Community-Acquired Pneumonia in Adults: Diagnosis and Management

Diagnosis

DIFFERENTIAL DIAGNOSIS

Although Streptococcus pneumoniae remains the most commonly isolated pathogen in CAP, the relative frequency of other pathogens has increased. Clinical suspicion should be driven by comorbidities and other risk factors (Table 1).6,9–11 Commonly used diagnostic methods may identify a pathogen in only 30% to 40% of patients.12

HISTORY AND PHYSICAL EXAMINATION

Most patients with CAP present with a combination of cough, dyspnea, pleuritic pain, fever or chills, and malaise. Risk and severity of CAP, including infection with less common pathogens (e.g., Legionella species), increase with older age, cardiopulmonary disease, poor baseline functional status, low socioeconomic status, and recent weight loss or underweight status.4,9 Although a thorough history is an essential component in the diagnosis of CAP, no individual symptom can adequately predict its presence. Across four studies, the most predictive findings were fever greater than 100°F (37.8°C) (positive likelihood ratio [LR+] is approximately 2.7) and egophony (LR+ = 5.3).13  Clinical prediction rules that combine symptoms and examination findings (Table 214) can be helpful in generating a likelihood ratio that can be applied to patients with different prior probabilities of CAP and aid in diagnosis and management.14

Physician judgment has better discriminatory ability to rule out pneumonia (negative likelihood ratio [LR–] = 0.25), but ability to clinically diagnose pneumonia is less certain (LR+ = 2.0).13 Patients with no vital sign abnormality and normal lung examination findings are unlikely to have pneumonia.15 Thus, lung imaging is helpful for patients presenting with possible CAP who have any vital sign or examination abnormalities (given the absence of asthma).16

Guidelines from the Infectious Diseases Society of America advise diagnosing CAP based on suggestive examination findings and characteristic infiltrate on chest radiography with or without microbiologic data.6 Caution should be used when diagnosing CAP in older patients and those who are immunocompromised because they may not exhibit typical symptoms such as a fever greater than 100.4°F (38°C). However, most patients exhibit at least one respiratory symptom; acute functional or cognitive decline; or repeat temperatures of 99°F (37.2°C) or greater.15

IMAGING

Lung imaging with chest radiography has been the standard method of diagnosing pneumonia6 (Figure 1). Lung ultrasonography has the potential to more accurately and efficiently diagnose pneumonia, as well as pleural effusions, pneumothorax, pulmonary embolism, and pulmonary contusions.17 Two recent meta-analyses using chest computed tomography as the comparative standard show that lung ultrasonography has a pooled sensitivity of 0.94 to 0.95 (95% confidence interval [CI], 0.92 to 0.97) and a specificity of 0.90 to 0.96 (95% CI, 0.86 to 0.97), with LR+ = 16.8 (95% CI, 7.7 to 37.0) and LR− = 0.07 (95% CI, 0.05 to 0.10), compared with chest radiography (pooled sensitivity = 0.77 [95% CI, 0.73 to 0.80]; specificity = 0.91 [95% CI, 0.87 to 0.94]) for diagnosis of pneumonia.17,18 Because lung ultrasonography can be performed at the bedside in an average of 13 minutes and lacks ionizing radiation, it is a promising diagnostic option in primary care and emergency department settings.18 Physicians should consider use of chest computed tomography when concern for alternative or concurrent diagnoses remains high (e.g., interstitial lung disease, cavitary lesions, sarcoidosis, malignancy).

  Enlarge      Print

Figure 1.

Chest radiograph showing right upper lobe infiltrate in a patient with pneumonia. [corrected]

---

Figure 1.

Chest radiograph showing right upper lobe infiltrate in a patient with pneumonia. [corrected]

DIAGNOSTIC TESTING

Pulse oximetry should be assessed in all patients with possible CAP. Patients who require supplemental oxygen should receive inpatient treatment. Routine microbiologic testing of outpatients with CAP is unnecessary.6  Testing may be indicated according to patient-specific risk factors (Table 3).6,19  Testing for human immunodeficiency virus infection, tuberculosis, and pneumocystis pneumonia should be considered in those with high-risk sexual exposures or a history of injection drug use. Blood and sputum cultures should be obtained in the presence of specific risk factors or with severe CAP (Table 46,20) when culture results can alter antibiotic selection.6 A study of 833 patients with pneumococcal CAP, 47% of whom were bacteremic, showed a marginal but statistically significant increase in the length of stay, time to clinical stability, and in-hospital mortality for bacteremic patients.21 However, an earlier study showed no change in outcomes and demonstrated the potential for false-positive blood cultures to cause prolonged hospitalization and unnecessary vancomycin use.22

