Clinical Expert Series
Treating Spontaneous and Induced Septic Abortions David A. Eschenbach,
MD
Worldwide, abortion accounts for approximately 14% of pregnancy-related deaths, and septic abortion is a major cause of the deaths from abortion. Today, septic abortion is an uncommon event in the United States. The most critical treatment of septic abortion remains the prompt removal of infected tissue. Antibiotic administration and fluid resuscitation provide necessary secondary levels of treatment. Most young physicians have never treated septic abortion. Many obstetrician–gynecologists experience, or plan to experience, global health activities and will likely care for women with septic abortion. Thus, updated knowledge of the pathophysiology, clinical presentation, microbes, and proper treatment is needed to optimally treat this emergency condition when it exists. The pathophysiology of septic abortion involves infection of the placenta, especially the maternal villous space that leads to a high frequency of bacteremia. Symptoms and signs range from mild to severe. The microbes involved are usually common vaginal bacteria, including anaerobes, but occasionally potentially very serious and lethal infection is caused by bacteria that produce toxins. The primary treatment is early curettage to remove infected and devitalized tissue even in the face of continued fetal heart tones. Important secondary treatments are the administration of fluids and antibiotics. Updated references of sepsis and septic shock are reviewed. (Obstet Gynecol 2015;125:1042–8) DOI: 10.1097/AOG.0000000000000795
T
he most recent data that address the fifth Millennium Development Goal to reduce maternal mortality by 75% between 1990 and 2015 indicates that an estimated worldwide decrease of 1.3% has occurred each year since 1990 to approximately 293,000 maternal deaths in 2013.1 Overall, approximately 14% of pregnancy-related deaths worldwide are attributed to complications of both induced and spontaneous abortion or approximately 40,000 pregnancy-related deaths annually.1 Although this represents a decrease in pregnancy-related death from abortion from 1990,
From the Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington. Continuing medical education for this article is available at http://links.lww. com/AOG/A625. Corresponding author: David A. Eschenbach, MD, Department of Obstetrics and Gynecology, Box 356460, University of Washington, Seattle, WA 98195; e-mail: [email protected]. Financial Disclosure The author did not report any potential conflicts of interest. © 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0029-7844/15
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the number of pregnancy-related deaths from abortion in 2013 now equals maternal death from hemorrhage.1 A maternal death leads to a substantial number of years of life lost2 and it also has a major effect on the stability and viability of families everywhere, but this is especially true in developing countries. A septic abortion is an infection of the placenta and fetus (products of conception) of a previable pregnancy. Infection is centered in the placenta and there is risk of spreading to the uterus, causing pelvic infection or becoming systemic to cause septicemia and potential damage of distant vital organs. Septic abortion can rapidly become a dangerous and even lethal infection when infected tissue remains in the uterus, especially when toxin-producing bacteria are present and gain entrance into the uterus. Worldwide, the majority of septic abortion occurs as a result of unsafe abortion. The World Health Organization defines unsafe abortion as “a procedure for terminating an unintended pregnancy either by individuals without the necessary skills or in an environment that does not conform to minimum medial standards or both.”3 Several other publications review
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the need and requirements of safe abortion.4,5 In developing countries, up to five million women are admitted to hospitals yearly from complications of unsafe abortion.6 Among women with severe complications from abortion, severe infection from septic abortion is the second most common complication, only behind severe trauma to the cervix or uteruscausing hemorrhage.7 Most maternal deaths occur in developing countries where sepsis still is estimated to cause approximately 10% of all maternal deaths. In developing countries, sepsis is common in both illegal and spontaneous abortions.8,9 In a literature review of 35 studies of women largely admitted to primary and secondary hospitals in developing countries, the overall percent of severe infections ranged from 3% to 15% with a median of 5%.7 However, among women with severe complications of abortion admitted to tertiary hospital centers, the prevalence of sepsis also is variable, but it can be as high as 31–54% of such patients.10,11 Considering severe complications from septic abortion alone, the case-fatality rates in tertiary centers also are extremely variable, ranging from more than 5% to 20% in many developing countries.12,13 The estimated case-to-fatality ratio per 100,000 abortions ranges from 10 in Latin America to 100 in Eastern Africa,14 well more than 100 times greater than in the United States. Much of this elevated fatality rate relates to a delay in removal of the infected placenta, severe uterine trauma, and severe hemorrhage because of patient delay, the stigma associated with illegal abortion, and physician scarcity. Developing countries have the double disadvantage of 1) untrained personnel and patients themselves attempting to induce abortion with either instruments or chemicals that leave dead tissue remaining in the uterus to become infected and 2) the lack of trained health care workers to surgically remove tissue in cases in which prolonged bleeding in spontaneous abortion leads to sepsis or when sepsis or trauma occurs from unsafe abortion. By contrast, septic abortion is uncommon in the United States and other developed countries when both the surgical treatment of spontaneous abortion is readily available and illegal abortion is uncommon. For example, the estimated case-to-fatality ratio per 100,000 abortions in the United States is approximately 0.6 for spontaneous abortion8 and similar (from 0.78 to 0.57) for induced abortions performed between 1979 and 2008.15,16 After the legalization of abortion in the United States in 1973, the number of deaths from abortion in the United States dropped by 50% in the first 5 years and by another 83% in the
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following years.15 Between 2004 and 2008, only 6–12 women annually died in the United States after a legal induced abortion.15 The precise case-tofatality ratio of illegal abortion in the United States is even more difficult to know because the lack of a reliable denominator, but only 14 deaths were detected after illegal abortion in the 29 years between 1979 and 2008.15 Before 1973, septic abortions were an integral part of obstetric and gynecologic residency training and of practicing physician’s knowledge as to the need to immediately remove the infected placenta. For example, the number of hospital admissions for septic abortion was 105 women to Boston City Hospital in 1955–195617 and was 87 women to a Pittsburgh hospital in 1965–1967.18 However, most physicians who have been trained in the 40 years since Roe v. Wade never cared for a patient with a septic abortion or were provided detailed training on its treatment. The objective of this review is to update physicians on the identification and treatment of septic abortion. This review also is particularly relevant now as a result of the commitment of many obstetricians and gynecologists, both in training and out, to provide care in the developing world. It is important to realize that the death ratio after spontaneous abortion and induced abortion is virtually identical (0.7/100,000 abortions).19,20 Other data also point to similar findings of an estimated death ratio per 100,000 abortions in the United States of approximately 0.6 for spontaneous abortion8 and from 0.78 to 0.57 for induced abortions performed between 1979 and 2008.16 Infection accounts for the vast majority of death (59%) after spontaneous abortion.19 The most common cause of death after induced abortion also is infection (27%) followed by hemorrhage (24%).20 Thus, septic abortion can become serious after either spontaneous or induced abortion. The other key fact is that gestational age strongly influences the death rate after both spontaneous and induced abortion. As gestation advances, the placenta becomes increasingly large, which provides a greater volume of tissue to become infected. The death ratio per 100,000 spontaneous abortions is 0.3 before 13 weeks of gestation, 1.5 at 13–15 weeks of gestation, and 4.1 at 16–19 weeks of gestation.19 The death ratio per 100,000 induced abortions is 0.1–0.4 before 13 weeks of gestation, 1.7 at 13–15 weeks of gestation, 3.4 at 16–20 weeks of gestation, and 8.9 beyond 20 weeks of gestation.20 Thus, physicians need to be particularly aware of the potential for greater risk to the woman when infection develops at the more advanced gestational ages.
