Twins are born at 37-5/7 weeks gestation to a 41-year-old G4P2 woman who had unremarkable serology results. The delivery is via cesarean section because of a nonreassuring fetal heart rate. Twin B appears to be acrocyanotic and initially requires positive-pressure ventilation for 30 seconds before being able to maintain her oxygen saturation on her own. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She also appears to be “jittery,” and her screening glucose concentration is 24 mg/dL (1.3 mmol/L). She consumes 20 mL of infant formula and a 10% dextrose (D10) infusion is begun at a rate of 60 mL/kg per day. Three hours after birth, a follow-up glucose evaluation measures 30 mg/dL (1.7 mmol/L), prompting administration of a 4-mL/kg bolus of D10 over 20 minutes and increase of the maintenance infusion rate to 100 mL/kg per day. Six hours after birth, glucose measures 80 mg/dL (4.4 mmol/L), and the infusion rate is decreased to 60 mL/kg per day. She is transferred to a hospital that has a neonatal intensive care unit (NICU) for close monitoring. On transfer, the oxygen saturation dips into the upper 80s/lower 90s, and nasal cannula administration of oxygen is initiated. Furthermore, during transfer (8 to 9 hours after birth), the blood glucose value is 44 mg/dL (2.4 mmol/l), so the D10 infusion rate is increased back to 100 mL/kg per day. On arrival at the second hospital, her oxygen saturation is about 85% and glucose is 50 mg/dL (2.8 mmol/L). In the NICU, she receives noninvasive respiratory support as well as 15% dextrose (D15) at a rate of 70 mL/kg per day. Twin A remains stable and continues to receive routine newborn care in the newborn nursery of the first hospital.Two days after birth, twin B continues to have glucose measurements of slightly more than 40 mg/dL (2.2 mmol/L) while receiving D15 infusions. She also continues to have oxygen saturation at about 85% when not receiving oxygen, thus requiring ongoing nasal cannula support. Routine blood testing reveals a progressively rising hematocrit (64% [0.64] via venous sample). The persistent hypoglycemia and increased oxygen requirement are believed to be due to polycythemia, based on the steadily rising hematocrit. In anticipation of a continued increase in her hematocrit, she receives a prophylactic partial exchange transfusion that she tolerates well. She also continues to require aggressive glucose replacement.On the fourth day after birth, glucose appears to be well maintained in the range of 60 to 70 mg/dL (3.3 to 3.9 mmol/L), and she is slowly weaned off of the glucose supplementation. On the sixth day after birth, she can maintain her oxygenation without the nasal canula, which is discontinued.Seven days after birth, she has multiple episodes of back arching, lower extremity shaking, and lip smacking. Neurologic examination reveals grossly intact cranial nerves, symmetric tone/bulk/strength in all extremities, brisk deep tendon reflexes in the lower extremities, and ankle clonus bilaterally with downgoing toes. While assessing the neonatal reflexes, the clinician appreciates a mildly weakened suck/latch, weak palmer grasp, and symmetric Moro reflex.Twins are born in October at 34 weeks gestational age to a 37-year-old G3 woman whose antenatal screening results are normal and group B Streptococcus status is unknown. The healthy woman had her dichorionic, diamniotic pregnancy diagnosed at 10 weeks by ultrasonography. All antenatal scans were normal. The maternal medical history is unremarkable. The woman presents on her due date at a regional hospital feeling “unwell.” She has acute abdominal pain, is not having contractions, and is afebrile. An emergency cesarean section is performed because Twin A's heart rate is 200 beats/min.Apgar scores for both twins are 9 at 1 minute and 9 at 5 minutes. The infants have appropriate growth for gestational age. No resuscitation is required, and they are transferred to the nursery for a partial sepsis evaluation that includes a blood culture and treatment with ampicillin and gentamicin for 48 hours. Initial complete blood count (CBC) shows normal results, and they start feedings 2 days after birth.On Day 5, Twin B develops a maculopapular rash, feeding intolerance, apnea, and lethargy. Twin A experiences similar symptoms 1 day later. Both infants are transferred to a tertiary NICU, where blood cultures are repeated, lumbar puncture is performed, and cefazolin and gentamicin therapy is initiated. Chest radiographs are unremarkable. CBC and lumbar puncture reveal the following: The cerebrospinal fluid (CSF) analysis shows: Physical examination of both infants shows hypotonia, lethargy, a weak cry, and poor sucking response. They appear jaundiced and have occasional apnea requiring stimulation. There is no audible murmur, they are normotensive, capillary refill time is 3 seconds, liver is palpable at the costal margin, chest sounds are clear, and both infants require low-flow oxygen 20 to 40 mL/min to maintain normal oxygen saturation (>95%). Neurologically, twin B has unequal and sluggish pupils with nystagmus but no clinical seizure activity. Of note, twin B is always more active than twin