Maternal sepsis is a life-threatening condition with organ dysfunction resulting from infection during pregnancy, childbirth, post-abortion, or in the postpartum period.1 The World Health Organization estimated that the global prevalence of maternal sepsis is 4.4% among live births, with an incidence of 9–49 per 100 000 deliveries in high-income countries depending on the definition used and population studied.1 The incidence of pregnancy-associated severe sepsis in the USA has increased by 236% over the past decade, rising from 11 hospitalizations per 100 000 annual total estimated pregnancies in 2001–2002 to 26 in 2009–2010.2 Prospective studies in the UK have suggested that labor and the puerperium may have a 2- to 3-fold increased risk of sepsis compared to the antenatal period.3 Several studies from developed countries have shown that the rate of maternal sepsis has been increasing in the last decade, with high mortality rates.2–6
Maternal sepsis is the main cause of maternal death and a major contributor to severe maternal morbidity worldwide,5,7–24 accounting for 11% of maternal deaths worldwide and is the third most common direct cause of maternal death.20 Maternal sepsis is currently the third or fourth leading cause of maternal mortality in the USA, accounting for 13% of all maternal deaths with a cause-specific maternal mortality ratio of 2.2 deaths per 100 000 live births5,6 In low- and middle-income countries, rates of fatality after puerperal infection can be as high as 50%.1 Under new sepsis definitions,25 some representative reports gave ranges on the mortality of sepsis in the general population of 25%–30%. The mortality range for septic shock was 40%–70%.26
Failure to recognize sepsis early is a significant cause of preventable morbidity, resulting in delayed treatment and escalated care, which are critical if lives are to be saved.27 There are only a few evidence-based and pregnancy-specific guidelines for healthcare providers regarding how to best treat, prevent and recognize the early warning signs of peripartum sepsis.20,21 In this review, we aim to discuss the new definitions regarding sepsis and recommended diagnosis and management strategies of sepsis adapted to pregnant and postpartum women.
The pathophysiology core issue is a multifaceted host response to an infecting pathogen that may be significantly amplified by endogenous factors. The “sepsis 1” and “sepsis 2” focused solely on inflammatory excess. Sepsis is now recognized to involve early activation of both pro- and anti-inflammatory responses, along with major modifications in nonimmunologic pathways such as cardiovascular, neuronal, autonomic, hormonal, bioenergetic, metabolic, and coagulation, all of which have prognostic significance. Patients with sepsis can have clinical presentations in various systems, including respiratory, cardiovascular, hepatic and gastrointestinal, renal, hematological, endocrinological, and central nervous systems.25 Maternal sepsis may cause intra-amniotic infection, which results in (1) premature rupture of membranes or preterm labor or birth; (2) cerebral white matter damage or cerebral palsy or neurodevelopmental delay; (3) stillbirth; (4) early- or late-onset sepsis; (5) perinatal death.28–31Figure 1 shows the pathophysiology and manifestation of sepsis. Figure 2 shows the microscopic findings in the placenta of one 26 weeks pregnant woman with septic shock and stillbirth caused by Listeria monocytogenes infection.
Causes, risk factors, and microorganisms
Causes and risk factors
Changes in maternal immune responses occur during pregnancy to protect the unborn fetus from rejection. These changes may predispose pregnant patients to the development of infections. Sepsis may be due to obstetric or non-obstetric causes.32 The obstetric causes include uterine infection, such as chorioamnionitis and endomyometritis, septic abortion, and wound infection. Sepsis may follow invasive procedures such as amniocentesis, chorionic villus sampling, cervical cerclage, or percutaneous umbilical blood sampling. In a French study, the most common source of bacteremia was chorioamnionitis (47%).33 The non-obstetric causes of sepsis include pyelonephritis and pneumonia.32
Maternal sepsis may also be from obstetrical critical illness, such as obstetric severe hemorrhage,34 obstetric (amniotic fluid/pulmonary) embolism, acute fatty liver of pregnancy (AFLP),35 and congestive heart failure, cardiopulmonary arrest, major trauma, and 2019 coronavirus disease infection.36–38 In an Indonesian study, 12 of 18 patients with AFLP died due to maternal sepsis, and AFLP was the common direct cause of maternal death.39–41