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Treating Septic Abortion
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PATHOPHYSIOLOGY Sepsis starts with the invasion of vaginal bacteria into the uterus usually preceded by uterine instrumentation or prolonged uterine bleeding. Once in the uterus, bacteria can gain access into the maternal intervillous space of the placenta to initiate a septic abortion.21 From the intervillous space, maternal bacteremia occurs in more than 60% of septic abortions.18 The finding that much of the infection is in the intervillous space also may explain why fetal heart tones can remain despite life-threatening maternal bacteremia. The presence of toxins produced by Clostridium species and group A streptococci and an overwhelming immune response to infection can lead to systemic disease and distant multiorgan failure. If the infected placental tissue remains for a prolonged time, bacteria can invade into the decidua of the endometrium and from there into the myometrium.21,22 This time can be as short as 6–12 hours when very virulent bacteria are present or significant trauma has occurred. Infections that involve the uterus are not readily treated by simple removal of the placenta. Such infections require high doses of antibiotics. Infection from toxin-producing bacteria such as Clostridium species or group A streptococcus are particularly serious and potentially lethal on uterine invasion. Tissue necrosis of not only the placenta, but the uterus can be produced by these toxins that can limit the effectiveness of antibiotic therapy. When serious infection occurs, the source of the toxinproducing site needs to be removed, which leads at least to curettage for removal of the placenta and to hysterectomy if the toxin production arises from a uterine source. Of course, septic abortion also causes death of the fetus. Fetal death is inevitable with septic abortion, so uterine curettage should be promptly performed without waiting for the absence of fetal heart activity.
MICROBES Most bacteria that cause septic abortion are those arising from vaginal flora.8,18,23,24 However, in part because of placental devitalization with unsafe or incomplete abortion, a high rate of infection with anaerobic bacteria is associated with septic abortion. Anaerobic bacteria were present in approximately 60% of women with positive blood cultures.18,23 Bacteremia is common because the infection often localizes in the maternal intervillous space. Bacteremia occurs in 38–61% of women with septic abortion.18,23 As expected, a high concordance occurs between blood and cervical isolates.18 However, anaerobic Peptostreptococcus, the most common blood isolate from cases of
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septic abortion, can be isolated in approximately 40% of all cases.18 A culture from the cervix or products of conception is necessary in septic abortion. The main aim of this culture is to identify the presence of toxin producers or antibiotic-resistant bacteria such as Staphylococcus aureus. The identification of toxin producers in these cultures is critical to alert caregivers that a potentially serious infection may exist and that prompt removal of infected tissue is needed with especially diligent follow-up. Most infection with septic abortion remains localized to the placenta. However, given enough time to replicate in dead tissue, some bacterial species can cause particularly serious sepsis and septic shock. The toxin-producing groups of bacteria, especially Clostridium species and group A streptococcus, but also some toxin-producing strains of Escherichia coli, deserve special mention. These strains have a propensity to proliferate within dead tissue of both the placenta and the uterus in septic abortion, where they can cause local tissue destruction. It is within this dead tissue that antibiotics are not able to penetrate because the bacteria have become isolated from the vasculature. S aureus is important because of its resistance to common antibiotic therapy. In these situations, antibiotics become ineffective treatment tools. Furthermore, these particular bacterial species also can produce very potent toxins that when released from the infected site have a propensity to cause endothelial vascular damage, leading to damage of distant organs function of the lung, kidney, heart, and coagulation systems. Clostridium perfringens is isolated from the vagina in approximately 1% and from the rectum in 10% of young women.25 However, C perfringens is isolated from up to 5% of all septic abortions18 and an especially high number of women who die.24 C perfringens appears more common in unsafe septic abortion where delay in the removal of dead tissue allows proliferation of these slow-growing bacteria in an anaerobic tissue environment.8 Group A streptococcus is an even rarer isolate in septic abortion, but it has the same toxin-producing propensity and pathology as C perfringens. Certain strains of E coli and of S aureus can also produce potent toxins. Recently, Clostridium sordellii was associated with death from sepsis after medical abortion.22 A review of original series of these infections with additional cases was recently updated.26 Fortunately, C sordellii infection is rare, but the infection is particularly lethal when present in any pelvic site.26 C sordellii are infrequently found in the vagina (less than 0.5%) and rectum (approximately 2%) of reproductive-aged women.25 Detailed autopsy examination of those women with
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Box 1. Clinical Steps to Identify and Treat Septic Abortion History documentation of Prior uterine instrumentation Length of vaginal bleeding Length of fever Other symptoms Confirm pregnancy Document gestational age Risk assessment for Products of conception remaining in the uterus Unsafe abortion IUD in situ Perform physical examination of Temperature, blood pressure, pulse, respirations Abdominal examination for degree of direct and rebound tenderness Pelvic speculum examination for cervical or vaginal trauma, foul-smelling or purulent cervical–vaginal discharge Bimanual examination for cervical and uterine tenderness and adnexal tenderness or mass Culture Aerobic and anaerobic cultures of the cervix (especially to identify virulent pathogens that produce toxins), products of conception (if present), or both Blood Blood examination Complete blood count Lactic acid level Coagulation studies Hemolysis determination Renal function studies Check of Rh(D)-negative blood type Imaging studies Ultrasonography for products of conception remaining in the uterus Radiograph or computed tomography scan of the pelvis and abdomen for free air in the abdomen and gas in the myometrium Intravenous medication: Fluid, antibiotics (Box 3) Vasopressors, if needed Uterine curettage Under anesthesia using a vacuum suction catheter Examine and culture products of conception Pathologic examination of products of conception to confirm pregnancy and identify degree of inflammation Monitor vital signs and treat ongoing sepsis Frequent blood pressure Pulse oximeter use for tachypnea Central venous pressure use for shock (Box 2) IUD, intrauterine device.