A.Due to the abnormal CSF results, CSF reverse-transcriptase polymerase chain reaction (PCR) and nasopharyngeal swabs and stools are sent for viral detection. An infectious disease consultation is requested. The infants are placed in contact isolation and the antibiotics are changed to cefotaxime and acyclovir. Ampicillin is added for Listeria coverage. Both infants receive platelet transfusions, and further investigations are ordered, including a coagulation screen and liver function tests (LFTs). Cranial ultrasonography is completed on both infants and shows a small left intraventricular hemorrhage (IVH) for Twin B. Ophthalmologic examinations reveal no chorioretinitis. The infectious disease team suggests continuing acyclovir pending the PCR results and recommends repeating the lumbar puncture in 4 to 6 days because herpes simplex virus PCR can be falsely negative early in the disease course. They agree that the CSF results point to bacterial infection, but other differential diagnoses should be considered. If viral and bacterial testing results are negative, they propose a 14-day course of ampicillin and 21 days of cefotaxime.In total, the twins require two to three ongoing platelet transfusions for thrombocytopenia and the coagulation profile is normal. The LFTs show: Twin A develops cholestasis and is treated with ursodiol, with follow-up evaluation by the gastroenterology service.Head magnetic resonance imaging (MRI) on twin B 10 days after birth reveals a left subependymal germinal matrix hemorrhage extending into the lateral ventricle and mild ventriculomegaly (Fig. 1), a small IVH in the occipital horns of the lateral ventricles bilaterally, and T1 hyperintensities bilaterally in the peritrigonal locations and in the region of the frontal lobes (Fig. 2). The final diagnosis is obtained on day 10. Antibiotics are discontinued and the infants are restarted on feedings. They are weaned from their respiratory support and discharged from the hospital on day 11.A 22-day-old term newborn male, who was born via normal spontaneous vaginal delivery to a 29-year-old G3P2A0 healthy mother and whose birthweight was 3,700 g, presents to the emergency department because of rash, poor feeding, diarrhea, and irritability. Antenatal serologic testing was negative for syphilis and hepatitis B surface antigen and immune to rubella and toxoplasmosis. Group B Streptococcus screening results are unknown. There were no complications during delivery, and Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. The infant has been breastfeeding since birth but was stopped 5 days ago because the mother developed bilateral mastitis and she was started on amoxicillin-clavulanic acid. The infant has been fed with regular formula since that time.The infant's illness started 3 days ago with frequent (>7 times) watery nonbloody stools, progressive poor feeding, fussiness, and diaper rash. The mother, without medical advice, gave her baby a herbal supplement (anise) 120 mL three times daily, and she decided to prepare the formula by adding 80 mL water in place of 60 mL for each scoop of milk powder (diluted formula). She believed that these measures would improve her baby's appetite and compensate for the water loss. Today the baby became lethargic and very irritable, and his diaper rash extended to cover the lower limbs and the abdomen. The mother applied zinc oxide cream to the rash many times. On admission, the infant exhibits right hemibody tonic-clonic movements with uprolling of his eyes, and the admitting physician administers diazepam twice to stop the convulsions.On physical examination, the ill-looking, lethargic infant has a respiratory rate of 65 breaths/min, heart rate of 170 beats/min, temperature of 36.5°C, blood pressure of 50/30 mm Hg, and transcutaneous oxygen saturation of 95% on room air. He has normal fontanelles, cracked lips, strawberry tongue, and dry mouth. He has normal fast heart sounds, no audible murmur, adequate air entry bilaterally, mild subcostal retractions, and a soft and moderately distended abdomen with no organomegaly. He has poor suck, weak grasp, and incomplete Moro reflex. He exhibits very red confluent patches over both lower limbs and the abdomen, with clearly demarcated borders, painful and edematous skin in the affected areas, and moderate scrotal edema (Fig. 3). The rash spares the feet. Vesicles, bullae, purpura, and crusts are not present. Yellowish secretions are noted over the umbilicus, although the cord stump fell off 10 days before presentation.The clinician administers an urgent bolus of normal saline and supplemental oxygen. A complete sepsis evaluation is undertaken, including CSF analysis and culture, stool analysis and culture, and umbilical swab culture. In addition, intravenous cefotaxime, vancomycin, and acyclovir are administered with dopamine 10 μg/kg per minute and phenobarbital.Blood tests that include electrolytes, blood glucose, creatinine, blood urea nitrogen, calcium, phosphorus, magnesium, and LFTs are ordered. Laboratory results yield a WBC count of 2.9×103/μL (2.9×109/L) with 45% segmented forms and 47% lymphocytes, C-reactive protein of 180 mg/L (18 