The extensive list of potential etiologic agents in CAP includes bacteria, fungi, viruses, and protozoa. Newly identified pathogens include hantaviruses, metapneumoviruses, the coronavirus responsible for severe acute respiratory syndrome (SARS), and community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA). Most cases of CAP, however, are caused by relatively few pathogens (Table 257-2). Although Streptococcus pneumoniae is most common, other organisms must also be considered in light of the patient's risk factors and severity of illness. In most cases, it is most useful to think of the potential causes as either "typical" bacterial pathogens or "atypical" organisms. The former category includes S. pneumoniae, Haemophilus influenzae, and (in selected patients) S. aureus and gram-negative bacilli such as Klebsiella pneumoniae and Pseudomonas aeruginosa. The "atypical" organisms include Mycoplasma pneumoniae and Chlamydia pneumoniae (in outpatients) and Legionella spp. (in inpatients) as well as respiratory viruses such as influenza viruses, adenoviruses, and respiratory syncytial viruses. Data suggest that a virus may be responsible for up to 18% of cases of CAP that require admission to the hospital. The atypical organisms cannot be cultured on standard media, nor can they be seen on Gram's stain. The frequency and importance of atypical pathogens have significant implications for therapy. These organisms are intrinsically resistant to all β-lactam agents and must be treated with a macrolide, a fluoroquinolone, or a tetracycline. In the ~10–15% of CAP cases that are polymicrobial, the etiology often includes a combination of typical and atypical pathogens.
Table 257-2 Microbial Causes of Community-Acquired Pneumonia, by Site of Care |Favorite Table|Download (.pdf)
Table 257-2 Microbial Causes of Community-Acquired Pneumonia, by Site of Care
|Streptococcus pneumoniae||S. pneumoniae||S. pneumoniae|
|Mycoplasma pneumoniae||M. pneumoniae||Staphylococcus aureus|
|Haemophilus influenzae||Chlamydia pneumoniae||Legionella spp.|
|C. pneumoniae||H. influenzae||Gram-negative bacilli|
|Respiratory virusesa||Legionella spp.||H. influenzae|
Anaerobes play a significant role only when an episode of aspiration has occurred days to weeks before presentation for pneumonia. The combination of an unprotected airway (e.g., in patients with alcohol or drug overdose or a seizure disorder) and significant gingivitis constitutes the major risk factor. Anaerobic pneumonias are often complicated by abscess formation and significant empyemas or parapneumonic effusions.
S. aureus pneumonia is well known to complicate influenza infection. However, MRSA has been reported as the primary etiologic agent of CAP. While this entity is still relatively uncommon, clinicians must be aware of its potentially serious consequences such as necrotizing pneumonia. Two important developments have led to this problem: the spread of MRSA from the hospital setting to the community and the emergence of genetically distinct strains of MRSA in the community. The former circumstance is more likely to result in HCAP, whereas the novel community-acquired MRSA (CA-MRSA) strains have infected healthy individuals who have had no association with health care.
Unfortunately, despite a careful history and physical examination as well as routine radiographic studies, the causative pathogen in a case of CAP is difficult to predict with any degree of certainty; in more than one-half of cases, a specific etiology is never determined. Nevertheless, epidemiologic and risk factors may suggest the involvement of certain pathogens (Table 257-3).
