Group A Streptococcus Research Articles

LiaR-dependent gene expression contributes to antimicrobial responses in group A Streptococcus.

The ability to sense and respond to host defenses is essential for pathogen survival. Some mechanisms involve two-component systems (TCSs) that respond to host molecules, such as antimicrobial peptides (AMPs), and activate specific gene regulatory pathways to aid in survival. Alongside TCSs, bacteria coordinate cell division proteins, chaperones, cell wall sortases, and secretory translocons at discrete locations within the cytoplasmic membrane, referred to as functional membrane microdomains (FMMs). In group A Streptococcus (GAS), the FMM or "ExPortal" coordinates protein secretion, cell wall synthesis, and sensing of AMP-mediated cell envelope stress via the LiaFSR three-component system. Previously, we showed that GAS exposure to a subset of AMPs (α-defensins) activates the LiaFSR system by disrupting LiaF and LiaS co-localization in the ExPortal, leading to increased LiaR phosphorylation, expression of the transcriptional regulator SpxA2, and altered GAS virulence gene expression. The mechanisms by which LiaFSR integrates cell envelope stress with responses to AMP activity and virulence are not fully elucidated. Here, we show the LiaFSR regulon is comprised of genes encoding SpxA2 and three membrane-associated proteins: a PspC domain-containing protein (PCP), the lipoteichoic acid-modifying protein LafB, and the membrane protein insertase YidC2. Our data support that phosphorylated LiaR induces transcription of these genes via a conserved operator, whose disruption attenuates GAS virulence and increases susceptibility to AMPs in a manner primarily dependent on differential expression of SpxA2. Our work expands our understanding of the LiaFSR regulatory network in GAS and identifies targets for further investigation of mechanisms of cell envelope stress tolerance contributing to GAS pathogenesis.

Brain abscess caused by Streptococcus pyogenes with atypical symptoms: a case report and literature review.

Streptococcus pyogenes is a common gram-positive bacterium, belonging to group A Streptococcus (GAS), and is responsible for causing a range of clinical conditions. Brain abscess caused by GAS is uncommon in pediatric infectious diseases, and GAS brain abscess without acute infectious symptoms has been rarely reported. We present a case of one GAS brain abscess in a previously healthy child with unusual clinical manifestations of decreased muscle strength in the left limbs. The right frontal lobe mass lesion was resected using a microscope-based neuronavigation system. A sole defectively beta-hemolytic Streptococcus pyogenes was isolated from the lesion. The patient's peripheral blood whole-exome and the pathogen's whole-genome sequencing were performed respectively, revealing a heterozygous mutation in the interferon regulatory factor-8 (IRF8) gene in the patient and lack of hyaluronic acid capsules in Streptococcus pyogenes (genotype emm22). The patient eventually recovered after prompt surgical drainage of the abscess and appropriate antibiotic treatment. It is important to pay attention to Streptococcus pyogenes brain abscesses with mild clinical manifestations. Upon reviewing all the cases of pediatric GAS brain abscess reported in the published literature, we discovered that early diagnosis and treatment are crucial factors that impact the prognosis of GAS brain abscess.

Centor scores associated poorly with rapid antigen test findings in children with sore throat.

The Centor score alone does not seem to be of any utility in guiding the diagnosis of suspected streptococcal pharyngitis. Microbiological testing remains necessary for accurate diagnosis and CRP should not be used to differentiate viral and bacterial pharyngitis cases. • The Centor score is a clinical prediction model for differentiating Group A streptococcal (GAS) pharyngitis from viral pharyngitis. • Finnish Current Care Guideline recommends rapid antigen testing in patients with Centor score ≥ 3 for diagnosing GAS infections and antibiotics prescribed based on confirmed test results. • The Centor score alone does not seem to have any use in guiding the diagnosis of suspected streptococcal pharyngitis in children. • Microbiological testing remains necessary for accurate diagnosis in patients with sore throat.

