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Pregnancy-related group A streptococcal infection

Pregnancy-related group A streptococcal infection
Literature review current through: May 2024.
This topic last updated: Dec 13, 2023.

INTRODUCTION — Group A Streptococcus (GAS), also known as Streptococcus pyogenes, is an aerobic gram-positive coccus that causes a broad array of infections. It is most commonly associated with pharyngitis or skin infection. Less commonly, GAS causes invasive disease, which can include necrotizing soft tissue infection, bacteremia (with or without another infection site), or pneumonia. Toxic shock syndrome (TSS) occurs as a complication of invasive GAS disease in one-fifth to one-third of pregnancy-related cases [1-3]. (See "Group A streptococcus: Virulence factors and pathogenic mechanisms".)

Pregnant and recently postpartum patients are at increased risk for developing invasive GAS infection, which typically manifests as sepsis, endomyometritis, cellulitis, necrotizing fasciitis, or TSS. In pregnant and recently postpartum patients with sepsis, invasive GAS infection is the leading cause of death, responsible for approximately 50 percent of fatal cases [1,2]. Death can occur within 24 hours of symptom onset, so a high index of suspicion, early administration of antibiotic therapy, prompt diagnosis, and surgical debridement (including hysterectomy), when indicated, can be lifesaving.

This topic will review issues involving GAS infection in the obstetric population. GAS infection in children and as a cause of acute rheumatic fever are discussed separately.

(See "Invasive group A streptococcal infections in children" and "Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features and diagnosis".)

(See "Acute rheumatic fever: Epidemiology and pathogenesis" and "Acute rheumatic fever: Clinical manifestations and diagnosis".)

GAS CARRIER STATE — Posterior pharynx cultures are GAS-positive in 2 to 5 percent of asymptomatic adults [3] and vaginal cultures are GAS-positive in 0 to 0.06 percent of healthy pregnant women [4,5]. The bacteria are acquired from contact with body fluids, typically from the nose, throat, or wound of a colonized or infected person (humans are the only known host). Asymptomatic vaginal colonization may result from contact with pharyngeal or cutaneous carriers or infected persons from contact with a colonized or infected individual [5-7].

EPIDEMIOLOGY — The risk of invasive GAS is 20-fold higher in postpartum people and two-fold higher in pregnant people compared with nonpregnant females [8,9]. In a surveillance study of the epidemiology of invasive GAS in the United States from 2005 to 2012, 20 percent of the cases among females of childbearing age were pregnancy-related [10]. However, when all cases of invasive GAS in the US population are considered, only 2 to 3 percent are pregnancy-related [11].

The incidence of pregnancy-related invasive GAS infection varies worldwide. In the United States, the annual incidence of GAS infection in postpartum people has been reported to be approximately 0.06 per 1000 live births, but recent data are not available [12]. In a systematic review of studies from high-income countries, the pooled incidence in pregnant/postpartum people was 0.12 cases per 1000 live births; the incidence in neonates was 0.02 cases per 1000 live births in high-income countries and 0.12 cases per 1000 live births in low- and middle-income countries [13]. Data in pregnant/postpartum people were scarce from low- and middle-income countries, but since the incidence of postpartum infection and newborn invasive GAS are higher in these countries, the incidence of invasive pregnancy-related GAS infections is probably higher as well.

In studies from the United States and Israel, approximately 80 percent of contemporary cases of peripartum invasive GAS infection were community-acquired from infected or colonized contacts, and the remaining 20 percent were nosocomially acquired [14,15]. Outbreaks of peripartum invasive GAS infections are sometimes traced to asymptomatic colonized health care workers in contact with the patient. Colonization among health care workers most frequently occurs in the oropharynx, but colonization of the health care worker's perianal area and vagina also appears to have led to outbreaks [16,17].

The epidemiology of invasive GAS in the general population is reviewed separately. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis", section on 'Epidemiology'.)

MICROBIOLOGY AND PATHOGENESIS — GAS is an aerobic gram-positive coccus that releases exotoxins that may act as superantigens; these toxins are capable of activating the immune system by bypassing the usual antigen-mediated immune response, resulting in the release of large quantities of inflammatory cytokines, which can lead to severe hypotension and diffuse capillary leaking. (See "Group A streptococcus: Virulence factors and pathogenic mechanisms".)

Most case reports of pregnancy-related GAS sepsis do not describe the site of origin. Since vaginal colonization is rare, most of these cases likely originate from the oropharynx. The increased risk of pregnancy-related invasive GAS in patients with pharyngitis suggests hematogenous seeding and tropism of GAS for the placenta/uterus, particularly postpartum when mucosal and other tissue barriers are disrupted (eg, an open/lacerated cervix, vaginal laceration/episiotomy, myometrial incision for cesarean birth). The pH of the vagina (normally 4.0 to 4.5) after rupture of membranes is transiently more neutral since the pH of amniotic fluid is ≥6.5, which might favor vaginal growth of the organism and ascending infection [18]. Other factors appear to be involved as well:

Pregnancy-related immune suppression – Alternatively activated M2 macrophages predominate in the postpartum uterus and are focused on uterine repair [19]; the relative absence of proinflammatory M1 macrophages in this setting could leave the host vulnerable to bacterial pathogens. In addition, a unique population of transitional cells present during uterine regeneration after parturition expresses the filament protein vimentin, a known GAS adhesin [20-22], which could mediate the increased risk of GAS infection in the postpartum setting.

Genetic susceptibility – Most colonized pregnant people do not develop invasive GAS infection, suggesting genetic susceptibility in a minority of patients, as has been observed in the general population where immunologic polymorphisms are known to play a role in susceptibility to invasive GAS infection [23]. During the third trimester, the frequency of GAS vaginal-rectal colonization has been reported to be 0.03 percent (30 per 100,000 pregnant people), whereas the frequency of GAS postpartum sepsis is reported to be only 0.006 percent (6 cases per 100,000 live births) [5]. Thus, innate or acquired mucosal immunity may protect some pregnant/postpartum people from invasive GAS disease.

