Open access peer-reviewed chapter

Hospital-Acquired Pneumonia

Written By

Sachin M. Patil

Submitted: August 26th, 2021 Reviewed: October 15th, 2021 Published: May 11th, 2022

DOI: 10.5772/intechopen.101236

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Abstract

Pneumonia acquired during hospitalization is called nosocomial pneumonia (NP). Nosocomial pneumonia is divided into two types. Hospital-acquired pneumonia (HAP) refers to hospital-acquired pneumonia, whereas ventilator-associated pneumonia (VAP) refers to ventilator-associated pneumonia. Most clinical literature stresses VAP’s importance and associated mortality and morbidity, whereas HAP is not given enough attention even while being the most common cause of NP. HAP, like VAP, carries a high mortality and morbidity. HAP is the commonest cause of mortality from hospital-acquired infections. HAP is a common determinant for intensive care unit (ICU) admits with respiratory failure. Recent research has identified definite risk factors responsible for HAP. If these are prevented or modified, the HAP incidence can be significantly decreased with improved clinical outcomes and lesser utilization of the health care resources. The prevention approach will need multiple strategies to address the issues. Precise epidemiological data on HAP is deficient due to limitations of the commonly used diagnostic measures. The diagnostic modalities available in HAP are less invasive than VAP. Recent infectious disease society guidelines have stressed the importance of HAP by removing healthcare-associated pneumonia as a diagnosis. Specific differences exist between HAP and VAP, which are gleaned over in this chapter.

Keywords

  • hospital-acquired pneumonia (HAP)
  • ventilator-associated pneumonia (VAP)
  • ICU
  • prevention

1. Introduction

Nosocomial pneumonia (NP) that occurs during a patient’s hospital course has been subclassified into hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). As per the latest Infectious Diseases Society of America (IDSA) and American Thoracic Society guidelines (ATS) [1], the category healthcare-associated pneumonia (HCAP) has been abandoned. The term NP and HAP should not be used interchangingly as before. HAP should be used only for pneumonia that occurs >48 h after admission to a hospital. VAP refers to pneumonia occurring >48 h post-intubation [2]. HAP is the most frequent hospital-acquired infection (HAI) [3]. As per the latest study done in the United States of America (USA), HAP prevalence in ICU was more frequent than VAP, and more than 75% of these patients developed severe respiratory failure due to pneumonia resulting in intubation and mechanical ventilatory support [4]. It is unknown whether the above trend is similar across all medical centers in the USA or is observed only in a few medical centers. Tertiary medical centers may have a different prevalence rate than other medical centers due to the higher presence of immunosuppressed patients (post-transplant). The lack of effective HAP surveillance systems in the USA and other countries adds to this tenuous issue. Also, the lack of definitive diagnostic criteria makes it difficult to identify HAP patients on the floor and in intensive care units, as fever and cough can have multiple diagnostic possibilities postadmission to a hospital.

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2. Epidemiology

HAP can occur in both patients with or without risk factors, and it is critical to realize that all acute care patients have an increased risk of HAP [5]. Specific patient subsets carry an increased risk than others, including elderly patients, chronic lung, cardiac and renal disease, hepatic cirrhosis, obesity, diabetes mellitus, cancer, neurological conditions such as stroke and dementia, malnutrition, and immunosuppressed patients [6, 7]. Specific therapeutic intervention modalities, including medications and procedures such as intubation, gastric tube placements, can increase the risk of HAP. Clinical literature on HAP inside the ICU is suboptimal, whereas on HAP outside the ICU is minuscule. NP accounts for around 21 admits per 1000 admissions to a hospital [8]. NP is responsible for close to 22% of HAI in the USA, and about 61% are HAP compared to VAP [9]. NP results in significant clinical outcomes such as increased healthcare costs, extended hospital stay, excess utilization of health care resources, and higher mortality and morbidity [10]. The actual prevalence rates of HAP and VAP are unknown; however, recent studies allude to a greater prevalence of HAP than VAP by a ratio of close to 2:1 in favor of HAP [11, 12]. A recent state study from Pennsylvania revealed that HAP risk factors and resulting complications are identical to those seen in VAP but were associated with an unfavorable higher economic cost and similar mortality [11]. Recent studies indicate an approximate incidence of 1.22 to 8.9 per 1000 patient days [5, 6, 9, 13, 14]. The total acute care cost for HAP is close to 40,000 dollars, with a hospital stay of 4 to 15.9 days, and the HAP influence on mortality was more significant than VAP [11, 13, 14]. Also, HAP patients, due to their increased occurrence, had a net increased economic cost than VAP and a higher need for postdischarge care [11, 14]. However, this cost did not include the interinstitutional transfer costs involved [14].

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3. Etiology and risk factors

As patients diagnosed with HAP are not intubated, they face multiple challenges, including an inability to perform minimally invasive procedures to obtain microbiological specimens from the lower airway leading to the absence of microbiological data and ineffective initial antimicrobial treatment. In a large European trial involving 27 ICU units among HAP patients, only 54.8% of patients had positive microbiology data. Enterobacteriaceaeare the most frequent cause, followed by Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii[15]. In another study, the microbial causes were similar between HAP and VAP except for an increased occurrence of Streptococcus pneumoniaein HAP patients [16]. 80% of cases were caused by Klebsiella spp., Enterobacter spp., Escherichia coli, Staphylococcus aureus, Acinetobacter spp., and Pseudomonas aeruginosaper the clinical data registered in the antimicrobial surveillance program SENTRY [17]. Also, in this study, severe sepsis and pneumonia occurred only in centers with >25% Multi-drug Resistance (MDR) prevalence, even in those lacking risk elements and early pneumonia. Upon reviewing the data mentioned above, gram-negative bacilli (GNB) cause most of these infections and are frequently resistant to antibiotics, making an empirical antibiotic decision difficult. In transplant patients, the microbial etiology differs based on the transplant type, duration post-transplant, and the antirejection mediations they are currently on. In hematopoietic stem cell transplants, bacterial causes were the highest, followed by fungal and viral [18]. Among the bacterial causes, the most common cause was Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pneumoniae. GNB was the most frequent in solid organ transplants, especially Pseudomonas aeruginosa, Enterobacteriaceae, followed by Staphylococcus aureus, often with an MDR profile [19]. The microorganisms responsible vary based on the patient population, MDR risk factors, geographical location, and duration of hospital stay before disease onset [2]. An essential factor to recognize is identifying any Multi-drug resistance organism (MDRO) risk factors, clinical severity, and local ecology before empirical antibiotic therapy. Tables 13 reveals the risk factors for Staphylococcus aureus[20, 21], Pseudomonas aeruginosa[22], and Acinetobacter baumannii[23, 24, 25, 26].