mg/dL) (normal, <5 mg/L [<0.5 mg/dL]), and sodium of 109 mEq/L (109 mmol/L). The other laboratory results are within normal ranges, including platelet count, prothrombin time (PT), and partial thromboplastin time (PTT). An intravenous bolus of hypertonic saline 3% is administered to correct the symptomatic hyponatremia.The infant is admitted to the NICU, where the rash worsens dramatically and characteristically over the next hours. One test helps to determine the diagnosis.This patient's evaluation included normal lumbar puncture results, which ruled out meningitis, and normal findings on metabolic evaluation. Electroencephalography revealed clinical and electrographic seizures, prompting administration of a loading dose of phenobarbital. MRI of the brain showed bilateral watershed infarctions (Figs. 4, 5, and 6).Although the cause of this patient's infarction is not certain, multiple factors could have contributed. The infarction may have been caused, in part, by polycythemia, as evidenced by a hematocrit of 64% (0.64). Polycythemia causes hyperviscosity in the blood and can compromise cerebral perfusion. Various neurologic sequelae have been documented in infants who have polycythemia and hyperviscosity, including jitteriness, lethargy, apnea, seizures, and ischemia. Treatment of symptomatic infants with partial exchange transfusion may aid in reducing potential neurologic complications. Studies have shown that cardiac output and cerebral blood flow velocity in affected neonates increase more than 30% during partial exchange transfusion. Thus, early intervention with partial exchange transfusion may be beneficial in a symptomatic neonate who has an elevated hematocrit.Although a hematocrit of 64% (0.64) is not critically high, it may have been an additional factor that created a cumulative effect with the hyperviscosity. The patient had documented profound hypoglycemia on multiple occasions, and the immature brain is vulnerable to hypoxemic injury in the setting of concomitant hypoglycemia. Diminished glucose reserves in the hypoglycemic brain are unable to match the energy demand under ischemic (anaerobic) conditions. Therefore, in a setting of decreased cerebral perfusion, as in cases of polycythemia, the potential for ischemia is notably increased. Various authors have documented that blood glucose should be maintained at greater than 60 mg/dL (3.3 mmol/L). According to Volpe's Neurology of the Newborn, glucose supplementation should be initiated to maintain a blood glucose value between approximately 75 and 100 mg/dL (4.2 and 5.6 mmol/L).Other potential causes for this infant's strokes were also considered. Whenever a patient has multiple infarctions in different vascular territories, the possibility of an embolic event should be considered. Polycythemia has been shown to cause arterial and venous thrombosis. Echocardiography should always be obtained to rule out structural abnormalities, such as a patent foramen ovale, which could permit an embolus to enter the arterial system, most commonly originating from involuting fetal vessels.This patient could have suffered her stroke pre/perinatally. The history of undergoing a cesarean section due to a nonreassuring fetal heart rate raises the possibility that the heart rate may have slowed to the extent where cerebral perfusion had become compromised, in turn causing a decrease in cerebral perfusion that ultimately led to ischemic strokes.Neonatal seizures are the most common clinical finding to trigger an investigation in cases of neonatal stroke. In this case, the episodes of back arching, lower extremity shaking, and lip smacking prompted a full evaluation. Frequently, neonates who have suffered a stroke may not have any signs indicating that an ischemic event has taken place. In such patients, stroke is only recognized retrospectively when children present with emerging hemiparesis, seizures, or even subtle findings such as tight heel cords.The neonatal brain is very sensitive to alterations in cerebral blood flow. Polycythemia is a known risk factor for cerebral ischemia and can be treated with partial exchange transfusion. Concomitant hypoglycemia can magnify the potential for stroke. Both of these issues can easily be investigated with simple blood tests. Echocardiography should always be obtained to search for structural abnormalities. Clinicians should suspect any potential culprit that could cause an additive effect for neonatal ischemic injury. Early identification and intervention are key.The clinical differentiation of infectious diseases in neonates is often difficult. It is important to consider a broad differential diagnosis in infants presenting with a sepsislike illness. This includes congenital heart disease and acquired viral myocarditis, disseminated bacterial infection with associated meningitis, and a broad spectrum of congenital viral illnesses. However, an astute clinician can attempt to narrow the differential diagnosis by examining details of the maternal history in conjunction with the infant's clinical presentation.In this case, the mother presented with intense abdominal pain during the month of October. On