The management of hospital-acquired pneumonia requires use of preventive bundles, mitigative of risk factors, and prompt diagnosis with initiation of treatment when highly suspected.
Hospital-acquired pneumonia (HAP), also known as nosocomial pneumonia, occurs in patients who have been hospitalized for more than 48 hours. It is delineated into ventilator-associated pneumonia (VAP) and nonventilator hospital-acquired pneumonia (NV-HAP) after ascertaining that it was not incubating at the time of admission.1 HAP is a well-documented cause of increased morbidity and mortality among hospitalized patients, including increased need for intensive care unit (ICU) admission, mechanical ventilation, and hospital length of stay.1-3 Although at first blush it appears as though NV-HAP is less common than VAP, recent studies show that this is likely due to underreporting, lack of clear guidelines to report, and a lack of consensus on the definition of NV-HAP.4
The 2016 American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) HAP/VAP guidelines allowed for a blend of subjective observation and objective data points to define its presence but not for a way to definitively diagnose the syndrome. For example, a patient admitted for pancreatitis who received 6 L of intravenous fluid vs one admitted with sepsis from a suspected urinary tract infection presenting as acute encephalopathy with subsequently suspected aspiration event may both have leukocytosis, fever, and hypoxia with lung infiltrate. Both may be diagnosed with NV-HAP during their admission. Whether either actually had pneumonia is unclear because making a specific diagnosis of NV-HAP remains difficult. It demands the clinician have a high index of suspicion but refrain from overdiagnosis based on basic diagnostic information available on the wards. More invasive tests such as obtaining sputum samples and performing invasive diagnostic procedures (ie bronchoscopy), for definitive diagnosis present their own risks and in many cases are unlikely to be essential.
The Society of Healthcare Epidemiology (SHEA) review from 2022 shows HAP as the most common hospital-acquired infection, affecting nearly 1 in every 100 patients and 1 in every 10 ventilated patients.4,5 Recent reviews have shown that more than 35 million Americans are discharged from the hospital annually, with more than 32 million at risk for HAP, whereas fewer than 4 million are at risk for VAP.6 NV-HAP carries a greater than 8.4 times the risk of inpatient mortality and 8 times the risk of need for mechanical ventilation. These patients also have an average length of stay of nearly 16 days, whereas those without NV-HAP spend an average of 4.4 days in the hospital.6 The HAPPI-2 study showed that 70.8% of NV-HAP was acquired outside the ICU, although 18.8% required subsequent ICU transfer.6
In discussing the epidemiology of NV-HAP, a brief review of health care–associated pneumonia (HCAP) is warranted. HCAP was first introduced in the 2005 IDSA pneumonia guidelines to assist practitioners in profiling patients at higher risk for developing pneumonia outside of a hospital admission but with microbiologic data and mortality rates similar to patients with NV-HAP. However, subsequent data have not supported this profile, and HCAP was removed from the 2016 ATS/IDSA guidelines with the hope of reducing the burden of antibiotic exposure and subsequent antibiotic-associated adverse events, such as infection from Clostridioides difficile and expansion of multidrug-resistant organisms.1,2,7-10
General antibiotic coverage for NV-HAP aligns with that of VAP and includes antimicrobials targeted against Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, and Enterobacteriaceae. However, NV-HAP has more non–multidrug resistant pathogens at play because of lower rates of repeated antibiotic usage outside the ICU and lower oxygen concentrations in the lower respiratory tracts contributing to a slightly different microbiome. There is also the consideration of more macroaspiration events, leading to higher rates of anaerobic organisms in these patients. However, these anaerobes are mostly oropharyngeal in origin and therefore are covered without the addition of targeted anaerobic coverage.1,11
The pathophysiology of HAP necessitates exposure to a pathogen, which can occur via aspiration of gastric contents, exposure to contaminated aerosols (as in the case of Legionella), or hematogenously (as in septic embolization). However, the most common mechanism is driven by the aspiration of pathogenic bacteria from the oropharynx into the distal lungs. The naso-oropharyngeal cavities of hospitalized patients are exposed to and colonized by nosocomial pathogens, including MRSA and gram-negative bacilli. Healthy patients are typically able to prevent significant aspiration of pathogenic material into the distal lung via host defenses including: (1) cough, which expels aspirated material; and (2) mucociliary clearance, which neutralizes and mobilizes bacterial pathogens out of the airway. Clearance of aspirated material is impaired in patients with decreased levels of consciousness and can lead to significant aspiration of a pathogenic bacteria, evasion of local host defenses, organism replication, and the development of pneumonia.11,12