Invasive MSSA* infection risk factorsMRSA** HAP risk factors
1. Cardiac disease1. Tobacco abuse
2. Diabetes mellitus2. Illicit drug abuse
3. Cancer3. Recent hospitalization <90 days
4. Chronic obstructive pulmonary disease4. Recent antibiotics
5. Hemodialysis5. Chronic obstructive pulmonary disease
6. Stroke6. Liver disease
7. Intravenous drug abuse7. HIV infection
8. Rheumatoid arthritis
9. Human immunodeficiency viral infection
10. Peritoneal dialysis
11. Solid organ transplantation
12. Systemic lupus erythematosus

Table 1.

Invasive MSSA infection risk factors, MRSA HAP risk factors.

MSSA—Methicillin-sensitive Staphylococcus aureus.


MRSA—Methicillin-resistant Staphylococcus aureus.


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1. Prior infection with pseudomonas spp.
2. Pseudomonas spp. colonization
3. Very severe COPD
4. Bronchiectasis
5. Tracheostomy
6. Neutropenia
7. Burns
8. Cystic fibrosis
9. Long term acute care residents

Table 2.

Pseudomonas spp.HAP risk factors.

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1. Long term acute care residents
2. Prior colonization/infection
3. Longer hospital duration stay
4. Prior antibiotics use
5. Acinetobacter skin infections
6. Poor healthcare worker hygeine
7. Contamined procedure equipment

Table 3.

Acinetobacter spp. HAP risk factors.

“Created with BioRender.”

A prospective study has revealed the intrinsic and extrinsic risk factors for HAP in non-ICU patients, as shown in Table 4 [6]. Demographically age > 60 years and males are at higher risk of acquiring HAP.

Intrinsic risk factorsExtrinsic risk factors
1. Cancer1. Duration of hospitalization >5 days
2. Chronic obstructive pulmonary disease2. Prior antibiotic therapy
3. Diabetes mellitus3. H2 antagonist
4. Congestive heart failure4. Steroids
5. Chronic renal failure5. Antacids
6. Depression6. Chemotherapy
7. Neutropenia7. Prior endotracheal intubation
8. Obesity8. Nasogstric tube
9. Malnutrition9. Nebulization
10. Liver cirrhosis10. Abdominal surgery
11. Human immunodeficiency virus infection11. Prior ICU admission
12. Thoracic surgery
13. Head and neck surgery
14. Tracheotomy

Table 4.

Intrinsic and extrinsic risk factors for HAP in non ICU patients.

“Created with BioRender.com.”

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4. Pathophysiology

The upper airway and the oropharynx are usually colonized with nonpathogenic microorganisms, including the virulent Staphylococcus aureusand Streptococcus pneumoniae, and anaerobes. The lower airway microbiome is not entirely void of bacteria, as thought before [27]. The lower airway microbiome changes during chronic lung disease or prolonged immunosuppression. Within a few days post-admission, the upper airway and the oropharynx flora changes on exposure to the hospital ecology and get colonized with MRSA (Methicillin-sensitive Staphylococcus aureus) and GNB [28, 29]. Most HAP occurs after aspiration of the oropharyngeal flora except for few bacterial microorganisms, viral and fungal microorganisms, which occur via respiratory droplets or inhalation. Once inhaled or aspirated, the intact mucociliary clearance, mucociliary and alveolar defense will try to clear it up [30, 31, 32, 33]. They are often successful, but in cases with a large aspiration in a healthy patient or microaspiration in an immunosuppressed individual, the protective mechanisms are overwhelmed and result in HAP with significant inflammation and systemic signs. This entire process has been outlined in Figure 1.

Figure 1.

Pathophysiology of HAP.

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5. Clinical features

The clinical features of HAP have been summarized as follows in Table 5.

Clinical symptomsClinical signs
1. Fever1. Tachycardia
2. Dyspnea2. Hypotension
3. Cough3. Tachypnea
4. Tachypnea4. Hypoxia
5. Chest pain5. Rales
6. Purulent sputum6. Wheezing
7. Hypothermia7. Use of accessory respiratory muscles
8. Generalized weakness8. Absent/decreased breath sounds
9. Confusion9. Altered mental status

Table 5.

Clinical features of hospital-acquired pneumonia.

“Created with BioRender.”

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6. Diagnosis and differential diagnosis

Due to the lack of diagnostic criteria, clinical features need to be supplemented by imaging or laboratory tests for a HAP diagnosis. Imaging is often a portable or a two-view chest radiograph that reveals new pulmonary infiltrates, cavitation, abscess, or pleural effusion. Chest computed tomography (CT) is a gold standard in comparison and has better sensitivity than chest X-rays [34]. Recently, bedside ultrasound has been used to identify new pulmonary infiltrates with 94% sensitivity and 96% specificity [35]. A retrospective trial has revealed that biomarkers procalcitonin and C-reactive protein correlate well with HAP severity and could be a better prognostic marker for mortality and morbidity than neutrophil/lymphocyte count ratio [36]. A complete blood count may demonstrate leukocytosis. The differential count is essential in identifying any neutrophilia, neutropenia, eosinophilia, and a peripheral smear may demonstrate Dohle bodies that are more suggestive of ongoing infection. Microbiological workup can be invasive or noninvasive. Blood cultures with the help of MALDI BioTyper and FilmArray BCID can help rapidly identify the bacteria [37]. In transplant patients, a fungal blood culture would be ideal. Urine legionella and Streptococcal antigens can help identify the cause of pneumonia. Serum Aspergillus antigen assay and β-D-glucan assay is a must in transplant and immunosuppressed individuals when suspected. Nasopharyngeal swab polymerase chain reaction (PCR), also called a respiratory pathogen panel, can be utilized to identify some of the common respiratory bacterial and viral pathogens causing community-acquired pneumonia, which can also cause HAP due to significant exposure prior to admission and in the hospital.