Table 257-3 Epidemiologic Factors Suggesting Possible Causes of Community-Acquired Pneumonia |Favorite Table|Download (.pdf)
Table 257-3 Epidemiologic Factors Suggesting Possible Causes of Community-Acquired Pneumonia
|Alcoholism||Streptococcus pneumoniae, oral anaerobes, Klebsiella pneumoniae, Acinetobacter spp., Mycobacterium tuberculosis|
|COPD and/or smoking|
Haemophilus influenzae, Pseudomonas aeruginosa, Legionella spp.,
S. pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae
|Structural lung disease (e.g., bronchiectasis)||P. aeruginosa, Burkholderia cepacia, Staphylococcus aureus|
|Dementia, stroke, decreased level of consciousness||Oral anaerobes, gram-negative enteric bacteria|
|Lung abscess||CA-MRSA, oral anaerobes, endemic fungi, M. tuberculosis, atypical mycobacteria|
|Travel to Ohio or St. Lawrence river valleys||Histoplasma capsulatum|
|Travel to southwestern United States||Hantavirus, Coccidioides spp.|
|Travel to Southeast Asia||Burkholderia pseudomallei, avian influenza virus|
|Stay in hotel or on cruise ship in previous 2 weeks||Legionella spp.|
|Local influenza activity||Influenza virus, S. pneumoniae, S. aureus|
|Exposure to bats or birds||H. capsulatum|
|Exposure to birds||Chlamydia psittaci|
|Exposure to rabbits||Francisella tularensis|
|Exposure to sheep, goats, parturient cats||Coxiella burnetii|
In the United States, ~80% of the 4 million CAP cases that occur annually are treated on an outpatient basis, and ~20% are treated in the hospital. CAP results in more than 600,000 hospitalizations, 64 million days of restricted activity, and 45,000 deaths annually. The overall yearly cost associated with CAP is estimated at $9–10 billion. The incidence rates are highest at the extremes of age. The overall annual rate in the United States is 12 cases per 1000 persons, but the figure increases to 12–18 per 1000 among children <4 years of age and to 20 per 1000 among persons >60 years of age.
The risk factors for CAP in general and for pneumococcal pneumonia in particular have implications for treatment regimens. Risk factors for CAP include alcoholism, asthma, immunosuppression, institutionalization, and an age of ≥70 years versus 60–69 years. Risk factors for pneumococcal pneumonia include dementia, seizure disorders, heart failure, cerebrovascular disease, alcoholism, tobacco smoking, chronic obstructive pulmonary disease (COPD), and HIV infection. CA-MRSA pneumonia is more likely in patients with skin colonization or infection with CA-MRSA. Enterobacteriaceae tend to infect patients who have recently been hospitalized and/or received antibiotic therapy or who have comorbidities such as alcoholism, heart failure, or renal failure. P. aeruginosa is a particular problem in patients with severe structural lung disease, such as bronchiectasis, cystic fibrosis, or severe COPD. Risk factors for Legionella infection include diabetes, hematologicmalignancy, cancer, severe renal disease, HIV infection, smoking, male gender, and a recent hotel stay or ship cruise. (Many of these risk factors would now reclassify as HCAP some cases that were previously designated CAP.)
CAP can vary from indolent to fulminant in presentation and from mild to fatal in severity. The various signs and symptoms that depend on the progression and severity of the infection include both constitutional findings and manifestations limited to the lung and associated structures. In light of the pathobiology of the disease, many of the findings are to be expected.
The patient is frequently febrile with tachycardia or may have a history of chills and/or sweats. Cough may be either nonproductive or productive of mucoid, purulent, or blood-tinged sputum. Depending on severity, the patient may be able to speak in full sentences or may be very short of breath. If the pleura is involved, the patient may experience pleuritic chest pain. Up to 20% of patients may have gastrointestinal symptoms such as nausea, vomiting, and/or diarrhea. Other symptoms may include fatigue, headache, myalgias, and arthralgias.
Findings on physical examination vary with the degree of pulmonary consolidation and the presence or absence of a significant pleural effusion. An increased respiratory rate and use of accessory muscles of respiration are common. Palpation may reveal increased or decreased tactile fremitus, and the percussion note can vary from dull to flat, reflecting underlying consolidated lung and pleural fluid, respectively. Crackles, bronchial breath sounds, and possibly a pleural friction rub may be heard on auscultation. The clinical presentation may not be so obvious in the elderly, who may initially display new-onset or worsening confusion and few other manifestations. Severely ill patients may have septic shock and evidence of organ failure.
When confronted with possible CAP, the physician must ask two questions: Is this pneumonia, and, if so, what is the likely etiology? The former question is typically answered by clinical and radiographic methods, whereas the latter requires the aid of laboratory techniques.
