Postpartum Infection

Etiology

The majority of postpartum infections result from physiologic and iatrogenic trauma to the abdominal wall and reproductive, genital, and urinary tracts that occur during childbirth or abortion, which allows for the introduction of bacteria into these normally sterile environments.

Epidemiology

In contrast to encouraging global trends, maternal mortality in the United States has been increasing in the past four decades, rising 140% between 1987 and 2013, and the United States has one of the highest pregnancy-related mortality rates of high-income countries.[4]  Unfortunately, this disturbing trend cannot be fully attributed to better record-keeping, and, notably, these figures exclude deaths that result following spontaneous and induced abortions as well as maternal deaths following stillbirths, all conditions which are associated with higher maternal morbidity and mortality than live births.[5] 

Studying rates of postpartum infections and their effects is difficult, as most of these infections occur following maternal hospital discharge, and decreasing hospital stay following childbirth further inhibits the detection of postpartum complications, including infection.[6] Available data shows that postpartum infections account for 19% of maternal deaths following stillbirth and 34% of deaths following spontaneous or induced abortions.[7] 

The latest data from the Centers for Disease Control show that infections are the leading cause of pregnancy-related deaths in Hispanic women in the United States and disproportionately affect ethnic minorities.[8] On the whole, postpartum infections are more common in women who underwent cesarean section as opposed to vaginal delivery, and the risk is further increased for women who underwent labor before the cesarean section.[9] 

The risk of postpartum infections is likewise increased in patients at the extremes of maternal age or with high body mass index, diabetes, hypertension, immune compromise, bacterial vaginosis, group-B streptococcus positive status, and sexually transmitted infections.[5] Birth events associated with increased risk of infection include preterm or post-term labor, prolonged rupture of membranes or labor, multiple internal exams, thick meconium staining, internal fetal or uterine monitoring, operative vaginal delivery, manual removal of the placenta, retained products of conception, use of a foley catheter, and postpartum hemorrhage.[5]

Pathophysiology

Postpartum infections can be roughly grouped into those caused by ascending vaginal microflora into the reproductive tract and those which result from iatrogenic trauma to the abdominal wall or perineum during delivery. Because of the complexity of the birthing process, it is important to remember that ascending vaginal flora plays a role in surgical site infections, and surgical intervention likewise plays a role in the ascension of vaginal microflora into the reproductive tract.

Infections resulting from ascending infection into the reproductive tract include endometritis and septic abortion. Endometritis is an infection of the endometrium and myometrium. Endometritis occurs most commonly in the postpartum period, as childbirth allows ascending vaginal bacterial flora to infect the upper reproductive tract. This infection is five to ten times more common following cesarean section compared to vaginal delivery.[10] Other risk factors include rupture of membranes >18 hours, chorioamnionitis, bacterial vaginosis, use of internal fetal monitoring, repeated vaginal examination, and maternal colonization with group A or B streptococcus.[10] The most common pathogens in endometritis are those normally associated with the reproductive and urinary tracts and include group B streptococci, enterococci, Escherichia coli, and Klebsiella pneumonia.[10] 

Chlamydia trachomatis should be suspected in endometritis presenting > 7 days postpartum and in high-risk populations, such as women under age 25. Septic abortion is an infection of the products of conception following spontaneous or induced abortion.[11] Septic abortions result from the migration of vaginal flora through an open os following an incomplete or improperly performed abortion, resulting in infection of the products of conception. Infection may also spread to the uterus. Septic abortions are associated with a high risk of bacteremia, as the infection can enter the maternal blood supply through the intervillous space of the placenta.[12] Mortality from septic abortion is directly correlated with gestational age at the time of pregnancy termination.[11] 

As the pregnancy progresses, the placenta enlarges, and there is more tissue to become infected; thus, mortality from septic abortion increases with increasing gestational age.[11] Because they are both caused by ascending urogenital flora, the microbiological profiles of endometritis and septic abortions are similar. However, because of the devitalized tissue present in septic abortions, infections with anaerobic bacteria are more common in this setting.[11]

Surgical site infections (SSI) are relatively common following birth, complicating 2-7% of cesarean deliveries.[13] Episiotomy sites can also become infected. SSI can be broadly divided into deep organ infections and incisional infections, which can be further divided into superficial incisional (involving the skin or subcutaneous tissues) and deep incisional (involving the muscle or fascia) infections.[14] Endometritis following surgical delivery is an example of a deep organ infection; other postpartum deep site infections include infected hematomas and pelvic abscesses.[15] A history of prior cesarean section is correlated with an increased risk of recurrent site infection, likely secondary to baseline poor vascularization of the scar tissue from the prior surgery.[16] 

