Engl J Med 2018; 379:2199.
  51. Cook D, Deane A, Lauzier F, et al. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med 2024; 391:9.
  52. Klompas M, Branson R, Cawcutt K, et al. Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update. Infect Control Hosp Epidemiol 2022; 43:687.
  53. Klompas M, Branson R, Eichenwald EC, et al. Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014; 35:915.
  54. Okgün Alcan A, Demir Korkmaz F, Uyar M. Prevention of ventilator-associated pneumonia: Use of the care bundle approach. Am J Infect Control 2016; 44:e173.
  55. DeLuca LA Jr, Walsh P, Davidson DD Jr, et al. Impact and feasibility of an emergency department-based ventilator-associated pneumonia bundle for patients intubated in an academic emergency department. Am J Infect Control 2017; 45:151.
  56. Khan R, Al-Dorzi HM, Al-Attas K, et al. The impact of implementing multifaceted interventions on the prevention of ventilator-associated pneumonia. Am J Infect Control 2016; 44:320.
  57. Marini AL, Khan R, Mundekkadan S. Multifaceted bundle interventions shown effective in reducing VAP rates in our multidisciplinary ICUs. BMJ Qual Improv Rep 2016; 5.
  58. Klompas M, Li L, Kleinman K, et al. Associations Between Ventilator Bundle Components and Outcomes. JAMA Intern Med 2016; 176:1277.
  59. Metersky ML, Wang Y, Klompas M, et al. Trend in Ventilator-Associated Pneumonia Rates Between 2005 and 2013. JAMA 2016; 316:2427.
  60. Writing Group for the CHECKLIST-ICU Investigators and the Brazilian Research in Intensive Care Network (BRICNet), Cavalcanti AB, Bozza FA, et al. Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients: A Randomized Clinical Trial. JAMA 2016; 315:1480.
  61. Wolfensberger A, Clack L, von Felten S, et al. Prevention of non-ventilator-associated hospital-acquired pneumonia in Switzerland: a type 2 hybrid effectiveness-implementation trial. Lancet Infect Dis 2023; 23:836.
  62. Weber M, Klein U, Weigert A, et al. Use of Pre- and Intensified Postprocedural Physiotherapy in Patients with Symptomatic Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement Study (the 4P-TAVR Study). J Interv Cardiol 2021; 2021:8894223.
  63. Giuliano KK, Penoyer D, Middleton A, Baker D. Original Research: Oral Care as Prevention for Nonventilator Hospital-Acquired Pneumonia: A Four-Unit Cluster Randomized Study. Am J Nurs 2021; 121:24.
  64. Boden I, Skinner EH, Browning L, et al. Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial. BMJ. 2018;360:j5916. AORN J 2018; 108:461.
  65. Manzano F, Fernández-Mondéjar E, Colmenero M, et al. Positive-end expiratory pressure reduces incidence of ventilator-associated pneumonia in nonhypoxemic patients. Crit Care Med 2008; 36:2225.
  66. Lucangelo U, Zin WA, Antonaglia V, et al. Effect of positive expiratory pressure and type of tracheal cuff on the incidence of aspiration in mechanically ventilated patients in an intensive care unit. Crit Care Med 2008; 36:409.
  67. Okuni I, Ebihara S. Are Oropharyngeal Dysphagia Screening Tests Effective in Preventing Pneumonia? J Clin Med 2022; 11.
  68. Duncan S, McAuley DF, Walshe M, et al. Interventions for oropharyngeal dysphagia in acute and critical care: a systematic review and meta-analysis. Intensive Care Med 2020; 46:1326.
  69. Wang L, Li X, Yang Z, et al. Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation. Cochrane Database Syst Rev 2016; 2016:CD009946.
  70. Li Bassi G, Panigada M, Ranzani OT, et al. Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia. Intensive Care Med 2017; 43:1572.
  71. Drakulovic MB, Torres A, Bauer TT, et al. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet 1999; 354:1851.
  72. Chen TJ, Chung YW, Chen PY, et al. Effects of daily sedation interruption in intensive care unit patients undergoing mechanical ventilation: A meta-analysis of randomized controlled trials. Int J Nurs Pract 2022; 28:e12948.
