Pneumonia is a commonly encountered lower respiratory infection in patients in EDs, hospitals, urgent care clinics, and primary care clinics throughout the United States. The spectrum of lower respiratory infections includes acute bronchitis, atypical pneumonia, viral pneumonia, lobar pneumonia, chronic obstructive pulmonary disease (COPD) or asthma exacerbation, sepsis, and acute respiratory failure. Pneumonia is classified based on the environment in which the infection was acquired: community-acquired or hospital-acquired, depending on whether the patient has had recent healthcare facility exposure.1,2
This article discusses recent literature on the diagnosis and management of community-acquired pneumonia (CAP). Many of the articles and reviews answer important clinical questions, such as which physical examination findings have been validated, how ultrasound compares with radiography to diagnose pneumonia, whether procalcitonin has a role in determining bacterial causes and patient dispositions, what utility and limitations characterize CURB-65, and what challenges exist in outpatient prescribing for CAP.
EVIDENCE-BASED PHYSICAL EXAMINATION
The stethoscope, once the central tool for diagnosing and following a patient with pneumonia, is seen by many clinicians as an afterthought.3 For example, Breunig and Kashiwagi state that “Physical examination is unreliable for the diagnosis of pulmonary pathology.”4 However, clinical questions not only include which disease is present but also which imaging, laboratory tests, and initial treatment will be essential, and what disposition will be safe. Physical examination provides a unique, immediate, and dynamically changing patient context for answering several clinical questions.
McGee reviewed physical examination techniques in more than 6,000 patients with acute fever, cough, sputum production, or dyspnea.3 Each patient eventually underwent chest radiography, which was used as the reference standard to diagnose pulmonary infiltrate. Table 1 includes likelihood ratios and associated effect on pneumonia probability for several physical examination findings. Some findings strongly increase probability if found on examination: asymmetric chest expansion (likelihood ratio [LR] = 44.1), egophony (LR = 4.1), cachexia (LR = 4), bronchial breath sounds (LR = 3.3), oxygen saturation less than 95% (LR = 3.1), and percussion dullness (LR = 3).3 Some findings only moderately increase probability if found on examination: respiratory rate greater than 28 (LR = 2.7), crackles (LR = 2.3), diminished breath sounds (LR = 2.2), temperature greater than 37.8° C (100° F) (LR = 2.2), and abnormal mental status (LR = 1.9).3 One finding has been shown to strongly decrease probability: all vital signs normal (LR = 0.3).3
Many of these physical examination findings in isolation will not greatly affect the clinical impression, but several of these findings can lead to a more definitive diagnosis. For example, the Heckerling score combines five findings to improve accuracy of bedside examination:
- temperature greater than 37.8° C (100° F)
- heart rate greater than 100 beats/minute
- diminished breath sounds
- absence of asthma.3,5
McGee found that both low and high scores on the decision rule perform well: a score of 0 to 1 argues against pneumonia (LR = 0.3) and a score of 4 to 5 argues for pneumonia (LR = 8.2).3 McGinn and colleagues suggested that this score, integrated with an electronic medical record (EMR), could contribute to decreased antibiotic use and meaningful use.6
POINT-OF-CARE LUNG ULTRASOUND
Since its discovery in the late 19th century, chest radiography has been the standard method for diagnosing pneumonia. The benefits of radiography include ease of use, cost-effectiveness compared with more advanced modalities such as CT, integration with EMRs, and recognition across medical disciplines. Its downfalls include patient radiation exposure and its low sensitivity in diagnosing several disorders, such as pneumonia, pulmonary edema, and pneumothorax. Chest radiograph has a sensitivity of 38% to 64% for the diagnosis of pneumonia, but many clinicians consider a negative chest radiograph as a means for ruling out pneumonia.3
A 2018 systematic review and meta-analysis found that point-of-care (POC) ultrasound ranks superior to chest radiography in diagnosing pneumonia and other pulmonary diseases.7 This review of 14 studies of pneumonia specified the accuracy of each sonographic sign in determining diagnosis. Many of these studies used different diagnostic reference standards (clinical judgment from a panel of experts, chest radiography, and chest CT). Table 2 shows LRs for several findings and profiles consistent with pneumonia on lung ultrasound. On ultrasound, consolidation found in the anterior, lateral, or posterior regions had the best overall profile (LR+ 15.8, LR- 0.18).7 Finding either this pattern of consolidation or focal interstitial syndrome had the best sensitivity (0.96); finding isolated focal interstitial syndrome or isolated anterior consolidation had the best specificity (0.97).7Figure 1 shows the Bedside Lung Ultrasound in Emergency (BLUE) protocol as a means for distinguishing pneumonia from other causes of acute dyspnea such as pulmonary edema and obstructive pulmonary disease such as COPD or asthma.8,9 The BLUE protocol, which includes most of the above signs, also was helpful in diagnosing pneumonia (LR+ 5.93, LR- 0.14, sensitivity 0.87, specificity 0.85).8
Because POC ultrasound is completed at the bedside, results are available to the clinician in real time to aid in diagnosis and decision-making. Serial examinations can be completed to monitor disease progression and treatment response. However, many facilities do not have a way to save POC ultrasound images, so other healthcare providers cannot see the images. Without a way to document what was seen, the POC diagnosis is unsubstantiated. Another important limitation is the experience of the clinician who performs and interprets the examination. However, competence has been demonstrated after 9 hours or 1 day of training.10,11 Finally, availability and cost of POC ultrasound machines in healthcare settings remains a burden. Each of these limitations prevents the clinical translation of POC ultrasound for diagnosing pneumonia.
