PMID- 32591087
OWN - NLM
STAT- MEDLINE
DCOM- 20200820
LR  - 20220716
IS  - 1097-6868 (Electronic)
IS  - 0002-9378 (Print)
IS  - 0002-9378 (Linking)
VI  - 223
IP  - 1
DP  - 2020 Jul
TI  - Antibiotic administration reduces the rate of intraamniotic inflammation in 
      preterm prelabor rupture of the membranes.
PG  - 114.e1-114.e20
LID - S0002-9378(20)30065-X [pii]
LID - 10.1016/j.ajog.2020.01.043 [doi]
AB  - BACKGROUND: Preterm prelabor rupture of the membranes (PPROM) is frequently 
      complicated by intraamniotic inflammatory processes such as intraamniotic 
      infection and sterile intraamniotic inflammation. Antibiotic therapy is 
      recommended to patients with PPROM to prolong the interval between this 
      complication and delivery (latency period), reduce the risk of clinical 
      chorioamnionitis, and improve neonatal outcome. However, there is a lack of 
      information regarding whether the administration of antibiotics can reduce the 
      intensity of the intraamniotic inflammatory response or eradicate microorganisms 
      in patients with PPROM. OBJECTIVE: The first aim of the study was to determine 
      whether antimicrobial agents can reduce the magnitude of the intraamniotic 
      inflammatory response in patients with PPROM by assessing the concentrations of 
      interleukin-6 in amniotic fluid before and after antibiotic treatment. The second 
      aim was to determine whether treatment with intravenous clarithromycin changes 
      the microbial load of Ureaplasma spp DNA in amniotic fluid. STUDY DESIGN: A 
      retrospective cohort study included patients who had (1) a singleton gestation, 
      (2) PPROM between 24+0 and 33+6 weeks, (3) a transabdominal amniocentesis at the 
      time of admission, and (4) intravenous antibiotic treatment (clarithromycin for 
      patients with intraamniotic inflammation and benzylpenicillin/clindamycin in the 
      cases of allergy in patients without intraamniotic inflammation) for 7 days. 
      Follow-up amniocenteses (7(th) day after admission) were performed in the subset 
      of patients with a latency period lasting longer than 7 days. Concentrations of 
      interleukin-6 were measured in the samples of amniotic fluid with a bedside test, 
      and the presence of microbial invasion of the amniotic cavity was assessed with 
      culture and molecular microbiological methods. Intraamniotic inflammation was 
      defined as a bedside interleukin-6 concentration >/=745 pg/mL in the samples of 
      amniotic fluid. Intraamniotic infection was defined as the presence of both 
      microbial invasion of the amniotic cavity and intraamniotic inflammation; sterile 
      intraamniotic inflammation was defined as the presence of intraamniotic 
      inflammation without microbial invasion of the amniotic cavity. RESULTS: A total 
      of 270 patients with PPROM were included in this study: 207 patients delivered 
      within 7 days and 63 patients delivered after 7 days of admission. Of the 63 
      patients who delivered after 7 days following the initial amniocentesis, 40 
      underwent a follow-up amniocentesis. Patients with intraamniotic infection (n = 
      7) and sterile intraamniotic inflammation (n = 7) were treated with intravenous 
      clarithromycin. Patients without either microbial invasion of the amniotic cavity 
      or intraamniotic inflammation (n = 26) were treated with benzylpenicillin or 
      clindamycin. Treatment with clarithromycin decreased the interleukin-6 
      concentration in amniotic fluid at the follow-up amniocentesis compared to the 
      initial amniocentesis in patients with intraamniotic infection (follow-up: 
      median, 295 pg/mL, interquartile range [IQR], 72-673 vs initial: median, 2973 
      pg/mL, IQR, 1750-6296; P = .02) and in those with sterile intraamniotic 
      inflammation (follow-up: median, 221 pg/mL, IQR 118-366 pg/mL vs initial: median, 
      1446 pg/mL, IQR, 1300-2941; P = .02). Samples of amniotic fluid with Ureaplasma 
      spp DNA had a lower microbial load at the time of follow-up amniocentesis 
      compared to the initial amniocentesis (follow-up: median, 1.8 x 10(4) copies 
      DNA/mL, 2.9 x 10(4) to 6.7 x 10(8) vs initial: median, 4.7 x 10(7) copies DNA/mL, 
      interquartile range, 2.9 x 10(3) to 3.6 x 10(7); P = .03). CONCLUSION: 
      Intravenous therapy with clarithromycin was associated with a reduction in the 
      intensity of the intraamniotic inflammatory response in patients with PPROM with 
      either intraamniotic infection or sterile intraamniotic inflammation. Moreover, 
      treatment with clarithromycin was related to a reduction in the load of 
      Ureaplasma spp DNA in the amniotic fluid of patients with PPROM <34 weeks of 
      gestation.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Kacerovsky, Marian
AU  - Kacerovsky M
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, US Department 
      of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of 
      Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, 
      MI; Biomedical Research Center, University Hospital Hradec Kralove, Hradec 
      Kralove, Czech Republic; Department of Obstetrics and Gynecology, University 
      Hospital Hradec Kralove, Charles University, Faculty of Medicine, Hradec Kralove, 
      Czech Republic. Electronic address: mkacerovsky@med.wayne.edu.
FAU - Romero, Roberto
AU  - Romero R
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, US Department 
      of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of 
      Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of 
      Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; 
      Center for Molecular Medicine and Genetics, Wayne State University, Detroit, 
      Michigan; Detroit Medical Center, Detroit, MI; Department of Obstetrics and 
      Gynecology, Florida International University, Miami, FL.