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a C sordellii septic abortion probably reflects the usual situation for all of these toxin producers; C sordellii antigen was found only in the necrotic endometrium and myometrium (the placenta has been previously removed) but antigen was not present in the lung, kidney, heart, or liver.22 Thus, it appears that these toxin producers can cause death from the release of potent toxins that cause distant vascular damage and organ failure without actual bacterial spread to these organs. In these situations, prompt hysterectomy to remove the site of toxin production becomes necessary to prevent death.27
CLINICAL RECOGNITION Most women with severe infection who die from septic abortion have no underlying medical comorbidity, in contrast to other causes of maternal death in the United States. Septic abortion typically occurs in the setting of intrauterine tissue damage such as retained products of conception after a spontaneous or induced abortion, an unsafe abortion involving instruments or chemicals, and a pregnancy with an intrauterine device in place. The differential diagnosis includes spontaneous abortion with endometritis and incomplete abortion with another cause of fever such as pyelonephritis, appendicitis, and the flu. In one series, virtually all women with a septic abortion had a fever. The exception was women with serious sepsis from C sordellii, who often were initially diagnosed with the flu.22 Clinical steps to identify and treat septic abortion are listed in Box 1; only a few of the steps are addressed in the text. The clinical presentation of septic abortion is varied, in part because the placental infection is localized within the uterus that acts to mask the severity of infection. Most women with septic abortion have a history of fever and uterine bleeding.17,18,23 Many women also will present with chills and abdominal pain. Inquiry about the date of any recent pregnancy and prior uterine procedure is critical. Serious infection is often present when symptoms are present for several days or when symptoms begin several days or weeks after an abortion has occurred.24 Very high temperatures indicate severe disease, although severe disease can be present with only a mild fever. Again, a word of caution, like in the cases of C sordellii, fever was not present.22,26 Prostration, marked tachycardia, marked tachypnea with or without respiratory difficulty, hypotension, and low urine output certainly indicate very severe sepsis. Usually, abdominal findings are limited to mild tenderness without rebound tenderness. Findings of general peritonitis indicate serious infection.15,17 On pelvic examination, one
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should examine for trauma to the cervix and pus or foul-smelling fluid from the cervix. The uterus is usually only mildly tender.17 Even in severe infection, the uterus can be deceivingly less tender than one might expect. Aerobic and anaerobic blood and cervical cultures should be obtained to alert caregivers to the presence of toxin producers. Isolation of common vaginal bacteria usually occurs in mild-to-moderate infection. However, the isolation of toxin producers (especially Clostridium species and group A streptococcus) puts the physician on alert that not only is a serious infection likely present, but that the infection is potentially lethal. Markedly elevated white blood cell counts higher than 20,000 also indicate severe infection, and a leukemoid reaction (white blood counts higher than 50,000) can be present in infection associated with toxin production. If severe infection is present, additional blood work includes lactic acid measurement, creatinine, and studies to diagnose disseminated intravascular coagulation and hemolysis. Anti-D immunoglobulin should be given to Rh(D)-negative women. Ultrasonograms should be used to determine the presence of products of conception. A detailed discussion exists in the use of ultrasonography to diagnose remaining products of conception.28 A completed abortion without remaining products of conception is likely when the endometrial stripe is less than 8 mm. Serial blood pressure, pulse oxygen measurement, and urine volume measurement are needed to monitor fluid resuscitation. It is worth noting that the typical central venous pressure is low in patients with severe infection from septic abortion.24 A low central venous pressure could be related to significant blood loss as well as to decreased systemic resistance from sepsis. Recent updates in the treatment of severe sepsis and septic shock are available as references in Box 2, but a detailed discussion is outside the scope of this report.
TREATMENT The complete treatment of septic abortion includes the initiation of intravenous fluid for maternal stabilization, culture collection, and antibiotic administra-
Box 2. Treatment of Severe Sepsis and Septic Shock 1. 2. 3. 4. 5.
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Severe sepsis and septic shock36 Acute respiratory distress syndrome37 Disseminated intravascular coagulation syndrome38 Acute renal failure and sepsis39 Treating severe sepsis and septic shock40
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tion followed by a prompt surgical evacuation of the infected products of conception4,8,9 (grade 1B evidence) independent of fetal heart activity, because septic abortion, especially in the second trimester, can occur with a live fetus. This report also reviews clinical findings that indicate the presence of infections with high mortality rates. Clinicians inexperienced in the identification and treatment of women with septic abortion may fail to realize the speed to which this infection can become serious, systemic, and even lethal. A major purpose of this document is to emphasize the necessity of prompt uterine curettage. A paradox is that both physicians who practiced in the United States before 1973 and those in developing countries recognize the necessity for prompt surgical evacuation. For all types of serious pelvic infection, U.S. physicians can be lulled into an absolute reliance on antibiotic therapy instead of considering surgical removal of infected tissue in life-threatening infections, because antibiotic treatment is usually successful. Prompt removal of infected products of conception is the key and most important treatment for septic abortion8,23 over which there is little dispute.9,24 Even death is related to incomplete products of conception removal.8 Because the bacteria reside in the maternal villous spaces and often not in the fetal villi,21 infection can occur predominantly on the maternal side of the placenta. This may explain both the early maternal febrile response and 60% rate of bacteremia, stimulating a robust maternal immune system response. Removal of infected tissue not only eliminates bacterial infection within the placenta, but it limits spread of bacteria into the uterus and into the systemic circulation. Antibiotic administration is recommended before the curettage to prevent septic shock that can also develop from overwhelming bacteremia during the curettage. Particularly severe infection is present when the following clinical findings exist: severe acute respiratory syndrome (SARS), disseminated intravascular coagulation, hemolysis, lactic acidosis, oliguria, and septic shock. In even otherwise healthy women, the mortality rates are very high when these conditions exist. Overall, postpartum maternal mortality is greater than 20% with septic shock and disseminated intravascular coagulation and 33–50% with SARS.29 Prompt resuscitation is necessary with fluid, blood pressure control with vasopressors, and, in some cases, blood transfusion. The medical treatment of severe sepsis with SARS, disseminated intravascular coagulation, and renal injury has been thoroughly reviewed for a reference in the publications listed in Box 2. However, in septic abortion, these clinical
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findings cannot be reversed without a complete removal of the infected placenta site by curettage. Mortality specific to septic abortion in a case series of women admitted to an intensive care unit in Argentina was 19% overall.24 Septic shock occurred in 32% of these patients and death occurred in 55% of women in septic shock as compared with 19% of all 63 patients.24 Death occurred in 26–31% of patients who developed SARS, disseminated intravascular coagulation, or the need for mechanical ventilation from severe sepsis.24 Prompt reversal of septic shock with resuscitation allows time to assess whether these other complications are beginning to occur and can be reversed with medical therapy alone.22,24 The need for and timing of hysterectomy in a case of severe sepsis that has not responded to the removal of products of conception and resuscitative efforts are more difficult to determine than the prompt need for curettage.30 Indications for hysterectomy include a worsening clinical response after curettage, the presence of widespread peritonitis, and a pelvic abscess. Clostridial myonecrosis (gas gangrene or myonecrosis from other gas producers), determined by air in the uterine wall or crepitation in the pelvis, free air in the abdomen from a uterine perforation, and clostridium or Group A streptococcus sepsis should prompt immediate laparotomy and hysterectomy if dead uterine tissue or trauma from a prior uterine instrumentation is detected. The development of continued septic shock, worsening of SARS or disseminated intravascular coagulation, or the need for mechanical ventilation indicates one or more individual organ failures that also should move one to consider hysterectomy. The death rate is already more than 50% in patients in septic shock from septic abortion, and, though the judgment to delay surgery may allow some patients added time to respond to medical treatment and avoid hysterectomy,31 such a delay also risks irreversible septic shock, widespread organ failure, and death.24,32 One should expect clinical improvements within 6 hours of curettage, fluid resuscitation, and antibiotic therapy.30 The clinical condition needs to be monitored on an hourly basis so one can proceed promptly with a laparotomy if the clinical situation worsens or does not improve over a short time. The concept of the patient being too sick for surgery needs to be abandoned in these cases, because surgery with hysterectomy can be lifesaving. Antibiotic selection needs to cover the large variety of possible anaerobic and aerobic bacteria23,24 (Box 3). Bacteria that produce most septic abortion are sensitive to antibiotics. However, anaerobic coverage is particularly necessary. As a reminder, Clos-
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Box 3. Antibiotic Treatment Choices for Septic Abortion 1. Gentamicin (5 mg/kg/d) and clindamycin (900 mg every 8 h) with or without ampicillin 2. Ampicillin (2 g every 4 h) and gentamicin with metronidazole (500 mg every 8 h) 3. Levofloxacin (500 mg daily) and metronidazole 4. Imipenem (500 mg every 6 h) 5. Piperacillin–tazobactam (4.5 g every 8 h) 6. Ticarcillin–clavulanate (3.1 g every 4 h)
tridium species and group A streptococcus infections remain very sensitive to penicillin. Still, most antibiotic regimens for serious pelvic infection include a combination of: gentamicin and clindamycin; ampicillin, gentamicin, and metronidazole; levofloxacin and metronidazole; or a single agent of imipenem; piperacillin–tazobactam; or ticarcillin–clavulanate. Intravenous antibiotics can be stopped 48 hours after clinical improvement in cases without an abscess.33 The final point again is that the antibiotic choice is secondary to the prompt removal of the infected dead placenta.9,21 Clindamycin deserves special mention in treating septic abortion. In vitro, clindamycin inhibits S aureus toxic shock toxin levels in concentrations well below the level needed to inhibit bacterial growth.34 Clindamycin also inhibits group A streptococcus and clostridium toxins in vitro35 and was more effective in treating deep group A streptococcus infection in children than cell wall-inhibiting agents.35 Thus, clindamycin should be considered for use in patients with infection suspected to be produced by toxins.