Procalcitonin is a peptide with levels that generally are elevated in bacterial rather than viral lower respiratory tract infections. A low procalcitonin level (less than 0.1 ng/mL) is helpful as a negative predictor for 30-day mortality in patients with a clinical and radiologic diagnosis of CAP (sensitivity 92%, LR- 0.22), even among patients deemed high-risk by the Pneumonia Severity Index (PSI) and CURB-65 (LR- 0.09).12 Among patients admitted to the hospital, a low procalcitonin level was associated with a shorter length of hospital stay, lower proportion of mechanical ventilation and ICU admission, and less-severe sepsis.12 Limitations of procalcitonin use include its cost (about $87 versus $25 for a complete blood cell count) and availability in many hospital systems.13
Several recent trials have studied whether procalcitonin can curb the use of antibiotics in patients with lower respiratory infections. Huang and colleagues found that the use of procalcitonin by ED and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infections.14 This study consisted of 1,656 patients, 826 in the procalcitonin group and 830 in the control group, diagnosed with acute lower respiratory infection but with clinical uncertainty regarding the need for an antibiotic. For patients in the procalcitonin group, clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and antibiotic-use guidelines with graded recommendations based on four tiers of procalcitonin levels. Clinicians adhered to these guidelines for 64.8% of patients.14 The primary outcome was total antibiotic days 30 days after enrollment. For this outcome, no significant difference was found between the two groups in total or among subgroups. Among the subgroup of patients with CAP, only a subtle difference was found between the percentage of patients who received antibiotics by day 30 (88.6% using procalcitonin versus 95.9% with usual care), but a greater difference for those diagnosed with acute bronchitis (37% using procalcitonin compared with 52.8% from usual care).14 No significant risk or adverse events were noted in the two groups.14
The main finding of this trial suggests that procalcitonin's use in changing prescribing practices is limited. However, several previous trials found that procalcitonin-based guidance reduced use of antibiotics with no apparent harm.15-17 A 2017 Cochrane meta-analysis of 26 randomized controlled trials and 6,708 patients concluded that use of procalcitonin to guide initiation and duration of antibiotics results in lower mortality, lower antibiotic consumption, and lower risk for antibiotic-associated adverse reactions.15 The FDA approved a procalcitonin assay to help clinicians determine when to start or stop antibiotic treatment in patients with suspected lower respiratory tract infection in the ED or hospital.18 However, considering the inconsistent results of procalcitonin, other national authorities and medical societies have reached varying conclusions.2,19 Whether procalcitonin adds a significant amount of additional information to standard practice remains to be seen.
Disposition is another important consideration in the management of pneumonia. The Infectious Diseases Society of America (IDSA), American Thoracic Society (ATS), and British Thoracic Society recommend incorporating clinical prediction rules into this decision-making along with clinical judgment.1,20 CURB-65 contains five variables and has a high positive predictive value for detecting patients at high risk for 30-day mortality.21 Its components—Confusion level, blood Urea nitrogen (BUN) levels greater than 19 mg/dL, Respiratory rate greater than 30, BP less than 90 mm Hg systolic or 60 mm Hg diastolic, and age 65 years or older—each count for one point.21 The authors of the original article suggested that patients with a score of 0 to 1 may be suitable for outpatient management and those with a score of 2 may be suitable for inpatient care or observation.22 A score of 3 or greater is associated with increased mortality (LR+ 2.6 for three findings, LR+ 5.9 for four findings, and LR+ 11.1 for five findings); absence of these findings is associated with reduced mortality (LR = 0.2).3
Despite the decision rule's validation in predicting mortality, Ilg and colleagues suggested in a 2018 retrospective validation study that a more proximal outcome than mortality needs to be measured for the decision rule to be clinically relevant.23 The authors instead studied whether a low or high CURB-65 score was associated with ICU admission and need for critical care interventions such as vasopressors, noninvasive positive-pressure ventilation, and endotracheal intubation. In this study of 2,322 patients admitted for CAP, the authors found a stepwise increase in association between CURB-65 score and both critical care intervention and mortality (Table 3).23 Still, of the 1,159 patients with a score of 0 to 1, 15.6% of patients were admitted to the ICU, 6.4% received a critical care intervention, and 0.6% died; 27% of patients with a score of 2 were admitted to the ICU and 15.4% received a critical care intervention.23 Thus, the authors state that CURB-65, although useful, should not be used in isolation for low-risk patients but in the context of a clinical impression.23 For example, many patients classified with sepsis per SIRS criteria can have a CURB-65 score of 0 or 1 because respiratory rate is the only similar variable. Other vital signs, such as heart rate and oxygen saturation, are not considered. Because this is a retrospective analysis, the study cannot test the predictive ability of the components of CURB-65 as the authors state. Also, because it only contained patients who were admitted, it left out a significant population of low-risk patients with CAP.
