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The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P = .02) and 3 (P = .04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P = .03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.

Abstract We evaluated the effect of intravenous immunoglobulin (IVIG) on mortality in clindamycin-treated streptococcal toxic shock syndrome using a meta-analysis. In association with IVIG, mortality fell from 33.7% to 15.7% with remarkable consistency across the single randomized and four nonrandomized studies.

Group B streptococcus is a leading cause of serious infection in young infants in many countries worldwide. We aimed to define the burden and clinical features of invasive group B streptococcal disease in infants younger than 90 days in the UK and Ireland, together with the characteristics of disease-causing isolates. Prospective, active national surveillance of invasive group B streptococcal disease in infants younger than 90 days was done from April 1, 2014, to April 30, 2015, through the British Paediatric Surveillance Unit, microbiology reference laboratories, and national public health agencies in the UK and Ireland. Early onset was defined as disease in the first 6 days of life and late onset was defined as 7–89 days of life. Incidence was calculated using livebirths in 2014 (after adjustment for the 13-month surveillance period). Isolates were characterised by serotyping, multilocus sequence typing, and antimicrobial susceptibility testing. 856 cases of group B streptococcus were identified in 2014–15, an incidence of 0·94 per 1000 livebirths (95% CI 0·88–1·00). Incidence for early-onset disease (n=517) was 0·57 per 1000 livebirths (95% CI 0·52–0·62), and for late-onset disease (n=339) was 0·37 per 1000 livebirths (0·33–0·41). 53 infants died (case fatality rate 6·2%), of whom 27 had early-onset disease (case fatality rate 5·2%) and 26 had late-onset disease (case fatality rate 7·7%). The predominant serotypes were III (241 [60%] of 402 serotyped isolates) and Ia (69 [17%]); five serotypes (Ia, Ib, II, III, V) accounted for 377 (94%) of all serotyped isolates. The incidence of invasive infant group B streptococcal disease in the UK and Ireland has increased since a comparable study done in 2000–01. The burden of early-onset disease has not declined despite the introduction of national prevention guidelines. New strategies for prevention are required. Meningitis Now.

Our study reveals a hitherto overlooked ecological threat of climate change. Studies of warming events in the ocean have typically focused on the events’ maximum temperature and duration as the cause of devastating disturbances in coral reefs, kelp forests, and rocky shores. In this study, however, we found that the rate of onset (Ronset), rather than the peak, was the likely trigger of mass mortality of coral reef fishes in the Red Sea. Following a steep rise in water temperature (4.2 °C in 2.5 d), thermally stressed fish belonging to dozens of species became fatally infected by Streptococcus iniae. Piscivores and benthivores were disproportionately impacted whereas zooplanktivores were spared. Mortality rates peaked 2 wk later, coinciding with a second warming event with extreme Ronset. The epizootic lasted ∼2 mo, extending beyond the warming events through the consumption of pathogen-laden carcasses by uninfected fish. The warming was widespread, with an evident decline in wind speed, barometric pressure, and latent heat flux. A reassessment of past reports suggests that steep Ronset was also the probable trigger of mass mortalities of wild fish elsewhere. If the ongoing increase in the frequency and intensity of marine heat waves is associated with a corresponding increase in the frequency of extreme Ronset, calamities inflicted on coral reefs by the warming oceans may extend far beyond coral bleaching.

Background. Streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis are the 2 most severe invasive manifestations caused by group A Streptococcus (GAS). Intravenous immunoglobulin (IVIG) therapy has been suggested as adjunctive treatment with a beneficial effect on mortality. However the clinical evidence is limited. Here we aim to further document the clinical efficacy of administered IVIG therapy in a comparative observational study of well-defined patients with STSS. Methods. The effect of IVIG was evaluated in patients with STSS prospectively identified in a nationwide Swedish surveillance study conducted between April 2002 and December 2004. Detailed data on symptoms, severity of disease, treatment, and outcome were obtained from 67 patients. Crude and adjusted analyses with logistic regression were performed. Results. Twenty-three patients received IVIG therapy compared with 44 who did not. No significant difference in comorbidities, severity of disease, organ failures, or sex was seen, but the IVIG group was slightly younger and had a higher degree of necrotizing fasciitis (56% vs 14%). The primary endpoint was 28-day survival. Adjusted analysis revealed that factors influencing survival in STSS were Simplified Acute Physiology Score II (odds ratio [OR], 1.1; P = .007), clindamycin (OR, 8.6; P = .007), and IVIG (OR, 5.6; P = .030). Conclusions. This comparative observational study of prospectively identified STSS patients demonstrates that both IVIG and clindamycin therapy contribute to a significantly improved survival in STSS.

Group A Streptococcus (GAS) causes a variety of diseases in humans but is not widely appreciated as a cause of meningitis. During 1997-2022, ten sites participating in the Active Bacterial Core Surveillance network in the United States identified GAS meningitis cases. We calculated annual incidence and case-fatality rates (CFRs) for 320 of those cases and determined antimicrobial resistance by whole-genome sequencing. Annual incidence of GAS meningitis ranged from 0.02 to 0.07 cases/100,000 persons. Children <1 year of age had the highest average annual incidence, 0.23 cases/100,000 children. GAS meningitis had a higher CFR (19.4%) than meningitis caused by group B Streptococcus, Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae. Clindamycin resistance among GAS meningitis isolates increased from 3.2% during 1997-2002 to 17.7% during 2018-2022. Clinicians should be aware that meningitis is an uncommon but severe manifestation of invasive GAS and has a higher CFR than more established meningitis etiologies.

