The obstetrician/gynecologist commonly faces the challenge of diagnosing clinical infection and initiating antimicrobial treatment. Most of the obstetric and gynecologic infections we treat are potentially life threatening. A particularly virulent pathogen producing toxins or other potentially harmful enzymes in a susceptible host can initiate a cascade of immunologic events that can result in a systemic inflammatory response and subsequent multiple organ dysfunction. Although such infections are uncommon, management of infected patients requires recognition of the diagnoses associated with this adverse but appropriate host response. Prompt medical therapy with appropriate antibiotics and judicious surgical intervention in most circumstances can lead to the successful treatment of these life-threatening infections.

This chapter does not address the routine postpartum or postoperative infections that respond promptly to antimicrobial treatment. Instead, the chapter focuses on the two most common reasons why antimicrobial regimens fail in the treatment of routine postpartum and postoperative infections: pelvic abscess formation and septic pelvic thrombophlebitis. It also covers the diagnosis and treatment of several toxic shock syndromes, necrotizing fasciitis, and finally septic shock.

An abscess is a circumscribed collection of pus formed by liquefaction necrosis within tissue. Fibrous tissue is deposited around these pus collections if they are not drained. This tends to isolate the purulent collection further, serving to localize microbial enzymes or toxins injurious to the host, thus making it more difficult for antimicrobial agents to penetrate the capsule and sterilize the contents. In addition, local exhaustion of complement and enzymatic degradation of immunoglobulins occur, favoring the persistence of the bacterial infection.¹

An abscess can result from a number of obstetric or gynecologic infections (Table 1).² The clinical diagnosis is generally based on the findings of fever and a palpable adnexal or pelvic mass. This mass may be distinctly palpable and fluctuant or less distinct and characterized by a “fullness” noted during bimanual pelvic examination. Diagnosis of a pelvic abscess commonly occurs after failure of an initial antibiotic treatment for an obstetric or gynecologic soft-tissue infection. In other cases, particularly pelvic inflammatory disease, a pelvic abscess is diagnosed at the initial evaluation. A concurrent leukocytosis and elevated erythrocyte sedimentation rate or C-reactive protein are commonly noted laboratory abnormalities.

TABLE 1. Pelvic Abscess

Magnetic resonance imaging is recommended to clarify or supplement ultrasound findings. If the origin of the pelvic mass is unclear, the fluid content is in question, or the extent of the disease is not determined by ultrasound, magnetic resonance imaging is useful. Radioisotope scanning with gallium-67 citrate or indium-III-labeled leukocytes can be used to locate abscesses. Scanning is not hampered by surgical dressing, distended bowel, surgical clips, open wounds, or ventilators. Isotope scanning is most useful in patients with no localizing signs because the whole body is imaged. If a focal area of increased tracer activity is found, ultrasound or computed tomographic scanning can be used to clarify the nature of the area of activity.³

The microbiology of pelvic abscesses is predominately anaerobic. The intra-abdominal abscess rat model of Weinstein and colleagues⁴ is an excellent description of the phases of pathogenesis of mixed aerobic-anaerobic infections of the abdomen and pelvis:

  Phase I: Initial stage of peritonitis, sepsis, and an associated high mortality rate of nearly 40% appeared to be due to facultative gram-negative bacteria, particularly Escherichia coli.
  Phase II: Abscesses developed in the surviving rats during the secondary phase of infection due to anaerobic bacteria, particularly Bacteroides fragilis.

A similar biphasic disease process occurs in many clinical entities that are encountered in obstetrics and gynecology. Pelvic inflammatory disease, pelvic cellulitis, and endomyometritis are analogous to the initial phase of peritonitis in this model,⁴ but if untreated or inadequately treated, these infections will progress to an abscess phase characterized by pelvic abscess formation.²

The traditional approach to the treatment of mixed anaerobic-aerobic soft-tissue pelvic infections sheds additional light on the pathophysiology of abscess formation and on the importance of using antimicrobials with activity against penicillin-resistant anaerobes as part of initial therapy (Fig. 1).⁵ Initial treatment with penicillin and gentamicin or with ampicillin alone has a relatively high failure rate. Most initially resistant infections respond to the addition of an antibiotic with extended anaerobic activity (e.g., clindamycin, metronidazole). Patients who do not improve with broad-spectrum antimicrobial therapy should be evaluated for the presence of an abscess, septic pelvic thrombophlebitis, or drug fever.

