Ramazan Ozdemir, Omer Erdeve, Evrim Alyamac Dizdar, Serife Suna Oguz,... Uras, Sibel Saygan, Erdem Karabulut and Ugur Dilmen Positive Preterm Infants

Ramazan Ozdemir, Omer Erdeve, Evrim Alyamac Dizdar, Serife Suna Oguz,... Uras, Sibel Saygan, Erdem Karabulut and Ugur Dilmen Positive Preterm Infants

Clarithromycin in Preventing Bronchopulmonary Dysplasia in Ureaplasma
urealyticum−Positive Preterm Infants
Ramazan Ozdemir, Omer Erdeve, Evrim Alyamac Dizdar, Serife Suna Oguz, Nurdan
Uras, Sibel Saygan, Erdem Karabulut and Ugur Dilmen
Pediatrics 2011;128;e1496; originally published online November 28, 2011;
DOI: 10.1542/peds.2011-1350
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/128/6/e1496.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2011 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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Clarithromycin in Preventing Bronchopulmonary
Dysplasia in Ureaplasma urealyticum–Positive
Preterm Infants
WHAT’S KNOWN ON THIS SUBJECT: Despite numerous studies,
controversy still exists about whether Ureaplasma urealyticum
colonization or infection of the respiratory tract contributes to
the development of bronchopulmonary dysplasia. Additional
controversy exists on the use of macrolides for the treatment of
U urealyticum.
WHAT THIS STUDY ADDS: Clarithromycin treatment prevents
development of bronchopulmonary dysplasia in preterm infants
who are born at 750 to 1250 g and colonized with U urealyticum.
AUTHORS: Ramazan Ozdemir, MD,a Omer Erdeve, MD,a
Evrim Alyamac Dizdar, MD,a Serife Suna Oguz, MD,a
Nurdan Uras, MD,a Sibel Saygan, MD,b Erdem Karabulut,
PhD,c and Ugur Dilmen, MDa
aNeonatal Intensive Care Unit and bDepartment of Microbiology,
Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey;
and cDepartment of Biostatistics, Hacettepe University, Ankara,
Turkey
KEY WORDS
bronchopulmonary dysplasia, clarithromycin, premature
infants, Ureaplasma urealyticum
ABBREVIATIONS
BPD—bronchopulmonary dysplasia
OR—odds ratio
CI—confidence interval
RDS—respiratory distress syndrome
PDA—patent ductus arteriosus
abstract
OBJECTIVE: To evaluate the efficacy and safety of clarithromycin treatment in preventing bronchopulmonary dysplasia (BPD) in Ureaplasma
urealyticum–positive preterm infants.
PATIENTS AND METHODS: Nasopharyngeal swabs for U urealyticum
culture were taken from infants with a birth weight between 750 and
1250 g in the first 3 postnatal days. Infants with a positive culture for U
urealyticum were randomly assigned to 1 of 2 groups to receive either
intravenous clarithromycin or placebo. All the patients were followed
at least up to the 36th postmenstrual week.
RESULTS: A total of 224 infants met the eligibility criteria of the study.
Seventy-four (33%) infants had a positive culture for U urealyticum in
the first 3 day cultures. The rate of BPD development was significantly
higher in patients with U urealyticum positivity (15.9% vs 36.4%; P ⬍
.01). However, multivariate logistic regression analysis failed to reveal
a significant association between the presence of U urealyticum and
BPD development (odds ratio: 2.4 [95% confidence interval: 0.9 – 6.3];
P ⫽ .06). Clarithromycin treatment resulted in eradication of U urealyticum in 68.5% of the patients. The incidence of BPD was significantly
lower in the clarithromycin group than in the placebo group (2.9% vs
36.4%; P ⬍ .001). Multivariate logistic regression analysis confirmed
the independent preventive effect of clarithromycin for the development of BPD (odds ratio: 27.2 [95% confidence interval: 2.5–296.1]; P ⫽
.007).