Virulence of the GAS strain – Some vaginal colonizing strains of GAS may be more capable than others of causing infection during pregnancy or postpartum. M protein is the major GAS virulence factor. Strains rich in M protein are resistant to phagocytosis by polymorphonuclear leukocytes, multiply rapidly in blood, and are capable of initiating disease, whereas strains not expressing M protein are nonvirulent. Certain subtypes of M protein (eg, M-type 1, M-type 28) are more commonly associated with invasive pregnancy-associated infections [24-27].

In addition to M-types, other virulence factors such as iron-binding proteins, superantigens, pyrogenic exotoxins, and adherence molecules are thought to play a role in virulence of GAS. In one study that compared vaginal isolates from postpartum patients who had invasive infection with asymptomatic colonized multiparous patients, invasive isolates were more likely to carry the iron-binding protein gene perR and less likely carry adherence-enhancing genes [27]. There was no difference in the superantigen profiles between groups of isolates.

RISK FACTORS — Maternal symptomatic GAS pharyngitis is a risk factor for pregnancy-related invasive GAS infection. Contact with young children during pregnancy represents an underappreciated risk factor for maternal GAS acquisition, presumably because the rate of pharyngeal GAS colonization is higher in children than in adults (as many as 20 percent of asymptomatic school-age children may be GAS carriers [28]) [3]. In a retrospective study, primiparity was an independent protective factor against postpartum GAS infection, presumably due to diminished exposure to children carrying GAS [29].

Other risk factors for GAS infection in pregnant/postpartum people include invasive or surgical procedures (eg, cesarean birth), prelabor or prolonged rupture of membranes, retained products of conception, and comorbid conditions (eg, diabetes, obesity, chronic kidney or liver disease) [30,31]. Outbreaks have been reported in healthcare settings [32,33].

CLINICAL MANIFESTATIONS

Clinical syndromes — Symptoms of invasive GAS infection in pregnant and postpartum patients are variable.

Antepartum/intrapartum presentation — Onset of GAS infection prior to childbirth is uncommon, ranging from 7 to 15 percent of reported pregnancy-related GAS infections [12,34]. Most infected patients were healthy and had uncomplicated pregnancies.

A literature review (1974 to 2009) of 67 cases of pregnancy-related GAS evaluated the likely source of pathogen acquisition, clinical signs and symptoms at onset, and patient outcomes to better inform early diagnosis [12]. The review included 10 antepartum cases, only one of which presented during the first trimester (the patient had streptococcal toxic shock syndrome [TSS]). Among the nine patients who presented in the third trimester, findings of interest included the following:

None had prelabor rupture of membranes or vaginal discharge.

Initial symptoms were:

Pharyngitis or upper respiratory infection (five patients, 56 percent)

Abdominal pain (four patients, 44 percent)

Chills (two patients, 22 percent)

Gastrointestinal symptoms (one patient, 11 percent)

Other clinical findings included fever (seven patients, 78 percent), hypotension (five patients, 56 percent), tachycardia (four patients, 44 percent), uterine tenderness (one patient, 11 percent), and extremity pain (one patient, 11 percent).

GAS was cultured from the blood (seven patients, 78 percent), oropharynx/respiratory tract (four patients, 44 percent), deep soft tissue of an extremity (one patient, 11 percent), and central nervous system (one patient, 11 percent).

Surgical/pathology findings were reported in five patients: two had necrosis, inflammation, or exudate involving the uterus, ovaries, and/or fallopian tube (without concomitant colonization of the vaginal vault) and three had normal placenta, uterus, and/or pelvic organs.

Five fetuses died, two fetuses survived; outcome was not available in the remaining two cases.

In a report of maternal sepsis-related deaths in Japan between 2010 and 2016, 13 out of 24 deaths (54 percent) were attributable to GAS [35]. An unusual finding in this series was that the onset of symptoms was antepartum rather than postpartum in most patients (10 out of 13). Most of these patients (9 out of 10) had a fetal demise. Maternal deterioration was rapid; seven out of the 13 patients died within 24 hours of hospital admission. (See "Group A streptococcus: Virulence factors and pathogenic mechanisms", section on 'M and M-like proteins'.)

In both of these reports, the degree to which fetal demise was related to maternal instability, fetal infection, or both was unclear [12,35].

Postpartum presentation — Two systematic reviews demonstrated that 85 to 92 percent of pregnancy-related GAS infections occur postpartum; the remainder occur antepartum or are related to a miscarriage or pregnancy termination [12,34]. Approximately 50 percent of postpartum patients presented within the first 48 hours, 37 percent within three to seven days, and 14 percent more than seven days post-delivery, and most deliveries were uncomplicated vaginal births [12,34].

Postpartum patients with GAS sepsis typically present with fever (90 percent), abdominal pain and tenderness (32 percent), and/or vaginal discharge (8 percent), which may be accompanied by hypotension, tachycardia, tachypnea, or leukocytosis [34]. Fever greater than 38.5°C (101.3°F) often develops within the first 48 hours after giving birth and persists for more than four hours. Other significant clinical manifestations are summarized in the table (table 1).

The site of infection may be the uterus, vagina, episiotomy or cesarian-section wound, external genitalia, breast, urinary tract, respiratory tract, or another site; sometimes, there is no identifiable site [36-38]. Endomyometritis and necrotizing soft tissue infection are the two most common types of infection.

Endomyometritis – In patients with typical signs and symptoms of postpartum endomyometritis (fever, uterine pain, purulent uterine discharge), clues that invasive GAS is the cause include fever exceeding 38.9°C (102°F), chills, nausea, vomiting, myalgia, dyspnea, rash, pharyngitis, headache, and confusion or combativeness [12,39]. High fever is not a universal finding and the presence of the other systemic symptoms may be the only initial finding to suggest GAS. In some patients who have undergone laparotomy, necrosis of the ovaries, fallopian tubes, and/or uterus has been observed [12]. (See "Postpartum endometritis" and "Postpartum endometritis", section on 'Clinical findings' and "Postpartum endometritis", section on 'Diagnosis'.)

