Journal Club Feature

LEGIONNAIRES DISEASE: A CASE STUDY

By Melinda Cramer, RN, BSN. From School of Nursing, University of Pennsylvania, Philadelphia, Pa.

egionella pneumophila, an aerobic, gram-negative insufciency, and coronary artery disease. His name

L bacillus, is 1 of the top 3 causes of community-

acquired pneumonia,1accounting for 3% to 15%
2
of all cases. According to estimates from the Centers
for Disease Control and Prevention, although 18 000 to
25 000 cases of pneumonia due to this organism occur
each year, the diagnosis is reported in only 1200 to 1500
cases because of the nonspecic signs and symptoms of
the disease and inadequate testing for Legionella. 3
High mortality is associated with pneumonia caused
by L pneumophila, especially in patients who are
immunocompromised. This case study presents infor-
mation about the epidemiology, pathophysiology, clini-
cal features, and treatment of legionnaires disease and
emphasizes the importance of early diagnosis.
Case Study
A 28-year-old man, N.C., came to the emergency
department because he had shortness of breath, fatigue,
a cough, diarrhea, and arthralgias. The shortness of
breath was associated with minimal exertion (1 ight of
stairs) and resolved after several minutes of rest. He did revealed dullness at the base of the right lung. Cardiac
not have pain on inspiration or chest pain. He described
the fatigue as overwhelming, and his activities were
restricted to essential activities of daily living. The
cough was nonproductive and did not have a pattern or
aggravating or relieving factors. It was not associated
with pain, positioning, or time of day. One day before
admission, he had had fever and chills, with a maxi-
mum body temperature of 38.6 C (101.4 F). Watery,
brown diarrhea occurred without other gastrointestinal
distress and was intermittent, approximately 7 to 8
times a day. No treatments had been instituted at home.
N.C. had had idiopathic dilated cardiomyopathy in
1990 and had received an orthotopic heart transplant in
1994. Other notable abnormalities and previous inter-
ventions included transplant arteriopathy, biventricular
heart dysfunction, placement of a pacemaker, recurrent
right-sided pleural effusions, pleurodesis, posttransplant serum
hypertension, hypercholesterolemia, treatment with
antibodies to cardiolipin, a thoracotomy, chronic renal
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was again on the list for a heart transplant, status 1B.
At the time of admission, he was taking intravenous
milrinone, warfarin, furosemide, antihypertensives,
and drugs to prevent rejection of his heart transplant.
He had a brother who also had received a heart trans-
plant because of idiopathic dilated cardiomyopathy.
N.C. did not use alcohol or tobacco. He lived in an
apartment with 2 roommates and worked at home as
an editor. He had no pets and he had not traveled
recently, but both roommates had had an upper respira-
tory infection within the preceding week.
In the emergency department, N.C. was afebrile
and mildly short of breath, with respirations 18/min,
blood pressure 90/40 mm Hg, and heart rate 110/min.
Cardiac rhythm was sinus tachycardia. Arterial oxygen
saturation was 84% when he was breathing room air
and increased to 95% when he was breathing 50%
oxygen via a face mask. Jugular venous distension was
present at the angle of the jaw. Rales were present in
one third of the lung fields bilaterally. Percussion
assessment revealed a regular rhythm with a hyperdy-
namic point of maximum impulse; S 1, S ,2 and S heart3
sounds; and a grade III/VI tricuspid murmur. He had
1+ edema in the lower extremities and 2+ pedal pulses.
Neurologically, he had no focal decits, and he fol-
lowed commands appropriately. The results of an
abdominal assessment were unremarkable. He had no
clubbing of the ngers or cyanosis.
Tests of blood samples obtained in the emergency
department indicated the following serum levels: sodi-
um 131 mmol/L, potassium 4.6 mmol/L, chloride 107
mmol/L, urea nitrogen 7.1 mmol/L (20 mg/dL), and
creatinine 115 mol/L (1.3 mg/dL). A complete blood
cell count was as follows: white blood cell count 16.8
9 9
x 10 /L and platelet count 319 x 10 /L. His hemoglobin
level was 88 g/L, and his hematocrit was 0.26. The
level of thyrotropin was 2.45 mIU/L. Blood lev-
els of digoxin, cyclosporine, and mycophenolate
(CellCept) were appropriate. A chest radiograph
showed bilateral diffuse basilar inltrates, otherwise
unchanged
cultures of blood, stool, and sputum; tests to detect