This trial has been registered at www.clinicaltrials.gov (identifier NCT01326611).
www.pediatrics.org/cgi/doi/10.1542/peds.2011-1350
doi:10.1542/peds.2011-1350
Accepted for publication Aug 15, 2011
Address correspondence to Ramazan Ozdemir, MD, Neonatal
Intensive Care Unit, Zekai Tahir Burak Maternity Teaching
Hospital, 06110 Hamamonu, Ankara, Turkey. E-mail: ramazanoz@
yahoo.com.tr
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2011 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
CONCLUSIONS: Clarithromycin treatment prevents development of
BPD in preterm infants who are born at 750 to 1250 g and colonized
with U urealyticum. Pediatrics 2011;128:e1496–e1501
e1496
OZDEMIR et al
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ARTICLES
Bronchopulmonary dysplasia (BPD) is
a significant cause of morbidity and
mortality in premature infants and occurs in 30% of infants born at ⱕ28
weeks’ gestation. The etiology of the
BPD is likely to be multifactorial. Because of the serious long-term health
consequences of BPD, prevention of
the disease is the focus of major
research.1
Ureaplasma urealyticum has long
been implicated in the pathogenesis of
chronic lung disease of prematurity,
but despite numerous studies, reviews
and meta-analyses, controversy still
exists about whether U urealyticum
colonization or infection of the respiratory tract contributes to the development of BPD. Inconsistence between
the studies may be because of small
sample sizes, vastly different inclusion
criteria, methods of sampling and testing, and different diagnostic criteria
for various outcomes including BPD. A
meta-analysis by Schelonka et al,2
which included 23 studies and 2216 infants, revealed an odds ratio (OR) of
2.83 (95% confidence interval [CI]:
2.29 –3.51) for the relationship between the presence of Ureaplasma
and BPD diagnosed at 28 days of life.
However, a causative role of U urealyticum could not be proven.
Additional controversy exists on the use
of macrolides, particularly erythromycin, for the treatment of U urealyticum
colonization. A recent Cochrane analysis3 identified 2 randomized studies. In
neither trial was a significant effect of
erythromycin shown on development of
BPD or death. But both studies had a
small sample size and underpowered to
detect a true benefit. The lack of efficacy
of erythromycin on the incidence of BPD
may also be secondary to low rate of
eradication of U urealyticum from the
airway.4
In this study, we aimed to determine
the relation of U urealyticum colonization to BPD in preterm infants with a
PEDIATRICS Volume 128, Number 6, December 2011
birth weight of ⱕ1250 g and to evaluate, for the first time, the efficacy and
safety of clarithromycin treatment in
eradicating U urealyticum in the respiratory tract and preventing BPD in
culture-positive preterm infants.
PATIENTS AND METHODS
This placebo-controlled, prospective,
randomized study was conducted in
Zekai Tahir Burak Maternity Teaching
Hospital, which is one of the largest
maternity hospitals in Turkey and performs 20 000 deliveries annually. The
NICU includes 150 incubators and admits ⬃4000 infants annually. Infants
who were eligible for the study were
determined as preterms with a birth
weight between 750 and 1250 g. Exclusion criteria consisted of the presence
of major congenital abnormalities,
lack of parental informed consent, and
intrauterine growth retardation with a
birth weight at the ⬍10th percentile
for gestational age.
The primary outcomes for this study
were eradication of U urealyticum in
the airways and the composite chronic
lung disease and/or death. BPD was
defined as a persistent oxygen requirement at 36 weeks’ postmenstrual age.
A physiologic test was used to confirm
the need for oxygen at the time when
BPD was being diagnosed. Infants with
moderate dependency on oxygen at 36
weeks’ postmenstrual age (⬍30% oxygen) were challenged with room air
breathing to determine if the supplemental oxygen was in fact needed.
Perinatal characteristics of the patients including birth weight, gestational age, route of delivery, prenatal
steroid use, the presence of premature rupture of membrane, chorioamnionitis, sepsis, respiratory distress
syndrome (RDS), surfactant use, pneumonia, patent ductus arteriosus (PDA),
as well as postnatal clinical parameters including duration of mechanical
ventilation, nasal continuous positive
airway pressure, O2 therapy, caffeine,
and diuretic treatment were recorded.
Infants were diagnosed with RDS if
they had tachypnea, grunting, and cyanosis within several hours of birth,
required mechanical ventilation including continuous positive airway
pressure and oxygen in the first hours
of life, and typical radiographic findings on the chest radiograph.5 BPD was
diagnosed by using the US National Institutes of Health diagnostic criteria
for BPD.1 PDA diagnosis required an
echocardiogram with Doppler verification and cardiology recommendation
of ibuprofen therapy on the basis of
significance of flow.6
Nasopharyngeal swabs for U urealyticum were taken in first 3 postnatal
days and on the 12th day after the commencing of the treatment only in
culture-positive infants, transported to
the laboratory, and cultured for U urealyticum immediately in special medium.