further discussion, she commented that the pain was similar in intensity to an appendicitis she had previously experienced. When asked about other illnesses within the family, she informed the medical team that her other children were unwell with febrile illnesses about 3 days before her delivery. The combination of the infant's symptoms, the seasonality in October, the presenting maternal abdominal pain, and the other sick contacts at home led clinicians to also consider enterovirus (EV) disease apart from generalized herpes infection.EV illness has a worldwide distribution, and infections in temperate climates occur primarily in summer and fall. Seasonality is less pronounced in the neonatal population because hospital personnel can introduce nosocomial infection. Although several epidemics with EVs in newborn nurseries have been studied, the most consistent source of original infection is maternal-child transmission.The clinical symptoms of EV infection in neonates range from minor illness to severe systemic illness and death. The onset of illness is generally characterized by fever, poor feeding, irritability, and lethargy. Approximately 50% of patients can develop a nonspecific rash and respiratory symptoms, including nasal discharge, cough, apnea, tachypnea, recessions, grunting, and nasal flaring. Fifty percent may also develop hepatitis and jaundice that may progress to acute hepatic necrosis. (1) About 20% develop gastrointestinal symptoms that can include vomiting, abdominal distension, and diarrhea. A smaller percentage may also develop myocarditis that is associated with arrhythmias, cardiomegaly, hypotension, congestive heart failure, and ischemia as well as neurologic manifestations such as meningitis or encephalitis. (2)Case studies consistently document that mothers may experience acute-onset fever and abdominal pain in the presence of an EV infection. (3) The abdominal pain is often so intense that it is compared to appendicitis or even abruptio placentae and has indiscriminately led to appendectomy with a pathologically normal appendix.Because infection in neonates is usually generalized, samples should be collected from the nose, throat, stool, blood, urine, and CSF. PCR rapidly identifies CSF EVs with better sensitivity but equal specificity to culture. However, the specific EV cannot be determined, necessitating concurrent standard culture. (4) PCR affects treatment because early EV identification translates into reduced length of hospital stay and decreased use of antibiotics and extensive diagnostic investigation. In this case, once the PCR in the CSF was determined to be EV-positive for both twins, antibiotics were discontinued and the infants were discharged from the hospital approximately 10 days earlier than if they had received the conventional 21-day neonatal course of antibiotics for meningitis of undetermined cause. Coxsackievirus B1 was subsequently cultured from the rest of the specimens.Generally, the CSF findings in neonatal EV infections are similar to those of bacterial disease. Chiou and associates (5) noted that the changes typically seen with a viral meningitis are mild pleocytosis with a WBC count less than 500/mm3 and a lymphocytic predominance. The protein value ranges from normal to slightly elevated, seldom more than two to three times the normal value. The CSF glucose concentration is two thirds of that in the serum. Twins A and B presented with 160 and 800/mm3 WBC in the CSF and 65% and 95% neutrophils, respectively. The findings of a pleocytosis of more than 500/mm3 WBCs in 60% of the cases that were EV-positive are supported in the literature. A neutrophilic predominance was noted in 62.5% of the cases, and hypoglycorrhachia occurred in 44%. (5)MRI findings similar to twin B were reported by Verboon-Maciolek and associates, (2) who concur that the prediction of neurodevelopment in neonates who have EV neurologic involvement is difficult. In the case series, all infants had mild-to-severe white matter disease. Although the site and extent of periventricular leukomalacia are usually important for prognosis, the three reported infants who had abnormal neurodevelopment were all born preterm, which may suggest a difference in the vulnerability of the white matter during maturation. (2) One infant who had similar bilateral, asymmetric punctate white matter lesions as Twin B developed cerebral palsy and epilepsy at 6 years. Currently, both twins in this case are 15 months old and developmentally normal.Immune globulin intravenous has been used for serious EV infections, but its role in acute illness remains unproven. (4) Pleconaril, available through compassionate release, has shown promise in the treatment of EV meningitis. A phase 2 double-blind, placebo-controlled trial of pleconaril for the treatment of neonatal EV sepsis is currently underway, but recruitment over 9 years has been slow.The overall prognosis for EV disease depends on the causative serotype and clinical manifestations. Studies examining risk factors associated with severe EV infection conclude that the following factors may increase the risk of life-threatening illness: earlier age