Version October 2024
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.
The category of health care-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 [1] and community-acquired pneumonia (CAP) [2] guidelines or the combined 2017 European and Latin American HAP guidelines [3]. 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 [4]. This category was used to identify patients at risk for infection with multidrug-resistant (MDR) pathogens. However, this categorization may have been overly sensitive and 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 [5-11].
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 [2]. 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 [12,13]. (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 and the European Centre for Disease Prevention and Control have developed standard terminology for antimicrobial-resistant gram-negative bacilli, which are important causes of HAP and VAP [14]:
●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 [15]. 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) [1].
RISK FACTORS — The most significant risk factor for HAP is intubation. Other risk factors, which have emerged from multivariate analyses, include [16-30]:
●Older age [22,31]
●Chronic lung disease [19]
●Depressed consciousness [32]
●Aspiration [19]
●Chest or upper abdominal surgery [19,26,32]
●Agents that increase gastric pH (H2 blockers, antacids, proton pump inhibitors [PPIs]) (see 'Role of gastric pH' below)
●Previous antibiotic exposure, especially broad spectrum [33,34]
●Reintubation or prolonged intubation [20,21,26,33,35,36]
●Mechanical ventilation for acute respiratory distress syndrome [24,37]
●Frequent ventilator circuit changes (see "The ventilator circuit")
●Total opioid exposure [38]
●Multiple trauma [33,35]
●Paralysis [35]
●Number of central venous catheter placements and surgeries [36]
●Use of muscle relaxants or glucocorticoids [36]
●The presence of an intracranial pressure monitor [16]
●Malnutrition, chronic renal failure, anemia, Charlson Comorbidity Index, previous hospitalization [32]
Role of gastric pH — Several studies have noted an increased incidence of HAP when the gastric pH is increased with the use of H2 blockers, antacids, or PPIs [39-42]. We avoid agents that raise gastric pH in patients who are not at high risk of developing a stress ulcer or stress gastritis.
Some meta-analyses have found decreased rates of pneumonia in critically ill patients using sucralfate for stress ulcer prophylaxis compared with H2 blockers and PPIs [40,43]. In one meta-analysis of 21 randomized trials, for example, the incidence of pneumonia was lower in critically ill patients receiving sucralfate compared with those receiving H2 blockers (relative risk [RR] 0.84, 95% CI 0.72-0.98) [43]. No difference in bleeding risk was detected. Similar findings were observed in a network meta-analysis of 57 trials evaluating 7293 critically ill patients receiving stress ulcer prophylaxis [40]. Both H2 blockers and PPIs were associated with an increased risk of pneumonia when compared with sucralfate (odds ratio [OR] 1.30, 95% CI 1.08-1.58, and OR 1.65, 95% CI 1.20-2.27, respectively). Other meta-analyses, however, have not reported an association between stress ulcer prophylaxis and HAP, particularly when restricting the analysis to randomized trials at low risk of bias [41].
Similarly, a large randomized trial of PPIs versus placebo reported no impact on HAP [44]. In this study, 3298 intensive care unit (ICU) patients were randomized to daily pantoprazole versus placebo. There was no difference between groups in 90-day mortality nor in the composite outcome of gastrointestinal bleeding, pneumonia, Clostridioides difficile infection, or myocardial ischemia. Specifically, pneumonia rates were identical between groups.
PREVENTION — The Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) issue updated practice recommendations to reduce the risk of VAP and NV-HAP (table 2) [45]. 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), minimizing sedation through the use of sedative protocols, implementing ventilator liberation protocols, maintaining and improving physical conditioning, elevating the head of the bed, providing oral care with toothbrushing but without chlorhexidine, 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 [46-53]. (See 'Prevention bundles' below.)
The following discussion will review some of the modalities that have been evaluated for preventing VAP. 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".)
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".)
Preventing aspiration — Aspiration is a major predisposing mechanism for both 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), and application of positive end-expiratory pressure are measures that have been proposed to minimize aspiration [54,55]. (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)".)
Patient positioning — Supine positioning appears to predispose to aspiration and the development of HAP, particularly in patients receiving enteral nutrition [53]. The head of the bed should therefore be elevated to 30 to 45° [46]. 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 [56]. 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 [57]. 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 (eg, transient oxygen desaturation and hemodynamic instability) among patients placed in lateral Trendelenburg. 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 [51,58].
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) [59-61]. However, these devices cost more than standard endotracheal tubes and are not widely available. When available, they should be used for patients expected to require >48 or 72 hours of mechanical ventilation [46]. 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) [62]. The authors initially reported a significant decrease in mortality but subsequently published a correction that indicated no change in mortality [63]. There were no significant differences in duration of mechanical ventilation or ICU length of stay.
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 [64-66]. Furthermore, a randomized trial has shown that the rate of VAP was not higher in patients who did not undergo monitoring of gastric residuals [67]. 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 intubated critically ill adult patients: Enteral nutrition", section on 'Monitoring and management of complications'.)
