Joey, a previously healthy and fully vaccinated toddler, initially presented to the emergency department with 3 days of fever, cough, and vomiting. In the emergency department, he had a fever and was experiencing tachycardia and tachypnea but maintained normal levels of oxygen saturation. He was diagnosed with a viral illness and discharged home.The next day, his mother brought him to urgent care due to worsening fast breathing, poor oral intake, and increased sleepiness. He was now experiencing hypoxemia, as well as marked tachycardia and tachypnea; clinicians also noted an erythematous rash. Emergency medical services transported him to a local emergency department, and he was subsequently transferred to a tertiary children’s hospital for escalation of care.In the pediatric intensive care unit (PICU), Joey received aggressive fluid resuscitation and antibiotics and was started on vasoactive support. Despite these interventions, he developed hypotension, required emergent intubation, and experienced a cardiac arrest with rapid return of spontaneous circulation. Ultimately, he required multiple, high-dose, vasoactive infusions and subsequent venoarterial extracorporeal membrane oxygenation (ECMO) cannulation. Although his only positive test was for rhinovirus/enterovirus, his clinical course was consistent with fulminant streptococcal toxic shock syndrome. Despite maximal therapies, Joey did not survive his illness.Teaching Point. This case highlights how quickly a previously healthy child can deteriorate with septic shock, the challenges of early recognition, and the importance of rapid escalation of care. Despite early assessments, Joey experienced a cardiac arrest, a critical event that significantly elevates the risk of mortality.Invasive group A Streptococcus (iGAS) represents a significant and growing public health concern, particularly among the pediatric population. It is caused by Streptococcus pyogenes, a common gram-positive bacterium, with effects seen along a continuum from minor to severe. Minor illness occurs with colonization of the skin—causing impetigo, pyoderma, and cellulitis—and of the throat, leading to pharyngitis or tonsillitis.1,2 Some children may develop poststreptococcal infections that affect the heart and kidneys, which can have long-term effects. However, if the bacterium becomes invasive to blood, lungs, or tissue, it can lead to serious life-threatening infections commonly termed iGAS disease. Severe infection can result in necrotizing fasciitis, sepsis, or the development of streptococcal toxic shock syndrome (STSS), which can be fatal.1–3In recent years, there has been an increase in cases of iGAS in the United States and around the world, in countries such as Australia,4 Canada,5 and Spain.6 According to the Centers for Disease Control and Prevention (CDC)—which has tracked iGAS infections in the United States since 1995—rates were relatively stable at 3.2 to 4.3 cases per 100 000 population until 2014, when cases started to increase.3 The most recent surveillance data, from 2013 to 2022, showed a marked increase in cases, ranging from 3.6 to 8.2 cases per 100 000 population for all ages. However, the incidence for children 18 years or younger was 0.6 to 2.1 cases per 100 000 population, which was actually a 73% decrease during the COVID-19 pandemic between 2019 and 2021.3 This decrease in rates during the COVID-19 pandemic may be attributed to masking procedures, school closures, and social distancing.7 However, since 2022, there has been an increase in iGAS cases, most likely due to the observed surge in respiratory viral infections leading to subsequent bacterial infections.8 This increase in association with respiratory viral infections suggests that vaccinations for influenza and varicella may decrease the incidence of iGAS pneumonia.9Because of the increase in iGAS infections over the past several years, clinicians are now more likely to care for children with this infection in the PICU. It is imperative that staff nurses and advanced practice providers understand the clinical manifestations, diagnostic evaluations, and management of severe, life-threatening iGAS sepsis that is associated with STSS.Streptococcal toxic shock syndrome can develop from 2 organisms, Staphylococcus aureus and Streptococcus pyogenes. These organisms produce a protein toxin that can cause extensive activation of the child’s cellular immune system. They act as superantigens that activate T cells. While typical antigens activate less than 1% of host T cells, these superantigens activate about 20% to 30%, leading to a massive production of inflammatory cytokines that manifest as rash, fever, hypotension, and shock.10,11Clinical manifestations of STSS begin with flu-like symptoms such as chills, fever, lethargy, myalgia, sore throat, abdominal pain, nausea, vomiting, and rash, which progress to hypotension, tachycardia, tachypnea, and signs of organ failure.10,12 Involved organ systems include the gastrointestinal, musculoskeletal, renal, hepatic, pulmonary, and hematologic.The diagnostic criteria for STSS is well described by the CDC and include both clinical and laboratory criteria, which are outlined in the Table. The clinical criteria include hypotension and multisystem involvement of 2 or more body systems (renal, hematologic, hepatic, pulmonary, skin, musculoskeletal).10–13 Laboratory criteria involve the isolation of group A Streptococcus, and cases are described as either probable or confirmed.The development of shock occurs when there is inadequate delivery of oxygen to the tissues to meet metabolic demands due to low cardiac output, inadequate oxygen-carrying capacity, and impaired ability to use nutrients. Injury occurs to the endothelium of the blood vessel cell wall lining, leading to capillary leak and activation of the coagulation cascade. The new pediatric sepsis and septic shock criteria, the Phoenix Sepsis Score, was designed to improve the identification and the definition of pediatric sepsis and septic shock, which may improve earlier recognition, guide future data collection, and support the development of future clinical tools.14 This scoring tool changes the focus from the use of severe inflammatory response, which is very broad, to organ dysfunction. The terms early sepsis and severe sepsis have been updated to sepsis and septic shock. The new criteria allow for improved identification of life-threatening septic shock across differently resourced settings, making the criteria globally applicable. The Phoenix Sepsis Score evaluates 4 body systems and assigns points for respiratory, cardiovascular, coagulation, and neurologic involvement.15 Sepsis is defined as a total score of 2 or more, along with a suspected infection. Septic shock is defined as sepsis