The sputum gram stain, sputum specimen PCR, and culture should be done to identify the suspected etiological agent. If there is a lack of sputum, production then it can be induced by inhaled hypertonic saline. Sputum PCR using BioFire FilmArray Pneumonia or Pneumonia plus panel yields excellent sensitivity and specificity but must be adopted judiciously, and it could provide appropriate clinical information for antimicrobial stewardship [38, 39]. It can also detect atypical bacteria, common viral causes of pneumonia, common mechanisms of resistance and provide semiquantitative results for the common colonizers [40]. It provides valuable data for the clinician to deescalate the antibiotics to a narrow spectrum. This PCR test does not detect oral anaerobes, and they need to be considered with positive imaging and a negative PCR test to cover them with appropriate antibiotics. The PCR test should be done early in the clinical course to avoid false negatives and must be corroborated with the culture as much as possible. A sputum fungal culture or stain also might be helpful in transplant patients.

The invasive strategy involves performing a fibreoptic bronchoscopy, obtaining a bronchioalveolar lavage (BAL) sample, and performing BAL tests, including gram stain, fungal stain, cytology with methenamine stain, and quantitative culture (bacterial and fungal). BAL Aspergillus antigen assay, β-D-glucan assay, fungal and viral PCR assays can detect the causative agent in immunosuppressed or transplant patients. Invasive tests are done seldomly in stable patients as most of these patients are sick, unstable and the procedure may clinically deteriorate them [41]. If the patient during his clinical course gets intubated, then a BAL should be obtained to obtain more clinical information.

The betaLACTA test (BLT) detects GNB insensitivity to third-generation cephalosporins due to carbapenemases, ESBL (extended-spectrum beta-lactamases), and beta-lactamases from acquired AmpC carbapenemases in less than 20 min after exposure to respiratory bacterial cell pellets via chromogenic analysis [42]. The test detects GNB resistance via a colorimetric indicator and can quickly be used for antibiotic de-escalation [43]. It is currently being evaluated for its clinical efficaciousness in France’s multicenter randomized controlled trial (RCT) called BLUE-CarbA [44].

A clinical diagnosis of HAP is currently considered with a new lung infiltrate and two of the four findings, including new-onset temperature > 38 degrees celsius, purulent sputum, and leukocytosis or leukopenia [45]. Most clinical diagnostic scores, including modified clinical pulmonary infection score (CPIS), the older National safety health network (NHSN) pneumonia definition, and the new infection-related Ventilator-associated complication (IVAC), have been used extensively in VAP and not in HAP. NHSN does suggest using the pneumonia definition for nonventilated adult patients for surveillance purposes (Table 6). However, the long-term clinical utility of its use is unknown due to its lack of accuracy and consistency in VAP [46].

1. Two or more serial chest imaging test results with at least one of the following new and persistent or Progressive and persistent (Radiological criteria)
*Infiltrate/Consolidation/Cavitation
PLUS
2. Atleast one of the following (Systemic criteria)
 • Fever (>38.0°C or > 100.4°F)
 • Leukopenia (≤4000 WBC/mm3) or leukocytosis (≥12,000 WBC/mm3)
 • For adults ≥70 years old, altered mental status with no other recognized cause
PLUS
3. And at least two of the following (Pulmonary criteria)
 • New onset of purulent sputum or change in character of sputum, or increased respiratory secretions, or increased suctioning requirements
 • New onset or worsening cough, or dyspnea, or tachypnea
 • Rales6 or bronchial breath sounds
 • Worsening gas exchange (for example: O2 desaturations (for example: PaO2/FiO2 ≤ 240)7, increased oxygen requirements, or increased ventilator demand)

Table 6.

National health safety network definition of pneumonia (NHSN PNEU).

Clinical conditions that may simulate HAP and may need to be considered part of the differential diagnosis are mentioned in Table 7.

1. Pulmonary contusion
2. Pulmonary inhalation injuries
3. Atelectasis
4. Pleural effusion
5. Pulmonary edema
6. Pulmonary hemorrhage
7. Drug-induced pneumonitis
8. Pulomary infarct/embolism
9. Vasculitis
10. Primary or secondary pulmonary neoplasm

Table 7.

Differential diagnosis of HAP.

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7. Treatment

Initial inappropriate antibiotic regimens and MDRO are independent indicators of ICU mortality and related to a longer mechanical ventilation duration [47]. Physicians always face a clinical scenario where they have to treat a patient with no lower respiratory specimen with the possibility of pending acute respiratory failure requiring mechanical ventilation [41]. Empirical antibiotic therapy can be based either on institutional epidemiology or a surveillance culture report updated annually. Although they yield similar results, the use of surveillance culture report results in reduced broad-spectrum antibiotics uses even in the presence of higher MDRO risk factors [48]. Individual patient risk factors need to be considered before an initial empirical regimen is started for HAP [49]. A suggestion is to use the local antibiogram in deciding the initial regimen. Most regimens include a broad-spectrum gram-positive coverage (vancomycin or linezolid) and a gram-negative coverage (carbapenem or fourth-generation cephalosporin or a piperacillin-tazobactam). It is prudent to use an antipseudomonal agent to cover gram-negative bacteria in the empirical regimen. MRSA screening of nares has a 96.1% negative predictive value for respiratory cultures [50]. Gram-positive bacterial coverage can be deescalated to MSSA coverage with a negative MRSA nasal screen if the clinical condition warrants it.

