Abstract: The use of sputum studies and blood cultures in patients hospitalized with community-acquired pneumonia (CAP) is somewhat controversial, and recommendations continue to evolve. A reasonable approach is to attempt to obtain sputum cultures from all patients before initiating antibiotic therapy. If antibiotics have already been given, sputum studies can be reserved for patients who are severely ill or who are at risk for infection with a resistant organism or an organism that is not covered by the usual empiric therapy. The Infectious Diseases Society of America and the American Thoracic Society both recommend obtaining blood cultures from all patients. However, cost considerations have led to alternative strategies, such as reserving blood cultures for those with severe CAP. (J Respir Dis. 2005;26(4):143-148)
At least 1 million adults are admitted to the hospital with community-acquired pneumonia (CAP) each year in the United States.1 In the past, standard practice was to obtain blood cultures and sputum cultures (if possible) from all these patients. Several factors make it important to explore the implications of this practice, including the performance characteristics of the culture techniques. Specifically, how often do sputum studies and blood cultures yield an organism, how often does the result reflect the infecting organism, and what are the consequences of a false-positive result?
Another important factor is the availability of newer broad-spectrum antibiotics that allow effective empiric coverage of the most common pathogens associated with CAP. Finally, the response of physicians to culture results is an important determinant of the clinical usefulness of obtaining cultures. If physicians rarely change antibiotic therapy in response to the results, the potential benefits of cultures are not being realized.
In this article, I will review the performance characteristics of sputum studies, blood cultures, and other diagnostic techniques. I will then present my recommendations for the use of these methods in patients with CAP.
Although the use of Gram stain and culture of expectorated sputum has been the mainstay of CAP diagnosis for more than 100 years, the benefits of sputum studies have been controversial for decades. The initial limitation is that approximately 50% of patients do not produce an adequate sample, defined as fewer than 10 squamous cells per low-power field.
Unfortunately, this problem is exacerbated by how patients are approached. Patients are more likely to produce an adequate sample when appropriately instructed by a physician about what is being asked and why. Despite these limitations, when a sputum sample has more than 25 polymorphonuclear cells per low-power field and there is a predominant organism, the causative organism is identified in more than 80% of cases.2,3 However, a predominant organism is often not visualized, so when these criteria are used, the sensitivity drops to under 50%.
The experience of the interpreter is also a factor. Less skilled interpreters more commonly miss Gram-negative organisms in the pink background of the cellular material and more often falsely identify Gram-positive oral flora as Streptococcus pneumoniae.
The interpretation of the sputum culture yields another set of problems. For samples that are adequately handled, the sensitivity is approximately 75%.4 However, this yield will not be realized if the sputum sample is obtained after the initiation of antibiotic therapy or if there is a delay in plating the sputum sample.
In addition, because of the possibility of culturing bacteria that colonize the oropharynx, false-positive results may occur. This is especially true for debilitated patients who are more likely to be colonized with pathogens. Therefore, culture results may not be reliable unless they are derived from an adequate sputum sample and they correlate with what was visualized on the Gram stain.
Certain organisms are always pathogenic and can be assumed to be causing disease if they are identified. These include Legionella species, Mycobacterium tuberculosis, and the endemic fungi.
About 7% to 10% of patients admitted to the hospital with CAP will have a pathogen cultured from their blood. In essentially all studies, the predominant organism associated with bacteremia is S pneumoniae;Staphylococcus aureus and enteric Gram-negative bacilli are the next most frequently cultured organisms.
Not all patients are at equal risk for bacteremia. Studies have demonstrated that low-risk patients, as defined by the pneumonia severity index (PSI) I-III and other criteria, are less likely to have bacteremia.5,6 However, one study demonstrated that a few specific clinical factors encompassed by the PSI can be used to define much more accurately the risk of bacteremia (Tables 1 and 2).7
Despite the definitive information that can be obtained from blood cultures, several factors affect their usefulness. The yield drops by about 50% if blood cultures are obtained after antibiotic therapy is given (whether therapy is provided before the patient arrives at the hospital or as a single dose of an antibiotic in the emergency department [ED]).7
Another important factor is that contamination with skin flora, usually coagulase-negative Staphylococcus, results in an approximately 5% frequency of false-positive results. Compared with negative blood cultures, a false-positive blood culture is independently associated with a 3-fold greater rate of vancomycin use and about a 1-day increase in risk-adjusted hospital length of stay. Thus, it becomes clear that obtaining blood cultures from patients who are at low risk for either bacteremia or mortality has limited benefits but truly negative consequences.7
A number of immunologic methods have long been used to identify pathogens in patients with CAP. There is essentially no role for the use of antibody titers in the clinical care of these patients. A high level of IgM can occasionally identify an atypical pathogen. However, the low sensitivity and specificity, combined with the increasing tendency to provide empiric treatment for infections caused by atypical pathogens, limit the usefulness of these tests. Acute and convalescent IgG titers become available too late to be clinically useful.
In contrast, the Legionella urinary antigen is approximately 80% sensitive and highly specific for Legionella pneumophila serogroup 1, which causes most cases of Legionella pneumonia.8 The pneumococcal urinary antigen test has a sensitivity for pneumococcal pneumonia of approximately 70%; it has a very low frequency of false-positive results,9 although false-positive results have been noted in healthy patients with nasopharyngeal carriage of pneumococci.
For the vast majority of patients with CAP, there is no need for bronchoscopy. The list of likely pathogens is small, and empiric antibiotic coverage is usually successful. Clinical failures are generally related to the severity of illness and underlying comorbidities.
