Postabortion Infection, Bacteremia, Sepsis, and Septic Shock

Even though these life-threatening infections are encountered infrequently by obstetrician-gynecologists, we play a key role in the outcomes. Although these patients are often treated in an intensive care unit and managed either primarily by, or in conjunction with, intensivists, primary functions of the obstetric gynecologists are:

Early recognition of these conditions
Prompt institution of effective therapy
Critical decision-making regarding surgical intervention
Ongoing coordination of care

This extensively revised chapter includes updates on the pathophysiology, epidemiology, and treatment of sepsis.

POSTABORTION INFECTION

In the last 30 years, medical and legal decisions have changed the practice and outcome of pregnancy termination (Fig. 12.1). Death and major complications from abortion decreased dramatically as a result of antibiotic availability and legalization of abortion. When death occurs as a result of induced abortion, however, infection is a leading cause.

Risk factors for death after legal abortion are advancing gestational age, advancing maternal age, “black and other” race, and method used (with the lowest risk accompanying procedures used at early gestational ages).

As with risk factors for death after legal abortion, risk factors for major complications after abortion are longer duration of pregnancy and technical difficulties. The rate of infection after first-trimester vacuum aspiration from six studies (1971 to 1987) was 0.1% to 4.7%, whereas for second-trimester procedures from five studies (1971 to 1990) the rate was 0.4% to 2.0%. In prospective studies of prophylactic antibiotics for abortion, the rate was 1% to 10% in those receiving antibiotics and 5% to 23% in those receiving placebo. These wide ranges are a result of the criteria for diagnosis of infection and the method of data collection.

For 2004, a total of 839,226 legal abortions were reported to the Centers for Disease Control (CDC) from 49 reporting areas. In 2005, there were 848,163 legal abortions and 10 deaths from complications of legal abortion.

Pathophysiology

Infection after abortion is an ascending process that occurs more commonly in the presence of retained products of conception or operative trauma (Fig. 12.2). Perforation of the uterus may be followed by severe infection, whether or not there is bowel trauma. Hysterotomy is rarely indicated for abortion because it has a very high complication rate. Infection after hysterotomy is frequent because there is necrosis, foreign body (suture material) and blood clot in the thick uterine incision, contamination from the lower genital flora, and, often, poor drainage of the uterine cavity.

Diagnosis

For patients who have had an abortion, the diagnosis of postabortion infection often is readily made. Symptoms may include fever, chills, malaise, abdominal pain, and vaginal bleeding, perhaps with passage of placental tissue. Postabortal infection may be more difficult to diagnose in patients who have illegal abortions because of patient denial of the procedure.

Although illegal abortion is now very rare in the United States, septic abortion should be considered in every woman with lower abdominal pain and vaginal bleeding, especially if there is fever and tenderness.

Physical findings may include elevated temperature, tachycardia, and tachypnea. Because bacteremia occurs more commonly with infected abortion than with other pelvic infections, shock may arise from sepsis as well as from blood loss. In the presence of sepsis, the patient may appear agitated, toxic, or disoriented. Usually there is lower abdominal tenderness. On pelvic examination, there often is blood and perhaps a foul odor in the vagina. It is important to look for cervical and vaginal lacerations, especially in a suspected illegal abortion. The cervix is most often open and will readily admit a sponge forceps. If a catheter from an illegal abortion is still in the cervix, it should not be removed immediately, because radiographic techniques can be used to rule out perforation.

On bimanual examination, uterine tenderness often is noted, and parametrial cellulitis or abscess may be detected. Rarely, gas gangrene of the uterus may be detected by crepitation in the pelvis (Figs. 12.3, 12.4, and 12.5).

Laboratory diagnostic evaluation should include complete blood count, urinalysis, culture and Gram stain of cervical material, two sets of blood cultures, anteroposterior roentgenogram of the abdomen and pelvis, and upright chest x-ray film. Free hemoglobin may be noted in the serum or in the urine in infections caused by Clostridium perfringens or other organisms with hematotoxins. Gram stain of cervical exudate may reveal the predominant organism immediately. Results of blood cultures commonly are positive in septic abortion. Roentgenograms in patients with suspected illegal abortions help rule out a foreign body or free air under the diaphragm resulting from perforation. Gas in the uterus is a late sign of uterine gangrene. Ultrasound examination may be used as the initial imaging technique, as it may detect retained placental tissue, foreign body, and possibly air in the pelvic structures. Blood should be obtained for typing and potential cross-matching.