Microbial profile of diabetic foot osteomyelitis from the northwest of England

BackgroundOsteomyelitis of the diabetic foot is a common and challenging complication affecting patients with diabetic foot ulcers and infections. The complexity of these infections lies in their polymicrobial nature, high rates of persistence and recurrence. This study examined the microbiological profile of diabetic foot osteomyelitis from a teaching hospital in Northwest England and their resistance patterns to understand its impact on infection persistence and to direct effective treatment.MethodsA retrospective review of 105 patients who underwent surgical management for diabetic foot osteomyelitis between 2019 and 2024. We analysed three consecutive culture samples for each patient to assess for the microbiological profile and resistance patterns of these infections and to monitor infection recurrence and persistence rates.ResultsA total of 105 patients were identified. Infection eradication was noted in 42% of the cohort, infection persistence in 18%, and late infection recurrence in 40%. Polymicrobial growth was evident in 72% of our study sample. Gram-positive bacteria made up the majority of the bacterial isolates in all 3 culture samples, 74.81% in sample 1, 69.31% in sample 2, and 55.1% in sample 3. Staphylococcus aureus was the most prevalent gram-positive bacteria, at 52.38% in sample 1, 36.19% in sample 2, and 18.09% in sample 3, followed by Haemolytic Streptococcus, Enterococcus and Corynebacterium. The frequently identified gram-negative bacteria were Pseudomonas in sample 1 (7.61%), E. coli and Proteus in sample 2 (5,71%), Pseudomonas and Proteus in sample 3 (2.85%). Gram-positive bacteria were resistant to penicillin and macrolides with resistance of staphylococcus aureus to clarithromycin identified among all 3 culture samples. Gram-negative bacteria were most resistant to amoxicillin. Staphylococcus aureus was responsible for infection persistence in most of our cohort (12/19) 63.15%. Among those patients, Staphylococcus was resistant to clarithromycin in 6 of the cases. The 5-year mortality rate for our study sample was 32.38%.ConclusionThis study highlights the prevalence of polymicrobial growth and multi-drug resistant pathogens in the scope of diabetic foot osteomyelitis. It highlights the predominance of Staphylococcus aureus and its resistant strains among patients affected by diabetic foot osteomyelitis in Greater Manchester.

Proper duration of antibiotics after video-assisted thoracoscopic surgery for the treatment of thoracic empyema

Background When chest tube drainage does not adequately resolve thoracic empyema, video assisted thoracoscopic surgery (VATS) is often needed. However, the proper duration of antibiotics after VATS is poorly defined. Consequently, the objective of this study was to evaluate if short antibiotic durations post-VATS was equally effective compared to longer durations. Methods Patients with thoracic empyema treated with VATS were identified retrospectively by a query of the hospital billing database. The bacterial causes of the empyema were divided into 8 different categories while the antibiotic duration after VATS was divided into two groups which included antibiotics ˂ 14 days and antibiotics >14 days. The primary outcome measured was rates of empyema recurrence. Statistical comparisons were conducted between the antibiotic duration groups overall and when stratified based on the different bacterial causes. Results 137 patients were included in this study with the main cause of empyema being culture negative empyema (37.2%) while alpha haemolytic Streptococcus spp. was the most cultured bacteria (26.3%). There was no statistical difference (p = 0.5168), in the rates of empyema recurrence, when short antibiotic durations (median 11.6 days)were compared to longer antibiotic durations (median 29.1 days)post-VATS. Nor was there a statistical difference in recurrence rates when stratifying based on bacterial cause. Conclusion This study reinforces that antibiotic durations less than 14 days post-VATS are equally effective as prolonged antibiotic durations. However, to determine the proper duration of antibiotic therapy post-VATS, a prospective clinical trial is needed to reduce complications of prolonged antibiotic therapies for these patients.

High-resolution cryo-EM analysis of a Streptococcus pyogenes M-protein/human plasminogen complex.

The importance of human plasminogen (hPg)/plasmin (hPm)/cell receptor complexes in invasiveness of cells has been amply established. The objective of this investigation was to determine a high-resolution structure of a major Group A Streptococcus (GAS) bacterial receptor (PAM) for hPg/hPm when bound on a cell surface to its major ligand, hPg. As a model cell surface with endogenous PAM, we employed engineered PAM-expressing lentivirus (LV) particles. We show that the ectodomain of a PAM-type M-Protein (M-Prt), in complex with hPg, is folded through distinct intra- and inter-domain interactions to a more compact form on the cell surface, thus establishing a new paradigm for membrane-bound M-Prt/ligand structures. These studies provide a framework for addressing the need for treatments of GAS disease by providing a molecular platform to solve structures of virulence-determining membrane proteins.

