Journal of Chemotherapy

ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20

Treatment of Atypical Pneumonia with

Azithromycin: Comparison of a 5-Day and a 3-Day
Course

M. Socan

To cite this article: M. Socan (1998) Treatment of Atypical Pneumonia with Azithromycin:
Comparison of a 5-Day and a 3-Day Course, Journal of Chemotherapy, 10:1, 64-68, DOI:
10.1179/joc.1998.10.1.64

To link to this article: http://dx.doi.org/10.1179/joc.1998.10.1.64

Published online: 18 Jul 2013.

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Journal of Chemotherapy Vol. 10 - n. 1 (64-68) - 1998

Treatment of Atypical Pneumonia with

Azithromycin: Comparison of a 5-Day and
a 3-Day Course
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M. SOCAN

Department of Infectious Diseases, University Medical Center, Japljeva 2, 1000 Ljubljana, Slovenia.
Fax: +386.61.302781.

Summary
The efficacy of a 5-day regimen consisting of 500 mg in a single dose on
the first day followed by 250 mg once daily for 4 consecutive days was com-
pared with that of a 3-day course of azithromycin given in single daily doses of
500 mg for treatment of atypical pneumonia. Adult patients hospitalized with
atypical pneumonia in the years 1990 to 1993 were studied retrospectively.
For each patient, the medical history, laboratory data, the results of serological
tests, chest radiographs and treatment outcome were reviewed. Out of 148
patients with atypical pneumonia, 40 were treated with azithromycin for 5 days
(Group 1) and 41 for 3 days (Group 2). The success rate in Group 1 was 80%
(32 patients). Eight patients did not respond to treatment: 5 had significant
complement fixing antibody titers to adenovirus and in 3 the etiology was
unknown. The success rate in Group 2 was 88% (36 patients). Azithromycin
was ineffective in all 3 patients with adenoviral pneumonia, in 1 patient with Q
fever, and in 1 patient with no identified pathogen. Azithromycin is equally
effective as treatment of atypical pneumonia in adult patients if given for 3 or
5 days at the same total dose.

Key words: Azithromycin, pneumonia in adults, pneumonia atypical.

INTRODUCTION tract infection, which develop only later in the

Treatment of pneumonia is usually empiri-
cal. The antibiotic is selected on the grounds of
clinical picture, blood tests and chest X-rays 1.
In patients with atypical pneumonia general
symptoms, such as malaise, headache and
fever prevail over manifestations of respiratory
course of the illness 2. Atypical pneumonia is
most commonly caused by Mycoplasma pneu-
moniae, intracellular bacteria (Chlamydia
pneumoniae and psittaci, Legionella pneu-
mophila), rickettsiae (Coxiella burnetii) and
some viruses (influenza A and B virus, respira-
tory syncytial virus and some types of aden-

