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17 Tan MJ, Tan JS, Hamor R, et al. The radiologic manifestations of Legionnaire’s disease: the Ohio Community-Based
Pneumonia Incidence Study Group. Chest 2000; 117:398 –
403
18 Roig J, Martinez-Benazet J, Salvador J. Radiologic features of
legionellosis. Curr Topics Radiol 1998; 1:101–105
19 Kroboth FJ, Yu VL, Reddy S, et al. Clinicoradiographic
correlations with the extent of Legionnaires disease. AJR
Am J Roentgenol 1983; 141:263–268
20 Dietrich P, Johnson R, Fairbank J, et al. The chest radiograph
in Legionnaires disease. Radiology 1978; 127:577–582
21 Lieberman D, Porath A, Schlaeffer F, et al. Legionella
species in community-acquired pneumonia: a review of 56
hospitalized adult patients. Chest 1996; 109:1243–1249
22 Sopena N, Sabria-Leal M, Pedro-Botet ML, et al. Comparative study of the clinical presentation of Legionella pneumonia and other community-acquired pneumonias. Chest 1998;
113:1195–1200
23 Muder RR, Yu VL, Parry M. Radiology of Legionella pneumonia. Semin Respir Infect 1987; 2:242–254
24 Woodhead MA, MacFarlane JT. Comparative clinical and
laboratory features of Legionella with pneumococcal and
mycoplasma pneumonias. Br J Dis Chest 1987; 81:133–139
25 Olaechea PM, Quintana MM, Gallardo MS, et al. A predictive model for the treatment approach to community-acquired pneumonia in patients needing ICU admission. Intensive Care Med 1996; 22:1294 –1300
26 Ostergaard L, Andersen PL. Etiology of community-acquired
pneumonia: evaluation by transtracheal aspiration, blood
culture, or serology. Chest 1993; 104:1400 –1407
27 Mundy LM, Oldach D, Auwaerter PG, et al. Implications for
macrolide treatment in community-acquired pneumonia.
Chest 1998; 113:1201–1206
28 Fang GD, Fine M, Orloff J, et al. New and emerging
etiologies for community-acquired pneumonia with implications for therapy: a prospective multicenter study of 359
cases. Medicine (Baltimore) 1990; 69:307–316
29 Roig J, Rello J, Yu VL. Legionnaires disease. J Respir Dis
2001 (in press)
30 Keller DW, Lipman HB, Marston BJ, et al. Clinical diagnosis
of Legionnaires disease using a multivariate model. In:
Proceedings of the 35th Interscience Conference of Antimicrobial Agents and Chemotherapy; September 17–20, 1995;
San Francisco, CA
31 Blatter M, Frei R, Widmer AI. Clinical predictors for cultureproven L. pneumophila pneumonia: a matched case control
study. Paper presented at: the European Congress of Clinical
Microbiology and Infectious Diseases, Lausanne, Switzerland, 1997
32 Niederman M, Mandell LA. Guidelines for the initial management of adults with community-acquired respiratory infections: diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 2001;
163:1730 –1754
33 Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines
for management of community-acquired pneumonia. Clin
Infect Dis 2000; 31:347–382
34 Vergis EN, Yu VL. New directions for future studies of
community-acquired pneumonia optimising impact on patient care. Eur J Clin Microbiol Infect Dis 1999; 18:847– 851
35 The Canadian Community-Acquired Pneumonia Working
Group. Canadian guidelines for the initial management of
community-acquired pneumonia: an evidence-based update
by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin Infect Dis 2000; 31:383– 421
Severe Community-Acquired
Pneumonia
The Need To Customize Empiric
Therapy
ven with extensive diagnostic regimens, most
E studies
of community-acquired pneumonia (CAP)
fail to determine the etiology in ⱖ 50% of cases. In
usual clinical practice, the diagnostic rate is closer to
15%, which results in most patients with CAP receiving an empiric antibiotic regimen rather than
individualized therapy. The choice of empiric antibiotic agents is often guided by consensus guidelines.1,2 These guidelines are in turn based on covering the majority of pathogens identified in
published findings from groups of patients with
CAP.