For de-escalation, at 48 to 72 h postadmission, procalcitonin plus C-reactive protein and a positive microbiological workup assist the clinical criteria [2]. De-escalation involves a transition from broad-spectrum to narrow-spectrum antimicrobial therapy. For atypical organism coverage, if suspected, rarely responsible for HAP, azithromycin or fluoroquinolone, or doxycycline can be used in addition to the empirical therapy. For P. aeruginosaHAP with no susceptibility results or absence of septic shock or high death risk, dual antipseudomonal coverage is indicated [2]. If the susceptibility pattern has resulted and in the absence of septic shock and increased risk of death, monotherapy is appropriate. P. aeruginosaHAP with carbapenemase resistance (CRE) can still be treated with ceftolozane/tazobactam combination as its primary resistance is via porin channels [51]. With ESBL GNB causing HAP, the recommended therapy is carbapenems with suggested alternatives, including ceftolozane/tazobactam combination. With Acinetobacter spp., the treatment is based on antimicrobial susceptibility and usually involves more than one drug. CRE GNB is treated with Ceftazidime/avibactam, and Aztreonam is added to combination in GNB carrying Metallo-carbapenemase. The usual duration of treatment is around 7 days as in VAP with some exceptions, which include MSSA, MRSA, nonfermenting GNB such as Pseudomonas, Stenotrophomonas, Acinetobacter, and Burkholderia spp., which have a higher rate of recurrence with 7 days of therapy (this data extrapolated from VAP studies) [52]. Regarding MSSA and MRSA HAP, the duration mentioned above is a recommended expert opinion due to the lack of RCTs on the course of therapy (7 vs. 14 days) [53]. Other exceptions to the seven-day course could be patients with immunosuppression and necrotizing pneumonia. Antimicrobial treatment should be based on the pharmacokinetics and pharmacodynamic data of the individual antimicrobial to avoid unwanted side effects.

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8. Prevention

The utilization of any preventive measures to halt HAP should effectively alter the pathophysiology of the disease. Multiple measures have been carried out over the last few decades to prevent HAP or, preferably, VAP with variable degrees of success (Table 8).

Active measures takenEffectiveness of measure
A. Exposure reduction: All the below-mentioned measures need further evaluation in HAP patients [54].
Limit admission to hospital as much as possibleIncreased hospitalization duration is associated with increased sepsis warning scores and increased exposure to HAP pathogens [55]. The risk in elderly patients increases at a rate of 0.3% per day [56]. Decreased duration of hospitalization results in decreased exposure and risk; however, this needs prospective assessment.
Healthcare worker and equipment hygieneIt prevents microbial spread between patients, health care workers, and essential equipment and improves VAP and catheter-associated bloodstream infection rates [57]. Stethoscopes and portable procedure equipment cleaning with chlorhexidine or alcohol-based sanitizer are ideal [58, 59]. The use of a portable stethoscope separately for each patient is another option [60]. Minimally invasive procedure equipment such as endoscopes and bronchoscopes should be sterilized with stringent protocols. Low compliance is frequent in healthcare workers and needs to be improved with structured educational programs and timely reinforcements [61].
Isolation measuresStandard isolation precautions such as universal gowns and gloves are ineffective in preventing the transmission of infections caused by MDRO [62]. However, they are highly effective in preventing Clostridium difficile (C. difficile)transmission [63]. Droplet precautions in hospitalized influenza infections prevent its spread.
B. Aspiration reduction: As mentioned above, the below-mentioned measures need validation in HAP patients.
Prevent and reduce xerostomiaXerostomia or oral dryness correlates with fever in dysphagia patients, but its association with HAP is unknown [64]. Also, the effect of xerostomia prevention and treatment with sialogogues on HAP incidence and prevalence is unknown [65].
Timely identification of dysphagiaIdentifying patients with a higher risk of dysphagia promptly by a higher screening adherence results in lower HAP rates [66]. This is especially important in patients with neurological disorders. Dysphagia evaluation by a speech therapist can lead to modified diets in specific population subsets with a lower incidence of pneumonia [67].
Feeding via enteral tubesJejunostomy tubes compared to gastric ones result in lower VAP and HAP rates [68]. The use of a motility agent has lead to variable results in a systematic review, and its benefit is questionable [69].
Patient position modificationA semi-recumbent position (30° to 45°) during feeding decreases acid reflux and the risk of aspiration with a decline in VAP rates [70].
MobilizationEarlier mobilization stops the functional decline, improves airway clearance, and prevents HAP [71]. Family member’s training helps in extending this benefit outside of the healthcare environment [72].
C. Active interventions
Oral hygieneBad oral hygiene results in increased colonization with airway pathogens and periodontal disease [73]. It can diminish cough reflex and impair airway hygiene leading to pneumonia [74, 75]. Interventions to improve oral hygiene are the best known cost-effective preventive strategy for HAP [5, 76]. Adequate training of nursing staff in oral care practices is critical with timely reinforcements.
Decontamination of oral, digestive, and skinSkin decontamination with chlorhexidine decreases VAP, HAI but its effect on HAP is unknown [77]. Oral decontamination with chlorhexidine diminishes VAP rates and increases mortality; however, its implication on HAP is unknown [12, 78]. Selective digestive decontamination (SDD) with oral, topical, and intravenous antibiotics decreased VAP and is thought to be adequate in HAP [79]. SDD use was in countries with lower antibiotic resistance levels, and its long-term effects are unknown [12].
VaccinationVaccination against hospital pathogens is ineffective [80], whereas monoclonal antibodies have shown promise adjunctively with antibiotics in early trials for Staphylococcus aureusand Pseudomonas aeruginosa[81].
Medications and other factorsAs medications preventing gastric-acid secretions are linked to increased HAP rates, preventing their indiscriminate use is necessary [82]. Adequate glucose control preventing hypo and hyperglycemia is critical in halting airway colonization and pneumonia risk [83, 84]. Probiotics may decrease the HAP rate; however, they have not been evaluated in HAP.
Airway hygieneWhen done preemptively in postoperative and hospitalized pneumonia patients, chest physical therapy has revealed modest preventive effects [85, 86].
Respiratory supportNoninvasive ventilation (NIV) decreased nosocomial pneumonia and improved outcomes in specific patient subsets [87]. Although it allows for better airway clearance and comfort, high-flow nasal cannula use did not decrease HAP incidence in two small randomized controlled trials [88, 89]. Recent helmet use in NIV did not decrease HAP rates compared to facemask [90].
Staffing practicesIncreased nursing staff to patient ratio results in lower HAP and HAI rates [91]. The presence of daytime intensivists correlates with improved mortality overall [92]. The effect of 24 h physician staffing on the HAP rates is unknown.

