J Clin Gynecol Obstet

Journal of Clinical Gynecology and Obstetrics, ISSN 1927-1271 print, 1927-128X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Gynecol Obstet and Elmer Press Inc

Journal website http://www.jcgo.org

Review

Volume 5, Number 1, March 2016, pages 1-16

Severe Infections in Obstetrics and Gynecology: How Early Surgical Intervention Saves Lives

Figure 1. Algorithm for diagnosing and managing suspected toxic shock syndrome in obstetrics and gynecology.

**Table 1.** Microorganisms Commonly Associated With Serious Infections in Obstetrics and Gynecology
S. aureus: Staphylococcus aureus.
Gram-positive bacteria
Staphylococcus aureus (including methicillin-resistant S. aureus)
Streptococcus pyogenes (group A streptococcus)
Necrotizing soft tissue infections
Mixed aerobes and anaerobes
Staphylococcus aureus (including methicillin-resistant S. aureus)
Streptococcus pyogenes (group A streptococcus)
Clostridium perfringens
Clostridium sordellii
Clostridium septicum
Toxic shock syndrome
Staphylococcus aureus (including methicillin-resistant S. aureus)
Streptococcus pyogenes (group A streptococcus)
Clostridium perfringens
Clostridium sordellii
Clostridium septicum

Table 1. Microorganisms Commonly Associated With Serious Infections in Obstetrics and Gynecology

S. aureus: Staphylococcus aureus.

Gram-positive bacteria

Staphylococcus aureus (including methicillin-resistant S. aureus)

Streptococcus pyogenes (group A streptococcus)

Necrotizing soft tissue infections

Mixed aerobes and anaerobes

Staphylococcus aureus (including methicillin-resistant S. aureus)

Streptococcus pyogenes (group A streptococcus)

Clostridium perfringens

Clostridium sordellii

Clostridium septicum

Toxic shock syndrome

Staphylococcus aureus (including methicillin-resistant S. aureus)

Streptococcus pyogenes (group A streptococcus)

Clostridium perfringens

Clostridium sordellii

Clostridium septicum

**Table 2.** Summary of Obstetric and Gynecologic *C. sordelli* Cases Reported in the Literature
Age	Procedure	Time from procedure to onset of symptoms	Time from symptom onset to death	As reported in
32	Cervical cone	12 days	6 h	Ho et al [20]
40	Cervical laser	3 days	2 days	Ho et al [20]
16	Oral and vaginal mifepristone	5 days	18 h	Reis et al [24]
21	Childbirth and vaginal laceration	4 days		Aldape et al [11]
29	Cesarean section	2 days		Bitti et al [18]
24	Childbirth and episiotomy	4 days		Soper [22]
24	Childbirth and episiotomy	24 h	5 days	Sosolik et al [13]
40	Childbirth	4 days	4 days	Rorbye et al [19]
18	Oral mifepristone, vaginal misoprostol	4 days	7 - 8 days	Fischer et al [14]
21	Oral mifepristone vaginal misoprostol	5 days	< 24 h	Fischer et al [14]
22	Oral mifepristone, vaginal misoprostol	5 days	23 h	Fischer et al [14]
34	Oral mifepristone, vaginal misoprostol	4 days	12 h	Fischer et al [14]
26	Medical abortion	7 days	< 3 days	Sinave et al [12]
39	Spontaneous endometritis	Not applicable	18 h	Hogan et al [23]
	Hysterectomy			Harvey et al [25]
29	Oral mifepristone, vaginal misoprostol	4 days	2 days	Meites et al [17]
21	Oral mifepristone, vaginal misoprostol	6 days	6 days	Meites et al [17]
	Cesarean section	2 months	37 h	Cohen et al [16]
28	Vaginal mifepristone	11 h	2 days	Cohen et al [16]
24	Oral mifepristone, vaginal misoprostol	1 day	7 days	Cohen et al [16]
25	Spontaneous abortion		Survived	Cohen et al [16]
18	Oral mifepristone, vaginal misoprostol	5 days	3 days	Cohen et al [16]
23	Childbirth and episiotomy	56 hours	2 days	Golde [26]
27	Oral mifepristone, vaginal misoprostol	3 days	4 days	Wiebe et al [21]
28	Childbirth and episiotomy with retained vaginal sponge	5 days	< 24 h	McGregor et al [15]
23	Cesarean section and cervical myoma degeneration	6 days	Survived	McGregor et al [15]
23	Childbirth	2 days	3 days	McGregor et al [15]