Urine antigen testing may be useful in select patients, especially if adequate sputum cannot be obtained or antibiotics were given, because antigen can be detected starting on the first day of illness and for several weeks thereafter.6,23 Pneumococcal urine antigen testing has a sensitivity of 60% to 80% and specificity greater than 90%, whereas Legionella testing has a sensitivity of 70% to 90% and specificity of 99% for serogroup 1, which accounts for 80% to 95% of Legionella-associated CAP.6  Testing is most useful in critically ill patients and in the scenarios listed in Table 3.6,19

The overall rate of pathogen detection among patients with CAP is 30% to 40%.12 Recent developments allow use of rapid multiorganism polymerase chain reaction–based testing for pathogen-directed treatment, with bacterial and viral detection rates as high as 86%.9,19 Such detection can potentially result in earlier de-escalation of therapy and decreased reliance on broad-spectrum antimicrobials.11,24 Additionally, because viral etiologies account for about 25% of all CAP cases, utilization of rapid viral respiratory panels can be useful to tailor treatment and limit antibiotic exposure.6,24–26

Although more readily available through newer polymerase chain reaction–based methods, routine testing for other atypical pathogens (e.g., Chlamydophila pneumoniae, Mycoplasma pneumoniae) in patients with CAP is not currently recommended.6,11,19

To improve patient outcomes and reduce unnecessary antibiotic exposure, procalcitonin is being studied as a potential biomarker of severe CAP. With a cost of $25 to $30 per test, the value of procalcitonin testing is dependent on laboratory capability, with a cutoff value of less than 0.1 ng per mL having superior prognostic accuracy for short-term mortality (relative risk = 4.18; 95% CI, 3.19 to 5.48), bacteremia, and disease severity.27,28 A 2012 Cochrane meta-analysis found the use of procalcitonin testing significantly decreased median antibiotic exposure from eight to four days and lowered the risk of treatment failure (19.1% vs. 21.9%) with no impact on mortality or length of hospitalization, regardless of clinical setting.29

A systematic review of 14 randomized controlled trials examining use of procalcitonin testing in European settings found a reduction in antibiotic prescribing in low-acuity settings and shorter duration of therapy in higher-acuity settings (i.e., emergency department and ICU) when results of high-sensitivity (detection limit 0.1 ng per mL) procalcitonin assays were used in clinical decision making.30 Further research is needed to evaluate the impact of procalcitonin testing among patients with acute respiratory illnesses in terms of patient-oriented outcomes, antibiotic exposure, and cost-effectiveness in U.S. populations.

Management

INPATIENT VS. OUTPATIENT CARE

The costs of hospitalization and potential for nosocomial infections and thromboembolic events necessitate careful consideration of risk factors for severe CAP when considering appropriate level of care (Table 4).6,20 Decision support tools such as the Pneumonia Severity Index (https://www.aafp.org/afp/2006/0201/p442.html#afp20060201p442-t3) assist in predicting the risk of 30-day mortality and severe CAP requiring ICU admission. Table 5 summarizes the more widely adopted CURB-65 and CRB-65 prediction scores,6,31 which have greater ease of use, but weaker predictive power for 30-day mortality.24,31,32 Among low-risk patients (Pneumonia Severity Index class less than 3 or CURB-65 score less than 2), the LR− for 30-day mortality using the index is 0.08, and 0.21 using CURB-65.31 Sensitivity for predicting ICU admission was reported as 74% vs. 39% to 50% for Pneumonia Severity Index vs. CURB-65, respectively.24,32

Although CURB-65 has a higher false-negative rate (i.e., incorrectly ruling out severe CAP) compared with other instruments, its relatively high specificity allows physicians to more accurately advance treatment for patients with a score of 3 or greater while taking further measures to determine risk in patients who score low.24,32,33 CRB-65 is more practical for use in the primary care setting without a significant compromise in prognostic value.6,31 Patients with a score of 0 or 1 can be managed safely as outpatients.6

SMART-COP (https://www.aafp.org/afp/2011/0601/p1299.html#afp20110601p1299-t6), a more recently developed predictive tool, was designed to identify patients with CAP who are most likely to need mechanical ventilation or vasopressor support (sensitivity = 92%).34 Other risk factors predictive of severe CAP include male sex and the presence of congestive heart failure or chronic obstructive pulmonary disease.35

ANTIBIOTIC THERAPY

Given the relatively low yield of standard culture techniques, empiric treatment using the 2007 Infectious Diseases Society of America and American Thoracic Society guidelines (Table 6 6,36–40) targets likely pathogens based on epidemiologic risk factors.6

