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Non-ventilator health care associated pneumonia (NV-HAP): Oncology

      Abstract

      Literature suggests that cancer patients can become colonized or infected with a variety of opportunistic and health care-associated pathogens, putting them at higher risk for nonventilator health care-associated pneumonia. This section will review the epidemiology of nonventilator health care-associated pneumonia and the importance of prevention strategies in this vulnerable population. Prevention strategies for cancer patients across the continuum of care are highlighted.

      Key Words

      Pneumonia is the most frequent type of health care-associated infection in cancer patients.
      • Rabello L
      • Azevedo L
      • de Souza I
      • et al.
      Severe pneumonia in critically ill cancer patients: clinical outcomes and a comparison between healthcare-associated pneumonia and community-acquired pneumonia.
      Malignancy is a risk factor in the development of pneumonia, and the coexistence of cancer is associated with increased severity of illness. When cancer and/or its treatment (eg, chemotherapy or radiation) cause an immunocompromised state, cancer patients can become colonized or infected with a variety of opportunistic and health care-associated pathogens,
      • Wong JL
      • Evans SE
      Bacterial pneumonia in patients with cancer: novel risk factors and management.
      putting them at higher risk for nonventilator health care-associated pneumonia (NV-HAP). Normal skin and gastrointestinal flora can become virulent pathogens in this population, leading to progressive pneumonia.
      • Safdar A
      • Armstrong D
      Infectious morbidity in critically ill patients with cancer.
      Pneumonia can lead to sepsis and is associated with high mortality. Torres and colleagues conducted a prospective study on clinical outcomes and mortality among critically ill cancer patients with severe sepsis and found that 48% of the cancer patients with septic shock had lung infections.
      • Torres VB
      • Azevedo LC
      • Silva UV
      • et al.
      Sepsis-associated outcomes in critically ill patients with malignancies.
      This underscores the importance of prevention strategies in this vulnerable population.
      Although it is beyond the scope of this document to address every type of cancer, the section will address overall risk for NV-HAP, pathogenesis, and prevention strategies specific to cancer patients.

      Pathogenicity and risk of NV-HAP

      Inhalation, aspiration, and hematogenous spread to the lungs are the 3 main mechanisms by which bacteria reach the lungs. The primary route by which organisms enter the lower airways is aspiration of oropharyngeal secretions into the trachea. Primary inhalation pneumonia develops when these organisms bypass normal respiratory defense mechanisms or when the patient inhales aerobic gram-negative organisms that colonize the upper respiratory tract or respiratory support equipment. Aspiration of colonized upper respiratory tract secretions is a risk factor for the development of pneumonia. The stomach may also be an important reservoir of gram-negative bacilli that can ascend and colonize the respiratory tract.
      • Smith LH
      Preventing aspiration: a common and dangerous problem for patients with cancer.
      Swallow function and cough reflex are important defenses against aspiration. Cancer patients may have impairments in swallowing function or airway protection, putting them at risk for aspiration. Head and neck lesions may cause neurological deficits, and patients with esophageal cancer may aspirate due to excessive gastric reflux or tracheoesophageal fistulas.
      • Purkey MT
      • Levine MS
      • Prendes B
      • et al.
      Predictors of aspiration pneumonia following radiotherapy for head and neck cancer.
      Cancer-related mucositis is also associated with pneumonia. High-dose chemotherapy or radiation therapy may cause injury to the tissues of the submucosa; this in turn may cause aspiration or hematogenous spread of pathogens that translocate from the upper and lower gastrointestinal tract to the lungs, resulting in pneumonia.
      • De Neve NY
      • Benoit DD
      • Depuydt PO
      • et al.
      Aspiration pneumonia: an underestimated cause of severe respiratory failure in patients with haematological malignancies and severe oral mucositis.
      Neutropenia (abnormally low neutrophils in blood) is the most common risk factor for pulmonary infection in immunocompromised patients. Neutropenic patients are at especially high risk of developing NV-HAP. White blood cell depletion and impaired pathogen recognition are important factors in the development of pneumonia in this population.
      • Evans SE
      • Ost DE
      Pneumonia in the neutropenic cancer patient.
      Neutropenia is most often caused by chemotherapy; however, neutropenia can be caused by solid tumor malignancies that affect the bone marrow and by some lymphomas. Radiation administered to multiple sites where bone marrow production occurs can also cause neutropenia.
      • Prabhu RS
      • Cassidy RJ
      • Landry JC
      Radiation therapy and neutropenia.
      Whether due to the source of malignancy, chemotherapy, or the side effects of other drugs, the duration of neutropenia is associated with the risk for infection.
      • Garcia JB
      • Lei X
      • Wierda W
      • et al.
      Pneumonia during remission induction chemotherapy in patients with acute leukemia.
      Frequent encounters with the health care system increases a patient's risk of exposure to multidrug-resistant organisms (MDROs).
      • Van de Louw A
      • Mirouse A
      • Peyrony O
      • Lemiale V
      • Azoulay E
      Bacterial pneumonias in immunocompromised patients.
      In patients with hematologic malignancies, NV-HAP may exceed 30% during their treatment course.
      • Evans SE
      • Ost DE
      Pneumonia in the neutropenic cancer patient.
      ,
      • Garcia JB
      • Lei X
      • Wierda W
      • et al.
      Pneumonia during remission induction chemotherapy in patients with acute leukemia.