Broad-spectrum antibiotics are given as the initial treatment for patients with a diagnosis of pelvic abscess. The gold standard of antimicrobial regimens for the treatment of pelvic abscess is combination therapy with either clindamycin or metronidazole in conjunction with an aminoglycoside, third-generation cephalosporin, or aztreonam. Other agents with therapeutic utility include single-agent treatment with an extended-spectrum cephalosporin (e.g., cefoxitin, cefotetan, cefotaxime, ceftizoxime), an extended-spectrum penicillin (e.g., mezlocillin, piperacillin), carbapenems (imipenem), and β-lactamase inhibitors plus a β-lactam (e.g., ampicillin/sulbactam, ticarcillin/clavulanate, piperacillin/tazobactam; see ahead to Table 3).

When antimicrobial treatment is started, a decision on the need for surgical intervention is required. Pelvic abscesses will occasionally respond to antimicrobial treatment alone. This is particularly true in patients with pelvic inflammatory disease that is complicated by a tubo-ovarian abscess. Treatment with broad-spectrum antimicrobials results in a satisfactory response to therapy without the need for surgery in 75% of cases.⁶ Patients with pelvic abscesses that complicate postoperative infections, such as postcesarean endomyometritis or posthysterectomy cuff cellulitis, usually require surgical intervention. Most abscesses complicating posthysterectomy infections are cuff abscesses and can be easily drained by dilating the vaginal cuff. Patients with postoperative adnexal abscesses (tubo-ovarian abscesses) are less likely to respond to antibiotic treatment alone, but trial use of antibiotic therapy is warranted before surgical drainage. Because of the high rate of persistence of infection after vaginal drainage,⁷ an adnexal abscess that fails to respond to antibiotics should be treated by abdominal exploration.

Surgical options for the drainage of pelvic abscesses have increased in the past several years. Most surgeons prefer laparotomy and drainage, with or without extirpation of the infected tissues, as the treatment of choice. An endoscopic approach has been used increasingly to drain or excise infected tissue. A percutaneous computed tomography-directed drain can be placed in some cases. The choice of options is based on the skills and facilities available at each hospital.

A ruptured pelvic abscess remains a surgical emergency. Such patients generally present with persistent fever, increasing leukocytosis, and a rigid abdomen. Immediate surgery after the initiation of antimicrobial therapy and fluid resuscitation is necessary. Standard treatment consists of drainage of the pelvic abscess and copious irrigation of the abdominal cavity.

Septic pelvic thrombophlebitis (SPT) is a rare but potentially serious complication of postpartum infections. The incidence of this disease ranges from 0.04% to 0.18% of obstetric procedures. This rate increases from 1% to 2% after postcesarean operative site infections. The disease occurs even less frequently after gynecologic surgical infections.

The pathophysiology of SPT is outlined by Virchow's triad:

  Venous stasis
  Injury to the vascular epithelium
  A hypercoagulable state

These factors explain why SPT is almost always a puerperal event that is most commonly diagnosed after postcesarean endomyometritis. Pregnancy predisposes the patient to a hypercoagulable state. Infection is believed to be the cause of injury to the vascular epithelium. After delivery, pelvic veins collapse and stasis occurs. These veins tend to be the smaller uterine pelvic veins. Occasionally, however, the ovarian veins—especially the right ovarian vein—are involved. The diagnosis of SPT usually is made after a patient's failure to respond to antimicrobial treatment for postpartum endomyometritis. The patient appears well and usually has a normal physical examination. The differential diagnosis includes drug fever.⁸

The diagnosis of SPT is distinctly different from the diagnosis of the patient presenting with an acute ovarian vein thrombosis (OVT). Patients with OVT are acutely ill and in pain. They present with localizing tenderness and a midquadrant mass. A computed tomographic scan confirms the presence of a clotted ovarian vein, a finding not usually seen in patients with SPT (Table 2).