Other necrotizing soft tissue infections – Necrotizing soft tissue infections include necrotizing forms of fasciitis, myositis, and cellulitis and are characterized clinically by fulminant tissue destruction, systemic signs of toxicity, and high mortality. Patients with necrotizing fasciitis often become septic and have severe local pain before marked skin changes occur. Symptoms usually present acutely (over hours) but sometimes can present subacutely (over days). Rapid progression to extensive tissue destruction can occur. The incision for cesarean birth or vulva lacerations are typically the primary site of postpartum infection, but an extremity may be involved due to hematogenous seeding or as the primary source of infection. (See "Necrotizing soft tissue infections".)

Newborn outcome is not well described in the literature. A study of all mothers and/or neonates with S. pyogenes bacteremia in three districts of England identified six cases: both mother and neonate were affected in three, the mother only in two, and the neonate only in one [40]. Maternal features included endometritis, septicemia, peritonitis, necrotizing fasciitis, and TSS, while neonatal infection was manifested by stillbirth or septicemia, cyanosis, jaundice, lethargy, and cellulitis. In three of four affected neonates, infection developed 2 to 4 days after birth and the other was stillborn. The mothers were infected in three of these cases, suggesting the neonates acquired their infection from their mothers. A systematic review of invasive GAS found high case fatality rates; more than one in five neonates with invasive GAS worldwide die from their infection [13].

Streptococcal toxic shock syndrome — Streptococcal TSS is a complication of invasive GAS disease and can accompany or be the presenting syndrome in antepartum or postpartum GAS infections. It is characterized by early onset (eg, within hours) of shock with fluid-refractory hypotension and multiorgan failure (eg, renal failure, acute respiratory distress syndrome). Fever is common; hypothermia may be present. Altered mental status occurs in about half of cases. An influenza-like prodrome characterized by fever, chills, myalgia, nausea, vomiting, and diarrhea occurs in about 20 percent of patients [41]. A diffuse, scarlatina-like erythema occurs in about 10 percent of cases [42]. Symptoms of underlying invasive GAS infection may or may not be present. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis" and "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention".)

Physical examination findings — In addition to signs of sepsis (eg, fever, tachycardia, tachypnea, hypotension), abdominal and bimanual examination may reveal abdominal and/or uterine tenderness or wound infection. Vulvovaginal examination may reveal vaginal or cervical purulent discharge or inflammation at the site of a laceration. Rarely, cellulitis elsewhere (eg, of an extremity) or a diffuse erythematous rash may be present.

Laboratory findings — Complete blood count (CBC) usually shows leukocytosis with left-shift (81 to 94 percent of patients [34]). Bandemia (greater than 10 percent) may be present even in the absence of a leukocytosis. Hemolysis, hemoconcentration, and thrombocytopenia may occur [43]. C-reactive protein is elevated in 96 to 100 percent of patients [34].

The white blood cell (WBC) count is normally elevated in pregnancy secondary to physiologic leukocytosis, and it is even higher during labor (mean WBC counts in laboring patients range from 10,000 to 16,000 cells/microL, with an upper level as high as 29,000 cells/microL). However, a left shift (bandemia) and a rising, rather than falling, neutrophil count postpartum are suggestive of an infectious process.

Blood cultures are positive in approximately 50 percent of cases [34].

In patients with streptococcal TSS, laboratory results may reveal evidence of end-organ damage (eg, elevated creatinine or aminotransferases).

DIAGNOSIS

Clinical suspicion and presumptive diagnosis — The importance of considering the diagnosis early in the clinical course cannot be over-emphasized. Patients with the best outcomes are those who receive early therapy based on a presumptive diagnosis made prior to confirmation by culture. If the diagnosis is delayed and shock develops, case fatality rates of over 40 percent have been reported in large studies of pregnant and nonpregnant populations [12,39].

The diagnosis should be suspected in pregnant or recently postpartum patients who develop fever, chills, and abdominal or postpartum wound pain, especially if fever is greater than 38.5°C (>101.3°F) or pain is out of proportion to findings on physical examination. Additional findings of leukocytosis, hypotension, and tachycardia are signs of developing streptococcal toxic shock syndrome (TSS) and are associated with higher mortality. (See 'Clinical manifestations' above.)

Recognition of invasive GAS infections during pregnancy or early in the postpartum period can be challenging due to the nonspecific symptoms and low incidence of the disease. Physicians may misconstrue the pain of developing infection as expected postpartum discomfort. Hypotension and tachycardia may be mistaken for hemorrhagic shock (postpartum hemorrhage [which may be occult] is more common than TSS) or other complications of pregnancy. Pain-relieving agents after childbirth can mask the signs of incubating infection, which can contribute to a delay in diagnosis with catastrophic outcomes [44].

Diagnostic evaluation and definitive diagnosis — A definitive diagnosis of invasive GAS infection requires a positive Gram stain or a culture that grows Group A Streptococcus from an appropriate clinical specimen in a patient with a clinical syndrome compatible with invasive GAS infection. Physical examination, other laboratory tests, and imaging may be helpful but cannot confirm or rule out the diagnosis.

Physical examination – A complete physical examination should be performed, including bimanual pelvic and speculum examinations to assess for pain and other abnormalities and to obtain samples of vaginal discharge for microbiologic testing. Typical findings are discussed above. (See 'Physical examination findings' above.)