Table 8.

HAP preventive measures.

A constant surveillance system absence regarding HAP has prevented effective detection and monitoring of HAP rates in the USA. An objective assessment is hampered by the lack of standard diagnostic criteria, microbiologic and diagnostic coding data [54]. Also, only a few preventive measures have been validated, and the remaining lack adequate clinical data for physicians to implement them successfully. It requires multidisciplinary team involvement for the effective implementation of these preventive measures.

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9. Conclusion

The administratively coded data (ACD) used for billing is limited, and its accuracy is imprecise in HAP detection and surveillance [14]. A better approach to this problem will be to use proven assessed techniques, and this practice should be utilized in HAP detection. The approach should start with creating a specific diagnostic criterion followed by evidence-based guidelines to help in decreasing its incidence and prevalence with additional stress on earlier detection and prevention.

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Acknowledgments

“No external funds were utilized in the manuscript preparation.”

Conflict of interest

“The author declares no conflict of interest.”

Notes/Thanks/Other declarations

“I thank the editor for letting me author this manuscript.”

Acronyms and abbreviations

NP

Nosocomial pneumonia

HAP

Hospital-acquired pneumonia

VAP

Ventilator-associated pneumonia

ICU

Intensive care unit

IDSA

Infectious Diseases Society of America

HCAP

Healthcare-associated pneumonia

HAI

Hospital-acquired infections

USA

United States of America

MDR

Multi-drug Resistance

MDRO

Multi-drug Resistance Organism

HIV

Human Immunodeficiency virus

MSSA

Methicillin-sensitive Staphylococcus aureus

MRSA

Methicillin-resistant Staphylococcus aureus

COPD

Chronic obstructive pulmonary disease

GNB

Gram-negative bacilli

CT

Computed tomography

MALDI

Matrix-assisted laser desorption ionization

BCID

Blood Culture ID Panel

PCR

Polymerase chain reaction

BAL

Bronchioalveolar lavage

BLT

betaLACTA test

ESBL

Extended-spectrum beta-lactamase

RCT

Randomized controlled trial

CPIS

Clinical pulmonary infection score

NHSN

National health safety network

IVAC

Infection-related Ventilator-associated complication

CRE

Carbapenemase resistance

SDD

Selective digestive decontamination

NIV

Noninvasive ventilation

ACD

Administratively coded data

References

  1. 1. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, 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. American Journal of Respiratory and Critical Care Medicine. 2019;200(7):e45-e67
  2. 2. Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, 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. Clinical Infectious Diseases. 2016;63(5):e61-e111
  3. 3. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. Journal of the American Medical Association. 2009;302(21):2323-2329
  4. 4. Kett DH, Cano E, Quartin AA, Mangino JE, Zervos MJ, Peyrani P, et al. Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: An observational, multicentre cohort study. The Lancet Infectious Diseases. 2011;11(3):181-189
  5. 5. Quinn B, Baker DL, Cohen S, Stewart JL, Lima CA, Parise C. Basic nursing care to prevent nonventilator hospital-acquired pneumonia. Journal of Nursing Scholarship. 2014;46(1):11-19
  6. 6. Sopena N, Sabria M, Neunos SG. Multicenter study of hospital-acquired pneumonia in non-ICU patients. Chest. 2005;127(1):213-219
  7. 7. Cilloniz C, Polverino E, Ewig S, Aliberti S, Gabarrus A, Menendez R, et al. Impact of age and comorbidity on cause and outcome in community-acquired pneumonia. Chest. 2013;144(3):999-1007
  8. 8. Chawla R. Epidemiology, etiology, and diagnosis of hospital-acquired pneumonia and ventilator-associated pneumonia in Asian countries. American Journal of Infection Control. 2008;36(4 Suppl):S93-S100
  9. 9. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care-associated infections. The New England Journal of Medicine. 2014;370(13):1198-1208
  10. 10. Eber MR, Laxminarayan R, Perencevich EN, Malani A. Clinical and economic outcomes attributable to health care-associated sepsis and pneumonia. Archives of Internal Medicine. 2010;170(4):347-353
  11. 11. Davis J, Finley AE, editors. The breadth of hospital-acquired pneumonia: Nonventilated versus ventilated patients in Pennsylvania. Pennsylvania Patient Safety Advisory. 2012;9(3):99-105. Available from:http://patientsafety.pa.gov/ADVISORIES/Documents/201209_99.pdf
  12. 12. Torres A, Niederman MS, Chastre J, Ewig S, Fernandez-Vandellos P, Hanberger H, 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 Asociacion Latinoamericana del Torax (ALAT). European Respiratory Journal. 2017;50(3):2
  13. 13. Micek ST, Chew B, Hampton N, Kollef MH. A case-control study assessing the impact of nonventilated hospital-acquired pneumonia on patient outcomes. Chest. 2016;150(5):1008-1014
  14. 14. Giuliano KK, Baker D, Quinn B. The epidemiology of nonventilator hospital-acquired pneumonia in the United States. American Journal of Infection Control. 2018;46(3):322-327
  15. 15. Koulenti D, Tsigou E, Rello J. Nosocomial pneumonia in 27 ICUs in Europe: Perspectives from the EU-VAP/CAP study. European Journal of Clinical Microbiology & Infectious Diseases. 2017;36(11):1999-2006
  16. 16. Esperatti M, Ferrer M, Theessen A, Liapikou A, Valencia M, Saucedo LM, et al. Nosocomial pneumonia in the intensive care unit acquired by mechanically ventilated versus nonventilated patients. American Journal of Respiratory and Critical Care Medicine. 2010;182(12):1533-1539
