Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.

OBJECTIVE: The reported rising global rates of invasive group A Streptococcus (iGAS) infection raise concern for disease related increase in critical illness and fatalities. An enhanced understanding of various presentations to health care and clinical course could improve early recognition and therapy in children with iGAS. The objective of this study was to describe the epidemiology of iGAS infections among children admitted to critical care.
METHODS: A retrospective cohort study of children admitted to the PICU at The Hospital for Sick Children, in Toronto, Canada, between March 2022 and June 2023. Eligible patients were 0 to 18 years, with a diagnosis of iGAS infection. We describe the proportion of children admitted to the PICU with iGAS over the study period, their clinical characteristics, the frequency and timing of therapies, discharge versus baseline function, and PICU mortality.
RESULTS: Among the 1820 children admitted to the PICU, 29 (1.6%) patients had iGAS infection. Of these 29 patients, 80% (n = 23) survived to hospital discharge. Patients who survived generally had favorable functional outcomes. Despite the high severity of illness and mortality described in this cohort, 61% returned to their baseline functional status by hospital discharge.
CONCLUSIONS: This is the first report of critically ill children with iGAS in Canada during the increased incidence reported worldwide. We describe the clinical course of iGAS infection in children admitted to PICU with access to advanced extracorporeal interventions. Though there is a high mortality rate in this cohort, those who survive have favorable outcomes.

BACKGROUND: Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance.
OBJECTIVE: To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children.
METHODS: We assessed 54 children aged 2-17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification.
RESULTS: The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36).
CONCLUSIONS: Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.

OBJECTIVE: To analyze the cases of acute mastoiditis, characteristics, management and complications in children attended in the emergency department.
METHODS: Retrospective study of acute mastoiditis in a Spanish tertiary hospital over a 6-year period (2018-2023).
RESULTS: One hundred two episodes of acute mastoiditis were analyzed (54% males, median age 1.8 years). Microorganisms were isolated in one third of cases, mainly Streptococcus pyogenes (64% of ear secretion cultures). Complications occurred in 27.5%, primarily subperiosteal abscess. A younger age, absence of vaccination schedule, previous history of otitis, cochlear implant carriers or white blood cell counts and C-reactive protein levels were not associated with complications. Complicated cases had longer hospitalizations. Treatment included antibiotics, corticosteroids, and surgery in 50% of cases.
CONCLUSIONS: This study shows an increase of acute mastoiditis during 2023, with a relevant role of S. pyogenes. A younger age, absence of vaccination, personal history of otitis or cochlear implant, blood cell counts and C-reactive protein levels were not associated with complications.

BACKGROUND: The prevalence of Group A streptococcus (GAS) carriage among adults is studied less than in children. The variability of reported carriage rates is considerably large and differs among diverse geographic areas and populations.
OBJECTIVE: To evaluate the prevalence of GAS carriage among adults in Israel.
METHODS: In this prospective study, conducted in a large healthcare maintenance organization in Israel, we obtained pharyngeal cultures from adults attending the clinic without upper respiratory tract complaints or fever. Patient data included sex, age, number of children, and religious sectors.
RESULTS: From May to December 2022, eight family physicians collected a total of 172 throat swabs (86% response rate). The median age was 37 years (range 18-65); 72.7% were females, 22.7% were ultra-Orthodox Jewish, and 69.2% had children. The prevalence of GAS carriage was 6.98%, 95% confidence interval (95%CI) 3.7%-11.9%. GAS carriers were younger (31.7 vs. 39.3 years, P = 0.046), and the majority were ultra-Orthodox Jews (58.3% vs. 20%, P = 0.006). All GAS carriers were from lower socioeconomic status. When assessing risk factors for GAS carriage using multivariate analysis, only being an ultra-Orthodox Jew was positively related to GAS carriage (adjusted odds ratio 5.6, 95%CI 1.67-18.8).
CONCLUSIONS: Being an ultra-Orthodox Jew was the single variable associated with a GAS carriage, which may be related to having many children at home and living in overcrowded areas. Primary care physicians in Israel should recognize this situation when examining patients with sore throats, mainly ultra-Orthodox Jews.

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.

OBJECTIVE: To quantify the associations between invasive group A streptococcal disease (iGAS) incidence and influenza, varicella, and chronic hepatitis C virus (HCV).
METHODS: We used individual-level linked data of iGAS cases from Victoria, Australia (2007-2017) to assess associations between these viral infections and iGAS. A self-controlled case series method was used to estimate the relative incidence of iGAS following an influenza or varicella infection, while the relative incidence of iGAS among HCV cases, and HCV cases who inject drugs, was estimated using population-level data and a negative binomial regression model.
RESULTS: Of the 1949 individuals with at least one iGAS diagnosis, 82 were diagnosed with influenza at least once, 30 with varicella, and 118 with HCV during the study period. The relative incidence of iGAS increased substantially following infection with influenza (incidence rate ratio [IRR]: 34.5, 95% confidence interval [CI]: 21.3-55.8) or varicella (IRR: 22.4, 95% CI: 10.3-48.8). iGAS incidence was higher among HCV cases (IRR: 5.7, 95% CI: 4.4-7.3) compared to individuals without HCV. iGAS incidence was also higher among HCV cases who inject drugs (IRR: 17.9, 95% CI: 13.0-24.4) compared to individuals without HCV who did not inject drugs.
CONCLUSIONS: We found a significantly higher risk of iGAS following an influenza or varicella infection and for chronic HCV cases, particularly those who inject drugs. These findings are relevant to public health practice and support the timely identification of iGAS cases.

