Analysis of bacteraemia caused by group C and G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis) in Western Sydney over a 6-year period (2015-2020).

PURPOSE: Streptococcus dysgalactiae subsp. equisimilis (SDSE) has increasingly been recognised as a significant pathogen that causes a myriad of infections, ranging from cellulitis to invasive infections, including bacteraemia and even toxic shock syndrome. The aim of this study was to examine the epidemiology and disease manifestations of bacteraemia caused by SDSE. METHODS: We retrospectively reviewed cases of SDSE bacteraemia in adults aged ≥ 18 years admitted to four public hospitals in Western Sydney, Australia, between January 2015 and December 2020. We reviewed demographics, comorbidities, disease manifestations, management, and outcomes. RESULTS: There were 108 patients with SDSE bacteraemia over a six-year period. The median age of individuals with SDSE bacteraemia was 70 years (interquartile range, IQR, 58-85 years). Cardiovascular disease (46%), chronic skin conditions (44%) and diabetes (37%) were the most common comorbidities. Ten patients (9%) with SDSE bacteraemia had healthcare-acquired infections. Skin and skin structure infections (SSTIs) were the most common presentations (59%), while bone and joint infections (BJIs) represented 13% of the cases. Twenty patients (19%) had septic shock on presentation. Fifteen patients (14%) were prescribed clindamycin, while one patient received intravenous immunoglobulin (IVIg). Infective endocarditis (IE) was present in 3% of patients; however, only 44% of the total patients had an echocardiogram. The 30-day mortality rate was 13%, but it was greater in those aged > 75 years (21%). The average length of hospital stay for patients who survived was 15 days, and the average duration of intravenous therapy was 12 days. CONCLUSION: SDSE bacteraemia is typically a community-onset infection with a fifth of patients in our cohort presenting with septic shock. Though complications such as BJI (13%) and IE (3%) are infrequent, 30-day mortality is high at 21% in those aged > 75 years.

Group A Streptococcal meningitis in children: a short case series and systematic review.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

Emergent emm4 group A Streptococcus evidences a survival strategy during interaction with immune effector cells.

The major gram-positive pathogen group A Streptococcus (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics have been ascribed to the emergence of clones producing increased amounts of key virulence factors such as streptolysin O (SLO). Herein, we sought to identify mechanisms underlying our recently identified temporal clonal emergence among emm4 GAS, given that emergent strains did not produce augmented levels of virulence factors relative to historic isolates. By creating and analyzing isoallelic strains, we determined that a conserved mutation in a previously undescribed gene encoding a putative carbonic anhydrase was responsible for the defective in vitro growth observed in the emergent strains. We also identified that the emergent strains survived better inside macrophages and killed macrophages at lower rates than the historic strains. Via the creation of isogenic mutant strains, we linked the emergent strain "survival" phenotype to the downregulation of the SLO encoding gene and upregulation of the msrAB operon which encodes proteins involved in defense against extracellular oxidative stress. Our findings are in accord with recent surveillance studies which found a high ratio of mucosal (i.e., pharyngeal) relative to invasive infections among emm4 GAS. Since ever-increasing virulence is unlikely to be evolutionarily advantageous for a microbial pathogen, our data further understanding of the well-described oscillating patterns of virulent GAS infections by demonstrating mechanisms by which emergent strains adapt a "survival" strategy to outcompete previously circulating isolates.

Clinical manifestations and biomarkers to predict mortality risk in adults with invasive Streptococcus dysgalactiae subsp. equisimilis infections.

PURPOSE: The incidence of invasive Streptococcus dysgalactiae subsp. equisimilis (iSDSE) infections is increasing in developed countries, but studies on the risk factors for death in iSDSE infections are scant. Here, we aimed to clarify risk factors and predictors of mortality in adults with iSDSE infections. METHODS: A multicentre observational study of adults with iSDSE infections was conducted to investigate the effects of host factors, disease severity, biomarkers, and antibiotic regimens, and bacterial factors on 28-day mortality. RESULTS: The overall mortality rate of 588 patients was 10.4%, with a significant increase in those aged ≥ 60 years. Most of the patients (97.4%) had underlying diseases. The mortality rate (70.4%) of patients with severe disease was significantly higher than that of patients with mild-to-moderate disease (4.3%; p < 0.001). The risk factors for death identified using multivariable analysis were age ≥ 60 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.0-11.3, p = 0.042); severe disease (HR, 15.0; 95% CI 7.7-29.2, p < 0.001); bacteraemia without primary focus (HR, 20.5; 95% CI 2.8-152.3, p = 0.003); serum creatinine ≥ 2.0 mg/dL (HR, 2.2; 95% CI 1.2-4.0, p = 0.010); serum creatine kinase ≥ 300 IU/L (HR, 2.1; 95% CI 1.1-3.8, p = 0.019); and macrolide resistance (HR, 1.8; 95% CI 1.0-3.3, p = 0.048). Treatment regimens and emm types were not associated with poor outcomes. CONCLUSION: Evaluation of clinical manifestations and biomarkers on admission is important to predict invasive SDSE infection prognosis.

