Adjunctive Clindamycin Versus Linezolid for β-lactam Treated Patients With Invasive Group A Streptococcal Infections

Study Overview
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Brief Summary
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This study aims to emulate a hypothetical target pragmatic multi-center, non-blinded trial of adult inpatients in the PINC AITM dataset with B-lactam treated culture confirmed monomicrobial invasive Group A streptococcus (GAS) between the years 2015-2021

Official Title
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Comparative Effectiveness of Adjunctive Clindamycin Versus Linezolid for β-lactam Treated Patients With Invasive Group A Streptococcal Infections: A Target Trial Emulation

Conditions
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Streptococcal Sepsis, Invasive Group A Beta-Haemolytic Streptococcal Disease, Infection, Bloodstream, Infection, Bacterial, Streptococcal Toxic Shock Syndrome, Necrotizing Soft Tissue Infection

Intervention / Treatment
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* Drug: Linezolid
* Drug: Clindamycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult inpatients patients (=> 18 y of age) Monomicrobial Group A streptococcus invasive infection Primary therapy with a B-lactam agent (initiated before or on same day as adjunctive anti-toxin therapy) Exclusion Criteria: Patients with a polymicrobial GAS culture (non-GAS organisms identified on eligibility GAS culture) Patients who received linezolid but have a documented linezolid resistant isolate Patients with GAS infections of non-sterile non-invasive sites (i.e sites which do not meet above mentioned inclusion criteria) which include but not limited to the lower urinary tract, upper respiratory tract Patient with concomitant MSSA/MRSA invasive infection (+/- seven days of index GAS eligibility culture) Patients who receive both anti-toxin agents (violation of protocol) Patient who do not complete at least 3 days of B-lactam (violation of protocol)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Linezolid|Adjunctive antitoxin therapy|
|Drug: Clindamycin|Adjunctive antitoxin therapy|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In hospital mortality or discharge to hospice | In hospital mortality or discharge to hospice | Hospital stay | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay among survivors | Duration of hospitalization among surviving participants | Hospital stay | 
| Clostridioides difficile infection | C. difficile positive (PCR or antigen) result within same encounter downstream of the antitoxin therapy within 30 days and/or presence of a non present on admission (POA) C. difficile diagnosis code in conjugation with receipt of C. difficile therapy (PO/rectal vancomycin or PO fidaxomicin or IV metronidazole) | Within hospital stay of interest | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Invasive GAS, necrotizing soft tissue infection, streptococcal toxic shock syndrome, linezolid, clindamycin, anti-toxin therapy