However, several clinical scenarios indicate the potential need for bronchoscopy. The most common indication is immunosuppression. Early bronchoscopy is not usually needed if the clinical presentation or a sputum result suggests bacterial pneumonia. However, bronchoscopy is usually indicated if the presentation suggests an opportunistic infection or if the patient does not respond to empiric antibacterial therapy and a diagnostic sputum sample cannot be obtained. This situation is common, since sputum samples are rarely diagnostic for common opportunistic pathogens, such as Pneumocystis carinii and Aspergillus species, with the exception of P carinii in AIDS.
Clinicians are often tempted to use invasive sampling methods in patients with CAP who have early respiratory failure. However, in most of these patients, a good-quality suctioned endotracheal sputum sample can readily be obtained. One interesting study demonstrated that with the use of blind nonbronchoscopic lavage, a pathogen was identified in 10 (83%) of 12 patients with CAP who were intubated in the ED. This success was probably related to the ability to perform the procedure before antibiotics were given.10
The role of bronchoscopy has also been investigated in patients with "nonresponding pneumonia," defined as lack of improvement or worsening despite 7 days of therapy.11 In one study, approximately two thirds of such patients had no diagnosis established despite bronchoscopy, but they improved with empiric therapy.11
Bronchoscopy with transbronchial biopsy yielded a diagnosis in more than 80% of the remaining patients in this study, demonstrating either an unusual infection, such as Cytomegalovirusinfection, actinomycosis, or tuberculosis, or a noninfectious imitator of pneumonia, such as malignancy or eosinophilic pneumonia.11
In contrast, early bronchoscopy has generally not been as useful for patients who are already receiving therapy for CAP but whose condition is deteriorating.
The current Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) guidelines have conflicting recommendations regarding sputum studies.12,13 The IDSA recommends these studies for all patients,12 while the ATS recommends sputum studies "if a drug-resistant pathogen or an organism not covered by usual empiric therapy is suspected."13 The ATS, citing the potential inaccuracy of sputum studies, further recommends that results of these studies never be used to narrow antibiotic therapy, but that they should be used to broaden therapy if an unsuspected pathogen is identified.13
When considering these differing recommendations, remember that antibiotic-resistant organisms are widely present and that most patients admitted to the hospital with CAP have comorbidities and are therefore at risk for either antibiotic resistance or infection caused by less common organisms not covered by the usual empiric regimens. My practice is to attempt to obtain sputum samples from all patients admitted to the hospital with CAP before antibiotics are given. If antibiotics have already been given, I generally request sputum studies only for more severely ill patients or those who are at risk for infection with organisms not covered by the usual empiric therapy (methicillin-resistant S aureus and Pseudomonas species). Given the association between delayed antibiotic therapy and increased mortality, antibiotic therapy should not be unduly delayed to obtain a sputum sample.
While sputum studies often do not contribute to patient management decisions, they are inexpensive and, unlike blood cultures, there is little evidence that misinterpreted results regularly lead to prolonged hospitalization or inappropriate antibiotic treatment. The ATS recommendation against narrowing antibiotic coverage on the basis of the sputum Gram stain is appropriate as a rule of thumb, but clinicians who are skilled in interpreting Gram stains occasionally encounter one that leaves no doubt as to the infecting organism--in such cases, they can safely focus the antibiotic coverage on that particular organism.
The current IDSA and ATS guidelines recommend obtaining blood cultures from all CAP patients admitted to the hospital.12,13 However, the cost associated with blood cultures has prompted consideration of strategies to limit their use to patients who are more likely to benefit. One suggestion has been to perform blood cultures only on patients in PSI class IV or V.6
An alternative suggestion is to obtain only 1 blood culture from patients at low risk for bacteremia.7 The rationale for this strategy is that using 1 instead of 2 blood cultures decreases the sensitivity for bacteremia by only 20%, but decreases the chance of a false-positive result by 50%. Since none of the organisms that contaminate blood cultures cause pneumonia, there is no danger that a contaminant in a single blood culture could mistakenly be identified as the cause of pneumonia.
Recognizing the costs associated with obtaining 2 sets of blood cultures from all hospitalized patients with CAP, the current ATS-IDSA guideline working group is planning to recommend blood cultures only for patients with severe CAP. It is, therefore, unlikely that the Centers for Medicare & Medicaid Services quality indicator for blood cultures will also change.
Regardless of the method chosen to target higher-risk patients, it is clear that blood cultures are valuable only if physicians appropriately act on the results. Studies have shown that physicians often ignore positive blood culture results and sometimes paradoxically broaden coverage when bacteremia is identified.
In a patient who is clinically improving, a preliminary report of Gram-positive cocci in clus- ters (suggestive of Staphylococcus species) should not prompt a switch to vancomycin, because it probably represents contamination with nonpathogenic coagulase-negative staphylococci. Similarly, the finding of S pneumoniae often allows narrower antibiotic coverage.
Recommendations regarding the use of microbiologic testing in patients admitted to the hospital with CAP are in flux (Table 3). There is currently greater appreciation for the costs of the indiscriminate use of blood cultures, which has prompted recommendations that blood cultures be performed preferentially in high-risk patients. The use of sputum studies remains controversial, but most experts agree that such studies should be done in patients at high risk for infection with unusual or resistant organisms (Table 4). For all cultures, the optimal benefits can be realized only when specimens are obtained before antibiotic therapy is initiated and when the results of cultures are appropriately acted on.
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