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Disclosures CHORIOAMNIONITIS: WHAT No Financial Disclosures IS THE EVIDENCE FOR CLINICAL MANAGEMENT? Juan M. Gonzalez, MD Assistant Professor Maternal-Fetal Medicine Department of Ob/Gyn & RS University of California, San Francisco

  1. Disclosures CHORIOAMNIONITIS: WHAT • No Financial Disclosures IS THE EVIDENCE FOR CLINICAL MANAGEMENT? Juan M. Gonzalez, MD Assistant Professor Maternal-Fetal Medicine Department of Ob/Gyn & RS University of California, San Francisco Definition Pathogenesis • Chorioamnionitis • Ascending of cervicovaginal flora • Facilitated by ROM • Amnionitis • Tranplacental • Intramamniotic infection • Listeria moncytogenes • Iatrogenic • Amnio, CVS, fetal surgery

  2. EPIDEMIOLOGY Clin Perinatol. 2010 Jun;37(2):339-54. Preterm Term Intramamniotic infection with pPROM • 2 to 4 % term deliveries • • Less than 27 weeks � 41 % • 28 to 36 weeks � 15 % • 12 % in labor who undergo a cesarean delivery Intraamniotic infection 1/3 of spontaneous • preterm labor with intact membranes Clin Obstet Gynecol. 1993 Dec;36(4):795-808. Am J Obstet Gynecol. 2001 Nov;185(5):1130-6.

  3. Risk Factors • Low parity • Prolonged labor • Prolonged rupture of membranes • Multiple vaginal examinations in labor (consequence of longer labors) • Internal fetal monitoring • Genital tract pathogens (STI, GBS, BV) Microbiology Microbiology • Clinical intraamniotic infection • Bacteroides species (25 %) • 35 % of patients with clinical chorioamnionitis yield Mycoplasm hominis • G. vaginalis (24 %) • GBS (12 %) • Aerobic streptococci (13 %) • E. coli (10%) • Aerobic gram-negative rods (10 %) J Infect Dis. 1983 Apr;147(4):650-3. J Infect Dis. 1982 Jan;145(1):1-8.

  4. Clinical Presentation Clinical Chorioamnionitis • Clinical chorioamnionitis • Maternal fever (oral temp ≥ 38.0C or 100.4F) (all cases) • Subclinical absence of clinical findings: • At least two of the following: • Most commonly presents as spontaneous • wbc > 15k (70-90% of cases) preterm labor or pPROM • maternal tachycardia (> 100 bpm) (50-80% of cases) • fetal tachycardia (> 160 bpm) (50-80% of cases) • uterine tenderness or foul odor of the amniotic fluid (4- 25% of cases) Clin Perinatol. 2010 Jun;37(2):339-54. Amniocentesis Test • Refractory to tocolytics Clinical parameters 95 – 100 sensitive Fever Temperature >100.4 F • pPROM to determine whether induction is Newton ER. Clin Obstet Gynecol 1993;36:795 indicated Maternal tachycardia > 100/min 50 – 80% sensitive Fetal tachycardia >160/min 40 – 70% sensitive • Discriminate between chorioamnionitis and other causes of fever and abdominal pain Fundal tenderness Tenderness on palpation 4 – 25% sensitive Vaginal discharge Foul-smelling discharge 5 – 22% sensitive

  5. TEST ABNORMAL FINDING COMMENT Amniocentesis Allows id of particularly virulent organism: TEST ABNORMAL FINDING COMMENT GBS. However, very sensitive to inoculum Labor and/or ≥ 15,000 cells/mm 3 with effect. Cannot id corticosteroids also may Amniotic fluid gram Maternal white blood Any organism in an oil pathogens such as preponderance of result in elevation of stain cell count (WBC) mycoplasmas. immersion field leukocytes WBC Growth of aerobic or Excellent correlation anaerobic Results are not with positive amniotic Amniotic fluid culture microorganism immediately available fluid culture and clinical Amniotic fluid glucose ≤ 10 to 15 mg% infection + in 5% to 10% of Excellent correlation patients; done in with positive amniotic seriously ill pts or at Amniotic fluid fluid culture and clinical risk for bacterial interleukin-6 ≥ 7.9 ng/mL infection endocarditis, Good correlation with Growth of aerobic or immunocompromised, positive amniotic fluid anaerobic or has a poor response Blood cultures Amniotic fluid culture and clinical microorganism to initial tx leukocyte esterase ≥ 1 + reaction infection Gabbe 6 th edition 2012 Gabbe 6 th edition 2012 Test Clinical Management Amniotic fluid parameters • Maternal bacteremia: Culture Microbial growth Diagnostic gold-standard 3 – 12 % of infected patients Bacteria or white blood Gram stain 24% sensitive, 99% specific cells (>6/HPF) Romero R, et al. Am J Obstet Gynecol 1993;169(4):839–51 • Cesarean delivery is required: Affected by maternal hyperglycemia Glucose level <15mg/dl 8 % develop a wound infection 57% sensitive, 74% specific Romero R, et al. Am J Obstet Gynecol 1993;169(4):839–51 1 % develop a pelvic abscess Interleukin 6 81% sensitive, 75% specific >7.9 ng/ml Romero R, et al. Am J Obstet Gynecol 1993;169(4):839–51 Increase risk of endomyometritis and venous thrombosis 57% sensitive, 78% specific White blood cell count >30/cubic mm Romero R, et al. Am J Obstet Gynecol 1993;169(4):839–51 85–91% sensitive, 95–100% Leukocyte esterase Positive (dipsticks) specific Gabbe 6 th edition 2012 Riggs JW, et al. Semin Perinatol 1998;22(4):251–9 Hoskins IA, et al. Am J Perinatol 1990;7(2):130–2