The differential diagnosis includes both infectious and noninfectious entities such as acute bronchitis, acute exacerbations of chronic bronchitis, heart failure, pulmonary embolism, and radiation pneumonitis. The importance of a careful history cannot be overemphasized. For example, known cardiac disease may suggest worsening pulmonary edema, while underlying carcinoma may suggest lung injury secondary to irradiation. Epidemiologic clues, such as recent travel to areas with known endemic pathogens (e.g., the U.S. southwest), may alert the physician to specific possibilities (Table 257-3).
Unfortunately, the sensitivity and specificity of the findings on physical examination are less than ideal, averaging 58% and 67%, respectively. Therefore, chest radiography is often necessary to differentiate CAP from other conditions. Radiographic findings may include risk factors for increased severity (e.g., cavitation or multilobar involvement). Occasionally, radiographic results suggest an etiologic diagnosis. For example, pneumatoceles suggest infection with S. aureus, and an upper-lobe cavitating lesion suggests tuberculosis. CT is rarely necessary but may be of value in a patient with suspected postobstructive pneumonia caused by a tumor or foreign body. For outpatients, the clinical and radiologic assessments are usually all that is done before treatment for CAP is started since most laboratory results are not available soon enough to influence initial management significantly. In certain cases, the availability of rapid point-of-care outpatient diagnostic tests can be very important (e.g., rapid diagnosis of influenza virus infection can prompt specific anti-influenza drug treatment and secondary prevention).
The etiology of pneumonia usually cannot be determined solely on the basis of clinical presentation; instead, the physician must rely upon the laboratory for support. Except for the 2% of CAP patients who are admitted to the intensive care unit (ICU), no data exist to show that treatment directed at a specific pathogen is statistically superior to empirical therapy. The benefit of establishing a microbial etiology can therefore be questioned, particularly in light of the cost of diagnostic testing. However, a number of reasons can be advanced for attempting an etiologic diagnosis. Identification of an unexpected pathogen allows narrowing of the initial empirical regimen that decreases antibiotic selection pressure, lessening the risk of resistance. Pathogens with important public safety implications such as Mycobacterium tuberculosis and influenza virus, may be found in some cases. Finally, without culture and susceptibility data, trends in resistance cannot be followed accurately, and appropriate empirical therapeutic regimens are harder to devise.
Gram's Stain and Culture of Sputum
The main purpose of the sputum Gram's stain is to ensure that a sample is suitable for culture. However, Gram's staining may also identify certain pathogens (e.g., S. pneumoniae, S. aureus, and gram-negative bacteria) by their characteristic appearance. To be adequate for culture, a sputum sample must have >25 neutrophils and <10 squamous epithelial cells per low-power field. The sensitivity and specificity of the sputum Gram's stain and culture are highly variable. Even in cases of proven bacteremic pneumococcal pneumonia, the yield of positive cultures from sputum samples is ≤50%.
Some patients, particularly elderly individuals, may not be able to produce an appropriate expectorated sputum sample. Others may already have started a course of antibiotics that can interfere with culture results at the time a sample is obtained. Inability to produce sputum can be a consequence of dehydration, and the correction of this condition may result in increased sputum production and a more obvious infiltrate on chest radiography. For patients admitted to the ICU and intubated, a deep-suction aspirate or bronchoalveolar lavage sample (obtained either via bronchoscopy or non-bronchoscopically) has a high yield on culture when sent to the microbiology laboratory as soon as possible. Since the etiologies in severe CAP are somewhat different from those in milder disease (Table 257-2), the greatest benefit of staining and culturing respiratory secretions is to alert the physician of unsuspected and/or resistant pathogens and to permit appropriate modification of therapy. Other stains and cultures (e.g., specific stains for M. tuberculosis or fungi) may be useful as well.
The yield from blood cultures, even when samples are collected before antibiotic therapy, is disappointingly low. Only ~5–14% of cultures of blood from patients hospitalized with CAP are positive, and the most frequently isolated pathogen is S. pneumoniae. Since recommended empirical regimens all provide pneumococcal coverage, a blood culture positive for this pathogen has little, if any, effect on clinical outcome. However, susceptibility data may allow narrowing of antibiotic therapy in appropriate cases. Because of the low yield and the lack of significant impact on outcome, blood cultures are no longer considered de rigueur for all hospitalized CAP patients. Certain high-risk patients—including those with neutropenia secondary to pneumonia, asplenia, or complement deficiencies; chronic liver disease; or severe CAP—should have blood cultured.
