Intrauterine Infection and Beyond

Edwin M. Thorpe, Jr., MD Division of Gynecologic Specialties Department of Obstetrics and Gynecology University of Tennessee Health Science Center

Chorioamnionitis
Amnionitis, intra-amniotic infection 1-5 percent of term pregnancies Clinical or subclinical infection up to 25% Hematogenous dissemination rare Ascending infection most common

- Bacteroides - Prevotella species - E. coli

- Anaerobic streptococci - Group B streptococci

Clinical Risk Factors for Choroiamnionitis

Young age Low socioeconomic status Nulliparity Extended duration of labor and ruptured membranes Multiple vaginal examinations Preexisting lower genital tract infections

Diagnosis of Chorioamnionitis
Based on clinical findings Maternal fever Maternal and fetal tachycardia Absence of localizing signs Uterine tenderness Purulent amniotic fluid

Differential Diagnosis of Chorioamnionitis

Upper respiratory infection Bronchitis Pneumonia Pyelonephritis Viral syndrome Appendicitis

Diagnostic Tests for Chorioamnionitis

Test
Maternal WBC count

Abnormal Finding
>15,000 cells/mm predominantly leukocytes <10 to 15 mm/dl

Comment
Labor/steroids may increase WBC count Excellent correlation with positive amniotic fluid culture and clinical infection Excellent correlation with positive amniotic fluid culture and clinical infection Good correlation with positive amniotic fluid culture and clinical infection

Amniotic fluid glucose

Amniotic fluid IL-6

>7.9 ng/ml

Amniotic fluid LE

>1+ reaction

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Diagnostic Tests for Chorioamnionitis

Test
Amniotic fluid Grams stain

Abnormal Finding
Any organism in OIF

Comment
Very sensitive to inoculum; May identify virulent organisms e.g. Group B streptococcus

Amniotic fluid culture

Growth of aerobic or anaerobic microorganism

Results usually not available for clinical management

Blood cultures

Growth of aerobic or anaerobic microorganism

Positive 5-10% of patients. Usually not of value clinically*

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Complications of Chorioamnionitis
Bacteremia 3 to 12 percent of infected women Wound infection up to 10% of cesarean deliveries Pelvic abscess 1% 5-10% of neonates pneumonia and bacteremia Perinatal mortality 1-4% term, up to 15% preterm Prompt intrapartum treatment!

Treatment of Chorioamnionitis

Most extensively tested IV antibiotic regimen

Ampicillin 2 g or Penicillin 5 million units q 6 hours plus Gentamicin 1.5 mg/kg every 8 hours

Allergic to -lactam antibiotics? Ampicillin or Penicillin substitutes:

Vancomycin 500 mg q 6hr or 1 g q 12hr Erythromycin 1 g q 6hr Clindamycin 900 mg q 8hr

Single Agents of Value in the Treatment of Chorioamnionitis

Drug Dosage and Dose Interval Relative Cost to the Pharmacy

Extended spectrum penicillins

Ampicillin-sulbactam Mezlocillin Piperacillin Piperacillin-tazobactam Ticarcillin-clavulanic acid

3.0 g q6h 3-4 g q6h 3-4 g q6h 3.375 g q6h 3.1 g q6h

Low Intermediate Intermediate Intermediate Low

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Single Agents of Value in the Treatment of Chorioamnionitis

Drug Dosage and Dose Interval Relative Cost to the Pharmacy

Extended spectrum cephalosporins Cefotaxime Cefotetan Cefoxitin Ceftizoxime Carbapenem Imipenem-cilastatin Meropenem 500 mg q6h 1 g q12h High High 2 g q8-12h 2 g q12h 2 g q 6h 2 g q12h Intermediate Intermediate High Intermediate

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Treatment of Chorioamnionitis
Risk of dysfunctional labor with chorioamnionitis
75% require augmentation 30-40% require cesarean delivery Careful fetal monitoring required

If patient with chorioamionitis requires cesarean delivery: Add anti-anaerobic antibiotic to regimen Clindamycin 900 mg every 8hr Metronidazole 500 mg every 6hr Without anaerobic coverage, treatment failure in 20 to 30 percent of patients

Treatment of Chorioamnionitis
Continue IV antibiotics until: Afebrile and asymptomatic for 24 hr Discharge home without oral antibiotics Except: Documented staphylococcal bacteremia longer IV therapy and extended oral antibiotics Rapid defervescence after vaginal delivery shortcourse of oral antibiotics as outpatient Amoxicillin-clavulanate 875/125 mg po BID for 3 days

Treatment of Chorioamnionitis
Single additional dose postpartum therapy for women with chorioamnionitis
- RK Edwards, PA Duff - Univ of Florida

Randomized trial
- Study group received next scheduled dose of drugs postpartum - Controls received antibiotics until afebrile for 24 hours - Cesarean delivery add clindamycin

N=292
- 151 study patients, 141 controls - No difference in treatment failure rate

Conclusion Following prompt intrapartum treatment, one additional dose is sufficient postpartum therapy

 and beyond

Postpartum (Puerperal) Endometritis

1% following vaginal delivery 5 to 15% after scheduled cesarean Extended labor and prolonged ruptured membranes
30 to 35% without antibiotic prophylaxis 15 to 20% with prophylaxis