Risk factors correlated with the development of sepsis during pregnancy are as follows. Obstetric-related risk factors: group A streptococcal infection in close contacts/family members; a history of group B streptococcal infection; the induction of labor; invasive procedures such as amniocentesis and cervical cerclage, prolonged rupture of membranes; instrumented or cesarean delivery; a lack of prenatal care; mastitis; preeclampsia; postpartum hemorrhage; retained products of conception; the use of antibiotics within 2 weeks of birth, including prophylaxis for cesarean sections; and wound hematoma. Patient-related risk factors: anemia; chronic hypertension; diabetes mellitus; decreased function of the spleen; group A streptococcal infection in patients with close contact with individuals with a history of pelvic infection; immunosuppression; obesity; poverty; and poor nutrition.42–48
The most commonly reported pathogens in maternal sepsis include Escherichia coli, Streptococcus, Staphylococcus, and other gram-negative bacteria.49–51Streptococcus type A, although currently infrequent, may cause maternal sepsis following abortion or labor and cause shock, with a mortality of 30%–60%.52–55 Group A streptococcal infections are invasive, and toxin production allows the organism to spread across tissue planes and cause necrosis while evading containment and abscess formation by the maternal immune system.53–57 Maternal sepsis caused by Candida has been reported. Maternal Candida sepsis could cause chorioamnionitis, stillborn birth, abortion, preterm birth, and congenital Candida infection in newborns.58–61 The reported rare microorganisms in maternal sepsis include Clostridium innocuum, Clostridium novyi, Plasmodium vivax, and Chlamydia psittacosis.28,62–64Figure 3 shows the organisms isolated from maternal blood cultures in sepsis during pregnancy and the puerperium.3,33,49,51,65–72
Screening and diagnosis
To recognize maternal sepsis early, many early warning scores have been developed. Bauer et al. studied screening tools for sepsis in pregnant women.51 The sensitivity and specificity of sepsis screening tools with the highest to lowest sensitivity were systemic inflammatory response syndrome, maternal early warning, and quick sequential organ failure assessment (qSOFA) criteria, and the highest to lowest specificity were qSOFA, maternal early warning, and systemic inflammatory response syndrome. Foeller and Gibbs proposed an obstetrically modified qSOFA.46 Currently, there are no ideal screening tools for sepsis in pregnancy. Table 1 shows the common screening tools for sepsis in pregnancy.25,46,73–76 The diagnosis of sepsis is based on a sequential organ failure assessment (SOFA) score of ≥2 with a suspicion of infection. In individuals with no baseline disease, the initial SOFA score should be zero. The higher SOFA score, the probability of mortality is more increased. The present definition of sepsis emphasizes signs of organ dysfunction rather than signs of infection. The main diagnosis procedures include blood cultures and cultures from any suspected source of infection, additional laboratory tests, and imaging to confirm the suspected anatomic site of infection.25,32Table 2 shows the SOFA score criteria.77
The differential diagnoses include hypovolemic or hemorrhagic shock, pulmonary embolism, myocardial infarction, acute pancreatitis, diabetic ketoacidosis, primary adrenal insufficiency, and transfusion reaction.45
The management includes initial respiratory and haemodynamic stabilization, the initiation of empiric antimicrobial treatment with broad-spectrum agent therapy within the first hour of diagnosis, source control within the first 12 hours if possible, and the prevention of complications and sequelae.
The elements of the 2018 bundle, intended to be initiated within the first hour, include blood cultures before antibiotics, lactate measurement, the administration of broad-spectrum antibiotics, the administration of a 30 mL/kg crystalloid fluid bolus in cases of hypotension or high serum lactate levels of at least 4 mmol/L, and the administration of vasopressors to maintain a mean arterial pressure of at least 65 mm Hg.78–80Figure 4 shows the main management of sepsis during pregnancy and the puerperium.32
The early and appropriate use of antibiotics is crucial in the management of maternal sepsis.81 Mortality is increased by 7.6% with each hour delay in appropriate antibiotic administration in the general population.82 The spectrum might need to be broad, covering both gram-positive and gram-negative pathogens. Antibiotic coverage for maternal sepsis should be aimed at covering the most common bacteria: E. coli, Staphylococcus, Streptococcus, and other gram-negative bacteria. Viral and fungal cover should be considered, if suspected. Combination therapy is preferred over monotherapy.