Infection route associated with invasive group A streptococcal toxic shock syndrome in maternal deaths: Nationwide analysis of maternal mortalities in Japan.

OBJECTIVES: To clarify the infection route in maternal death due to invasive group A streptococcal (GAS) infection and toxic shock syndrome (TSS). METHODS: A retrospective study was conducted on maternal deaths due to GAS-TSS in Japan between January 2010 and March 2024. The final causal diagnosis of maternal death and the infection routes of GAS were analysed using medical records, laboratory data and autopsy findings. RESULTS: Among the 616 maternal deaths during the study period, 48 (8%) involved infectious diseases. The most common infection was invasive GAS (56%, n = 27), 21 (78%) and six cases occurred during the antepartum and puerperium periods, respectively. In the GAS-TSS group, 71% (15/21) infections were originated the upper respiratory tract. However, in the puerperium cases, 67% (4/6) were infected from the genital tract. In addition, no maternal deaths due to GAS-TSS were reported during the COVID-19 pandemic period in Japan from 2020 to 2023. CONCLUSION: Most antepartum GAS infections were from the upper respiratory tract. They may be reduced by preventive measures, including frequent disinfection, wearing masks and isolation from persons at high risk of carrying GAS, such as symptomatic children. On the other hand, GAS-TSS during puerperium infection via the genital tract.

Burden of Invasive Group B Streptococcus Infection Among Omani Infants Less Than 90 Days Old: A Multicenter Study.

BACKGROUND: Group B Streptococcus (GBS) infection is the leading cause of neonatal morbidity and mortality worldwide. This study aims to investigate the incidence of invasive GBS disease among infants less than 90 days old in Oman and to describe their risk factors, clinical presentations and clinical outcomes. METHODS: We retrospectively collected the data of less than 90-day-old Omani infants with culture-positive GBS from sterile samples. This study was conducted in 3 tertiary hospitals in Oman from 2009 to 2018. RESULTS: Over 10 years, we identified 92 cases of culture-confirmed invasive GBS infection from 178,285 live births in the 3 hospitals, giving an overall incidence of 0.53 per 1000 live births [95% confidence interval (CI): 0.4-0.7)]. Of those, 59 (64.1%) had early-onset neonatal GBS disease and 33 (35.9%) had late-onset neonatal GBS disease. The incidence of invasive GBS disease was significantly higher in the last 5 years from 2014 to 2018 (0.69 per 1000 live births, 95% CI: 0.5-0.9) compared to the previous years from 2009 to 2013 (0.36 per 1000 live births, 95% CI: 0.2‒0.5), ( P = 0.004). Infants with late-onset neonatal GBS disease had a higher risk of meningitis compared to infants with early-onset neonatal GBS disease (30.3% vs. 10.2%, P = 0.021). The mortality rate was 13.5%. CONCLUSIONS: The incidence of invasive GBS disease in Oman is similar to what was reported worldwide, however, the burden of the disease in terms of mortality is high. In addition, a significant increase in the annual incidence of invasive GBS disease in Omani infants was found over the study period.

Clinical Course and Outcomes of Infants with Streptococcus bovis/Streptococcus Gallolyticus subspecies pasteurianus Infection: A Systematic Review and Meta-analysis.