DISCUSSION Treatment of septic abortion starts with a prompt and accurate recognition of placental infection in a previable pregnancy, genital and blood cultures, fluid and antibiotic administration, and the prompt removal of infected products of conception. Physicians need to be aware of the development of signs of severe infection that requires careful hourly monitoring of clinical signs and consideration of hysterectomy if the signs of severe infection worsen or are not reversed in a short time. REFERENCES 1. Kassebaum N, Bertozzi-Villa A, Coggeshall M, Shackelford K, Steiner C, Heuton K, et al. Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the global burden of disease study 2013. Lancet 2014;384:980–1004. 2. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic
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analysis for the global burden of disease study 2010. Lancet 2012;380:2095–128. 3. World Health Organization. The prevention and management of unsafe abortion—report of a technical working group. Geneva (Switzerland): World Health Organization; 1992. 4. Berer M. Making abortion safe: a matter of good public health policy and practice reproductive health matters. Bull World Health Organ 2000;78:580–92. 5. Rasch V. Unsafe abortion and postabortion care—an overview. Acta Obstet Gynecol Scand 2011;90:692–700. 6. Singh S. Hospital admissions resulting from unsafe abortion: estimates from 13 developing countries. Lancet 2006;368: 1887–92. 7. Adler AJ, Filippi V, Thomas SL, Ronsmans C. Quantifying the global burden of morbidity due to unsafe abortion: magnitude in hospital-based studies and methodological issues. Int J Gynecol Obstet 2012;118(suppl 2):565–77. 8. Grimes DA, Cates W Jr, Selik RM. Fatal septic abortion in the United States, 1975–77. Obstet Gynecol 1981;57:739–44. 9. Stubblefield PG, Grimes DA. Septic abortion. N Engl J Med 1994;331:310–4. 10. Adetoro OO, Barbarinsa AB, Sotiloye OS. Socio-cultural factors in adolescent septic illicit abortion in Ilorin, Nigeria. Afr J Med Sci 1991;20:149–53. 11. Nwogu-Ikojo EE, Ezegwui HU. Abortion related mortality in a tertiary medical center in Enugu, Nigeria. J Obstet Gynaecol 2007;27:835–7. 12. Sule-Odu AO, Olatunji AO, Akindele RA. Complicated induced abortion in Sagamu, Nigeria. J Obstet Gynaecol 2002;22:58–61. 13. Guleria K, Bansal S, Agarwal N, Grover V. Women with septic abortion: who, how, why? A prospective from tertiary care hospital in India. Indian J Public Health 2006;50:95–6.
22. Fischer M, Bhatnagar J, Guarner J, Reagan S, Hacker JK, Van Meter SH, et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005;353:2352–60. 23. Chow AW, Marshall JR, Guze LB. A double-blind comparison of clindamycin with penicillin plus chloramphenicol in treatment of septic abortion. J Infect Dis 1977;135(suppl):S35–9. 24. Finkielman JD, De Feo FD, Heller PG, Afessa B. The clinical course of patients with septic abortion admitted to an intensive care unit. Intensive Care Med 2004;30:1097–102. 25. Shannon C, Veatch M, Chong E, Agnew K, Nucatola D, Newhall E, et al. Vaginal and rectal clostridial colonization among women of reproductive age in the United States. Contraception 2010;82:214. 26. Zane S, Guarner J. Gynecologic Clostridial toxic shock in women of reproductive age. Curr Infect Dis Rep 2011;13:561–70. 27. Bryant AE, Stevens DL. Clostridial myonecrosis: new insights in pathogenesis and management. Curr Infect Dis Rep 2010; 12:383–91. 28. Rahangdale L. Infectious complications of pregnancy termination. Clin Obstet Gynecol 2009;52:198–204. 29. Callaghan WM, Creanga AA, Kuklina EV. Severe maternal morbidity among delivery and postpartum hospitalizations in the United States. Obstet Gynecol 2012;120:1029–36. 30. Reid DE. Assessment and management of the seriously ill patient following abortion. JAMA 1967;199:141–8. 31. Soper DE, Lee SI, Kim JY, McDonald AG. Case records of the Massachusetts General Hospital. Case 35-2011: A 33-year old woman with postpartum leukocytosis and Gram positive bacteremia. N Engl J Med 2011;365:1916–24. 32. Santamarina BA, Smith SA. Septic abortion and septic shock. Clin Obstet Gynecol 1970;13:291–304.
14. Ahman E, Shah I. New estimates and trends regarding unsafe abortion mortality. Int J Gynaecol Obstet 2011;115:121–6.
33. Savaris RF, de Moraes GS, Cristovam RA, Braun RD. Are antibiotics necessary after 48 hours of improvement in infected/septic abortions? A randomized controlled trial followed by a cohort study. Am J Obstet Gynecol 2011;204:301.e1–5.
15. Pazol K, Creanga AA, Zane SB, Burley KD, Jamieson DJ; Centers for Disease Control and Prevention (CDC). Abortion surveillance United States, 2009. MMWR Surveill Summ 2012;61:1–44.
34. Schlievert PM, Kelly JA. Clindamycin-induced suppression of toxic shock syndrome-associated exotoxin production. J Infect Dis 1984;149:471.
16. Raymond EG, Grimes DA. The comparative safety of legal induced abortion and childbirth in the United States. Obstet Gynecol 2012;119:215–9.