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 colonization of the upper respiratory 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 applied to the oropharynx and administered orally, with or without intravenous antibiotics.
Chlorhexidine — The SHEA/IDSA guidelines recommend daily oral care with toothbrushing but without chlorhexidine due to the lack of clear evidence that chlorhexidine reduces pulmonary infections and the possible increase in mortality [45].
Chlorhexidine use is controversial because of its uncertain efficacy and possible association with increased mortality [51,68-72]. Several meta-analyses of randomized trials have reported an association between chlorhexidine and lower VAP rates [68-70,72,73]. 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 [73]. 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 effect amongst blinded trials (RR 0.88, 95% CI 0.66-1.16) [72]. 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.
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) [70]. 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) [51]. Other observational studies have raised the same concern [74]. 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.
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) [75]. 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.
Selective decontamination of the digestive tract — Selective decontamination of the digestive tract (SDD) refers to use of nonabsorbable antibiotics applied to the oropharynx and 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.
Meta-analyses have shown that SDD reduces the risk of VAP and HAP [76-79], particularly when the SDD regimen includes an intravenous component [80]. Both SOD and SDD have shown mortality benefits in trials of ICU patients performed mainly in regions with low baseline antimicrobial resistance rates [81,82]. The applicability of the studies showing benefit to other settings has been questioned since very low rates of antibiotic resistance were present at the institutions included in the key trials [83,84].
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% chlorhexidine oral care when compared with standard practice [85]. Because standard practice included oral care with 0.12 or 0.20% 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.
Because of the potential for promoting antimicrobial resistance with widespread SDD use, the practice has not been routinely adopted in North America [4,46,84,86,87]; the Society for Healthcare Epidemiology of America guidelines and combined European and Latin American HAP and VAP guidelines recommend against SDD [3,45] in settings with high baseline rates of antimicrobial utilization and antimicrobial resistance.
Additional detail on SDD is discussed separately. (See "Nosocomial infections in the intensive care unit: Epidemiology and prevention", section on 'Digestive and oropharyngeal decontamination'.)
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 [88,89]. Available results do not provide sufficient evidence to draw conclusions regarding the efficacy or safety of probiotics for the prevention of VAP. Therefore, we do not use probiotics for the prevention of VAP.
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) [90]. 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) [91]. 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 [92].
Silver-coated endotracheal tube — 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 [93,94]. This was illustrated in a randomized single-blinded trial (NASCENT) in which a silver-coated ETT was compared with an uncoated ETT in 2003 patients requiring mechanical ventilation [93]. Among patients intubated for more than 24 hours, the rate of microbiologically confirmed VAP was significantly lower with the silver-coated ETT (4.8 versus 7.5 percent). The silver-coated ETT was also associated with a significant delay in the occurrence of VAP. There were no differences between groups, however, in the duration of intubation, ICU stay, or hospital stay; mortality; or the frequency or severity of adverse events.
Inhaled antibiotics — The efficacy of inhaled antibiotics for the prevention of VAP is uncertain. In a meta-analysis of over 1000 patients on mechanical ventilation, receipt of inhaled antibiotics reduced occurrence of VAP compared with placebo (RR 0.7, 95% CI 0.59-0.82) but did not reduce mortality [95]. In another 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) [96]. However, there was no difference detected 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 amikacin may select for colonization with multidrug resistant bacteria.
Prevention bundles — VAP prevention bundles involve the integrated implementation of a combination of measures aimed at reducing the incidence of VAP among patients at risk. Bundling multiple measures together is hypothesized to provide synergistic protection against HAP or VAP. Typical bundle components include educational programs, technical measures, surveillance, and feedback [97]. Developing VAP prevention bundles is a practical way to enhance care. However, there is no consensus about which care processes to include in bundles [46,98].
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 VAP 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 VAP rates, and bundle implementations by nature are implemented in an open-label fashion.
Examples of studies that evaluated VAP prevention bundles include the following:
●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 [99].
●In another cohort study, VAP incidence declined from 23 to 13 episodes per 1000 ventilator days with the institution of a bundle that contained hand hygiene, glove and gown compliance, elevation of the head of the bed, oral care with chlorhexidine, maintaining an endotracheal tube cuff pressure >20 cm H20, orogastric rather than nasogastric feeding tubes, avoiding gastric overdistention, and eliminating nonessential tracheal suctioning [97].
●In a multicenter cohort study, VAP incidence declined from 5.5 to 0 cases per 1000 ventilator days across 110 ICUs with institution of a bundle that included semirecumbent positioning, minimization of sedation, daily assessments for extubation, stress ulcer prophylaxis, and deep vein thrombosis prophylaxis [100].
One retrospective cohort study sought to determine which components of VAP prevention bundles are efficacious [51]. 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. By contrast, stress ulcer prophylaxis was associated with an increased risk of VAP (HR 7.69, 95% CI 1.44-41.1), 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 'Decontamination of the oropharynx and digestive tract' above.)
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) [101]. 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.
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). 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 'Prevention' above.)
ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.
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