234 AMERICAN JOURNAL OF CRITICAL CARE, May 2003, Volume 12, No. 3
acid-fast bacilli; assays of nasal swabs for detection of
inuenza viruses A and B; and urine test for Legionella
antigen were pending.
N.C. was admitted to the cardiac intermediate care
unit for further observation and treatment. Small doses
of diuretics were given for fluid overload, previous
medications were continued, and administration of lev-
ooxacin was started.
On hospital day 3, N.C. was less short of breath
than before, but he continued to have a nonproductive
cough. His vital signs were body temperature 37.8 C
(99.9F), heart rate 78/min, blood pressure 96/50 mm
Hg, and respirations 16/min. He was weaned from 50%
oxygen via a face mask to 2 L of oxygen by nasal can-
nula; oxygen saturation by pulse oximetry was 96%.
The diarrhea had improved. His electrolyte levels were
unremarkable, but his white blood cell count increased
9
to 26.0 x 10 /L. The cultures for influenza A and B
viruses were negative as were stool cultures for ova and
parasites and blood cultures for bacteria and fungus.
The urine test for Legionella antigen was positive. The
infectious disease team recommended that levooxacin
500 mg orally once a day be continued for a total of 14
days. Samples of material from a humidifier from
N.C.s apartment were cultured as a potential source of
the Legionella.
N.C. showed clinical improvement and was dis-
charged on hospital day 8. He was taking all of his
previous medications and would continue to take lev-
ooxacin to complete the 14-day course of treatment.
His white blood cell count had decreased to 15.2 x
109/L, and his nal chest radiograph showed bilateral
patchy inltrates compatible with pneumonia. He was
afebrile and had stable vital signs, including an oxygen
saturation of 99% when he was breathing room air.
The patient was scheduled to have a follow-up
appointment, as well as another chest radiograph and
laboratory tests (including a complete blood cell count,
blood chemistries, and measurement of levels of
immunosuppressant medications) 10 days after dis-
charge. He was not to return to his home until the cul-
tures of the samples from the humidier were known to
be negative for Legionella. The culture was negative,
and the source of Legionella was not ascertained.
Discussion
Legionnaires disease was rst described after an
outbreak in 1976 in Philadelphia at the American
Legion convention. Several outbreaks and numerous
individual cases have occurred since. The disease is due
to L pneumophila, which causes an atypical pneumo-
nia. The natural habitat for L pneumophila is fresh
water or protozoan biolms, in which the bacteria para-
AMERICAN JOURNAL OF CRITICAL CARE, May 2003, Volume 12, No.235
4
sitize and proliferate inside the protozoa. Within the
natural aquatic environment, the concentrations of L
pneumophila are relatively low. Once the water is trans-
ferred into man-made water reservoirs, the Legionella
organisms proliferate because of favorable conditions
(Table 1). Warmer temperatures, stagnation, presence of
other organisms, and scale and sediment lead to
5
increased concentrations of L pneumophila. Legionella
is transmitted to humans via inhalation of colonized
aerosols or droplets, which are produced by air condi-
