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Septic shock due to Klebsiella pneumoniae after medical abortion with misoprostol-only regimen

      Objective

      To report a case of a healthy woman who was admitted to the hospital with septic shock caused by a common uropathogen after self-administration of misoprostol for pregnancy termination.

      Design

      Case report.

      Setting

      Tertiary hospital.

      Patient(s)

      A 38-year-old woman, gravida 5, para 3, who developed septic shock after medical termination of pregnancy.

      Intervention(s)

      Suction curettage, antibiotic treatment, plasma and platelet transfusions.

      Main Outcome Measure(s)

      Klebsiella pneumoniae was isolated from blood samples.

      Result

      Ten days after her admission she was discharged home in good condition on oral antibiotics.

      Conclusion(s)

      Severe infections leading to septic shock from common pathogen bacteria can occur after medical termination of pregnancy, independently of the regimen used.

      Key Words

      First-trimester medical termination of pregnancy that doesn't require admission to the hospital or anesthesia is now the alternative to surgical termination. The incidence of uterine infection after medical termination of pregnancy is very low. However, severe and fatal infections have been reported in certain cases; most of them were associated with Clostridrium infections and development of toxic shock syndrome (
      • Fischer M.
      • Bhatnagar J.
      • Guarner J.
      • Reagan S.
      • Hacker J.K.
      • Van Meter S.H.
      • et al.
      Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion.
      ,
      • Cohen A.L.
      • Bhatnagar J.
      • Reagan S.
      • Zane S.B.
      • D'Angeli M.A.
      • Fischer M.
      • et al.
      Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion.
      ,
      • Sinave C.
      • Le Templier G.
      • Blouin D.
      • Leveille F.
      • Deland E.
      Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease.
      ). We report here a case of a young healthy woman who was admitted to the hospital because of septic shock caused by Klebsiella pneumoniae after self-administration of misoprostol at home for pregnancy termination.

      Case report

      A 38-year-old woman, gravida 5, para 3, with a medical history of nephrolithiasis, presented in our clinic requesting pregnancy termination. A vaginal ultrasound scan revealed an intrauterine pregnancy of ∼6 weeks' gestation. After counseling, medical termination of pregnancy with misoprostol-only regimen was decided. The woman left the hospital with instructions to take misoprostol 800 μg vaginally and 200 μg orally. A follow-up appointment 3 days later was suggested for an ultrasound examination. She was also encouraged to call the clinic for any problem or concern. The patient did not attend the regular appointment and she never called.
      Ten days later, this patient was admitted to the hospital with high fever (40°C), pain in the lower abdomen, and malodorous blood-stained vaginal discharge. She reported that 3 days earlier she was suffering “kidney pain” and fever (38°C). Several times in the past she had the same problem because of her nephrolithiasis, and the symptoms regressed the same day with oral administration of paracetamol and amoxicillin.
      On clinical examination, she appeared to be lethargic but conscious, with a pulse rate of 110/min, tachypnea with respiratory rate of 24/min, and low blood pressure (70/40 mm Hg). Vaginal examination revealed a large, soft, and tender uterus and malodorous vaginal discharge. Transvaginal sonography showed the presence of endometrial remnants in the uterine cavity. Laboratory examination results were as follows: white blood cell count 40 × 106/L with 87% neutrophils; platelets at 56,000/cm2 with d-dimers more than 2,000; concentration of creatinine and urea 2.7 mg/dL and 84 mg/dL, respectively; and C-reactive protein equal to 331 mg/L. A urine analysis showed a high number of red blood cells. Septic shock syndrome was diagnosed. Owing to her medical history of nephrolithiasis, a urinary culture was taken at the time of admission. The urinary culture was negative.
      The patient was intubated, transfered immediately to the intensive care unit, and treated with high doses of imipenem and metronidazole, as well as with intravenously administered fluid, vasopressors, and transfusions of plasma and platelets. Owing to the severity of her condition, suction curettage, under sonographic guidance, was performed for the removal of the endometrial remnants 4 hours after admission. Bacterial cultures of the samples obtained from the uterus and blood cultures yielded Klebsiella pneumoniae. The antibiotic scheme was modified with the addition of ciprofloxacine and aminoglycoside. The fever subsided after 5 days. Ten days after her admission she was discharged on oral antibiotics.