Two commercially available tests detect pneumococcal and certain Legionella antigens in urine. The test for L. pneumophila detects only serogroup 1, but this serogroup accounts for most community-acquired cases of Legionnaires' disease. The sensitivity and specificity of the Legionella urine antigen test are as high as 90% and 99%, respectively. The pneumococcal urine antigen test is also quite sensitive and specific (80% and >90%, respectively). Although false-positive results can be obtained with samples from pneumococcus-colonized children, the test is generally reliable. Both tests can detect antigen even after the initiation of appropriate antibiotic therapy. Other antigen tests include a rapid test for influenza virus and direct fluorescent antibody tests for influenza virus and respiratory syncytial virus; the latter tests are only poorly sensitive.
Polymerase Chain Reaction
Polymerase chain reaction (PCR) tests, which amplify a microorganism's DNA or RNA, are available for a number of pathogens, including L. pneumophila and mycobacteria. In addition, a multiplex PCR can detect the nucleic acid of Legionella spp., M. pneumoniae, and C. pneumoniae. However, the use of these PCR assays is generally limited to research studies. In patients with pneumococcal pneumonia, an increased bacterial load documented by PCR is associated with an increased risk of septic shock, need for mechanical ventilation, and death. Such a test could conceivably help identify patients suitable for ICU admission.
A fourfold rise in specific IgM antibody titer between acute- and convalescent-phase serum samples is generally considered diagnostic of infection with the pathogen in question. In the past, serologic tests were used to help identify atypical pathogens as well as selected unusual organisms such as Coxiella burnetii. Recently, however, they have fallen out of favor because of the time required to obtain a final result for the convalescent-phase sample.
Treatment: Community-Acquired Pneumonia
The cost of inpatient management exceeds that of outpatient treatment by a factor of 20, and hospitalization accounts for most CAP-related expenditures. Thus the decision to admit a patient with CAP to the hospital has considerable implications. Certain patients clearly can be managed at home, and others clearly require treatment in the hospital, but the choice is sometimes difficult. Tools that objectively assess the risk of adverse outcomes, including severe illness and death, can minimize unnecessary hospital admissions. There are currently two sets of criteria: the Pneumonia Severity Index (PSI), a prognostic model used to identify patients at low risk of dying; and the CURB-65 criteria, a severity-of-illness score.
To determine the PSI, points are given for 20 variables, including age, coexisting illness, and abnormal physical and laboratory findings. On the basis of the resulting score, patients are assigned to one of five classes with the following mortality rates: class 1, 0.1%; class 2, 0.6%; class 3, 2.8%; class 4, 8.2%; and class 5, 29.2%. Clinical trials demonstrate that routine use of the PSI results in lower admission rates for class 1 and class 2 patients. Patients in classes 4 and 5 should be admitted to the hospital, while those in class 3 should ideally be admitted to an observation unit until a further decision can be made.
The CURB-65 criteria include five variables: confusion (C); urea >7 mmol/L (U); respiratory rate ≥30/min (R); blood pressure, systolic ≤90 mmHg or diastolic ≤60 mmHg (B); and age ≥65 years (65). Patients with a score of 0, among whom the 30-day mortality rate is 1.5%, can be treated outside the hospital. With a score of 2, the 30-day mortality rate is 9.2%, and patients should be admitted to the hospital. Among patients with scores of ≥3, mortality rates are 22% overall; these patients may require admission to an ICU.
It is not clear which assessment tool is superior. The PSI is less practical in a busy emergency room setting because of the need to assess 20 variables. While the CURB-65 criteria are easily remembered, they have not been studied as extensively. Whichever system is used, these objective criteria must always be tempered by careful consideration of factors relevant to individual patients, including the ability to comply reliably with an oral antibiotic regimen and the resources available to the patient outside the hospital. In fact, neither the PSI nor CURB-65 is ideal for determining the need for ICU care. The severity criteria proposed by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in their guidelines for the management of CAP are better suited to this purpose.