  73. Quenot JP, Ladoire S, Devoucoux F, et al. Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia. Crit Care Med 2007; 35:2031.
  74. Singer P, Blaser AR, Berger MM, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr 2019; 38:48.
  75. Zang K, Chen B, Wang M, et al. The effect of early mobilization in critically ill patients: A meta-analysis. Nurs Crit Care 2020; 25:360.
  76. Wang J, Ren D, Liu Y, et al. Effects of early mobilization on the prognosis of critically ill patients: A systematic review and meta-analysis. Int J Nurs Stud 2020; 110:103708.
  77. Waldauf P, Jiroutková K, Krajčová A, et al. Effects of Rehabilitation Interventions on Clinical Outcomes in Critically Ill Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit Care Med 2020; 48:1055.
  78. Zhang L, Hu W, Cai Z, et al. Early mobilization of critically ill patients in the intensive care unit: A systematic review and meta-analysis. PLoS One 2019; 14:e0223185.
  79. Stolbrink M, McGowan L, Saman H, et al. The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay. J Hosp Infect 2014; 88:34.
  80. Ståhl A, Westerdahl E. Postoperative Physical Therapy to Prevent Hospital-acquired Pneumonia in Patients Over 80 Years Undergoing Hip Fracture Surgery-A Quasi-experimental Study. Clin Interv Aging 2020; 15:1821.
  81. Wunderink RG. Welkommen to our world. Emergence of antibiotic resistance with selective decontamination of the digestive tract. Am J Respir Crit Care Med 2010; 181:426.
  82. Oostdijk EA, de Smet AM, Blok HE, et al. Ecological effects of selective decontamination on resistant gram-negative bacterial colonization. Am J Respir Crit Care Med 2010; 181:452.
  83. Kollef MH, Micek ST. Rational use of antibiotics in the ICU: balancing stewardship and clinical outcomes. JAMA 2014; 312:1403.
  84. D'Amico R, Pifferi S, Leonetti C, et al. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ 1998; 316:1275.
  85. Silvestri L, van Saene HK, Casarin A, et al. Impact of selective decontamination of the digestive tract on carriage and infection due to Gram-negative and Gram-positive bacteria: a systematic review of randomised controlled trials. Anaesth Intensive Care 2008; 36:324.
  86. Roquilly A, Marret E, Abraham E, Asehnoune K. Pneumonia prevention to decrease mortality in intensive care unit: a systematic review and meta-analysis. Clin Infect Dis 2015; 60:64.
  87. Minozzi S, Pifferi S, Brazzi L, et al. Topical antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving mechanical ventilation. Cochrane Database Syst Rev 2021; 1:CD000022.
  88. Hammond NE, Myburgh J, Seppelt I, et al. Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis. JAMA 2022; 328:1922.
  89. de Smet AM, Kluytmans JA, Cooper BS, et al. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med 2009; 360:20.
  90. Oostdijk EAN, Kesecioglu J, Schultz MJ, et al. Notice of Retraction and Replacement: Oostdijk et al. Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial. JAMA. 2014;312(14):1429-1437. JAMA 2017; 317:1583.
  91. Bonten MJ. Healthcare epidemiology: Ventilator-associated pneumonia: preventing the inevitable. Clin Infect Dis 2011; 52:115.
  92. Wittekamp BH, Plantinga NL, Cooper BS, et al. Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial. JAMA 2018; 320:2087.
  93. Torres A, Serra-Batlles J, Ros E, et al. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992; 116:540.
  94. Smulders K, van der Hoeven H, Weers-Pothoff I, Vandenbroucke-Grauls C. A randomized clinical trial of intermittent subglottic secretion drainage in patients receiving mechanical ventilation. Chest 2002; 121:858.
  95. Kollef MH, Skubas NJ, Sundt TM. A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients. Chest 1999; 116:1339.
