Assessing the Procalcitonin-guidance and Molecular-guided Diagnosis for Therapy of Severe Infections (the MODIFY Trial)

Inclusion Criteria:

• Male or female

• For women of child-bearing potential, willingness to avoid pregnancy during thestudy and agreement to notify investigator if pregnancy occurs.

• Age more than or equal to 18 years

• Patients who have completed their participation in another study for more than 30days can be included in this study.

• Written informed consent provided by the patient or by their legal representative incase of patients unable to consent due to sepsis onset affecting their mentalcapacity.

• Sepsis defined by the Sepsis-3 definition; this is defined separately forcommunity-acquired sepsis and for hospital-acquired sepsis. Community-acquiredsepsis is defined as any SOFA score 2 points or more for patients admitted inhospital emergencies with community-acquired pneumonia (CAP), community-acquiredacute pyelonephritis (AP) or community-acquired primary bacteremia (BSI). CAP, APand BSI are considered community-acquired for patients who have no history ofhospitalization lasting more than 2 days the last 90 days or who are not underhemodialysis or who are not residents of long-term care facilities.Hospital-acquired sepsis is defined as any SOFA score increase by 2 points or morefrom the admission SOFA score for patients with onset of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), acute pyelonephritis (AP) or primarybacteremia (BSI) at least 48 hours after hospital admission. For patients withhistory of hospitalization lasting more than 2 days the last 90 days or who areunder hemodialysis or who are residents of long-term care facilities and areadmitted to hospital with HAP, VAP, AP and BSI the definition of hospital-acquiredsepsis applies. In this case, the baseline SOFA score is considered as the knownSOFA score before infection onset.

• Presence of one of the following infections: community-acquired pneumonia (CAP),hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), acutepyelonephritis (AP) and primary bacteremia (BSI).

• Positive blood culture

Exclusion Criteria:

• Failure to obtain written consent to participate

• Previous enrollment in this study within the past 90 days. Patients enrolled inanother study will not be accepted.

• Patients in pregnancy or breastfeeding. Women of child-bearing potential will bescreened by a urine pregnancy test before inclusion in the study

• Patients receiving prolonged antibiotic therapies (e.g. endocarditis, implantabledevice-associated infection, cerebral/hepatic abscess, osteomyelitis, meningitis)

• Patients with severe infections due to viruses or parasites (e.g. Dengue, Toxoplasmagondii, Plasmodium spp.)

• Patients with infection due to Mycobacterium tuberculosis.

• Patients suffering from cystic fibrosis

• Severely immunocompromised patients such as a) patients with infection by the humanimmunodeficiency virus and with a CD4 count of less than 200 cells/mm3; b)neutropenic patients with less than 500 neutrophils/mm3; and c) patients with solidorgan transplantation.