Most often, a broad-spectrum carbapenem (eg, meropenem, imipenem/cilastatin, or doripenem) or extended-range penicillin/β-lactamase inhibitor combination (eg, piperacillin/tazobactam or ticarcillin/clavulanate) is used. Several third- or higher-generation cephalosporins can also be used, especially as part of a multidrug regimen.79 The surviving sepsis campaign strongly recommends antibiotic stewardship in the de-escalation of antibiotics tailored to specific microorganisms to prevent drug resistance. Optimal antibiotic duration remains contentious, and few prospective randomized controlled trials have been performed. The surviving sepsis campaign guidelines suggest 7–10 days.79 Procalcitonin levels can be used as a biomarker for the initiation, de-escalation, and discontinuation of antimicrobial therapy.79,83–85 Schuetz et al. found that the inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality.86 When suspected, invasive group A streptococcal infections should be treated emergently with aggressive fluid resuscitation, antibiotic administration (penicillin and clindamycin), and source control that may be extensive and may involve hysterectomy. Table 3 proposes broad-spectrum empiric antibiotic coverages in sepsis during pregnancy and the puerperium.32,44,75,79,87–92
Once a source of sepsis is identified, source control is a priority and may involve abscess drainage or the delivery of the fetus if the uterus is found to be the source of the infection. There is a direct increase in mortality with each 6-hour delay in achieving source control.32,75,79 If surgical intervention for source control, including cesarean section, is required, the decision about regional or general anesthesia should be made on a case-by-case basis. When sepsis is diagnosed in the antepartum period, one prospective case-control study of a national database in the UK from 2011 to 2012 found the median gestational age to be 35 weeks (interquartile range 27–40 weeks) and the median diagnosis-to-delivery interval was 0 day (interquartile range 0–36 days).49 Hysterectomy were performed on 5.4% of severe sepsis cases.93
Extracorporeal membrane oxygenation (ECMO)
As a treatment for respiratory failure in patients in the intensive care unit, ECMO has been used increasingly during pregnancy and the puerperium.94–96 Based on published reports, overall maternal and fetal survival rate on ECMO were 80% and 70%, respectively.97 ECMO may be a choice for the treatment of refractory sepsis.
It is imperative to stabilize the mother first, and the fetal status will also improve. The decision of whether to deliver the fetus or to continue the pregnancy is influenced by a number of factors, including the patient's condition, the gestational age of the foetus, the fetal condition, the presence of chorioamnionitis and the stage of labor. In the setting of antenatal sepsis, there should be frequent assessment of fetal status after viability. Efforts should be aimed at treating maternal sepsis and prolonging pregnancies that are far from term if the source of infection is outside the uterus. If the source of sepsis is from the uterus, delivery of the fetus is required. If delivery is imminent, then betamethasone should be administered if gestational age is less than 34 weeks. A previable fetus (<23 to 24 weeks, depending on institutional practice) may not need fetal monitoring.32
Gaps and future directions
Seacrist et al.98 studied quality improvement opportunities identified through a review of cases of maternal death from sepsis and found several key deficiencies in the care of women who died from sepsis. Quality improvement opportunities were identified in the readiness, recognition, response, and reporting domains of the 4R framework. The single most common theme in their findings was women's lack of recognition of the signs and symptoms of sepsis or of the risk for sepsis during the initial birth hospitalization or postpartum period. Health-care facilities and providers need to reduce barriers for women who seek care, recognize early symptoms, and respond with appropriate treatment. Many cases of maternal sepsis give rise to litigation. The reasons for the litigations include failure to recognize sepsis; failure to instigate appropriate investigation; delayed treatment; incomplete treatment; failure to consider urgent delivery; failure to isolate the source of infection; failure to involve senior clinicians at an early stage; failure to utilize a multidisciplinary team, including anesthetists, intensivists, microbiologists, and infectious disease specialists, at an early stage; delay in recognizing failed treatment and instigating additional or alternative antimicrobials; and failure to transfer to the critical care setting.
It is important from both a clinical and research viewpoint to remain up to date and understand the change in terminology of sepsis. Further research into risk factors for maternal sepsis is required to reduce the incidence and to facilitate early identification and treatments. Interventions such as ECMO have gained increasing support and require more studies to assess their role in the management of maternal sepsis.
Conclusions and recommendations
Sepsis remains a major cause for the admission of pregnant women to the intensive care unit and is a leading cause of maternal morbidity and mortality. The causes of maternal sepsis include obstetric and non-obstetric causes. Maternal sepsis may also be from obstetrical critical illness. The most commonly reported pathogens in maternal sepsis include E. coli, Streptococcus, Staphylococcus, and other gram-negative bacteria. The management of sepsis during pregnancy should follow the same basic principles as that in the nonpregnant population, including early recognition, fluid therapy, timely broad-spectrum antibiotics, and source control.
Figure 1 was drawn by Shengmenart.
This research was supported by the Shenzhen Science and Technology Innovation Commission (JCYJ20180228162311024).
