Infektionsmanagement bei drohender Frühgeburt – eine Umfrage an deutschen Perinatalzentren

Zusammenfassung

Einleitung Internationalen und nationalen Leitlinien fehlt es an detaillierten Empfehlungen zur Infektionsdiagnostik und -therapie bei drohender Frühgeburt. Ziel der Studie war es, Daten zur Versorgungssituation an deutschen Perinatalzentren zu erheben.

Methoden Onlineumfrage zum Infektionsmanagement bei drohender Frühgeburt an allen 212 deutschen Perinatalzentren der Versorgungsstufen Level I und II.

Ergebnisse Die Rücklaufquote betrug 31,6% (n=67). Bei drohender Frühgeburt unter 34 vollendeten SSW ohne Blasensprung verzichten 78,8% auf eine kalkulierte Antibiotikagabe. Von den verbleibenden vierzehn Zentren (21,2%) würde die Hälfte generell bei klinischen Zeichen einer drohenden Frühgeburt antibiotisch behandeln. Fast alle Zentren (94%) führen eine vaginale Erregerdiagnostik durch. Eine mikroskopische Abstrichbeurteilung mittels Nugent- oder Amsel-Score erfolgt in 37,3%. Abweichungen von der physiologischen vaginalen Mikrobiota werden mehrheitlich antibiotisch behandelt (bakterielle Vaginose 79,1%, n=53, Candida spp. 77,6%, n=52, Ureaplasma spp. 49,3%, n=33). Kontrollabstriche erfolgen in 70,1%. Konsens besteht hinsichtlich einer Antibiotikagabe bei frühem vorzeitigem Blasensprung. 72,6% bevorzugen eine Monotherapie mit einem β-Laktam-Antibiotikum. Uneinheitlich waren hier die Angaben zur Dauer der Therapie, wobei 58% der Zentren länger als sieben Tage behandeln.

Schlussfolgerung An deutschen Perinatalzentren besteht eine hohe Bereitschaft zur Infektionsdiagnostik und -therapie bei drohender Frühgeburt. Das Infektionsmanagement ist jedoch uneinheitlich und partiell widersprüchlich zu den vorliegenden Leitlinien. Es besteht ein Bedarf an qualitativ hochwertigen Studien zu diesem Thema.

Abstract

Introduction In spite of insufficient evidence, we assume a high willingness to diagnose and treat vaginal infections in threatened preterm births in Germany.

Methods Online survey on the management of infection in threatened preterm birth in all 212 German perinatal centers.

Results The response rate was 31.6% (n=67). 78.8% disclaim an empirical antibiotic treatment in threatened preterm birth below 34 weeks of gestation. Half of the remaining 14 centers always start an antibiotic treatment in cases with signs or symptoms of threatened preterm birth. 94% perform vaginal swabs for culture. 37.3% use a microscopic assessment by vaginal Nugent score or Amsel score. An abnormal vaginal microbiota is mostly treated (bacterial vaginosis 79.1%, n=53, Candida spp. 77.6%, n=52, Ureaplasma spp. 49.3%, n=33). After treatment, 70.1% agree with repeating the culture diagnosis. There is common consensus for antibiotic treatment in cases with preterm premature rupture of membranes. 72.6% favor a monotherapy with a β-lactam antibiotic. Statements on duration of therapy were inconsistent, whereby 58% of centers treat for more than 7 days.

Conclusion In German perinatal centers, we observed a great willingness to diagnose and treat infections in threatened preterm birth. However, the management of infection is heterogeneous and partly contradicts the present guidelines.