Antimicrobial resistance is a significant problem that threatens to diminish our therapeutic armamentarium. Misuse of antibiotics results in increased antibiotic selection pressure that can affect resistance locally or even globally by clonal dissemination. For CAP, the main resistance issues currently involve S. pneumoniae and CA-MRSA.
In general, pneumococcal resistance is acquired (1) by direct DNA incorporation and remodeling resulting from contact with closely related oral commensal bacteria, (2) by the process of natural transformation, or (3) by mutation of certain genes.
The cutoff for penicillin susceptibility in pneumonia has recently been raised from a minimal inhibitory concentration (MIC) of ≤0.6 μg/mL to an MIC of ≤2 μg/mL. Cutoffs for intermediate resistance have been raised to 4 μg/mL (from 0.1–1 μg/mL) and ≥8 μg/mL (from ≥2 μg/mL), respectively. These changes in susceptibility thresholds have resulted in a dramatic decrease in the proportion of pneumococcal isolates considered nonsusceptible. For meningitis, MIC thresholds remain at the former levels. Fortunately, resistance to penicillin appeared to plateau even before the change in MIC thresholds. Pneumococcal resistance to β-lactam drugs is due solely to low-affinity penicillin-binding proteins. Risk factors for penicillin-resistant pneumococcal infection include recent antimicrobial therapy, an age of <2 years or >65 years, attendance at day-care centers, recent hospitalization, and HIV infection.
In contrast to penicillin resistance, resistance to macrolides is increasing through several mechanisms. Target-site modification is caused by ribosomal methylation in 23S rRNA encoded by the ermB gene, resulting in resistance to macrolides, lincosamides, and streptogramin B–type antibiotics. This MLSb phenotype is associated with high-level resistance, with typical MICs of ≥64 μg/mL. The efflux mechanism encoded by the mef gene (M phenotype) is usually associated with low-level resistance (MICs, 1–32 μg/mL). These two mechanisms account for ~45% and ~65%, respectively, of resistant pneumococcal isolates in the United States. High-level resistance to macrolides is more common in Europe, whereas lower-level resistance seems to predominate in North America. Although clinical failures with macrolides have been reported, many experts think that these drugs still have a role to play in the management of pneumococcal pneumonia in North America.
Pneumococcal resistance to fluoroquinolones (e.g., ciprofloxacin and levofloxacin) has been reported. Changes can occur in one or both target sites (topoisomerases II and IV); changes in these two sites usually result from mutations in the gyrA and parC genes, respectively. The increasing number of pneumococcal isolates that, although still testing susceptible to fluoroquinolones, already have a mutation in one target site is of concern. Such organisms may be more likely to undergo a second step mutation that will render them fully resistant to fluoroquinolones. In addition, an efflux pump may play a role in pneumococcal resistance to fluoroquinolones.
Isolates resistant to drugs from three or more antimicrobial classes with different mechanisms of action are considered MDR. The propensity for an association of pneumococcal resistance to penicillin with reduced susceptibility to other drugs such as macrolides, tetracyclines, and trimethoprim-sulfamethoxazole, is also of concern. In the United States, 58.9% of penicillin-resistant pneumococcal isolates from blood are also resistant to macrolides.
The most important risk factor for antibiotic-resistant pneumococcal infection is use of a specific antibiotic within the previous 3 months. Therefore, a patient's history of prior antibiotic treatment is a critical factor in avoiding the use of an inappropriate antibiotic.
CAP due to MRSA may be caused by infection with the classic hospital-acquired strains or with the more recently identified, genotypically and phenotypically distinct community-acquired strains. Most infections with the former strains have been acquired either directly or indirectly by contact with the health care environment and would now be classified as HCAP. In some hospitals, CA-MRSA strains are displacing the classic hospital-acquired strains—a trend suggesting that the newer strains may be more robust.