FAU - Stepan, Martin
AU  - Stepan M
AD  - Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, 
      Charles University, Faculty of Medicine, Hradec Kralove, Czech Republic.
FAU - Stranik, Jaroslav
AU  - Stranik J
AD  - Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, 
      Charles University, Faculty of Medicine, Hradec Kralove, Czech Republic.
FAU - Maly, Jan
AU  - Maly J
AD  - Department of Pediatrics, University Hospital Hradec Kralove, Charles University, 
      Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
FAU - Pliskova, Lenka
AU  - Pliskova L
AD  - Institute of Clinical Biochemistry and Diagnosis, University Hospital Hradec 
      Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec 
      Kralove, Czech Republic.
FAU - Bolehovska, Radka
AU  - Bolehovska R
AD  - Institute of Clinical Biochemistry and Diagnosis, University Hospital Hradec 
      Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec 
      Kralove, Czech Republic.
FAU - Palicka, Vladimir
AU  - Palicka V
AD  - Institute of Clinical Biochemistry and Diagnosis, University Hospital Hradec 
      Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec 
      Kralove, Czech Republic.
FAU - Zemlickova, Helena
AU  - Zemlickova H
AD  - Institute of Clinical Microbiology, University Hospital Hradec Kralove, Charles 
      University, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech 
      Republic.
FAU - Hornychova, Helena
AU  - Hornychova H
AD  - Fingerland's Department of Pathology, University Hospital Hradec Kralove, Charles 
      University, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech 
      Republic.
FAU - Spacek, Jiri
AU  - Spacek J
AD  - Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, 
      Charles University, Faculty of Medicine, Hradec Kralove, Czech Republic.
FAU - Jacobsson, Bo
AU  - Jacobsson B
AD  - Department of Obstetrics and Gynecology, Institute of Clinical Science, 
      Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of 
      Obstetrics and Gynecology, Region Vastra Gotaland, Sahlgrenska University 
      Hospital, Gothenburg Sweden; Department of Genetics and Bioinformatics, Domain of 
      Health Data and Digitalisation, Institute of Public Health, Oslo, Norway.
FAU - Pacora, Percy
AU  - Pacora P
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, US Department 
      of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of 
      Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, 
      MI.
FAU - Musilova, Ivana
AU  - Musilova I
AD  - Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, US Department 
      of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of 
      Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, 
      MI; Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, 
      Charles University, Faculty of Medicine, Hradec Kralove, Czech Republic.
LA  - eng
GR  - HHSN275201300006C/HD/NICHD NIH HHS/United States
GR  - Z01 HD002400/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Obstet Gynecol
JT  - American journal of obstetrics and gynecology
JID - 0370476
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (DNA, Bacterial)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 3U02EL437C (Clindamycin)
RN  - H1250JIK0A (Clarithromycin)
RN  - Q42T66VG0C (Penicillin G)
SB  - IM
MH  - Adult
MH  - Amniotic Fluid/chemistry
MH  - Anti-Bacterial Agents/*therapeutic use
MH  - Bacterial Infections/etiology/*prevention & control
MH  - Chorioamnionitis/etiology/*prevention & control
MH  - Clarithromycin/*therapeutic use
MH  - Clindamycin/*therapeutic use
MH  - Cohort Studies
MH  - DNA, Bacterial/analysis
MH  - Female
MH  - *Fetal Membranes, Premature Rupture
MH  - Humans
MH  - Interleukin-6/analysis
MH  - Penicillin G/*therapeutic use
MH  - Pregnancy
MH  - Retrospective Studies
MH  - Ureaplasma/genetics
PMC - PMC9125527
MID - NIHMS1800220
OTO - NOTNLM
OT  - 16S ribosomal RNA
OT  - Ureaplasma
OT  - amniocentesis
OT  - amniotic fluid
OT  - bacteria
OT  - benzylpenicillin
OT  - biomarker
OT  - chorioamnionitis
OT  - clarithromycin
OT  - funisitis
OT  - genital mycoplasmas
OT  - great obstetrical syndromes
OT  - inflammation
OT  - interleukin-6
OT  - intraamniotic infection
OT  - microbial invasion of the amniotic cavity
OT  - neonatal outcome
OT  - neonatal sepsis
OT  - nucleic acid
OT  - polymerase chain reaction
OT  - pregnancy
OT  - prematurity
OT  - preterm birth
OT  - rapid point of care test
OT  - sterile intraamniotic inflammation
COIS- Disclosures: The authors report no conflict of interest.
EDAT- 2020/06/28 06:00
MHDA- 2020/08/21 06:00
PMCR- 2022/05/23
CRDT- 2020/06/28 06:00
PHST- 2019/10/10 00:00 [received]
PHST- 2020/01/22 00:00 [revised]
PHST- 2020/01/24 00:00 [accepted]
PHST- 2020/06/28 06:00 [entrez]
PHST- 2020/06/28 06:00 [pubmed]
PHST- 2020/08/21 06:00 [medline]
PHST- 2022/05/23 00:00 [pmc-release]
AID - S0002-9378(20)30065-X [pii]
AID - 10.1016/j.ajog.2020.01.043 [doi]
PST - ppublish
SO  - Am J Obstet Gynecol. 2020 Jul;223(1):114.e1-114.e20. doi: 
      10.1016/j.ajog.2020.01.043.