Conflicts of Interest
1. Bonet M, Nogueira Pileggi V, Rijken MJ, et al. Towards a consensus definition of maternal sepsis: results of a systematic review and expert consultation. Reprod Health
2017; 14 (1):67doi:10.1186/s12978-017-0321-6.
2. Oud L, Watkins P. Evolving trends in the epidemiology, resource utilization, and outcomes of pregnancy-associated severe sepsis: a population-based cohort study. J Clin Med Res
2015; 7 (6):400–416. doi:10.14740/jocmr2118w.
3. Knowles SJ, O'Sullivan NP, Meenan AM, et al. Maternal sepsis incidence, etiology and outcome for mother and fetus: a prospective study. BJOG
2015; 122 (5):663–671. doi:10.1111/1471-0528.12892.
4. Al-Ostad G, Kezouh A, Spence AR, et al. Incidence and risk factors of sepsis mortality in labor, delivery and after birth: population-based study in the USA. J Obstet Gynaecol Res
2015; 41 (8):1201–1206. doi:10.1111/jog.12710.
5. Creanga AA. Maternal mortality in the United States: a review of contemporary data and their limitations. Clin Obstet Gynecol
2018; 61 (2):296–306. doi:10.1097/GRF.0000000000000362.
6. Albright CM, Mehta ND, Rouse DJ, et al. Sepsis in pregnancy: identification and management. J Perinat Neonatal Nurs
2016; 30 (2):95–105. doi:10.1097/JPN.0000000000000159.
7. Bailey PE, Andualem W, Brun M, et al. Institutional maternal and perinatal deaths: a review of 40 low -and- middle income countries. BMC Pregnancy Childbirth
2017; 17 (1):295doi:10.1186/s12884-017-1479-1.
8. Bauer ME, Lorenz RP, Bauer ST, et al. Maternal deaths due to sepsis in the state of Michigan, 1999-2006. Obstet Gynecol
2015; 126 (4):747–752. doi:10.1097/AOG.0000000000001028.
9. Bwana VM, Rumisha SF, Mremi IR, et al. Patterns and causes of hospital maternal mortality in Tanzania: a 10-year retrospective analysis. PLoS One
2019; 14 (4):e0214807doi:10.1371/journal.pone.0214807.
10. Engin-Üstün Y, Sanisoğlu S, Keskin HL, et al. Changing trends in the Turkish maternal deaths, with a focus on direct and indirect causes. Eur J Obstet Gynecol Reprod Biol
2019; 234:21–25. doi:10.1016/j.ejogrb.2018.12.031.
11. Geller SE, Koch AR, Garland CE, et al. A global view of severe maternal morbidity: moving beyond maternal mortality. Reprod Health
2018; 15: (Suppl 1): 98doi:10.1186/s12978-018-0527-2.
12. Gon G, Leite A, Calvert C, et al. The frequency of maternal morbidity: a systematic review of systematic reviews. Int J Gynaecol Obstet
2018; 141: (Suppl 1): 20–38. doi:10.1002/ijgo.12468.
13. Hensley MK, Bauer ME, Admon LK, et al. Incidence of maternal sepsis and sepsis-related maternal deaths in the United States. JAMA
2019; 322 (9):890–892. doi:10.1001/jama.2019.9818.
14. Kendle AM, Salemi JL, Tanner JP, et al. Delivery-associated sepsis: trends in prevalence and mortality. Am J Obstet Gynecol
2019; 220 (4):391.e1–391.e16. doi:10.1016/j.ajog.2019.02.002.
15. Liu Yq, Tan G, Shang C, et al. The ICU is becoming a main battlefield for severe maternal rescue in China: an 8-year single-center clinical experience. Crit Care Med
2017; 45 (11):e1106–e1110. doi:10.1097/CCM.0000000000002597.
16. Mittal P, Kapoor G, Kumari N, et al. Review of maternal mortality at a tertiary care hospital: what have we achieved? J Obstet Gynaecol India
2019; 69 (2):149–154. doi:10.1007/s13224-018-1129-1.
17. Mu Y, Wang X, Li X, et al. The national maternal near miss surveillance in China: a facility-based surveillance system covered 30 provinces. Medicine (Baltimore)
2019; 98 (44):e17679doi:10.1097/MD.0000000000017679.
18. Ngonzi J, Tornes YF, Mukasa PK, et al. Puerperal sepsis, the leading cause of maternal deaths at a tertiary university teaching hospital in Uganda. BMC Pregnancy Childbirth
2016; 16 (1):207doi:10.1186/s12884-016-0986-9.
