Hospital Medicine

Recurrent pneumonias

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Recurrent pneumonia

I. What every physician needs to know.

Recurrent pneumonia is defined as two or more episodes of nontuberculous pulmonary infection separated by at least a one-month asymptomatic interval, complete radiographic clearing of the infiltrate, or both. Recurrent pneumonia most commonly occurs in patients with underlying lung disease such as chronic obstructive pulmonary disease (COPD) or bronchiectasis, immunocompromised patients, and those with a local obstructive process such as a tumor.

An episode of community-acquired pneumonia can predispose the patient to a second episode by a local loss of resistance in the lung parenchyma or by persistence of a virulent organism. Physiologic mechanisms of recurrence vary depending on the underlying cause of recurrence but can include depressed immune response, alterations of mucociliary clearance, decreased surfactant, or local obstruction. Aspiration pneumonia is a common cause of recurrent pneumonia, especially in older patients, patients with dementia or other neurologic disorders, and those with substance abuse.

There is some debate about the expected time course of clinical and radiographic resolution of pneumonia, and much of the data is from older case series. Most experts agree that in community-acquired bacterial pneumonia, significant clinical improvement should occur within 48 to 72 hours of appropriate antibiotic therapy, although cough and fatigue can persist for 14 days or longer. Radiographic resolution usually occurs within four to six weeks in healthy patients under age 50, but this can take longer in older patients and those with multiple comorbidities.

Nonresolving pneumonia, chronic pneumonia and slowly resolving pneumonia are related entities to recurrent pneumonia and have been used in the literature interchangeably to refer to pneumonia with persistence of radiographic abnormalities beyond the expected time course, without interval clearing of the infiltrate.

II. Diagnostic Confirmation: Are you sure your patient has recurrent pneumonia?

Patients with pneumonia have fever, infiltrate on chest radiograph and usually also have purulent sputum and leukocytosis. If a patient with suspected recurrent or non-resolving pneumonia has not had a clinical response to appropriate antibiotic therapy, consider alternate non-infectious diagnoses (see C below).

In the case of a patient with suspected recurrent aspiration pneumonia, it is important to distinguish between aspiration pneumonitis and aspiration pneumonia. Aspiration pneumonitis is an acute inflammatory process caused by inhalation of gastric contents. Gastric contents are usually sterile and bacterial infection does not usually occur in acute aspiration pneumonitis, although patients who take proton-pump inhibitors, those with gastroparesis, small bowel obstruction or who receive enteral feedings are at higher risk for aspiration pneumonia because their gastric contents may be colonized by bacteria. Aspiration pneumonia occurs when a patient inhales colonized oropharyngeal secretions rather than gastric contents.

A. History Part I: Pattern Recognition:

The radiographic location of recurrent pneumonia can be helpful in determining the underlying etiology. Recurrent infections in one anatomic region suggest an anatomic abnormality (such as pulmonary sequestration) or a bronchial obstruction by a tumor or a foreign body. Lesions which can cause obstruction include bronchogenic carcinoma, bronchial adenoma, or hamartoma. Extrinsic compression of the bronchi from lymphadenopathy (from malignancy or other conditions such as sarcoidosis) can also occur and predispose to recurrent pneumonia.

Recurrent infections in distinct areas of the lungs are more common in patients with underlying lung disease such as COPD, asthma or chronic bronchiectasis (see Bronchiectasis). Recurrent pneumonia is also more common in patients with heart failure, diabetes, and alcohol dependence. Heavy alcohol users are predisposed to recurrent pneumonia through multiple mechanisms: they are predisposed to recurrent aspiration pneumonia because of periods of altered consciousness, are likely to have gram-negative colonization of the oropharynx, impaired mucociliary clearance and depressed immunity, including low complement levels.

Recurrent infections in different locations can also suggest a pulmonary defect such as cystic fibrosis or immotile cilia syndrome (especially in a younger patient), or a primary or secondary immunodeficiency. Cystic fibrosis usually presents in childhood, but can present in young adulthood (see Bronchiectasis). Primary immune deficiencies are rare but occasionally diagnosed in adults; common variable immunodeficiency and selective IgA deficiency are the immunodeficiency syndromes most likely to be diagnosed in adulthood.