Microbiologic samples – In patients with pregnancy-related sepsis, blood cultures (at least two sets) should be urgently obtained prior to antibiotic administration, if possible. Following administration of antibiotics, we obtain Gram stain and culture from the following anatomic sites: vagina (including discharge if present), endometrial aspiration, placenta, open wounds, oropharynx, and any other sites of suspected infection; we also obtain blood cultures (at least two sets) if they were not obtained prior to antibiotic administration.

A Gram stain that shows gram-positive cocci in pairs or chains is suggestive of streptococci. Recovery of GAS from cultures usually takes 8 to 24 hours.

Growth of GAS (or a positive rapid antigen or molecular test) from the oropharynx may provide an early diagnostic clue in compatible cases, but the positive and negative predictive value of oropharyngeal tests are poor for diagnosing invasive infection (ie, oropharyngeal colonization is common in many uninfected people, and many patients with invasive GAS infection do not have oropharyngeal colonization).

Laboratory tests – Routine laboratory tests include complete blood count (CBC), chemistry panels, and coagulation tests. Typical results are discussed above. (See 'Laboratory findings' above.)

Imaging – The diagnosis of invasive GAS infection cannot be confirmed or ruled out with imaging. Ultrasonography, computed tomography, and magnetic resonance imaging may appear normal for the postpartum state and should not delay aggressive management. Typically, imaging demonstrates an edematous uterus that is larger than expected. GAS does not generally form abscesses or produce gas, whereas postpartum infections caused by Clostridium perfringens or mixed aerobic/anaerobic pathogens are usually associated with gas in the tissues. (see "Overview of the postpartum period: Normal physiology and routine maternal care", section on 'Findings on ultrasound')

Work-up for other infections – The differential for invasive GAS infection is broad and includes common causes of sepsis. Additional studies may be warranted to rule out other sources, including urinalysis and culture and chest radiograph, among others. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of pregnancy-related invasive GAS infection includes infections due to organisms that cause necrotizing infections, toxic shock syndrome (TSS), endometritis, or septic shock.

Toxic shock syndrome and necrotizing soft tissue infections – TSS and necrotizing soft tissue infections due to organisms other than streptococci present in a fulminant fashion similarly to streptococcal disease. There are a few distinguishing features, although most lack specificity.

Clostridium perfringens and Clostridium sordellii – These clostridial species can cause rapidly progressive necrotizing infections of the uterus, external genitalia, and episiotomy site. C. sordellii can also cause TSS. Infections with these organisms are relatively uncommon but are associated with severe illness, high mortality, and devastating morbidity [45]. (See "Clostridial myonecrosis" and "Toxic shock syndrome due to Paeniclostridium sordellii".)

Clinical clues for clostridial infection include lack of fever, hemoconcentration (hematocrit of 60 to 80 percent) or hemolysis, leukemoid reaction (white blood cell count of 50,000 to 200,000 cells/microL), and diffuse capillary leak syndrome [46,47]. A strong clinical clue is the presence of gas in the tissue, detectable by clinical findings of crepitus and/or radiographically; however, not all patients will have detectable gas at the time of diagnosis.

Staphylococcus aureusS. aureus, including methicillin-resistant S. aureus (MRSA), can cause TSS and necrotizing soft tissue infection.

Staphylococcal TSS usually occurs in females with recent tampon use or individuals with recent surgery or wound infection. Staphylococcal TSS can be difficult to differentiate from streptococcal TSS. Features that favor staphylococcal TSS over streptococcal TSS include the presence of a diffuse fleeting erythroderma rash and negative blood cultures. (See "Staphylococcal toxic shock syndrome" and "Necrotizing soft tissue infections".)

Endometritis – Endometritis that is not due to streptococcal infection is usually polymicrobial, involving anaerobic or facultative bacteria, mycoplasmas, and/or aerobic bacteria including gram-negative bacilli.

Typical signs and symptoms include fever, uterine tenderness, tachycardia that parallels the rise in temperature, and midline lower abdominal pain. Although these symptoms are similar to those of invasive GAS infection, they are typically less severe when due to organisms other than GAS. (See "Postpartum endometritis".)

Severe sepsis or septic shock – Like other patients, postpartum patients are at risk for common infections that can cause severe sepsis or septic shock. Examples include pyelonephritis, abscess (including breast abscess), pneumonia, and C. difficile infection. (See "Overview of the postpartum period: Disorders and complications", section on 'Fever/infection/wound complications'.)

TREATMENT — Prompt treatment is critical to management of pregnancy-related invasive GAS infection. Management consists of supportive care, antibiotic therapy, and source control. Intravenous immune globulin (IVIg) is added in some cases.

Supportive care — For patients with sepsis and septic shock, aggressive fluid resuscitation and other resuscitative measures are paramount. Details regarding these interventions are found elsewhere. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Immediate evaluation and management' and "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Initial therapy'.)

Antibiotic selection — Antibiotics are a cornerstone of management and should be administered with urgency (ie, before culture results return).

Empiric antibiotic therapy — Before a definitive diagnosis is made, broad spectrum treatment is important because GAS, Clostridium species, Bacteroides, Prevotella, and other organisms can cause shock and necrotizing infection in the postpartum period. We suggest the following regimen:

Vancomycin (intravenous dosing summarized in table (table 2))

PLUS

Clindamycin (900 mg intravenously every eight hours)

PLUS one of the following:

A carbapenem (meropenem [1 g intravenously every eight hours] or imipenem [500 mg IV every six hours; higher dosing of 1 g every six to eight hours may be used for patients with obesity, recent broad-spectrum antibiotic treatment, or recent colonization with multidrug-resistant organisms])

OR

Piperacillin-tazobactam (4.5 g intravenously every six hours)

OR

Ceftriaxone (2 g intravenously once daily) plus metronidazole (500 mg intravenously every eight hours)

Although many patients have reported beta-lactam allergies, most do not have allergies that would prohibit the use of beta-lactams. In particular, many with penicillin allergies can still take a cephalosporin or carbapenem. For patients who cannot take a beta-lactam or carbapenem, we suggest combining intravenous vancomycin and clindamycin with either aztreonam or a fluoroquinolone.