U urealyticum is detected according to
method defined by Biernat-Sudolska et
al7 and culture results were obtained in
a maximum of 48 hours.
Infants with a positive culture for U
urealyticum in the first 3 days were
randomly assigned to 1 of 2 groups to
receive either intravenous clarithromycin (10 mg/kg twice per day for 10
days) or placebo. Randomization was
performed by the use of sealed envelopes with the allocation of the patients to either clarithromycin treatment or placebo. Colonization by other
potential pathogens was treated as
warranted, according to the attending
physician. Repeat cultures were obtained in the clarithromycin group to
determine U urealyticum eradication.
All the patients were followed up to at
least the 36th postmenstrual week of
gestation, when the presence of BPD
was assessed, or death.
Statistical analysis was performed by
using SPSS 17.0 (SPSS Inc, Chicago, IL).
It was calculated that a sample size of
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e1497
Randomization
Allocation
Follow-up
Excluded (n = 48)
Assesed for enrollment
(N = 272)
— Major congenital abnormality (n = 7)
— Refused to participate (n = 21)
— Death (n = 12)
— Intrauterine growth retardation (n = 8)
Randomly assigned
Culture-negative (n = 150)
-Death (n = 12)
Culture-positive (n = 74)
Clarithromycin treatment
No treatment
(n = 37)
(n = 37)
Discontinued intervention
Discontinued intervention
Death; sepsis (1), necrotizing
Death; sepsis (3), necrotizing
enterocolitis (1)
enterocolitis (1)
Analyzed: 35
Analyzed: 33
Analysis
The study was approved by the institutional local ethics committee, and informed parental consent was obtained
from all participants.
Enrollment
250 infants was required to yield
⬎90% power to detect a 7% reduction
in BPD incidence resulting from clarithromycin treatment.8 Independent
samples t test or Mann-Whitney U test
was used to compare continuous variables and ␹2 test or Fisher’s exact test
for categorical variables. Multivariate
(backward) logistic regression analysis was performed to simultaneously
measure the influence of the independent variables with BPD as the dependent variable. Variables that had a P
value of ⬍.25 in the univariate analysis
were used in multivariate analysis as
possible risk factors. A P value of ⬍.05
was considered statistically significant.
FIGURE 1
Flowchart.
RESULTS
During the study period, 272 infants
with a birth weight between 750 and
1250 g were enrolled in the study.
Forty-eight infants were excluded because of major congenital abnormalities, lack of parental informed consent, intrauterine growth retardation,
or death. There were a total of 224 infants who met the eligibility criteria,
and 150 infants were culture-negative
for U urealyticum in the first 3 days,
whereas 12 infants in the culturenegative group died by follow-up.
Seventy-four (33%) infants had a positive culture for U urealyticum in the
first 3 day cultures (Fig 1).
To search for an association between
U urealyticum positivity and the development of BPD, we have assessed the
characteristics and outcomes of the U
urealyticum–negative patients and U
urealyticum–positive patients who did
not receive clarithromycin (Table 1).
BPD development was significantly
higher in patients with U urealyticum
positivity (15.9% vs 36.4%; P ⬍ .01).