M proteins of group A Streptococcus bind hyaluronic acid via arginine-arginine/serine-arginine motifs.

Tissue injury, including extracellular matrix (ECM) degradation, is a hallmark of group A Streptococcus (GAS) skin infection and is partially mediated by M proteins which possess lectin-like properties. Hyaluronic acid is a glycosaminoglycan enriched in the cutaneous ECM, yet an interaction with M proteins has yet to be explored. This study revealed that hyaluronic acid binding was conserved across phylogenetically diverse M proteins, mediated by RR/SR motifs predominantly localized in the C repeat region. Keratinocyte wound healing was decreased through the recruitment of hyaluronic acid by M proteins in an M type-specific manner. GAS strains 5448 (M1 serotype) and ALAB49 (M53 serotype) also bound hyaluronic acid via M proteins, but hyaluronic acid could increase bacterial adherence independently of M proteins. The identification of host-pathogen mechanisms that affect ECM composition and cell repair responses may facilitate the development of nonantibiotic therapeutics that arrest GAS disease progression in the skin.

Nosocomial Transmission of Necrotizing Fasciitis: A Molecular Characterization of Group A Streptococcal DNases in Clinical Virulence

Streptococcus pyogenes, or Group A Streptococcus (GAS), is responsible for over 500,000 deaths per year. Approximately 15% of these deaths are caused by necrotizing soft-tissue infections. In 2008, we isolated an M5 GAS, named the LO1 strain, responsible for the nosocomial transmission of necrotizing fasciitis between a baby and a nurse in Belgium. To understand this unusual transmission route, the LO1 strain was sequenced. A comparison of the LO1 genome and transcriptome with the reference M5 Manfredo strain was conducted. We found that the major differences were the presence of an additional DNase and a Tn916-like transposon in the LO1 and other invasive M5 genomes. RNA-seq analysis showed that genes present on the transposon were barely expressed. In contrast, the DNases presented different expression profiles depending on the tested conditions. We generated knock-out mutants in the LO1 background and characterized their virulence phenotype. We also determined their nuclease activity on different substrates. We found that DNases are dispensable for biofilm formation and adhesion to both keratinocytes and pharyngeal cells. Three of these were found to be essential for blood survival; Spd4 and Sdn are implicated in phagocytosis resistance, and Spd1 is responsible for neutrophil extracellular trap (NET) degradation.

Distinguishing Gram-Positive and Gram-Negative Bloodstream Infections through Leukocytes, C-reactive protein, Procalcitonin, and D-Dimer: An Empirical Antibiotic Guidance.

This retrospective study aimed to compare the difference of the levels of white blood cells (WBC), C-reactive protein (CRP), procalcitonin, and D-Dimer in the bloodstream infection (BSI) patients, and their values in distinguishing bacterial categories. A total of 847 bloodstream infection patients were analyzed and divided into Gram-positive BSI (GP-BSI) and Gram-negative BSI (GN-BSI) groups. Most frequently isolated pathogens in GP-BSI were Staphylococcus epidermidis (35.75%), followed by Staphylococcus hominis (18.33%), and Streptococcus haemolyticus (10.16%), while in GN-BSI, Escherichia coli (30.07%), Klebsiella pneumoniae (23.98%), and Acinetobacter baumannii (13.18%) were the most common. The predictive value was evaluated based on three years of patient data, which showed an area under the curve (AUC) of 0.828. It was further validated using two years of data, which yielded an AUC of 0.925. Significant differences existed in the procalcitonin, D-Dimer, and CRP levels between GN-BSI and GP-BSI. The current results provide a more effective strategy for early differential diagnosis in bacterial categorization of BSI when combining WBC, CRP, procalcitonin, and D-Dimer measurements.