TABLE 2. Pelvic Vein Thrombophlebitis⁸

The treatment of SPT includes the use of broad-spectrum antibiotic therapy. The use of an antibiotic that covers Bacteroides species (e.g., clindamycin, metronidazole) is important because these microorganisms have been shown to produce a heparinase and may lead to persistent or progressive disease. The patient should be therapeutically anticoagulated, although response occurs in patients treated with heparin despite a normal coagulation profile. Treatment should be continued for 7 days. No long-term or outpatient therapy is needed. The cause of the thrombosis is related to the infection and pregnancy (both are nonrecurring risk factors). Anticoagulated patients with pulmonary embolism should be considered candidates for inferior vena cava ligation or for placement of a Greenfield filter. Hysterectomy is not indicated in these patients.

Necrotizing fasciitis is a serious infection of the superficial fascia and is associated with extensive necrosis of the superficial fascia and subcutaneous fat. The most common sites affected in the obstetric and gynecologic patient are the vulva and the anterior abdominal wall. This process starts with a simple infection of the subcutaneous tissue often associated with an abrasion or furuncle or a surgical wound. The inflammatory process then extends along superficial fascial planes (Fig. 2).⁹ Thrombosis of small vessels occurs, devitalizing the subcutaneous tissue and resulting in the destruction of superficial nerves. The anatomic realities of this disease explain its spread. The superficial fascia of the vulva (Camper's fascia) is contiguous with the same fascia on the anterior abdominal wall and inner thighs. In addition, this fascia comprises most of the labia majora. The deeper fascia of the vulva (Colles' fascia) is contiguous with Scarpa's fascia of the anterior abdominal wall. These planes allow the infectious process to spread from the vulva to the anterior abdominal wall and into the inner thighs.

Patients with this disorder invariably have an underlying disease that impairs host immunity. Diabetes mellitus is the most common predisposing disease, but women with atherosclerosis or those who are on steroid therapy are also at risk. Rarely, necrotizing fasciitis develops in postpartum patients who have had episiotomies. Necrotizing fasciitis in the retropsoas and subgluteal spaces complicating pudendal anesthesia also has been reported.

The bacterial pathogenesis of necrotizing fasciitis is polymicrobial. Aerobic and anaerobic bacteria, especially streptococci, E. coli, Clostridum sp., and Bacteroides sp., found in the genital tract can manufacture proteases that break down collagen and elastin and allow the infection to spread along tissue planes. In addition, Streptococcus pyogenes (group A streptococcus), alone or in combination with Staphylococcus aureus, is an important pathogen associated with this disease.

Symptoms associated with necrotizing fasciitis include the presence of a superficial skin lesion, swelling of the affected area, and local pain followed by numbness. Patients appear acutely ill, and fever is common. Physical examination reveals skin changes that progress from an erythema to a blue-grey discoloration. Bullous changes in the skin may be present in advanced disease. During palpation of the affected area, crepitance may suggest the presence of subcutaneous gas. The hallmark of the diagnosis of vulvar necrotizing fasciitis is the presence of woody induration extending into the inner thighs.

Laboratory studies usually confirm an anemia and associated leukocytosis. Patients may be hypocalcemic from the saponification of calcium in the subcutaneous tissue. X-ray examination may suggest the presence of subcutaneous gas.

The mainstay of therapy for patients with necrotizing fasciitis is surgical debridement. After patients have been started on broad-spectrum antimicrobial therapy (Table 3) and resuscitated with fluids, immediate surgery is in order. The first order of business is to remove all necrotic tissue with its overlying skin. Infected tissue should be resected to bleeding edges. The deep fascia should be inspected. Do not tunnel beneath the skin to remove necrotic tissue. This approach makes continued care on the ward impossible. Leave an incision that can be unpacked and inspected on the ward. Pack the wound open with povidone-iodine-impregnated gauze. Consider observing the patient in a critical care setting if her condition warrants it. A planned second exploration of the wound in 24 hours may be considered to ensure that the infectious process has ceased to spread.