tioners, cooling towers and condensers, water fountains,
shower heads, faucets, whirlpools, ice machines, spas,
nebulizers, and humidiers.6
The incidence of legionnaires disease depends on
several factors. The concentration of L pneumophila in
aerosols or droplets, the immune susceptibility of the
person exposed, and the time and intensity of the
7
exposure are all contributory. Associated risk factors
include advanced age, immunocompromised state,
cigarette smoking, chronic lung disease, and male
sex.1 Postoperative patients and transplant recipients
are also at increased risk.
Pathophysiology
Once inhaled, L pneumophila adheres to the respi-
ratory tract by means of pili that ensure attachment
and prevent dislocation by mucociliary clearance. 2
Conditions that cause damage to the respiratory cilia,
such as smoking, alcohol consumption, and lung dis-
ease, increase the rate of infection by L pneumophila. 2
The immune system mounts a cell-mediated reaction in
which macrophages attach to the outer walls of the bac-
teria for active phagocytosis. The engulfed bacteria pro-
liferate within the macrophages. 8 As phagocytosis
continues, some of the bacteria are eradicated, but a sig-
nicant number replicate until the macrophage lyses.
As the bacteria are released from the newly lysed cell,
more macrophages begin the process of phagocytosis,
and the cycle continues. A8
humoral immune reaction
(IgM and IgG antibodies) also occurs2(see Figure).
Clinical Manifestations
The clinical manifestations of legionnaires disease
are summarized in Table 2. The signs and symptoms are
nonspecic and are similar to those of an atypical pneu-
Table 1 Conditions favorable for the growth and
proliferation of Legionella
Water temperatures in the range of 38
C to 49C
Presence of sediment, sludge, scale, and organic matter
Presence of other bacteria or algae
Biofilm on the surface of water
Biofilms, sludge, and corrosion
3
 Table 2 Clinical features of legionnaires disease
A. Environment
General malaise Change in level of
Fever consciousness
Dry cough Abdominal pain
Minimal amount, if present, Diarrhea
blood-tinged sputum Nausea/vomiting
VBNC bacteria Intracellular growth in Thoracic pain Arthralgias
Survival in biofilms protozoa Headache Hematuria
B. Infection
diarrhea.10 If the disease is untreated, it may progress to
neurological disturbances ranging from lethargy and
confusion to a comatose state or stupor. Multiple sys-
tems can be affected. Liver dysfunction, renal dysfunc-
tion, and hematologic disturbances have been associated
with progression of legionnaires disease.
Transmission by Inhalation of Examination of the lungs may initially reveal focal
technical vectors contaminated aerosols
rales that will eventually become diffuse. Findings on an
C. Intracellular replication in macrophages initial radiograph of the chest may be normal, but even-
5 tually a pulmonary inltrate will develop.11
1 Diarrhea is common in legionnaires disease, and
4
usually hyponatremia occurs because of the loss of sodi-
L um and water. Other abnormalities include elevated
N serum levels of liver enzymes, hypophosphatemia,
3
thrombocytopenia, hematuria, and moderate elevation of
serum levels of creatine kinase.11

