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, ventilator-associated, and healthcare-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 fever, cough, crackles, leukocytosis, arterial oxygenation (PaO2), and level of C-reactive protein (table 1). However, 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:
- Comorbidities — Comorbid conditions often slow the resolution of pneumonia (table 2). Whereas patients without associated medical illnesses usually demonstrate clearing of radiographic infiltrates by four weeks, only 20 to 30 percent of patients with a comorbid condition will clear by four weeks [4,5].
- Age — Approximately 90 percent of patients younger than 50 years of age show radiographic resolution by four weeks, compared with only 30 percent of patients older than 50, even in the absence of concurrent disease .
- Severity — Radiographic resolution of severe pneumonia is estimated at 10 weeks, compared with three to four weeks for mild to moderate pneumonia.
- Infectious agent — The rate of radiographic and clinical improvement varies with the particular infectious agent causing the pneumonia. In general, resolution is more rapid with Mycoplasma pneumoniae, non-bacteremic Streptococcus pneumoniae, Chlamydophila (formerly Chlamydia) species, and Moraxella catarrhalis than with other organisms (table 3) .