Unveiling the Group A Streptococcus Vaccine-Based L-Rhamnose from Backbone of Group A Carbohydrate: Current Insight Against Acute Rheumatic Fever to Reduce the Global Burden of Rheumatic Heart Disease

Group A Streptococcus (GAS) is a widely distributed bacterium that is Gram-positive and serves as the primary cause of acute rheumatic fever (ARF) episodes. Rheumatic heart disease (RHD) is a sequela resulting from repeated ARF attacks which are also caused by repeated GAS infections. ARF/RHD morbidity and mortality rates are incredibly high in low- and middle-income countries. This is closely related to poor levels of sanitation which causes the enhanced incidence of GAS infections. Management of carditis in RHD cases is quite challenging, particularly in developing countries, considering that medical treatment is only palliative, while definitive treatment often requires more invasive procedures with high costs. Preventive action through vaccination against GAS infection is one of the most effective steps as a solution in reducing RHD morbidity and mortality due to curative treatments are expensive. Various developments of M-protein-based GAS vaccines have been carried out over the last few decades and have recently begun to enter the clinical stage. Nevertheless, this vaccination generates cross-reactive antibodies that might trigger ARF assaults as a result of the resemblance between the M-protein structure and proteins found in many human tissues. Consequently, the development of a vaccine utilizing L-Rhamnose derived from the poly-rhamnose backbone of Group A Carbohydrate (GAC) commenced. The L-Rhamnose-based vaccine was chosen due to the absence of the Rhamnose biosynthesis pathway in mammalian cells including humans thus this molecule is not found in any body tissue. Recent pre-clinical studies reveal that L-Rhamnose-based vaccines provide a protective effect by increasing IgG antibody titers without causing cross-reactive antibodies in test animal tissue. These findings demonstrate that the L-Rhamnose-based vaccine possesses strong immunogenicity, which effectively protects against GAS infection while maintaining a significantly higher degree of safety.

Rheumatic heart disease: an ongoing public health concern in vulnerable communities

Abstract Background Acute rheumatic fever (ARF) results from an autoimmune response triggered by group A streptococcus (GAS) infection (1). Severe or recurrent ARF episodes can cause permanent heart valve damage, leading to complications including heart failure, stroke, arrhythmias, carditis, and decompensation during pregnancy (2). Purpose Rheumatic fever (RF) remains a public health concern in Australia, particularly among Indigenous, migrant populations and socioeconomically disadvantaged communities. Europe and various regions worldwide have experienced significant migration from areas with a high prevalence of RHD (3). Amongst the more than 1 million asylum seekers who arrived in Europe in 2015, an estimated 1% could potentially be affected by RHD (3). This migration influx underscores the pressing need for the implementation of strategies in health policy and practice. We aimed to outline the attributes of our RF-RHD cohort to aid in the formulation of a Model of Care (MoC). Methods Cases were identified on a quarterly basis either through the NSW Public Health Rapid, Emergency, Disease, and Syndromic Surveillance (PHREDSS) system or via clinical diagnoses reported to the Public Health Unit (PHU) from January 2015 to June 2023. Demographic profiles, clinical particulars, and patient outcomes were collected from patients in the South Western Sydney Local Health District (SWSLHD), NSW, Australia. Results A total of 45 cases were reported (Table 1). This consisted predominantly of females with an average age at diagnosis of 14 years. A majority were obese (69%). Most were in the Maori and Pacific Islander populations (62%), while a smaller portion of patients were of Aboriginal or Torres Strait Islander descent (9%) (Australian Indigenous community). Notably, 84% of patients diagnosed with ARF subsequently progressed to RHD. Among the reported cases, 16 patients underwent valvular surgery, 2 patients progressed to end-stage heart failure, and there was 1 mortality. 39% (11) of female patients were pregnant during the study period, with 6 (55%) of these patients decompensating during their pregnancy (Table 2). Conclusion Rheumatic fever persists as a public health concern on a global scale. Our findings emphasize the need for a high index of clinical awareness in considering RF/RHD in socioeconomically disadvantaged communities. In our setting, there is a disproportionate burden of disease among the Pacific Islander population. The high occurrence of cardiac decompensation during pregnancy, underscores the need for close monitoring in this demographic. Despite the prevalence of rheumatic fever predominantly affecting young patients in vulnerable groups, we found a significant proportion of individuals lost to follow-up or not connected with Cardiology services. Addressing rheumatic fever requires a comprehensive approach that encompasses improved healthcare accessibility, targeted health education initiatives, and socioeconomic interventions.