Empiric therapy that does not cover the infecting
pathogen is an independent predictor of poor outcome,3–5 and patients with subsequent changes in
antibiotic therapy based on culture results still have
a significant mortality.6,7 The adverse implications
for inadequate empiric therapy make it imperative
that the antibiotic regimen chosen has as few “holes”
as possible, especially in patients with severe CAP,
where the mortality is ⱖ 20%. As the study by Chen
and colleagues in this edition of CHEST demonstrates (see page 1072), significant holes in antibiotic
coverage may result when the local etiology of CAP
differs from the etiology in “standard” populations
(predominantly North American and Western European) on which the guidelines are based. To achieve
the best outcome, physicians need to have knowledge of local variations in the etiology of CAP, and
they must be aware of which pathogens may not be
covered by standard empiric regimens, and the risk
factors for infection with these pathogens.
Deficiencies in empiric antibiotic coverage can
result from either unexpected antibiotic resistance in
the common pathogens or because unusual pathogens are the cause of CAP. The impact of antibiotic
resistance is dependent on the empiric antibiotic
regimen used. In the case of penicillin-resistant
Streptococcus pneumoniae infection, the impact is
relatively small because empiric regimens in areas
with a high prevalence of penicillin resistance are
designed to cover this eventuality. Conversely, while
Staphylococcus aureus is not an unexpected pathogen, the presence of methicillin resistance in community-acquired infections is increasing8 and the
inadequacy of usual empiric regimens may significantly impact outcome.4
The occurrence of etiologies other than the usual
pathogens, S pneumoniae, Mycoplasma pneumoniae,
Chlamydia pneumoniae, Legionella spp, and respiCHEST / 120 / 4 / OCTOBER, 2001
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ratory viruses, increases the complexity of CAP
management. It is reassuring that aggressive diagnostic procedures, such as percutaneous needle aspirates and preantibiotic bronchoscopy, or research
protocols, such as polymerase chain reaction testing
regularly find that the pneumococcus is the most
common etiology for these otherwise undiagnosed
cases. Convalescent serologic studies also consistently confirm that the usual “atypical” microorganisms cause another large percentage of cases, although the relative frequency of each varies
depending on the geographic location of the study.
However, a disturbing percentage of patients with
CAP, particularly those with severe CAP, are infected
with pathogens not covered by the usual empiric
antibiotic regimens. The more serious of this second
tier of causative microorganisms are the Gram-negative
bacilli. A study by Ruiz and coworkers9 found that
Gram-negative bacilli (other than Haemophilus spp)
caused 11% of CAP in patients requiring ICU admission. The mortality of severe Gram-negative CAP was
55.5%, the highest case fatality rate for any etiology.9
Gram-negative pathogens, particularly Klebsiella pneumoniae and Pseudomonas aeruginosa, are also frequently identified in patients presenting with CAP and
shock,10 where the mortality is ⬎ 50%.
In this issue of CHEST, Chen and colleagues present
a case series of severe CAP due to another Gramnegative bacillus, Acinetobacter baumannii. While usually considered a nosocomial pathogen, numerous cases
of A baumannii CAP have been reported over many
years, particularly in patients with severe CAP.10,11 One
of the most helpful hints from the series reported by
Chen et al is the geographic and temporal distribution
of Acinetobacter CAP cases to areas and seasons of
heat and humidity. The other helpful hint on diagnosis
is that Acinetobacter CAP often has a presentation
similar to the alcoholism, leukopenia, and pneumococcal bacteremia syndrome.11,12
Obviously, the greatest concern when unusual pathogens cause CAP is whether they are susceptible to the
usual empiric antibiotic regimens. Although not as
active as ciprofloxacin, empiric use of the newer quinolones for empiric therapy of CAP may provide some
coverage of Pseudomonas, while the other common
regimen of a nonpseudomonal cephalosporin and a
macrolide would not. Acinetobacter CAP presents an
even greater challenge because even antipseudomonal
cephalosporins are infrequently effective. Carbapenems (imipenem and meropenem), seldom used but
mentioned as an alternative by both American Thoracic
Society and Infectious Disease Society of America
guidelines, are the most reliable antibiotic agents for
Acinetobacter pneumonia. However, Chen et al found
that the addition of an aminoglycoside to a ␤-lactam
was associated with better outcome.
