amoxicillin-potassium-clavulanate-combination and Enterocolitis--Necrotizing

In the 'Overview of the role of antibiotics in curtailing labour and early delivery' (ORACLE I)-trial in women with premature rupture of membranes, the use of erythromycin was found to be associated with a decrease in the primary composite outcome (neonatal death, chronic lung disease or major cerebral abnormality on ultrasound; p = 0.08) and in single adverse neonatal outcomes (p = 0.02) when compared to placebo. The positive results were more significant in the singleton group (p = 0.02 for the composite outcome), while no effects were found in twin pregnancies. The combination of amoxycillin and clavulanic acid, with or without erythromycin, was associated with some improvements in outcome, but was also accompanied by a higher rate of neonatal necrotising enterocolitis. Another trial (ORACLE II) found no effects of antibiotic use in women with premature labour with intact membranes. Although both trials were of good quality, the stratification into singleton and twin pregnancies should have been done more consistently. Because premature rupture of membranes in singleton pregnancies is more likely to be associated with a pre-existing infection than in multiple pregnancies, the potential benefit of treatment with antibiotics is larger in singleton pregnancies.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Therapy, Combination; Enterocolitis, Necrotizing; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Randomized Controlled Trials as Topic

Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. We did a randomised multicentre trial to try to resolve this issue.. 4826 women with pPROM were randomly assigned 250 mg erythromycin (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat.. Two women were lost to follow-up, and there were 15 protocol violations. Among all 2415 infants born to women allocated erythromycin only or placebo, fewer had the primary composite outcome in the erythromycin group (151 of 1190 [12.7%] vs 186 of 1225 [15.2%], p=0.08) than in the placebo group. Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 [11.2%] vs 166 of 1149 [14.4%], p=0.02). Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only. Use of erythromycin was also associated with prolongation of pregnancy, reductions in neonatal treatment with surfactant, decreases in oxygen dependence at 28 days of age and older, fewer major cerebral abnormalities on ultrasonography before discharge, and fewer positive blood cultures. Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy, they were also associated with a significantly higher rate of neonatal necrotising enterocolitis.. Erythromycin for women with pPROM is associated with a range of health benefits for the neonate, and thus a probable reduction in childhood disability. However, co-amoxiclav cannot be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis. A follow-up study of childhood development and disability after pPROM is planned.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Therapy, Combination; Enterocolitis, Necrotizing; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Treatment Outcome

Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue.. 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat.. None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection.. This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Therapy, Combination; Drug Utilization; Enterocolitis, Necrotizing; Erythromycin; Female; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Treatment Outcome

Necrotising enterocolitis (NEC) was diagnosed in a term infant with Down's syndrome exposed to maternal human immunodeficiency virus (HIV) infection and antiretroviral therapy.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Retroviral Agents; Combined Modality Therapy; Down Syndrome; Enterocolitis, Necrotizing; Female; Gentamicins; HIV Infections; Humans; Infant, Newborn; Mothers

Topics: Amoxicillin-Potassium Clavulanate Combination; Birth Weight; Case-Control Studies; Drug Therapy, Combination; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Regional Blood Flow; Risk; Umbilical Veins

Topics: Amoxicillin-Potassium Clavulanate Combination; Drug Therapy, Combination; Enterocolitis, Necrotizing; Female; Fetal Membranes, Premature Rupture; Humans; Pregnancy; Risk Factors

Topics: Amoxicillin-Potassium Clavulanate Combination; Drug Therapy, Combination; Enterocolitis, Necrotizing; Female; Fetal Membranes, Premature Rupture; Humans; Pregnancy