Table 2. Summary of Obstetric and Gynecologic C. sordelli Cases Reported in the Literature

Age

Procedure

Time from procedure to onset of symptoms

Time from symptom onset to death

As reported in

Cervical cone

12 days

6 h

Ho et al [20]

Cervical laser

3 days

2 days

Ho et al [20]

Oral and vaginal mifepristone

5 days

18 h

Reis et al [24]

Childbirth and vaginal laceration

4 days

Aldape et al [11]

Cesarean section

2 days

Bitti et al [18]

Childbirth and episiotomy

4 days

Soper [22]

Childbirth and episiotomy

24 h

5 days

Sosolik et al [13]

Childbirth

4 days

Rorbye et al [19]

Oral mifepristone, vaginal misoprostol

4 days

7 - 8 days

Fischer et al [14]

Oral mifepristone vaginal misoprostol

5 days

< 24 h

Fischer et al [14]

Oral mifepristone, vaginal misoprostol

5 days

23 h

Fischer et al [14]

Oral mifepristone, vaginal misoprostol

4 days

12 h

Fischer et al [14]

Medical abortion

7 days

< 3 days

Sinave et al [12]

Spontaneous endometritis

Not applicable

18 h

Hogan et al [23]

Hysterectomy

Harvey et al [25]

Oral mifepristone, vaginal misoprostol

4 days

2 days

Meites et al [17]

Oral mifepristone, vaginal misoprostol

6 days

Meites et al [17]

Cesarean section

2 months

37 h

Cohen et al [16]

Vaginal mifepristone

11 h

2 days

Cohen et al [16]

Oral mifepristone, vaginal misoprostol

1 day

7 days

Cohen et al [16]

Spontaneous abortion

Survived

Cohen et al [16]

Oral mifepristone, vaginal misoprostol

5 days

3 days

Cohen et al [16]

Childbirth and episiotomy

56 hours

2 days

Golde [26]

Oral mifepristone, vaginal misoprostol

3 days

4 days

Wiebe et al [21]

Childbirth and episiotomy with retained vaginal sponge

5 days

< 24 h

McGregor et al [15]

Cesarean section and cervical myoma degeneration

6 days

Survived

McGregor et al [15]

Childbirth

2 days

3 days

McGregor et al [15]

**Table 3.** Pertinent Laboratory Findings Associated With Infections Resulting in Invasive *Streptococcus pyogenes* (Group A Streptococcus), Clostridial Species and *Staphylococcus aureus* in Obstetrics and Gynecology
mmol: millimole; dL: deciliter; mEq: milliequivalent; mg: milligram; mL: milliliter.
Complete blood count (CBC)
White blood cells (WBC) are generally > 25,000/mL or < 4,000/mL.
Marked bandemia (> 10%), independent of the total WBC
Hemolysis: hemoglobin level < 11 mg/dL
Massive hemoconcentration (hematocrit > 45%) secondary to fluid pouring into necrotic areas, resulting in third-spacing and edema and an intravascular depletion of fluid
Thrombocytopenia, as a result of disseminated intravascular coagulopathy
Complete metabolic profile (CMP)
Serum sodium of < 135 mEq/L
Creatinine level of > 1.6 mg/dL
Glucose level of >180 mg/dL
Anion gap metabolic acidosis
Bicarbonate < 15 mg/dL
Lactic acid > 2.2 mmol/L
Blood cultures
Infrequently positive, but if present would note:
Gram-positive cocci in chains indicate Streptococcus pyogenes
Gram-positive anaerobic rods indicate clostridial species
Gram-positive cocci in clusters indicate Staphylococcus aureus
Tissue diagnosis
Isolation of microbe or its associated virulence factors from infected tissue
Tissue should be sent to microbiology lab, or to a tertiary testing facility, such as the Center for Disease Control and Prevention (CDC), for molecular microbiologic analysis.

Table 3. Pertinent Laboratory Findings Associated With Infections Resulting in Invasive Streptococcus pyogenes (Group A Streptococcus), Clostridial Species and Staphylococcus aureus in Obstetrics and Gynecology

mmol: millimole; dL: deciliter; mEq: milliequivalent; mg: milligram; mL: milliliter.

Complete blood count (CBC)

White blood cells (WBC) are generally > 25,000/mL or < 4,000/mL.