  17. 17. Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clinical Infectious Diseases. 2010;51(Suppl 1):S81-S87
  18. 18. Aguilar-Guisado M, Jimenez-Jambrina M, Espigado I, Rovira M, Martino R, Oriol A, et al. Pneumonia in allogeneic stem cell transplantation recipients: A multicenter prospective study. Clinical Transplantation. 2011;25(6):E629-E638
  19. 19. Giannella M, Munoz P, Alarcon JM, Mularoni A, Grossi P, Bouza E, et al. Pneumonia in solid organ transplant recipients: A prospective multicenter study. Transplant Infectious Disease. 2014;16(2):232-241
  20. 20. Laupland KB, Church DL, Mucenski M, Sutherland LR, Davies HD. Population-based study of the epidemiology of and the risk factors for invasive Staphylococcus aureus infections. The Journal of Infectious Diseases. 2003;187(9):1452-1459
  21. 21. Wooten DA, Winston LG. Risk factors for methicillin-resistant Staphylococcus aureus in patients with community-onset and hospital-onset pneumonia. Respiratory Medicine. 2013;107(8):1266-1270
  22. 22. Restrepo MI, Babu BL, Reyes LF, Chalmers JD, Soni NJ, Sibila O, et al. Burden and risk factors forPseudomonas aeruginosacommunity-acquired pneumonia: A multinational point prevalence study of hospitalised patients. European Respiratory Journal. 2018;52(2):2, 9, 10
  23. 23. Turton JF, Shah J, Ozongwu C, Pike R. Incidence of acinetobacter species other thanA. baumanniiamong clinical isolates of acinetobacter: Evidence for emerging species. Journal of Clinical Microbiology. 2010;48(4):1445-1449
  24. 24. Thom KA, Johnson JK, Lee MS, Harris AD. Environmental contamination because of multidrug-resistantAcinetobacter baumanniisurrounding colonized or infected patients. American Journal of Infection Control. 2011;39(9):711-715
  25. 25. Wong D, Nielsen TB, Bonomo RA, Pantapalangkoor P, Luna B, Spellberg B. Clinical and pathophysiological overview of acinetobacter infections: A century of challenges. Clinical Microbiology Reviews. 2017;30(1):409-447
  26. 26. Falagas ME, Rafailidis PI. Attributable mortality of acinetobacter baumannii: No longer a controversial issue. Critical Care. 2007;11(3):134
  27. 27. Charlson ES, Bittinger K, Haas AR, Fitzgerald AS, Frank I, Yadav A, et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. American Journal of Respiratory and Critical Care Medicine. 2011;184(8):957-963
  28. 28. Johanson WG Jr, Pierce AK, Sanford JP, Thomas GD. Nosocomial respiratory infections with gram-negative bacilli. The significance of colonization of the respiratory tract. Annals of Internal Medicine. 1972;77(5):701-706
  29. 29. Johanson WG, Pierce AK, Sanford JP. Changing pharyngeal bacterial flora of hospitalized patients. Emergence of gram-negativebacilli. The New England Journal of Medicine. 1969;281(21):1137-1140
  30. 30. Ware SM, Aygun MG, Hildebrandt F. Spectrum of clinical diseases caused by disorders of primary cilia. Proceedings of the American Thoracic Society. 2011;8(5):444-450
  31. 31. Voynow JA, Rubin BK. Mucins, mucus, and sputum. Chest. 2009;135(2):505-512
  32. 32. Parker D, Prince A. Innate immunity in the respiratory epithelium. American Journal of Respiratory Cell and Molecular Biology. 2011;45(2):189-201
  33. 33. Holt PG, Strickland DH, Wikstrom ME, Jahnsen FL. Regulation of immunological homeostasis in the respiratory tract. Nature Reviews. Immunology. 2008;8(2):142-152
  34. 34. Self WH, Courtney DM, McNaughton CD, Wunderink RG, Kline JA. High discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ED patients: Implications for diagnosing pneumonia. The American Journal of Emergency Medicine. 2013;31(2):401-405
  35. 35. Chavez MA, Shams N, Ellington LE, Naithani N, Gilman RH, Steinhoff MC, et al. Lung ultrasound for the diagnosis of pneumonia in adults: A systematic review and meta-analysis. Respiratory Research. 2014;15:50
  36. 36. Zheng N, Zhu D, Han Y. Procalcitonin and C-reactive protein perform better than the neutrophil/lymphocyte count ratio in evaluating hospital acquired pneumonia. BMC Pulmonary Medicine. 2020;20(1):166
  37. 37. Fiori B, D’Inzeo T, Giaquinto A, Menchinelli G, Liotti FM, de Maio F, et al. Optimized use of the MALDI biotyper system and the filmarray BCID panel for direct identification of microbial pathogens from positive blood cultures. Journal of Clinical Microbiology. 2016;54(3):576-584
  38. 38. Gastli N, Loubinoux J, Daragon M, Lavigne JP, Saint-Sardos P, Pailhories H, et al. Multicentric evaluation of biofire filmarray pneumonia panel for rapid bacteriological documentation of pneumonia. Clinical Microbiology and Infection. 2021;27(9):1308-1314
  39. 39. Murphy CN, Fowler R, Balada-Llasat JM, Carroll A, Stone H, Akerele O, et al. Multicenter evaluation of the biofire filmarray pneumonia/pneumonia plus panel for detection and quantification of agents of lower respiratory tract infection. Journal of Clinical Microbiology. 2020;58(7):1
  40. 40. Buchan BW, Windham S, Balada-Llasat JM, Leber A, Harrington A, Relich R, et al. Practical comparison of the biofire filmarray pneumonia panel to routine diagnostic methods and potential impact on antimicrobial stewardship in adult hospitalized patients with lower respiratory tract infections. Journal of Clinical Microbiology. 2020;58(7):1-2
  41. 41. Ranzani OT, De Pascale G, Park M. Diagnosis of nonventilated hospital-acquired pneumonia: How much do we know? Current Opinion in Critical Care. 2018;24(5):339-346
  42. 42. Garnier M, Rozencwajg S, Pham T, Vimont S, Blayau C, Hafiani M, et al. Evaluation of early antimicrobial therapy adaptation guided by the BetaLACTA(R) test: A case-control study. Critical Care. 2017;21(1):161
