Epidemiology and Outcomes of Gram Negative Urosepsis
Epidemiology and Outcomes of Gram Negative Urosepsis
The study aims to get an insight on the causative bacteria of sepsis derived from the urinary
 tract. Furthermore, it is the intention to understand the outcomes of these patients. For
 this purpose a non-interventional, observational study will be conducted.
In this prospective, non-interventional, observational registry participants diagnosed with
 urosepsis will be registered to the study to capture the events and outcomes of interest.
 There will be no additional intervention and evaluation for the purpose of this study.

 -Primary objectives:

 1. Pathogens: Causative pathogens and their susceptibility profile

 2. Clinical outcomes: Development of organ failure and mortality.

 3. Costs: Hospital resources used and costs acquired

 -  Secondary objective:

 1. Risk factors: Influence of patient characteristics (medical & urological history,
 comorbidities) on severity of urosepsis (simple, severe & septic shock), causative
 pathogens profile and outcomes

 2. Appropriateness of antibiotic treatment: The influence of appropriate antibiotic
 treatment, identified through empirical treatment provided and the pre-treatment culture
 results, on the clinical outcomes.

 3. Economic evaluation: Identify the cost and health state changes according to
 appropriateness of treatment.

 -Rationale: Results of the GPIU registries 2003 to 2013 showed, that the rate of
 urosepsis in "health-care" associated infections of urological patients increased from
 15% in 2003 to 25% in 2013. This creates an extra burden of health systems that needs to
 be better understood in detail.

 Early management in urosepsis is imperative. An important step of the management is
 appropriate empirical antibiotic treatment that requires an understanding of local and
 global pathogen susceptibility profiles. Furthermore, our pilot analysis from GPIU has
 shown that individual patient characteristics can be helpful in guiding empirical
 treatment. Appropriate empirical antibiotic treatment has shown to be associated with
 better clinical outcomes and lower length of stay (LOS).

 -Objectives

 The aim of this registry is to investigate the epidemiology of urosepsis primarily in
 Europe, with specific examination of causative pathogens and their resistance, the
 associated risk factors, clinical data, costs associated and value of initial
 appropriate antimicrobial treatment.

 3.1. Primary objectives:

 - Describe the prevalence of organisms causing urosepsis

 - Describe the susceptibility profile of organisms causing urosepsis.

 - Describe the clinical and economic burden of urosepsis caused by resistant Gram
 negative pathogens of interest.

 3.2. Secondary objectives:

 -  Characterize risk factors for infection with resistant gram negative pathogens of
 interest.

 -  Examine the impact of initial inappropriate antibiotic therapy on clinical and
 economic outcomes.

 -  Design

 This is a prospective, longitudinal data collection as an ancillary registry to the 2013
 Global Prevalence of Infections in Urology (GPIU) point prevalence registry performed
 annually by the European Association of Urology (European Section of Infection in
 Urology). Participating hospitals will perform data collection with a goal of collecting
 complete hospital course data on 600 cases of urosepsis. The GPIU group will handle
 contracting, data collection, and data analysis for this part of the registry.

 - Participants

 The population to be observed will be adults patients with clinical diagnosis of
 urosepsis. Observations will be initiated when a patient is diagnosed with urosepsis
 based on the clinical symptoms and findings as part of routine clinic practice through
 emergency and accident, urology or internal medicine units.

 The data of the bacterial isolates and their susceptibility results used in this study
 will be obtained as part of routine clinical care. The necessity of informed patient
 consent is at the discretion of the participating institution. All patient data will be
 analyzed anonymously.

 -Patients to be observed

 Identification of observations:

 Patients to be observed will be identified through emergency and accident, urology,
 intensive care and internal medicine units at participating sites. Eligibility criteria
 checklist of all cases considered to be observed will be filled in by participating
 principal investigator (PI). Clinical information from the initial diagnosis should be
 used to asses eligibility.