In 2005, four cases were reported of fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. All occurring in young, previously healthy women, death occurred within 1 week of the medically induced abortion.
Notable features included absence of fever but a dramatic leukemoid reaction (45 to 120,00/mm³), fluid sequestration, hemoconcentration, refractory tachycardia and hypotension, and marked edema of infected tissues, without gas or extensive myonecrosis. The estimated attack rate was 1 in 100,000 medical abortions in the United States.

FIGURE 12.1 Deaths from induced abortion in the United States, 1940 to 1985. (Data from Council in Scientific Affairs, American Medical Association. Induced termination of pregnancy before and after Roe v. Wade: trends in mortality and morbidity of women. JAMA 1992;268:3231-3239.)

C. sordellii is an infrequent human pathogen, having been reported to cause pneumonia, endocarditis, arthritis, peritonitis, myonecrosis, and rarely, bacteremia/sepsis, mainly in debilitated patients. It is rarely found in the genital tract, although other clostridial species are found in 4% to 18% of vaginal cultures of healthy women. This postmedical abortion toxic shock is fulminant and results from specific exotoxins. There are limited data regarding treatment, but current recommendations are:

FIGURE 12.2 Uterus removed at autopsy from lethal septic abortion. Note retained products of conception and site of uterine perforation at fundus.

FIGURE 12.3 Clostridial “gas gangrene” of uterus.

As with the other several histotoxic clostridial infections (such as C. perfringens myonecrosis), removal of infected tissues, usually by hysterectomy;
Administration of intravenous antibiotics with good anaerobic activity, such as penicillin, ampicillin, cefoxitin, clindamycin, metronidazole, or others; and
Administration of exquisite supportive care, typically in an ICU.
There are no data on the use of immunoglobulins or antilethal toxin antibodies.

Prevention

Prevention of infected abortion consists of avoiding unplanned pregnancies by access to, and proper use of, contraceptives. Because infection is less common after legal abortion than after illegal abortion, an additional important means to prevent postabortion infection is to provide access to all women to early, safe, legal abortion. Technical considerations include avoiding perforation and incomplete abortions during curettage procedures. Hysterotomy is accompanied by so large an increase in risk that it is rarely if ever indicated. Hysterectomy for abortion and sterilization is best reserved for women with additional uterine conditions.

In a meta-analysis, it was shown that antibiotics at induced abortion led to a substantial protective effect in both high-risk (history of pelvic inflammatory disease, C. trachomatis, or bacterial vaginosis) and low-risk women. It was estimated that periabortal antibiotics may prevent up to half of all postabortal infections.

FIGURE 12.4 Clostridial “gas gangrene” of uterus (x-ray).

Treatment

The essentials of treating infected abortion are (a) supportive therapy including replacement of blood and fluids; (b) surgical removal of any infected tissue; and (c) appropriate antibiotic therapy. After proper diagnostic studies have been carried out, vigorous parenteral antibiotic therapy should be administered. Because of the likelihood of multiple organisms and bacteremia in septic abortion, broad-spectrum antibiotic therapy such as clindamycin plus gentamicin is appropriate for initial therapy. For the patient in septic shock, addition of penicillin G or ampicillin is advisable.

FIGURE 12.5 Septic abortion with clostridial myonecrosis.

BOX 12.1 ▪ MEASURES TO AVOID WATER INTOXICATION IN PATIENTS RECEIVING HIGH-DOSE OXYTOCIN

Administer oxytocin in an electrolyte solution (not in 5% dextrose)
Avoid administration of electrolyte-free solution via other intravenous catheters
Observe closely for decrease in urine output
Determine serum sodium concentration, if symptoms arise. One recommended regimen is to give 50 U in 500 mL of saline over 3 hours (approximately 300 mU/min), followed by a 1-hour rest. The regimen is repeated, each time increasing the amount of oxytocin by 50 U per 500 mL of saline, until the fetus aborts or a total dose of 300 U of oxytocin in 500 mL is reached.

After antibiotic therapy is initiated, surgical drainage is essential unless there is confidence that infection is confined to the endometrium and there is no retained placental tissue. Prompt curettage usually suffices. In experienced hands and with special instruments, the uterus may be safely evacuated transcervically at up to 20 to 24 weeks, with ultrasound guidance. Delaying evaluation of the uterus because of the patient’s poor condition is a mistake in management that may prove fatal.