Antibiotics should be continued until wound induration and the systemic signs of sepsis have disappeared. The wound should appear beefy red with granulation tissue. Continued wet-to-dry dressing changes allow many wounds to heal by secondary intention. In some cases, secondary closure or skin grafting is necessary. Consultation with a plastic surgeon may be appropriate to obtain the best cosmetic result in patients with extensive vulvar or abdominal incisions, or both.

TABLE 3. Antibiotic Regimens Useful in the Treatment of Serious Obstetric and Gynecologic Infections

  Combination Therapy
  Regimen A

  Clindamycin (900 mg q 8 h) or metronidazole (500 mg q 6 h)

  Plus

  Plus

  Extended-spectrum penicillin with β-lactamase inhibitor
  Ticarcillin with clavulanate (3 g/200 mg q 6 h)
  Ampicillin/sulbactam (2 g/1 g q 6 h)
  Piperacillin with tazobactam (3 g/375 mg q 6 h)

  Plus

  Imipenem/cilastatin (500 mg q 6 h)

Now, more than 20 years after the highly publicized epidemic of staphylococcal toxic shock syndrome, less than 300 cases are reported annually to the Centers for Disease Control. Recently, however, two additional microorganisms, S. pyogenes (group A streptococcus) and Clostridium sordellii, have been associated with toxic shock syndromes in obstetric and gynecologic patients. These rare but usually fatal infections challenge clinicians both diagnostically and therapeutically (Table 4).

TABLE 4. Clinical Manifestations of Toxic Shock Syndromes

The toxic shock syndrome (TSS) associated with S. aureus is commonly recognized by fever (greater than 102°F), a diffuse or palmar erythroderma progressing to subsequent peripheral desquamation, and mucous membrane hyperemia. Vomiting and diarrhea are common, and multiple organ system dysfunction with rapid progression to hypotension and shock can be seen in severe cases. Staphylococcal TSS classically occurs in young women ages 16 to 30 years, with a peak onset of symptoms on day 4 of menses. The disease is less common in sexually active women. It has been associated with tampon use, especially those with synthetic fibers such as carboxymethylcellulose and polyacrylate rayon that allow increased absorption of menstrual fluid.¹⁰

The pathogenesis of staphylococcal TSS involves the colonization of the vagina with S. aureus and the elaboration of an exotoxin, toxic shock syndrome toxin 1 (TSST-1), unique to S. aureus. The production of toxin appears to be amplified by vaginal tampons rich in synthetic fibers. More than 75% of young adult women have a demonstrable antibody for this toxin, and more than 95% are TSST-1 antibody-positive by the fourth decade of life. This antibody is protective and explains the low incidence of the syndrome. It also explains why the disease is more likely to occur in younger women who are less likely to have the protective antibody.

Cases of nonmenstrually related staphylococcal TSS have been associated with surgical wound infections, postpartum infections, and local infections, such as mastitis, vaginitis, and pelvic inflammatory disease. Although the occurrence is rare, given the pathogenesis of the disease, TSS is a potential outcome in any clinical scenario in which S. aureus infects tissues and produces toxin.

The diagnostic workup of a patient with suspected TSS starts with a complete physical examination to investigate signs of multiorgan involvement. A pelvic examination is performed, which includes the removal of a tampon if one is present. The organ systems potentially involved and their appropriate laboratory studies are as follows:

  Cardiac: electrocardiography, cardiac enzymes
  Respiratory: chest x-ray, arterial blood gas
  Hepatic: liver function tests
  Renal: creatinine, blood urea nitrogen, urinalysis
  Hematologic: complete blood count, platelets, coagulation profile
  Musculoskeletal: creatinine phosphokinase

Multiple cultures to document the presence of S. aureus and to rule out the presence of the group A streptococcus should be performed. Sites to be considered for culture should include mucous membranes (e.g., conjunctivae, oropharynx, vagina), blood (although bacteremia is uncommon), focal lesions, stool, urine, and cerebrospinal fluid (if neurologic signs are present).