19. Souza JP, Gulmezoglu AM, Vogel J, et al. Moving beyond essential interventions for reduction of maternal mortality (the WHO Multicountry Survey on Maternal and Newborn Health): a cross-sectional study. Lancet
2013; 381 (9879):1747–1755. doi:10.1016/S0140-6736(13)60686-8.
20. Say L, Chou D, Gemmill A, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Heal
2014; 2 (6):e323–e333. doi:10.1016/S2214-109X(14)70227-X.
22. Global Maternal and Neonatal Sepsis Initiative Working Group. The Global Maternal and Neonatal Sepsis Initiative: a call for collaboration and action by 2030. Lancet Glob Health
2017; 5 (4):e390–e391. doi:10.1016/S2214-109X(17)30020-7.
23. Vousden N, Lawley E, Nathan HL, et al. Effect of a novel vital sign device on maternal mortality and morbidity in low-resource settings: a pragmatic, stepped-wedge, cluster-randomised controlled trial. Lancet Glob Health
2019; 7 (3):e347–e356. doi:10.1016/S2214-109X(18)30526-6.
24. Zhao Z, Han S, Yao G, et al. Pregnancy-related ICU admissions from 2008 to 2016 in China: a first multicenter report. Crit Care Med
2018; 46 (10):e1002–e1009. doi:10.1097/CCM.0000000000003355.
25. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA
2016; 315 (8):801–810. doi:10.1001/jama.2016.0287.
26. Gauer RL. Early recognition and management of sepsis in adults: the first six hours. Am Fam Physician
2013; 88 (1):44–53.
27. Lawton B, MacDonald EJ, Brown SA, et al. Preventability of severe acute maternal morbidity. Am J Obstet Gynecol
2014; 210 (6):557.e1–557.e6. doi:10.1016/j.ajog.2013.12.032.
28. Liu P, Fan S, Liu X, et al. Puerperal sepsis caused by Clostridium innocuum
in a patient with placenta accreta and literature review. Maternal Fetal Med
2020; 2 (3):181–188.
29. Kim CJ, Romero R, Chaemsaithong P, et al. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol
2015; 213: (4 Suppl): S29–S52. doi:10.1016/j.ajog.2015.08.040.
30. Tann CJ, Nakakeeto M, Willey BA, et al. Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study. Arch Dis Child Fetal Neonatal Ed
2018; 103 (3):F250–F256. doi:10.1136/archdischild-2017-312744.
31. Helmo FR, Alves EAR, Moreira RAA, et al. Intrauterine infection, immune system and premature birth. J Matern Fetal Neonatal Med
2018; 31 (9):1227–1233. doi:10.1080/14767058.2017.1311318.
32. Plante LA, Pacheco LD, et al. Society for maternal-fetal medicine (SMFM). SMFM consult series #47: sepsis during pregnancy and the puerperium. Am J Obstet Gynecol
2019; 220 (4):B2–B10. doi:10.1016/j.ajog.2019.01.216.
33. Surgers L, Valin N, Carbonne B, et al. Evolving microbiological epidemiology and high fetal mortality in 135 cases of bacteremia during pregnancy and postpartum. Eur J Clin Microbiol Infect Dis
2013; 32 (1):107–113. doi:10.1007/s10096-012-1724-5.
34. Touhami O, Marzouk SB, Kehila M, et al. Efficacy and safety of pelvic packing after emergency peripartum hysterectomy (EPH) in postpartum hemorrhage (PPH) setting. Eur J Obstet Gynecol Reprod Biol
2016; 202:32–35. doi:10.1016/j.ejogrb.2016.04.013.
35. Nelson DB, Yost NP, Cunningham FG. Acute fatty liver of pregnancy: clinical outcomes and expected duration of recovery. Am J Obstet Gynecol
2013; 209 (5):456.e1–456.e7. doi:10.1016/j.ajog.2013.07.006.
36. Wu Z, Huang P, Gong Y, et al. Treating acute fatty liver of pregnancy with artificial liver support therapy: systematic review. Medicine (Baltimore)
2018; 97 (38):e12473doi:10.1097/MD.0000000000012473.
37. Huls CK, Detlefs C. Trauma in pregnancy. Semin Perinatol
2018; 42 (1):13–20. doi:10.1053/j.semperi.2017.11.004.
38. Rasmussen SA, Smulian JC, Lednicky JA, et al. Coronavirus disease 2019 (COVID-19) and pregnancy: what obstetricians need to know. Am J Obstet Gynecol
2020; 222 (5):415–426. doi:10.1016/j.ajog.2020.02.017.