© E.I.F.T. srl - Firenze ISSN 1120-009X

 TREATMENT OF ATYPICAL PNEUMONIA WITH AZITHROMYCIN: COMPARISON OF A 5-DAY AND A 3-DAY COURSE
ovirus 3. Since the above listed pathogens are
not sensitive to beta-lactam antibiotics, the
infection is treated with tetracycline or
macrolide antibiotics 4.
Azithromycin is a recently introduced azalide
antibiotic, differing from other macrolides in its
pharmacokinetic profile. Thanks to its long
half-life and high tissue concentrations, it
requires only once-daily administration, and is
given for shorter time than other macrolide
antibiotics 5.
At this Department, azithromycin is the
most commonly used antimicrobial for the
treatment of atypical pneumonia. The purpose
of our retrospective study was to assess the effi-
cacy of azithromycin, and to compare the
results of 3-day and 5-day treatments with
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azithromycin in a total dosage of 1.5 g.
PATIENTS AND METHODS
We examined retrospectively medical
records of all adult patients (older than 15
years) with atypical pneumonia treated with
oral azithromycin at this Department between
1990 and 1993. The patients were divided
into two groups: Group 1 patients were given
azithromycin 500 mg in a single dose the first
day, and then 250 mg for 4 consecutive days;
and Group 2 was treated with azithromycin
500 mg in a single daily dose for 3 days. Both
groups received an equal total dose of the drug.
The collected patient data included age and the
sex of the patients, some symptoms and signs,
history of previous antibiotic treatment, ESR,
serum C-reactive protein concentration, WBC,
transaminase activity and site of pulmonary
involvement (unilateral, bilateral).
To identify the etiologic agent of atypical
pneumonia in our patients we used a comple-
ment fixation test demonstrating antibodies to
M. pneumoniae, chlamydiae, C. burnetii,
influenza A and B virus, parainfluenza 1, 2 and
3 virus, respiratory syncytial virus and aden-
ovirus. In patients hospitalized in 1993, specific
IgM and IgG antibodies to M. pneumoniae in
serum were determined by ELISA, to C. pneu-
moniae and psittaci by micro-IF test and to C.
burnetii by indirect fluorescent antibody assay.
A pathogen was considered responsible for
pneumonia when the determined specific anti-
65
body titer was at least 1 in 256, or a four-fold
rise or fall in antibody titer was found, or the
presence of specific IgM antibodies in serum
were confirmed by other techniques. Pneu-
monia due to C. pneumoniae was diagnosed in
patients who had a four-fold rise or fall in spe-
cific IgG antibody titers, or showed a single
titer equal to or greater than 512 as deter-
mined by the microimmunofluorescence test.
Assessment of the efficacy of treatment was
based on the time required by the patient to
become afebrile. If fever persisted longer than
96 hours after the institution of antibiotic thera-
py, the drug was considered ineffective. A com-
parison of data for both groups was done with
the chi-square test (p<0.05).
RESULTS
Between 1990 and 1993, 148 patients
with atypical pneumonia were treated at the
Department of Infectious Diseases. Forty
patients received azithromycin for 5 days and
41 patients for 3 days. Demographic data and
the most common symptoms and signs are
indicated in Table 1. Dry cough and headache
were prevailing symptoms in both groups,
while signs characteristic of upper respiratory
involvement occurred less frequently. There
were no statistically significant differences
between the groups concerning their demo-
graphic data, and symptoms and signs
(p<0.05). In Group 1, 19 patients presented
with a history of unsuccessful treatment with
beta-lactam antibiotics and 5 failed to respond
to previous treatment with other antimicrobials,
such as quinolones and trimethoprim/sul-
famethoxasole. In Group 2, 9 patients received
beta-lactams and 3 other antibiotics with no
response.
On auscultation of the lungs pathological
respiratory phenomena were found in 22
patients (55%) of Group 1, and in 19 patients
(46%) of Group 2. In a small number of
patients, i.e. 6 in both groups, enlarged liver
was palpated.
Increased erythrocyte sedimentation rate
was established in 30 patients of Group 1 and
34 in Group 2. C-reactive protein determina-
tions were done in 27 and 28 patients of
Group 1 and Group 2, respectively. Levels
 66
TABLE 1 - Demographic data, symptoms and signs in patients receiving azithromycin for 5 days (40 patients) and
3 days (41 patients).
Azithromycin 5 days
N. patients (%)
Mean age (years) 38.7
Sex (male/female) 23/17 (57.5/42.5)
Headache 32 (80)
Myalgia, arthralgia 11 (27.5)
Dry cough 36 (90)
Conjuctivitis 7 (17.5)
Sore throat 11 (27.5)
Pathological lung auscultation 22 (55)
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exceeding 100 mg were found in 10 patients
of Group 1 and in 13 patients of Group 2. The
majority of patients had normal or moderately
elevated WBC. The highest elevation (16.109/l)
occurred in a patient with adenoviral pneumo-
nia. Leukopenia was present in only 3 patients
of each group. The liver function tests (ALT,
AST and γGT) were modestly abnormal in 16
patients (40%) of Group 1 and in 19 patients
(46%) of Group 2. In some patients lumbar
puncture was performed. One female patient
had pathological cerebrospinal fluid (CSF), yet
the etiology of infection remained unknown.
Chest X-ray indicated bilateral pulmonary
involvement in 6 patients of Group 1 and 9