BACKGROUND: Streptococcus gallolyticus subspecies pasteurianus (SGP), a subtype of Streptococcus bovis , is an uncommon but important cause of neonatal sepsis. Although uncommon, SGP infections during infancy have been associated with an increased risk of morbidity and mortality. METHODS: This is a systematic review and meta-analysis of available literature on the clinical course and outcomes of infants with SGP infection. Studies were identified using the following MeSH keywords: " Streptococcus gallolyticus ," " Streptococcus bovis ," "newborn" and "infant." Data including perinatal factors, clinical presentation, investigations, treatment and outcomes were extracted and analyzed. RESULTS: A total of 46 articles were identified (116 cases: 60 S. bovis , 56 SGP). The cases were predominantly term (52%), male (57%) and born via vaginal delivery (67%). The most common symptom was fever [67% (95% confidence interval (CI): 43%-84%)], lethargy [66% (95% CI: 32%-89%)], tachypnea [59% (95% CI: 27%-85%)] and irritability [59% (95% CI: 34%-79%)]. Infants with early-onset infections (<3 days of life) were more likely to have respiratory symptoms and bacteremia (73%), whereas late-onset infections presented predominantly with gastrointestinal symptoms. Four mortalities were reported which occurred before antibiotic administration. Isolated bacteria were mostly penicillin-susceptible [95% (95% CI: 78-99%)] and cases treated with penicillin derivative had good recovery. CONCLUSIONS: SGP is an important cause of neonatal sepsis and meningitis. Penicillin derivative is an effective treatment for SGP, and outcomes appear to be favorable.

Predictors of Mortality of Streptococcal Bacteremia and the Role of Infectious Diseases Consultation: A Retrospective Cohort Study.

BACKGROUND: Streptococcal bacteremia is associated with high mortality. Thia study aims to identify predictors of mortality among patients with streptococcal bacteremia. METHODS: This retrospective study was conducted at the Lausanne University Hospital, Switzerland, and included episodes of streptococcal bacteremia among adult patients from 2015 to 2023. RESULTS: During the study period, 861 episodes of streptococcal bacteremia were included. The majority of episodes were categorized in the Mitis group (348 episodes; 40%), followed by the Pyogenic group (215; 25%). Endocarditis was the most common source of bacteremia (164; 19%). The overall 14-day mortality rate was 8% (65 episodes). The results from the Cox multivariable regression model showed that a Charlson comorbidity index >4 (P .001; hazard ratio [HR], 2.87; confidence interval [CI]: 1.58-5.22), Streptococcus pyogenes (P = .011; HR, 2.54;CI: 1.24-5.21), sepsis (P < .001; HR, 7.48; CI: 3.86-14.47), lower respiratory tract infection (P = .002; HR, 2.62; CI: 1.42-4.81), and absence of source control interventions within 48 hours despite being warranted (P = .002; HR, 2.62; CI: 1.43-4.80) were associated with 14-day mortality. Conversely, interventions performed within 48 hours of bacteremia onset, such as infectious diseases consultation (P < .001; HR, 0.29; CI: .17-.48) and appropriate antimicrobial treatment (P < .001; HR, .28; CI: .14-.57), were associated with improved outcome. CONCLUSIONS: Our findings underscore the pivotal role of infectious diseases consultation in guiding antimicrobial treatment and recommending source control interventions for patients with streptococcal bacteremia.

Clindamycin but not Intravenous Immunoglobulins reduces mortality in a retrospective cohort of critically ill patients with bacteremic Group A Streptococcal infections / Tratamiento con clindamicina, y no con inmunoglobulinas intravenosas, disminuye la mortalidad en una cohorte retrospectiva de pacientes críticos con bacteriemia por Streptococcus del Grupo A

Objectives. Mortality of patients requiring Intensive Care Unit (ICU) admission for an invasive group A streptococcal (GAS) infection continues being high. In critically ill patients with bacteremic GAS infection we aimed at determining risk factors for mortality. Patients and methods. Retrospective multicentre study carried out in nine ICU in Southern Spain. All adult patients admitted to the participant ICUs from January 2014 to June 2019 with one positive blood culture for S. pyogenes were included in this study. Patient characteristics, infection-related variables, therapeutic interventions, failure of organs, and outcomes were registered. Risk factors independently associated with ICU and in-hospital mortalities were determined by multivariate regression analyses. Results. Fifty-seven patients were included: median age was 63 (45-73) years, median SOFA score at admission was 11 (7-13). The most frequent source was skin and soft tissue infection (n=32) followed by unknown origin of bacteremia (n=12). In the multivariate analysis, age (OR 1.079; 95% CI 1.016-1.145), SOFA score (OR 2.129; 95% CI 1.339-3.383) were the risk factors for ICU mortality and the use of clindamycin was identified as a protective factor (OR 0.049; 95% CI 0.003-0.737). Age and SOFA were the independent factors associated with hospital mortality however the use of clindamycin showed a strong trend but without reaching statistical significance (OR 0.085; 95% CI 0.007-1.095). (AU)