Unfortunately, outcomes analyses of CAP treatment
have cast aminoglycoside use in a bad light. A large
study14 of CAP treatment regimens suggested the
inclusion of an aminoglycoside was associated with an
increased risk of death. Rather than substandard empiric therapy, the association between mortality and
aminoglycosides may be due to physicians correctly
suspecting a Gram-negative pathogen with its attendant greater mortality. Combination therapy with a
␤-lactam and an aminoglycoside has been demonstrated to lead to improved mortality in Klebsiella
CAP,14 and aminoglycosides are routinely used in combination therapy for suspected pseudomonal infections.
Physicians want to select empiric antibiotic therapy that is likely to cover all likely pathogens,
particularly in patients with severe CAP. How then
should physicians select antibiotic regimens in patients with severe CAP in order to plug the occasional holes in standard empiric therapy? Indiscriminate use of a carbapenem or addition of an
aminoglycoside to all patients with severe CAP is
clearly not appropriate. However, the epidemiologic
clues for unusual etiologies of CAP can justify selective use of these agents. Severe CAP occurring
during hot, humid weather probably is an adequate
indication for empiric carbapenem use for suspected
Acinetobacter CAP, particularly if occurring in an
active alcoholic or associated with neutropenia.
Most importantly, physicians need to be aware of
the local differences in the etiology of CAP and the
risk factors for pathogens likely to be resistant to
standard empiric antibiotic regimens. When very
broad-spectrum empiric therapy is selected to cover
for drug-resistant pathogens, adequate blood and
respiratory specimens must be collected to maximize
the possibility of converting to specific therapy as
soon as possible. Empiric therapy is indicated for
infections in which the diagnostic yield is low or until
diagnostic culture results are available. The success
of empiric therapy in a majority of cases also does not
justify laxity in diagnostic efforts in individual highrisk, high-yield cases.
Richard G. Wunderink, MD, FCCP
Memphis, TN
Grant W. Waterer, MBBS, FCCP
Perth, Western Australia
Dr. Wunderink is Director of Clinical Research, Methodist Le
Bonheur Healthcare, and Dr. Waterer is Senior Lecturer in
Respiratory Medicine, Department of Medicine, University of
Western Australia, Royal Perth Hospital.
Correspondence to: Richard G. Wunderink, MD, FCCP, Methodist
Le Bonheur Healthcare, 1265 Union Ave, 501 Crews Wing,
Memphis, TN 38104-2499; e-mail: [email protected]
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Editorials
References
1 Niederman MS, Mandell LA, Anzueto A, et al. Guidelines for
the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 2001;
163:1730 –1754
2 Bartlett JG, Breiman RF, Mandell LA, et al. Communityacquired pneumonia in adults: guidelines for management;
The Infectious Diseases Society of America. Clin Infect Dis
1998; 26:811– 838
3 Leroy O, Santré C, Beuscart C, et al. A five-year study of
severe community-acquired pneumonia with emphasis on
prognosis in patients admitted to an intensive care unit.
Intensive Care Med 1995; 21:24 –31
4 Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections: a risk factor for hospital
mortality among critically ill patients. Chest 1999; 115:462–
474
5 Torres A, Serra-Batlles J, Ferrer A, et al. Severe communityacquired pneumonia: epidemiology and prognostic factors.
Am Rev Respir Dis 1991; 144:312–318
6 Sanyal S, Smith PR, Saha AC, et al. Initial microbiologic
studies did not affect outcome in adults hospitalized with
community-acquired pneumonia. Am J Respir Crit Care Med
1999; 160:346 –348
7 Waterer GW, Wunderink RG. The impact of severity on the
utility of blood cultures in community-acquired pneumonia.