Over the last decade, resistance patterns have complicated outpatient antibiotic management of pneumonia. Many outpatients without comorbidities are treated with a macrolide such as azithromycin or clarithromycin. This class has previously been effective against Streptococcus pneumoniae and Mycoplasma pneumoniae, the most common pathogens causing CAP.1 A recent study found streptococcal resistance to macrolide antibiotics to be greater than 25% in patients with CAP in EDs across the United States.24 In the southeastern United States, macrolide resistance ranges from 53% to 61%.24 The current state of macrolide resistance across the United States clouds the use of these drugs as a first-line treatment.
Fluoroquinolones are another commonly used class, particularly in patients with comorbidities or when previous antibiotic therapy has not worked. These antibiotics, which include ciprofloxacin, levofloxacin, and moxifloxacin, are effective because of their broad spectrum. However, their use became complicated in 2008 when the FDA issued a black-box warning about their association with tendon rupture.25 The risk for tendon rupture is particularly great among patients over age 60 years, men, patients with chronic kidney disease, those who use corticosteroids, and recipients of solid organ transplants.26 Most (90%) tendinopathy involves the Achilles tendon.26 Symptoms usually begin about 1 week after the onset of treatment, but the risk for exposure can last up to several months.26 In 2016, an additional black-box warning was issued in response to findings that 1% to 2% of patients developed psychiatric and neuropathic adverse reactions.27 Although the FDA issued a statement that healthcare professionals should not routinely prescribe fluoroquinolones for acute sinusitis and exacerbation of chronic bronchitis, the benefit of therapy may outweigh the risk in patients with CAP and comorbidities.28 Delaney advises discussing risks and benefits with patients, engaging in shared decision-making, and documenting carefully.29
IDSA and ATS guidelines for treating CAP recommend a macrolide or doxycycline for previously healthy patients with no comorbidities.1 For patients with cardiac, pulmonary, or renal comorbidities and those with diabetes, alcohol abuse, or recent antibiotic use, and for patients with macrolide resistance, the guidelines recommend dual therapy with a beta-lactam plus doxycycline or a macrolide; alternatively, a respiratory fluoroquinolone may be used.1 Doxycycline has a weak recommendation with poor evidence for use as monotherapy, and average US resistance has risen to more than 25%.1 Outpatient beta-lactams include amoxicillin with or without clavulanate, cefuroxime, and cefdinir. One downside to beta-lactams is the lack of atypical coverage, for example, for M. pneumoniae. Despite evidence supporting S. pneumoniae as the principal cause of CAP in the United States, international trends highlight the rising incidence of atypical pathogens, and the IDSA recommends that empiric treatment include antibiotics covering typical and atypical organisms.1
In the last two centuries, the diagnosis and management of pneumonia has certainly changed. However, vital signs and chest physical examination findings can guide clinical decision-making. Lung ultrasound outperforms chest radiography, but unfamiliarity among providers and lack of acceptance among healthcare systems have limited clinical translation. Procalcitonin has had inconsistent results in trials and its added benefit is yet to be determined. In immunocompetent patients with CAP, CURB-65 can identify high-risk patients, including those who will require ICU admission and a critical care intervention. However, CURB-65 is less adept in identifying low-risk patients. Macrolide resistance and fluoroquinolone adverse reactions complicate antibiotic choice in outpatient management of CAP. Risk/benefit, bacteria coverage, and resistance patterns should guide the decision. As these research findings are translated to clinical practice and further studies are conducted, the imaging, laboratory assessment, disposition, and management of CAP will continue to be refined.
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