Endometritis is inflammation of the endometrial lining of the uterus. In addition to the endometrium, inflammation may involve the myometrium and, occasionally, the parametrium.
Endometritis can be divided into pregnancy-related endometritis and endometritis unrelated to pregnancy. When the condition is unrelated to pregnancy, it is referred to as pelvic inflammatory disease (PID). Endometritis is often associated with inflammation of the fallopian tubes (salpingitis), ovaries (oophoritis), and pelvic peritoneum (pelvic peritonitis). The Centers for Disease Control and Prevention (CDC) 2015 sexually transmitted diseases treatment guideline defines PID as any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis.[1, 2]
The diagnosis of endometritis is usually based on clinical findings, such as fever and lower abdominal pain (see Clinical Presentation).
Most cases of endometritis, including those following cesarean delivery, should be treated in an inpatient setting. For mild cases following vaginal delivery, oral antibiotics in an outpatient setting may be adequate (see Treatment and Management, as well as Medication).
Infection of the endometrium, or decidua, usually results from an ascending infection from the lower genital tract. From a pathologic perspective, endometritis can be classified as acute versus chronic. Acute endometritis is characterized by the presence of neutrophils within the endometrial glands. Chronic endometritis is characterized by the presence of plasma cells and lymphocytes within the endometrial stroma.
In the nonobstetric population, pelvic inflammatory disease and invasive gynecologic procedures are the most common precursors to acute endometritis. In the obstetric population, postpartum infection is the most common predecessor.
Chronic endometritis in the obstetric population is usually associated with retained products of conception after delivery or elective abortion. In the nonobstetric population, chronic endometritis has been seen with infections (eg, chlamydia, tuberculosis, bacterial vaginosis) and the presence of an intrauterine device.
The intrauterine device as a factor in the etiology of pelvic inflammatory disease was associated with early forms of the device, in particular, the Dalkon Shield. The incidence of pelvic inflammatory disease is not higher in users of modern intrauterine devices than in non-users.[3, 4, 5]
Endometritis is a polymicrobial disease involving, on average, 2-3 organisms. In most cases, it arises from an ascending infection from organisms found in the normal indigenous vaginal flora.
Commonly isolated organisms include Ureaplasma urealyticum, Peptostreptococcus, Gardnerella vaginalis, Bacteroides bivius, and group B Streptococcus. Chlamydia has been associated with late-onset postpartum endometritis. Enterococcus is identified in up to 25% of women who have received cephalosporin prophylaxis.
Herpes and tuberculosis are rare causes, although in some countries tuberculosis is not an uncommon etiologic agent.[6, 7, 8]
The incidence of postpartum endometritis in the United States varies depending on the route of delivery and the patient population. After a vaginal delivery, incidence is 1-3%. Following cesarean delivery, the incidence ranges from 13-90%, depending on the risk factors present and whether perioperative antibiotic prophylaxis had been given. In the nonobstetric population, concomitant endometritis may occur in up to 70-90% of documented cases of salpingitis.
Nearly 90% of women treated with an approved regimen note improvement in 48-72 hours. Delay in initiation of antibiotic therapy can result in systemic toxicity.
Endometritis is associated with increased maternal mortality due to septic shock. However, mortality is rare in the United States because of aggressive antimicrobial management.
In the PID Evaluation and Clinical Health (PEACH) study, endometritis was not found to be associated with subsequent pregnancy-related complications, chronic pelvic pain, or infertility.[9]
For patient education information, see the Women's Health Center, Pregnancy and Reproduction Center, and Sexually Transmitted Diseases Center, as well as Pelvic Inflammatory Disease, Sexually Transmitted Diseases, Cesarean Childbirth, and Dilation and Curettage (D&C).
Diagnosis usually is based on clinical findings, as follows:
In postpartum cases, patients present with fever, chills, lower abdominal pain, and foul-smelling lochia. Patients with PID present with lower abdominal pain, vaginal discharge, dyspareunia, dysuria, fever, and other systemic signs. However, PID caused by Chlamydia tends to be indolent, with no significant constitutional symptoms.
Physical examination findings include the following:
Uterine tenderness is the hallmark of the disease.
An oral temperature of 38°C or higher within the first 10 days postpartum or 38.7°C within the first 24 hours postpartum is required to make the diagnosis of postpartum endometritis. For PID, the minimum diagnostic criteria are lower abdominal tenderness, cervical motion tenderness, or adnexal tenderness. In severe cases, the patient may appear septic.