35. Zimbelman J, Palmer A, Todd J. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive streptococcus pyogenes infection. Pediatr Infect Dis J 1999; 18:1096–100.
17. Tenney B, Little A, Wamsteker E. Septic abortion. N Engl J Med 1957;257:1022–5. 18. Rotheram EB Jr, Schick SF. Nonclostridial anaerobic bacteria in septic abortion. Am J Med 1969;46:80–9. 19. Saraiya M, Green C, Berg C, Hopkins F, Koonin L, Atrash H. Spontaneous abortion-related deaths among women in the United States—1981–1991. Obstet Gynecol 1999;94:172–6. 20. Bartlett L, Berg C, Shulman H, Zane S, Green C, Whitehead S, et al. Risk of factors for legal induced abortion-related mortality in the United States. Obstet Gynecol 2004;103:729–37. 21. Studdiford WE, Douglas GW. Placental bacteremia: a significant finding in septic abortion accompanied by vascular collapse. Am J Obstet Gynecol 1956;71:842–58.
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36. Angus D, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:840–51. 37. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000;342:1334–49. 38. Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999;341:586–92. 39. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004;351:159–69. 40. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165–228.
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Treating Spontaneous and Induced Septic Abortions David A. Eschenbach,
MD
Worldwide, abortion accounts for approximately 14% of pregnancy-related deaths, and septic abortion is a major cause of the deaths from abortion. Today, septic abortion is an uncommon event in the United States. The most critical treatment of septic abortion remains the prompt removal of infected tissue. Antibiotic administration and fluid resuscitation provide necessary secondary levels of treatment. Most young physicians have never treated septic abortion. Many obstetrician–gynecologists experience, or plan to experience, global health activities and will likely care for women with septic abortion. Thus, updated knowledge of the pathophysiology, clinical presentation, microbes, and proper treatment is needed to optimally treat this emergency condition when it exists. The pathophysiology of septic abortion involves infection of the placenta, especially the maternal villous space that leads to a high frequency of bacteremia. Symptoms and signs range from mild to severe. The microbes involved are usually common vaginal bacteria, including anaerobes, but occasionally potentially very serious and lethal infection is caused by bacteria that produce toxins. The primary treatment is early curettage to remove infected and devitalized tissue even in the face of continued fetal heart tones. Important secondary treatments are the administration of fluids and antibiotics. Updated references of sepsis and septic shock are reviewed. (Obstet Gynecol 2015;125:1042–8) DOI: 10.1097/AOG.0000000000000795
T
he most recent data that address the fifth Millennium Development Goal to reduce maternal mortality by 75% between 1990 and 2015 indicates that an estimated worldwide decrease of 1.3% has occurred each year since 1990 to approximately 293,000 maternal deaths in 2013.1 Overall, approximately 14% of pregnancy-related deaths worldwide are attributed to complications of both induced and spontaneous abortion or approximately 40,000 pregnancy-related deaths annually.1 Although this represents a decrease in pregnancy-related death from abortion from 1990,
From the Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington. Continuing medical education for this article is available at http://links.lww. com/AOG/A625. Corresponding author: David A. Eschenbach, MD, Department of Obstetrics and Gynecology, Box 356460, University of Washington, Seattle, WA 98195; e-mail: [email protected]. Financial Disclosure The author did not report any potential conflicts of interest. © 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0029-7844/15
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the number of pregnancy-related deaths from abortion in 2013 now equals maternal death from hemorrhage.1 A maternal death leads to a substantial number of years of life lost2 and it also has a major effect on the stability and viability of families everywhere, but this is especially true in developing countries. A septic abortion is an infection of the placenta and fetus (products of conception) of a previable pregnancy. Infection is centered in the placenta and there is risk of spreading to the uterus, causing pelvic infection or becoming systemic to cause septicemia and potential damage of distant vital organs. Septic abortion can rapidly become a dangerous and even lethal infection when infected tissue remains in the uterus, especially when toxin-producing bacteria are present and gain entrance into the uterus. Worldwide, the majority of septic abortion occurs as a result of unsafe abortion. The World Health Organization defines unsafe abortion as “a procedure for terminating an unintended pregnancy either by individuals without the necessary skills or in an environment that does not conform to minimum medial standards or both.”3 Several other publications review
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the need and requirements of safe abortion.4,5 In developing countries, up to five million women are admitted to hospitals yearly from complications of unsafe abortion.6 Among women with severe complications from abortion, severe infection from septic abortion is the second most common complication, only behind severe trauma to the cervix or uteruscausing hemorrhage.7 Most maternal deaths occur in developing countries where sepsis still is estimated to cause approximately 10% of all maternal deaths. In developing countries, sepsis is common in both illegal and spontaneous abortions.8,9 In a literature review of 35 studies of women largely admitted to primary and secondary hospitals in developing countries, the overall percent of severe infections ranged from 3% to 15% with a median of 5%.7 However, among women with severe complications of abortion admitted to tertiary hospital centers, the prevalence of sepsis also is variable, but it can be as high as 31–54% of such patients.10,11 Considering severe complications from septic abortion alone, the case-fatality rates in tertiary centers also are extremely variable, ranging from more than 5% to 20% in many developing countries.12,13 The estimated case-to-fatality ratio per 100,000 abortions ranges from 10 in Latin America to 100 in Eastern Africa,14 well more than 100 times greater than in the United States. Much of this elevated fatality rate relates to a delay in removal of the infected placenta, severe uterine trauma, and severe hemorrhage because of patient delay, the stigma associated with illegal abortion, and physician scarcity. Developing countries have the double disadvantage of 1) untrained personnel and patients themselves attempting to induce abortion with either instruments or chemicals that leave dead tissue remaining in the uterus to become infected and 2) the lack of trained health care workers to surgically remove tissue in cases in which prolonged bleeding in spontaneous abortion leads to sepsis or when sepsis or trauma occurs from unsafe abortion. By contrast, septic abortion is uncommon in the United States and other developed countries when both the surgical treatment of spontaneous abortion is readily available and illegal abortion is uncommon. For example, the estimated case-to-fatality ratio per 100,000 abortions in the United States is approximately 0.6 for spontaneous abortion8 and similar (from 0.78 to 0.57) for induced abortions performed between 1979 and 2008.15,16 After the legalization of abortion in the United States in 1973, the number of deaths from abortion in the United States dropped by 50% in the first 5 years and by another 83% in the
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following years.15 Between 2004 and 2008, only 6–12 women annually died in the United States after a legal induced abortion.15 The precise case-tofatality ratio of illegal abortion in the United States is even more difficult to know because the lack of a reliable denominator, but only 14 deaths were detected after illegal abortion in the 29 years between 1979 and 2008.15 Before 1973, septic abortions were an integral part of obstetric and gynecologic residency training and of practicing physician’s knowledge as to the need to immediately remove the infected placenta. For example, the number of hospital admissions for septic abortion was 105 women to Boston City Hospital in 1955–195617 and was 87 women to a Pittsburgh hospital in 1965–1967.18 However, most physicians who have been trained in the 40 years since Roe v. Wade never cared for a patient with a septic abortion or were provided detailed training on its treatment. The objective of this review is to update physicians on the identification and treatment of septic abortion. This review also is particularly relevant now as a result of the commitment of many obstetricians and gynecologists, both in training and out, to provide care in the developing world. It is important to realize that the death ratio after spontaneous abortion and induced abortion is virtually identical (0.7/100,000 abortions).19,20 Other data also point to similar findings of an estimated death ratio per 100,000 abortions in the United States of approximately 0.6 for spontaneous abortion8 and from 0.78 to 0.57 for induced abortions performed between 1979 and 2008.16 Infection accounts for the vast majority of death (59%) after spontaneous abortion.19 The most common cause of death after induced abortion also is infection (27%) followed by hemorrhage (24%).20 Thus, septic abortion can become serious after either spontaneous or induced abortion. The other key fact is that gestational age strongly influences the death rate after both spontaneous and induced abortion. As gestation advances, the placenta becomes increasingly large, which provides a greater volume of tissue to become infected. The death ratio per 100,000 spontaneous abortions is 0.3 before 13 weeks of gestation, 1.5 at 13–15 weeks of gestation, and 4.1 at 16–19 weeks of gestation.19 The death ratio per 100,000 induced abortions is 0.1–0.4 before 13 weeks of gestation, 1.7 at 13–15 weeks of gestation, 3.4 at 16–20 weeks of gestation, and 8.9 beyond 20 weeks of gestation.20 Thus, physicians need to be particularly aware of the potential for greater risk to the woman when infection develops at the more advanced gestational ages.