Marked bandemia (> 10%), independent of the total WBC

Hemolysis: hemoglobin level < 11 mg/dL

Massive hemoconcentration (hematocrit > 45%) secondary to fluid pouring into necrotic areas, resulting in third-spacing and edema and an intravascular depletion of fluid

Thrombocytopenia, as a result of disseminated intravascular coagulopathy

Complete metabolic profile (CMP)

Serum sodium of < 135 mEq/L

Creatinine level of > 1.6 mg/dL

Glucose level of >180 mg/dL

Anion gap metabolic acidosis

Bicarbonate < 15 mg/dL

Lactic acid > 2.2 mmol/L

Blood cultures

Infrequently positive, but if present would note:

Gram-positive cocci in chains indicate Streptococcus pyogenes

Gram-positive anaerobic rods indicate clostridial species

Gram-positive cocci in clusters indicate Staphylococcus aureus

Tissue diagnosis

Isolation of microbe or its associated virulence factors from infected tissue

Tissue should be sent to microbiology lab, or to a tertiary testing facility, such as the Center for Disease Control and Prevention (CDC), for molecular microbiologic analysis.

**Table 4.** Antibiotic Treatment for Invasive Infections Caused by Invasive *Streptococcus pyogenes* (Group A Streptococcus), Clostridial Species and *Staphylococcus aureus* in Obstetrics and Gynecology
IV: intravenous; MRSA: methicillin-resistant Staphylococcus aureus.
Recommended first line regimen
Penicillin G 20 million units IV every 24 h
Or
Meropenem 1 - 2 g IV every 8 h
If MRSA - vancomycin 15 mg/kg IV every 12 h
Plus
Clindamycin 600 mg IV every 8 h
Alternative therapy (penicillin allergy - not anaphylaxis)
Cefazolin 1 - 2 g IV every 6 h
If MRSA - vancomycin 15 mg/kg IV every 12 h
Plus
Clindamycin 600 mg IV every 8 h
Alternative therapy (penicillin allergy - anaphylaxis)
Vancomycin 15 mg/kg IV every 12 h
Plus
Clindamycin 600 mg IV every 8 h

Table 4. Antibiotic Treatment for Invasive Infections Caused by Invasive Streptococcus pyogenes (Group A Streptococcus), Clostridial Species and Staphylococcus aureus in Obstetrics and Gynecology

IV: intravenous; MRSA: methicillin-resistant Staphylococcus aureus.

Recommended first line regimen

Penicillin G 20 million units IV every 24 h

Meropenem 1 - 2 g IV every 8 h

If MRSA - vancomycin 15 mg/kg IV every 12 h

Plus

Clindamycin 600 mg IV every 8 h

Alternative therapy (penicillin allergy - not anaphylaxis)

Cefazolin 1 - 2 g IV every 6 h

If MRSA - vancomycin 15 mg/kg IV every 12 h

Plus

Clindamycin 600 mg IV every 8 h

Alternative therapy (penicillin allergy - anaphylaxis)

Vancomycin 15 mg/kg IV every 12 h

Plus

Clindamycin 600 mg IV every 8 h

**Table 5.** Infectious Sequelae From Untreated *Streptococcus pyogenes* (Group A Streptococcus) in Obstetrics and Gynecology
GAS: group A streptococcus.
Sepsis
Presentation: sudden onset of high fever, generally > 102 °F, shaking chills, flushing and surprising minimal amount of abdominal or uterine tenderness.
Blood cultures are frequently positive.
Postpartum endometritis
Presentation: influenza-like symptoms, chills, myalgia, nausea, vomiting, and diarrhea.
Fever usually exceeds 102 °F.
Pelvic organ tenderness or other physical findings may be minimal and not indicative of the severity of infection.
Wound infections
Presentation: rapid onset of acute cellulitis (subcutaneous tissue inflammation with marked local pain, tenderness, swelling, and erythema).
Quickly progresses to involve both the upper and superficial lymph nodes.
Generally occurs within hours of an abdominal incision for a laparotomy, cesarean delivery or in the perineum after an episiotomy or vaginal laceration.
Necrotizing soft tissue infections
Presentation: marked skin edema, bullae formation, local skin necrosis, and thrombosis of surrounding perforating vessels, ischemia and devitalized tissue, which is noted when tissue fails to bleed when cut into.
Severe local pain out of proportion to the observed abnormality with progression of erythema and edema are hallmark features.
The death rate from necrotizing fasciitis of patients who do not undergo surgical debridement approaches 100%.
Toxic shock syndrome
Presentation: initiates as an endometritis, cellulitis, or vulvar infection caused by GAS, non-focal abdominal pain that is out of proportion to physical findings, associated with a fever, leukocytosis, bandemia, and metabolic acidosis.
Progresses to fulminant multi-organ failure, shock and ultimately death within 48 - 96 h, if left untreated.
Release of superantigens by GAS results in a massive inflammatory storm.