Objetivo. La mortalidad de los pacientes que requieren ingreso en la Unidad de Cuidados Intensivos (UCI) por una infección invasiva por estreptococos del grupo A (GAS) continúa siendo inaceptablemente alta. El objetivo del estudio fue determinar los factores de riesgo de mortalidad en pacientes críticos con infección estreptocócica bacterémica del grupo A. Pacientes y métodos. Estudio retrospectivo multicéntrico realizado en nueve UCI del sur de España. Se incluyeron pacientes consecutivos ingresados en las UCI participantes desde enero de 2014 hasta junio de 2019 con un hemocultivo positivo para S. pyogenes. Se registraron las características de los pacientes, las variables relacionadas con la infección, las intervenciones terapéuticas, el fracaso de los órganos y el pronóstico. Se determinaron mediante análisis de regresión multivariante los factores de riesgo asociados de forma independiente con la mortalidad en UCI y hospitalaria. Resultados. Se incluyeron cincuenta y siete pacientes: la mediana de edad fue de 63 (45-73) años, la mediana de la puntuación SOFA al ingreso fue de 11 (7-13). El foco más frecuente fue la infección de la piel y los tejidos blandos (n=32) seguida de la bacteriemia de origen desconocido (n=12). En el análisis multivariante, la edad (OR 1,079; IC del 95%: 1,016-1,145), y la puntuación SOFA (OR 2,129; IC del 95%: 1,339-3,383) se identificaron como factores de riesgo para la mortalidad en UCI. El uso de clindamicina se identificó como un factor protector (OR 0,049; IC del 95%: 0,003-0,737). La edad y la SOFA se asociaron de forma independiente con la mortalidad hospitalaria, mientras que el tratamiento con clindamicina mostró una tendencia fuerte pero sin alcanzar significación estadística (OR 0,085; IC del 95%: 0,007-1,095). (AU)

Fatal Pediatric Streptococcal Infection: A Clinico-Pathological Study.

PURPOSE AND CONTEXT: Streptococcal Infection (SI) is an important cause of pediatric death in children, yet limited reports exist on autopsy findings in fatal SI cases. METHOD: Case records (1997-2019) of SI with no pre-existing risk factors were reviewed and selected. Their clinical and pathological findings in the autopsy reports were analyzed. RESULTS: In our cohort of 38 cases based on bacterial culture results, SI was most commonly caused by Streptococcus pneumoniae (SPn; 45%) and Streptococcus pyogenes (SPy; 37%). 92% of decedents had some prodromal symptoms prior to terminal presentation. The clinical course was often rapid, with 89% found unresponsive, suddenly collapsing, or dying within 24 hours of hospital admission. 64% of deaths were attributed to sepsis, more frequently diagnosed in the SPy group than in the SPn group (71% vs 48%). Pneumonia was found in both SPn and SPy groups, whereas meningitis was exclusively associated with SPn. CONCLUSION: Our study shows fatal SI is most commonly caused by either SPn or SPy, both of which are frequently associated with prodromal symptoms, rapid terminal clinical course, and evidence of sepsis. Postmortem diagnosis of sepsis is challenging and should be correlated with clinical features, bacterial culture results, and autopsy findings.

Association between adjunct clindamycin and in-hospital mortality in patients with necrotizing soft tissue infection due to group A Streptococcus: a nationwide cohort study.