Women are particularly vulnerable to endometritis after birth or abortion. In both the postpartum and postabortal state, risk is increased because of the open cervical os, presence of large amounts of blood and debris, and uterine instrumentation.
Major risk factors for obstetric endometritis include the following:
A study by Tuuli et al indicated that the risk of endometritis is significantly higher in cesarean deliveries performed during the second stage of labor (10 cm cervical dilation) than in those performed during the first stage (less than 10 cm dilation). Comparing 400 second-stage deliveries with 2105 first-stage procedures, the investigators found endometritis rates of 4.25% and 1.52%, respectively. A study by Asicioglu et al also found a higher endometritis rate, along with greater risk of other complications, in second-stage cesarean deliveries.[11, 12]
Minor risk factors include the following:
The following factors increase the risk for endometritis in general:
Potential complications of endometritis include the following:
Spread of infection from the endometrium to the fallopian tubes, ovaries, or the peritoneal cavity may result in salpingitis, oophoritis, localized peritonitis, or tubo-ovarian abscesses. Salpingitis subsequently leads to tubal dysmotility and adhesions that result in infertility, higher incidence of ectopic pregnancy, and chronic pelvic pain.
Although the diagnosis of endometritis is principally made on clinical grounds, laboratory studies can be helpful for supporting the diagnosis and excluding or identifying other diagnostic possibilities.
The 2010 and 2015 CDC guidelines on sexually transmitted diseases treatment agree that cervicitis can be a sign of endometritis and that women who are experiencing a new episode of cervicitis should be tested for endometritis, as well as other PID, gonorrhea, and chlamydia.[1, 2]
Endometrial biopsy can be obtained to assess chronic endometritis in the nonobstetric population. Chronic endometritis is associated with abnormal bleeding, recurrent abortion, and infertility. It is a subtle condition and is therefore difficult to diagnose. The diagnosis is ultimately based on the presence of plasma cells in the endometrial stroma upon histopathological examination.[15]
Pathologically, endometritis is defined as the presence of 5 or more neutrophils per high-power field (400×) in the superficial endometrium and 1 or more plasma cells per high-power field (120×) in the endometrial stroma.
The CBC count typically reveals leukocytosis with a left shift. However, in the postpartum period, this finding may reflect the physiological leukocytosis of pregnancy and it is therefore unreliable for diagnosis.
Anemia is a risk factor for the development of endometritis.
Blood culture is positive in 10-30% of cases, and a urine culture should be ordered.
The role of endocervical cultures is controversial. They are not generally helpful in management, as positive results are usually the result of contamination from normal resident cervicovaginal flora. However, endocervical cultures (or DNA probe) are obtained for gonorrhea and chlamydia when appropriate.
Gram stain or wet mount of the vaginal discharge may be useful in ruling out endometritis. If no pus cells are observed in the Gram stain, the negative predictive value for endometritis is 95%.
Perform imaging studies on patients who do not respond to adequate antimicrobial therapy in 48-72 hours. CT scanning of the abdomen and pelvis may be helpful for excluding broad ligament masses, septic pelvic thrombophlebitis, ovarian vein thrombosis, and phlegmon.
Ultrasonography of the abdomen and pelvis may yield normal findings in patients with a clinical diagnosis of endometritis. Abnormal findings overlap with those of retained products of conception and intrauterine hematoma.
After making the diagnosis of endometritis and excluding other sources of infection, the physician should promptly initiate broad-spectrum antibiotics. Improvement will be noted within 48-72 hours in nearly 90% of women treated with an approved regimen.
Most cases of endometritis, including those following cesarean delivery, should be treated in an inpatient setting. For mild cases following vaginal delivery, oral antibiotics in an outpatient setting may be adequate. Pregnant women with symptoms of bacterial vaginosis (BV) should be treated because BV is associated with adverse pregnancy outcomes. Although treatment has not been demonstrated to prevent these outcomes, treatment does reduce signs and symptoms of vaginal infection.[2]
In adolescents who undergo termination of pregnancy, subsequent endometritis with associated salpingitis poses a significant risk of infertility. Therefore, earlier and more aggressive antibiotic therapy is warranted in this group.
