- David Ost, MD, MPH
David Ost, MD, MPH
- Professor, Department of Pulmonary Medicine
- The University of Texas MD Anderson Cancer Center
- Alan Fein, MD
Alan Fein, MD
- Director, Center for Pulmonary and Critical Care Medicine
- North Shore University Hospital
- Steven H Feinsilver, MD
Steven H Feinsilver, MD
- Professor of Medicine
- Hofstra Northwell School of Medicine
Slow or incomplete resolution of pneumonia despite treatment is a common clinical problem, estimated to be responsible for approximately 15 percent of inpatient pulmonary consultations and 8 percent of bronchoscopies . There are a variety of reasons that a case of pneumonia might resolve slowly or incompletely, including those relating to the etiology of the pneumonia (misdiagnosis of the pathogen or the presence of a resistant pathogen); those relating to the host, including mechanical processes; and the development of complications from the initial infection. In addition, noninfectious etiologies of pulmonary infiltrates can mimic infectious pneumonia, thus making it appear that resolution is not following the expected course. Approximately 20 percent of presumed nonresponding community-acquired pneumonia is due to noninfectious causes . Despite the frequency of this problem, there has been a paucity of studies specifically addressing this issue.
In this review, we will use the term "nonresolving pneumonia" to include those cases of presumed pneumonia that progress, resolve slowly, or fail to achieve complete resolution despite what is thought to be appropriate therapy. We will first discuss those factors that normally affect the resolution of pneumonia, and we will then focus on specific causes of nonresolving pneumonia. Aspiration pneumonia, community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, and the approach to fever and pulmonary infiltrates in the immunocompromised patient are discussed separately. (See "Aspiration pneumonia in adults" and "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults" and "Diagnostic approach to community-acquired pneumonia in adults" and "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults" and "Clinical presentation and diagnosis of ventilator-associated pneumonia" and "Approach to the immunocompromised patient with fever and pulmonary infiltrates".)
NORMAL VERSUS DELAYED RESOLUTION OF PNEUMONIA
Normal resolution of pneumonia is not easily defined and may vary depending upon the underlying cause. Patients typically note subjective improvement within three to five days of treatment; more specific clinical criteria for resolution include improvement in tachycardia and hypotension, which are expected to improve in two days; fever, tachypnea, and arterial oxygenation (PaO2), which are expected to improve within three days; and cough and fatigue, which may take 14 days or longer to improve [3,4] (table 1). The 2009 British Thoracic Society guidelines for the management of community-acquired pneumonia suggest that chest radiograph and hospitalization be considered for outpatients with pneumonia who fail to improve after 48 hours of treatment .
Most studies on the natural history of pneumonia have focused upon the resolution of chest radiographic abnormalities, with "slow resolution" often being defined as the persistence of radiographic abnormalities for greater than one month in a clinically improved host .
Determining whether a patient has nonresolving or progressive pneumonia must also take into account several factors that affect the expected rate of resolution. These include:
- Marrie TJ. Mycoplasma pneumoniae pneumonia requiring hospitalization, with emphasis on infection in the elderly. Arch Intern Med 1993; 153:488.
- Arancibia F, Ewig S, Martinez JA, et al. Antimicrobial treatment failures in patients with community-acquired pneumonia: causes and prognostic implications. Am J Respir Crit Care Med 2000; 162:154.
- Rosón B, Carratalà J, Fernández-Sabé N, et al. Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia. Arch Intern Med 2004; 164:502.
- Marrie TJ, Beecroft MD, Herman-Gnjidic Z. Resolution of symptoms in patients with community-acquired pneumonia treated on an ambulatory basis. J Infect 2004; 49:302.
- Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009; 64 Suppl 3:iii1.
- Fein AM, Feinsilver S, Niederman MS. Slow resolving pneumonia in the elderly. In: Respiratory Infections in the Elderly, Niederman MS (Ed), Raven Press, New York 1991. p.293.
- Jay SJ, Johanson WG Jr, Pierce AK. The radiographic resolution of Streptococcus pneumoniae pneumonia. N Engl J Med 1975; 293:798.
- Macfarlane JT, Miller AC, Roderick Smith WH, et al. Comparative radiographic features of community acquired Legionnaires' disease, pneumococcal pneumonia, mycoplasma pneumonia, and psittacosis. Thorax 1984; 39:28.
