A Fatal Case of Streptococcal Toxic Shock Syndrome Caused By Genotype Emm1 In The Third Trimester of Pregnancy, China

Background: Group A streptococcal (GAS) toxic shock syndrome (TSS) is a rare invasive disease, causing a high risk of maternal and fetal mortality during pregnancy. We report a fatal case of a female caused by GAS-TSS in the third trimester of pregnancy in Guangzhou, China. Case presentation: The patient is a 33-year-old female who presented at 37 weeks’ gestation with a history of three hours fever. The patient underwent an early onset and rapid progression with dramatic clinical picture and laboratory characters within 24 hours. The neonate survived after an aggressive anti-infection treatment.The GAS strains were isolated from two bottles of blood cultures and airway secretion culture, which confirmed as Streptococcus pyogenes associated with genotype emm1 by molecular analysis.Conclusion: Dramatic clinical picture and laboratory characters of the pregnant woman presented here might help improve clinicians' awareness and recognition of Streptococcus pyogenes, which could be of great importance for the early diagnosis of GAS- TSS in pregnancy.

1158. Pediatric Group A Streptococcal Peritonitis: A Single-Center Eleven Patient Case Series

Background Pediatric group A streptococcal peritonitis (GASP) is a rare but serious infection, with few cases reported in the literature. Utah has an unusually high incidence of invasive GAS (iGAS) disease, but the frequency and characteristics of pediatric GASP are unknown. Methods We performed a retrospective chart review to identify GASP in Utah children from 2000-2019. GASP was defined as isolation of GAS from peritoneal fluid or blood and clinical signs of peritonitis. Results : Eleven children with GASP were identified, with slight female predominance (n=6). Median age was 6 years; males were significantly younger than females (1.4 versus 7.2 years, p=0.01). GAS was isolated from 4 of 8 blood and 8 of 11 peritoneal cultures obtained. Peritoneal fluid PCR was positive for GAS in one patient. Ten patients underwent laparotomy. Peri-appendiceal inflammation prompted appendectomy in 7 patients; only one had pathologic findings of acute appendicitis. Four patients developed streptococcal toxic shock syndrome and 7 required intensive care. Non-white race (n=4) and lack of appendectomy (n=5) were associated with more severe outcomes. Median antibiotic duration was 27 days. Median hospitalization was 8 days. All patients survived. Figure 1. Schematic representation of GAS peritonitis patient clinical course. Each patient is represented by a single line. Duration of symptoms prior to hospitalization, as well as duration of hospitalization (day 0 representing admission), intensive care, antibiotic administration, and timing of procedural interventions are noted. Duration of antibiotics after discharge for patient 3 was unable to be verified, as indicated by a question mark. Hospitalization, general pediatric hospital care. PICU, pediatric intensive care unit. IR, interventional radiology. Conclusion We present the largest pediatric case series of GASP to date. Diagnostic hallmarks included gastrointestinal symptoms, fever, systemic inflammation, and peritoneal enhancement without an abdominal source. Peri-appendiceal inflammation was common, although acute appendicitis was rare, and appendectomy was associated with a less severe course. GASP should be considered in patients with acute abdominal processes given increasing incidence of iGAS infections. Disclosures All Authors: No reported disclosures

AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A Streptococcus

Streptococcus pyogenes (group A Streptococcus (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection.

Intravenous Immunoglobulin Use In Critically Ill Children

Purpose: The use of intravenous immunoglobulins (IVIG) has increased significantly in the last decade causing challenges for blood suppliers to respond to the demand. Indications for which IVIG infusion should be given to critically ill children remain unclear. The objective of this study is to characterize the epidemiology of IVIG use in this population. Methods: We performed a single-center retrospective cohort study of all patients aged between 3 days and 18 years who received at least one IVIG infusion while hospitalized in the pediatric intensive care unit of the Centre hospitalier universitaire (CHU) Sainte-Justine, Montréal Quebec (Canada) between January 1, 2013 and December 31, 2018. Results: One hundred and seventy-two patients received a total of 342 IVIG infusions over the study period. Most common indications for IVIG infusions were staphylococcal or streptococcal toxic shock syndrome (n=53/342, 15.5%), immunoglobulin replacement in chylothorax (n=37/342, 10.9%), prophylaxis following bone marrow transplantation (n=31/342, 9.1%), myocarditis (n=25/342, 7.3%) and post-solid organ transplant complications (n=21/342, 6.1%). The median dose of IVIG per infusion was 0.95 g/kg (IQR 0.5-1.0) and median number of IVIG infusions per patient was one (IQR: 1-2). Seventy-nine percent of IVIG infusions given were administrated for off-label indications with regards to Health Canada recommendations. Conclusion: This study identified the most common indications for IVIG infusion in critically ill children in a tertiary care pediatric intensive care unit. Given the costs, the known adverse events associated with IVIG and the pressure that blood suppliers are facing to meet the demands, clinical trials are needed to evaluate the efficacy and safety of IVIG in conditions where use is significant.