of presentation, maternal history of illness, prematurity, multisystemic disease, hepatic necrosis, positive serum viral culture, and higher WBC and lower hemoglobin values. (6) Also, infections with coxsackievirus B1 through B5 and echovirus 11 have an ominous prognosis. (1)(3) Information related to long-term outcomes is limited. A minority of infants can experience residual hepatic dysfunction, ventricular dysfunction, or rhythm abnormalities or develop dilated cardiomyopathy.Differences in neurologic prognosis exist for infants who have aseptic meningitis versus meningoencephalitis. Encephalitis due to EVs may cause more devastating long-term sequelae, and several reports describe persistent neurologic deficits, including spasticity, seizure disorders, and learning difficulties. (7)Even while attempting to narrow the differential diagnosis for viral and bacterial sepsis, it is important to treat infants with the necessary antibiotics and antiviral agents to ensure broad-spectrum coverage until cultures prove otherwise. EV infections are not uncommon and have a wide spectrum of clinical manifestations with significant morbidity and mortality. The seasonality may be less pronounced with neonatal infections. More severe disease is associated with an earlier age of onset of illness, a positive maternal history, prematurity, and neonatal multiorgan involvement. The overall prognosis depends on the causative serotype and clinical manifestations.A few hours after admission to the NICU, the baby became hemodynamically stable on supplemental oxygen and intravenous perfusion. Purpuric skin lesions were evident over the legs, with two large bullae over the lateral aspects of both legs and black necrotic lesions in the base of bullae and around them (Fig. 7). These lesions are compatible with necrotizing fasciitis. The rash extended to involve the thorax up to the nipple line. Three days after admission, extensive skin desquamation occurred over the affected areas (Fig. 8) as well as the hands and feet.At this time, blood and umbilical swab cultures grew group A Streptococcus (GAS) sensitive to penicillin, cefotaxime, and vancomycin. The other cultures, including CSF, were negative. Clinically, the baby was stable but remained irritable. Laboratory tests obtained on the third day of hospitalization revealed: WBC count, 18×103/μL (18×109/L) with 80% segmented forms and 17% lymphocytes; platelet count, 7×103/μL (7×109/L); PT, 20 sec (normal, 11.9 sec); and PTT, 84 sec (normal, 30.4 sec). Vitamin K, platelets, and fresh frozen plasma transfusion were administered twice as part of treatment for disseminated intravascular coagulation (DIC). Blood tests revealed albumin within normal range, high D-dimer, and low fibrinogen.The findings of GAS in blood culture with hypotension, characteristic rash, and DIC confirmed the diagnosis of streptococcal toxic shock syndrome (STSS), even though the findings were serial and not simultaneous. Over the next 2 days, platelet counts, PT, and PTT normalized.Multiple skin nodules appeared scattered throughout the desquamated skin at day 8 of hospitalization (Fig. 9). They were drained surgically and yielded pus that grew S epidermidis sensitive to vancomycin. The necrotic lesions over the legs were debrided, and surgical findings confirmed the presence of necrotizing fasciitis. Despite appropriate therapy, new diffuse abscesses continued to appear but always were limited to the areas previously affected by the initial cellulitis. To rule out immunodeficiency, a complete immunologic profile that included immune globulin dose and peripheral blood flow cytometry was performed and yielded normal results. Skin biopsy also demonstrated no abnormalities.The baby was discharged from the hospital after 7 weeks of treatment, and no new abscesses appeared over the last week of hospitalization. Three weeks after discharge, the 3- month-old baby is healthy, thriving, and without new skin lesions, although the scars of old abscesses and necrotizing fasciitis are obvious (Fig. 10). The abscesses most likely were due to superinfection after breakdown of normal skin barriers due to the severe cellulitis and desquamation. The parents were encouraged to continue close follow-up monitoring and to repeat the dose of immunoglobulin E after 6 months of age to rule out hyper-IgE syndrome (Job syndrome), a known cause of recurrent skin abscesses.GAS causes the broadest spectrum of clinical syndromes of any bacteria, varying from mild infections such as mild skin infection and omphalitis to invasive life-threatening infections such as STSS and meningitis. The incidence of invasive GAS infection is highest in infants and older people. In neonates, infection can result from intrapartum transmission, especially in early-onset infection up to 5 days of age, or from contact transmission in both early- and late-onset types, with the primary focus of infection being omphalitis and cellulitis. The source of infection generally is not identified in late-onset infection.GAS had been recognized as a major causative agent of neonatal sepsis before the antibiotic era and subsequently almost disappeared. (1) However, an