When the uterus is too large for an operator to undertake suction curettage, high-dose oxytocin administration often is successful. Rather than increasing the dose of oxytocin stepwise, we start with 300 mU/min of oxytocin in normal saline (0.9%) or in Ringer’s solution. At this dose, oxytocin exerts an antidiuretic effect. See Box 12.1 for measures to avoid water intoxication.

Fifteen-methyl prostaglandin F2a (carboprost tromethamine), 250 mg intramuscularly every 2 to 3 hours, has been recommended. If none of these drugs is available, a large Foley catheter (50-mL balloon) may be placed in the lower uterus. The use of prostaglandin E2 (PGE2) suppositories is contraindicated in the presence of sepsis because it causes fever.

In some situations, laparotomy may be indicated to control infection. Indications for exploratory laparotomy are shown in Box 12.2.

It must be emphasized that the mere isolation of Clostridium species from the pelvis does not necessarily signify life-threatening infection or the need for laparotomy. Instead, the initial treatment for a patient with presumed clostridial infection is penicillin in large doses, curettage, and supportive therapy. A pelvic roentgenogram should be obtained because it may reveal myometrial gas, but this occurs late if at all (Fig. 12.4). If there is no response or deterioration, laparotomy is indicated.

Prognosis

The overall outlook for a patient with infected abortion is good, but this condition must be considered a life-threatening infection. In the United States from 1972 to 1981, 273 women died of abortion complications, many from infection. Of these, 180 were from legal abortion, 83 from illegal abortion, and 10 from unknown type of abortion. From 1982 to 1991, there were 121 abortion deaths (111 legal, 7 illegal, and 3 unknown), whereas for 1992 to 2002, there were 92 abortion-related deaths (86 legal, 4 illegal, and 2 unknown). In 2003, there were 10 deaths from complications of illegal abortions (a rate of 1.18 deaths/100,000 procedures). There were no deaths reported in 2003 that were caused by legal abortion. Reasons for these improvements in outcome are improvement in physician skills; introduction of improved methods (suction curettage); and availability of safe, early, and legal abortion.

TABLE 12.1 ▪ QUALITY STANDARD FOR THE TREATMENT OF BACTEREMIA

Patients with bloodstream infection documented by a positive blood culture should be given an antibiotic to which the pathogen is susceptible in vitro.
Common skin-dwelling organisms, such as coagulase-negative Staphylococcus, Micrococcus, Bacillus, Corynebacterium, and Propionibacterium sp, may be significant when they are isolated from one or more cultures of blood from a patient without an intravascular catheter or from multiple cultures of blood from a patient without a catheter; when the patient appears septic; and when there is no apparent source of sepsis except the catheter.
The appropriateness of antibiotic therapy should be reviewed within 24 hours after the final susceptibility report is available from the laboratory.
When bacteremia is associated with meningitis, the antibiotic chosen should penetrate the blood-brain barrier.
No patient should receive an antibiotic who has elicited allergic or other serious adverse reactions.
The treatment of infections caused by organisms that are resistant to multiple antibiotics may require the use of drug combinations or of agents not included on the susceptibility report. Under these circumstances, additional communication among the prescriber, the infectious disease clinician, the microbiologist, and the pharmacist may be required.
If selective reporting of antimicrobial susceptibility is the usual practice, communication with the microbiology laboratory about the need for additional testing may be necessary.
Some bacteremic patients (e.g., those with neutropenia, endocarditis, or compromised immune systems) may require two appropriate antimicrobial agents instead of one, but such treatment is not part of the standard.
On occasion, a report indicating antimicrobial susceptibility may be clinically irrelevant. For example, methicillin-resistant staphylococci should be reported as resistant to cephalosporins, carbapenems, and β-lactam/β-lactamase inhibitor combinations despite apparent in vitro susceptibility. Cefuroxime, cephapirin, cephradine, and cefazolin may be used against organisms susceptible to cephalothin. For enterococci isolated from the bloodstream, vancomycin, penicillin G, or ampicillin plus gentamicin are preferred, but resistance has been documented. Macrolides, cephalosporins, clindamycin, and aminoglycosides alone are not effective.

From Gross PA, Barrett TL, Dellinger EP, et al. Quality standard for the treatment of bacteremia. Clin Infect Dis 1994;18:428-430.

