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Non-ventilator health care-associated pneumonia (NV-HAP): Pathogenesis and microbiology of NV-HAP

      Abstract

      Studies demonstrate that those at risk for developing nonventilator associated pneumonia (NV-HAP) include the very young and the very old, as well as persons with compromised immune systems cardiovascular and/or pulmonary disease. This section includes a review of the pathogenesis and microbiology of NV-HAP, including bacterial as well as viral and fungal pathogens. Etiology, modes of transmission, and specific prevention strategies associated with various causative microorganisms are highlighted.

      Key Words

      Pneumonia is the most common health care-associated infection in the United States and is associated with substantial morbidity and mortality.
      • Magill S
      • O'Leary E
      • Janelle SJ
      • et al.
      Changes in prevalence of health care-associated infections in U.S. hospitals.
      While ventilator-associated pneumonia has received more attention in the literature, nonventilator health care-associated pneumonia (NV-HAP) is recognized as also contributing to patient mortality, increasing lengths of stay, and antibiotic misuse.
      American Thoracic SocietyInfectious Diseases Society of America
      Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
      Those at risk for developing NV-HAP include the very young and the very old as well as persons with compromised immune systems or cardiovascular and/or pulmonary disease.
      American Thoracic SocietyInfectious Diseases Society of America
      Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
      Understanding the pathogenesis of the etiologic agents of NV-HAP, their modes of transmission, and their diagnosis are essential for optimal patient care and safety. This section addresses bacterial and viral etiologies of NV-HAP along with their pathogenesis and diagnosis. NV-HAP caused by Aspergillus is also discussed.

      Bacterial NV-HAP pneumonia

      Pathogenesis

      Bacteria can gain access to the lower respiratory tract by several possible routes, including aspiration of organisms colonizing the upper respiratory tract, or inhalation of contaminated aerosols (see Fig 1).
      • Zakharkina T
      • Martin-Loeches I
      • Matamoros S
      The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia.
      Aspiration is believed to be the primary route for acquisition of NV-HAP.
      • Ranzani OT
      • De Pascale G
      • Park M
      Diagnosis of nonventilated hospital-acquired pneumonia: how much do we know?.
      ,
      • Hakansson AP
      • Orihuela CJ
      • Bogaert D
      Bacterial-host interactions: physiology and pathophysiology of respiratory infection.
      Gram-negative bacteria are responsible for most bacterial cases of NV-HAP with rates ranging from 50%-80%. This is due to changes in the colonizing microflora of the upper respiratory tract and their subsequent aspiration into the lower respiratory tract.
      • Mandell LA
      • Niederman MS
      Aspiration pneumonia.
      The stomach is another body site that can harbor organisms that cause NV-HAP. Microorganisms can survive and multiply in the stomachs of patients receiving enteral feeding, antacids, or histamine-2 blockers due to the ability of these therapies to alter the gastric pH.
      • Lopetuso LR
      • Scaldaferri F
      • Franceschi F
      • Gasbarrini A
      The gastrointestinal microbiome–functional interference between stomach and intestine.
      Dental biofilm contains bacteria that can also cause NV-HAP via aspiration.
      • Sands KM
      • Twigg JA
      • Lewis MA
      • et al.
      Microbial profiling of dental plaque from mechanically ventilated patients.
      In addition to aspiration, bacteria can gain entry to the lower respiratory tract through inhalation of contaminated aerosols. The etiology of these aerosols might be from respiratory equipment that has not been disinfected per manufacturer's recommendations, contaminated lots of inhaled medications, or contaminated water.
      • O'Malley CA.
      Device cleaning and infection control in aerosol therapy.
      ,
      • Dolan SA
      • Dowell E
      • LiPuma JJ
      • Valdez S
      • Chan K
      • James JF
      An outbreak of Burkholderia cepacia complex associated with intrinsically contaminated nasal spray.
      Bacteria can also be transmitted by self-inoculation and hand to face transmission highlighting the importance of hand hygiene.

      Diagnosis

      The clinical criteria used to diagnose bacterial pneumonia include fever, cough, and the development of purulent sputum, in combination with abnormal chest imaging. Leukocytosis, positive Gram stain, culture of respiratory specimens, and urine antigen testing aid in the diagnosis.
      Sputum is the most common lower respiratory tract specimen received by the clinical microbiology laboratory. The most important step in evaluating the appropriateness of a sputum specimen is the Gram stain.
      • Del Rio-Pertuz G
      • Gutiérrez JF
      • Triana AJ
      • et al.
      Usefulness of sputum Gram stain for etiologic diagnosis in community-acquired pneumonia: a systematic review and meta-analysis.
      It will determine whether the sputum specimen is adequate for further processing and interpretation.
      Clinical microbiology labs use exclusion criteria to evaluate the quality of sputum samples. These criteria include cutoffs of the minimum number of epithelial cells and polymorphonuclear leukocytes that are present. However, many purulent sputum specimens lack the presence of a single morphologic type; therefore, even a high-quality sputum Gram stain may not be helpful in determining the bacterial etiology of the patient's pneumonia. On the other hand, if a specimen demonstrates a predominant organism, that result can guide initial antibiotic therapy.
      Bronchoscopy can be used to acquire samples of lower respiratory tract secretions in patients who cannot produce sputum or in whom such samples have been nondiagnostic. Lower respiratory specimens can be obtained by bronchoalveolar lavage, routine brushing, or washing.