Nearly doubled infection rates in highly indigent populations

Postpartum (Puerperal) Endometritis

Polymicrobial, ascending infection (Normal) vaginal microorganisms Most common pathogenic bacteria:
Group B streptococci Anaerobic streptococci (Peptostreptococci) Aerobic gram-negative bacilli (E.coli, Klebsiella pneumoniae, Proteus species Anaerobic gram-negative bacilli (Bacteroides, Prevotella) Chlamydia late-onset infection

Prophylactic Antibiotics for Prevention of Postcesarean Endometritis

Most appropriate agent limited spectrum cephalsporin Cefazolin 1-2 g immediately after cord clamped Second dose 8 hours after first dose High-risk patients Operating time greater than 1 hour Extended spectrum penicillins and cephalosporins effective, but no advantage Use of extended spectrum drugs may limit usefulness for treatment For -lactam hypersensitivity Clindamycin 900 mg plus gentamicin 1.5 mg/kg as a single dose

Postpartum (Puerperal) Endometritis

Fever - 38C (100.4F) or higher within first 36 hours Malaise, tachycardia, lower abdominal pain, uterine tenderness, discolored, malodorous lochia Differential diagnosis: - Endometritis - Atelectasis - Pneumonia

Viral syndrome Pyelonephritis Appendicitis

Combination Antibiotic Regimens for the Treatment of Postpartum Endometritis

Relative Cost to the the Pharmacy

Antibiotics

Intravenous Dose

Regimen 1

Clindamycin Gentamicin

900 mg q8h 1.5 mg/kg q8h or 5-7 mg/kg ideal body weight q 24h

Intermediate Low

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Combination Antibiotic Regimens for the Treatment of Postpartum Endometritis

Antibiotics Regimen 2 Clindamycin Aztreonam Regimen 3 Metronidazole Penicillin or Ampicillin Gentamicin 500 mg q 12h 5 million units q 6h 2 g q 6h 1.5 mg/kg q 8h 5-7 mg/kg ideal weight q 24 h Low Low Low Low Low 900 mg q8h 1-2 g q8h Intermediate High Intravenous Dose Relative Cost to the the Pharmacy

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Treatment of Resistant Microorganisms in Patients with Postpartum Endometritis

Initial Antibiotic(s) Extended spectrum cephalosporins Principal Weakness in Coverage Some aerobic and anaerobic gram-negative bacilli, Enterococci Modification of Therapy Change treatment to clindamycin or MTZ plus penicillin or Amp+Gent

Extended spectrum penicillins

Some aerobic and anaerobic gram-negative bacilli Enterococci, some anaerobic gram-negative bacilli

As above

Clindamycin plus gentamicin or aztreonam

Add Amp or PCN Consider substitution of MTZ for clindamycin

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Principal Risk Factors for Postcesarean Wound Infection

Poor surgical technique Low socioeconomic status Extended duration of labor and ruptured membranes Preexisting infection such as chorioamnionitis Obesity Type 1 (insulin-dependent) diabetes Immunodeficiency disorder Corticosteroid therapy Immunosuppressive therapy

Postcesarean Wound Infection

3-5% of patients with endometritis Principal causative organisms - Staphylococcus aureus - Aerobic streptococci - Aerobic and anaerobic bacilli Strong consideration patients with poor response to treatment of endometritis

Diagnosis of Postcesarean Wound Infection

Erythema, induration, tenderness Probed with sterile cotton-tipped applicator or fine-needle Extensive cellulitis without pus Gram stain and culture Rule-out MRSA

Diagnosis of Postcesarean Wound Infection

Open wound, drain completely Antibiotic therapy targeted toward staphylococci Nafcillin 2 g IV q 6hr Vancomycin 1 g IV q 6hr Careful inspection of fascia for disruption Irrigation with warm saline, clean dressing 2-3 times/day Antibiotics continued until all signs of cellulitis resolved, wound base clean

Differential Diagnosis of Persistent Postpartum Fever

Condition Diagnostic Test(s) Treatment

Resistant microorganism Wound infection

Endometrial culture Blood culture Physical examination Needle aspiration Ultrasound Physical examination Ultrasound, CT, MRI Ultrasound, CT, MRI

Modify antibiotic therapy

Incision and drainage, antibiotics Drainage Antibiotics Heparin anticoagulation Antibiotics

Pelvic abscess Septic pelvic vein thrombophlebitis

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Differential Diagnosis of Persistent Postpartum Fever

Condition Recrudescence of connective tissue disease Diagnostic Test(s) Serology Treatment Corticosteroids

Drug fever

Inspection of temperature WBC eosinophilia

Discontinue antibiotics

Mastitis

Physical examination

Modify antibiotics to cover staphylococca l microorganisms

Adapted from PA Duff in Obstetrics: Normal and Abnormal, Churchill Livingstone, 2002

Intrauterine Infection and Beyond: Summary Recognition of risk factors for intraamniotic infection Prompt diagnosis and treatment of chorioamnionitis Recognition of potential sequelae of intrapartum infection Prompt and appropriate treatment of postpartum complications

 off into the sunset!