Methicillin resistance in S. aureus is determined by the mecA gene, which encodes for resistance to all β-lactam drugs. At least five staphylococcal chromosomal cassette mec (SCCmec) types have been described. The typical hospital-acquired strain usually has type II or III, whereas CA-MRSA has a type IV SCCmec element. CA-MRSA isolates tend to be less resistant than the older hospital-acquired strains and are often susceptible to trimethoprim-sulfamethoxazole, clindamycin, and tetracycline in addition to vancomycin and linezolid. However, CA-MRSA strains may also carry genes for superantigens, such as enterotoxins B and C and Panton-Valentine leukocidin, a membrane-tropic toxin that can create cytolytic pores in polymorphonuclear neutrophils, monocytes, and macrophages.
A detailed discussion of resistance among gram-negative bacilli is beyond the scope of this chapter (see Chap. 149). Fluoroquinolone resistance among isolates of Escherichia coli from the community appears to be increasing. Enterobacter spp. are typically resistant to cephalosporins; the drugs of choice for use against these bacteria are usually fluoroquinolones or carbapenems. Similarly, when infections due to bacteria producing extended-spectrum β-lactamases are documented or suspected, a fluoroquinolone or a carbapenem should be used; these MDR strains are more likely to be involved in HCAP.
Initial Antibiotic Management
Since the physician rarely knows the etiology of CAP at the outset of treatment, initial therapy is usually empirical and is designed to cover the most likely pathogens (Table 257-4). In all cases, antibiotic treatment should be initiated as expeditiously as possible. The CAP treatment guidelines in the United States (summarized in Table 257-4) represent joint statements from the IDSA and the ATS; the Canadian guidelines come from the Canadian Infectious Disease Society and the Canadian Thoracic Society. In these guidelines, coverage is always provided for the pneumococcus and the atypical pathogens. In contrast, guidelines from some European countries do not always include atypical coverage based on local epidemiologic data. The U.S.–Canadian approach is supported by retrospective data from several studies of administrative databases including thousands of patients. Atypical pathogen coverage provided by the addition of a macrolide to a cephalosporin or by the use of a fluoroquinolone alone has been consistently associated with a significant reduction in mortality rates compared with those for β-lactam coverage alone.
Table 257-4 Empirical Antibiotic Treatment of Community-Acquired Pneumonia |Favorite Table|Download (.pdf)
Table 257-4 Empirical Antibiotic Treatment of Community-Acquired Pneumonia
|Previously healthy and no antibiotics in past 3 months|
|• A macrolide [clarithromycin (500 mg PO bid) or azithromycin (500 mg PO once, then 250 mg qd)] or|
|• Doxycycline (100 mg PO bid)|
|Comorbidities or antibiotics in past 3 months: select an alternative from a different class|
|• A respiratory fluoroquinolone [moxifloxacin (400 mg PO qd), gemifloxacin (320 mg PO qd), levofloxacin (750 mg PO qd)] or|
|• A β-lactam [preferred: high-dose amoxicillin (1 g tid) or amoxicillin/clavulanate (2 g bid); alternatives: ceftriaxone (1–2 g IV qd), cefpodoxime (200 mg PO bid), cefuroxime (500 mg PO bid)] plus a macrolidea|
|In regions with a high rate of "high-level" pneumococcal macrolide resistance,b consider alternatives listed above for patients with comorbidities.|
|• A respiratory fluoroquinolone [moxifloxacin (400 mg PO or IV qd), gemifloxacin (320 mg PO qd), levofloxacin (750 mg PO or IV qd)]|
|• A β-lactamc [cefotaxime (1–2 g IV q8h), ceftriaxone (1–2 g IV qd), ampicillin (1–2 g IV q4–6h), ertapenem (1 g IV qd in selected patients)] plus a macrolided [oral clarithromycin or azithromycin (as listed above for previously healthy patients) or IV azithromycin (1 g once, then 500 mg qd)]|
|• A β-lactame [cefotaxime (1–2 g IV q8h), ceftriaxone (2 g IV qd), ampicillin-sulbactam (2 g IV q8h)] plus|
|• Azithromycin or a fluoroquinolone (as listed above for inpatients, non-ICU)|
|If Pseudomonas is a consideration|
|• An antipneumococcal, antipseudomonal β-lactam [piperacillin/tazobactam (4.5 g IV q6h), cefepime (1–2 g IV q12h), imipenem (500 mg IV q6h), meropenem (1 g IV q8h)] plus either ciprofloxacin (400 mg IV q12h) or levofloxacin (750 mg IV qd)|
|• The above β-lactams plus an aminoglycoside [amikacin (15 mg/kg qd) or tobramycin (1.7 mg/kg qd) and azithromycin]|
|• The above β-lactamsf plus an aminoglycoside plus an antipneumococcal fluoroquinolone|
|If CA-MRSA is a consideration|
|• Add linezolid (600 mg IV q12h) or vancomycin (1 g IV q12h).|
Therapy with a macrolide or a fluoroquinolone within the previous 3 months is associated with an increased likelihood of infection with a resistant strain of S. pneumoniae. For this reason, a fluoroquinolone-based regimen should be used for patients recently given a macrolide, and vice versa (Table 257-4).
