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Clinical and Experimental Obstetrics & Gynecology  2020, Vol. 47 Issue (2): 194-198    DOI: 10.31083/j.ceog.2020.02.5046
Original Research Previous articles | Next articles
The efficacy of third-generation cephalosporin plus metronidazole versus third-generation cephalosporin plus clarithromycin in neonatal outcomes and oxidative stress markers in women with preterm premature rupture of membranes
J. W. Kim1, Y. H. Kim1, *(), J. H. Moon1, H. A. Jung1, E. J. Noh1
1Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, Republic of Korea
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Abstract  Purpose of Investigation: The purpose of this study is to compare neonatal outcomes and oxidative stress markers of preterm premature rupture of membranes (PPROM) treated with third-generation cephalosporin plus metronidazole (regimen A) with those treated with third-generation cephalosporin plus clarithromycin (regimen B). Materials and Methods: The present study included patients with singleton pregnancies with PPROM at earlier than 34 gestational weeks who were admitted to the Chonnam National University, Gwangju, Korea, between February 2007 and December 2015. Latency period, neonatal outcomes, and oxidative stress markers (including oxygen radical absorbance capacity, malondialdehyde (MDA), protein carbonyl, and interleukin-6) were compared between two groups. Results: Latency period from PPROM to delivery did not differ between the groups (11.0 ± 13.1 vs. 11.5 ± 8.6, p = 0.791). However, there were no significant differences in rate of latency period longer than seven days. More women were delivered after 48 hour in the regimen B group than in the regimen A group (83.6% vs. 94.7%, p = 0.022). However, there were no significant differences in rate of latency period longer than seven days. There was no significant difference in oxidative stress markers after the administration of antibiotics between regimens A and B. Conclusion: The present results show that there was no difference between the two regimens on the latency period and improvement of neonatal outcomes. Although there was no significant difference in neonatal outcomes, the regimen using third-generation cephalosporin plus clarithromycin may have a beneficial effect for short-term prolongation of pregnancy (up to 48 hours) to allow for the administration of antenatal corticosteroids and transfer to the tertiary center.
Key words:  Premature rupture of membranes      Antibiotics      Oxidative stress      Latency period     
Published:  15 April 2020     
Fund: CRI 14006-1/Chonnam National University Hospital Biomedical Research Institute
*Corresponding Author(s):  Y. H. Kim     E-mail:  kimyh@jnu.ac.kr

Cite this article: 

J. W. Kim, Y. H. Kim, J. H. Moon, H. A. Jung, E. J. Noh. The efficacy of third-generation cephalosporin plus metronidazole versus third-generation cephalosporin plus clarithromycin in neonatal outcomes and oxidative stress markers in women with preterm premature rupture of membranes. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(2): 194-198.

URL: 

https://ceog.imrpress.com/EN/10.31083/j.ceog.2020.02.5046     OR     https://ceog.imrpress.com/EN/Y2020/V47/I2/194

Figure 1.  — Flow chart of study population. Regimen A = 3rd-generation cephalosporin plus metronidazole. Regimen B = 3rd-generation cephalosporin plus clarithromycin. PPROM = Preterm premature rupture of membranes. Values are expressed as mean ± SD. Data are presented as n (%).

Table 1  — Patient characteristics.
Regimen A Regimen B p value
(n=110) (n=76)
Maternal age (years) 31.6 ± 4.6 32.3 ± 4.8 0.074
Nulliparous (%) 58 (52.7%) 32 (42.1%) 0.154
Gestational age at
PPROM (weeks)
29.4 ± 2.7 28.9 ± 2.5 0.211
Previous preterm birth (%) 10 (9.1%) 9 (11.8%) 0.542
Table 2  — Pregnancy outcomes.
Regimen A Regimen B p value
(n=110) (n=76)
Latency period (days) 11.0 ± 13.1 11.5 ± 8.6 0.791
Latency period ≥ 48 hrs (%) 92 (83.6%) 72 (94.7%) 0.022
Latency period ≥ 7 days (%) 64 (58.2%) 48 (63.2%) 0.495
Histology (%)
Non-specific

51 (46.4%)

36 (47.4%)
0.724
Chorioamnionitis 52 (47.3%) 32 (42.1%)
Amnionitis 3 (2.7%) 4 (5.3%)
Chorionitis 4 (3.6%) 4 (5.3%)
Cesarean delivery (%) 49 (44.5%) 32 (42.1%) 0.741
Table 3  — Neonatal outcomes.
Regimen A (n=110) Regimen B (n=76) p value
Birth weight (g) 1665.1 ± 524.8 1603.6 ± 457.1 0.409
RDS (%) 47 (42.7%) 40 (52.6%) 0.183
Sepsis (early) (%) 1 (0.9%) 0 (0.0%) 1.000
Sepsis (late) (%) 3 (2.7%) 0 (0.0%) 0.271
IVH 24 (21.8%) 18 (23.7%) 0.765
PVL 2 (1.8%) 3 (3.9%) 0.400
NEC 0 (0.0%) 2 (2.6%) 0.166
CP 0 (0.0%) 0 (0.0%)
Neonatal death 1 (0.9%) 0 (0.0%) 1.000
Table 4  — Laboratory results.
Regimen A (n=110) Regimen B (n=76) p value
ORAC day 0 (μM/μL) 112.0×103 ± 2.9×103 105.6×103 ± 2.7×103 0.856
ORAC day 3 (μM/μL) 98.1×103 ± 3.8×103 111.5×103 ± 1.9×103 0.743
ORAC day 7 (μM/μL) 113.3×103 ± 1.6×103 105.6×103 ± 2.7×103 0.172
MDA day 0 (nmol/mg protein) 6.46 ± 1.78 6.75 ± 1.38 0.535
MDA day 3 (nmol/mg protein) 6.61 ± 1.68 6.96 ± 3.28 1.000
MDA day 7 (nmol/mg protein) 6.41 ± 1.31 7.00 ± 1.76 0.400
Protein carbonyl day 0 (nmol/mg protein) 7.86 ± 3.41 8.36 ± 2.81 0.585
Protein carbonyl day 3 (nmol/mg protein) 6.99 ± 2.14 8.60 ± 5.15 0.488
Protein carbonyl day 7 (nmol/mg protein) 7.27 ± 3.11 8.02 ± 2.55 0.360
IL-6 day 0 (ng/L) 46.36 ± 84.13 47.39 ± 66.06 0.856
IL-6 day 3 (ng/L) 54.71 ± 100.37 26.47 ± 31.66 0.535
IL-6 day 7 (ng/L) 185.17 ± 239.36 104.83 ± 173.12 0.689
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