  6. Clinical Management Clinical Management • Three separate investigations show intrapartum • 2002 meta-analysis (N = 181) compared treatment is superior to treatment after delivery. intrapartum versus postpartum antibiotic therapy • Decrease in bacteremia • Intrapartum: • Decrease pneumonia • Reduction in neonatal sepsis (RR 0.08; CI 0.00 - 1.44) • Decrease in maternal fever and hospitalization • Pneumonia (RR 0.15; CI 0.01 – 2.92) Sperling RS et al. Obstet Gynecol 70:861, 1987. Gilstrap LC et al. Am J Obstet Gynecol 159:579, 1988. Gibbs RS et al. Obstet Gynecol 72:823, 1988. Hopkins L, Cocharane Database Syst Rev 2002 Regimen Regimen • Antibiotic should be initiated as soon as Dx is • Ampicillin (2 g every 6 hours) or penicillin (5 made million units every 6 hours) plus • Administer broad spectrum antibiotics to cover: • Gentamicin (1.5 mg/kg every 8 hours or 7 mg/kg/ideal body weight every 24 hours) • Beta-lactamase producing aerobes • Anaerobes • Main goal is to target GBS and E.coli

  7. Other Regimens Regimen • Penicillin-allergic patients • Ampicillin-sulbactam • Substitute ampicillin for: • 3 grams intravenously every six hours • Ticarcillin-clavulanate • Vancomycin 1 gram every 12 hours • If GBS+ and Clinda resistant/resistance • 3.1 grams intravenously every four hours unknown: Vancomycin /Gentamicin • Cefoxitin OR • 2 grams intravenously every six hours • Clindamycin 900 mg every 8 hours • If GBS-negative or Clinda-sensitive GBS: Clindamycin /Gentamicin Regimen Duration Postpartum Chorioamnionitis and Cesarean delivery: • Post-partum management if vaginal delivery: • antibiotics are continued for one dose after delivery unless the woman is diagnosed with endometritis • If Amp/Gent or Vanco/Gent used • add Clindamycin No difference in treatment failure or infection-related complications in RCT evaluating: or • Metronidazole • single postpartum dose of antibiotics (Amp/Gent in study) versus (ideally prior to skin incision) for anaerobic • continuing until 24 hours afebrile postpartum coverage Edwards et al. Obstet Gynecol 102:957, 2003.

  8. Duration Postpartum Regimen • Post-partum management of chorioamnionitis if Cesarean • There is NO evidence for oral antibiotics after delivery: discontinuation of parental therapy. • If Amp/Gent or Vanco/Gent used • add Clindamycin or • Metronidazole Edwards’ study included vaginal delivery and cesarean. Underpowered to compare single-dose vs. continued dose just including Cesarean. Given the high risk of endometritis in the setting of chorioamnionitis and Cesarean, continue antibiotics until 24 hours afebrile postpartum Dinsmoor MJ et al. Obstet Gynecol 1991; 77:60. Edwards et al. Obstet Gynecol 102:957, 2003. Antipyretics Route of Delivery • Maternal fever + fetal acidosis confers a 12.5% • Bactericidal concentrations in fetus one-half to risk of neonatal encephalopathy (OR 94, 95 % CI one hour after infusion 29 - 307) • Average time between diagnosis and delivery is 3 • Independent effect: to 5 hours • Fever OR 8.1, 95 % CI 3.5 - 18.6 • Neonatal acidosis OR 11.5, 95 % CI 5.0 – 26.5 • No evidence that duration of infection correlates with outcomes Gibbs RS et al Am J Obstet Gynecol 1991; 164:1317 Impey LW et al Am J Obstet Gynecol 2008; 198:49. Gilstrap LC 3 rd et al Obstet Gynecol Clin North Am 1989; 16:373

  9. Rouse DJ et al Am J Obstet Gynecol 2004; 191:211 • Prolonged first or second stage of labor has been associated with an increased risk of chorioamnionitis • Whether this relationship is causal is unclear � evolving chorioamnionitis may predispose to longer labor • Neither chorioamnionitis nor its duration should be an indication for cesarean delivery ACOG Number 1, March 2014 Rouse DJ et al Am J Obstet Gynecol 2004; 191:211

  10. Short-Term Outcomes Short-Term Outcomes • Case-control study (N = 67) microbiologically • Among preterm neonates those with confirmed clinical chorioamnionitis at term. chorioamnionitis had higher: • Pneumonia 4 % • Perinatal death (13 % vs 3 %, P < .05) • Neonatal bacteremia 4 % • RDS (34 % vs 16 %, P < .01) • No difference in low Apgar scores • Infection (17 % vs 7 %, P < .05) Yoder RP et al Am J Obstet Gynecol. 145:695 1983. Garite TJ Obstet Gynecol. 59:539-545 1982. Short-Term Outcomes Long-Term Outcomes • More likely to require cesarean • Uterine dysfunction • Inadequate uterine response to oxytocin • Abnormal labor progress Creasy and Resink 7 th Edition 2014

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