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PATHOPHYSIOLOGY Sepsis starts with the invasion of vaginal bacteria into the uterus usually preceded by uterine instrumentation or prolonged uterine bleeding. Once in the uterus, bacteria can gain access into the maternal intervillous space of the placenta to initiate a septic abortion.21 From the intervillous space, maternal bacteremia occurs in more than 60% of septic abortions.18 The finding that much of the infection is in the intervillous space also may explain why fetal heart tones can remain despite life-threatening maternal bacteremia. The presence of toxins produced by Clostridium species and group A streptococci and an overwhelming immune response to infection can lead to systemic disease and distant multiorgan failure. If the infected placental tissue remains for a prolonged time, bacteria can invade into the decidua of the endometrium and from there into the myometrium.21,22 This time can be as short as 6–12 hours when very virulent bacteria are present or significant trauma has occurred. Infections that involve the uterus are not readily treated by simple removal of the placenta. Such infections require high doses of antibiotics. Infection from toxin-producing bacteria such as Clostridium species or group A streptococcus are particularly serious and potentially lethal on uterine invasion. Tissue necrosis of not only the placenta, but the uterus can be produced by these toxins that can limit the effectiveness of antibiotic therapy. When serious infection occurs, the source of the toxinproducing site needs to be removed, which leads at least to curettage for removal of the placenta and to hysterectomy if the toxin production arises from a uterine source. Of course, septic abortion also causes death of the fetus. Fetal death is inevitable with septic abortion, so uterine curettage should be promptly performed without waiting for the absence of fetal heart activity.
MICROBES Most bacteria that cause septic abortion are those arising from vaginal flora.8,18,23,24 However, in part because of placental devitalization with unsafe or incomplete abortion, a high rate of infection with anaerobic bacteria is associated with septic abortion. Anaerobic bacteria were present in approximately 60% of women with positive blood cultures.18,23 Bacteremia is common because the infection often localizes in the maternal intervillous space. Bacteremia occurs in 38–61% of women with septic abortion.18,23 As expected, a high concordance occurs between blood and cervical isolates.18 However, anaerobic Peptostreptococcus, the most common blood isolate from cases of
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septic abortion, can be isolated in approximately 40% of all cases.18 A culture from the cervix or products of conception is necessary in septic abortion. The main aim of this culture is to identify the presence of toxin producers or antibiotic-resistant bacteria such as Staphylococcus aureus. The identification of toxin producers in these cultures is critical to alert caregivers that a potentially serious infection may exist and that prompt removal of infected tissue is needed with especially diligent follow-up. Most infection with septic abortion remains localized to the placenta. However, given enough time to replicate in dead tissue, some bacterial species can cause particularly serious sepsis and septic shock. The toxin-producing groups of bacteria, especially Clostridium species and group A streptococcus, but also some toxin-producing strains of Escherichia coli, deserve special mention. These strains have a propensity to proliferate within dead tissue of both the placenta and the uterus in septic abortion, where they can cause local tissue destruction. It is within this dead tissue that antibiotics are not able to penetrate because the bacteria have become isolated from the vasculature. S aureus is important because of its resistance to common antibiotic therapy. In these situations, antibiotics become ineffective treatment tools. Furthermore, these particular bacterial species also can produce very potent toxins that when released from the infected site have a propensity to cause endothelial vascular damage, leading to damage of distant organs function of the lung, kidney, heart, and coagulation systems. Clostridium perfringens is isolated from the vagina in approximately 1% and from the rectum in 10% of young women.25 However, C perfringens is isolated from up to 5% of all septic abortions18 and an especially high number of women who die.24 C perfringens appears more common in unsafe septic abortion where delay in the removal of dead tissue allows proliferation of these slow-growing bacteria in an anaerobic tissue environment.8 Group A streptococcus is an even rarer isolate in septic abortion, but it has the same toxin-producing propensity and pathology as C perfringens. Certain strains of E coli and of S aureus can also produce potent toxins. Recently, Clostridium sordellii was associated with death from sepsis after medical abortion.22 A review of original series of these infections with additional cases was recently updated.26 Fortunately, C sordellii infection is rare, but the infection is particularly lethal when present in any pelvic site.26 C sordellii are infrequently found in the vagina (less than 0.5%) and rectum (approximately 2%) of reproductive-aged women.25 Detailed autopsy examination of those women with
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Box 1. Clinical Steps to Identify and Treat Septic Abortion History documentation of Prior uterine instrumentation Length of vaginal bleeding Length of fever Other symptoms Confirm pregnancy Document gestational age Risk assessment for Products of conception remaining in the uterus Unsafe abortion IUD in situ Perform physical examination of Temperature, blood pressure, pulse, respirations Abdominal examination for degree of direct and rebound tenderness Pelvic speculum examination for cervical or vaginal trauma, foul-smelling or purulent cervical–vaginal discharge Bimanual examination for cervical and uterine tenderness and adnexal tenderness or mass Culture Aerobic and anaerobic cultures of the cervix (especially to identify virulent pathogens that produce toxins), products of conception (if present), or both Blood Blood examination Complete blood count Lactic acid level Coagulation studies Hemolysis determination Renal function studies Check of Rh(D)-negative blood type Imaging studies Ultrasonography for products of conception remaining in the uterus Radiograph or computed tomography scan of the pelvis and abdomen for free air in the abdomen and gas in the myometrium Intravenous medication: Fluid, antibiotics (Box 3) Vasopressors, if needed Uterine curettage Under anesthesia using a vacuum suction catheter Examine and culture products of conception Pathologic examination of products of conception to confirm pregnancy and identify degree of inflammation Monitor vital signs and treat ongoing sepsis Frequent blood pressure Pulse oximeter use for tachypnea Central venous pressure use for shock (Box 2) IUD, intrauterine device.