increase in the incidence of invasive infections caused by GAS has been noted since 1980. After an extensive review of the literature published since 1966 using the entire database available online, we found only 42 cases of invasive neonatal GAS, including two nursery outbreaks, and almost all cases were in the past 20 years. (1)(2)(3)(4)M protein, encoded by the emm gene, is an important virulence factor in the pathogenesis of GAS infections. Emm types 1 and 3 were reported to be more frequently encountered in invasive infections both in neonates and adults. (3)(5)Data on GAS prophylaxis for either neonatal or maternal disease prevention are limited. Results of population-based surveillance for postpartum GAS disease suggested that maternal postpartum disease might be preventable. (3) Prenatal GAS screening is more controversial because of the low rate of vaginal-rectal carriage in late pregnancy. More studies are needed to assess the importance of maternal GAS screening during pregnancy and prophylactic perinatal treatment.The major clinical expressions of early-onset invasive disease are pneumonia or empyema, soft-tissue infection, and STSS. Common characteristics of early-onset disease include respiratory distress, rapid deterioration, and a high mortality rate, regardless of the focus of infection. Nearly 25% of neonates had an exanthema on presentation. A lack of fever is common. Approximately one third of neonates in the early-onset group were delivered preterm, which may, in part, have been the result of GAS-associated chorioamnionitis. The fulminant nature and concurrent maternal factors indicate that early-onset GAS disease may be a manifestation of hematogenous dissemination or a toxin-mediated syndrome with an in utero onset.The major clinical expression of late-onset disease is soft-tissue infections and meningitis; pneumonia and STSS are less common. Rash is also seen in a significant percentage of patients. In contrast to early-onset infection, fever is a common presenting sign in late-onset sepsis.STSS is often accompanied by focal infection such as cellulitis or necrotizing fasciitis. STSS plus necrotizing fasciitis are associated with a high mortality rate. Defining characteristics of classic STSS include hypotension or shock plus at least two of the following six criteria occurring concurrently or serially: scarlatiniform rash, hepatic abnormalities, renal abnormalities, DIC, respiratory distress syndrome, or extensive soft-tissue necrosis (necrotizing fasciitis). These disorders must occur in the absence of other explanations or other positive bacterial cultures.GAS omphalitis is a potentially invasive infection if not adequately treated at early stages. The umbilical stump is colonized while the infant is in the nursery. Similar to staphylococcal infections, clinical manifestations may be few or absent while the infant is still in the nursery. Most often, a colonized infant develops chronic, oozing omphalitis days later. Colonization of the umbilical cord by GAS may persist for up to 8 weeks after birth.Leukocytosis is common in both early- and late-onset infections, but leukopenia is almost exclusively seen in the early-onset type of infection, unlike in this case. C-reactive protein is high in most cases. In suspected invasive GAS infection, complete sepsis evaluation must be performed, including cultures of blood, CSF, and any suspected focal site. In necrotizing fasciitis, imaging studies often delay, rather than facilitate, the diagnosis. Clinical suspicion of necrotizing fasciitis should prompt surgical inspection of the deep tissues, with Gram stain and culture of surgical specimens.GAS is sensitive to a variety of antibiotics administered either alone or in combination. Penicillin is the most commonly prescribed antibiotic for GAS invasive infection in children. Combination treatment with a beta-lactam agent and clindamycin may improve the outcome, especially in STSS. (6) Other antibiotics used include aminoglycosides, second- and third-generation cephalosporins, and vancomycin. Accessible sites of infection should be aggressively drained and irrigated as soon as possible. If necrotizing fasciitis is suspected, immediate surgical exploration or biopsy is crucial to identify deep soft-tissue infection that should be debrided immediately. To decrease the risk of superinfection, skin care of the affected site with local antiseptic is important, especially after desquamation. In addition, all supportive measures should be considered, including fluids, inotropic agents, and blood products.The increasing incidence of invasive GAS in all age groups, including neonates, should prompt clinicians to consider GAS as an offending agent in neonatal sepsis, especially in the presence of any maternal perinatal GAS infection and if the newborn presents with initial skin lesions or omphalitis. Prompt and appropriate treatment may reduce complications and mortality. Omphalitis and cellulitis must always be treated early and appropriately. To decrease the risk of superinfection, skin care of the affected site with local antiseptic is crucial, especially after desquamation.