      Viral NV-HAP

      NV-HAP can also have a viral etiology with influenza virus and respiratory syncytial virus accounting for most cases. Influenza and RSV infections contribute substantially to the morbidity and mortality associated with NV-HAP.
      • Vanhems P
      • Bénet T
      • Munier-Marion E
      • et al.
      Nosocomial influenza: encouraging insights and future challenges.
      ,
      • Nabeya D
      • Kinjo T
      • Parrott GL
      The clinical and phylogenetic investigation for a nosocomial outbreak of respiratory syncytial virus infection in an adult hemato-oncology unit.

      RSV-associated pathogenesis

      RSV infectious particles are present in respiratory secretions and can be transmitted directly via contact with respiratory secretions or indirectly via contaminated hands or fomites. Infants and immunocompromised adults shed large amounts of virus in their respiratory secretions and can contaminate their immediate surroundings.
      • French CE
      • McKenzie BC
      • Coope C
      • et al.
      Risk of nosocomial respiratory syncytial virus infection and effectiveness of control measures to prevent transmission events: a systematic review.

      Influenza-associated pathogenesis

      Influenza virus is commonly transmitted by direct inhalation of infected droplets. The most effective measure for reducing influenza incidence in the health care setting is by the vaccination of health care workers and patients. In addition to vaccination, antiviral agents used for prophylaxis for those exposed as well as for treatment of cases can help reduce incidence.
      • O'Reilly F
      • Dolan GP
      • Nguyen-Van-Tam J
      • Noone P
      Practical prevention of nosocomial influenza transmission, “a hierarchical control” issue.

      Diagnosis

      Historically, etiologies of viral pneumonia were identified by viral cytopathic effect in tissue culture or by detection of viral antigens in nasopharyngeal secretions. Nucleic acid–based diagnostic testing now permits timely diagnosis and treatment, provides a basis for rapid patient isolation and prophylaxis of those exposed. Most clinical microbiological laboratories offer a seasonal viral respiratory panel performed from nasopharyngeal swab specimens.

      Fungal pneumonia

      Fungi are commonly found in the environment and are inhaled quite often. Fortunately, their virulence is low, and exposure usually results in respiratory tract colonization, which is cleared by the host's immune system. However, the increasing number of immunocompromised hosts has led to an increased incidence of invasive fungal pneumonia, with Aspergillus being one of the species encountered in the health care setting.
      • Young AY
      • Leiva Juarez MM
      • Evans SE
      Fungal pneumonia in patients with hematologic malignancy and hematopoietic stem cell transplantation.
      ,
      • Suleyman G
      • Alangaden GJ
      Nosocomial fungal infections: epidemiology, infection control, and prevention.

      Aspergillus-associated pathogenesis

      Aspergillosis pneumonia results from inhalation of Aspergillus spores and subsequent lung tissue invasion. Prolonged neutropenia is a risk factor for Aspergillus infection as neutrophils present in pulmonary tissue are the first line of defense.
      • Cumbo TA
      • Segal BH.
      Prevention, diagnosis, and treatment of invasive fungal infections in patients with cancer and neutropenia.

      Diagnosis

      Direct microscopy of clinical specimens can be a cost-effective, screening test. Microscopy does not require highly specialized equipment, and turnaround time is usually within several hours of receiving the specimen in the laboratory.
      • Surya Kirani KR
      • Chandrika VS
      Efficacy of in-house fluorescent stain for fungus.
      Cultures should be performed on all acceptable clinical specimens regardless of the direct microscopy results. In general, for respiratory samples, the most purulent and/or bloody portions of the specimen should be inoculated for culture because these portions would be the most clinically relevant.
      • Lease ED
      • Alexander BD.
      Fungal diagnostics in pneumonia.
      The diagnosis of pulmonary aspergillosis requires both its histopathologic presence in lung tissue and isolation in culture.
      • Hage CA
      • Carmona EM
      • Epelbaum O
      • et al.
      Microbiological laboratory testing in the diagnosis of fungal infections in pulmonary and critical care practice. An official American Thoracic Society clinical practice guideline.
      Culture isolation of Aspergillus from respiratory tract specimens may indicate colonization; when Aspergillus is recovered from the sputum of a febrile, neutropenic patient with a new pulmonary infiltrate, it is likely to be clinically significant.
      • Pergam S.
      Fungal pneumonia in patients with hematologic malignancies and hematopoietic cell transplantation.
      Detection of A. galactomannan antigen in serum or urine can be used as a nonculture-based test to aid in the diagnosis.
      Key points
      • Bacteria, viruses, and fungi can all cause pneumonia in certain patient populations and under specific conditions (see Table 1).
        Table 1Pathogens that may cause pneumonia
        OrganismMode of transmission/sourceVaccine preventablePrevention strategies
        Staphylococcus aureusPerson to personNoHand hygiene, decolonization
        Streptococcus pneumoniaePerson to personYesHand hygiene, decrease aspiration risk
        Enterobacteriaceae speciesPerson to personNoHand hygiene, decrease aspiration risk
        Legionella speciesInhalationNoHand hygiene, decrease aspiration risk, water management programs
        Respiratory Syncytial VirusPerson to personNoHand hygiene, contact precautions
        InfluenzaPerson to personYesHand hygiene, droplet isolation
        Aspergillus speciesInhalationNoHand hygiene, protective isolation, containment during construction/renovation
      • Understanding the pathogenesis of each type of pneumonia can advance diagnostic and surveillance strategies.
      • Pathogen-specific prevention strategies must be implemented to curtail the transmission of these organisms in health care settings.