Surgical management is not usually necessary in acute endometritis in the obstetric population. Dilation and curettage may be advised for retained products of conception, however. In rare instances of overwhelming infection nonresponsive to conservative therapy, hysterectomy may be necessary as a life-saving intervention.[16]
The combination of clindamycin and gentamicin administered intravenously every 8 hours has been considered the criterion standard treatment. Some studies have revealed adequate efficacy with once-daily dosing, as well.[17, 18, 19, 20] The combination of a second- or third-generation cephalosporin with metronidazole is another popular choice.
The CDC 2015 STD treatment guidelines include details of recommended antibiotic regimens.[1, 2]
In teenagers, postabortion endometritis may be caused by organisms that cause pelvic inflammatory disease (PID). The initial treatment regimen in these patients usually includes intravenous cefoxitin and doxycycline, in the same doses as for PID.
A trend toward the use of broad-spectrum monotherapy has emerged; these agents are generally effective in 80-90% of patients. Cephalosporins, extended-spectrum penicillins, and fluoroquinolones are used as monotherapy.[21]
Improvement is noted within 48-72 hours in nearly 90% of women. Parenteral therapy is continued until the patient has been afebrile for longer than 24 hours. If the physical examination findings are benign, the patient may be discharged at that time. Further outpatient antibiotic therapy has proved to be unnecessary. If the patient does not improve in the expected 48- to 72-hour period, reevaluate for complications such as abscess.
Prophylactic antibiotics reduce the incidence of postpartum febrile morbidity in patients undergoing cesarean delivery. Current research supports the use of preoperative administration of prophylactic antibiotics.[22, 23, 24, 25] Single-agent therapy with a first- or second-generation cephalosporin (eg, cefazolin) has been considered the best choice.
A joint publication by the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) supports the administration of antibiotics prior to skin incision rather than immediately after cord clamping. However, current research is also assessing the use of extended-spectrum regimens with a cephalosporin plus either azithromycin or metronidazole after cord clamping.[26, 27, 28] Head-to-head comparisons between narrow-spectrum prophylaxis given before skin incision and extended-spectrum prophylaxis given after cord clamping still need to be done.[28]
A study by Ward et al found that the combination of cefazolin plus azithromycin when administered before skin incision was significantly more effective than the administration of cefazolin after cord clamping.[29]
A Cochrane database systematic review concluded that the use of vaginal chlorhexidine douching during labor does not prevent endometritis.[30] Preoperative use of povidone-iodine vaginal preparation prior to cesarean delivery appears to decrease the incidence of postcesarean endometritis but does not seem to decrease the overall risk of postoperative fever or wound infection.
A systematic review and meta-analysis by Caissutti et al reported that compared to the control group, vaginal cleansing (most commonly with 10% povidone-iodine) before cesarean delivery significantly lowered the incidence of endometritis (4.5% vs 8.8%; RR 0.52, 95% CI 0.37-0.72; 15 studies, 4,726 participants) and also lowered the risk of postoperative fever (9.4% vs 14.9%; RR 0.65, 95% CI 0.50-0.86; 11 studies, 4,098 participants).[31]
Clinical guidelines on postpartum endometritis were released in March 2019 by the Collège National des Gynécologues et Obstétriciens Français (CNGOF) and Société de Pathologie Infectieuse de Langue Française (SPILF).[32]
Caesarean delivery is the most significant risk factor for postpartum endometritis, particularly if performed after labor has begun.
Presentation and Diagnosis
Symptoms of postpartum endometritis include abdominopelvic pain, hyperthermia, and abnormal lochia. Uterine mobilization pain confirms the diagnosis.
Treatment
Preferred: The first-line antibiotic is amoxicillin-clavulanic acid 3-6 g/d (depending on weight) IV or PO.
Penicillin allergy: In patients with penicillin allergy, a combination of clindamycin 600 mg 4 times/day plus gentamicin 5 mg/kg once a day may be used (caution in breastfeeding women).
Duration: Treatment is administered until 48 hours of apyrexia and resolved pelvic pain. If fever or pelvic pains pain persists for more than 72 hours of antibiotic therapy, perform pelvic imaging to evaluate for placental retention, septic thrombophlebitis, deep abscess, or other surgical complications.
Septic thrombophlebitis, if present, should be treated with heparin therapy for 6 weeks or more if embolism or thrombotic risk factors are also present.