Reproductive potential after an infected abortion may be compromised by Asherman syndrome, pelvic adhesions, or incompetent cervix. However, the CDC concluded that vacuum aspiration overall does not adversely affect fecundity but that dilation and evacuation for second-trimester termination increases the risk of subsequent spontaneous abortion, prematurity, and low birth weight infants.

BACTEREMIA

The principal pathogens responsible for bacteremia in obstetric-gynecologic patients are coliform organisms, particularly Escherichia coli, group B streptococci, anaerobic streptococci, and Bacteroides sp. Other significant causative organisms include Clostridium sp, enterococci, and, rarely, Staphylococcus aureus and Streptococcus pneumoniae. Multiple aerobic and anaerobic organisms may be responsible for bacteremia in certain patients. The reported overall incidence of bacteremia is about 7.0 per 1,000 obstetric-gynecologic admissions.

Most obstetric-gynecologic patients with bacteremia respond promptly to intravenous antibiotic therapy, and their prognosis is better than that of medical patients with bacteremia. It has been reported that overall, bacteremic obstetric patients and nonbacteremic obstetric patients with similar infections have similar outcomes. However, sepsis develops occasionally, with an appreciable mortality rate.

Recognizing that antibiotic use often is inappropriate (22% to 64% of the time in recent reviews) and that inappropriate antibiotic use is accompanied by adverse results, standards of treatment for bacteremia have been published. These standards are given in Table 12.1.

Most nonbacteremic obstetric-gynecologic patients who have genital tract infections respond promptly to antibiotic and do no require therapy for more than 24 to 48 hours after resolution of fever and other signs of infection. Patients with
a bacteremic genital tract infection should be considered differently. For most bacteremic patients, we continue an appropriate intravenous antibiotic therapy for 48 hours after resolution of infection and then prescribe an oral antibiotic to complete a 7- to 10-day course. Some bacteremias such as those caused by S. aureus should be treated with intravenous therapy for a longer period (e.g., 10 to 14 days) to prevent metastatic infection.

TABLE 12.2 ▪ RECENT DEFINITIONS OF TERMS USED IN DESCRIBING SEPSIS AND RELATED CONDITIONS

Bacteremia	Positive blood culture
Infection	Inflammatory response to micro-organisms or invasion of normally sterile fluids or tissues.
Shock	Inadequate perfusion of tissues leading to cell dysfunction and cell death (if prolonged)
Systemic inflammatory response syndrome	Clinical signs of systemic response to endothelial inflammation, commonly occurring in the setting of infection, but also with other conditions such as trauma (Table 12.3)
Sepsis	Systemic response to serious infection
	Clinical evidence of infection plus evidence of systemic response including tachypnea (>20/min), tachycardia (>90/min), and/or hyper- or hypothermia (rectal temperature >38.3°C or <35.6°C) confirmed or suspected infection plus two or more systemic inflammatory response syndrome criteria.
	Manifestations of systemic inflammatory response syndrome in association with infection (Table 12.3)
Severe sepsis	Sepsis and one or more organ dysfunction.
Septic shock	Sepsis with hypotension (systolic blood pressure <90 mm Hg) despite fluid resuscitation.
Adapted from Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993;328:1471-1477; Bone RC. Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA 1992;268:3452-3455; Martin MA, Silverman HJ. Gram-negative sepsis and the adult respiratory distress syndrome. Clin Infect Dis 1992;14:1213-1218; Harry W, Foley MR. Treating septic shock in Ob/Gyn patients. Cont Ob/Gyn 2005;March:49-55; Grooper MA. Evidence based management of critically ill patients: analysis and implementation. Anesth Analg 2004;99:566-572.

SEPSIS, SEPTIC SHOCK, AND THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

Terms including infection, bacteremia, sepsis, severe sepsis, and septic shock are defined in Tables 12.2 and 12.3. Only a small percentage of infected obstetric-gynecologic patients are bacteremic (in nearly all series, <10% of patients with infection). An even smaller percentage of these women, probably less than 2% to 5%, develop sepsis. Approximately half of all patients with sepsis have bacteremia. Sepsis has been defined as a subset of patients with systemic inflammatory response syndrome. About 15% of all patients with systemic inflammatory response syndrome do not have infection but rather other precipitating causes, such as trauma or pancreatitis. Sepsis, sepsis syndrome, and septic shock can be thought of as a continuum.

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