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a C sordellii septic abortion probably reflects the usual situation for all of these toxin producers; C sordellii antigen was found only in the necrotic endometrium and myometrium (the placenta has been previously removed) but antigen was not present in the lung, kidney, heart, or liver.22 Thus, it appears that these toxin producers can cause death from the release of potent toxins that cause distant vascular damage and organ failure without actual bacterial spread to these organs. In these situations, prompt hysterectomy to remove the site of toxin production becomes necessary to prevent death.27
CLINICAL RECOGNITION Most women with severe infection who die from septic abortion have no underlying medical comorbidity, in contrast to other causes of maternal death in the United States. Septic abortion typically occurs in the setting of intrauterine tissue damage such as retained products of conception after a spontaneous or induced abortion, an unsafe abortion involving instruments or chemicals, and a pregnancy with an intrauterine device in place. The differential diagnosis includes spontaneous abortion with endometritis and incomplete abortion with another cause of fever such as pyelonephritis, appendicitis, and the flu. In one series, virtually all women with a septic abortion had a fever. The exception was women with serious sepsis from C sordellii, who often were initially diagnosed with the flu.22 Clinical steps to identify and treat septic abortion are listed in Box 1; only a few of the steps are addressed in the text. The clinical presentation of septic abortion is varied, in part because the placental infection is localized within the uterus that acts to mask the severity of infection. Most women with septic abortion have a history of fever and uterine bleeding.17,18,23 Many women also will present with chills and abdominal pain. Inquiry about the date of any recent pregnancy and prior uterine procedure is critical. Serious infection is often present when symptoms are present for several days or when symptoms begin several days or weeks after an abortion has occurred.24 Very high temperatures indicate severe disease, although severe disease can be present with only a mild fever. Again, a word of caution, like in the cases of C sordellii, fever was not present.22,26 Prostration, marked tachycardia, marked tachypnea with or without respiratory difficulty, hypotension, and low urine output certainly indicate very severe sepsis. Usually, abdominal findings are limited to mild tenderness without rebound tenderness. Findings of general peritonitis indicate serious infection.15,17 On pelvic examination, one
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should examine for trauma to the cervix and pus or foul-smelling fluid from the cervix. The uterus is usually only mildly tender.17 Even in severe infection, the uterus can be deceivingly less tender than one might expect. Aerobic and anaerobic blood and cervical cultures should be obtained to alert caregivers to the presence of toxin producers. Isolation of common vaginal bacteria usually occurs in mild-to-moderate infection. However, the isolation of toxin producers (especially Clostridium species and group A streptococcus) puts the physician on alert that not only is a serious infection likely present, but that the infection is potentially lethal. Markedly elevated white blood cell counts higher than 20,000 also indicate severe infection, and a leukemoid reaction (white blood counts higher than 50,000) can be present in infection associated with toxin production. If severe infection is present, additional blood work includes lactic acid measurement, creatinine, and studies to diagnose disseminated intravascular coagulation and hemolysis. Anti-D immunoglobulin should be given to Rh(D)-negative women. Ultrasonograms should be used to determine the presence of products of conception. A detailed discussion exists in the use of ultrasonography to diagnose remaining products of conception.28 A completed abortion without remaining products of conception is likely when the endometrial stripe is less than 8 mm. Serial blood pressure, pulse oxygen measurement, and urine volume measurement are needed to monitor fluid resuscitation. It is worth noting that the typical central venous pressure is low in patients with severe infection from septic abortion.24 A low central venous pressure could be related to significant blood loss as well as to decreased systemic resistance from sepsis. Recent updates in the treatment of severe sepsis and septic shock are available as references in Box 2, but a detailed discussion is outside the scope of this report.
TREATMENT The complete treatment of septic abortion includes the initiation of intravenous fluid for maternal stabilization, culture collection, and antibiotic administra-
Box 2. Treatment of Severe Sepsis and Septic Shock 1. 2. 3. 4. 5.
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Severe sepsis and septic shock36 Acute respiratory distress syndrome37 Disseminated intravascular coagulation syndrome38 Acute renal failure and sepsis39 Treating severe sepsis and septic shock40
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tion followed by a prompt surgical evacuation of the infected products of conception4,8,9 (grade 1B evidence) independent of fetal heart activity, because septic abortion, especially in the second trimester, can occur with a live fetus. This report also reviews clinical findings that indicate the presence of infections with high mortality rates. Clinicians inexperienced in the identification and treatment of women with septic abortion may fail to realize the speed to which this infection can become serious, systemic, and even lethal. A major purpose of this document is to emphasize the necessity of prompt uterine curettage. A paradox is that both physicians who practiced in the United States before 1973 and those in developing countries recognize the necessity for prompt surgical evacuation. For all types of serious pelvic infection, U.S. physicians can be lulled into an absolute reliance on antibiotic therapy instead of considering surgical removal of infected tissue in life-threatening infections, because antibiotic treatment is usually successful. Prompt removal of infected products of conception is the key and most important treatment for septic abortion8,23 over which there is little dispute.9,24 Even death is related to incomplete products of conception removal.8 Because the bacteria reside in the maternal villous spaces and often not in the fetal villi,21 infection can occur predominantly on the maternal side of the placenta. This may explain both the early maternal febrile response and 60% rate of bacteremia, stimulating a robust maternal immune system response. Removal of infected tissue not only eliminates bacterial infection within the placenta, but it limits spread of bacteria into the uterus and into the systemic circulation. Antibiotic administration is recommended before the curettage to prevent septic shock that can also develop from overwhelming bacteremia during the curettage. Particularly severe infection is present when the following clinical findings exist: severe acute respiratory syndrome (SARS), disseminated intravascular coagulation, hemolysis, lactic acidosis, oliguria, and septic shock. In even otherwise healthy women, the mortality rates are very high when these conditions exist. Overall, postpartum maternal mortality is greater than 20% with septic shock and disseminated intravascular coagulation and 33–50% with SARS.29 Prompt resuscitation is necessary with fluid, blood pressure control with vasopressors, and, in some cases, blood transfusion. The medical treatment of severe sepsis with SARS, disseminated intravascular coagulation, and renal injury has been thoroughly reviewed for a reference in the publications listed in Box 2. However, in septic abortion, these clinical