Initial empiric therapy should cover a broad range of potential pathogens because signs and symptoms of GAS infection are nonspecific and many other organisms can cause sepsis in peripartum people. Although empiric antibiotic regimens for endometritis include activity against GAS if they include a beta-lactam (penicillin, ampicillin, or cephalosporin) plus clindamycin, they do not reliably cover other potential pathogens that can cause septic shock or toxic shock syndrome (TSS; eg, MRSA, aerobic gram-negative bacilli, Bacteroides spp). Inclusion of a beta lactam plus clindamycin in the empiric regimen is crucial when GAS endometrial or intra-uterine infection is suspected.

Tailored antibiotic therapy — Once the diagnosis of GAS has been confirmed and susceptibilities are known, treatment consists of the following regimen:

Penicillin G (4 million units intravenously every four hours)

PLUS

Clindamycin (900 mg intravenously every eight hours) [48].

Vancomycin (table 2) or daptomycin (6 mg/kg intravenously every 24 hours) are acceptable alternatives to penicillin for patients with serious beta-lactam hypersensitivity.

For patients whose isolates are resistant to clindamycin, linezolid (600 mg intravenously every 12 hours) or tedizolid (200 mg intravenously once daily) are acceptable alternative agents. Clindamycin resistance is emerging, as are reports of treatment failures in cases of clindamycin resistance [49-51]. Like clindamycin, linezolid and tedizolid are capable of suppressing toxin production of virulent GAS strains [52-54].

The above-described antibiotic suggestions are based on studies of invasive GAS infection in nonpregnant people, in vitro susceptibility data, and results from animal studies; there are no trials of antibiotic therapy for pregnancy-related GAS infection in humans.

Duration of therapy — Combination therapy should be continued until patients are clinically and hemodynamically stable for at least 48 to 72 hours; thereafter, monotherapy (eg, penicillin) may be administered.

The total duration of antibiotic therapy should be individualized. Patients with bacteremia should be treated for at least 14 days. In patients with complicated deep-seated infection, length of therapy depends on the clinical course and the adequacy of surgical debridement; therapy is usually continued for 14 days from the last positive culture obtained during surgical debridement or from a sterile site.

Role of surgery — All cases of necrotizing soft tissue infection should undergo emergent surgical intervention. Source control may require wound or vulvar debridement, hysterectomy, or a combination of these. Hysterectomy may be life-saving in GAS sepsis and should be the default management given the high mortality rate.

For patients with TSS without necrotizing infection, most experts agree that medical management along with surgical consultation is appropriate [12,39]. There are no trials comparing outcomes between conservative and surgical approaches.

Patients without TSS or necrotizing infection may be managed with antibiotic therapy alone with a plan to move to operative intervention if the condition worsens. Some important indicators for progression of infection are worsening signs and symptoms as well as increasing white blood cell (WBC) count with left shift, renal impairment, C-reactive protein (CRP), or creatine kinase.

Role of intravenous immune globulin — We suggest administration of intravenous immune globulin for patients with streptococcal TSS. This issue is discussed further separately. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Intravenous immune globulin'.)

PREVENTION

Role for screening and prophylaxis — In most situations, there is no clear role for screening, prophylaxis, or pre-emptive treatment to prevent invasive GAS infection in pregnant and recently postpartum patients. Specific circumstances are described below:

Asymptomatic pregnant patients – We suggest not performing GAS screening of asymptomatic pregnant people or their asymptomatic household contacts because subsequent invasive infection is rare [4,55].

Vaginal colonization during normal pregnancy is rare (0 to 0.06 percent), and most patients who develop intrauterine infection due to GAS do not have vaginal GAS colonization [5,12].

In contrast to vaginal colonization, pharyngeal colonization (ie, chronic carriage) is common in adults, ranging from 2 to 5 percent in healthy adults [3,56,57]. Despite these rates of chronic carriage, invasive GAS infection remains rare during pregnancy (0.06 cases per 1000 live births in the United States) [24]. Additionally, data suggest that pharyngeal colonization is not present in most pregnant patients with invasive GAS infection [12,14,29]. These data suggest that the substantial burden of pharyngeal screening and effects of unnecessary antibiotics on mothers and fetuses from screening would not balance any potential benefit [4].

Many pregnant patients receive antibiotic prophylaxis with activity against streptococci near the time of birth (eg, patients with known Group B Streptococcus vaginal colonization, preterm prelabor rupture of membranes, cesarean birth). It is unknown whether these interventions reduce the risk of GAS infection. (See "Prelabor rupture of membranes at term: Management", section on 'Antibiotic prophylaxis' and "Prevention of early-onset group B streptococcal disease in neonates" and "Cesarean birth: Preoperative planning and patient preparation", section on 'Antibiotic prophylaxis and antiseptic preparation'.)

Incidental discovery of GAS colonization – We suggest not providing prophylaxis or pre-emptive treatment for asymptomatic GAS vaginal colonization if identified in the course of routine prenatal care. However, expert opinion varies given lack of data [58].

Some laboratories report GAS if it is identified in routine GBS screening cultures. The risk of developing GAS infection in this setting is unknown (case reports have been described [12,59]), but is likely to be low because the annual incidence of invasive GAS infection in postpartum patients is rare [24].

In some situations, consultation with an infectious diseases expert may be helpful, such as for pregnant or postpartum patients with the incidental finding of GAS on routine GBS screening who have risk factors for pregnancy-related GAS infection. (See 'Diagnosis' above and 'Treatment' above.)

Pregnant household contacts of an individual with invasive GAS infection – Some experts give prophylaxis to a pregnant person who is a household contact of an individual diagnosed with invasive Group A streptococcal infection [55]. Prophylactic regimens that are considered safe in pregnancy include clindamycin (300 mg orally every eight hours for 10 days) or azithromycin (500 mg orally once daily for five days) [4,55]. Further information for prophylaxis of contacts is found elsewhere. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Prophylaxis for contacts'.)