  96. "Subglottic secretion drainage for preventing ventilator-associated pneumonia: an overview of systematic reviews and an updated meta-analysis". Diana P. Pozuelo-Carrascosa, Ángel Herráiz-Adillo, Celia Alvarez-Bueno, Jose Manuel Añón, Vicente Martínez-Vizcaíno and Iván Cavero-Redondo. Eur Respir Rev 2020; 29: 190107. Eur Respir Rev 2022; 31.
  97. Pozuelo-Carrascosa DP, Klompas M, Alvarez-Bueno C, et al. Correction to subglottic secretion drainage for preventing ventilator-associated pneumonia: an overview of systematic reviews and an updated meta-analysis. Eur Respir Rev 2022; 31.
  98. Alhazzani W, Almasoud A, Jaeschke R, et al. Small bowel feeding and risk of pneumonia in adult critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care 2013; 17:R127.
  99. Deane AM, Adam MD, Dhaliwal R, et al. Comparisons between intragastric and small intestinal delivery of enteral nutrition in the critically ill: a systematic review and meta-analysis. Crit Care 2013; 17:R125.
  100. Chorath K, Hoang A, Rajasekaran K, Moreira A. Association of Early vs Late Tracheostomy Placement With Pneumonia and Ventilator Days in Critically Ill Patients: A Meta-analysis. JAMA Otolaryngol Head Neck Surg 2021; 147:450.
  101. Villemure-Poliquin N, Lessard Bonaventure P, Costerousse O, et al. Impact of Early Tracheostomy Versus Late or No Tracheostomy in Nonneurologically Injured Adult Patients: A Systematic Review and Meta-Analysis. Crit Care Med 2023; 51:310.
  102. Hadley-Brown K, Hailstone L, Devane R, et al. Prophylactic Antibiotics in Adults With Acute Brain Injury Who Are Invasively Ventilated in the ICU: A Systematic Review and Meta-Analysis. Chest 2025; 167:1079.
  103. François B, Cariou A, Clere-Jehl R, et al. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med 2019; 381:1831.
  104. Dahyot-Fizelier C, Lasocki S, Kerforne T, et al. Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial. Lancet Respir Med 2024; 12:375.
  105. Klompas M. Antibiotic prophylaxis for patients with acute brain injury. Lancet Respir Med 2024; 12:340.
  106. Harms H, Prass K, Meisel C, et al. Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PLoS One 2008; 3:e2158.
  107. Vermeij JD, Westendorp WF, Dippel DW, et al. Antibiotic therapy for preventing infections in people with acute stroke. Cochrane Database Syst Rev 2018; 1:CD008530.
  108. Westendorp WF, Vermeij JD, Zock E, et al. The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial. Lancet 2015; 385:1519.
  109. Ehrmann S, Barbier F, Demiselle J, et al. Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. N Engl J Med 2023; 389:2052.
  110. 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.
  111. Li J, Lyu S, Luo J, et al. Prophylactic Antibiotics Delivered Via the Respiratory Tract to Reduce Ventilator-Associated Pneumonia: A Systematic Review, Network Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials. Crit Care Med 2024; 52:1612.
  112. Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ 2007; 334:889.
  113. Labeau SO, Van de Vyver K, Brusselaers N, et al. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis 2011; 11:845.
  114. Price R, MacLennan G, Glen J, SuDDICU Collaboration. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ 2014; 348:g2197.
  115. Hua F, Xie H, Worthington HV, et al. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev 2016; 10:CD008367.
  116. Klompas M, Speck K, Howell MD, et al. Reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: systematic review and meta-analysis. JAMA Intern Med 2014; 174:751.
  117. Deschepper M, Waegeman W, Eeckloo K, et al. Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study. Intensive Care Med 2018; 44:1017.
  118. Zhao T, Wu X, Zhang Q, et al. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev 2020; 12:CD008367.