Adjunctive clindamycin use is associated with survival in invasive group A streptococcus (GAS) infections but increasing clindamycin resistance in GAS has called into question its durability for this indication. Linezolid also inhibits GAS toxin and virulence factor production, but clinical efficacy data remain sparse. We retrospectively emulated a target multicentre, non-blinded, non-inferiority trial to assess the efficacy of adjunctive linezolid compared with clindamycin in adult inpatients with invasive GAS infection treated with a β-lactam using the PINC AI database between 2016 and 2021. Patients were eligible if they had a monomicrobial GAS culture and received adjunctive therapy within 3 days of culture either concurrently or after β-lactam initiation and completed at least 3 days of β-lactam therapy. The primary outcome was adjusted risk ratio (aRR) of in-hospital mortality assessed by overlap-weighting using propensity scores. Secondary outcomes were length of stay among survivors and Clostridium difficile infection. Of 1095 β-lactam-treated patients with GAS, 829 (76%) received clindamycin and 266 (24%) received linezolid. In the overlap weighted cohort, the receipt of linezolid was not associated with a statistically significant different aRR of in-hospital mortality compared with clindamycin (linezolid: 9·8% [26/266] vs clindamycin: 7·0% [58/829]; aRR: 0·92 [95% CI 0·42 to 1·43]; p=0·76). The risk difference was –0·005 (95% CI –0·05 to 0·04; p=0·81) and fell within the non-inferiority margin of 0·05. The primary analysis results were consistent across important subgroups and sensitivity analyses. Among survivors, median length of stay (adjusted ratio 0·96 [95% CI 0·16 to 0·08]; p=0·47) and C difficile infection risk (aRR 1·76 [95% CI 0·37 to 1·75]; p=0·29) were not statistically significantly different between the two groups. In this emulated trial of adult patients with invasive GAS infections treated with β-lactam, linezolid appeared non-inferior to clindamycin suggesting linezolid as an alternative for adjunctive antitoxin therapy. The Intramural Research Program of the US National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Disease.

Abstrac t Background In the management of bacteremia, positive repeat blood cultures (persistent bacteremia) are associated with increased mortality. However, blood cultures are costly and it is likely unnecessary to repeat them for many patients. We assessed predictors of persistent bacteremia that should prompt repeat blood cultures. Methods We conducted a retrospective cohort study of bacteremias at an academic hospital from April 2010 to June 2014. We examined variables associated with patients undergoing repeat blood cultures, and with repeat cultures being positive. A nested case control analysis was performed on a subset of patients with repeat cultures. Results Among 1801 index bacteremias, repeat cultures were drawn for 701 patients (38.9 %), and 118 persistent bacteremias (6.6 %) were detected. Endovascular source (adjusted odds ratio [aOR], 7.66; 95 % confidence interval [CI], 2.30-25.48), epidural source (aOR, 26.99; 95 % CI, 1.91-391.08), and Staphylococcus aureus bacteremia (aOR, 4.49; 95 % CI, 1.88-10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1 %, P  = 0.006), viridans group (1.7 %, P  = 0.035) and β-hemolytic streptococci (0 %, P  = 0.028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 h of the index event (29.7 % vs 52.5 %, P  < .001), but after variable reduction, source control was not retained in the final multivariable model. Conclusions Patients with S. aureus bacteremia or endovascular infection are at risk of persistent bacteremia. Achieving source control within 48 h of the index bacteremia may help clear the infection. Repeat cultures after 48 h are low yield for most Gram-negative and streptococcal bacteremias.

PurposeThe 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.MethodsA 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.ResultsThe 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.ConclusionEvaluation of clinical manifestations and biomarkers on admission is important to predict invasive SDSE infection prognosis.

Background Studies have identified significant morbidity and mortality with necrotising soft tissue infections relating to invasive group A Streptococcus (iGAS). However, no studies have analysed the reconstructive, functional and psychological outcomes of invasive group A Streptococcus infections across its clinical spectrum, including the more common non-necrotising presentations. This study was a retrospective cohort study that aimed to review as primary outcomes the management, reconstructive burden and functional outcomes of soft tissue iGAS infections at a tertiary-care U.K. Plastic Surgery unit between 2013 and 2022. The secondary outcome was to identify associations between patient factors and limb amputation and mortality. Methods All positive iGAS cultures isolated in patients aged 16 and over were identified. Medical records, operative records, and microbiology samples were examined. Results 96 cases of iGAS were identified in 95 patients over the study period. 63 patients (66%) were male; 34 patients (36%) were current smokers; and 35 patients (37%) were immunocompromised, including 18 patients (19%) with diabetes. 88 cases (92%) affected the upper or lower limbs, with 11 cases (13% of limb iGAS) requiring amputation of the involved digit or limb. Reconstructive surgery was performed in 15 cases (16%), requiring a mean number of 3.7 ± 1.88 operations. Reconstruction methods involved acelluar dermal matrices and/or skin grafts (14 cases; 15%) and locoregional flaps (8 cases; 8.3%). At follow up, 13 cases (14%) had functional complications relating to their iGAS episode, including neuropathic pain and limited movement. Mortality was 5.2% (5 patients) within the index admission and 7.3% (7 patients) within 90 days. Diabetes was significantly associated with 90-day mortality ( p  = 0.023; odds ratio [OR] 7.05, 95% confidence interval [CI] 1.41–35.00) and amputation ( p  = 0.033; OR 4.51, 95% CI 1.19–17.19). Other systemic comorbidities were not significantly associated with mortality or amputation. Conclusions Soft tissue iGAS infections principally affect the limbs and require multimodal management to mitigate the high rates of infection-related morbidity and mortality. Diabetes is significantly associated with higher amputation and mortality rates in our study population. Appropriate services should be in place to manage long-term functional disability and mental health morbidity after iGAS.