The purpose of this study is to collect real-world data about the non-controlled prescribing use and impact of daptomycin. Therefore, a non-interventional, multicentre, retrospective design was chosen. Investigators were asked to voluntarily include as many patients as available. Patients could be retrospectively included if they were treated with at least one dose of daptomycin and if all relevant information was entered in the case report form (CRF). Patients who received daptomycin as part of a controlled clinical trial were not eligible for inclusion. Investigators at >100 institutions across Europe collected anonymous demographic, antibiotic, microbiological and clinical data from medical records using a standardized CRF and protocol. Argentinean sites were also allowed to participate, as overall enrolment predictions were uncertain and daptomycin had just been approved in that country. Written informed consent that complies with the ICH Good Clinical Practice guideline was obtained if required by the institutional review board or ethics committee and/or local data privacy regulations, and the protocol was approved by the health authority and the institutional review board or ethics committee, as required, in each country. Investigators were trained on the CRF and received written instructions to further guide the collection of patient data. Each patient is uniquely identified in the study by a combination of his/her centre number and patient number. All data are entered on standardized CRFs exclusively according to the investigator's judgement. Data from the CRFs are entered into the study database by certified contract research organization staff working on behalf of the sponsor. After database lock, all available data were distributed to all authors of the manuscript, who take part in scheduled publication committee meetings. All information collected reflected standard practice in each site. There was no intervention or restriction in clinical practice. Patient data can be recorded into this registry after a minimum of 30 days from the end of daptomycin therapy to permit the capture of AEs/serious AEs (SAEs). The CRFs collected the following information: treatment period; demographics; underlying diseases; pregnancy; neutropenia; antimicrobials; use of other antibiotics and statins; renal function; creatine phosphokinase (CPK) concentrations; diagnosis and current infection details; doses of current antibiotic treatment; duration of inpatient and/or outpatient treatment; outcomes; AEs and SAEs occurring between treatment onset and 30 days after last dose of daptomycin; and discharge information. No instructions were provided concerning drug discontinuation, study completion or post-study treatment. However, the reasons for study drug discontinuation, reason for completion of daptomycin treatment and antibiotic use after daptomycin treatment were captured. In cases of multiple infection, investigators entered the type of infection in order of clinical significance (i.e. primary or secondary infection) for which the patient received daptomycin.
In the database, the primary infection was always automatically assigned to the disease of higher hierarchy according to the following predefined severity classification (in order of most to least severe): endocarditis; osteomyelitis; bacteraemia; other [CNS infection, foreign body/prosthetic infection, metastatic abscess, necrotizing fasciitis, necrotizing infection, surgical/non-surgical antibiotic prophylaxis, septic arthritis and urinary tract infection (UTI)/pyelonephritis]; cSSTI; uncomplicated skin and soft tissue infection (uSSTI). This classification was needed to allow for analysis standardization and was based on experts’ and sponsor's judgement taking into consideration clinical prognosis, probability of microbiology eradication and consequences of treatment failure. Safety analysis included all reports of AEs, the severity of which was determined by the investigators. AEs were recorded regardless of their relationship to daptomycin therapy. The overall methodology of this registry, including the definitions mentioned in the following section, is aligned with the CORE registry methodology. It is possible to merge the databases to perform combined or comparative analyses between different regions, as recently published by Gonzalez-Ruiz et al.9
In the database, the primary infection was always automatically assigned to the disease of higher hierarchy according to the following predefined severity classification (in order of most to least severe): endocarditis; osteomyelitis; bacteraemia; other [CNS infection, foreign body/prosthetic infection, metastatic abscess, necrotizing fasciitis, necrotizing infection, surgical/non-surgical antibiotic prophylaxis, septic arthritis and urinary tract infection (UTI)/pyelonephritis]; cSSTI; uncomplicated skin and soft tissue infection (uSSTI). This classification was needed to allow for analysis standardization and was based on experts’ and sponsor's judgement taking into consideration clinical prognosis, probability of microbiology eradication and consequences of treatment failure. Safety analysis included all reports of AEs, the severity of which was determined by the investigators. AEs were recorded regardless of their relationship to daptomycin therapy. The overall methodology of this registry, including the definitions mentioned in the following section, is aligned with the CORE registry methodology. It is possible to merge the databases to perform combined or comparative analyses between different regions, as recently published by Gonzalez-Ruiz et al.9