Use of point-of-care tests in pharyngotonsillitis – a registry-based study in primary health care

Background Point-of-care (POC) tests, including C-reactive protein (CRP) tests and rapid antigen detection tests (RADT) for group A streptococci (GAS), are widely used in Swedish primary health care (PHC). This study quantifies their use in pharyngotonsillitis and explore their association with antibiotic prescribing. Material and methods Retrospective data from 2012–2016 in Region Kronoberg, Sweden, included all PHC visits with a pharyngotonsillitis diagnosis. Patient characteristics, test usage and antibiotic prescriptions were linked by visit date and personal identification number. Descriptive statistics were used for POC test analysis. Logistic regression assessed the association between CRP levels and antibiotic prescribing. Results Of 24,237 visits, 68% included RADT and 36% included a CRP test, with 89% of CRP tests performed alongside RADT. CRP testing was more frequent in patients with negative (56%) than positive RADTs (42%) (p < .001). Overall, 66% of RADTs were positive. Median CRP levels were 23 mg/l for positive RADT and 31 mg/l for negative RADT (p < .001). Antibiotics were prescribed for 95% of positive RADTs and 43% of negative RADTs (p < .001). In patients with negative RADTs, CRP testing was associated with higher antibiotic prescribing (57%) compared to no CRP testing (26%) (p < .001). Among these patients, CRP levels were associated with prescribing (aOR 1.032; 95% CI 1.029–1.035; p < .001), with 50% of prescriptions occuring at CRP levels ≤ 20 mg/l. Conclusion The use of RADTs and the proportion of positive test were higher than expected, indicating inappropriate use and diagnostic bias. CRP testing, contrary to guidelines, was common and associated with increased antibiotic prescribing.

ICESp1109, a novel hybrid Integrative Conjugative Element of macrolide-resistant Streptococcus pyogenes serotype M77 collected between 2003 and 2017 in Poland.

Genetic characterization of the antibiotic resistance determinants and associated mobile genetic elements (MGEs) among Streptococcus pyogenes [Group A streptococci (GAS)] clinical isolates of an M77 serotype collected in Poland between 2003 and 2017. The genomes of 136 M77 GAS isolates were sequenced using Illumina, and selected with long-read approach (Oxford Nanopore). Whole genome sequences were analyzed to determine the presence of macrolide resistance determinants, and their genetic context. The strains used in the study were collected in the two multicenter surveys from in- and outpatients. Sequencing data analysis revealed that all strains carried the tet(O) gene (100%, N=136). They were classified as a single sequence type ST63. For erythromycin resistance, the unique determinant was erm(TR) detected in 76.5% (N=104) isolates. A single appearance of tet(M) and erm(B) on Tn3872 was noticed. The mefA, mefE, and msr(D) genes were detected in neither of the genomes. This correlated with the detected strain phenotypes - 11 exhibited cMLSB, 93 - iMLSB, and no M phenotype.The erm(TR) gene was predominantly (N=74) found within a novel hybrid Integrative Conjugative Element composed of the ICESp1108-like sequence and ICESp2906 variant which was then named ICESp1109. However, in strains isolated before 2008, erm(TR) was located within ICESp2905 (N=27). The erm(TR) gene was detected within stand-alone ICESp1108-like sequences in 3 strains. Based on phylogenetic analysis results the clonal dissemination of the macrolide-resistant S. pyogenes M77/ST63 strain with hybrid ICESp1109 was observed between 2008 and 2017. ICESp1109 is the novel hybrid ICE in Gram-positive bacteria.

Prompt diagnosis and treatment of peri-orbital necrotising fasciitis caused by group A β-haemolytic Streptococcus (GAS): a case report.

Necrotising fasciitis is a devastating infection characterised by rapidly progressing necrotising infection of the superficial fascia with secondary necrosis of the overlying skin. To describe the pathophysiology, differential diagnosis, and outcome in a rare case of periorbital necrotising fasciitis caused by group A β-haemolytic Streptococcus. A 60-year-old female with insulin-dependent diabetes presented with pyrexia and bilateral peri-orbital swelling, progressing to left periorbital necrotising fasciitis. It was caused by dual infection with group A β-haemolytic Streptococcus and Herpes Simplex Virus 1. A combination of intravenous antibiotics and surgical debridement and subsequent skin grafting resulted in a beneficial outcome in our patient. Differentiating cellulitis and necrotising fasciitis can be difficult when presenting signs and symptoms are non-specific. If not treated quickly with antibiotics and debridement of the infected tissue, the patient may develop septic shock within hours.