Prevention
If possible, swab the vagina with iodinated polyvidone or chlorhexidine before caesarean delivery. In addition, extraction of the placenta must be spontaneous.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Clinical Context: Clindamycin, which is used in combination with gentamicin, is a lincosamide that is useful as a treatment against serious skin and soft tissue infections caused by most staphylococci strains. It is also effective against aerobic and anaerobic streptococci, except enterococci.
Clindamycin inhibits bacterial protein synthesis by inhibiting peptide chain initiation at the bacterial ribosome. It preferentially binds to the 50S ribosomal subunit, causing bacterial growth inhibition.
Clinical Context: An aminoglycoside antibiotic used for gram-negative bacterial coverage, gentamicin is used in combination with either clindamycin or in combination with metronidazole and ampicillin. Dosing regimens are numerous and are adjusted based on creatinine clearance and changes in the volume of distribution. Doses may be given IV or IM.
Clinical Context: Ampicillin is used in combination with gentamicin and metronidazole. It interferes with bacterial cell-wall synthesis during active multiplication, causing bactericidal activity against susceptible organisms.
Clinical Context: Used in combination with gentamicin and ampicillin, metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Metronidazole appears to be absorbed into the cells and the intermediate-metabolized compounds that are formed bind DNA and inhibit protein synthesis, causing cell death.
Clinical Context: The combination of ampicillin with the beta-lactamase inhibitor sulbactam sodium has been found to be effective as monotherapy in 80-90% of patients. This agent covers skin, enteric flora, and anaerobes. It is not ideal for nosocomial pathogens.
Clinical Context: Doxycycline is used if Chlamydia is the cause of the endometritis. It inhibits protein synthesis and thus bacterial growth by binding with the 30S and possibly the 50S ribosomal subunits of susceptible bacteria.
Clinical Context: The bactericidal activity of ertapenem results from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins. This agent is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. It is hydrolyzed by metallo-beta-lactamases.
Clinical Context: Cefoxitin is a second-generation cephalosporin indicated for gram-positive cocci and gram-negative rod infections. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.
Clinical Context: The combination of ampicillin with the beta-lactamase inhibitor sulbactam sodium has been found to be effective as monotherapy in 80-90% of patients. This agent covers skin, enteric flora, and anaerobes. It is not ideal for nosocomial pathogens.
Clinical Context: Cefotetan is second generation and is used as a single-drug therapy to provide broad gram-negative coverage, broad anaerobic coverage, and some coverage against gram-positive bacteria. It inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, and it inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death.
Clinical Context: Cefotaxime is a third generation cephalosporin with a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. It arrests bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, which, in turn, inhibits bacterial growth. It is used for septicemia and the treatment of gynecologic infections caused by susceptible organisms.
Clinical Context: Ceftazidime is a third generation cephalosporin with broad-spectrum, gram-negative activity, including pseudomonal organisms. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins, which, in turn, inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell wall synthesis, thus inhibiting cell wall biosynthesis.
Clinical Context: Cefazolin is a first-generation cephalosporin, which by binding to 1 or more penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial replication. Prophylactic antibiotics reduce the incidence of postpartum febrile morbidity in patients undergoing cesarean delivery. Current research supports the use of preoperative administration of prophylactic antibiotics. Single-agent therapy with a first-generation such as cefazolin or a second-generation cephalosporin has been considered the best choice.
Clinical Context: Levofloxacin is a fluoroquinolone antibiotic. It is used for pseudomonal infections and infections due to multidrug resistant gram-negative organisms. A trend toward the use of broad-spectrum monotherapy has emerged, and these agents are generally effective in 80-90% of patients. Cephalosporins, extended-spectrum penicillins, and fluoroquinolones are used as monotherapy. If gonococcal infection is suspected, levaquin is contraindicated because many strains of the organism are now resistant to the quinolones.
A combination therapy with clindamycin and an aminoglycoside is considered the criterion standard by which most antibiotic clinical trials are judged. A combination regimen of ampicillin, gentamicin, and metronidazole provides coverage against most of the organisms that are encountered in serious pelvic infections. Doxycycline should be used if Chlamydia is the cause of the endometritis.
Ampicillin sulbactam can be used as monotherapy. Single-agent therapies have been found to be effective in 80-90% of patients.