Patients with common variable immunodeficiency may have recurrent sinus infections and conjunctivitis as well as pneumonia, and are susceptible to infection with S. pneumoniae, H. influenzae and Mycoplasma. Onset of common variable immune deficiency (CVID) is typically before age 30, and usually in young childhood. Chronic granulomatous disease can also be diagnosed in adulthood, but this is quite rare.

Lastly, recurrent pneumonia in the basal segments of the lower lobes (in patients who have been upright or semi-recumbent) or in the posterior upper lobes and apical lower lobes (for patients who have been recumbent) in susceptible patients should suggest aspiration pneumonia. The clinical presentation of aspiration pneumonia is often more indolent than that of community-acquired pneumonia, with slowly progressive symptoms developing over days to weeks. Chills are often absent.

B. History Part 2: Prevalence:

The overall prevalence of recurrent pneumonia is not clear; estimates of the percentage of patients who have had one episode of pneumonia and then present with a second episode vary from 7.5% to over 20%.

Young patients without known comorbidities should not develop recurrent pneumonia and repeated episodes of pneumonia should trigger a search for an underlying cause. Younger patients presenting with recurrent bacterial pneumonia are more likely to have immune deficiencies or cystic fibrosis (see Bronchiectasis). Older patients with recurrent pneumonia are more likely to have aspiration pneumonia (related to alcohol use or dementia), COPD, or a secondary immune deficiency such as HIV, multiple myeloma or chronic lymphocytic leukemia.

C. History Part 3: Competing diagnoses that can mimic recurrent pneumonias.

In patients with recurrent fever and pulmonary infiltrate in whom an immune defect, comorbidity such as COPD or anatomic abnormality has not been found, non-infectious conditions such as malignancy or immune-mediated conditions should be considered.

Multiorgan involvement should raise suspicion for a vasculitic process, Goodpasture's syndrome or connective tissue disease. Eosinophilia could indicate immune-mediated lung disease such as vasculitis, drug reaction, chronic eosinophilic pneumonia or allergic bronchopulmonary aspergillosis.

Hypersensitivity pneumonitis presents acutely with fever, non-productive cough and pulmonary infiltrates 4 to 6 hours after exposure to an inhaled antigen or drug; there may be transient leukocytosis. Repeated episodes may follow re-exposure to the antigen. There is also an indolent, progressive form of this condition caused by persistent exposure to the antigen (see Hypersensitivity Pneumonitis).

Chronic eosinophilic pneumonia is most common in women in their 30's to 50's and presents with wheezing, cough, dyspnea and fever; weight loss and night sweats are also common. The characteristic radiographic pattern is peripheral alveolar infiltrates, often in upper lobes and with central sparing. Eosinophilia is found in BAL fluid and often in peripheral blood (see Eosinophilic Pneumonia).

Bronchiolitis obliterans-organizing pneumonia or cryptogenic organizing pneumonia is characterized by a subacute presentation of cough, fever, dyspnea, weight loss, malaise and focal alveolar infiltrates. It is often preceded by upper or lower respiratory tract infection or influenza-like illness. ESR is often elevated and there may be peripheral leukocytosis. Chest radiographs may show multifocal segmental or lobar alveolar infiltrates with air bronchograms.

Some drugs, such as methotrexate and amiodarone, can rarely cause pulmonary toxicity that could present similarly to recurrent or nonresolving pneumonia with cough, dyspnea, fever and pulmonary infiltrates.

Pulmonary vasculitides including granulomatous polyangiitis (GPA; formerly known as Wegener's granulomatosis) and Churg-Strauss syndrome can sometimes present similarly to recurrent pneumonia, with pulmonary and constitutional symptoms; extrapulmonary symptoms would distinguish these syndromes from recurrent pneumonia but are not always present in GPA.

Alveolar hemorrhage syndromes caused by connective tissue disease or other disorders could occasionally be mistaken for recurrent pneumonia, especially if hemoptysis is minimal or absent.

Pulmonary alveolar proteinosis is a rare disorder presenting with diffuse alveolar infiltrates, cough, hypoxemia, progressive dyspnea and occasionally fever.