Incisional site infections present with erythema and purulent drainage at the site and can be associated with systemic symptoms such as fever and malaise. Like endometritis and septic abortion, SSI can be caused by contamination of the wound with microflora from the genitourinary tract; however, they can also be caused by commonly isolated skin flora.[17] Infections occurring within the first two postoperative days are most commonly caused by group A or B streptococci. Other commonly isolated pathogens include Ureaplasma urealyticum, Enterococcus faecalis, Escherichia coli, Proteus mirabilis, and Staphylococcal species.[15][17]

More rarely, necrotizing fasciitis of the surgical site can develop, characterized by rapid necrosis of the fascia and subcutaneous tissue with relative sparing of the musculature. Postpartum patients who develop necrotizing fasciitis typically have underlying medical comorbidities, with diabetes being the most commonly reported. Type I necrotizing fasciitis results from polymicrobial infection with aerobic and anaerobic organisms; type II results from infection with group A streptococcus. Both types can occur in the postpartum period and can complicate cesarean deliveries as well as episiotomies.[18][19][20]

History and Physical

In addition to the classic portions of the history of present illness, important details to elicit during history taking include: 

• Time of delivery or abortion
• Surgical or vaginal delivery
• Prior surgical and medical history history
• Gestational age at the time of the delivery or abortion
• Complications of the pregnancy, including gestational diabetes, intrapartum infections, premature or prolonged rupture of membranes, chorioamnionitis, or preeclampsia/eclampsia
• Complications of the delivery, including prolonged labor, need for operative vaginal delivery, unplanned cesarean section, and postpartum hemorrhage 
• GBS status 
• Presence of foul-smelling lochia or excessive vaginal bleeding

Physical examination should include:

• Evaluation of the surgical incision (if present)
• Examination of the skin for crepitance, bullae, erythema, induration or drainage
• Palpation of the abdomen and the uterine fundus
• Sterile speculum and bimanual examination  

In endometritis, fever is often the first sign, with uterine tenderness, bleeding, and foul-smelling lochia as additional signs. Patients presenting with signs of severe systemic illness, shock, and/or abdominal pain out of proportion to examination findings should raise suspicion for infection with GAS, which can cause endometritis associated with toxic shock syndrome as well as necrotizing fasciitis.[11] 

Fever is common in septic abortion but may not be present.[11] Usually, only mild abdominal pain is present, although generalized peritonitis can be seen in severe infection.[11] In addition to GAS, septic abortion associated with sepsis or shock can also occur in the setting of infection with Clostridium species or toxin-producing strains of Escherichia coli.[11]

Superficial incisional site infections typically present with erythema, warmth, and pain at the site; purulent drainage may also be present.[21] These infections occur most commonly 4 to 7 days following surgery; as mentioned above, signs of infection in the first 48 hours should raise suspicion for group A or B streptococci.[15] 

Deep incisional infections may show minimal external examination findings, in fact, pain out of proportion to examination is a hallmark of necrotizing fasciitis. Unlike superficial site infections, deep incisional infections are more likely to be associated with fever and hemodynamic compromise.[15] The examination may show skin necrosis or ecchymosis, crepitus, and bullae.[15] Imaging studies may show gas in the soft tissues, but definitive diagnosis and management are surgical; surgery should not be delayed for diagnostic studies, as these infections are rapidly progressive and fatal if not managed promptly.  

Septic pelvic thrombophlebitis (SPT) should be suspected in patients with persistent pain, leukocytosis, and fever despite adequate antibiotic therapy for the above conditions for more than 3 to 5 days.[15] Deep organ infections such as an infected hematoma or pelvic abscess should likewise be considered if the patient is not responding to appropriate antibiotics.[15]

Evaluation

As in all infectious conditions, evaluation should include blood and/or wound cultures prior to the initiation of antibiotics. Laboratory findings typical of infection include leukocytosis with neutrophilia and a left shift as well as lactic acidosis. Notably, no postpartum infection can be excluded based on lab work alone, and clinicians should not be falsely reassured if laboratory diagnostics are unremarkable. Endometritis is largely a clinical diagnosis. Findings suggestive of endometritis include fever, abdominal tenderness, and foul-smelling lochia. If septic abortion is suspected based on history, an ultrasound should be obtained to evaluate for retained products of conception.[11] 