Outpatient. Evidence is lacking on the optimum antibiotic regimen for treatment of CAP in the outpatient setting.41 In the absence of significant comorbidities, macrolides (e.g., azithromycin [Zithromax]) should be used for outpatient therapy of adult CAP, with doxycycline as an alternative, because S. pneumoniae and atypical pathogens account for most cases of CAP, especially in North America.6,16 Exposure to antibiotics in the preceding three months or presence of comorbid illness necessitates the preferential use of fluoroquinolones followed by a beta-lactam antibiotic (e.g., high-dose amoxicillin, amoxicillin-clavulanate [Augmentin], cefuroxime [Ceftin], cefpodoxime) combined with a macrolide as an alternative. Evidence from randomized controlled trials shows a modest reduction in treatment failure, adverse events, and treatment discontinuation with fluoroquinolones compared with combination beta-lactam and macrolide antibiotics.36,37

Facility-specific antibiograms should be used whenever available to account for variable resistance patterns. Given the risk of pneumococcal resistance, an antibiotic from a different class should be used when recent antibiotic exposure is known. A five-day treatment course for low-severity CAP has been shown to be sufficient in clinical trials, whereas a seven- to 10-day course should be provided in patients with moderate- and high-severity CAP (based on CURB-65 and CRB-65 scores).42

Inpatient, No ICU. Hospitalized patients who are not admitted to the ICU should receive a respiratory fluoroquinolone or a beta-lactam antibiotic and a macrolide. Observational data suggest lower short-term mortality when antibiotic therapy is administered within four to eight hours of hospital arrival in patients with moderate or severe pneumonia.36  Table 7 provides recommended criteria for transitioning patients from intravenous to oral antibiotics.36

Although oral doxycycline is not included in existing guidelines, observational studies show that it has similar effectiveness as levofloxacin (Levaquin) alone or in combination with ceftriaxone in the inpatient, non-ICU setting, and is associated with fewer Clostridium difficile infections.39,40,43,44 Trials of a new cephalosporin (ceftaroline [Teflaro]) show promising results, although treatment should be reserved for patients with highly resistant gram-positive organisms.38

Inpatient, ICU. Patients with severe CAP who are admitted to the ICU—about 10% of patients hospitalized with CAP—should receive dual antibiotic therapy, which has been shown to improve survival6,7,43  (Table 66,36–40). Anaerobic coverage should be considered if risk factors are present, including aspiration, stroke with bulbar symptoms, alcoholism, and loss of consciousness. Such agents include carbapenems, clindamycin, metronidazole (Flagyl), amoxicillin/clavulanate, and piperacillin/tazobactam (Zosyn).7 Coverage for methicillin-resistant Staphylococcus aureus and Pseudomonas species should be administered depending on risk factors (Table 16,9–11  and Table 36,19). Physicians must be aware that up to one in four cases of CAP has a viral etiology, which may account for poor response to antibiotics or atypical features.6,26 Prompt recognition and antiviral treatment, especially during influenza season, improve outcomes and reduce mortality.45

ADJUNCTIVE THERAPIES

Meta-analyses of randomized trials of corticosteroids for CAP demonstrate a decreased risk of adult respiratory distress syndrome (relative risk = 0.21; 95% CI, 0.08 to 0.59) and modest reductions in lengths of ICU and hospital stays, duration of intravenous antibiotic treatment, and time to clinical stability without a corresponding increase in major adverse events.46 Additional observations include reduced need for mechanical ventilation (number needed to treat = 20) and 3% reduction in mortality with a typical regimen consisting of methylprednisolone 0.5 mg per kg every 12 hours for five to seven days, administered within 36 hours of admission.47,48

Prevention

The 2015 Advisory Committee on Immunization Practices recommends that adults 65 years and older receive both the 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23), preferably with PCV13 administered first, followed by PPSV23 in 12 months.49 If PPSV23 was already given after age 65, PCV13 should be offered after one year. When PPSV23 is administered before age 65, PCV13 should be offered if at least one year has elapsed, followed by another dose of PPSV23 after at least 12 months and if at least five years have elapsed following the previous PPSV23 dose.

In the presence of immunocompromising conditions (e.g., functional or anatomic asplenia, cochlear implants, cerebrospinal fluid leak), a minimum of eight weeks between doses of PCV13 before PPSV23 is recommended.49 In adults 19 to 64 years of age, a dose of PPSV23 should be given in the presence of diabetes mellitus, chronic lung or heart disease, tobacco use, alcoholism, chronic liver disease or cirrhosis, cerebrospinal fluid leaks, or cochlear implant.50 Additionally, either PPSV23 or PCV13 can be safely co-administered with the influenza vaccine.26 Evidence supports the influenza vaccine in preventing pneumonia, hospitalization, and death, particularly among older patients.51

Data Sources: A PubMed search was completed in Clinical Queries using the key term community-acquired pneumonia. The search included meta-analyses, randomized controlled trials, clinical trials, practice guidelines, and reviews. The limits included English language, humans, and all adults 18 years and older. We also searched Best Evidence Review, Cochrane Database of Systematic Reviews, National Guideline Clearinghouse, and the U.S. Preventive Services Task Force. Search dates: October 2015 through February 2016.