Pulmonary neoplasms such as bronchoalveolar carcinoma and pulmonary lymphangitic carcinomatosis can sometimes mimic nonresolving pneumonia in radiographic appearance.

D. Physical Examination Findings.

Patients with pneumonia usually have fever, dyspnea, decreased breath sounds and/or crackles on pulmonary exam (see Pneumonia). Recurrent or persistent infiltrate on chest radiograph without these clinical findings may suggest an alternate diagnosis. Clubbed digits suggest chronic underlying respiratory disease.

E. What diagnostic tests should be performed?

A patient presenting acutely with a suspected recurrence of pneumonia should have a chest radiograph, blood and sputum cultures, and a CBC with differential. Perform an arterial blood gas in hypoxic patients. If present, parapneumonic effusions should be tapped as usual in order to provide diagnostic information about the pathogen.

A comprehensive swallow evaluation should be performed in patients with suspected recurrent aspiration pneumonia; aspiration is often silent and simple observation of swallowing is not sensitive for the detection of aspiration.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

A CBC with differential, blood and sputum cultures should be obtained with each episode of pneumonia. Leukocytosis is common in patients with pneumonia; leukopenia can also be present.

The diagnostic value of expectorated sputum gram stain and culture is debated; S. pneumoniae and H. influenzae are difficult to grow in culture and 50% of patients with pneumonia and S. pneumoniae bacteremia will have negative sputum cultures. However, if a specimen is produced correctly, it can sometimes be helpful in guiding antibiotic therapy.

A sputum culture with sensitivities may be helpful in determining if recurrent or nonresolving pneumonia was caused by antibiotic failure. It should be obtained before starting antibiotic therapy, more than one hour after eating, and after the patient rinses his or her mouth. The sample should be promptly transported to the laboratory (see Typical Bacterial Pneumonia).

In a younger patient with recurrent bacterial pneumonia, IgA, IgG and IgM levels should be ordered to screen for common variable immunodeficiency or an IgG subclass deficiency.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

A chest CT scan is recommended if a patient has a recurrence in the same anatomic location, because it suggests localized intrathoracic disease. Pulmonary consultation and bronchoscopy should also be considered in patients with recurrent pneumonia in the same anatomic location or with multiple recurrences of pneumonia without obvious risk factors.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

None

III. Default Management.

The initial management of a patient presenting with a recurrence of pneumonia is similar to the initial management of any patient with pneumonia (see Typical Bacterial Pneumonia). Additional considerations for a patient with a recurrence rather than a first episode of pneumonia include a careful review of previous imaging, if possible, to compare anatomic locations of the current and previous infections; review of previous culture data, if possible, and review of the patient's risk factors for recurrent pneumonia as detailed above.

A. Immediate management.

Immediate management, as in any patient presenting with pneumonia, includes oxygen therapy and intravenous fluids if necessary. Timely initiation of antibiotics, as in any case of pneumonia, is very important.

As in community acquired pneumonia, S. pneumoniae is the most frequently isolated organism in recurrent pneumonia. S. pneumoniae, H. influenzae and M. catarrhalis were the three most common organisms isolated in one series of immunocompetent adults over the age of 50 with recurrence of pneumonia after hospitalization.

However, other organisms are also common in recurrent pneumonia and consideration should be given to the patient's risk factors. H. influenzae is a common pathogen in patients with COPD. Smokers and those with COPD and other chronic respiratory conditions are predisposed to infection with Legionella. Patients with alcohol dependence are susceptible to infections by S. pneumoniae, H. influenzae, Klebsiella pneumoniae and anaerobes. Patients with recurrent pneumonia related to bronchiectasis (such as patients with cystic fibrosis) are susceptible to infections with Pseudomonas, H. influenzae and S. pneumoniae (see Bronchiectasis and Cystic fibrosis).

One study showed a relatively high prevalence of infection by H. influenzae and Moraxella catarrhalis even among non-smokers with recurrent pneumonia. Mycoplasma pneumoniae may also be an important cause of recurrent pneumonia. Consideration should be given to patients' risk factors for typical and atypical bacteria, viruses and health-care associated pathogens and antibiotics should be chosen accordingly (see Typical Bacterial Pneumonia, Atypical Bacterial Pneumonia, Viral Pneumonia and Hospital-Acquired Bacterial Pneumonia).