      References

        • Magill S
        • 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: 1732-1744
        • 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: 388-416
        • Zakharkina T
        • Martin-Loeches I
        • Matamoros S
        The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia.
        Thorax. 2017; 72: 803-810
        • Ranzani OT
        • De Pascale G
        • Park M
        Diagnosis of nonventilated hospital-acquired pneumonia: how much do we know?.
        Curr Opin Crit Care. 2018; 24: 339-346
        • Hakansson AP
        • Orihuela CJ
        • Bogaert D
        Bacterial-host interactions: physiology and pathophysiology of respiratory infection.
        Physiol Rev. 2018; 98: 781-811
        • Mandell LA
        • Niederman MS
        Aspiration pneumonia.
        N Engl J Med. 2019; 380: 651-663
        • Lopetuso LR
        • Scaldaferri F
        • Franceschi F
        • Gasbarrini A
        The gastrointestinal microbiome–functional interference between stomach and intestine.
        Best Pract Res Clin Gastroenterol. 2014; 28: 995-1002
        • Sands KM
        • Twigg JA
        • Lewis MA
        • et al.
        Microbial profiling of dental plaque from mechanically ventilated patients.
        J Med Microbiol. 2016; 65: 147-159
        • O'Malley CA.
        Device cleaning and infection control in aerosol therapy.
        Respir Care. 2015; 60: 917-927
        • Dolan SA
        • Dowell E
        • LiPuma JJ
        • Valdez S
        • Chan K
        • James JF
        An outbreak of Burkholderia cepacia complex associated with intrinsically contaminated nasal spray.
        Infect Control Hosp Epidemiol. 2011; 32: 804-810
        • Del Rio-Pertuz G
        • Gutiérrez JF
        • Triana AJ
        • et al.
        Usefulness of sputum Gram stain for etiologic diagnosis in community-acquired pneumonia: a systematic review and meta-analysis.
        BMC Infect Dis. 2019; 19: 403
        • Vanhems P
        • Bénet T
        • Munier-Marion E
        • et al.
        Nosocomial influenza: encouraging insights and future challenges.
        Curr Opin Infect Dis. 2016; 29: 366-372
        • Nabeya D
        • Kinjo T
        • Parrott GL
        The clinical and phylogenetic investigation for a nosocomial outbreak of respiratory syncytial virus infection in an adult hemato-oncology unit.
        J Med Virol. 2017; 89: 1364-1372
        • French CE
        • McKenzie BC
        • Coope C
        • et al.
        Risk of nosocomial respiratory syncytial virus infection and effectiveness of control measures to prevent transmission events: a systematic review.
        Influenza Other Respir Viruses. 2016; 10: 268-290
        • O'Reilly F
        • Dolan GP
        • Nguyen-Van-Tam J
        • Noone P
        Practical prevention of nosocomial influenza transmission, “a hierarchical control” issue.
        Occup Med (Lond). 2015; 65: 696-700
        • Young AY
        • Leiva Juarez MM
        • Evans SE
        Fungal pneumonia in patients with hematologic malignancy and hematopoietic stem cell transplantation.
        Clin Chest Med. 2017; 38: 479-491
        • Suleyman G
        • Alangaden GJ
        Nosocomial fungal infections: epidemiology, infection control, and prevention.
        Infect Dis Clin North Am. 2016; 30: 1023-1052
        • Cumbo TA
        • Segal BH.
        Prevention, diagnosis, and treatment of invasive fungal infections in patients with cancer and neutropenia.
        J Natl Compr Canc Netw. 2004; 2: 455-469
        • Surya Kirani KR
        • Chandrika VS
        Efficacy of in-house fluorescent stain for fungus.
        Indian J Pathol Microbiol. 2017; 60: 57-60
        • Lease ED
        • Alexander BD.
        Fungal diagnostics in pneumonia.
        Sem Respir Crit Care Med. 2011; 32: 663-672
        • Hage CA
        • Carmona EM
        • Epelbaum O
        • et al.
        Microbiological laboratory testing in the diagnosis of fungal infections in pulmonary and critical care practice. An official American Thoracic Society clinical practice guideline.
        Am J Respir Crit Care. 2019; 200: 535-550
        • Pergam S.
        Fungal pneumonia in patients with hematologic malignancies and hematopoietic cell transplantation.
        Clin Chest Med. 2017; 38: 279-294