6472 Methimazole Induced Agranulocytosis: Uncommon Complication of a Common Medication

Abstract Disclosure: R. Kaur: None. L. Kaur: None. A. Sridhar: None. T. Chaudhary: None. N. Patel: None. Methimazole (MMI) induced agranulocytosis is a rare and life threatening adverse effect that usually occurs within 3 months of drug initiation and can rapidly lead to overwhelming infection. It is reported in 0.1 to 0.5 % of patients on treatment with methimazole. MMI is a standard drug used in graves disease and toxic multinodular goiter. We report a case of MMI induced agranulocytosis in an elderly female with recently diagnosed toxic multinodular goiter. A 66 year old female with past medical history of recently diagnosed toxic multinodular goiter for which she was started on methimazole 80mg/day two months ago presented to the emergency department with chief complaint of severe sore throat associated with rapidly increasing pharyngeal pain and fever over the past 24 hours. She was lethargic, febrile with temperature of 102 F, tachycardic with heart rate of 115/minute and hypotensive with blood pressure of 108/64 mm Hg. Physical examination revealed diffuse pharyngeal and tonsillar erythema with bilateral purulent exudate with tender anterior cervical lymphadenopathy. Thyroid was enlarged, firm, irregular and nontender. Pulmonary, cardiac and abdominal exam was unremarkable. Lab work showed severe leukopenia with WBC count of 1,600/mm3, neutropenia with absolute neutrophil count of 0.0 x 1000/ul (normal range 1.8-7.3 x 1000/ul) and erythrocyte sedimentation rate and C reactive protein were both elevated. Blood cultures and fungal cultures showed no growth. Urinalysis and urine culture were both unremarkable. She had an extensive haematological, rheumatological and infectious disease workup for neutropenia, which was largely unrevealing. Rapid streptococcal testing was negative but throat cultures grew beta haemolytic streptococci. Treatment included suspending methimazole, administering antimicrobial therapy with piperacillin - tazobactam, acyclovir and fluconazole. She was also started on a granulocyte colony stimulating factor. Patient presented satisfactory evolution with progressive increase in leukocyte count and remission of symptoms by day 5 of treatment, rendering further bone marrow testing unnecessary. Antibiotics were changed to oral amoxicillin-clavulanic acid after throat culture results were available and the patient was discharged in stable condition. One month after discharge she underwent total thyroidectomy for definitive cure and is currently followed up as an outpatient by endocrinology. The objective of this case report is to present an uncommon case of agranulocytosis secondary to use of methimazole and to increase awareness among the physicians about the need to consider this diagnosis in patients on this medication. It is also advised that these patients be educated about the drugs side effects, a practice that may avert suffering and unnecessary costs. Presentation: 6/3/2024

A-351 Versatile and Sensitive Microfluidic Immunoassay for Improved Point-of-Care Diagnostics

Abstract Background Healthcare professionals must choose between sensitivity and ease-of-use in diagnostics, particularly for diseases like COVID-19 and strep throat. Traditional enzyme-linked immunosorbent assays (ELISAs) are sensitive but are manually intensive and lengthy. Lateral flow assays (LFAs) are an alternative with low cost, ease-of-use, and rapid results; but LFAs suffer from low sensitivity. Burst Diagnostics presents a groundbreaking solution with the capillary-driven immunoassay (CaDI), a novel microfluidic device delivering sensitivity comparable to ELISA with the ease of LFAs. Methods The CaDI is made of flow channels defined by layered transparency and adhesive sheets containing reagent pads with HRP-conjugated antibody and luminol. The system requires only a sample addition step by the user. Sample flow initiates sequential steps of a sandwich ELISA, fully automated by the device, to provide a chemiluminescent signal in 10 minutes or less, depending on sample matrix. Results We have demonstrated success with preliminary studies for the detection of SARS-CoV-2 nucleocapsid protein (NP) and group A streptococcus (GAS). Detection of NP was achieved by assembling and optimizing COVID-19 CaDI’s using anti-NP antibodies. Then, spiked nasal swab samples were tested ranging from 10 to 1000 PFU/mL with positive detection as low as 10 PFU/mL, much less than the same samples in a traditional LFA (see figure). Additionally, we have demonstrated successful detection of GAS in optimized buffer conditions up to 100-fold less than commonly used LFAs. Finally, multiplexed CaDI’s increase throughput and cost-effectiveness in the point-of-care setting. Conclusions The CaDI platform bridges the ease of LFAs and sensitivity/specificity of laboratory tests. Currently, the CaDI can detect SARS-CoV-2 NP and GAS with higher sensitivity than existing LFAs. Development is underway for a reader to accompany the CaDI and further simplify the test. Importantly, the potential targets for detection are immense due to the sensitivity, simplicity, and adaptability of the platform.