      Pathogens of concern in the oncology population

      Pathogen exposure in the oncology patient population may be endogenous or exogenous. Endogenous organisms can be aspirated or inhaled, arriving from the oropharynx, trachea, nares, or sinus or gastric fluids, or they may be seeded from the blood.
      • Reynolds H
      Host defense impairments that may lead to respiratory infections.
      ,
      • Siegel SJ
      • Weiser JN
      Mechanisms of bacterial colonization in the respiratory tract.
      Exogenous pathogens can come from a variety of sources, including the hands of health care workers, biofilms, water, mold, and environmental and construction-related sources. Many of these exogenous pathogens can cause opportunistic infections in cancer patients and others with immunocompromised systems.
      Although cancer patients are at risk for many types of pneumonia, including opportunistic infections caused by fungal pathogens, bacteria are the most common causes of pulmonary infections in this population.
      • Wong JL
      • Evans SE
      Bacterial pneumonia in patients with cancer: novel risk factors and management.
      The bacterial causes of NV-HAP in cancer patients include Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. Additional bacteria that may cause pneumonia in cancer patients include gram-negative organisms such as Pseudomonas spp., Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Stenotrophomonas maltophilia, Citrobacter spp., Serratia marcescens, Acinetobacter baumannii-complex and Proteus spp.
      • Garcia JB
      • Lei X
      • Wierda W
      • et al.
      Pneumonia during remission induction chemotherapy in patients with acute leukemia.
      Legionella may be identified in cancer patients, especially those that are immunosuppressed or at risk of aspiration.
      • Jacobson K
      • Micel M
      • Tarrand J
      Legionella pneumonia in cancer patients.
      Invasive fungal infections occur primarily as a consequence of prolonged neutropenia and immunosuppression and are among the most serious infectious complications seen among cancer patients. Fungal pneumonias are a common cause of morbidity and mortality in hospitalized patients and in the immunocompromised population. The predisposing factors among the immunocompromised population include neutropenia, hematopoietic stem cell transplant (HSCT) solid organ transplant and new chemotherapeutic agents. Among the fungal pathogens causing NV-HAP, Aspergillus is the most common.
      • Suleyman G
      • Alangaden GJ
      Nosocomial fungal infections: epidemiology, infection control, and prevention.
      The presence of Aspergillus spores in the hospital has been linked to periods of construction or renovation.
      • Kanamori H
      • Rutala W
      • Sickbert Bennett E
      • et al.
      Review of fungal outbreaks and infection prevention in healthcare settings during construction and renovation.

      Risk across the continuum of care

      Cancer care takes place in a variety of settings across the continuum of care, with most care taking place in outpatient settings, such as oncology clinics, diagnostic imaging and radiation therapy centers, and wound care clinics.
      • Thom K
      • Kleinberg M
      • Roghmann M
      Infection prevention in the cancer center.
      Patients undergoing outpatient treatment may be exposed to a variety of bacterial or fungal pathogens, some of which are MDROs, putting them at risk for NV-HAP. IPs and others responsible for care of these patients should be aware of the local epidemiology, the local prevalence of MDROs, and clinically significant pathogens prevalent in the cancer population. A robust infection prevention program is essential in the outpatient as well as the inpatient setting.

      Prevention strategies

      NV-HAP prevention strategies for patients with cancer should be consistent across the continuum of care. Baker and colleagues have highlighted the role of the oropharynx in contributing to NV-HAP.
      • Baker D
      • Quinn B
      • Ewan V
      • et al.
      Sustaining quality improvement: long-term reduction of non-ventilator hospital-acquired pneumonia.
      Because the oral cavity is an important source of potentially pathogenic bacteria, stringent periodontal health is important. Complete periodontal examination followed by necessary treatment is recommended before management of head and neck cancers, high-dose chemotherapy, HSCT, or any cancer regimen that is expected to lead to significant immunosuppression.