However, multivariate logistic regrese1498
OZDEMIR et al
TABLE 1 Characteristics and Outcomes of U urealyticum–Negative and Untreated U urealyticum–
Positive Patients
Birth weight, mean ⫾ SD, g
Gestational age, mean ⫾ SD, wk
Male, n/N (%)
Cesarean delivery, n/N (%)
Prenatal steroids, n/N (%)
PROM ⬎ 18 h, n/N (%)
Histologic chorioamnionitis, n/N (%)
Sepsis, n/N (%)
Pneumonia, n/N (%)
PDA, n/N (%)
RDS, n/N (%)
Poractant alfa treatment, n/N (%)
Caffeine treatment, n/N (%)
Diuretic treatment, n/N (%)
Duration of mechanical ventilation,
mean ⫾ SD, d
Duration of n-CPAP, mean ⫾ SD, d
BPD at 36 wk, n/N (%)
U urealyticum–Negative
(N ⫽ 138)
U urealyticum–Positive,
Clarithromycin-Negative
(N ⫽ 33)
P
1028 ⫾ 160
28.2 ⫾ 1.6
57/138 (41.3)
116/138 (84)
101/138 (73)
22/138 (15.9)
5/138 (3.6)
55/138 (38.4)
13/138 (9.4)
46/138 (33.3)
87/138 (63)
59/87 (67.8)
114/138 (82.6)
13/138 (9.4)
1.9 ⫾ 4.3
978 ⫾ 195
27.3 ⫾ 1.8
17/33 (51.5)
19/33 (57.6)
20/33 (60.6)
3/33 (9.1)
0/33 (0)
14/33 (42.4)
3/33 (9.1)
15/33 (45.5)
21/33 (63.6)
13/21 (61.9)
28/33 (84.8)
1/33 (3)
3.1 ⫾ 4.6
.13
⬍.01
.28
⬍.01
.15
.41
.33
.67
.95
.19
.94
.60
.75
.31
.16
3.6 ⫾ 3.9
22/138 (15.9)
5.8 ⫾ 6.2
12/33 (36.4)
.01
⬍.01
PROM indicates premature rupture of membrane; n-CPAP, nasal continuous positive airway pressure.
sion analysis including birth weight,
gestational age, gender, presence of
RDS, pneumonia and PDA, culture
positivity for U urealyticum, caffeine
treatment, and mechanical ventilation
in model failed to demonstrate a significant association between the pres-
ence of U urealyticum and BPD development, although P bordered significance (OR: 2.4 [95% CI: 0.9 – 6.3]; P ⫽
.06). The only significant variable associated with BPD development was duration of mechanical ventilation (OR:
1.1 [95% CI: 1–1.2]; P ⫽ .01).
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ARTICLES
TABLE 2 Characteristics and Outcomes of U urealyticum–Positive Patients Treated With
Clarithromycin or Placebo
Birth weight, mean ⫾ SD, g
Gestational age, mean ⫾ SD, wk
Male, n/N (%)
Cesarean delivery, n/N (%)
Prenatal steroids, n/N (%)
PROM ⬎ 18 h, n/N (%)
Histologic chorioamnionitis, n/N (%)
Sepsis, n/N (%)
Pneumonia, n/N (%)
PDA, n/N (%)
RDS, n/N (%)
Poractant alfa treatment, n/N (%)
Caffeine treatment, n/N (%)
Diuretic treatment, n/N (%)
Duration of mechanical ventilation,
mean ⫾ SD, d
Duration n-CPAP, mean ⫾ SD, d
BPD at 36 wk, n/N (%)
U urealyticum–Positive
Clarithromycin-Treated
(N ⫽ 35)
U urealyticum–Positive,
Clarithromycin-Negative
(N ⫽ 33)
P
988 ⫾ 104
27.4 ⫾ 1.3
13/35 (37.1)
22/35 (62.9)
24/35 (68.6)
7/35 (20)
1/35 (2.9)
16/35 (45.7)
3/35 (8.6)
10/35 (28.6)
20/35 (57.1)
11/20 (55)
26/35 (74.3)
3/35 (8.6)
1.8 ⫾ 4.7
978 ⫾ 195
27.3 ⫾ 1.8
17/33 (51.5)
19/33 (57.6)
20/33 (60.6)
3/33 (9.1)
0/33 (0)
14/33 (42.4)
3/33 (9.1)
15/33 (45.5)
21/33 (63.6)
13/21 (61.9)
28/33 (84.8)
1/33 (3)
3.1 ⫾ 4.6
.79
.65
.23
.65
.49
.20
.33
.78
.94
.14
.58
.65
.28
.33
.25
3.7 ⫾ 3.6
1/35 (2.9)
5.8 ⫾ 6.2
12/33 (36.4)
.10
⬍.001
PROM indicates premature rupture of membrane; n-CPAP, nasal continuous positive airway pressure.