Necrotizing soft tissue infection (NSTI) due to group A Streptococcus (GAS) is a severe life-threatening microbial infection. The administration of adjunct clindamycin has been recommended in the treatment of NSTIs due to GAS. However, robust evidence regarding the clinical benefits of adjunct clindamycin in NSTI patients remains controversial. We aimed to investigate the association between early administration of adjunct clindamycin and in-hospital mortality in patients with NSTI attributed to GAS. The present study was a nationwide retrospective cohort study, using the Japanese Diagnosis Procedure Combination inpatient database focusing on the period between 2010 and 2018. Data was extracted on patients diagnosed with NSTI due to GAS. We compared patients who were administered clindamycin on the day of admission (clindamycin group) with those who were not (control group). A propensity score overlap weighting method was adopted to adjust the unbalanced backgrounds. The primary endpoint was in-hospital mortality and survival at 90 days after admission. We identified 404 eligible patients during the study period. After adjustment, patients in the clindamycin group were not significantly associated with reduced in-hospital mortality (19.2% vs. 17.5%; odds ratio, 1.11; 95% confidence interval, 0.59-2.09; p = 0.74) or improved survival at 90 days after admission (hazard ratio, 0.92; 95% confidence interval, 0.51-1.68; p = 0.80). In this retrospective study, early adjunct clindamycin does not appear to improve survival. Therefore, the present study questions the benefits of clindamycin as an adjunct to broad spectrum antibiotics in patients with NSTI due to GAS.

Blood culture time to positivity in non-ß-hemolytic streptococcal bacteremia as a predictor of infective endocarditis-a retrospective cohort study.

Non-ß-hemolytic streptococci (NBHS) cause infective endocarditis (IE) and a short blood culture time to positivity (TTP) is associated with risk of IE in bacteremia with other pathogens. In this retrospective population-based cohort study, we investigate if TTP is associated to IE or mortality. Of 263 episodes with NBHS bacteremia, 28 represented IE and the median TTP did not differ significantly between episodes with IE (15 h) and non-IE (15 h) (p=0.51). TTP was similar among those who survived and those who died within 30 days. However, TTP significantly differed when comparing the different streptococcal groups (p<0.001).

Top 10 Pearls for the Recognition, Evaluation, and Management of Maternal Sepsis.

Maternal sepsis is an obstetric emergency and a leading cause of maternal morbidity and mortality. Early recognition in a pregnant or postpartum patient can be a challenge as the normal physiologic changes of pregnancy may mask the signs and symptoms of sepsis. Bedside assessment tools may aid in the detection of maternal sepsis. Timely and targeted antibiotic therapy and fluid resuscitation are critical for survival in patients with suspected sepsis. Once diagnosed, a search for etiologies and early application of source control measures will further reduce harms. If the patient is in septic shock or not responding to initial treatment, multidisciplinary consultation and escalation of care is necessary. Health care professionals should be aware of the unique complications of sepsis in critically ill pregnant and postpartum patients, and measures to prevent poor outcomes in this population. Adverse pregnancy outcomes may occur in association with sepsis, and should be anticipated and prevented when possible, or managed appropriately when they occur. Using a standardized approach to the patient with suspected sepsis may reduce maternal morbidity and mortality.

Necrotizing Skin and Soft Tissue Infections Admitted to Intensive Care Unit in Reunion Island: A Retrospective Cohort Study.

This retrospective and single-center study in Reunion Island (Indian Ocean) assessed frequency, mortality, causative pathogens of severe necrotizing skin, and necrotizing skin and soft tissue infections (NSSTIs) admitted in intensive care unit (ICU). Sixty-seven consecutive patients were included from January 2012 to December 2018. Necrotizing skin and soft tissue infection represented 1.06% of total ICU admissions. We estimate the incidence of NSSTI requiring ICU at 1.21/100,000 person/years in Reunion Island. Twenty (30%) patients were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) prior to admission in ICU and 40 (60%) were diagnosed patients with diabetes. Sites of infection were the lower limb in 52 (78%) patients, upper limb in 4 (6%), and perineum in 10 (15%). The surgical treatment was debridement for 40 patients, whereas 11 patients required an amputation. The most commonly isolated microorganisms were Streptococci (42%) and Gram-negative bacteria (22%).The mortality rate was 25.4%. NSAIDs did not influence mortality when interrupted upon admission to ICU.

Increasing incidence of invasive group A streptococcal disease in Western Australia, particularly among Indigenous people.