Once the etiologic agent(s) and susceptibilities are known, therapy may be altered to target the specific pathogen(s). However, this decision is not always straightforward. If blood cultures yield S. pneumoniae sensitive to penicillin after 2 days of treatment with a macrolide plus a β-lactam or with a fluoroquinolone alone, should therapy be switched to penicillin alone? The concern here is that a β-lactam alone would not be effective in the potential 15% of cases with atypical co-infection. No standard approach exists. In all cases, the individual patient and the various risk factors must be considered.
Management of bacteremic pneumococcal pneumonia is also controversial. Data from nonrandomized studies suggest that combination therapy (especially with a macrolide and a β-lactam) is associated with a lower mortality rate than monotherapy, particularly in severely ill patients. The exact reason is unknown, but possible explanations include an additive or synergistic antibacterial effect, antimicrobial tolerance, atypical co-infection, or the immunomodulatory effects of the macrolides.
For patients with CAP who are admitted to the ICU, the risk of infection with P. aeruginosa or CA-MRSA is increased, and coverage should be considered when a patient has risk factors or a Gram's stain suggestive of these pathogens (Table 257-4). If CA-MRSA infection is suspected, either linezolid or vancomycin should be added to the initial empirical regimen. There is concern about vancomycin's loss of potency against MRSA; in addition, vancomycin does not reach significant concentrations in epithelial lining fluid, whereas concentrations of linezolid at this site exceed the MIC for MRSA during the entire dosing interval.
Although hospitalized patients have traditionally received initial therapy by the IV route, some drugs—particularly the fluoroquinolones—are very well absorbed and can be given orally from the outset to select patients. For patients initially treated IV, a switch to oral treatment is appropriate as long as the patient can ingest and absorb the drugs, is hemodynamically stable, and is showing clinical improvement.
The duration of treatment for CAP has generated considerable interest. Patients were previously treated for 10–14 days, but studies with fluoroquinolones and telithromycin suggest that a 5-day course is sufficient for otherwise uncomplicated CAP. Even a single dose of ceftriaxone has been associated with a significant cure rate. A longer course is required for patients with bacteremia, metastatic infection, or infection with a virulent pathogen such as P. aeruginosa or CA-MRSA.
In addition to appropriate antimicrobial therapy, certain general considerations apply in dealing with CAP, HCAP, or HAP/VAP. Adequate hydration, oxygen therapy for hypoxemia, and assisted ventilation when necessary are critical to the success of therapy. Patients with severe CAP who remain hypotensive despite fluid resuscitation may have adrenal insufficiency and may respond to glucocorticoid treatment. Immunomodulatory therapy in the form of drotrecogin alfa (activated) should be considered for CAP patients with persistent septic shock and APACHE II scores of ≥25, particularly if the infection is caused by S. pneumoniae. The value of other forms of adjunctive therapy, including glucocorticoids, statins, and angiotensin-converting enzyme inhibitors, remains unproven in the management of CAP.
