172 / 236
Varvyanskaya and Lopatin
FIGURE 6.
Evaluation of ECP concentration in the nasal discharge, in
ng/mL. ECP
=
eosinophil cationic protein.
aminotransferase [AST], and alkaline phosphatase [ALP])
remained normal in all patients.
Microbiological study of the swabs from the middle mea-
tus revealed a wide spectrum of bacteria. The most common
organismwas
Staphylococcus aureus
(30%of patients), fol-
lowed by
Staphylococcus epidermidis
(25%),
Streptococcus
haemolyticus
(11%),
Escherichia coli
(9%),
Pseudomonas
aeruginosa
(6%), and
Enterobacter aerogenes
(6%). Bacte-
rial spectrum changed significantly after the surgery, but the
proportion between clarithromycin-resistant strains (13%)
and clarithromycin-sensitive strains (87%) remained the
same. At the study conclusion, some macrolide-sensitive
bacterial strains did acquired resistance to clarithromycin.
Interestingly, an opposite phenomenon occurred as well;
initially some bacterial strains resistant to macrolides were
replaced by some bacterial strains sensitive to macrolides.
In general, the number of clarithromycin-resistant strains
(13%) remained constant throughout the course of long-
term clarithromycin treatment.
Discussion
The current evidence supports the idea that long-term low-
dose treatment with macrolides is effective when reserved
for recalcitrant nonatopic CRS patients in whom topical
nasal steroids and saline irrigations have failed to control
symptoms.
14,15
In atopic CRSwNP patients, BA and AERD
macrolide therapy has not been useful.
16,17
In the more recent literature long-term low-dose
macrolide therapy has been reported to be effective in CRS,
including those patients with elevated immunoglobulin E
(IgE) levels and BA. A recent prospective study demon-
strated that an 8-week course of clarithromycin therapy
was equally effective in both atopic and nonatopic patients
with nasal polyposis.
18
In a retrospective study, CRS pa-
tients with atopy responded well to long-term macrolide
treatment, whereas patients who smoked had the poorest
treatment outcome.
19
The results of our study demonstrated that long-term
low-dose macrolide therapy prevents early recurrence of
nasal polyps after FESS, including patients with atopy and
BA. There was a clear correlation between atopy and the
severity of disease because our atopic patients had higher
VAS scores (Spearman’s rank correlation coefficient 0.332;
p
=
0.01). The presence of atopy correlated with higher
TABLE 10.
ECP level in nasal secretion (ng/mL)
Visits
Group 1
(antibiotics
24 weeks)
Group 2
(antibiotics
12 weeks)
Group 3 (control
no antibiotic)
Baseline
412.2
±
123.1 279.4
±
85.9
330.8
±
104.5
6 weeks
553.2
±
115.5 604.0
±
173.2 660.0
±
171.6
12 weeks
153.6
±
98.8
*
290.4
±
77.2
*
654.0
±
184.9
24 weeks
154.8
±
89.8
**
338.1
±
83.1
*
1000.0
±
222.7
*Significant differences between study and control groups (
p
<
0.05).
**Significant difference between the group 1 and both control group 3 and group
2 (
p
<
0.05).
ECP
=
eosinophil cationic protein.
ECP levels in the nasal discharge (0.834;
p
=
0.01). These
findings suggest that symptom severity is directly related
to the intensity of the eosinophilic inflammation. Unfortu-
nately, we did not investigate total IgE levels in a majority
of patients; therefore, subgroup analysis of those patients
with low IgE levels was not possible.
A most remarkable study finding was the changing ECP
levels in the nasal secretions after FESS and during the post-
operative period with macrolide therapy. In group 3 (con-
trol no antibiotics) we noted an almost 3-fold increase of the
mean ECP level 6 weeks after surgery. This finding of an ele-
vated ECP level after FESS in these group 3 patients reflects
an exacerbation of the eosinophilic inflammation caused
by the surgery that could not be adequately controlled with
intranasal topical steroids alone. On the other hand, in
treatment groups 1 (antibiotics for 24 weeks) and 2 (an-
tibiotics for 12 weeks) there was a gradual decrease of the
ECP levels with long-term low-dose clarithromycin treat-
ment, reflecting control and reduction of the eosinophilic
inflammation.
One goal of this work was to study the efficacy of a
longer (6 months) treatment course when compared to the
relatively short (3 months) course of low-dose macrolide
therapy. The data suggested some benefit from a longer
antibiotic course but the difference between group 1 (an-
tibiotic 24 weeks) and group 2 (antibiotic for 12 weeks)
failed to reach statistical significance in the majority of pa-
tients. Nonetheless, there is some evidence that a longer
duration of treatment group 1 (antibiotics 24 weeks) ap-
pears to be more effective than a shorter course seen in
group 2 (antibiotics for 12 weeks).
The CT scores for group 1 (antibiotics 24 weeks) pa-
tients was 9.71
±
2.21, which was significantly lower than
in group 3 (control no antibiotics), with readings of 16.66
±
2.32 at endpoint. The difference between group 2 (antibi-
otics for 12 weeks) and group 3 (control no antibiotics)
did not reach statistical significance (Table 8). There were
significant differences in the mean ECP levels in groups
1 and 2 at the endpoint, indirectly confirming that a
6-month antibiotic course reduces the eosinophilic inflam-
mation, thereby preventing early recurrence of nasal polyps.
Obviously, oral steroid use would certainly be considered
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