with a score of 1 or more within the cardiovascular system specifically. The respiratory system scores are based on the child’s partial pressure of oxygen (PaO2):fraction of inspired oxygen (Fio2; P/F ratio) or oxygen saturation (SpO2): Fio2 (S/F ratio) and any respiratory support being provided. The cardiovascular system evaluates the number of vasoactive medications, lactate levels, and mean arterial pressure by age. Coagulation considers platelet levels, international normalized ratio, D-dimer, and fibrinogen levels. Finally, scores in the neurologic section are based on the Glasgow Coma Scale score as well as pupil reactivity.15Treatment for STSS is consistent with the Surviving Sepsis Campaign. Initial therapy should include supplemental oxygen and respiratory support, obtaining intravenous access, and collecting blood cultures, along with fluid resuscitation and antibiotic coverage within the first hour of identification of sepsis.10,16 In children with suspected organ dysfunction but without shock, antibiotics should be given within the first 3 hours of recognition. Broad-spectrum empiric coverage should be initiated until sensitivities are available to appropriately narrow coverage.10,16 Empiric treatment for adequate gram-positive coverage includes a third-generation cephalosporin, such as ceftriaxone, due to their bactericidal properties of binding to the cell wall causing cell death.10 Clindamycin was originally recommended for use as an adjunct therapy in treating iGAS, as it stops toxin production by inhibiting bacterial protein synthesis and is associated with increased survival. It specifically binds to the 50S ribosomal subunits, preventing peptide formation.17 However, in more recent years there has been an increase in group A Streptococcus resistance and an increase in Clostridioides difficile (formerly Clostridium difficile) infections associated with the use of clindamycin. Linezolid has become more popular as it has a similar mechanism of inhibiting bacterial protein synthesis at the S23 ribosomal protein of the 50S subunit and it provides broad-spectrum activity that includes methicillin-resistant Staphylococcus aureus.18 However, studies in US adults have shown that linezolid is noninferior to clindamycin despite global increase in clindamycin resistance.18During the initial recognition of septic shock, fluid resuscitation using a balance buffered crystalloid intravenous solution up to 40 to 60 mL/kg total fluids can be administered within the first hour. In the event of fluid refractory shock, continuous vasoactive medications such as epinephrine, norepinephrine, and/or vasopressin should be promptly initiated.10,16 Continuous hemodynamic monitoring and respiratory support such as mechanical ventilation should be included in the ongoing continuous management of septic shock, if available. In addition, the use of hydrocortisone in refractory shock can be considered.16 Extracorporeal membrane oxygenation should be considered in cases of refractory shock or persistent oxygenation or ventilation failure.Mary, a previously healthy toddler, was first seen at urgent care for vomiting, fever, and irritability. She was diagnosed with strep throat and otitis media, treated with antibiotics, and discharged. At home, however, her vomiting persisted, and she was unable to tolerate oral intake.Her parents brought her to the emergency department the next day, and she was triaged quickly as critically ill. She had a temperature of 40.2 °C, was experiencing profound tachycardia with hypotension, and had significant laboratory result abnormalities, including an elevated lactate level and severe leukopenia. Her Phoenix Sepsis score included 1 point for cardiovascular dysfunction, 1 point for vasoactive requirement indicating septic shock, and another point for respiratory failure requiring ventilatory support. She was intubated and transferred immediately to the PICU.In the PICU, Mary required continued aggressive fluid resuscitation and significant vasoactive support. Despite these measures, she remained in refractory shock and received cannulation to VA-ECMO. Soon after cannulation, she underwent an atrial septostomy to reduce left ventricular distension and improve cardiac function.Her treatment course included broad-spectrum antibiotics and steroids. Blood cultures confirmed group A Streptococcus, and her antibiotic regimen was adjusted per infectious disease recommendations. After 3 days of ECMO therapy, Mary was successfully decannulated, later extubated, and discharged home with a good neurological outcome.This case illustrates how group A streptococcal sepsis can progress rapidly to life-threatening invasive group A streptococcal septic shock, requiring advanced therapies such as ECMO and atrial septostomy as well as highlighting the increased potential for survival if a cardiac arrest is avoided.We included these case studies to assist clinicians in identifying the significance of iGAS infections in the pediatric population. Early recognition of sepsis and septic shock is vital for establishing an early diagnosis and prompt interventions. Both cases illustrate that initial examinations did not reveal early signs of sepsis, such as persistent fever, tachycardia, or hypotension. Rapid clinical deteriorations including symptoms that mimicked common viral illnesses were initially present in both cases, and both children quickly progressed to septic shock, requiring admission to a children’s hospital for high-level care. These examples highlight the unpredictable and fulminant nature of STSS and, in the context of increased cases, the importance of early consideration for transfer to a facility with ECMO capabilities. Despite aggressive fluid resuscitation and vasoactive support, both patients required ECMO due to the nature of their refractory shock. Optimal outcomes were achieved for Mary through the collaboration of a multidisciplinary team that included emergency medicine, pediatric critical care, infectious disease, cardiology, and ECMO team members. However, Joey’s case highlights the even higher mortality associated with iGAS if a child with septic shock suffers a cardiac arrest. The Phoenix Sepsis Score serves to identify life-threatening organ dysfunction in children with sepsis or septic shock, which can assist hospitals without ECMO services to consider transfer. An early screening tool to identify pediatric sepsis and septic shock is still desperately needed. Continued reviews and research using the globally applicable Phoenix Sepsis Score criteria may provide the data needed to guide future evidence-based guidelines, as well as the creation of an early screening tool with the goal to prevent children from dying of sepsis.
Maymi et al. (Fri,) studied this question.