  43. 43. Laurent T, Huang TD, Bogaerts P, Glupczynski Y. Evaluation of the betaLACTA test, a novel commercial chromogenic test for rapid detection of ceftazidime-nonsusceptiblepseudomonas aeruginosaisolates. Journal of Clinical Microbiology. 2013;51(6):1951-1954
  44. 44. Garnier M, Gallah S, Vimont S, Benzerara Y, Labbe V, Constant AL, et al. Multicentre randomised controlled trial to investigate usefulness of the rapid diagnostic betaLACTA test performed directly on bacterial cell pellets from respiratory, urinary or blood samples for the early de-escalation of carbapenems in septic intensive care unit patients: The BLUE-CarbA protocol. BMJ Open. 2019;9(2):e024561
  45. 45. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. American Journal of Respiratory and Critical Care Medicine. 2005;171(4):388-416
  46. 46. Stevens JP, Silva G, Gillis J, Novack V, Talmor D, Klompas M, et al. Automated surveillance for ventilator-associated events. Chest. 2014;146(6):1612-1618
  47. 47. Tumbarello M, De Pascale G, Trecarichi EM, Spanu T, Antonicelli F, Maviglia R, et al. Clinical outcomes ofpseudomonas aeruginosapneumonia in intensive care unit patients. Intensive Care Medicine. 2013;39(4):682-692
  48. 48. De Bus L, Saerens L, Gadeyne B, Boelens J, Claeys G, De Waele JJ, et al. Development of antibiotic treatment algorithms based on local ecology and respiratory surveillance cultures to restrict the use of broad-spectrum antimicrobial drugs in the treatment of hospital-acquired pneumonia in the intensive care unit: A retrospective analysis. Critical Care. 2014;18(4):R152
  49. 49. Di Pasquale M, Ferrer M, Esperatti M, Crisafulli E, Giunta V, Li Bassi G, et al. Assessment of severity of ICU-acquired pneumonia and association with etiology. Critical Care Medicine. 2014;42(2):303-312
  50. 50. Mergenhagen KA, Starr KE, Wattengel BA, Lesse AJ, Sumon Z, Sellick JA. Determining the utility of methicillin-resistant staphylococcus aureus nares screening in antimicrobial stewardship. Clinical Infectious Diseases. 2020;71(5):1142-1148
  51. 51. Haidar G, Philips NJ, Shields RK, Snyder D, Cheng S, Potoski BA, et al. Ceftolozane-tazobactam for the treatment of multidrug-resistantpseudomonas aeruginosainfections: Clinical effectiveness and evolution of resistance. Clinical Infectious Diseases. 2017;65(1):110-120
  52. 52. Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: A randomized trial. Journal of the American Medical Association. 2003;290(19):2588-2598
  53. 53. Que Y-A, Moreillon P. 196—Staphylococcus aureus(Including staphylococcal toxic shock syndrome). In: Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (Eighth Edition). Philadelphia: W.B. Saunders; 2015. pp. 2237-71.e5
  54. 54. Lyons PG, Kollef MH. Prevention of hospital-acquired pneumonia. Current Opinion in Critical Care. 2018;24(5):370-378
  55. 55. Churpek MM, Snyder A, Han X, Sokol S, Pettit N, Howell MD, et al. Quick sepsis-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores for detecting clinical deterioration in infected patients outside the intensive care unit. American Journal of Respiratory and Critical Care Medicine. 2017;195(7):906-911
  56. 56. Burton LA, Price R, Barr KE, McAuley SM, Allen JB, Clinton AM, et al. Hospital-acquired pneumonia incidence and diagnosis in older patients. Age and Ageing. 2016;45(1):171-174
  57. 57. Boyce JM, Pittet D. Healthcare infection control practices advisory C, Force HSAIHHT. Guideline for hand hygiene in health-care settings. Recommendations of the healthcare infection control practices advisory committee and the HICPAC/SHEA/APIC/IDSA hand hygiene task force. Society for healthcare epidemiology of America/Association for professionals in infection control/Infectious diseases society of America. MMWR Recommendations Report. 2002;51(RR-16):1-45
  58. 58. O’Flaherty N, Fenelon L. The stethoscope and healthcare-associated infection: A snake in the grass or innocent bystander? The Journal of Hospital Infection. 2015;91(1):1-7
  59. 59. Alvarez JA, Ruiz SR, Mosqueda JL, Leon X, Arreguin V, Macias AE, et al. Decontamination of stethoscope membranes with chlorhexidine: Should it be recommended? American Journal of Infection Control. 2016;44(11):e205-e2e9
  60. 60. Maki DG. Stethoscopes and health care-associated infection. Mayo Clinic Proceedings. 2014;89(3):277-280
  61. 61. Whitby M, Pessoa-Silva CL, McLaws ML, Allegranzi B, Sax H, Larson E, et al. Behavioural considerations for hand hygiene practices: The basic building blocks. The Journal of Hospital Infection. 2007;65(1):1-8
  62. 62. Harris AD, Pineles L, Belton B, Johnson JK, Shardell M, Loeb M, et al. Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: A randomized trial. Journal of the American Medical Association. 2013;310(15):1571-1580
  63. 63. Nelson RE, Jones M, Leecaster M, Samore MH, Ray W, Huttner A, et al. An Economic analysis of strategies to control clostridium difficile transmission and infection using an agent-based simulation model. PLoS One. 2016;11(3):e0152248
  64. 64. Saito T, Oobayashi K, Shimazaki Y, Yamashita Y, Iwasa Y, Nabeshima F, et al. Association of dry tongue to pyrexia in long-term hospitalized patients. Gerontology. 2008;54(2):87-91
  65. 65. Riley P, Glenny AM, Hua F, Worthington HV. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database of Systematic Reviews. 2017;7:CD012744
  66. 66. Titsworth WL, Abram J, Fullerton A, Hester J, Guin P, Waters MF, et al. Prospective quality initiative to maximize dysphagia screening reduces hospital-acquired pneumonia prevalence in patients with stroke. Stroke. 2013;44(11):3154-3160