Respir Med 2001; 95:78 – 82
8 Diekema DJ, Pfaller MA, Schmitz FJ, et al. Survey of
infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in
the United States, Canada, Latin America, Europe, and the
Western Pacific Region for SENTRY antimicrobial surveillance program, 1997–1999. Clin Infect Dis 2001; 32(suppl
2):S114 –S132
9 Ruiz M, Ewig S, Torres A, et al. Severe community-acquired
pneumonia. Am J Respir Crit Care Med 1999; 160:923–929
10 Marik PE. The clinical features of severe community-acquired pneumonia presenting as septic shock. J Crit Care
2000; 15:85–90
11 Anstey NM, Currie BJ, Withnall KM. Community-acquired
Acinetobacter pneumonia in the Northern Territory of Australia. Clin Infect Dis 1993; 17:820 – 821
12 Perlino CA, Rimland D. Alcoholism, leukopenia, and pneumococcal sepsis. Am Rev Respir Dis 1985; 132:757–760
13 Gleason PP, Meehan TP, Fine JM, et al. Associations between initial antimicrobial therapy and medical outcomes for
hospitalized elderly patients with pneumonia. Arch Intern
Med 1999; 159:2562–2572
14 Feldman C, Smith C, Levy H, et al. Klebsiella pneumoniae
bacteraemia at an urban general hospital. J Infect 1990;
20:21–31
Hypersensitivity Pneumonitis
Just Think of It!
air contains variable amounts of respiraA mbient
ble foreign substances. Some of these substances
are capable of inciting immune responses in the host
inhaling them. Hypersensitivity pneumonitis (HP)
represents one possible response of the lung to the
inhalation of these antigenic substances. Subjects
who are exposed to respirable antigens occasionally
react to this by a complex immune response, involving both T-lymphocyte and B-lymphocyte activation
in the lower respiratory tract.1 Disease resulting from
antigen exposure is uncommon, even among subjects
with similar exposures to the relevant antigens. This
variability in disease expression following exposure
suggests that the genetic background of affected individuals2 or other factors such as concomitant viral infection3 may be responsible for disease expression.
Although the exact pathogenesis of HP is not
known, patients with the disease have several characteristic features that allow a firm diagnosis in most
cases. These features include a history of exposure to
respirable antigens, the relief from symptoms with
antigen avoidance, and a recrudescence of symptoms
with re-exposure. The symptom complex can be
quite variable and includes severe presentations that
are similar to that of ARDS, subacute presentations
with malaise, cough, and weight loss, and the development of chronic fibrosis. These variable forms of
presentation pose a considerable challenge to the
clinician. The clinician must first consider the possibility that HP may be causing the disease. Then the
physician must question the patient about exposure
to relevant antigens. Unfortunately, the spectrum of
potential antigens is quite broad, and these antigens
may be concealed in the environment. However, in
most cases the amount of antigen in the inhaled air is
quite large. Thus, affected patients usually have an
idea that they are being exposed to something. They
may notice that the air that they breathe is dusty or
has an objectionable odor. In some cases, the patient’s occupation is a powerful clue to a potential
exposure.
Once the possibility of exposure has been determined, support of the diagnosis may be provided by
a CT scan of the chest and by lung function tests. HP
is associated with the combination of ground glass
changes and small nodular lesions that are visible on
the CT scan.4 Pulmonary physiology usually shows a
mixture of restrictive and obstructive changes. Neither a CT scan nor a lung function test provides a
diagnosis, but both provide soft support. Subsequently, the clinician may proceed by attempting to
identify immune responses against the probable
antigens. The easiest test to perform is the search for
precipitating antibodies. The antigens responsible
for common forms of HP such as farmer’s lung5 and
pigeon-breeder’s disease6 are well-characterized and
can be tested by commercial laboratories. In other
cases, antibodies may be difficult to detect, and
previously unknown antigens cannot be assessed by
standard antibody methods in commercial laboratories. If antibodies cannot be detected, the patient
CHEST / 120 / 4 / OCTOBER, 2001
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