Fulminant necrotizing streptococcal myositis with dramatic outcome – a rare case report

Necrotizing myositis represents a rare, aggressive form of bacterial-induced soft tissue necrotizing infection. We present a fulminant case of a 44-year-old patient with a necrotizing soft tissue infection and a history of rheumatoid arthritis transferred to our service, Cluj-Napoca Emergency County Hospital, from a local hospital where he had been admitted two days before with chills and light-headedness after an accidental minor blunt trauma in the right thigh region. After admission to our hospital and first assessment, broad spectrum antibiotherapy was started with Meropenem, Vancomycin and Metronidazole along with surgical debridement. The evolution was fulminant with rapid development of multiple organ dysfunction syndrome, therefore he was transferred to the intensive care unit, intubated, and started the volemic resuscitation and vasopressor therapy. The blood culture was positive for group A beta-hemolytic streptococcus (GAS) and high dose Penicillin G was added to the therapeutic scheme. Despite all efforts, the patient developed disseminated intravascular coagulation syndrome and died in the next hours. The clinical picture together with the findings from the autopsy were suggestive for a streptococcal toxic shock syndrome developed as a complication of GAS induced necrotizing myositis.

Comprehensive comparative genomics analysis for the emerging human pathogen Streptococcus dysgalactiae subsp. equisimilis (SDSE): A case study and Pan-subspecies genomic analysis

Background: Streptococcus dysgalactiae subsp. equisimilis (SDSE) is the causal agent of various diseases that include wound infection, erysipelas, cellulitis, life-threatening necrotizing fasciitis, and streptococcal toxic shock syndrome. It is capable of infecting both humans and animals. In this investigation, we present a comprehensive genomic analysis for the SDSE strain SCDR1 that belongs to Lancefield group G, emm type (stG6) and (MLST) sequence type (ST44) that is the first time to be documented in Saudi Arabia and the middle east. Besides, we present the most comprehensive comparative genomics analysis for the emerging human pathogen SDSE. Methodology: We utilized next-generation sequencing techniques (NGS), bioinformatics, phylogenetic analysis, and comparative pathogenomics to characterize SCDR1 and all publicly available SDES genomes. Results: We found that SCDR1 consisted of a circular genome of 2179136 bp. Comparative analyses among bacterial genomes indicated that SCDR1 was most closely related to AC-2713 and GGS_124. Genome annotation of SCDR-1 strain showed that it contains many genes with homology to known virulence factors, including genes involved in cellular invasion, Antiphagocytosis, immune evasion, invasion of skin and soft tissue, host mortality and tissue damage, toxins, pore-forming proteins, cytotoxins, beta-hemolysis agents. Two CRISPR arrays were identified in SCDR1 that are consist of 35 CRISPR repeats and 33 CRISPR spacers. Two CAS systems were observed in the SCDR-1 genome, namely, CAS-TypeIIA and CAS-TypeIC. SDSE core Resistome is consisting of 22 genes, including folA, gyrA, gyrB, and FabK. SDSE core Virulome consisting of 38 genes including, fba, fbp54, gidA, and lsp. Conclusion: Our study confirmed that the SDSE strains possess different characteristics in producing virulence factors for pathogenicity to humans and based on its genome sequence and close relationship with GAS. Our study shed light on the proposed pathogenic mechanisms of SDSE and may form the basis of molecular epidemiological research on these highly virulent bacteria.