39. Ilham Aldika Akbar M, Mayang Sari I, Aditiawarman, et al. Clinical characteristics of acute fatty liver of pregnancy in a tertiary Indonesian hospital. J Matern Fetal Neonatal Med
2017; 32 (5):826–832. doi:10.1080/14767058.2017.1393067.
40. Pereira SP, O’Donohue J, Wendon J, et al. Maternal and perinatal outcome in severe pregnancy-related liver disease. Hepatology
1997; 26 (5):1258–1262. doi:10.1002/hep.510260525.
41. Vincent LJ, Frise CJ. Management of the critically-ill obstetric patient. Obstet Gynaecol Reprod Med
2018; 28 (8):243–252. doi:10.1016/j.ogrm.2018.07.005.
42. Ali A, Lamont RF. Recent advances in the diagnosis and management of sepsis in pregnancy. F1000Res
2019; 8 (F1000 Faculty Rev):1546doi:10.12688/f1000research.18736.1.
43. Mohamed-Ahmed O, Hinshaw K, Knight M. Operative vaginal delivery and post-partum infection. Best Pract Res Clin Obstet Gynaecol
2019; 56:93–106. doi:10.1016/j.bpobgyn.2018.09.005.
44. Padilla C, Palanisamy A. Managing maternal sepsis: early warning criteria to ECMO. Clin Obstet Gynecol
2017; 60 (2):418–424. doi:10.1097/GRF.0000000000000269.
45. Burlinson CEG, Sirounis D, Walley KR, et al. Sepsis in pregnancy and the puerperium. Int J Obstet Anesth
2018; 36:96–107. doi:10.1016/j.ijoa.2018.04.010.
46. Foeller ME, Gibbs RS. Maternal sepsis: new concepts, new practices. Curr Opin Obstet Gynecol
2019; 31 (2):90–96. doi:10.1097/GCO.0000000000000523.
47. Knight M, Chiocchia V, Partlett C, et al. Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial. Lancet
2019; 393 (10189):2395–2403. doi:10.1016/S0140-6736(19)30773-1.
48. Cornelissen L, Woodd S, Shakur-Still H, et al. Secondary analysis of the WOMAN trial to explore the risk of sepsis after invasive treatments for postpartum hemorrhage. Int J Gynaecol Obstet
2019; 146 (2):231–237. doi:10.1002/ijgo.12860.
49. Acosta CD, Kurinczuk JJ, Lucas DN, et al. Severe maternal sepsis in the UK 2012: a national case-control study. PLoS Med
2014; 11 (7):e1001672doi:10.1371/journal.pmed.1001672.
50. Bauer ME, Bateman BT, Bauer ST, et al. Maternal sepsis mortality and morbidity during hospitalizationfor delivery: temporal trends and independent associations for severe sepsis. Anesth Analg
2013; 117 (4):944–950. doi:10.1213/ANE.0b013e3182a009c3.
51. Bauer ME, Housey M, Bauer ST, et al. Risk factors, etiologies, and screening tools for sepsis in pregnant women: a multicenter case-control study. Anesth Analg
2019; 129 (6):1613–1620. doi:10.1213/ANE.0000000000003709.
52. Anderson BL. Puerperal group A streptococcal infection: beyond Semmelweis. Obstet Gynecol
2014; 123 (4):874–882. doi:10.1097/AOG.0000000000000175.
53. Tanaka H, Katsuragi S, Hasegawa J, et al. The most common causative bacteria in maternal sepsis-related deaths in Japan were group A Streptococcus: a nationwide survey. J Infect Chemother
2019; 25 (1):41–44. doi:10.1016/j.jiac.2018.10.004.
54. Rottenstreich A, Benenson S, Levin G, et al. Risk factors, clinical course and outcomes of pregnancy-related group A streptococcal infections: retrospective 13-year cohort study. Clin Microbiol Infect
2019; 25 (2):251.e1–251.e4. doi:10.1016/j.cmi.2018.10.002.
55. Belokrinitskaya T, Filippov O, Chugai O. Recurrent group A streptococcal severe sepsis in the postpartum period. Int J Gynaecol Obstet
2019; 144 (2):235–236. doi:10.1002/ijgo.12725.
56. Leonard A, Wright A, Saavedra-Campos M, et al. Severe group A streptococcal infections in mothers and their newborns in London and the South East 2016: assessment of risk and audit of public health management. BJOG
2019; 126 (1):44–53. doi:10.1111/1471-0528.15415.