Screening of these patients for GAS colonization before or after prophylaxis is not recommended by the United States Centers for Disease Control and Prevention (CDC) [55].

Pregnant patients with sore throat or purulent vaginal discharge – Some pregnant patients develop mild symptoms from GAS infection and should be treated. It is uncertain whether treatment prevents invasive disease.

For pregnant patients with pharyngitis, pharyngeal testing for GAS is appropriate, and patients with positive tests should be treated accordingly. This is particularly relevant for those who have close contact with young children. (See "Treatment and prevention of streptococcal pharyngitis in adults and children", section on 'Prevention'.)

Pregnant patients who present with purulent vaginal discharge, especially with associated pelvic pain, should be evaluated for pelvic inflammatory disease (PID) (see "Pelvic inflammatory disease: Clinical manifestations and diagnosis"). Sometimes, evaluation reveals the presence of GAS with no evidence of other more typical organisms (eg, gonorrhea and chlamydia). In these situations, treatment of GAS may be indicated although GAS is an uncommon cause of vulvovaginitis in adults. Clinical features suggestive of GAS vaginitis include acute onset of frankly purulent discharge accompanied by pruritus, soreness and irritation, erythema, labial edema, and possibly dysuria from burning of the skin with voiding. Vaginal pH can be normal or mildly increased. Microscopy of the discharge reveals a marked increase in polymorphonuclear leukocytes and Gram stain shows pairs and chains of gram-positive cocci. (See "Vaginitis in adults: Initial evaluation", section on 'Pain'.)

Infection control — In a large, multi-database systematic review of pregnancy-related GAS infections, 31 percent were confirmed nosocomial infections [34]. In the United States, approximately 14 percent of GAS postpartum infections are nosocomially acquired [15].

Hospital-associated epidemics of postpartum GAS infection can occur due to transmission from colonized or contaminated health care workers [32,33]. A single case of nosocomial postpartum or postsurgical invasive GAS infection should prompt enhanced surveillance within the hospital, and two or more cases within a six-month period should prompt an epidemiologic investigation that includes screening of epidemiologically linked health care workers [55].

Patients with GAS in the absence of toxic shock syndrome (TSS) may be managed with standard precautions. Patients with streptococcal TSS warrant droplet precautions (in addition to standard precautions); droplet precautions may be discontinued after the first 24 hours of antimicrobial therapy [60].

SUMMARY AND RECOMMENDATIONS

Epidemiology – The risk of invasive Group A Streptococcus (GAS) is 20-fold higher in postpartum people and two-fold higher in pregnant people compared with nonpregnant females. (See 'Epidemiology' above.)

Risk factors – These include upper respiratory tract GAS infection, contact with young children, premature rupture of membranes, and cesarean birth. (See 'Risk factors' above.)

Clinical manifestations – Most cases occur during the postpartum period, although antepartum infections have been reported. Endomyometritis and necrotizing soft tissue infection (of the vagina, wound, or surgical site) are the two most common types of infection. (See 'Clinical manifestations' above.)

Signs and symptoms include fever, abdominal pain, and hypotension with or without tachycardia or leukocytosis. Hypotension, tachycardia, and end-organ damage (eg, elevated creatinine or aminotransferases) are signs of streptococcal toxic shock syndrome (TSS) and are associated with higher mortality.

Diagnosis – Invasive GAS infection should be suspected in pregnant or recently postpartum patients who develop fever and abdominal or postpartum wound pain, especially if fever is greater than 38.5°C (101.3°F) or pain is out of proportion to findings on physical examination, which should include bimanual pelvic and speculum examinations. (See 'Clinical suspicion and presumptive diagnosis' above.)

Diagnostic evaluation and definitive diagnosis – A definitive diagnosis of invasive GAS infection requires a positive Gram stain (with gram-positive cocci in pairs or chains) or a culture that grows Group A Streptococcus from an appropriate clinical specimen in a patient with a clinical syndrome compatible with invasive GAS infection. (See 'Diagnostic evaluation and definitive diagnosis' above.)

Gram stain and culture from the following anatomic sites should be obtained: blood (at least two sets obtained prior to antibiotic administration, if possible), vagina (including discharge if present), endometrial aspiration, placenta, open wounds, oropharynx, and any other sites of suspected infection.

Differential diagnosis – The differential diagnosis includes other infections that cause sepsis, endomyometritis, or TSS during pregnancy. Such infections include clostridial or staphylococcal TSS or necrotizing fasciitis, polymicrobial endometritis, pneumonia, pyelonephritis, and others. (See 'Differential diagnosis' above.)

Treatment – Aggressive fluid resuscitation, blood pressure support, antibiotic therapy, and source control are the mainstays of therapy. Prompt intervention is critical. (See 'Treatment' above.)

Antibiotic selection

-Empiric therapy – For pregnant patients with sepsis of unknown etiology, it is essential to have a low threshold to empirically treat for GAS infection until a definitive diagnosis is made. Other organisms should be covered as well while awaiting test results. An example regimen is parenteral vancomycin, clindamycin, and meropenem. (See 'Empiric antibiotic therapy' above.)

-Tailored therapy – For patients with confirmed GAS infection, we suggest combination antibiotic therapy with parenteral penicillin G and clindamycin (rather than penicillin G alone) (Grade 2C). (See 'Tailored antibiotic therapy' above.)

Role of surgery – For necrotizing GAS infections, source control is essential and may require wound or vulvar debridement, hysterectomy, or both. Patients without necrotizing infection may be managed with antibiotic therapy alone with plan to move to operative intervention if the condition worsens. (See 'Role of surgery' above.)

Role of intravenous immune globulin – Patients with streptococcal TSS are generally treated with intravenous immune globulin (IVIg) as an adjunct to antibiotic therapy. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Intravenous immune globulin'.)