OBJECTIVE: To quantify the burden of invasive group A Streptococcus (GAS) disease in Western Australia during 2000-2018. DESIGN, SETTING: Population-based data linkage study: Hospital Morbidity Data Collection (HMDC; all WA public and private hospital records), PathWest pathology data (government-owned pathology services provider), and death registrations. PARTICIPANTS: People with invasive GAS disease, defined by an isolate from a normally sterile site (PathWest) or a hospital-based principal ICD-10-AM diagnosis code (HMDC). MAIN OUTCOME MEASURES: Incidence of invasive GAS disease; median length of hospital stay; all-cause mortality. RESULTS: We identified 2237 cases of GAS disease during 2000-2018; 1283 were in male patients (57%). 1950 cases had been confirmed by GAS isolates from normally sterile tissues (87%; including 1089 from blood [56% of cases] and 750 from tissue [38%]). The age-standardised incidence increased from 2.0 (95% CI, 1.4-2.7) cases per 100 000 population in 2000 to 9.1 (95% CI, 7.9-10.2) cases per 100 000 in 2017 (by year, adjusted for age group and sex: incidence rate ratio [IRR], 1.09; 95% CI, 1.08-1.10). Incidence was consistently higher among Indigenous than non-Indigenous Australians (year-adjusted IRR, 13.1; 95% CI, 11.3-15.1). All-cause 30-day mortality was 5% (116 deaths), and 90-day mortality 7% (156 deaths); 30-day mortality, adjusted for age group and sex, was not statistically significantly different for cases involving Indigenous or non-Indigenous patients (adjusted odds ratio, 0.8; 95% CI, 0.6-1.1). CONCLUSIONS: The incidence of invasive GAS disease in WA increased between 2000 and 2018, particularly among Indigenous Australians. Mandatory notification of invasive GAS disease would therefore be appropriate. The social determinants of differences in incidence should be addressed, and other relevant host, pathogen, and health system factors investigated.

Emergency hip disarticulations for severe necrotising fasciitis of the lower limb: a series of rare cases from a rural district general hospital.

Hip disarticulation is the removal of the entire lower limb through the hip joint by detaching the femur from the acetabulum. This major ablative procedure is rarely performed for infection but may be required in severe necrotising fasciitis. We present a single centre retrospective review of all cases of emergency hip disarticulations in patients with necrotising fasciitis between 2010 and 2020. All five patients included in the review presented with acute lower limb pain and sepsis. Three patients had comorbidities predisposing them to necrotising fasciitis. Three were deemed to be high risk and two were at intermediate risk of developing necrotising fasciitis. There were two deaths in the postoperative period. Of the three survivors, two required revision surgery for a completion hindquarter amputation and one for flap closure. All three survivors had good functional outcomes after discharge from hospital. Despite its associated morbidity, emergency amputation of the entire lower limb is a life-saving treatment in cases of rapidly progressing necrotising fasciitis and should be considered as a first-line option in managing this condition.

Effects on the survival rates, hematological parameters, and neurotransmitters in olive flounders, Paralichthys olivaceus, reared in bio-floc and seawater by Streptococcus iniae challenge.

Bacterial infections cause huge losses to aquaculture globally, and increased antibiotic resistance means that alternative methods of reducing mortality from bacterial diseases are required. We compared the resistance of Juvenile olive flounders, Paralichthys olivaceus, to Streptococcus iniae between those reared in biofloc and seawater conditions for ten months. Experimental fish were challenged with S. iniae at concentrations of 0, 3.36 × 106, 3.36 × 107, 3.36 × 108, and 3.36 × 109 colony forming units (CFU)/g fish for 96 h to evaluate the difference in S. iniae susceptibility of flounders reared in biofloc and seawater. The 96 h lethal concentration 50% (LC50) of fish injected with S. iniae was 2.41 × 109 CFU/g fish in biofloc and 1.51 × 108 CFU/g fish in seawater. Hematological parameters such as hemoglobin and hematocrit significantly decreased when fish were challenged by S. iniae. Plasma components such as calcium, glucose, cholesterol, total protein, GOT, GPT, and ALP were significantly altered by S. iniae infection and acetylcholinesterase activity was significantly inhibited. These results indicate that S. iniae infection affects the survival rates, hematological parameters, and neurotransmitter levels of flounders reared in biofloc and seawater, and that S. iniae susceptibility was higher in flounders reared in seawater than those reared in biofloc.

Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study.

BACKGROUND: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands. METHODS: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts. FINDINGS: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], p<0·0001) and hospital admissions (1·33 [1·27-1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts. INTERPRETATION: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATIONS: For the Dutch and Danish translations of the abstract see Supplementary Materials section.