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findings cannot be reversed without a complete removal of the infected placenta site by curettage. Mortality specific to septic abortion in a case series of women admitted to an intensive care unit in Argentina was 19% overall.24 Septic shock occurred in 32% of these patients and death occurred in 55% of women in septic shock as compared with 19% of all 63 patients.24 Death occurred in 26–31% of patients who developed SARS, disseminated intravascular coagulation, or the need for mechanical ventilation from severe sepsis.24 Prompt reversal of septic shock with resuscitation allows time to assess whether these other complications are beginning to occur and can be reversed with medical therapy alone.22,24 The need for and timing of hysterectomy in a case of severe sepsis that has not responded to the removal of products of conception and resuscitative efforts are more difficult to determine than the prompt need for curettage.30 Indications for hysterectomy include a worsening clinical response after curettage, the presence of widespread peritonitis, and a pelvic abscess. Clostridial myonecrosis (gas gangrene or myonecrosis from other gas producers), determined by air in the uterine wall or crepitation in the pelvis, free air in the abdomen from a uterine perforation, and clostridium or Group A streptococcus sepsis should prompt immediate laparotomy and hysterectomy if dead uterine tissue or trauma from a prior uterine instrumentation is detected. The development of continued septic shock, worsening of SARS or disseminated intravascular coagulation, or the need for mechanical ventilation indicates one or more individual organ failures that also should move one to consider hysterectomy. The death rate is already more than 50% in patients in septic shock from septic abortion, and, though the judgment to delay surgery may allow some patients added time to respond to medical treatment and avoid hysterectomy,31 such a delay also risks irreversible septic shock, widespread organ failure, and death.24,32 One should expect clinical improvements within 6 hours of curettage, fluid resuscitation, and antibiotic therapy.30 The clinical condition needs to be monitored on an hourly basis so one can proceed promptly with a laparotomy if the clinical situation worsens or does not improve over a short time. The concept of the patient being too sick for surgery needs to be abandoned in these cases, because surgery with hysterectomy can be lifesaving. Antibiotic selection needs to cover the large variety of possible anaerobic and aerobic bacteria23,24 (Box 3). Bacteria that produce most septic abortion are sensitive to antibiotics. However, anaerobic coverage is particularly necessary. As a reminder, Clos-
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Box 3. Antibiotic Treatment Choices for Septic Abortion 1. Gentamicin (5 mg/kg/d) and clindamycin (900 mg every 8 h) with or without ampicillin 2. Ampicillin (2 g every 4 h) and gentamicin with metronidazole (500 mg every 8 h) 3. Levofloxacin (500 mg daily) and metronidazole 4. Imipenem (500 mg every 6 h) 5. Piperacillin–tazobactam (4.5 g every 8 h) 6. Ticarcillin–clavulanate (3.1 g every 4 h)
tridium species and group A streptococcus infections remain very sensitive to penicillin. Still, most antibiotic regimens for serious pelvic infection include a combination of: gentamicin and clindamycin; ampicillin, gentamicin, and metronidazole; levofloxacin and metronidazole; or a single agent of imipenem; piperacillin–tazobactam; or ticarcillin–clavulanate. Intravenous antibiotics can be stopped 48 hours after clinical improvement in cases without an abscess.33 The final point again is that the antibiotic choice is secondary to the prompt removal of the infected dead placenta.9,21 Clindamycin deserves special mention in treating septic abortion. In vitro, clindamycin inhibits S aureus toxic shock toxin levels in concentrations well below the level needed to inhibit bacterial growth.34 Clindamycin also inhibits group A streptococcus and clostridium toxins in vitro35 and was more effective in treating deep group A streptococcus infection in children than cell wall-inhibiting agents.35 Thus, clindamycin should be considered for use in patients with infection suspected to be produced by toxins.
DISCUSSION Treatment of septic abortion starts with a prompt and accurate recognition of placental infection in a previable pregnancy, genital and blood cultures, fluid and antibiotic administration, and the prompt removal of infected products of conception. Physicians need to be aware of the development of signs of severe infection that requires careful hourly monitoring of clinical signs and consideration of hysterectomy if the signs of severe infection worsen or are not reversed in a short time. REFERENCES 1. Kassebaum N, Bertozzi-Villa A, Coggeshall M, Shackelford K, Steiner C, Heuton K, et al. Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the global burden of disease study 2013. Lancet 2014;384:980–1004. 2. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic
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analysis for the global burden of disease study 2010. Lancet 2012;380:2095–128. 3. World Health Organization. The prevention and management of unsafe abortion—report of a technical working group. Geneva (Switzerland): World Health Organization; 1992. 4. Berer M. Making abortion safe: a matter of good public health policy and practice reproductive health matters. Bull World Health Organ 2000;78:580–92. 5. Rasch V. Unsafe abortion and postabortion care—an overview. Acta Obstet Gynecol Scand 2011;90:692–700. 6. Singh S. Hospital admissions resulting from unsafe abortion: estimates from 13 developing countries. Lancet 2006;368: 1887–92. 7. Adler AJ, Filippi V, Thomas SL, Ronsmans C. Quantifying the global burden of morbidity due to unsafe abortion: magnitude in hospital-based studies and methodological issues. Int J Gynecol Obstet 2012;118(suppl 2):565–77. 8. Grimes DA, Cates W Jr, Selik RM. Fatal septic abortion in the United States, 1975–77. Obstet Gynecol 1981;57:739–44. 9. Stubblefield PG, Grimes DA. Septic abortion. N Engl J Med 1994;331:310–4. 10. Adetoro OO, Barbarinsa AB, Sotiloye OS. Socio-cultural factors in adolescent septic illicit abortion in Ilorin, Nigeria. Afr J Med Sci 1991;20:149–53. 11. Nwogu-Ikojo EE, Ezegwui HU. Abortion related mortality in a tertiary medical center in Enugu, Nigeria. J Obstet Gynaecol 2007;27:835–7. 12. Sule-Odu AO, Olatunji AO, Akindele RA. Complicated induced abortion in Sagamu, Nigeria. J Obstet Gynaecol 2002;22:58–61. 13. Guleria K, Bansal S, Agarwal N, Grover V. Women with septic abortion: who, how, why? A prospective from tertiary care hospital in India. Indian J Public Health 2006;50:95–6.
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33. Savaris RF, de Moraes GS, Cristovam RA, Braun RD. Are antibiotics necessary after 48 hours of improvement in infected/septic abortions? A randomized controlled trial followed by a cohort study. Am J Obstet Gynecol 2011;204:301.e1–5.
15. Pazol K, Creanga AA, Zane SB, Burley KD, Jamieson DJ; Centers for Disease Control and Prevention (CDC). Abortion surveillance United States, 2009. MMWR Surveill Summ 2012;61:1–44.
34. Schlievert PM, Kelly JA. Clindamycin-induced suppression of toxic shock syndrome-associated exotoxin production. J Infect Dis 1984;149:471.
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17. Tenney B, Little A, Wamsteker E. Septic abortion. N Engl J Med 1957;257:1022–5. 18. Rotheram EB Jr, Schick SF. Nonclostridial anaerobic bacteria in septic abortion. Am J Med 1969;46:80–9. 19. Saraiya M, Green C, Berg C, Hopkins F, Koonin L, Atrash H. Spontaneous abortion-related deaths among women in the United States—1981–1991. Obstet Gynecol 1999;94:172–6. 20. Bartlett L, Berg C, Shulman H, Zane S, Green C, Whitehead S, et al. Risk of factors for legal induced abortion-related mortality in the United States. Obstet Gynecol 2004;103:729–37. 21. Studdiford WE, Douglas GW. Placental bacteremia: a significant finding in septic abortion accompanied by vascular collapse. Am J Obstet Gynecol 1956;71:842–58.
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36. Angus D, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:840–51. 37. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000;342:1334–49. 38. Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999;341:586–92. 39. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004;351:159–69. 40. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165–228.
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