      Discussion

      Severe infection and development of toxic shock syndrome has been rarely reported after medical termination of pregnancy; most of these cases resulted in the woman's demise (Table 1) (
      • Fischer M.
      • Bhatnagar J.
      • Guarner J.
      • Reagan S.
      • Hacker J.K.
      • Van Meter S.H.
      • et al.
      Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion.
      ,
      • Cohen A.L.
      • Bhatnagar J.
      • Reagan S.
      • Zane S.B.
      • D'Angeli M.A.
      • Fischer M.
      • et al.
      Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion.
      ,
      • Sinave C.
      • Le Templier G.
      • Blouin D.
      • Leveille F.
      • Deland E.
      Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease.
      ,
      • Daif J.L.
      • Levie M.
      • Chudnoff S.
      • Kaiser B.
      • Shahabi S.
      Group A Streptococcus causing necrotizing fasciitis and toxic shock syndrome after medical termination of pregnancy.
      ). Four women in the U.S.A. and one in Canada died of sepsis after medical termination of pregnancy with a mifepristone-misoprostol regimen (
      • Fischer M.
      • Bhatnagar J.
      • Guarner J.
      • Reagan S.
      • Hacker J.K.
      • Van Meter S.H.
      • et al.
      Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion.
      ). All of them presented with absence of fever and rash but with refractory hypotension, marked edema of infected tissues, hemoconcentration, effusions in multiple serous cavities, and marked leukocytosis. All of the cases were positive for Clostridium sordellii infection. Moreover, Cohen et al. (
      • Cohen A.L.
      • Bhatnagar J.
      • Reagan S.
      • Zane S.B.
      • D'Angeli M.A.
      • Fischer M.
      • et al.
      Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion.
      ) reported that another three women had developed toxic shock syndrome associated with Clostridium species infection after medical abortion. Two of them had fatal infections due to C. perfrigens and one due to C. sordellii. All three patients had a rapidly progressive illness with necrotizing endomyometritis.
      Table 1Reports of septic shock syndrome and severe infections after medical termination of pregnancy.
      AuthorYearRegimenGestational ageComplicationOutcome
      Sinave et al.
      • Sinave C.
      • Le Templier G.
      • Blouin D.
      • Leveille F.
      • Deland E.
      Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease.
      2002Mifepristone-misoprostol10 wkToxic shock syndrome (Clostridium sordellii)Deceased
      Hausknecht2003MisoprostolNMAdult respiratory distress syndrome (negative cultures)Recovery
      FDA2005Mifepristone-misoprostolFirst trimester4 cases of toxic shock syndrome (Clostridium sordellii)Deceased
      Cohen et al.
      • Cohen A.L.
      • Bhatnagar J.
      • Reagan S.
      • Zane S.B.
      • D'Angeli M.A.
      • Fischer M.
      • et al.
      Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion.
      2007Laminaria-misoprostol mifepristone-misoprostol mifepristone–oral misoprostolSecond trimester; 8 wk; 6 wk3 cases of toxic shock syndrome (Clostridium perfrigens; Clostridium sordellii)Deceased
      Daif et al.
      • Daif J.L.
      • Levie M.
      • Chudnoff S.
      • Kaiser B.
      • Shahabi S.
      Group A Streptococcus causing necrotizing fasciitis and toxic shock syndrome after medical termination of pregnancy.
      2009Mifepristone-misoprostolNMNecrotizing fasciitis, myonecrosis, and toxic shock syndrome (group A Streptococcus)Recovery
      Note: FDA = U.S. Food and Drug Administration; NM = not mentioned.
      Clostridium species colonize the vagina in 4%–18% of healthy women and are commonly associated with postpartum endometritis and septic abortion (
      • Miech R.P.
      Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii.
      ). Abortions may predispose a small number of women to acquire Clostridium species in the vaginal tract, and dilatation of the cervix may allow the ascending spread of microorganisms into the endometrium, where they proliferate (
      • Fischer M.
      • Bhatnagar J.