patients of Group 2.
Blood for serology was obtained from 29
patients of Group 1 and 36 patients of Group
2. The etiologic pathogen of atypical pneumo-
nia was identified in nearly half the patients: C.
psittaci in 7 patients, M. pneumoniae in 2, C.
pneumoniae in 1, and adenovirus in 5 patients
of Group 1. In Group 2, the evidence of M.
pneumoniae infection was obtained from 6
patients, 5 patients had ornithosis, 2 were
infected with C. pneumoniae and 2 with C.
burnetii. Three patients had diagnostic titers of
antibodies to adenovirus. Of 9 patients with
ornithosis, diagnosed by complement fixation
test, 7 gave a history of exposure to a healthy
or diseased parrot. Since the complement fixa-
tion test demonstrates the presence of antibody
to antigens shared by all chlamydial species,
infection with C. pneumoniae cannot be com-
pletely ruled out.
M. SOCAN
Azithromycin 3 days
N. of patients (%)
36.1
26/15 (63.4/36.6)
36 (88)
15 (36.5)
33 (80)
5 (12)
11 (27)
19 (46)
Before the beginning of therapy all patients
had elevated temperature, but none were seri-
ously affected on admission. In Group 1, 11
patients became afebrile by the second day of
antibiotic therapy, 16 patients by the third day
and 5 by the fourth day of treatment. A similar
response to azithromycin was noted in Group
2: in 15 patients defervescence occurred in 2
days, in 19 patients in 3 days and in 2 patients
in 4 days. No statistically significant difference
was found between the groups concerning the
length of the febrile course (p<0.05). The treat-
ment was unsuccessful in 8 patients (20%) of
Group 1: pneumonia due to adenovirus was
confirmed in 5 cases, while the etiologic agent
remained unknown in 3 patients. The therapy
failed to produce improvement in 5 patients
(12%) of Group 2: 3 patients with adenovirus
infection, 1 patient infected with C. burnetii,
and 1 with pneumonia of unknown etiology.
DISCUSSION
High azithromycin concentrations have been
found after a single oral dose of 500 mg in
alveolar macrophages, as well as in mucous
membrane, bronchial epithelium fluid and spu-
tum 6. In the lungs, azithromycin concentra-
tions of 3 µg/g were present for 5 days after
oral administration of a single 500 mg dose of
the drug 7. Thanks to these pharmacokinetic
properties, oral azithromycin can be given in a
single daily dose for either 5 or 3 days 8,9. C.
pneumoniae 10, M. pneumoniae 11 and L.
 TREATMENT OF ATYPICAL PNEUMONIA WITH AZITHROMYCIN: COMPARISON OF A 5-DAY AND A 3-DAY COURSE
pneumophila 12 showed high in-vitro suscepti-
bility to azithromycin. The experimental animal
model was made only with L. pneumophila.
All guinea pigs treated with intraperitoneal
azithromycin survived infection. In the group of
animals receiving erythromycin the survival rate
was 83.3% 13.
There is a paucity of controlled clinical stud-
ies on the efficacy of azithromycin treatment
for community-acquired pneumonia. More data
are available on the therapy of acute bronchitis
14,15. A comparison of patients placed on a 10-
day course of cefaclor 500 mg every 8 hours
and those treated with azithromycin for 5 days
showed good clinical response in all patients
with bacterial pneumonia receiving cefaclor and
in 97.3% of patients treated with azithromycin
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16. Myburg, who studied the efficacy of a 3-day
regimen of azithromycin in 40 patients with
community-acquired pneumonia of known etiol-
ogy, reported a 98% success rate. Improve-
ment occurred as soon as 2 days after the insti-
tution of drug therapy. The reported group
comprised 8 patients with serologically
confirmed legionellosis. The therapy proved
successful in all patients 17 . In his study,
Schonwald compared the efficacy of a 5-day
course of azithromycin and a 10-day regimen
of erythromycin 500 mg/6 hourly, as well as a
3-day and a 5-day azithromycin treatment and
found excellent clinical response 18,19. Both
studies included solely patients with atypical
pneumonia of known etiology, in most cases
caused by M. pneumoniae. All investigations
hitherto have shown a low rate of side effects.
Sixteen patients showed a favorable response
to azithromycin treatment in a study of commu-
nity-acquired pneumonia caused by L. pneu-
mophila. All patients but one became afebrile
48 hours after administration of the initial dose
20.
Our study presents retrospective results as
well. Treatment with azithromycin was success-
ful in the majority of patients with atypical
pneumonia in both groups. Five patients had
viral pneumonia and failure of azithromycin
therapy was therefore anticipated. The same
holds true for 3 unsuccessfully treated patients
in Group 2. The therapy failed to produce
improvement in 1 patient with C. burnetii
infection. C. burnetii is susceptible to tetracy-
cline; some strains are modestly sensitive, and
some resistant to erythromycin 21 . Despite
67
favorable clinical results of erythromycin thera-
py, tetracycline rather than macrolide antibi-
otics have been prevailingly used as the therapy
of choice in patients with Q fever.
CONCLUSIONS
The results of our study show that
azithromycin in a total dose of 1.5 g is equally
effective whether given for 3 or for 5 days.
Considering the benefits of short and effective
antibiotic therapy for the patient, we recom-
mend a 3-day course of azithromycin for treat-
ing atypical pneumonia which is not considered
life-threatening.
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