Schlüsselwörter

Frühgeburt - Perinatalzentren - Infektion - Umfrage

Key words

preterm birth - perinatal centre - infection - survey

Publication History

Received: 26 October 2020

Accepted after revision: 21 February 2021

Article published online:
09 April 2021

• Literatur

• 1 Romero R, Gomez R, Chaiworapongsa T. et al. The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol 2001; 15 (Suppl 2): 41-56
• 2 Agrawal V, Hirsch E. Intrauterine infection and preterm labor. Semin Fetal Neonatal Med 2012; 17: 12-19
• 3 Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med 2000; 342: 1500-1507
• 4 Watts DH, Krohn MA, Hillier SL. et al. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol 1992; 79: 351-357
• 5 Galask RP, Varner MW, Petzold CR. et al. Bacterial attachment to the chorioamniotic membranes. Am J Obstet Gynecol 1984; 148: 915-928
• 6 Yoon BH, Romero R, Moon JB. et al. Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol 2001; 185: 1130-1136
• 7 DiGiulio DB, Romero R, Amogan HP. et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One 2008; 3: e3056
• 8 Prince AL, Ma J, Kannan PS. et al. The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis. Am J Obstet Gynecol 2016; 214: 627, e621-627, e616
• 9 Romero R, Gomez-Lopez N, Winters AD. et al. Evidence that intra-amniotic infections are often the result of an ascending invasion – a molecular microbiological study. J Perinat Med 2019; 47: 915-931
• 10 Gravett MG, Hummel D, Eschenbach DA. et al. Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol 1986; 67: 229-237
• 11 Hay PE, Lamont RF, Taylor-Robinson D. et al. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ 1994; 308: 295-298
• 12 Hillier SL, Nugent RP, Eschenbach DA. et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 1995; 333: 1737-1742
• 13 McDonald HM, O'Loughlin JA, Jolley P. et al. Prenatal microbiological risk factors associated with preterm birth. Br J Obstet Gynaecol 1992; 99: 190-196
• 14 DiGiulio DB, Callahan BJ, McMurdie PJ. et al. Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci U S A 2015; 112: 11060-11065
• 15 Farr A, Kiss H, Hagmann M. et al. Role of Lactobacillus Species in the Intermediate Vaginal Flora in Early Pregnancy: A Retrospective Cohort Study. PLoS One 2015; 10: e0144181
• 16 Petricevic L, Domig KJ, Nierscher FJ. et al. Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery. Sci Rep 2014; 4: 5136
• 17 Flenady V, Hawley G, Stock OM. et al. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst Rev 2013; CD00024.
• 18 Lamont RF.. Advances in the Prevention of Infection-Related Preterm Birth. Front Immunol 2015; 6: 566
• 19 Lamont RF, Nhan-Chang CL, Sobel JD. et al. Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis. Am J Obstet Gynecol 2011; 205: 177-190
• 20 Medley N, Poljak B, Mammarella S. et al. Clinical guidelines for prevention and management of preterm birth: a systematic review. BJOG 2018; 125: 1361-1369
• 21 R Core Team (2020) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL: http://www.R-project.org/
• 22 Cunningham CT, Quan H, Hemmelgarn B. et al. Exploring physician specialist response rates to web-based surveys. BMC Med Res Methodol 2015; 15: 32
• 23 Kenyon SL, Taylor DJ, Tarnow-Mordi W. et al. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group. Lancet 2001; 357: 989-994
• 24 Gravett MG. Successful treatment of intraamniotic infection/inflammation: a paradigm shift. Am J Obstet Gynecol 2019; 221: 83-85
• 25 Svare J, Langhoff-Roos J, Andersen LF. et al. Ampicillin-metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial. Br J Obstet Gynaecol 1997; 104: 892-897
• 26 Norman K, Pattinson RC, de Souza J. et al. Ampicillin and metronidazole treatment in preterm labour: a multicentre, randomised controlled trial. Br J Obstet Gynaecol 1994; 101: 404-408
• 27 McGregor JA, French JI, Seo K. Adjunctive clindamycin therapy for preterm labor: results of a double-blind, placebo-controlled trial. Am J Obstet Gynecol 1991; 165: 867-875
• 28 Yoon BH, Romero R, Park JY. et al. Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. Am J Obstet Gynecol 2019; 221: 142 e141-142 e122
• 29 Oh KJ, Romero R, Park JY. et al. Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency. Am J Obstet Gynecol 2019; 221: 140, e141-140, e118