Patients who are slow to respond to therapy should be reevaluated at about day 3 (sooner if their condition is worsening rather than simply not improving), and a number of possible scenarios should be considered. A number of noninfectious conditions can mimic pneumonia, including pulmonary edema, pulmonary embolism, lung carcinoma, radiation and hypersensitivity pneumonitis, and connective tissue disease involving the lungs. If the patient has CAP and treatment is aimed at the correct pathogen, the lack of response may be explained in a number of ways. The pathogen may be resistant to the drug selected, or a sequestered focus (e.g., a lung abscess or empyema) may be blocking access of the antibiotic(s) to the pathogen. The patient may be getting either the wrong drug or the correct drug at the wrong dose or frequency of administration. It is also possible that CAP is the correct diagnosis but that an unsuspected pathogen (e.g., CA-MRSA, M. tuberculosis, or a fungus) is the cause. Nosocomial superinfections—both pulmonary and extrapulmonary—are possible explanations for failure to improve or worsening. In all cases of delayed response or deteriorating condition, the patient must be carefully reassessed and appropriate studies initiated. These studies may include such diverse procedures as CT and bronchoscopy.
As in other severe infections, common complications of severe CAP include respiratory failure, shock and multiorgan failure, coagulopathy, and exacerbation of comorbid illnesses. Three particularly noteworthy conditions are metastatic infection, lung abscess, and complicated pleural effusion. Metastatic infection (e.g., brain abscess or endocarditis), although unusual, deserves immediate attention by the physician, with a detailed workup and proper treatment. Lung abscess may occur in association with aspiration or with infection caused by a single CAP pathogen such as CA-MRSA, P. aeruginosa, or (rarely) S. pneumoniae. Aspiration pneumonia is typically a mixed polymicrobial infection involving both aerobes and anaerobes. In either scenario, drainage should be established, and antibiotics that cover the known or suspected pathogens should be administered. A significant pleural effusion should be tapped for both diagnostic and therapeutic purposes. If the fluid has a pH of <7, a glucose level of <2.2 mmol/L, and a lactate dehydrogenase concentration of >1000 U/L or if bacteria are seen or cultured, then the fluid should be drained; a chest tube is usually required.
Fever and leukocytosis usually resolve within 2–4 days in otherwise healthy patients with CAP, but physical findings may persist longer. Chest radiographic abnormalities are slowest to resolve and may require 4–12 weeks to clear, with the speed of clearance depending on the patient's age and underlying lung disease. Patients may be discharged from the hospital once their clinical conditions are stable, with no active medical problems requiring hospital care. The site of residence after discharge (nursing home, home with family, home alone) is an important consideration, particularly for elderly patients. For a patient whose condition is improving and who (if hospitalized) has been discharged, a follow-up radiograph can be done ~4–6 weeks later. If relapse or recurrence is documented, particularly in the same lung segment, the possibility of an underlying neoplasm must be considered.
The prognosis of CAP depends on the patient's age, comorbidities, and site of treatment (inpatient or outpatient). Young patients without comorbidity do well and usually recover fully after ~2 weeks. Older patients and those with comorbid conditions can take several weeks longer to recover fully. The overall mortality rate for the outpatient group is <1%. For patients requiring hospitalization, the overall mortality rate is estimated at 10%, with ~50% of deaths directly attributable to pneumonia.
The main preventive measure is vaccination. The recommendations of the Advisory Committee on Immunization Practices should be followed for influenza and pneumococcal vaccines. In the event of an influenza outbreak, unprotected patients at risk from complications should be vaccinated immediately and given chemoprophylaxis with either oseltamivir or zanamivir for 2 weeks—i.e., until vaccine-induced antibody levels are sufficiently high. Because of an increased risk of pneumococcal infection, even among patients without obstructive lung disease, smokers should be strongly encouraged to stop smoking.
An available 7-valent pneumococcal conjugate vaccine produces T cell–dependent antigens that result in long-term immunologic memory. Administration of this vaccine to children has led to an overall decrease in the prevalence of antimicrobial-resistant pneumococci and in the incidence of invasive pneumococcal disease among both children and adults. However, vaccination can be followed by the replacement of vaccine serotypes with nonvaccine serotypes (e.g., 19A and 35B).