Antibiotic therapy for suspected recurrent aspiration pneumonia should generally cover gram-negatives as well as S. pneumoniae, Staph aureus, H. influenzae and Enterobacteriaceae. Gram negatives including pseudomonas are more common in patients with recurrent aspiration pneumonia in a health care setting. Anaerobic therapy may not always be necessary. While earlier studies suggested that anaerobic organisms are very common pathogens in aspiration pneumonia, more recent studies suggest that anaerobic organisms are fairly rare pathogens in this syndrome.

Good initial antibiotic regimens for patients with suspected recurrent aspiration pneumonia include clindamycin, amoxicillin-clavulanate or amoxicillin combined with metronidazole. Quinolones and ceftriaxone are also thought to be effective. Metronidazole is not sufficient monotherapy.

One study of elderly patients with mild to moderate aspiration pneumonia compared ampicillin-sulbactam to IV clindamycin and a carbapenem and concluded that all three regimens were effective but that patients treated with IV clindamycin had a lower rate of post-treatment staph aureus colonization of their sputum; clindamycin is also less expensive. Patients with risk factors for anaerobic infection including severe periodontal disease, putrid sputum or alcoholism, or those with evidence of necrotizing pneumonia or lung abscess should be covered for anaerobic organisms with a regimen such as piperacillin-tazobactam, imipenem or clindamycin.

If an aspiration event is witnessed in a hospitalized patient, the upper airway should be suctioned immediately. If the patient cannot protect their airway, they should be intubated. The use of prophylactic antibiotics after witnessed or suspected aspiration events in hospitalized patients is not recommended unless patients have a small-bowel obstruction or other conditions associated with colonization of gastric contents. Antibiotics should be initiated in a patient with aspiration pneumonitis that does not resolve within 48 hours.

B. Physical Examination Tips to Guide Management.

Daily lung exams and monitoring of oxygen saturation will help monitor response to therapy.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

The patient's clinical status including resolution of cough and hypoxia and ability to ambulate should be monitored. Daily chemistry panels and CBCs are routinely ordered but may not be necessary if the patient is clinically improving. Repeated chest X-rays while the patient is hospitalized are only indicated if the patient has had a clinical decompensation to look for worsening infiltrate, new effusion or empyema.

D. Long-term management.

Patients with recurrent pneumonia may benefit from outpatient follow-up by a pulmonary specialist.

Enteral feeding by gastrostomy or nasogastric tube has not been shown to reduce recurrences of aspiration pneumonia in patients with advanced dementia or prolong survival. Aspiration pneumonia in fact is the most common cause of death in patients fed by gastrostomy tube. A diet of thickened liquids and positioning strategies while eating, including the "chin tuck", are routinely recommended to prevent aspiration in the elderly but have not been proven effective in randomized controlled trials and have been associated with an increased risk of dehydration.

IV. Management with Co-Morbidities

N/A

A. Renal Insufficiency.

Antibiotics may need to be renally dosed in this population; always calculate creatinine clearance when dosing antibiotics in elderly patients as creatinine is not a reliable measure of renal function in the elderly.

B. Liver Insufficiency.

No change in management.

C. Systolic and Diastolic Heart Failure

Patients with heart failure are at increased risk for recurrent pneumonia. These patients should have careful attention to volume status and renal function when hospitalized for pneumonia.

D. Coronary Artery Disease or Peripheral Vascular Disease

No change in management.

E. Diabetes or other Endocrine issues

Diabetes is a risk factor for recurrence of pneumonia. Good glucose control in inpatients with pneumonia is important; one study showed increased risk of death and complications in diabetic patients admitted with pneumonia whose admission glucose was greater than 11mmol/l (198 mg/dl).

F. Malignancy

Lung malignancy is one risk factor for recurrent pneumonia, often due to obstruction. Interventional pulmonary procedures including bronchoscopy with stenting, airway dilation and laser therapy may be helpful in palliation of symptoms caused by malignancy and post-obstructive pneumonia.