  1. Center for Maternal and Child Enquiries. Saving mother's lives: Reviewing maternal deaths to make motherhood safer: 2006-2008. The eight report of the confidential enquiries inot maternal deaths in the United Kingdom. https://www.publichealth.hscni.net/sites/default/files/Saving%20Mothers%27%20Lives%202006-2008_0.pdf (Accessed on April 01, 2022).
  2. Hasegawa J, Ikeda T, Sekizawa A, et al. Recommendations for saving mothers' lives in Japan: Report from the Maternal Death Exploratory Committee (2010-2014). J Obstet Gynaecol Res 2016; 42:1637.
  3. Oliver J, Malliya Wadu E, Pierse N, et al. Group A Streptococcus pharyngitis and pharyngeal carriage: A meta-analysis. PLoS Negl Trop Dis 2018; 12:e0006335.
  4. Donders G, Greenhouse P, Donders F, et al. Genital Tract GAS Infection ISIDOG Guidelines. J Clin Med 2021; 10.
  5. Mead PB, Winn WC. Vaginal-rectal colonization with group A streptococci in late pregnancy. Infect Dis Obstet Gynecol 2000; 8:217.
  6. Dei M, Di Maggio F, Di Paolo G, Bruni V. Vulvovaginitis in childhood. Best Pract Res Clin Obstet Gynaecol 2010; 24:129.
  7. Randjelovic G, Otasevic S, Mladenovic-Antic S, et al. Streptococcus pyogenes as the cause of vulvovaginitis and balanitis in children. Pediatr Int 2017; 59:432.
  8. Deutscher M, Lewis M, Zell ER, et al. Incidence and severity of invasive Streptococcus pneumoniae, group A Streptococcus, and group B Streptococcus infections among pregnant and postpartum women. Clin Infect Dis 2011; 53:114.
  9. 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.
  10. Nelson GE, Pondo T, Toews KA, et al. Epidemiology of Invasive Group A Streptococcal Infections in the United States, 2005-2012. Clin Infect Dis 2016; 63:478.
  11. O'Loughlin RE, Roberson A, Cieslak PR, et al. The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000-2004. Clin Infect Dis 2007; 45:853.
  12. Hamilton SM, Stevens DL, Bryant AE. Pregnancy-related group a streptococcal infections: temporal relationships between bacterial acquisition, infection onset, clinical findings, and outcome. Clin Infect Dis 2013; 57:870.
  13. Sherwood E, Vergnano S, Kakuchi I, et al. Invasive group A streptococcal disease in pregnant women and young children: a systematic review and meta-analysis. Lancet Infect Dis 2022; 22:1076.
  14. Shinar S, Fouks Y, Amit S, et al. Clinical Characteristics of and Preventative Strategies for Peripartum Group A Streptococcal Infections. Obstet Gynecol 2016; 127:227.
  15. O'Brien KL, Beall B, Barrett NL, et al. Epidemiology of invasive group a streptococcus disease in the United States, 1995-1999. Clin Infect Dis 2002; 35:268.
  16. Berkelman RL, Martin D, Graham DR, et al. Streptococcal wound infections caused by a vaginal carrier. JAMA 1982; 247:2680.
  17. Schaffner W, Lefkowitz LB Jr, Goodman JS, Koenig MG. Hospital outbreak of infections with group a streptococci traced to an asymptomatic anal carrier. N Engl J Med 1969; 280:1224.
  18. Sitkiewicz I, Green NM, Guo N, et al. Adaptation of group A Streptococcus to human amniotic fluid. PLoS One 2010; 5:e9785.
  19. Timmons BC, Fairhurst AM, Mahendroo MS. Temporal changes in myeloid cells in the cervix during pregnancy and parturition. J Immunol 2009; 182:2700.
  20. Patterson AL, Zhang L, Arango NA, et al. Mesenchymal-to-epithelial transition contributes to endometrial regeneration following natural and artificial decidualization. Stem Cells Dev 2013; 22:964.
  21. Hamilton SM, Bayer CR, Stevens DL, et al. Muscle injury, vimentin expression, and nonsteroidal anti-inflammatory drugs predispose to cryptic group A streptococcal necrotizing infection. J Infect Dis 2008; 198:1692.
  22. Bryant AE, Bayer CR, Huntington JD, Stevens DL. Group A streptococcal myonecrosis: increased vimentin expression after skeletal-muscle injury mediates the binding of Streptococcus pyogenes. J Infect Dis 2006; 193:1685.
  23. Nooh MM, Nookala S, Kansal R, Kotb M. Individual genetic variations directly effect polarization of cytokine responses to superantigens associated with streptococcal sepsis: implications for customized patient care. J Immunol 2011; 186:3156.
  24. Chuang I, Van Beneden C, Beall B, Schuchat A. Population-based surveillance for postpartum invasive group a streptococcus infections, 1995-2000. Clin Infect Dis 2002; 35:665.
  25. Byrne JL, Aagaard-Tillery KM, Johnson JL, et al. Group A streptococcal puerperal sepsis: initial characterization of virulence factors in association with clinical parameters. J Reprod Immunol 2009; 82:74.
  26. Turner CE, Dryden M, Holden MT, et al. Molecular analysis of an outbreak of lethal postpartum sepsis caused by Streptococcus pyogenes. J Clin Microbiol 2013; 51:2089.
  27. Golińska E, van der Linden M, Więcek G, et al. Virulence factors of Streptococcus pyogenes strains from women in peri-labor with invasive infections. Eur J Clin Microbiol Infect Dis 2016; 35:747.
  28. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis 2012; 55:e86.
  29. 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; 25:251.e1.
  30. Burlinson CEG, Sirounis D, Walley KR, Chau A. Sepsis in pregnancy and the puerperium. Int J Obstet Anesth 2018; 36:96.
  31. Buddeberg BS, Aveling W. Puerperal sepsis in the 21st century: progress, new challenges and the situation worldwide. Postgrad Med J 2015; 91:572.