If the infection has spread to the uterus, gas may be seen in the myometrium on plain film or computed tomography (CT).[11] Surgical site infections are likewise a clinical diagnosis suggested by history and physical examination. If post-surgical deep organ infection is suspected, CT with intravenous contrast may help with diagnosis. Workup for pelvic thrombophlebitis should be initiated if the patient does not defervesce following 3-5 days of appropriately broad-spectrum antibiotics. Pelvic vein thrombosis is typically seen radiologically with CT or magnetic resonance imaging (MRI).[22]

Treatment / Management

Knowledge of the microbiological profiles of different postpartum infections, local resistance patterns, and the severity of the patient’s illness should guide antibiotic choices. As a general rule, antibiotic regimens, particularly in very sick patients, should have a broad-spectrum of antimicrobial coverage at the beginning and should be narrowed as more clinical evidence from cultures or pathology specimens becomes available. Pharmacists can often help tailor initial antibiotic choices and aid in narrowing the spectrum as care progresses. Consideration should be given to whether the patient is breastfeeding, and all efforts should be made to use antibiotics that will allow the patient to continue breastfeeding safely. 

While antibiotic regimens may differ for specific postpartum infections, the foundation of the treatment of most infectious conditions is the same. In patients with hemodynamic compromise, balanced crystalloid fluids should be given to a maximum of 30 ml/kg of ideal body weight.[23] If mean arterial pressure is persistently below 65 mmHg despite adequate fluid resuscitation, a vasopressor should be started.[23] Broad-spectrum antibiotics should be given as soon as possible, and blood cultures should be obtained before antibiotic administration if doing so does not significantly delay antibiotics.[23] If the infection requires surgical intervention, prompt consultation of a surgical service is of utmost importance.  (B3)

The treatment of endometritis varies with severity. Patients with mild, early endometritis may be able to receive outpatient treatment; shared decision-making between the provider and the patient should always precede the decision to treat on an outpatient basis. Intramuscular and oral regimens can also be used in low-resource settings where intravenous antibiotics may not be an option. In patients who are appropriate for outpatient treatment, potential 14-day regimens include clindamycin 600 mg orally every 6 hours plus gentamicin intramuscularly 4.5 mg/kg every 24 hours; amoxicillin-clavulanate 875 mg orally twice daily; cefotetan 2g intramuscularly every 8 hours; meropenem or imipenem-cilastatin 500 mg intramuscularly every 8 hours; or amoxicillin 500 mg and metronidazole 500 mg every 8 hours.[24] (A1)

The listed regimens are safe for breastfeeding patients and resulted in a greater than 85% cure rate in early endometritis.[24] As with all patients receiving outpatient treatment, strict return precautions for worsening symptoms should be given. In patients who will receive intravenous therapy for endometritis, the empiric combination of clindamycin (900 mg every 8 hours or 600 mg every 6 hours) and gentamicin (5 mg/kg daily or 1.5 mg/kg every 8 hours) is the most effective [25]. Ampicillin (3g intravenously every 6 hours) can be added for better coverage of enterococcus and in patients who are GBS positive, as there is increasing resistance to clindamycin among GBS isolates.[15][25] Parenteral therapy should continue until the patient defervesces and their pain improves. Improvement should be seen in 48 to 96 hours. If the patient does not improve, consider a pelvic abscess or infected hematoma, septic pelvic thrombophlebitis, or infection with enterococcus. (A1)

The mainstay of treatment for septic abortion is the removal of the infected products of conception. Broad-spectrum antibiotics should be initiated within an hour of making the diagnosis.[26] In addition to the clindamycin and gentamicin with/or without ampicillin regimen mentioned above, other parenteral regimens include ampicillin (2g every 8 hours), gentamicin (5 mg/kg daily), and metronidazole (500 mg every 12 hours); levofloxacin (500 mg every 12 hours) and metronidazole (500 mg every 12 hours); imipenem (500 mg every 6 hours); piperacillin-tazobactam (4.5 g every 8 hours); or ticarcillin-clavulanate (3.1g every 4 hours).[11] In cases not complicated by a pelvic abscess, intravenous antibiotics should be continued until 48 hours after the patient shows clinical improvement [27]).(A1)

For mild superficial surgical infections without systemic symptoms or purulence, an oral course of antibiotics is typically sufficient. A first-generation cephalosporin like cephalexin should be used when there is no associated purulence.[28] If there is superficial purulence without evidence of an abscess, consider possible infection with methicillin-resistant Staphylococcus aureus and expand coverage accordingly.[29] If the area of erythema and induration extends fewer than 5 centimeters from the incision, there are systemic signs of infection, or there is a concern for an underlying abscess, the wound should be opened, explored, cultured, then packed with moist gauze, which should be changed twice daily.[28] Empiric coverage for genitourinary (as above) organisms should be started. 