  119. Dale CM, Rose L, Carbone S, et al. Effect of oral chlorhexidine de-adoption and implementation of an oral care bundle on mortality for mechanically ventilated patients in the intensive care unit (CHORAL): a multi-center stepped wedge cluster-randomized controlled trial. Intensive Care Med 2021; 47:1295.
  120. Food and Agriculture Organization of the United Nations and World Health Organization. Guidelines for the evaluation of probiotics in food. http://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf (Accessed on January 10, 2011).
  121. Morrow LE, Kollef MH, Casale TB. Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial. Am J Respir Crit Care Med 2010; 182:1058.
  122. Su M, Jia Y, Li Y, et al. Probiotics for the Prevention of Ventilator-Associated Pneumonia: A Meta-Analysis of Randomized Controlled Trials. Respir Care 2020; 65:673.
  123. Johnstone J, Meade M, Lauzier F, et al. Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial. JAMA 2021; 326:1024.
  124. Sharif S, Greer A, Skorupski C, et al. Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit Care Med 2022; 50:1175.
  125. Kollef MH, Afessa B, Anzueto A, et al. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAMA 2008; 300:805.
  126. Tokmaji G, Vermeulen H, Müller MC, et al. Silver-coated endotracheal tubes for prevention of ventilator-associated pneumonia in critically ill patients. Cochrane Database Syst Rev 2015; :CD009201.
  127. Ashiq N, Munir F, Khan S, et al. Noble element coatings on endotracheal tubes for ventilator-associated pneumonia prevention: A systematic review and meta-analysis of randomized controlled trials in emergency care settings. Medicine (Baltimore) 2024; 103:e39750.
  128. Yang Y, Xiong X, Wang X, et al. Prevention of ventilator-associated pneumonia by metal-coated endotracheal tubes: a meta-analysis. Crit Care 2024; 28:309.
  129. Mentec H, Dupont H, Bocchetti M, et al. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Crit Care Med 2001; 29:1955.
  130. McClave SA, Lukan JK, Stefater JA, et al. Poor validity of residual volumes as a marker for risk of aspiration in critically ill patients. Crit Care Med 2005; 33:324.
  131. Montejo JC, Miñambres E, Bordejé L, et al. Gastric residual volume during enteral nutrition in ICU patients: the REGANE study. Intensive Care Med 2010; 36:1386.
  132. Reignier J, Mercier E, Le Gouge A, et al. Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: a randomized controlled trial. JAMA 2013; 309:249.
  133. Bouadma L, Deslandes E, Lolom I, et al. Long-term impact of a multifaceted prevention program on ventilator-associated pneumonia in a medical intensive care unit. Clin Infect Dis 2010; 51:1115.
  134. Klompas M. What is new in the prevention of nosocomial pneumonia in the ICU? Curr Opin Crit Care 2017; 23:378.
  135. Álvarez-Lerma F, Palomar-Martínez M, Sánchez-García M, et al. Prevention of Ventilator-Associated Pneumonia: The Multimodal Approach of the Spanish ICU "Pneumonia Zero" Program. Crit Care Med 2018; 46:181.
  136. Berenholtz SM, Pham JC, Thompson DA, et al. Collaborative cohort study of an intervention to reduce ventilator-associated pneumonia in the intensive care unit. Infect Control Hosp Epidemiol 2011; 32:305.
  137. Pileggi C, Mascaro V, Bianco A, et al. Ventilator Bundle and Its Effects on Mortality Among ICU Patients: A Meta-Analysis. Crit Care Med 2018; 46:1167.
  138. Rosario BH, Shafi H, Yii ACA, et al. Evaluation of multi-component interventions for prevention of nosocomial pneumonia in older adults: a randomized, controlled trial. Eur Geriatr Med 2021; 12:1045.
  139. Lacerna CC, Patey D, Block L, et al. A successful program preventing nonventilator hospital-acquired pneumonia in a large hospital system. Infect Control Hosp Epidemiol 2020; 41:547.
  140. Sopena N, Isernia V, Casas I, et al. Intervention to reduce the incidence of non-ventilator-associated hospital-acquired pneumonia: A pilot study. Am J Infect Control 2023; 51:1324.
Topic 6995 Version 51.0