  32. From the Centers for Disease Control and Prevention. Nosocomial group A streptococcal infections associated with asymptomatic health-care workers--Maryland and California, 1997. JAMA 1999; 281:1077.
  33. Stamm WE, Feeley JC, Facklam RR. Wound infections due to group A streptococcus traced to a vaginal carrier. J Infect Dis 1978; 138:287.
  34. Harris K, Proctor LK, Shinar S, et al. Outcomes and management of pregnancy and puerperal group A streptococcal infections: A systematic review. Acta Obstet Gynecol Scand 2023; 102:138.
  35. 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; 25:41.
  36. Ahnfeldt-Mollerup P, Petersen LK, Kragstrup J, et al. Postpartum infections: occurrence, healthcare contacts and association with breastfeeding. Acta Obstet Gynecol Scand 2012; 91:1440.
  37. Ganchimeg T, Ota E, Morisaki N, et al. Pregnancy and childbirth outcomes among adolescent mothers: a World Health Organization multicountry study. BJOG 2014; 121 Suppl 1:40.
  38. Stevens DL, Bryant AE. Necrotizing Soft-Tissue Infections. N Engl J Med 2017; 377:2253.
  39. Rimawi BH, Soper DE, Eschenbach DA. Group A streptococcal infections in obstetrics and gynecology. Clin Obstet Gynecol 2012; 55:864.
  40. Barnham MR, Weightman NC. Bacteraemic Streptococcus pyogenes infection in the peri-partum period: now a rare disease and prior carriage by the patient may be important. J Infect 2001; 43:173.
  41. Agerson AN, Wilkins EG. Streptococcal toxic shock syndrome after breast reconstruction. Ann Plast Surg 2005; 54:553.
  42. Defining the group A streptococcal toxic shock syndrome. Rationale and consensus definition. The Working Group on Severe Streptococcal Infections. JAMA 1993; 269:390.
  43. Anderson BL. Puerperal group A streptococcal infection: beyond Semmelweis. Obstet Gynecol 2014; 123:874.
  44. Gallup DG, Freedman MA, Meguiar RV, et al. Necrotizing fasciitis in gynecologic and obstetric patients: a surgical emergency. Am J Obstet Gynecol 2002; 187:305.
  45. Stevens DL, Aldape MJ, Bryant AE. Life-threatening clostridial infections. Anaerobe 2012; 18:254.
  46. Aldape MJ, Bryant AE, Stevens DL. Clostridium sordellii infection: epidemiology, clinical findings, and current perspectives on diagnosis and treatment. Clin Infect Dis 2006; 43:1436.
  47. Kaiser JE, Bakian AV, Silver RM, Clark EAS. Clinical Variables Associated With Adverse Maternal Outcomes in Puerperal Group A Streptococci Infection. Obstet Gynecol 2018; 132:179.
  48. 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:e10.
  49. DeMuri GP, Sterkel AK, Kubica PA, et al. Macrolide and Clindamycin Resistance in Group a Streptococci Isolated From Children With Pharyngitis. Pediatr Infect Dis J 2017; 36:342.
  50. Peng XM, Yang P, Liu S, et al. [The genetic features of drug resistance to group A streptococcus and macrolides antibiotics among pediatric patients in Beijing 2012]. Zhonghua Yu Fang Yi Xue Za Zhi 2013; 47:1040.
  51. Lewis JS 2nd, Lepak AJ, Thompson GR 3rd, et al. Failure of clindamycin to eradicate infection with beta-hemolytic streptococci inducibly resistant to clindamycin in an animal model and in human infections. Antimicrob Agents Chemother 2014; 58:1327.
  52. Bryant AE, Bayer CR, Aldape MJ, et al. Emerging erythromycin and clindamycin resistance in group A streptococci: Efficacy of linezolid and tedizolid in experimental necrotizing infection. J Glob Antimicrob Resist 2020; 22:601.
  53. Cortés-Penfield N, Ryder JH. Should Linezolid Replace Clindamycin as the Adjunctive Antimicrobial of Choice in Group A Streptococcal Necrotizing Soft Tissue Infection and Toxic Shock Syndrome? A Focused Debate. Clin Infect Dis 2023; 76:346.
  54. Dorazio J, Chiappelli AL, Shields RK, et al. Clindamycin Plus Vancomycin Versus Linezolid for Treatment of Necrotizing Soft Tissue Infection. Open Forum Infect Dis 2023; 10:ofad258.
  55. Prevention of Invasive Group A Streptococcal Infections Workshop Participants. Prevention of invasive group A streptococcal disease among household contacts of case patients and among postpartum and postsurgical patients: recommendations from the Centers for Disease Control and Prevention. Clin Infect Dis 2002; 35:950.
  56. Gunnarsson RK, Holm SE, Söderström M. The prevalence of beta-haemolytic streptococci in throat specimens from healthy children and adults. Implications for the clinical value of throat cultures. Scand J Prim Health Care 1997; 15:149.
  57. Heidari-Bateni G, Brar AK, Hall M, et al. Maternal β-hemolytic streptococcal pharyngeal exposure and colonization in pregnancy. Infect Dis Obstet Gynecol 2014; 2014:639141.
  58. Steer JA, Lamagni T, Healy B, et al. Guidelines for prevention and control of group A streptococcal infection in acute healthcare and maternity settings in the UK. J Infect 2012; 64:1.
  59. Stefonek KR, Maerz LL, Nielsen MP, et al. Group A streptococcal puerperal sepsis preceded by positive surveillance cultures. Obstet Gynecol 2001; 98:846.
  60. Siegel JD, Rhinehart E, Jackson M, et al. 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings. Am J Infect Control 2007; 35:S65.
Topic 97358 Version 27.0

References

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