Unresolved Acute Pneumonia: a “BAD OMEN”
Laren Tan, MD, and Samuel Louie, MD
Tan L, Louie S. Unresolved acute pneumonia: a “BAD OMEN.” Consultant. 2017;57(8):500-503.
The most widespread and fatal of all acute infectious diseases, pneumonia, is the “Captain of the Men of Death,” asserted Sir William Osler in the 1901 edition of Principles and Practice of Medicine.1 Pneumonia and influenza were responsible for the largest number deaths from infectious disease in the 20th century.2
Even with the arsenal of antibiotics and vaccines available in the 21st century, community-acquired pneumonia (CAP) has lost none of its virulence. In 2014, pneumonia and influenza together were the leading cause of infectious disease-related death and the eighth leading cause of death overall, with a generalized mortality rate between 15% and 20% in US adults.3
More women than men die from pneumonia and influenza in the United States, but men are 25% more likely than women to die from these diseases, given that there are more women than men in the United States.4 Approximately 85% of all deaths from pneumonia and influenza occur in persons aged 65 years or older.4 More than 1 million hospitalizations due to pneumonia and 7000 due to influenza occurred in 2010 in the United States.4 Death from CAP in the United Kingdom, for example, is reportedly less than 1% among outpatients and 8% to 14% among hospitalized adults and can reach 50% when intensive care unit admission is needed for the management of severe sepsis or acute respiratory failure.5
The most frequent causes of lethal CAP are Streptococcus pneumoniae and Legionella pneumophila.6 The mortality from acute pneumonia has not declined significantly since the introduction of sulfa drugs in the mid-1930s and penicillin in the mid-1940s because of year-to-year variations in influenza virulence and increasing longevity with chronic diseases, including some cancers. The improvement in mortality from infectious diseases has been attributed to better population hygiene, sanitation, and vaccinations.7 The emergence of antibiotic drug resistance in the absence of new antibiotic development and choices threatens to worsen mortality from CAP worldwide.
DIAGNOSIS OF PNEUMONIA
Delay in diagnosis of CAP and further delay in instituting empiric antibiotic treatment and supportive care within 4 hours after diagnosis in a hospital setting may result in increased morbidity and mortality.8 Delay in antibiotic treatment of CAP, along with specific patient characteristics, can portend complications from continuing pneumonia despite appropriate antibiotic treatment, including parapneumonic effusions, empyema, and lung abscess, leading to unresolved acute pneumonia (URAP).
The symptoms and signs of CAP include a patient acutely feeling very ill or tired with accompanying fever and shaking chills, along with a cough producing purulent sputum; crackles, localized bronchial breathing, and decreased breath sounds; tachypnea (a respiration rate greater than 20 breaths/min); sinus tachycardia; and pleuritic chest pain.9
The key feature distinguishing acute pneumonia from chronic pneumonia is simply the sudden onset (hours to days) of symptoms in acute pneumonia and the late onset of symptoms in chronic pneumonia, with symptoms occurring for at least 6 weeks in the latter.
Mortality and severity prediction scores should be calculated and used to determine which patients should be hospitalized for CAP and which patients should be treated as outpatients.9
Patients with CAP are at risk for sepsis even after diagnosis and treatment with antibiotics. Fever, tachycardia, tachypnea, and altered consciousness are symptoms of sepsis that overlap with the clinical presentation of acute pneumonia; early diagnosis of CAP is therefore essential to avoid or forestall severe sepsis, septic shock, and death. Chest radiography is essential to confirm the diagnosis of acute pneumonia and to distinguish it from severe acute bronchitis. Computed tomography (CT) of the chest is generally not indicated unless a complication of CAP is suspected (eg, abscess, parapneumonic effusion, empyema).
Early management of CAP is supportive with antipyretics and oxygen, if needed, and therapeutic with empiric antibiotics. Only the patient’s progress over the next 3 to 5 days can confirm whether the diagnosis and initial treatment are correct. It is a dangerous pitfall to think that antibiotic algorithms effectively cover the treatment of all pneumonias, because not all pneumonias are caused by bacteria or are even infectious (eg, extrinsic allergic alveolitis, pulmonary aspiration syndromes).10,11
Chest radiography and hospitalization of outpatients with CAP should be considered in patients who remain very ill after 48 hours of treatment with an antibiotic such as a macrolide or doxycycline.5 A respiratory fluoroquinolone, or cefpodoxime plus a macrolide, or amoxicillin-clavulanate plus a macrolide should be considered in outpatients with significant comorbidities (eg, chronic obstructive pulmonary disease [COPD], alcoholism) or who have used antibiotics in the previous 3 months.9
Empiric treatment of CAP in the hospital should include dual antibiotic therapy (eg, a β-lactam plus azithromycin or respiratory fluoroquinolone), particularly if the patient requires admittance to the intensive care unit.9 At the University of California, Davis, we recommend a third-generation cephalosporin (ceftriaxone), plus azithromycin or levofloxacin, with or without vancomycin (if methicillin-resistant Staphylococcus aureus infection is suspected), but the selection of empiric antibiotic treatment should always conform to the epidemiology of local infectious disease trends and antibiotic resistance patterns.
The majority of inpatients and outpatients with pneumonia feel better with the disappearance of fever and the lessening of productive cough within 3 to 5 days of initiation of antibiotics and supportive care. Other signs of resolving pneumonia include the disappearance of leukocytosis or leukopenia in 3 to 5 days and the patient’s restored ability to sleep well.
Radiographic resolution of acute bacteremic pneumococcal pneumonia should take no longer than 6 to 10 weeks and very often lags behind the patient’s clinical improvement.12 All patients with pneumonia should have follow-up chest radiography approximately 8 weeks after the initial diagnosis and treatment. If radiography findings have not returned to baseline after 8 weeks, consider the possibility of URAP. Follow-up chest radiographs are important, since CAP resolves radiographically by 4 weeks in only approximately 30% of patients older than 50 years.13,14
The current literature continues to cite the conventional wisdom that viral and “atypical” or uncommon pathogens such as Mycoplasma and Chlamydia tend to clear up on chest radiographs sooner than more common bacterial pneumonias.
Unless complications ensue in the hospital (eg, progressive pneumonia with development of effusions, empyema, acute respiratory failure, or septic shock), inpatients are discharged home after a median hospital length of stay of 5 days,8 with instructions to complete a full course of oral antibiotics. It is during this period of anticipated recovery from pneumonia that patients can develop URAP.
Important lessons can be learned from the time course of inpatients with CAP who fail to improve clinically during their hospital stay. Arancibia and colleagues found the following15:
- Antibiotic treatment failures were mainly infectious in origin, including primary, persistent, and nosocomial infections.
- Persistent infections were mostly due to microbial resistance to the administered empiric antibiotics.
- Nosocomial infections were very frequent among patients with progressive pneumonia and were the only cause of treatment failure to be independently associated with death.
Regardless of whether a patient with pneumonia is sent home from a clinic or emergency department or is hospitalized and later discharged home for acute pneumonia, 2 follow-up clinic visits are recommended. The first visit should take place approximately 1 week after initiating antibiotic treatment to ensure that symptoms of infection are disappearing and that normal activities of daily living are resuming. The second visit should take place approximately 8 weeks after initiating antibiotics and should include chest radiography to confirm radiographic resolution of pneumonia, or to confirm URAP.Increasingly shorter hospital stays in the United States may not work to pneumonia patients’ benefit. It is a very dangerous pitfall to treat and forget about patients with acute pneumonia once antibiotics have been initiated. Progressive pneumonia can kill a patient, so get patients back to the clinic for follow-up, and track them down if necessary.