Treatment of this disorder involves correcting the hypotension with fluid replacement and supporting other organ functions. Calcium supplementation, blood product transfusion, mechanical ventilation, and even renal dialysis may be necessary in severely affected patients. Antimicrobial treatment with a β-lactamase-resistant penicillin (e.g., oxacillin, nafcillin) or cephalosporin (e.g., cefazolin) is also important.

Streptococcal Toxic Shock Syndrome

A similar TSS occurs as a result of infection with a toxin-producing strain of S. pyogenes (group A streptococcus). The case definition of streptococcal TSS involves the presence of hypotension (systolic BP less than 90 mmHg) and multisystem organ involvement (more than two systems).¹¹

The pathogenesis of streptococcal TSS involves the acquisition of S. pyogenes. Mucous membranes serve as the source of this microorganism; signs of a symptomatic infection usually are not manifested. Tissue invasion occurs, usually associated with bacterial M types 1 and 3, and the presence of pyrogenic exotoxins A or B, or both, leads to shock, multiorgan failure, and tissue destruction. Antibody to these exotoxins is probably protective. Streptococcal TSS has been reported in cases of septic abortion, postpartum endomyometritis, necrotizing fasciitis, and postoperative infection.

Localized pain is the most common presenting symptom occurring in 85% of cases. Influenza-like symptoms are also common. Patients typically are febrile and appear toxic, and they also may be mentally confused. There may be evidence of a localized soft-tissue infection. Most (95%) patients with streptococcal TSS have S. pyogenes bacteremia. A rash is not a prominent presenting sign in patients with streptococcal TSS.

Treatment of this serious infection involves an antibiotic with good activity against group A streptococci (e.g., penicillin) and, in many cases, prompt surgical debridement. Intravenous immunoglobulin therapy also may be helpful.¹² Obviously, severely affected patients will require supportive measures as well.

Clostridium sordellii -Associated Toxic Shock Syndrome

The TSS associated with C. sordellii is characterized by the sudden onset of weakness, nausea, and vomiting followed by progressive refractory hypotension associated with local and spreading edema. It is distinguished from staphylococcal TSS by the absence of: (1) S. aureus, (2) fever, and (3) rash. C. sordellii associated toxic shock (CATS) has been described in patients with episiotomy infection, and it has also been associated with postpartum infections, wound infections, a vaginal foreign body, and a degenerating cervical myoma.¹³

The pathogenesis involves the production of edema-producing C. difficile-like toxins by C. sordellii. This microorganism is fortunately only a rare inhabitant of the vagina. Antibody to the toxins is probably protective.

Treatment with broad-spectrum antibiotic therapy with activity against anaerobic bacteria such as C. sordellii should be initiated. Surgical therapy to debride necrotic soft tissue should be instituted promptly. Intravenous immunoglobulin therapy may be helpful.

All TSS patients present with an evolving clinical picture resulting in shock. Management involves clinically supporting the patient, beginning broad-spectrum antimicrobial therapy, and in selected cases, surgical intervention. Once the diagnosis is clarified, more specific antibiotic treatment, such as penicillin for streptococcal TSS or a β-lactamase-resistant antibiotic for staphylococcal TSS, can be initiated. Initial considerations during the physical examination involve the removal of tampons, sponges, or other foreign bodies from the vagina. Aerobic and anaerobic cultures of the mucous membranes (e.g., oropharynx, vagina), blood, focal lesions (e.g., endometrium), and urine should be performed to determine the pathogen involved. Fluid replacement to correct hypotension, and intensive-care monitoring is required. Recent reports suggest that intravenous immunoglobulin therapy may play an important role in the treatment of TSS.

Septic shock primarily occurs in elderly, hospitalized patients, particularly those with underlying diseases, such as disseminated malignancies or immunodeficiency. The occurrence of septic shock in a gynecologic patient is rare; however, it can occur in otherwise healthy patients who have undergone genitourinary surgery. In gynecology, the most important predisposing conditions for septic shock include septic abortion, severe postoperative infection, and ruptured tubo-ovarian abscess.