  67. 67. Ebihara T, Ebihara S, Yamazaki M, Asada M, Yamanda S, Arai H. Intensive stepwise method for oral intake using a combination of transient receptor potential stimulation and olfactory stimulation inhibits the incidence of pneumonia in dysphagic older adults. Journal of the American Geriatrics Society. 2010;58(1):196-198
  68. 68. Alhazzani W, Almasoud A, Jaeschke R, Lo BW, Sindi A, Altayyar S, et al. Small bowel feeding and risk of pneumonia in adult critically ill patients: A systematic review and meta-analysis of randomized trials. Critical Care. 2013;17(4):R127
  69. 69. Liu Y, Dong X, Yang S, Wang A, Wang M. Metoclopramide for preventing nosocomial pneumonia in patients fed via nasogastric tubes: A systematic review and meta-analysis of randomized controlled trials. Asia Pacific Journal of Clinical Nutrition. 2017;26(5):820-828
  70. 70. Wang L, Li X, Yang Z, Tang X, Yuan Q, Deng L, et al. Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation. Cochrane Database of Systematic Reviews. 2016;1:CD009946
  71. 71. Stolbrink M, McGowan L, Saman H, Nguyen T, Knightly R, Sharpe J, et al. The Early Mobility Bundle: A simple enhancement of therapy which may reduce incidence of hospital-acquired pneumonia and length of hospital stay. The Journal of Hospital Infection. 2014;88(1):34-39
  72. 72. Cuesy PG, Sotomayor PL, Pina JO. Reduction in the incidence of poststroke nosocomial pneumonia by using the “turn-mob” program. Journal of Stroke and Cerebrovascular Diseases. 2010;19(1):23-28
  73. 73. Scannapieco FA, Bush RB, Paju S. Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary disease. A systematic review. Annals of Periodontology. 2003;8(1):54-69
  74. 74. Watando A, Ebihara S, Ebihara T, Okazaki T, Takahashi H, Asada M, et al. Daily oral care and cough reflex sensitivity in elderly nursing home patients. Chest. 2004;126(4):1066-1070
  75. 75. Nakajoh K, Nakagawa T, Sekizawa K, Matsui T, Arai H, Sasaki H. Relation between incidence of pneumonia and protective reflexes in post-stroke patients with oral or tube feeding. Journal of Internal Medicine. 2000;247(1):39-42
  76. 76. El-Rabbany M, Zaghlol N, Bhandari M, Azarpazhooh A. Prophylactic oral health procedures to prevent hospital-acquired and ventilator-associated pneumonia: A systematic review. International Journal of Nursing Studies. 2015;52(1):452-464
  77. 77. Swan JT, Ashton CM, Bui LN, Pham VP, Shirkey BA, Blackshear JE, et al. Effect of chlorhexidine bathing every other day on prevention of hospital-acquired infections in the surgical ICU: A single-center, randomized controlled trial. Critical Care Medicine. 2016;44(10):1822-1832
  78. 78. Klompas M, Speck K, Howell MD, Greene LR, Berenholtz SM. Reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: Systematic review and meta-analysis. JAMA Internal Medicine. 2014;174(5):751-761
  79. 79. Roquilly A, Marret E, Abraham E, Asehnoune K. Pneumonia prevention to decrease mortality in intensive care unit: A systematic review and meta-analysis. Clinical Infectious Diseases. 2015;60(1):64-75
  80. 80. Shinefield H, Black S, Fattom A, Horwith G, Rasgon S, Ordonez J, et al. Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. The New England Journal of Medicine. 2002;346(7):491-496
  81. 81. Francois B, Luyt CE, Dugard A, Wolff M, Diehl JL, Jaber S, et al. Safety and pharmacokinetics of an anti-PcrV PEGylated monoclonal antibody fragment in mechanically ventilated patients colonized withPseudomonas aeruginosa: A randomized,double-blind, placebo-controlled trial. Critical Care Medicine. 2012;40(8):2320-2326
  82. 82. Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. Journal of the American Medical Association. 2009;301(20):2120-2128
  83. 83. Gill SK, Hui K, Farne H, Garnett JP, Baines DL, Moore LS, et al. Increased airway glucose increases airway bacterial load in hyperglycaemia. Scientific Reports. 2016;6:27636
  84. 84. Garnett JP, Baker EH, Baines DL. Sweet talk: Insights into the nature and importance of glucose transport in lung epithelium. The European Respiratory Journal. 2012;40(5):1269-1276
  85. 85. Yang M, Yan Y, Yin X, Wang BY, Wu T, Liu GJ, et al. Chest physiotherapy for pneumonia in adults. Cochrane Database of Systematic Reviews. 2013;2:CD006338
  86. 86. Pasquina P, Tramer MR, Granier JM, Walder B. Respiratory physiotherapy to prevent pulmonary complications after abdominal surgery: A systematic review. Chest. 2006;130(6):1887-1899
  87. 87. Girou E, Schortgen F, Delclaux C, Brun-Buisson C, Blot F, Lefort Y, et al. Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients. Journal of the American Medical Association. 2000;284(18):2361-2367
  88. 88. Stephan F, Barrucand B, Petit P, Rezaiguia-Delclaux S, Medard A, Delannoy B, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: A randomized clinical trial. Journal of the American Medical Association. 2015;313(23):2331-2339
  89. 89. Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. The New England Journal of Medicine. 2015;372(23):2185-2196
  90. 90. Rocco M, Dell’Utri D, Morelli A, Spadetta G, Conti G, Antonelli M, et al. Noninvasive ventilation by helmet or face mask in immunocompromised patients: A case-control study. Chest. 2004;126(5):1508-1515
  91. 91. Kane RL, Shamliyan TA, Mueller C, Duval S, Wilt TJ. The association of registered nurse staffing levels and patient outcomes: Systematic review and meta-analysis. Medical Care. 2007;45(12):1195-1204
  92. 92. Wilcox ME, Chong CA, Niven DJ, Rubenfeld GD, Rowan KM, Wunsch H, et al. Do intensivist staffing patterns influence hospital mortality following ICU admission? A systematic review and meta-analyses. Critical Care Medicine. 2013;41(10):2253-2274

Written By

Sachin M. Patil

Submitted: August 26th, 2021 Reviewed: October 15th, 2021 Published: May 11th, 2022