Table 5. Infectious Sequelae From Untreated Streptococcus pyogenes (Group A Streptococcus) in Obstetrics and Gynecology

GAS: group A streptococcus.

Sepsis

Presentation: sudden onset of high fever, generally > 102 °F, shaking chills, flushing and surprising minimal amount of abdominal or uterine tenderness.

Blood cultures are frequently positive.

Postpartum endometritis

Presentation: influenza-like symptoms, chills, myalgia, nausea, vomiting, and diarrhea.

Fever usually exceeds 102 °F.

Pelvic organ tenderness or other physical findings may be minimal and not indicative of the severity of infection.

Wound infections

Presentation: rapid onset of acute cellulitis (subcutaneous tissue inflammation with marked local pain, tenderness, swelling, and erythema).

Quickly progresses to involve both the upper and superficial lymph nodes.

Generally occurs within hours of an abdominal incision for a laparotomy, cesarean delivery or in the perineum after an episiotomy or vaginal laceration.

Necrotizing soft tissue infections

Presentation: marked skin edema, bullae formation, local skin necrosis, and thrombosis of surrounding perforating vessels, ischemia and devitalized tissue, which is noted when tissue fails to bleed when cut into.

Severe local pain out of proportion to the observed abnormality with progression of erythema and edema are hallmark features.

The death rate from necrotizing fasciitis of patients who do not undergo surgical debridement approaches 100%.

Toxic shock syndrome

Presentation: initiates as an endometritis, cellulitis, or vulvar infection caused by GAS, non-focal abdominal pain that is out of proportion to physical findings, associated with a fever, leukocytosis, bandemia, and metabolic acidosis.

Progresses to fulminant multi-organ failure, shock and ultimately death within 48 - 96 h, if left untreated.

Release of superantigens by GAS results in a massive inflammatory storm.

**Table 6.** Indications for Hysterectomy in Women With Invasive *Streptococcus pyogenes* (Group A Streptococcus), Clostridial Species and *Staphylococcus aureus* in Obstetrics and Gynecology
TSS: toxic shock syndrome; WBC: white blood cell; mmol/L: millimole per liter.
Major indications
Failure to respond to antimicrobial therapy alone in the first 24 h
Rapid deterioration in clinical status with medical therapy intervention
Evidence of necrotizing soft tissue infection
Evidence of intraabdominal or pelvic fluid collection concerning for abscess collection
Evidence of gas within the uterine myometrial tissue, concerning for necrotizing soft tissue infection with clostridial species
Source expected to be the uterus
Postpartum (cesarean or vaginal delivery)
Postabortal or septic abortion
Worsening laboratory signs of TSS and/or tissue necrosis, despite medical therapy
Refer to Table 3.
Systemic signs of sepsis
Septic shock
Adult respiratory distress syndrome
Disseminated intravascular coagulation
Hemolysis

Table 6. Indications for Hysterectomy in Women With Invasive Streptococcus pyogenes (Group A Streptococcus), Clostridial Species and Staphylococcus aureus in Obstetrics and Gynecology

TSS: toxic shock syndrome; WBC: white blood cell; mmol/L: millimole per liter.

Major indications

Failure to respond to antimicrobial therapy alone in the first 24 h

Rapid deterioration in clinical status with medical therapy intervention

Evidence of necrotizing soft tissue infection

Evidence of intraabdominal or pelvic fluid collection concerning for abscess collection

Evidence of gas within the uterine myometrial tissue, concerning for necrotizing soft tissue infection with clostridial species

Source expected to be the uterus

Postpartum (cesarean or vaginal delivery)

Postabortal or septic abortion

Worsening laboratory signs of TSS and/or tissue necrosis, despite medical therapy

Refer to Table 3.

Systemic signs of sepsis

Septic shock

Adult respiratory distress syndrome

Disseminated intravascular coagulation

Hemolysis