      • Guarner J.
      • Reagan S.
      • Hacker J.K.
      • Van Meter S.H.
      • et al.
      Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion.
      ). Elaboration of potent large Clostridial cytotoxins may lead to the activation of cytokine cascade, resulting in the clinical manifestations of toxic shock syndromes.
      It was postulated that mifepristone action may favor the development of infection that leads to septic shock (
      • Miech R.P.
      Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii.
      ). Mifepristone administration blocks both progesterone and glucocorticoid receptors, interfering with the protective function of the innate immune system (
      • Miech R.P.
      Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii.
      ). However, additional data are needed to evaluate further the possible association between medical abortion and Clostridium infections. In contrast, no causal relationship between septic shock syndrome and the use of misoprostol has been established.
      In the present case, the optimal dose of misoprostol for first-trimester termination of pregnancy was administered. The patient did not attend the scheduled appointment after the drug administration and the early symptoms of pyrexia were erroneously considered to be due to a kidney infection. Septic shock syndrome was developed 10 days after misoprostol administration, and this is the first reported case of septic shock syndrome following pregnancy termination with a misoprostol-only regimen.
      Klebsiella pneumoniae was detected in bacterial cultures of blood samples and of samples obtained from the uterus. Klebsiella is the cause for bacteremia in ∼6% of the total bacteremia episodes, whereas septic shock develops in 22% of these patients (
      • Garcia de la Torre M.
      • Romero-Vivas J.
      • Martinez-Beltran J.
      • Guerrero A.
      • Meseguer M.
      • Bouza E.
      Klebsiella bacteremia: an analysis of 100 episodes.
      ). The overall mortality in such cases was reported to be as high as 32% (
      • Yinnon A.M.
      • Butnaru A.
      • Raveh D.
      • Jerassy Z.
      • Rudensky B.
      Klebsiella bacteraemia: community versus nosocomial infection.
      ). Although this pathogen is a common uropathogen bacterium, dilatation of the cervix and the loss of the cervical mucus plug during the abortion permit the passage of vaginal pathogens through the cervix, resulting in the infection of the endometrium. Increased local vascular permeability due to endometrial infection and/or infected endometrial remnants allow the passage of the pathogen into the systemic circulation and consequently to the generation of septic shock syndrome.
      The present case shows that even common pathogens can cause septic shock syndrome after medical abortions. Recently, Daif et al. (
      • Daif J.L.
      • Levie M.
      • Chudnoff S.
      • Kaiser B.
      • Shahabi S.
      Group A Streptococcus causing necrotizing fasciitis and toxic shock syndrome after medical termination of pregnancy.
      ) reported the development of toxic shock syndrome after medical termination of pregnancy due to group A Streptococcus infection. Goneim and Krylov (
      • Goneim A.T.
      • Krylov L.A.
      Klebsiella aerogenes as the causative agent of postabortion sepsis complicated by acute renal insufficiency.
      ) have also described the development of post-abortion septic shock syndrome due to a gram-negative pathogen, Klebsiella aerogenes. Curettage for removal of endometrial remnants and parenteral antimicrobial therapy are reasonable therapeutic options resulting in a rapid decrease of the bacterial load.
      We report here, for the first time, the development of septic shock syndrome due to Klebsiella pneumoniae after self-administration of misoprostol-only regimen, showing that independently of the regimen used, severe infections can occur after medical termination of pregnancy, even from common pathogen bacteria. Clinicians must be aware of this rare but potentially fatal adverse event and counsel the patients appropriately.

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