U urealyticum–positive patients were
prospectively randomly assigned to receive either clarithromycin (n ⫽ 37) or
placebo (n ⫽ 37). Characteristics of
the U urealyticum–positive patients
who received clarithromycin or placebo are shown in Table 2. According
to the repeat cultures 2 days after the
discontinuation of the treatment, clarithromycin treatment resulted in eradication of U urealyticum in 68.5% of the
patients. Groups did not have significant difference in incidences of PDA,
sepsis, and pneumonia, whereas the
incidence of BPD was significantly
lower in the clarithromycin group
(2.9% vs 36.4%; P ⬍ .001). Deaths in the
groups had occurred before the evaluation of BPD at the 36th postmenstrual
week, and they were not related to pulmonary problems; therefore, we did
not choose to use the composite outcome of death or BPD. However, when
statistical analysis was performed for
the composite outcome defined as death
or BPD, there was still a highly significant
difference between the treatment and
control groups (P ⫽ .001).
Variables that had a P value of ⬍.25 in
the univariate analysis were used in
PEDIATRICS Volume 128, Number 6, December 2011
multivariate analysis as possible risk
factors in subgroup analysis. Multivariate logistic regression analysis including birth weight, presence of
pneumonia and PDA, caffeine and clarithromycin treatment, mechanical
ventilation, and nasal continuous positive airway pressure in model confirmed the independent preventive effect of the clarithromycin (OR: 27.2
[95% CI: 2.5–296.1]; P ⫽ .007) for the
development of BPD. No serious adverse event related to clarithromycin
use was documented.
DISCUSSION
We demonstrated that 33% of the preterm infants with birth weight between
750 and 1250 g had U urealyticum positivity in nasopharyngeal swabs. U
urealyticum positivity was associated
with higher rate of BPD development,
but we failed to demonstrate this association in multivariate analysis, probably because of low number of patients;
the P value and 95% CI bordered significance. Treatment of these infants with
clarithromycin resulted in lower rates
of BPD than those treated with
placebo.
Ureaplasma comprises 2 species (U
parvum and U urealyticum) and 14 serovars. Ureaplasma is a commensal in
the adult female genital tract with low
virulance. However, previous studies
have shown association of U urealyticum with infertility, adverse pregnancy outcomes, and perinatal
death.9–12 Vertical transmission rate is
inversely related to gestational age
(18%–55% in term infants versus
29%– 60% in preterm infants)10–13 and
increases with duration of rupture of
membranes.14–16 Respiratory tract colonization was detected in 20% of infants born at ⬍1500 g by cultures and
25% to 48% by polymerase chain reaction. Culture positivity was 30% in our
study, consistent with the literature.
Differences in colonization rates may
be a result of differences in communities or in specimen collection and
processing.
Since the 1980s, many studies have
searched for the link between U urealyticum colonization and BPD development.17–19 Although not all the studies
have confirmed the association, the
meta-analysis by Wang et al20 in 1995
showed that the relative risk for the
development of BPD in U urealyticum
colonized infants was 1.72 (95% CI:
1.5–1.96). These findings were confirmed by Schelonka et al2 in their
meta-analysis in 2005, which revealed
a significant association between
Ureaplasma infection and development of BPD, at both 28 days (P ⬍ .001)
and 36 weeks (P ⬍ .001) by definition.
In a number of subsequent trials, the
therapeutic efficacy of erythromycin
therapy was searched for in the first
few weeks of life, given the in vitro sensitivity of U urealyticum to erythromycin. In 1 study, Lyon et al21 randomly
assigned 75 infants born at ⬍30
weeks’ gestation and ventilated from
birth for lung disease to receive erythromycin (n ⫽ 34) intravenously for 7
days or to no treatment (n ⫽ 41). Nine
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e1499
infants (13%) were positive for U urealyticum by culture or polymerase chain
reaction. Those treated with erythromycin had a similar incidence of BPD
as untreated infants. A small number
of infected patients made it impossible
to analyze infected infants alone. In the
second study, Jonsson et al22 investigated colonization with U urealyticum
in 155 infants born at ⬍30 weeks’ gestation and assessed the effect of treatment with erythromycin. The rate of
colonization was 29 of 155 (19%). More
colonized infants needed supplemental oxygen at 36 weeks’ postconceptional age compared with noncolonized infants. Colonized infants were
randomly assigned to treatment with
erythromycin 40 mg/kg per day, intravenously or orally (n ⫽ 14), or no treatment (n ⫽ 14). Erythromycin treatment eradicated colonization in 12 of
14 (86%) treated infants. However,
there was no significant difference between treated and untreated infants in
the rate of BPD at 36 weeks’ postconceptional age (64% in treated infants