Pathophysiology of legionnaires disease. Diagnosis

L indicates lysosome: N, nucleus; VBNC, viable but nonculturable;
1, uptake of Legionella ; 2, inhibition of phagolysosome fusion;
3, organelle recruitment; 4, intracellular replication; 5, release of
Legionella by host cell lysis.
4
Reprinted from Steinert et al, with permission from Elsevier Science.
monia, but more severe. The incubation period is 2 to 10
days9; during this time, the signs and symptoms are typi-
cally mild. Initial signs and symptoms are generalized
malaise, chills, fevers, headaches, arthralgias, and a non-
productive cough.10 Gastrointestinal distress is common
and is characterized by nausea, vomiting, and watery
Four tests are predominantly used to detect the
presence of Legionella: culture of specimens, direct
uorescent antibody test, urine antigen test, and serum
antibody assay. The availability, cost, and sensitivity
and specicity of the tests should be considered when
infection with Legionella is suspected. Table 3 details
specic test characteristics. The cost and availability of
the tests may depend on the institution in which the
testing is performed. Individual practitioners should
be aware of the availability and costs of the tests and
the time required for test results at institutions where
they practice.

2
Table 3 Diagnostic tests for detecting Legionnella

Test Procedure Sensitivity, % Specificity, % Time until results

Culture Culture, on special agar, of sputum, 80 100 3-5 days

pleural fluid, tissue, or specimens
obtained via bronchoscopy
Direct fluorescent Staining of sputum with fluorescent 50-96 70-99 Rapid
antibody test antibody and examination under a
fluorescent microscope
Urine antigen test Detection of Legionella antigen in 70 100 24 hours
urine
Serum antibody test Detection of antibodies to Legionella 40-96 60-99 4-12 weeks
in serum

236 AMERICAN JOURNAL OF CRITICAL CARE, May 2003, Volume 12, No. 3
 2
Table 4 Suitable and effective antibiotic choices in the treatment of legionnaires disease

Antibiotic Characteristics/comments Cost per dose, US$

Quinolones* High intracellular activity Levofloxacin (Levaquin): 17 for

Can be used in transplant recipients without intravenous, 6.25 for oral
interaction with cyclosporine and tacrolimus
Can attain high concentrations in the lungs
Require smaller amount of intravenous fluid
than erythromycin does
Once- or twice-a-day doses
Macrolides (newer High intracellular activity Azithromycin: 21 for intravenous,
generation)* Can attain high concentration in the lungs 10.60 for oral
Once- or twice-a-day doses
Require lower amount of intravenous fluid than
erythromycin does
Interact with cyclosporine and tacrolimus
Erythromycin High intracellular activity 14.80 for intravenous, 0.80 for oral
Requires dosing four times a day
Requires a large amount of intravenous fluid
Can cause symptomatic ototoxic effects and
gastrointestinal distress
Tetracycline, doxycycline, High intracellular activity Doxycycline: 14.10 for intravenous,
minocycline More frequent doses needed with tetracycline 0.20 for oral
than with doxycycline and minocycline
Trimethoprim- Positive and negative reports of efficacy Trimethoprim-sulfamethoxazole: 6.60
sulfamethoxazole, for oral, double-strength 0.30 for
imipenem, clindamycin oral
Clindamycin: 100.88 for intravenous,
10.40 for oral
*Drug of choice.
Costs were obtained from a local hospital in Pennsylvania.

The urine antigen test is highly specic, provides
rapid results, and is particularly useful when sputum
samples are not readily available. Although this test
detects only L pneumophila serology group 1, and not
other forms of the bacterium, 12 this serology group
accounts for 80% of the cases of legionnaires disease. 12
Culture of sputum and direct uorescent antibody tests
may be difcult to use because of the lack of sputum,
the need for a special agar, and special preparation of
the medium. On the other hand, the specicity of the
sputum test is remarkably high. The test for serum anti-
bodies to Legionella has a high specicity, but the low-
est sensitivity, in part because a 4-fold increase in
antibody levels is necessary for detection of the anti-
bodies.13 Additionally, an antibody response may not be
detectable until after 4 to 12 weeks of infection.13
Treatment
The goal of treatment in legionnaires disease is
rapid detection and appropriate antibiotic therapy.
Mortality due to the infection increases to 5% to 10%
when treatment is delayed. 14 The choice of antibiotic
depends mostly on the patients comorbid conditions,
the volume required of the intravenous antibiotic, the
ease of eventual oral intake of antibiotics, drug-drug
interactions, superiority of antibiotic actions, and cost.
All of these factors should be considered at the time of
prescribing. Table 4 summarizes suitable and effective
antibiotic choices in the treatment of legionnaires dis-
ease. Intravenous antibiotics should be administered for
the initial 3 to 5 days until clinical improvement occurs.
Then a switch to oral antibiotics can be made for a total
of a 10- to 14-day course of treatment.
Patients with legionnaires disease can be effectively
treated, and a better outcome may occur if the disease
is detected early. All practitioners involved in the care
of these patients should be knowledgeable about the
prevalence, pathophysiology, evaluation, and treatment
of the disease.
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