BACKGROUND: As pleural inflammation plays a central role in pleural infection (PI), corticosteroids are increasingly being considered as a potential therapy. However, the timing of treatment and the identification of patients who might benefit most remain unresolved. The aim of this study was therefore to investigate the inflammatory trajectories of children with PI.
METHODS: This retrospective single-center study included children aged 3 months to 17 years and 11 months hospitalized for PI due to Streptococcus pyogenes, Streptococcus pneumonia, and Staphylococcus aureus over 10 years. An inflammatory rebound was defined biologically as a reincrease in C-reactive protein (CRP) of at least 50 mg/L after an initial decrease in CRP of at least 50 mg/L.
RESULTS: We included 53 cases of PI, including 16 due to S. pyogenes, 27 due to S. pneumonia, and 10 due to S. aureus. An inflammatory rebound occurred in 20 patients (38%) after a median of 4.5 (3-6) days. This inflammatory rebound occurred in 9 (56%) children with S. pyogenes, 8 (30%) children with S. pneumonia, and 3 (30%) children with S. aureus. Children with an inflammatory rebound also had a higher rate of persistent fever after Day 7 and a longer length of stay (p = .01 for both).
CONCLUSIONS: We postulate that the inflammatory rebound identified in nearly 40% of our patients corresponds to an early postinfectious inflammatory response, and thus that corticosteroids may be most beneficial for children with PI if administered early (between Days 2 and 5).

Rapid antigen detection tests (RADT) for Group A streptococci (GAS) and point-of-care tests for C-reactive protein (CRP) are commonly used in patients with pharyngotonsillitis in Sweden and Denmark although CRP testing is not supported by guidelines. We aimed to describe (1) the proportion of patients tested with RADT and/or CRP, (2) the relation between test results and antibiotic prescribing, and (3) the association between CRP level and microbial aetiology.
We used a post-hoc-analysis of data collected in primary health care in a prospective aetiological study of 220 patients 15-45 years old diagnosed with pharyngotonsillitis. The outcomes of RADTs and CRP tests were related to antibiotic prescribing and microbial aetiology.
A RADT was used in 94% of the patients. A CRP test was used in 50% of the patients but more commonly in those with a negative RADT (59%) than in those with a positive RADT (38%) (p = 0.005). Most (74%) CRP tests were used in patients with a negative RADT. Antibiotic prescribing differed greatly between patients with a positive RADT (96%) and patients with a negative RADT (17%) (p < 0.001). In patients with a negative RADT, there was a positive association between CRP value and antibiotic prescribing (OR 1.05; 95% CI 1.02-1.07; p < 0.001). Patients with CRP values ≤ 30 mg/l were seldomly prescribed antibiotics. Patients with GAS in culture had the highest median CRP (46 mg/l), which was higher than in patients without GAS (8 mg/l; p < 0.001). However, the positive predictive value for GAS never exceeded 0.60 (95% CI 0.31-0.83) at the investigated CRP levels.
The widespread use of tests is a major deviation from national guidelines. Most CRP tests were used in patients with a negative RADT, suggesting a belief in the added value of a CRP test, and the CRP result seemed to influence antibiotic prescribing. However, as an aetiological test, CRP is not useful for predicting GAS.

Group A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data. We aimed to compare the incidence of iGAS infection before and after the COVID-19 pandemic, describe iGAS patients\' characteristics, and determine ICU mortality associated factors.
We performed a retrospective multicenter cohort study in 37 French ICUs, including all patients admitted for iGAS infections for two periods: two years before period (October 2018 to March 2019 and October 2019 to March 2020) and a one-year after period (October 2022 to March 2023) COVID-19 pandemic. iGAS infection was defined by Group A Streptococcus isolation from a normally sterile site. iGAS infections were identified using the International Classification of Diseases and confirmed with each center\'s microbiology laboratory databases. The incidence of iGAS infections was expressed in case rate.
Two hundred and twenty-two patients were admitted to ICU for iGAS infections: 73 before and 149 after COVID-19 pandemic. Their case rate during the period before and after COVID-19 pandemic was 205 and 949/100,000 ICU admissions, respectively (p < 0.001), with more frequent STSS after the COVID-19 pandemic (61% vs. 45%, p = 0.015). iGAS patients (n = 222) had a median SOFA score of 8 (5-13), invasive mechanical ventilation and norepinephrine in 61% and 74% of patients. ICU mortality in iGAS patients was 19% (14% before and 22% after COVID-19 pandemic; p = 0.135). In multivariate analysis, invasive mechanical ventilation (OR = 6.08 (1.71-21.60), p = 0.005), STSS (OR = 5.75 (1.71-19.22), p = 0.005), acute kidney injury (OR = 4.85 (1.05-22.42), p = 0.043), immunosuppression (OR = 4.02 (1.03-15.59), p = 0.044), and diabetes (OR = 3.92 (1.42-10.79), p = 0.008) were significantly associated with ICU mortality.
The incidence of iGAS infections requiring ICU admission increased by 4 to 5 after the COVID-19 pandemic. After the COVID-19 pandemic, the rate of STSS was higher, with no significant increase in ICU mortality rate.