• 30 Dinglas C, Chavez M, Vintzileos A. Resolution of intra-amniotic sludge after antibiotic administration in a patient with short cervix and recurrent mid-trimester loss. American Journal of Obstetrics and Gynecology 2019; 221: 159
• 31 Hatanaka AR, Franca MS, Hamamoto T. et al. Antibiotic treatment for patients with amniotic fluid “sludge” to prevent spontaneous preterm birth: A historically controlled observational study. Acta Obstet Gynecol Scand 2019; 98: 1157-1163
• 32 Pustotina O. Effects of antibiotic therapy in women with the amniotic fluid “sludge” at 15-24 weeks of gestation on pregnancy outcomes. J Matern Fetal Neonatal Med 2020; 33: 3016-3027
• 33 Fuchs F, Boucoiran I, Picard A. et al. Impact of amniotic fluid “sludge” on the risk of preterm delivery. J Matern Fetal Neonatal Med 2015; 28: 1176-1180
• 34 Voormolen DN, DeVries JH, Sanson RME. et al. Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial. Diabetes Obes Metab 2018; 20: 1894-1902
• 35 Seelbach-Goebel B. Antibiotic Therapy for Premature Rupture of Membranes and Preterm Labor and Effect on Fetal Outcome. GebFra - DGGG-Gesellschaftsausgaben 2013; 73: 1218-1227
• 36 Mendling M. Diagnostik und Therapie beim Symptom Fluor. Frauenarzt 2018; 59: 120-128
• 37 Donders GG, Van Calsteren K, Bellen G. et al. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG 2009; 116: 1315-1324
• 38 Kirschner WJ, Freitag J, Döbler U, Skonietzki TS. Reduzierte Frühgeburtenrate nach systematischer Vaginaldiagnostik und Therapie Frauenarzt 2020; 61: 278-282
• 39 Payne MS, Newnham JP, Doherty DA. et al. A Specific Bacterial DNA Signature in the Vagina of Australian Women in Mid-Pregnancy Predicts High Risk of Spontaneous Preterm Birth (The Predict1000 Study). Am J Obstet Gynecol 2021; 224: 206
• 40 Bianchi-Jassir F, Seale AC, Kohli-Lynch M. et al. Preterm Birth Associated With Group B Streptococcus Maternal Colonization Worldwide: Systematic Review and Meta-analyses. Clin Infect Dis 2017; 65: S133-S142
• 41 Valkenburg-van den Berg AW, Sprij AJ, Dekker FW. et al. Association between colonization with Group B Streptococcus and preterm delivery: a systematic review. Acta Obstet Gynecol Scand 2009; 88: 958-967
• 42 Lee AC, Mullany LC, Quaiyum M. et al. Effect of population-based antenatal screening and treatment of genitourinary tract infections on birth outcomes in Sylhet, Bangladesh (MIST): a cluster-randomised clinical trial. Lancet. Glob Health 2019; 7: e148-e159
• 43 Donders GG, Donders F, Bellen G. et al. Screening for abnormal vaginal microflora by self-assessed vaginal pH does not enable detection of sexually transmitted infections in Ugandan women. Diagn Microbiol Infect Dis 2016; 85: 227-230
• 44 Choi SJ, Park SD, Jang IH. et al. The prevalence of vaginal microorganisms in pregnant women with preterm labor and preterm birth. Ann Lab Med 2012; 32: 194-200
• 45 Abele-Horn M, Scholz M, Wolff C. et al. High-density vaginal Ureaplasma urealyticum colonization as a risk factor for chorioamnionitis and preterm delivery. Acta Obstet Gynecol Scand 2000; 79: 973-978
• 46 Kenyon S, Pike K, Jones DR. et al. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Lancet 2008; 372: 1319-1327
• 47 Marlow N, Bower H, Jones D. et al. The ORACLE Children Study: educational outcomes at 11 years of age following antenatal prescription of erythromycin or co-amoxiclav. Arch Dis Child Fetal Neonatal Ed 2017; 102: F131-F135
• 48 Subtil D, Brabant G, Tilloy E. et al. Early clindamycin for bacterial vaginosis in pregnancy (PREMEVA): a multicentre, double-blind, randomised controlled trial. Lancet 2018; 392: 2171-2179
• 49 Lee J, Romero R, Kim SM. et al. A new antibiotic regimen treats and prevents intra-amniotic inflammation/infection in patients with preterm PROM. J Matern Fetal Neonatal Med 2016; 29: 2727-2737
• 50 Chatzakis C, Papatheodorou S, Sarafidis K. et al. Effect on perinatal outcome of prophylactic antibiotics in preterm prelabor rupture of membranes: network meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol 2020; 55: 20-31
• 51 Kenyon SL, Taylor DJ, Tarnow-Mordi W. et al. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Lancet 2001; 357: 979-988