Systemic Infection
Conditions
Keywords
Systemic infection, Sepsis, Biomarkers, C reactive protein, Antibiotic, Antibiotic stewardship
Brief summary
The growing resistance of microorganisms to antimicrobials is a major threat to public health nowadays. Reducing the consumption of antibiotics is one of the main strategies to control this issue. Protocols using biomarkers to guide antimicrobial therapy have been studied, with promising results in safely reducing patient exposure to these drugs by reducing duration of treatments. Procalcitonin (PCT) and C-reactive protein (CRP) represent the most promising biomarkers in this context. Although less studied, CRP has the potential advantages of lower cost and wide availability when compared to PCT. However, decision algorithms involving biomarkers proposed in studies published so far are very far from daily medical practice in hospitals, mainly because there is poor accessibility to these protocols, and because most of them do not contemplate each patients clinical variables. The objective of this project is to evaluate the efficacy and safety of a multimodal protocol using clinical variables and the CRP value to guide antibiotic therapy in hospitalized patients. This protocol will be applied diretcly by the assistant medical teams through a digital clinical decision support tool available in the form of an application for mobile devices developed by the research team.
Detailed description
The research team will perform a randomized, controlled, concurrent, open, single-center clinical trial. The proposed intervention is the application of a protocol that uses clinical variables and the CRP value to guide the duration of antibiotic therapy in patients with suspected or confirmed bacterial infection. As for the control group, the duration of antibiotic therapy will be suggested according to the best available evidence, considering the primary site of infection and other characteristics of this process. For both groups, the study protocol will be applied through a digital application for use on smartphones or tablets, developed specifically for this project. Participants will be adults admitted to the internal medicine ward of the Hospital das Clínicas of the Federal University of Minas Gerais (HC-UFMG), for whom the assistant physician team has started antibiotic therapy in the last 72 hours. Patients will be allocated after signing a free and informed consent form. Follow-up will be carried out until hospital discharge, death or 90 days, whichever occurs first. The project was submitted for consideration to the Research Ethics Committee of the Federal University of Minas Gerais (COEP-UFMG) and approved. As primary outcome, the duration of antibiotic therapy will be evaluated for the infectious episode that motivated inclusion in the study. Duration of antibiotic therapy will be measured by antimicrobial days (defined by the aggregate of days a specific antimicrobial agent was administered to an individual patient) per 1000 present days (defined by the length of time during which a given patient is at risk for antimicrobial exposure at a given institution). As secondary outcomes, the investigators will assess total exposure to antimicrobials, antibiotic-free days, user satisfaction after using the digital tool, protocol adherence rate, length of stay, estimated cost of antimicrobial therapy, all-cause hospital mortality, therapeutic failure, reinfection rate, subsequent infections with multidrug-resistant microorganisms, Clostridioides difficile infection.
Interventions
OTHERC reactive protein algorithm
Antibiotic therapy discontinuation will be encouraged under the following conditions: If the peak CRP is below 100 mg/L: Consider stopping antibiotics when CRP falls below 35 mg/L, with a minimum treatment duration of 3 days. If the peak CRP is above 100 mg/L or the patient meets criteria for sepsis or septic shock: Consider stopping antibiotics when CRP has decreased by 50%, after a minimum of 5 days. If the patient does not meet the CRP criteria: Antibiotic discontinuation will be recommended after 5-7 days, provided there is clinical improvement. Before discontinuing antibiotic therapy, physicians should confirm that the patient is clinically improving, with no signs of a persistent infectious focus. Additionally, they will be encouraged to verify that the Sequential Organ Failure Assessment (SOFA) score is stable or decreasing. These factors will assist in determining the appropriateness of stopping antibiotics.
Sponsors
Conselho Nacional de Desenvolvimento Científico e Tecnológico
FAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas Gerais
Federal University of Minas Gerais
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients over 18 years of age, * Clinical suspicion or microbiological confirmation of bacterial infection, with initiation of antibiotic therapy in the last 72 hours. * Signing of the free and informed consent term by the patient or companion if the patient is unable to sign it (Annex 1). * Patient admitted to the unit participating in the study.
Exclusion criteria
* HIV-infected patients with a CD4 count \< 200 cells/mm3; neutropenic with neutrophil count \< 500 cells/mm3; solid organ or bone marrow transplants; patients who received chemotherapy in the last 14 days at high risk of febrile neutropenia (\> 20%), defined by the assistant team responsible for the treatment of the neoplasm; use of immunosuppressants, such as cyclophosphamide, azathioprine, cyclosporine, rituximab, tacrolimus, sirolimus or TNF inhibitors; use of corticosteroid therapy at a dose greater than 0.5mg/Kg of prednisone (or equivalent) over the last 30 days or pulse therapy in the last 14 days with these drugs; primary immunodeficiency (eg, X-linked agammaglobulinemia, common variable immunodeficiency) or patients with another condition that determines a clear impairment of immunological defenses, whether humoral, cellular or mixed. * Conditions that require prolonged antibiotic therapy (infective endocarditis, necrotizing pneumonia, deep abscesses, osteomyelitis, complicated soft tissue infections, S. aureus bacteremia, among others), identified before randomization (ie, up to 72 hours of antibiotic therapy) . * Patients with the perspective of hospital discharge in less than 72 hours from inclusion. * Patients in exclusive palliative care. * Patients with life expectancy \< 24h.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of antibiotic therapy | From enrollment to the end of treatment. | Duration of antibiotic therapy for the index infectious episode (the one that prompted inclusion in the study), measured in days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total exposure to antimicrobials | 90 days | Total antimicrobial exposure, defined as the number of days of antibiotic exposure considering all therapeutic cycles during patient follow-up, measured in Antimicrobial days / days of follow-up x 1,000. Antimicrobial days = total number of days antibiotics were given. If a patient is on 2 antibiotics, both are counted (i.e., the number of days for both drugs are added together). Days of follow-up = sum of days of follow-up in the study. |
| Antibiotic-free days | 90 days | Defined by the ratio of the number of days of follow-up without the use of antibiotics by the number of days of follow-up in total, corrected by a denominator of 100. |
| Length of hospital stay | 90 days | Measured in days. |
| Cost estimate of antimicrobial therapy. | 2 years | Considering Brazilian market prices. |
| Subsequent infections by multidrug-resistant microorganisms | 90 days | Measured by the ratio of cultured isolates per 100 patients. |
| All-cause 90 days mortality | 90 days | All-cause 90 days mortality. |
| Therapeutic failure | 2 days | Defined as persistence or recurrence of signs and symptoms of the same focus of infection that motivates resumption of antibiotic therapy in less than 48 hours after suspension. |
| Reinfection rate | 90 days | Defined as a new episode of infection with a different focus or with isolation of new microorganisms or after 48 hours of discontinuation of antibiotic therapy directed at the initial infectious condition. |
| Clostridioides difficile infection | 90 days | Measured by diagnostic methods avaiable in Hospital das Clínicas da Universidade Federal de Minas Gerais. |
| Adherence rate to the protocol in both the intervention and control groups. | 90 days | The research team will closely monitor the daily progress of patients in each group, and will actively encourage adherence to the protocol associated with the respective group. For the intervention group, this may involve explaining the benefits of following the new algorithm, while for the control group, it may focus on adherence to the standard care. Any deviations from the algorithm will be noted for analysis. |
Countries
Brazil
Outcome results
None listed