- Fein AM. Pneumonia in the elderly: overview of diagnostic and therapeutic approaches. Clin Infect Dis 1999; 28:726.
- Fein AM, Feinsilver SH, Niederman MS, et al. "When the pneumonia doesn't get better". Clin Chest Med 1987; 8:529.
- Johansson N, Kalin M, Tiveljung-Lindell A, et al. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis 2010; 50:202.
- Kuru T, Lynch JP 3rd. Nonresolving or slowly resolving pneumonia. Clin Chest Med 1999; 20:623.
- Grossman RF, Fein A. Evidence-based assessment of diagnostic tests for ventilator-associated pneumonia. Executive summary. Chest 2000; 117:177S.
- Feinsilver SH, Fein AM, Niederman MS, et al. Utility of fiberoptic bronchoscopy in nonresolving pneumonia. Chest 1990; 98:1322.
- Rodrigues J, Niederman MS, Fein AM, Pai PB. Nonresolving pneumonia in steroid-treated patients with obstructive lung disease. Am J Med 1992; 93:29.
- Coletta FS, Fein AM. Radiological manifestations of Legionella/Legionella-like organisms. Semin Respir Infect 1998; 13:109.
- Grayston JT. Chlamydia pneumoniae, strain TWAR pneumonia. Annu Rev Med 1992; 43:317.
- Farley MM, Stephens DS, Brachman PS Jr, et al. Invasive Haemophilus influenzae disease in adults. A prospective, population-based surveillance. CDC Meningitis Surveillance Group. Ann Intern Med 1992; 116:806.
- Heath PT, Booy R, Azzopardi HJ, et al. Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era. Pediatr Infect Dis J 2001; 20:300.
- Saubolle MA. Fungal pneumonias. Semin Respir Infect 2000; 15:162.
- Ahmed RA, Marrie TJ, Huang JQ. Thoracic empyema in patients with community-acquired pneumonia. Am J Med 2006; 119:877.
- Dumont P, Gasser B, Rougé C, et al. Bronchoalveolar carcinoma: histopathologic study of evolution in a series of 105 surgically treated patients. Chest 1998; 113:391.
- Cadranel J, Wislez M, Antoine M. Primary pulmonary lymphoma. Eur Respir J 2002; 20:750.
- Abers MS, Sandvall BP, Sampath R, et al. Postobstructive Pneumonia: An Underdescribed Syndrome. Clin Infect Dis 2016; 62:957.
- Ebara H, Ikezoe J, Johkoh T, et al. Chronic eosinophilic pneumonia: evolution of chest radiograms and CT features. J Comput Assist Tomogr 1994; 18:737.
- Allen JN, Pacht ER, Gadek JE, Davis WB. Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure. N Engl J Med 1989; 321:569.
- Philit F, Etienne-Mastroïanni B, Parrot A, et al. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 2002; 166:1235.
- Primack SL, Hartman TE, Ikezoe J, et al. Acute interstitial pneumonia: radiographic and CT findings in nine patients. Radiology 1993; 188:817.
- Olson J, Colby TV, Elliott CG. Hamman-Rich syndrome revisited. Mayo Clin Proc 1990; 65:1538.
- Shah PL, Hansell D, Lawson PR, et al. Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis. Thorax 2000; 55:67.
- White DA, Camus P, Endo M, et al. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med 2010; 182:396.
- NORMAL VERSUS DELAYED RESOLUTION OF PNEUMONIA
- EVALUATION OF NONRESOLVING PNEUMONIA
- Approach to diagnosis
- Imaging studies
- Thoracoscopic or open lung biopsy
- INFLUENCE OF SPECIFIC BACTERIAL PATHOGENS
- Streptococcus pneumoniae
- Legionella infection
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Haemophilus influenzae
- MISDIAGNOSIS OF PATHOGENS
- Nocardia and Actinomyces
- RESISTANT BACTERIAL PATHOGENS
- HOST FACTORS
- Primary humoral immune deficiencies
- DEVELOPMENT OF COMPLICATIONS FROM THE INITIAL PNEUMONIA
- Lung abscess
- NONINFECTIOUS ETIOLOGIES
- Neoplastic disorders
- Inflammatory disorders
- Drug-induced lung disease
- Pulmonary embolism
- Hydrostatic pulmonary edema
- SUMMARY AND RECOMMENDATIONS