References

1 : Descriptive Epidemiology and Outcomes of Nonventilated Hospital-Acquired, Ventilated Hospital-Acquired, and Ventilator-Associated Bacterial Pneumonia in the United States, 2012-2019.

2 : 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.

3 : Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.

4 : International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT).

5 : Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.

6 : Health care-associated pneumonia: perception versus reality.

7 : The challenge of identifying resistant-organism pneumonia in the emergency department: still navigating on the erie canal?

8 : Is healthcare-associated pneumonia a distinct entity needing specific therapy?

9 : Epidemiology, antibiotic therapy, and clinical outcomes in health care-associated pneumonia: a UK cohort study.

10 : Is the present definition of health care-associated pneumonia the best way to define risk of infection with antibiotic-resistant pathogens?

11 : Should nursing home-acquired pneumonia be treated as nosocomial pneumonia?

12 : Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis.

13 : Validation of a clinical score for assessing the risk of resistant pathogens in patients with pneumonia presenting to the emergency department.

14 : Derivation and Multicenter Validation of the Drug Resistance in Pneumonia Clinical Prediction Score.

15 : Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance.

16 : Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia.

17 : Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation.

18 : Nosocomial pneumonia in patients with acute respiratory distress syndrome.

19 : Incidence and risk factors for ventilator-associated pneumonia after major heart surgery.

20 : Ventilator-associated pneumonia in a tertiary care intensive care unit: Analysis of incidence, risk factors and mortality.

21 : The risk factors for hospital-acquired pneumonia in the Intensive Care Unit.

22 : Incidence and risk factors for ventilator-associated pneumonia in the surgical intensive care unit, Siriraj Hospital.

23 : Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome. Incidence, prognosis, and risk factors. ARDS Study Group.

24 : Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals.

25 : Healthcare-associated pneumonia in acute care hospitals in European Union/European Economic Area countries: an analysis of data from a point prevalence survey, 2011 to 2012.

26 : Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation.

27 : Prevention of hospital-associated pneumonia and ventilator-associated pneumonia.

28 : Sedation, sucralfate, and antibiotic use are potential means for protection against early-onset ventilator-associated pneumonia.

29 : Nosocomial pneumonia. A multivariate analysis of risk and prognosis.

30 : Patient transport from intensive care increases the risk of developing ventilator-associated pneumonia.

31 : Ventilator-associated pneumonia. A multivariate analysis.

32 : Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia.

33 : Strategies to prevent ventilator-associated pneumonia in acute care hospitals.

34 : Factors predicting non-ventilated hospital-acquired pneumonia: systematic review and meta-analysis.

35 : PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the ICU.

36 : Trends of Incidence and Risk Factors of Ventilator-Associated Pneumonia in Elderly Patients Admitted to French ICUs Between 2007 and 2014.

37 : Using flexible methods to determine risk factors for ventilator-associated pneumonia in the Netherlands.

38 : Incidence, risk factors, and outcome of ventilator-associated pneumonia.

39 : Risk factors for hospital-acquired pneumonia outside the intensive care unit: a case-control study.

40 : Ventilator-associated pneumonia.

41 : Risk factors for ventilator-associated events: a case-control multivariable analysis.

42 : Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection.

43 : Association Between Daily Toothbrushing and Hospital-Acquired Pneumonia: A Systematic Review and Meta-Analysis.

44 : The association between accessing dental services and nonventilator hospital-acquired pneumonia among 2019 Medicaid beneficiaries.

45 : Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: a systematic review and meta-analysis.

46 : Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials.

47 : Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis.

48 : Risks and Benefits of Stress Ulcer Prophylaxis for Patients With Severe Sepsis.