Necrotizing fasciitis is a surgical emergency that cannot be sufficiently treated with antibiotics. However, pending emergent surgical intervention, broad-spectrum antibiotics should be started. A common regimen is vancomycin and piperacillin-tazobactam with clindamycin, which is used for its anti-toxin activity.[30](A1)

Finally, treatment for SPT is intravenous ampicillin (2 g then 1 g every 4 hours), gentamicin (5 mg/kg daily), and clindamycin (900 mg every 8 hours).[22] The use of heparin remains controversial, as there have been no studies to date that suggest it provides clinical benefit beyond appropriate antibiotic administration.[22]

Differential Diagnosis

Postpartum fever is defined as an oral temperature ≥38.0°C (≥100.4°F) on any two of the first 10 days postpartum, excluding the first 24 hours.[31] The first postpartum day is excluded because fevers are common in this period, not associated with increased maternal morbidity, and are typically self-limiting.[31] High temperatures in the postpartum period can be caused by fever or by hyperthermia. Other than infections, deep vein thrombosis, and breast engorgement can also cause fever in the postpartum period. Breast engorgement can be associated with a slight increase in maternal temperature.[32] 

Unfortunately, there is no documented cut-off point for what temperature is too high just to be caused by breast engorgement. The presence of myalgias and breast erythema suggest mastitis rather than engorgement as the diagnosis.[32] It is important to remember that postpartum patients can develop infections exclusive of their puerperal status; screening for common infections like urinary tract infections and pneumonia can be done by history and physical examination. 

Causes of hyperthermia include serotonin syndrome, neuroleptic malignant syndrome, an overdose of sympathomimetic or anticholinergic agents, withdrawal from ethanol or benzodiazepines, aspirin toxicity, and thyroid storm.[33] History and physical examination are the foundation of evaluation for these diagnoses. A review of the patient's medication list and inquiry regarding initiation of new serotonergic or neuroleptic agents, which may be used for postpartum depression or psychosis, can screen for serotonin syndrome and neuroleptic malignant syndrome.[33] 

The hallmark physical examination finding for serotonin syndrome is hyperreflexia and clonus, while for neuroleptic malignant syndrome, lead-pipe rigidity is characteristic.[34] Aspirin toxicity is usually suggested by history; physical examination may show altered mental status, hyperpnea, and abdominal tenderness.[33] 

The overdose of sympathomimetic agents presents with tachycardia, hypertension, diaphoresis, and agitation. Withdrawal from benzodiazepines or ethanol can present with tremors, tachycardia, hypertension, and hyperthermia and progress to seizures.[35] Anticholinergic toxicity is characterized by altered mental status, anhidrotic hyperthermia, mydriasis, flushing, and urinary retention.[36] Finally, delivery can precipitate thyroid storm, which presents with hyperthermia, hyperreflexia, nausea, vomiting, and abdominal pain.[37]

Prognosis

Morbidity from postpartum infections affects 5 to 10% of pregnant patients.[38] The prognosis of puerperal infections is directly related to the severity of the infection. Patients who develop sepsis have estimated mortality of 20%. Mortality for septic shock is approximately 40%.[39]

Complications

All postpartum infections can progress to sepsis, bacteremia, shock, and death if not treated appropriately. Necrotizing fasciitis is especially notable for its rapid progression to fulminant infection and death. A notable complication of endometritis and deep space infections of the pelvis is SPT. Endometritis affects the endometrium and myometrium but can progress beyond the uterus to include abscess, peritonitis, and pelvic thrombophlebitis.[40] SPT results from intimal pelvic vein injury caused by adjacent uterine infection, bacteremia, or trauma from vaginal or surgical delivery. Infection can also involve the ovarian veins and the inferior vena cava. Risk factors include cesarean section and chorioamnionitis.[41]