G. Immunosuppression (HIV, chronic steroids, etc.)

Immunosuppressed patients are at risk for pneumonia caused by Pneumocystis and fungii (see Pneumocystis pneumonia and Fungal Pneumonia) as well as typical and atypical bacteria.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in management.

I. Gastrointestinal or Nutrition Issues

No change in management.

J. Hematologic or Coagulation Issues

No change in management.

K. Dementia or Psychiatric Illness/Treatment

Patients with moderate to advanced dementia are at high risk for recurrent aspiration pneumonia and additional work-up for other underlying causes of recurrent pneumonia is probably not warranted if the patient has evidence of dysphagia.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

As with any patient with pneumonia, a sudden respiratory decompensation in a patient hospitalized for recurrent or non-resolving pneumonia should trigger attention to the patient's respiratory and hemodynamic status. The patient should be stabilized and a repeat chest radiograph should be obtained as well as an arterial blood gas if indicated. Consideration should be given to broadening antibiotic therapy in this case.

B. When is the Patient Ready for Discharge.

Patients with pneumonia are generally ready for discharge when fever, tachycardia and tachypnea have resolved and when the patient can eat, drink, ambulate and take medications by mouth.

C. Arranging for Clinic Follow-up

N/A

1. When should clinic follow up be arranged and with whom.

The patient should follow up with their primary care provider within one month, with strict instructions to call their provider if their symptoms do not continue to improve. Chest radiographs to assess radiographic resolution are not routinely recommended. Outpatient pulmonary follow-up may be helpful for patients with recurrent pneumonia.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

None.

E. Placement Considerations.

Elderly patients admitted with recurrent pneumonia should have physical and occupational therapy to help prevent deconditioning and assure that they are safe to return home after hospitalization.

F. Prognosis and Patient Counseling.

Some studies have suggested that cases of recurrent pneumonia are less often fatal than the initial event and that patients are less often bacteremic with subsequent episodes.

Aspiration pneumonia is a frequent reason for hospital admission in elderly patients with advanced dementia. Families should be counseled that this is likely to recur and that there is no evidence that placement of a gastrostomy tube for artificial nutrition leads to improved outcomes. Careful hand-feeding when the patient indicates hunger and good oral care are indicated.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

See Typical Bacterial Pneumonia.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Most patients admitted with recurrent pneumonia should have pharmacologic deep vein thrombosis prophylaxis.

What's the evidence?

Loeb, MB, Becker, M, Eady, A. "Interventions to Prevent Aspiration Pneumonia in Older Adults: A Systematic Review". J Am Geriatr Soc. vol. 51. 2003. pp. 1018-22.

Hedlund, H, Kalin, L, Ortqvist, A. "Recurrence of Pneumonia in Middle-aged and Elderly Adults after Hospital-Treated Pneumonia: Aetiology and Predisposing Conditions". Scand J Infect Dis. vol. 29. 1997. pp. 387-92.

Jay, SJ, Johanson, WG, Pierce, AK. "The Radiographic Resolution of Streptococcus Pneumoniae Pneumonia". New Engl J Med. vol. 293. 1975. pp. 798-801.

Kadowaki, M, Demura, Y, Mizuno, S. "Reappraisal of Clindamycin IV Monotherapy for Treatment of Mild-to-Moderate Aspiration Pneumonia in Elderly Patients". Chest. vol. 127. 2005. pp. 1276-82.

Kuru, T, Lynch III, JP. "Nonresolving or Slowly Resolving Pneumonia". Clin Chest Med. vol. 20. 1999. pp. 623-51.

Marik, PE. "Aspiration Pneumonitis and Aspiration Pneumonia". New Engl J Med. vol. 344. 2001. pp. 665-70.

Marik, PE. "Pulmonary aspiration syndromes". Curr Opin Pulm Med. vol. 17. 2011. pp. 148-54.

Mehta, RM, Cutaia, M. "The Role of Interventional Pulmonary Procedures in the Management of Post-obstructive Pneumonia". Current Infectious Disease Reports. vol. 8. 2006. pp. 207-14.

Robbins, JoAnne, Gensler, G, Hind, J. "Comparison of 2 Interventions for Liquid Aspiration on Pneumonia Incidence: A Randomized Trial". Ann Intern Med. vol. 148. 2008. pp. 509-18.

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