Prevention of NV-HAP depends on identification of at-risk populations and mitigation of risk factors, with particular emphasis on avoiding aspiration events. Populations at high risk for developing HAP include patients who are encephalopathic, those who avoid cough due to pain, the elderly, and those with an impaired immune system at baseline.13
Encephalopathy is commonly encountered within the hospital and represents a cohort that is at particular risk for aspiration. Encephalopathy may be precipitated by administration of sedating medications, preexisting neurologic conditions, or acute delirium. It limits the aforementioned host defenses and causes recalcitrance to airway clearance techniques via incentive spirometers and mobilization of secretions. Delirium precautions are important in every ward of the hospital and include maintenance of day/night hygiene, familiarization techniques, disturbance reductions, and early mobilization.14,15
Additional precautions include elevating the head of bed to at least 30°, which can prevent silent to large aspirations.16 Although nasogastric tube feedings are helpful for meeting caloric goals in hospitalized patients, they can both exacerbate inpatient delirium and timing of aspiration events. Patients may waiver between trickle and bolus feedings and at times are fed throughout the night, indicating that a return to oral feeding should be advanced whenever safe and able. Additionally, nasogastric tubes can allow for transit of nasopharyngeal flora into the posterior oropharynx and in short order into the lower respiratory tracts.17 As discussed above, the bacterial burden in hospitalized patients contributes to the risk of resistant bacteria or pathogens uncommonly found in the lung microbiome to enter the lower airway and create a nidus for infection. The hospitalized patient’s microbiome may continue to alter with continued hospital exposure, underscoring diligence to common hospital practices such as hand hygiene. Intermittent or prolonged antibiotic exposure, as is not uncommon in the hospital, also alters the tenuous balance of our microbiomes. Lastly, exposure to proton pump inhibitors and histamine-2 receptor antagonists can allow oropharyngeal flora to propagate into the gut with subsequent silent or large aspiration events contributing to the concern of NV-HAP development.18
Apart from mitigation of inpatient risk factors, it is important to consider NV-HAP prevention prior to hospitalization. Vaccination against common bacterial and viral pathogens may play a pivotal role in limiting a given patient’s risk of developing NV-HAP. Vaccination against Streptococcus pneumoniae has a proven benefit in the reduction of both pneumonia and meningitis severity and mortality.3 Although Haemophilus influenzae type B vaccination allowed for nontypeable Haemophilus influenzae (NTHi) to propagate as the more prominent gram-negative bacteria in syndromes such as chronic obstructive pulmonary disease exacerbations, the clinical and societal benefits outweigh the subsequent NTHi infection rates and morbidity and mortality.3 Notably, a 2016 study showed prevalence of viral causes for NV-HAP, which presumably has increased further since the 2020 SARS-CoV-2 pandemic and underscores the importance of vaccination against COVID- 19.3,19 Indeed, the SHEA compendium suggests implementation of multimodal interventions including prevention bundles to reduce viral infections with little risk of harm.5
Prompt, accurate diagnosis of NV-HAP remains challenging for many clinicians. Clinical acumen, laboratory studies, and chest radiography are all important in the evaluation of a patient with suspected NV-HAP. However, the use of each of these tests is limited given other conditions that may overlap with the findings of NV-HAP. The Clinical Pulmonary Infection Score has been used with some success in identifying patients with VAP but has not been included in past IDSA guidelines and lacks robust evidence for use in NV-HAP.20 In ventilated patients, a sputum sample is often obtained, but this remains a challenge in nonventilated patients. Although pursuing CT of the chest or bronchoscopy is helpful in diagnosis, this may pose unnecessary risk to the patient and must be considered on a case-by-case basis.
Given the frequency of NV-HAP and its impact on mortality and morbidity, future directions should be focused on prompt diagnosis and treatment of NV-HAP. Additionally, the nonspecificity of many of the current diagnostic tools remains problematic and may lead to inaccurate statistics regarding diagnosis of NV-HAP. As point-of-care ultrasound becomes more ubiquitous in the general wards, it may add additional diagnostic value to the evaluation of patients with suspected NV-HAP, given its demonstrated benefit in profiling other pneumonia profiles.21 Additionally, since the 2016 IDSA HAP/VAP guidelines were published, SARS-CoV-2 precipitated a viral pneumonia pandemic. Given the previously discussed burden of viruses in NV-HAP, it is likely that SARS-CoV-2 will complicate this further. For now, risk mitigation should focus on vaccination, masking within the hospital, hand hygiene, and rapid testing when appropriate. Overall, NV-HAP remains a significant nosocomial entity that should elicit a diligent investigation when suspected.
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