A multidisciplinary approach to identify and analyse not only the causes but also the risk factors for increased mortality in invasive infections caused by Streptococcus pyogenes

ISRCTN	ISRCTN52769435
DOI	https://doi.org/10.1186/ISRCTN52769435
Sponsor	General University Hospital in Prague
Funder	Ministerstvo Zdravotnictví Ceské Republiky

Submission date: 23/04/2026
Registration date: 24/04/2026
Last edited: 24/04/2026

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Vaclava Adamkova
Principal investigator

Ke Karlovu 2
Prague
12000
Czech Republic

ORCID ID	0000-0002-7629-5365
Phone	+420 (0)725344741
Email	vaclava.adamkova@vfn.cz

Dr Jan Zavora
Scientific

Ke Karlovu 2
Prague 2
12000
Czech Republic

Phone	+420 (0)224967264
Email	jan.zavora@vfn.cz

Dr Gabriela Kronieslová
Public

Ke Karlovu 2, Praha 2
Prague 2
12000
Czech Republic

Phone	+420 (0)224967265
Email	gabriela.kroneislova@vfn.cz

Study information

Primary study design	Observational
Observational study design	Cohort study
Scientific title	A multidisciplinary investigation of molecular mechanisms and clinical risk factors predicting increased mortality in invasive Streptococcus pyogenes infections
Study objectives	1. To investigate the minimum inhibitory concentrations (MIC) of all S. pyogenes isolates for relevant antibiotics and determine whether the MIC values are higher in invasive isolates than in non-invasive ones 2. To find the virulence factor(s) of S. pyogenes responsible for the higher invasiveness into the bloodstream 3. Determine biomarkers, routinely diagnosable and available in urgent mode, that will function as prognostic 4. To evaluate disproportionate or inadequate answer of the immune system to S. pyogenes infection
Ethics approval(s)	Approved 20/06/2024, Ethics Committee of the General University Hospital in Prague (U Nemocnice 2, Prague, 12800, Czech Republic; +420 (0)224 961 111; eticka.komise@vfn.cz), ref: 47/24 Grant AZV VES 2025
Health condition(s) or problem(s) studied	Streptococcus pyogenes infection
Intervention	This is a multicentre, prospective, non-interventional cohort study. The enrolment will take place in three centres in the Czech Republic. We plan to enrol 300 adult patients in total. Patients over 18 years of age with evidence of skin and soft tissue infection or unclear origin caused by S. pyogenes are enrolled in the study. In patients admitted with signs of infection and possible streptococcal aetiology, blood cultures are taken, standard biomarkers are collected. Patients are assigned a protocol number so that blood samples can be preserved for possible further analysis if the aetiology of S. pyogenes is confirmed. S. pyogenes is identified by latex agglutination and matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. For all strains of S. pyogenes isolated from patients with invasive infection, minimum inhibitory concentration of selected antibiotics will be determined by gradient strip method. To identify virulence factor(s), molecular genetic approaches including whole genome sequencing, transcriptomics and comparative proteomics will be used. Biomarkers and immunological markers levels are measured in a hospital laboratory using commercially available assays as part of routine care. In the case of a confirmed S. pyogenes aetiology, biomarkers and special immunological markers will be tested from stored samples.
Intervention type	Other
Primary outcome measure(s)	S. pyogenes identification measured using latex agglutination and matrix-assisted laser desorption ionisation at a single timepoint The minimum inhibitory concentrations (MIC) of all S. pyogenes isolates for relevant antibiotics (penicillin, erythromycin, clindamycin, tetracycline, rifampicin, linezolid, co-trimoxazole, vancomycin and daptomycin) measured using gradient strip at a single timepoint The virulence factor(s) of S. pyogenes responsible for the higher invasiveness into the bloodstream, measured using molecular genetic approaches including whole genome sequencing (WGS) using next-generation sequencing (NGS) technologies, transcriptomics and comparative proteomics, at a single timepoint Procalcitonin (PCT), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), white blood cell (WBC) count, Intensive Care Infection Score (ICIS), albumin, lactate, creatinine, myoglobin measured using commercially available assays as part of routine care in hospital laboratory at a single timepoint Mid-regional pro-adrenomedullin (MR-proADM) and vitamin D measured using chemiluminescence immunoassay (CLIA) by Liaison XL at a single timepoint Heparin-binding protein measured using enzyme-linked immunosorbent assay kit at a single timepoint Pancreatic stone protein measured using point-of-care testing (POCT) at a single timepoint Vascular endothelial growth factor (VEGF) measured using enzyme-linked immunosorbent assay kit at a single timepoint Presence of activating molecules on selected immune cells of naïve immunity in whole blood (CD64 on neutrophils, CD169 on monocytes) measured using flow cytometry at a single timepoint Activation of cell-specific immunity in human whole blood samples measured using flow cytometry at a single timepoint
Key secondary outcome measure(s)
Completion date	31/12/2028

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	99 Years
Sex	All
Target sample size at registration	45
Key inclusion criteria	1. Aged >18 years 2. Invasive S. pyogenes infections 3. Skin and soft tissue infections caused by S. pyogenes
Key exclusion criteria	1. Aged <18 years 2. Other bacterial finding in blood cultures and clinically valid samples than S. pyogenes
Date of first enrolment	23/05/2025
Date of final enrolment	30/06/2028

Locations

Countries of recruitment

Czech Republic

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

Editorial Notes

24/04/2026: Study's existence confirmed by the Ethics Committee of the General University Hospital in Prague.