Pathophysiology

Septic shock traditionally has been recognized as a consequence of gram-negative bacterial infection (usually E. coli or Klebsiella sp.), but it may also be caused by gram-positive microorganisms (Staphylococcus sp.) and fungi, and probably by viruses and parasites. Initial studies of the pathophysiologic features of septic shock concentrated on the interactions of lipopolysaccharide from the gram-negative cell wall with various humoral pathways. Attention is now focused, however, on the central role of macrophages, endothelium, and cytokines that are released upon stimulation by most (if not all) of the recognized agents of septic shock.^14,15

The prime initiator of gram-negative bacterial septic shock is endotoxin, a lipopolysaccharide component of the bacterial outer membrane. Lipopolysaccharide in the blood activates the coagulation and complement cascades and induces a broad array of mediators from macrophages and other cells, including endothelial cells. Complement components induce vasodilation and increased vascular permeability, which can result in hemodynamic changes, aggregation of platelets, and aggregation and activation of neutrophils. The subsequent release of arachidonic acid derivatives, cytotoxic products of molecular oxygen, and lysosomal enzymes exerts additional local vasoactive effects (dilatation) on the microvasculature and causes endothelial cell cytotoxicity, which results in capillary leakage. Macrophages and endothelial cells synthesize and release increased amounts of nitrous oxide, a potent vasodilator.

Both gram-positive and gram-negative microorganisms activate factor XII (Hageman factor), which triggers the production of tissue factor both by the intrinsic coagulation pathway and by endothelial cells and macrophages. In turn, tissue factor activates the extrinsic coagulation pathway. Activation of these pathways leads to the consumption of coagulation factors and to disseminated intravascular coagulation. Lipopolysaccharide-activated Factor XII also results in the conversion of prekallikrein to kallikrein, which in turn leads to the release of bradykinin, another potent vasodilator.

Vascular endothelium plays an active role in the development of septic shock. Cytokines, tumor necrosis factor, and interleukin-1, enhance leukocyte adhesion on endothelial cells and leukocyte margination. They also result in an increase of procoagulant activity, depressing the expression of fibrinolytic activity and resulting in a trend toward intravascular coagulation. The intravascular activation of inflammatory systems involved in septic shock is mainly the consequence of an overproduction of various cytokines.

Rackow and Astiz¹⁵ note that during the early stages of septic shock, the influence of vasodilatory mediators predominates, and patients present with warm extremities (“warm shock”). Cardiac output is usually increased, with decreases in systemic vascular resistance and cardiac filling pressures. Heart rate typically increases and is partially responsible for maintaining the increased cardiac output.

Decreases in effective circulating blood volume are major factors contributing to decreases in cardiac output in patients with septic shock. Filling pressures and venous return decrease as an initial response to sepsis. Increases in systemic microvascular permeability have been demonstrated clinically during sepsis, which may lead to loss of intravascular volume (“third spacing”). Venous return is markedly decreased by peripheral and hepatosplanchnic venous pooling.

Lactic acidosis serves as an extremely useful marker of tissue hypoperfusion and tissue hypoxia during septic shock. In association with a hyperdynamic circulatory state, oxygen extraction is characteristically reduced, and mixed venous saturation is normal or increased, with concomitant lactic acidosis. This combination suggests impairment of oxygen utilization.

Distributive changes in systemic and microcirculatory blood flow patterns are postulated to be major factors contributing to impaired oxygen utilization. The release of vasoactive substances is hypothesized to result in the loss of normal mechanisms of vascular autoregulation, producing regional and microcirculatory imbalances in blood flow. Tissue edema and the presence of microthrombi may also limit diffusion of oxygen from the capillaries. Regional arteriovenous shunting results in the mismatching of blood flow with metabolic demand, causing excessive blood flow to some areas and relative hypoperfusion of other areas, thus limiting optimal systemic utilization of oxygen.