versus 71% in untreated group). These
2 randomized trials of erythromycin
had low number of infected infants
and no specific analysis in this subgroup could be made in the first trial,
whereas only 14 patients could be evaluated in both arms in the second trial,
which increases the possibility to miss
a true benefit of erythromycin because
of type II error. Another reason why
erythromycin was ineffective in preventing BPD development might be
relatively lower anti-inflammatory activity of erythromycin in preterm
infants.4,21,23
We preferred to use clarithromycin in
our study instead of erythromycin. In
vitro activity of clarithromycin against
U urealyticum is much higher than
erythromycin.24,25 Second, penetration
of clarithromycin into bronchial mucosa, bronchial secretions, and epithelial lining as reflected by the tissue/
e1500
OZDEMIR et al
fluid-to-serum ratio is higher than that
for erythromycin. Twice-daily use and
a better toxicity profile are other
advantages of clarithromycin over
erythromycin.26
In a recent study by Ballard et al,27 220
infants who had a birth weight of
⬍1250 g were randomly assigned to
azithromycin 10 mg/kg per day for 7
days followed by 5 mg/kg per day for a
maximum of 6 weeks (n ⫽ 111) or placebo (n ⫽ 109) within 12 h of beginning
mechanical ventilation and within 72 h
of birth. The incidence of BPD in the U
urealyticum–positive subgroup was
73% in those treated with azithromycin
versus 94% in the placebo group (P ⫽
.03). The authors concluded that early
treatment of U urealyticum colonized/
infected patients might be beneficial.27
Our study also yielded benefit from
treatment in culture-positive infants,
similar to this study. BPD incidence
was overall lower in our study than in
the study of Ballard et al.27 This might
be secondary to the differences in patient characteristics of studies. Mean
birth weight was 803 g in their study
versus 1013 g in our study, and mean
gestational age was 25.7 vs 27.9 weeks,
respectively.
Several studies in the literature show
that macrolides affect many inflammatory processes including migration of
neutrophils, the oxidative burst in
phagocytes, and production of proinflammatory cytokines.28 Clarithromycin inhibits superoxide production by
activated neutrophils and also has a
membrane-stabilizing activity.29 Clarithromycin was also found to suppress
interleukin 1␤ gene expression in human nasal epithelial cells.30 We believe
that anti-inflammatory effects of clarithromycin also contribute to overall
lower incidence of BPD in the treatment group, but we could not evaluate
pure anti-inflammatory effect of clarithromycin in our study because no
culture-negative infants received clari-
thromycin. However, the benefit of azithromycin was observed selectively in
culture-positive infants but not in the
whole group in the study of Ballard et
al.27 Thus, anti-microbial activity seems
to be more considerable compared
with anti-inflammatory activity in prevention of BPD. Prospective trials are
needed to confirm these hypotheses.
Because of an overall low rate of BPD
in patients treated with clarithromycin, we could not assess whether failure to eradicate U urealyticum was associated with higher incidence of BPD.
There are a number of limitations to our
study. First, ours was a single-center
study, and our findings should be confirmed by additional well-designed clinical trials in different settings. Second,
although there were not significant differences in incidences of PDA, sepsis and
pneumonia between groups, there was a
tendency to lower rates of these parameters in treatment group, which might
affect BPD development. Third, this study
was a pioneering one, and it seems that
there is a requirement for additional
studies with larger sample size estimates for the cohort of infants randomly
assigned to the treatment and placebo
groups.
CONCLUSIONS
Clarithromycin treatment for U
urealyticum–positive very low birth
weight infants was shown to reduce the
incidence of BPD development in this
study. The benefit of clarithromycin in U
urealyticum–negative infants is currently unclear. Given the advantage of
early use of antibiotics in these patients,
early treatment after obtaining respiratory cultures for U urealyticum, and discontinuation of treatment in culturenegative patients, might be a feasible
strategy. Additional randomized studies
are needed to establish routine use of
macrolides in this high-risk population.
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ARTICLES
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e1501
Clarithromycin in Preventing Bronchopulmonary Dysplasia in Ureaplasma
urealyticum−Positive Preterm Infants
Ramazan Ozdemir, Omer Erdeve, Evrim Alyamac Dizdar, Serife Suna Oguz, Nurdan
Uras, Sibel Saygan, Erdem Karabulut and Ugur Dilmen
Pediatrics 2011;128;e1496; originally published online November 28, 2011;
DOI: 10.1542/peds.2011-1350
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