Adjunctive linezolid versus clindamycin for toxin inhibition in β-lactam-treated patients with invasive group A streptococcal infections in 195 US hospitals from 2016 to 2021: a retrospective cohort study with target trial emulation

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.

Acute disseminated encephalomyelitis (ADEM) in a patient with post streptococcal glomerulonephritis (PSGN): A case report.

Concurrent recurrence of acute disseminated encephalomyelitis (ADEM) and poststreptococcal glomerulonephritis (PSGN) in a thalassemia intermedia patient is rare and underscores the complexity of autoimmune disorders. This case emphasizes the importance of considering ADEM in the differential diagnosis of children presenting with PSGN accompanied by neurological symptoms. Post-streptococcal glomerulonephritis (PSGN) is a common group A streptococcal (GAS) infection sequela. The pathophysiology of PSGN involves immune complex deposition, with type 3 hypersensitivity reaction triggered by GAS. Certain neurological conditions may also arise following a GAS infection, possibly due to molecular mimicry in the brain, a pathophysiology similar to rheumatic fever, another common sequel of GAS infection. We present the case of a child with β-thalassemia intermedia who exhibited the classic triad (edema, hypertension, hematuria) of PSGN along with neurological manifestations, including a low glasgow coma scale (GCS) score and seizures. Magnetic resonance imaging (MRI) of the brain indicated changes consistent with acute disseminated encephalomyelitis (ADEM). Initially treated with methylprednisolone, the patient eventually received intravenous immunoglobulin (IVIG) due to lack of response. The patient had a good outcome, with complete resolution of all symptoms and no residual neurological deficits. This case underscores the importance of considering ADEM in the differential diagnosis for patients presenting with neurological signs and symptoms following a recent throat infection with GAS. Furthermore, given the increased risk of infection in thalassemia, patients with thalassemia who have a throat infection and neurological symptoms should be evaluated for the possible presence of ADEM.

Carrier rates of group A streptococci in Australian wet tropics and their impact on the clinical usefulness of throat swabs.

Rapid point-of-care tests (POCT) are likely to assist with the detection of group A streptococci (GAS), but their usefulness is determined by the presence of carriers of GAS. This is insufficiently explored in the wet tropics. This study included 77 patients attendingprimary care in the wet tropics complaining of a sore throat, and 49healthy controls. Carrier rates of GAS and the positive and negative etiological predictive values (P-EPV and N-EPV, respectively) of a POCT were calculated. The carrier rates were 8.3% among healthy children and 2.7% for adults. TheP-EPV for children was 71% (95%confidence interval [CI]: 0.0-100%) and for adults it was 85% (95% CI: 0.0-100%). The corresponding N-EPV was99% (95% CI: 95-100%) for children and99% (95% CI: 98-100%) for adults. N-EPV, ruling out GAS, was sufficiently high with narrow CIs to allow for defining a stopping rule to avoid unnecessary antibiotic prescribing.

Carrier rates of group A streptococci in Australian wet tropics and their impact on the clinical usefulness of throat swabs.

Rapid point-of-care tests (POCT) are likely to assist with the detection of group A streptococci (GAS), but their usefulness is determined by the presence of carriers of GAS. This is insufficiently explored in the wet tropics. This study included 77 patients attendingprimary care in the wet tropics complaining of a sore throat, and 49healthy controls. Carrier rates of GAS and the positive and negative etiological predictive values (P-EPV and N-EPV, respectively) of a POCT were calculated. The carrier rates were 8.3% among healthy children and 2.7% for adults. TheP-EPV for children was 71% (95%confidence interval [CI]: 0.0-100%) and for adults it was 85% (95% CI: 0.0-100%). The corresponding N-EPV was99% (95% CI: 95-100%) for children and99% (95% CI: 98-100%) for adults. N-EPV, ruling out GAS, was sufficiently high with narrow CIs to allow for defining a stopping rule to avoid unnecessary antibiotic prescribing.