Energy expenditure is significantly increased during sepsis. The hypermetabolic response is mediated by the interaction between cytokines and the neuroendocrine axis. Tumor necrosis factor and interleukin-1 induce fever, activation of the stress response, synthesis of acute-phase reactants, and hypercatabolism. The neuroendocrine axis, particularly catecholamines, corticosteroids, and glucagon, contributes to the hypermetabolism and mediates some of the cytokine-induced metabolic changes.

The majority of patients who die of septic shock have multiorgan failure, which commonly occurs in the second to third week of their illness. The development of multiorgan failure represents the terminal phase of the hypermetabolic process that begins during the initial stages of shock and resuscitation. Organ insufficiency results from microvascular injury induced by local and systemic inflammatory responses to infection. Ongoing, uncontrolled sepsis and unperceived tissue hypoperfusion appear to be major factors contributing to the death of these patients. A characteristic pattern of sequential pulmonary, hepatic, and renal failure frequently is observed.¹⁶

Clinical Presentation

In a review of the clinical features of the sepsis syndrome, Rackow and Astiz¹⁵ describe a systemic response to infection characterized by fever or hypothermia, tachycardia, and tachypnea. When these findings are associated with evidence of organ hypoperfusion (e.g., altered cerebral function, hypoxemia, oliguria, lactic acidosis), patients are considered to have a sepsis syndrome. The sepsis syndrome identifies a group of patients at high risk for the development of septic shock. Septic shock is often identified by the development of hypotension (systolic blood pressure less than 90 mmHg or decrease from baseline systolic arterial pressure of greater than 40 mmHg); however, it should be recognized that systemic hypoperfusion usually precedes hypotension (Table 5).

TABLE 5. Septic Shock: Clinical Presentation

  Infection

  Fever (or hypothermia)
  Tachycardia
  Tachypnea

Leukocytosis is common, but neutropenia occurs in a small proportion of patients and is associated with an increased mortality. Thrombocytopenia is present in more than 50% of cases. Only a small percentage of patients have laboratory evidence of disseminated intravascular coagulation (e.g., prolonged prothrombin time, elevated fibrin and fibrinogen degradation products, decreased fibrinogen levels). Clinical bleeding due to disseminated intravascular coagulation is uncommon. Hyperglycemia is commonly present, and increases in transaminase and bilirubin concentration are frequently noted. Marked increases in transaminase levels should suggest severe ischemic liver injury (shock liver). In the absence of ischemic injury, laboratory tests characteristically show disproportionate hyperbilirubinemia, with modest elevations of transaminase and alkaline phosphatase concentrations. Hypoxemia may be present, representing a ventilation/perfusion mismatch. The development of lactic acidosis reflects inadequate tissue perfusion and anaerobic metabolism. The causes of metabolic acidosis during septic shock are multifactorial, and decreases in bicarbonate concentrations in excess of measured increases in lactic acid often are observed (Table 6).¹⁵

TABLE 6. Septic Shock: Laboratory Manifestations

  Arterial blood gas

  Acidosis
  Hypoxemia

The administration of appropriate antibiotics significantly enhances survival. Before the initiation of therapy, two or three separate blood specimens should be sent for aerobic and anaerobic cultures; appropriate genital tract cultures (including urine) also should be sent. Therapy should be initiated promptly and usually should include at least two bactericidal antibiotics, one being an aminoglycoside, because of the frequency of gram-negative sepsis as the cause of shock. Particularly useful regimens are noted in Table 3. Clindamycin has excellent anaerobic coverage, gentamicin covers aerobic gram-negative rods, and ampicillin covers most gram-positive pathogens, including the enterococci. Increased aminoglycoside loading doses may be required because of an expanded volume of distribution. Imipenem/cilastatin monotherapy can be used in this clinical scenario because its antimicrobial spectrum includes all pelvic pathogens. Lack of response to appropriate antibiotic therapy should suggest the presence of an abscess (Table 7).