57. Gustafson LW, Blaakær J, Helmig RB. Group A streptococci infection. A systematic clinical review exemplified by cases from an obstetric department. Eur J Obstet Gynecol Reprod Biol
2017; 215:33–40. doi:10.1016/j.ejogrb.2017.05.020.
58. Pineda C, Kaushik A, Kest H, et al. Maternal sepsis, chorioamnionitis, and congenital Candida kefyr infection in premature twins. Pediatr Infect Dis J
2012; 31 (3):320–322. doi:10.1097/INF.0b013e31823eee1a.
59. Jackel D, Lai K. Candida glabrata sepsis associated with chorioamnionitis in an in vitro fertilization pregnancy: case report and review. Clin Infect Dis
2013; 56 (4):555–558. doi:10.1093/Acid/cis936.
60. Tan SQ, Ng OT, Khong CC. Candida glabrata sepsis associated with chorioamnionitis in an IVF twin pregnancy: should we deliver? J Obstet Gynaecol Res
2015; 41 (6):962–966. doi:10.1111/jog.12656.
61. Potasman I, Leibovitz Z, Sharf M. Candida sepsis in pregnancy and the postpartum period. Rev Infect Dis
1991; 13 (1):146–149. doi:10.1093/clinids/13.1.146.
62. Black B, Bignal JK, Gupta M. It is all in the smear: an unusual cause of puerperal sepsis. Infect Dis Clin Pract
2014; 22 (3):177–179. doi:10.1097/ipc.0b013e31828f4d99.
63. Herrera C, Meehan R, Podduturi V, et al. Maternal death due to Clostridium novyi
in an injection drug user. Obstet Gynecol
2016; 128 (4):876–879. doi:10.1097/AOG.0000000000001561.
64. Gherman RB, Leventis LL, Miller RC. Chlamydial psittacosis
during pregnancy: a case report. Obstet Gynecol
1995; 86 (4 Pt 2):648–650. doi:10.1016/0029-7844(94)00378-q.
65. Ahmed MI, Alsammani MA, Babiker RA. Puerperal sepsis in a rural hospital in Sudan. Mater Sociomed
2013; 25 (1):19–22. doi:10.5455/msm.2013.25.19-22.
66. Admas A, Gelaw B, Belay T, et al. Proportion of bacterial isolates, their antimicrobial susceptibility profile and factors associated with puerperal sepsis among post-partum/aborted women at a referral Hospital in Bahir Dar, Northwest Ethiopia. Antimicrob Resist Infect Control
67. Abir G, Akdagli S, Butwick A, et al. Clinical and microbiological features of maternal sepsis: a retrospective study. Int J Obstet Anesth
2016; 29:26–33. doi:10.1016/j.ijoa.2016.09.003.
68. Duan R, Xu X, Wang X, et al. Perinatal outcome in women with bacterial sepsis: a cross-sectional study from West China. Medicine (Baltimore)
2019; 98 (44):e17751doi:10.1097/MD.0000000000017751.
69. Lucas DN, Robinson PN, Nel MR. Sepsis in obstetrics and the role of the anaesthetist. Int J Obstet Anesth
2012; 21 (1):56–67. doi:10.1016/j.ijoa.2011.11.001.
70. Mabie WC, Barton JR, Sibai B. Septic shock in pregnancy. Obstet Gynecol
1997; 90 (4 Pt 1):553–561. doi:10.1016/s0029-7844(97)00352-9.
71. Kiponza R, Balandya B, Majigo MV, et al. Laboratory confirmed puerperal sepsis in a national referral hospital in Tanzania: etiological agents and their susceptibility to commonly prescribed antibiotics. BMC Infect Dis
2019; 19 (1):690doi:10.1186/s12879-019-4324-5.
72. Wilkie GL, Prabhu M, Ona S, et al. Microbiology and antibiotic resistance in peripartum bacteremia. Obstet Gynecol
2019; 133 (2):269–275. doi:10.1097/AOG.0000000000003055.
73. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine Chest
1992; 101 (6):1644–1655. doi:10.1378/chest.101.6.1644.
74. Mhyre JM, DʼOria R, Hameed AB, et al. The maternal early warning criteria: a proposal from the national partnership for maternal safety. Obstet Gynecol
2014; 124 (4):782–786. doi:10.1097/AOG.0000000000000480.
75. Bowyer L, Robinson HL, Barrett H, et al. SOMANZ guidelines for the investigation and management sepsis in pregnancy. Aust N Z J Obstet Gynaecol
2017; 57 (5):540–551. doi:10.1111/ajo.12646.