49 : Sucralfate versus histamine 2 receptor antagonists for stress ulcer prophylaxis in adult critically ill patients: A meta-analysis and trial sequential analysis of randomized trials.

50 : Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU.

51 : Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation.

52 : Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update.

53 : Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update.

54 : Prevention of ventilator-associated pneumonia: Use of the care bundle approach.

55 : Impact and feasibility of an emergency department-based ventilator-associated pneumonia bundle for patients intubated in an academic emergency department.

56 : The impact of implementing multifaceted interventions on the prevention of ventilator-associated pneumonia.

57 : Multifaceted bundle interventions shown effective in reducing VAP rates in our multidisciplinary ICUs.

58 : Associations Between Ventilator Bundle Components and Outcomes.

59 : Trend in Ventilator-Associated Pneumonia Rates Between 2005 and 2013.

60 : Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients: A Randomized Clinical Trial.

61 : Prevention of non-ventilator-associated hospital-acquired pneumonia in Switzerland: a type 2 hybrid effectiveness-implementation trial.

62 : Use of Pre- and Intensified Postprocedural Physiotherapy in Patients with Symptomatic Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement Study (the 4P-TAVR Study).

63 : Original Research: Oral Care as Prevention for Nonventilator Hospital-Acquired Pneumonia: A Four-Unit Cluster Randomized Study.

64 : Boden I, Skinner EH, Browning L, et al. Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial. BMJ. 2018;360:j5916.

65 : Positive-end expiratory pressure reduces incidence of ventilator-associated pneumonia in nonhypoxemic patients.

66 : Effect of positive expiratory pressure and type of tracheal cuff on the incidence of aspiration in mechanically ventilated patients in an intensive care unit.

67 : Are Oropharyngeal Dysphagia Screening Tests Effective in Preventing Pneumonia?

68 : Interventions for oropharyngeal dysphagia in acute and critical care: a systematic review and meta-analysis.

69 : Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.

70 : Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia.

71 : Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial.

72 : Effects of daily sedation interruption in intensive care unit patients undergoing mechanical ventilation: A meta-analysis of randomized controlled trials.

73 : Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia.

74 : ESPEN guideline on clinical nutrition in the intensive care unit.

75 : The effect of early mobilization in critically ill patients: A meta-analysis.

76 : Effects of early mobilization on the prognosis of critically ill patients: A systematic review and meta-analysis.

77 : Effects of Rehabilitation Interventions on Clinical Outcomes in Critically Ill Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

78 : Early mobilization of critically ill patients in the intensive care unit: A systematic review and meta-analysis.

79 : The Early Mobility Bundle: a simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay.

80 : Postoperative Physical Therapy to Prevent Hospital-acquired Pneumonia in Patients Over 80 Years Undergoing Hip Fracture Surgery-A Quasi-experimental Study.

81 : Welkommen to our world. Emergence of antibiotic resistance with selective decontamination of the digestive tract.

82 : Ecological effects of selective decontamination on resistant gram-negative bacterial colonization.

83 : Rational use of antibiotics in the ICU: balancing stewardship and clinical outcomes.

84 : Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials.

85 : Impact of selective decontamination of the digestive tract on carriage and infection due to Gram-negative and Gram-positive bacteria: a systematic review of randomised controlled trials.

86 : Pneumonia prevention to decrease mortality in intensive care unit: a systematic review and meta-analysis.

87 : Topical antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving mechanical ventilation.

88 : Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.

89 : Decontamination of the digestive tract and oropharynx in ICU patients.

90 : Notice of Retraction and Replacement: Oostdijk et al. Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial. JAMA. 2014;312(14):1429-1437.

91 : Healthcare epidemiology: Ventilator-associated pneumonia: preventing the inevitable.

92 : Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial.

93 : Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position.

94 : A randomized clinical trial of intermittent subglottic secretion drainage in patients receiving mechanical ventilation.

95 : A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients.