      Centers for Disease Control and Prevention. Preventing infection in cancer patients: my pocket guide. Available at: https://www.cdc.gov/hai/pdfs/bicapp/CDC_PocketGuide_final_508Compliant.pdf. Accessed November 2, 2019.

      The Centers for Disease Control and Prevention have developed a pocket guide for dental providers that provides detailed recommendations on pretreatment assessment and interventions.

      Centers for Disease Control and Prevention. Preventing infection in cancer patients: my pocket guide. Available at: https://www.cdc.gov/hai/pdfs/bicapp/CDC_PocketGuide_final_508Compliant.pdf. Accessed November 2, 2019.

      Continued routine oral hygiene is also important to minimize infections. Akutsu and colleagues evaluated the effectiveness of preoperative dental brushing to decrease the risk of postoperative pneumonia in thoracic esophageal cancer patients who were undergoing esophagectomy. Patients were divided into 2 groups: a control group with no specific oral care regime and an intervention group who were instructed to brush 5 times daily. Postoperative pneumonia was decreased from 32% to 9% (P = .13). They concluded that preoperative dental brushing is a simple and effective means to decrease postoperative pneumonia in an esophageal cancer population.
      • Akutsu Y
      • Matsubara H
      • Shuto K
      • et al.
      Pre-operative dental brushing can reduce the risk of postoperative pneumonia in esophageal cancer patients.
      Infection with common community respiratory viruses can lead to serious disease and significant morbidity and mortality among patients with cancer, especially HSCT recipients.
      • Weigt SS
      • Gregson AL
      • Deng JC
      • et al.
      Respiratory viral infections in hematopoietic stem cell and solid organ transplant recipients.
      Given the potential adverse outcomes and the relative ease by which such viral infections can spread, health care-associated and household transmission is a serious concern for cancer patients.
      • Thom K
      • Kleinberg M
      • Roghmann M
      Infection prevention in the cancer center.
      Significant effort to prevent and control the spread of these infections should be made. An effective infection prevention strategy includes:
      • Vaccination (influenza);
      • Vaccination (pneumococcal);
      • Community outbreak surveillance;
      • Hospital surveillance for health care transmission outbreaks;
      • Patient and health care personnel education regarding disease recognition, prevention strategies, and modes of transmission;
      • Rapid diagnosis with early isolation for suspected and confirmed cases;
      • Restriction of potentially infected visitors and health care personnel.
      Centers for Disease Control and Prevention has developed a guide for outpatient oncology settings. The guide presents fundamental principles of infection prevention as well as a comprehensive approach to standard precautions, including hand hygiene, personal protective equipment, respiratory and staff etiquette, injection safety, medication storage and handling, and cleaning and disinfection of environmental surfaces.

      Centers for Disease Control and Prevention. Basic infection control and prevention plan for outpatient oncology settings. Available at:https://www.cdc.gov/hai/settings/outpatient/basic-infection-control-prevention-plan-2011/index.html. Accessed December 7, 2019.

      Consensus related to a pneumonia prevention bundle for NV-HAP is lacking. Hamamatsu and colleagues conducted a case-control study to evaluate the effectiveness of 7 care procedures initiated preoperatively that had been suggested to decrease postoperative pneumonia in patients with esophageal cancer.
      • Hiramatsu T
      • Sugiyama M
      • Kuwabara S
      • et al.
      Effectiveness of an outpatient preoperative care bundle in preventing postoperative pneumonia among esophageal cancer patients.
      The incidence of postoperative pneumonia in the care bundle group was 3.8% vs 22.4% in the control group. Specific elements of the bundle included deep-breathing exercises twice daily, respiratory muscle stretching, professional oral cleaning preoperatively, cleaning the mouth and tongue, and smoking cessation. Although this was a small study, it suggests that care bundles may help reduce NV-HAP. Given the morbidity and mortality of NV-HAP in oncology patients, this approach may present an opportunity for active surveillance using standardized definitions as well as standardized preoperative and postoperative protocols.
      Key points
      • Pneumonia is the most frequent type of health care-associated infection in cancer patients.
      • Both cancer and cancer treatments can compromise immunity, leaving cancer patients especially vulnerable to opportunistic infections.
      • Because cancer care occurs in many settings, NV-HAP prevention and surveillance efforts must encompass the entire continuum of care.
      • The development of pneumonia prevention bundles for oncology patients may be a key to reducing the incidence of NV-HAP in this population.

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