76. Albright CM, Has P, Rouse DJ, et al. Internal validation of the sepsis in obstetrics score to identify risk of morbidity from sepsis in pregnancy. Obstet Gynecol
2017; 130 (4):747–755. doi:10.1097/AOG.0000000000002260.
77. Vincent JL, Moreno R, Takala J, et al. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med
1996; 22 (7):707–710. doi:10.1007/bf01709751.
78. Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Intensive Care Med
2018; 44 (6):925–928. doi:10.1007/s00134-018-5085-0.
79. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock. Intensive Care Med
2017; 43 (3):304–377. doi:10.1007/s00134-017-4683-6.
80. Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med
2008; 36 (1):296–327. doi:10.1097/01.CCM.0000298158.12101.41.
81. ACOG Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin, no. 211: critical care in pregnancy. Obstet Gynecol 2019;133(5):e303–e319. doi:10.1097/AOG.000000000 0003241.
82. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med
2006; 34 (6):1589–1596. doi:10.1097/01.CCM.0000217961.75225.E9.
83. Sager R, Kutz A, Mueller B, et al. Procalcitonin-guided diagnosis and antibiotic stewardship revisited. BMC Med
2017; 15 (1):15doi:10.1186/s12916-017-0795-7.
84. Bartoletti M, Antonelli M, Bruno Blasi FA, et al. Procalcitonin-guided antibiotic therapy: an expert consensus. Clin Chem Lab Med
2018; 56 (8):1223–1229. doi:10.1515/cclm-2018-0259.
85. Iankova I, Thompson-Leduc P, Kirson NY, et al. Efficacy and safety of procalcitonin guidance in patients with suspected or confirmed sepsis: a systematic review and meta-analysis. Crit Care Med
2018; 46 (5):691–698. doi:10.1097/CCM.0000000000002928.
86. Schuetz P, Birkhahn R, Sherwin R, et al. Serial procalcitonin predicts mortality in severe sepsis patients: results from the multicenter procalcitonin monitoring sepsis (MOSES) study. Crit Care Med
2017; 45 (5):781–789. doi:10.1097/CCM.0000000000002321.
87. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious disease society of America and the American thoracic society. Clin Infect Dis
2016; 63 (5):e61–e111. doi:10.1093/cid/ciw353.
88. Bridwell RE, Carius BM, Long B, et al. Sepsis in pregnancy: recognition and resuscitation. West J Emerg Med
2019; 20 (5):822–832. doi:10.5811/westjem.2019.6.43369.
89. Higgins RD, Saade G, Polin RA, et al. Evaluation and management of women and newborns with a maternal diagnosis of chorioamnionitis: summary of a workshop. Obstet Gynecol
2016; 127 (3):426–436. doi:10.1097/AOG.0000000000001246.
90. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis
2014; 59 (2):147–159. doi:10.1093/cid/ciu296.
91. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the surgical infection society and the infectious diseases society of America. Clin Infect Dis
2010; 50 (2):133–164. doi:10.1086/649554.
92. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis
2011; 52 (5):e103–e120. doi:10.1093/cid/ciq257.
93. Acosta CD, Harrison DA, Rowan K, et al. Maternal morbidity and mortality from severe sepsis: a national cohort study. BMJ Open
2016; 6 (8):e012323doi:10.1136/bmjopen-2016-012323.
94. Patel S, Loveridge R, Willars C, et al. Extracorporeal membrane oxygenation as salvage therapy in the peripartum period: a case series. ASAIO J
2020; 66 (7):1–5. doi:10.1097/MAT.0000000000001120.
95. Biderman P, Carmi U, Setton E, et al. Maternal salvage with extracorporeal life support: lessons learned in a single center. Anesth Analg
2017; 125 (4):1275–1280. doi:10.1213/ANE.0000000000002262.
96. Sangli SS, Noronha SF, Mourad B, et al. A systematic review of preexisting sepsis and extracorporeal membrane oxygenation. ASAIO J
2020; 66 (1):1–7. doi:10.1097/MAT.0000000000000934.
97. Sharma NS, Wille KM, Bellot SC, et al. Modern use of extracorporeal life support in pregnancy and postpartum. ASAIO J
2015; 61 (1):110–114. doi:10.1097/MAT.0000000000000154.
98. Seacrist MJ, Morton CH, VanOtterloo LR, et al. Quality improvement opportunities identified through case review of pregnancy-related deaths from sepsis. J Obstet Gynecol Neonatal Nurs
2019; 48 (3):311–320. doi:10.1016/j.jogn.2019.02.007.