96 : "Subglottic secretion drainage for preventing ventilator-associated pneumonia: an overview of systematic reviews and an updated meta-analysis". Diana P. Pozuelo-Carrascosa,Ángel Herráiz-Adillo, Celia Alvarez-Bueno, Jose Manuel Añón, Vicente Martínez-Vizcaíno and Iván Cavero-Redondo. Eur Respir Rev 2020; 29: 190107.

97 : Correction to subglottic secretion drainage for preventing ventilator-associated pneumonia: an overview of systematic reviews and an updated meta-analysis.

98 : Small bowel feeding and risk of pneumonia in adult critically ill patients: a systematic review and meta-analysis of randomized trials.

99 : Comparisons between intragastric and small intestinal delivery of enteral nutrition in the critically ill: a systematic review and meta-analysis.

100 : Association of Early vs Late Tracheostomy Placement With Pneumonia and Ventilator Days in Critically Ill Patients: A Meta-analysis.

101 : Impact of Early Tracheostomy Versus Late or No Tracheostomy in Nonneurologically Injured Adult Patients: A Systematic Review and Meta-Analysis.

102 : Prophylactic Antibiotics in Adults With Acute Brain Injury Who Are Invasively Ventilated in the ICU: A Systematic Review and Meta-Analysis.

103 : Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest.

104 : Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial.

105 : Antibiotic prophylaxis for patients with acute brain injury.

106 : Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial.

107 : Antibiotic therapy for preventing infections in people with acute stroke.

108 : The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial.

109 : Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia.

110 : Prophylactic antibiotics for preventing ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis.

111 : Prophylactic Antibiotics Delivered Via the Respiratory Tract to Reduce Ventilator-Associated Pneumonia: A Systematic Review, Network Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

112 : Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis.

113 : Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis.

114 : Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis.

115 : Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia.

116 : Reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: systematic review and meta-analysis.

117 : Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study.

118 : Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia.

119 : Effect of oral chlorhexidine de-adoption and implementation of an oral care bundle on mortality for mechanically ventilated patients in the intensive care unit (CHORAL): a multi-center stepped wedge cluster-randomized controlled trial.

120 : Effect of oral chlorhexidine de-adoption and implementation of an oral care bundle on mortality for mechanically ventilated patients in the intensive care unit (CHORAL): a multi-center stepped wedge cluster-randomized controlled trial.

121 : Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial.

122 : Probiotics for the Prevention of Ventilator-Associated Pneumonia: A Meta-Analysis of Randomized Controlled Trials.

123 : Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial.

124 : Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

125 : Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial.

126 : Silver-coated endotracheal tubes for prevention of ventilator-associated pneumonia in critically ill patients.

127 : Noble element coatings on endotracheal tubes for ventilator-associated pneumonia prevention: A systematic review and meta-analysis of randomized controlled trials in emergency care settings.

128 : Prevention of ventilator-associated pneumonia by metal-coated endotracheal tubes: a meta-analysis.

129 : Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications.

130 : Poor validity of residual volumes as a marker for risk of aspiration in critically ill patients.

131 : Gastric residual volume during enteral nutrition in ICU patients: the REGANE study.

132 : Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: a randomized controlled trial.

133 : Long-term impact of a multifaceted prevention program on ventilator-associated pneumonia in a medical intensive care unit.

134 : What is new in the prevention of nosocomial pneumonia in the ICU?

135 : Prevention of Ventilator-Associated Pneumonia: The Multimodal Approach of the Spanish ICU "Pneumonia Zero" Program.

136 : Collaborative cohort study of an intervention to reduce ventilator-associated pneumonia in the intensive care unit.

137 : Ventilator Bundle and Its Effects on Mortality Among ICU Patients: A Meta-Analysis.

138 : Evaluation of multi-component interventions for prevention of nosocomial pneumonia in older adults: a randomized, controlled trial.

139 : A successful program preventing nonventilator hospital-acquired pneumonia in a large hospital system.

140 : Intervention to reduce the incidence of non-ventilator-associated hospital-acquired pneumonia: A pilot study.