TABLE 7. Septic Shock: Treatment

  Reverse hypotension

  Fluid resuscitation
  β-Inotropic agents

  Dobutamine
  Dopamine

Some patients require surgical intervention in addition to antibiotic administration. Patients with septic abortion should undergo dilatation and curettage, those with necrotizing fasciitis should undergo extensive debridement of necrotic tissue, and patients with extensive uterine myonecrosis should undergo hysterectomy. If a pelvic abscess is present, drainage via laparotomy, colpotomy, or percutaneous catheter should be performed. Indicated surgery never should be delayed because the patient appears to be unstable. In point of fact, surgery may be the only means to stabilize a severely infected patient.¹⁷

The use of immunologic therapy for the prevention and treatment of septic shock in humans is being investigated. Attention has focused on interventions directed at endotoxin. The development of antibodies to the core lipid A component of the endotoxin molecule is protective in patients with gram-negative bacteremia. Intravenous immunoglobulin therapy has been used successfully in the treatment of patients with streptococcal toxic shock syndrome.

1. Lew P, Despont J, Perrin L et al: Demonstration of a local exhaustion of complement components and of an enzymatic degradation of immunoglobulins in pleural empyema: A possible factor favouring the persistence of local bacterial infections. Clin Exp Immunol 42: 506, 1980

2. Sweet RL, Gibbs RS: Mixed anaerobic-aerobic pelvic infection and pelvic abscess. In Sweet RL, Gibbs RS (eds): Infectious Diseases of the Female Genital Tract, pp 75–108. Baltimore, Williams & Wilkins, 1990

3. Clayton J: Radiologic considerations in pelvic and intra-abdominal infections. In Pastorek JG III (ed): Obstetric and Gynecologic Infectious Disease. New York, Raven Press, 1994

4. Weinstein WM, Onderdonk AB, Bartlett JG, Gorbach SL: Experimental intraabdominal abscesses in rats: Development of an experimental model. Infect Immun 10: 1250, 1974

5. Sweet RL, Gibbs RS: Postpartum infection. In Sweet RL, Gibbs RS (eds): Infectious Diseases of the Female Genital Tract, pp 356–373. Baltimore, Williams & Wilkins, 1990

6. Reed SD, Landers DV, Sweet RL: Antibiotic treatment of tuboovarian abscess: Comparison of broad-spectrum β-lactam agents versus clindamycin-containing regimens. Am J Obstet Gynecol 164: 1556, 1991

7. Hevron JE, Llorens AS: Management of postoperative abscess following gynecologic surgery. Obstet Gynecol 47: 553, 1976

8. Duff P, Gibbs RS: Pelvic vein thrombophlebitis: Diagnostic dilemma and therapeutic challenge. Obstet Gynecol Surv 38: 365, 1983

9. Soper DE: Necrotizing fasciitis. In Pastorek JG III (ed): Obstetric and Gynecologic Infectious Disease, pp 157–163. New York, Raven Press, 1994

10. Wager GP: Toxic shock syndrome: A review. Am J Obstet Gynecol 146: 93, 1983

11. Working Group on Severe Streptococcal Infections: Defining the group A streptococcal toxic shock syndrome: Rational and consensus definition. JAMA 269:390, 1993

12. Barry W, Hudgins L, Donta ST, Pesanti EL: Intravenous immunoglobulin therapy for toxic shock syndrome. JAMA 267: 3315, 1992

13. McGregor JA, Soper DE, Lovell G, Todd JK: Maternal deaths associated with Clostridium sordellii infection. Am J Obstet Gynecol 146: 93, 1989

14. Glauser MP, Heumann D, Baumgartner JD, Cohen J: Pathogenesis and potential strategies for prevention and treatment of septic shock: An update. Clin Infect Dis 18: S205, 1994

15. Rackow EC, Astiz ME: Pathophysiology and treatment of septic shock. JAMA 266: 548, 1991

16. Beal AL, Cerra FB: Multiple organ failure syndrome in the 1990s: Systemic inflammatory response and organ dysfunction. JAMA 271: 226, 1994

17. Frigoletto FD, Cox S, Duff P et al: Manual and Workbook on Infectious Diseases. Washington, DC, APGO, 1994