Affiliations: Memphis, TN
Dr. Wunderink is Director of Clinical Research and Dr. Waterer is Pulmonary Host Defense Fellow at Methodist Le Bonheur Healthcare. Dr. Waterer has been supported by the Methodist Le Bonheur Healthcare Foundation and the Athelstan and Amy Saw Medical Research Fellowship from the University of Western Australia.
Correspondence to: Richard G. Wunderink, MD, FCCP, Methodist Le Bonheur Healthcare, 1265 Union Ave, 501 Crews Wing, Memphis, TN 38104-2499; e-mail: wunderiR@methodisthealth.org
The appropriate microbiological investigation of the
patient admitted with community-acquired pneumonia (CAP) remains a
contentious issue. Several arguments favor microbiological
investigation. First, the pathogen identified may be resistant to the
chosen empiric antibiotic therapy. Second, identification of the
pathogen may allow streamlining of antibiotic therapy, thereby reducing
cost and possibly reducing the development of antibiotic resistance.
Third, accurate epidemiologic data are required in order to design
appropriate empiric therapy.
The countering arguments are that the currently available tests have
insufficient sensitivity to significantly influence the choice of
antibiotic therapy. Differences in the availability of microbiological
resources and expertise at individual institutions, as well as local
differences in microbiological etiology of CAP, significantly impact
the yield of common tests, such as sputum Gram’s staining.
Evidence that identifying a pathogen improves outcome in patients with
CAP is also lacking. Two studies of CAP have shown that infection with
an organism subsequently shown to be resistant to initial empiric
antibiotic therapy is an independent predictor of poor
outcome.1–2 However, when change is required due to
antibiotic failure, culture-based changes do not necessarily result in
better outcomes than does an empiric, non-culture-directed change in
therapy.3It may be argued that knowledge of a probable
pneumococcal infection is reassuring if a patient is not responding to
therapy several days later. However, in a recent study4 of
patients with CAP who were not responding to empiric therapy, secondary
nosocomial infection was not only the second most common cause, but the
only one independently associated with fatal outcomes. Knowledge of the
likely pathogen is, therefore, not necessarily helpful in managing
patients who are not responding to initial therapy.
The ability to streamline antibiotic therapy is also questionable. As
all current guidelines for empiric therapy of CAP
recognize,5–6 pneumococcal infection must be covered in
the choice of initial antibiotic therapy. Recognition of probable
pneumococcal infection on a sputum Gram’s stain or urinary antigen
test is therefore unlikely to alter a physician’s choice of antibiotic
therapy, particularly in regions with a significant incidence of
penicillin resistance. Even positive results of blood cultures do not
lead routinely to narrowing of the choice of antibiotic
therapy.7Given the increased recognition of
polymicrobial CAP (up to one third to one half of patients in some
regions),8–10 and some suggestion of improved outcome
with combination therapy of bacteremic pneumococcal CAP,11
the reluctance to switch to narrow-spectrum monotherapy may be
Accurate etiologic information to design appropriate empiric therapy
for patients with CAP is clearly needed. However, given the low yields
of investigations in patients with mild-to-moderate CAP, obtaining this
information in an ad hoc fashion has significant risks.
Since invasive pneumococcal isolates are significantly less likely to
be drug resistant than noninvasive specimens,12 reliance
on blood cultures alone would underestimate the true prevalence of
antibiotic resistance. If information were obtained only from blood and
sputum cultures, atypical pathogens would only rarely be identified,
skewing information regarding causative etiologies. Only with a
comprehensive microbiological survey, using all available diagnostic
techniques, can accurate etiologic data be obtained. This is clearly
too expensive and difficult to do on a routine basis, and a more
practical approach would be to use periodic comprehensive surveys.
In an ideal world, clinicians would always prefer to know the causative
organism and antibiotic sensitivity for patients with CAP, even if the
diagnostic yield of an individual test is low. However, in today’s
cost-conscious health-care environmental, the expense for that
reassurance may be excessive. For example, Chalasani et
al13 found that $34,000 was spent on blood cultures for
seven patients with a blood culture-directed change in therapy.
However, the current diagnosis-related group-based reimbursement
does recognize the importance of identifying a pathogen by providing a
financial incentive to do so, partially offsetting the cost of
So should diagnostic testing in patients with CAP be completely
abandoned or left only to certain institutions? The article in this
issue of CHEST by Theerthakarai and colleagues (see page
181) provides data to support a compromise position. They
demonstrated low yields of sputum Gram’s stain, sputum culture, and
blood culture in patients with mild CAP based on the pneumonia severity
index of Fine et al.14 Even the most ardent supporters of
aggressive diagnosis in patients with CAP do not recommend diagnostic
testing in outpatients with CAP. This study supports extending that
recommendation to hospitalized CAP patients whose severity indices
would suggest that they could have been managed as outpatients without
the social factors, age, or other concerns that led to inpatient
Conversely, in studies focused on patients with severe CAP, the yield
of standard microbiological techniques is substantially higher. This is
particularly true of the yield from blood cultures, a reflection of
bacteremia as an independent predictor of worse outcome from
CAP.15 Given the much greater risk of adverse outcome in
patients with severe CAP, and the much greater likelihood of positive
results, more aggressive investigation in patients with severe CAP
seems prudent. Investigation of patients with specific risk factors for
drug-resistant pathogens, such as those who received the frequent
antibiotics for bronchiectasis or chronic bronchitis,2,16
also would seem to be appropriate.
In addition to stratification by severity, the degree of diagnostic
workup should also be proportional to the type of empiric therapy. Most
recommended empiric regimens suggest coverage for the possibilities of
penicillin-resistant Streptococcus pneumoniae and
Legionella.5–6 If the empiric antibiotics do not cover
these microorganisms, a more aggressive diagnostic workup also may be
warranted, especially in patients with severe CAP. An aggressive
diagnostic approach to patients who either have nonresponding or
progressive CAP is also likely to be a high-yield exercise. Arancibia
et al4 recently have demonstrated that a definite etiology
could be established in 65% of these patients. In particular,
antibiotic-resistant microorganisms in patients with nonresponding
pneumonia and nosocomial superinfection in patients with progressive
pneumonia could frequently be documented.
Obtaining sputum and/or blood cultures should clearly not be used as a
marker of quality of care in patients with CAP, as suggested by some
external review agencies. Insistence on obtaining sputum or blood
cultures prior to the initiation of antibiotic therapy may conflict
directly with an emphasis on avoiding delay in providing the first dose
of an antibiotic, a quality-of-care issue that has been demonstrated to
Recommendations against routine diagnostic testing are based on the
lack of sensitivity of and the turnaround time of the currently
available tests. Newer diagnostic tools, such as the detection of
microbial DNA using a variety of polymerase chain reaction (PCR)-based
techniques, show considerable promise. The ability to rapidly screen
not only for pathogens but also for antibiotic resistance either with
PCR or other molecular diagnostic techniques could substantially alter
our approach to the management of patients with CAP in the future.
Until then, the stratification of the diagnostic workup by severity,
patient characteristics, and anticipated empiric antibiotic therapy is
likely to lead to the most cost-effective overall care of patients with
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