 -Observations Diagnosis observations

 Routine clinical signs and symptoms assessed by the managing physician should be used to
 evaluate the patient. The following observations should be carried out at the time of
 diagnosis:

 -  Medical history

 -  Microbiology cultures

 -  Clinical signs, symptoms and findings

 Treatment observations

 The following observations should be registered after the diagnosis and initiation of
 treatment:

 -  Medical treatment

 -  Surgical treatment

 -  Treatment unit

 Post-treatment observations

 Subsequent to initiation of treatment the following observations will be registered:

 • End organ failure

 -  Shift in treatments

 -  Mortality

 Registration will be carried out on post diagnosis day 3,7,9 and 30 to capture the
 changes within the following time-gaps respectively:

 -  Diagnosis day to day 3

 -  Post diagnosis day 4 to 7

 -  Post diagnosis day 8 to 9

 -  Post diagnosis day 10 to 30

 For patients where treatment extends beyond 30 days additional registrations will be
 carried out only when there is a change in the listed post-treatment observations.

 Completion of treatment - observations

 When treatment of patients is finalized due to either complete resolution of sepsis or
 death the following observations will be carried out:

 • Costs (optional)

 -  End-organ failure

 -  Mortality

 -  LOS

 -  HRQoL (optional)

 Post diagnosis 1 year follow-up

 At the end of 1st year of diagnosis centers willing to register further observations
 will fill in the following:

 • Costs (optional)

 • End-organ failure

 • Mortality

 • LOS

 • HRQoL (optional)

 Schedule of observations

 - Baseline: Medical history, Microbiological proof, management of urosepsis,
 HRQoL(optional)

 -Follow-up-1 (3rd day post diagnosis): Microbiological proof(if additional carried out),
 Management of urosepsis, Clinical outcomes

 -Follow-up-2 (7th day post diagnosis): Microbiological proof(if additional carried out),
 Management of urosepsis, Clinical outcomes

 -  Follow-up-3 (9th day post diagnosis): Microbiological proof(if additional carried
 out), Management of urosepsis, Clinical outcomes

 -  Follow-up-4 (30th day post diagnosis): Microbiological proof(if additional carried
 out), Management of urosepsis, Clinical outcomes

 -  Completion of treatment related with urosepsis episode: Management of urosepsis,
 Clinical outcomes, HRQoL (optional), Economic evaluation (optional)

 -  Statistical considerations Data measured on a continuous scale will be expressed as
 mean, standard deviation, range, and median. Categorical data will be expressed as
 counts and percentages of patients in the categories. Chi-square or Fisher's tests
 will be used to test for statistical differences in categorical variables and T- or
 Mann-Whitney tests will be utilized for determination of statistical differences in
 continuous variables where appropriate.

 -  Management The GPIU study team will provide support for the participating centers.
 The secretarial staff at the EAU-Research foundation will provide clerical support
 to the study.

 -  Administration, logistics & quality assurance

 Sharing of observations

 Electronic (e) case report forms (CRF) will be used for collection of observational
 information. EAU-RF will and study coordinator will provide guidance to sites to aid the
 completion of the eCRFs. The study scientific group reserves the right to amend or add
 to the eCRF template as appropriate. Such changes to not constitute a protocol amendment
 and revised or additional forms should be used by sites.

 Central data monitoring:

 After eCRFs are completed by the study site, the study coordinator will review it for
 protocol compliance, and for inconsistencies and missing values.

 Should any missing data or data abnormalities be found, queries will be raised for
 resolution by the site.

 Any systematic inconsistencies identified through central data monitoring may be subject
 to queries.

 Definition of end of registry:

 The end of the study will be the date of the last observation captured.
Inclusion Criteria:

 -  Microbiologically proven UTI

 -  Age>18

 -  Patients must meet at least two of the following four SIRS criteria, at least one of
 which must be the core temperature criterion or the WBC criterion; these criteria did
 not have to be met simultaneously:

 1. Hypothermia by core temperature <36ºC, or hyperthermia >38ºC measured via any
 means

 2. Heart rate (HR) >90 beats per minute

 3. Respiratory rate (RR) >20 breaths/minute related to septic event, or partial
 pressure of arterial carbon dioxide (PaCO2) <32 mmHg related to septic event or
 requiring mechanical ventilation related to septic event

 4. Total WBC absolute count >12,000 cells/mm3 presence of granulocyte-stimulating
 factor, for those patients whose WBC absolute count was >12,000 cells/mm3 one
 other criterion (RR or HR) or <4000 cells/mm3. In the , they must have had a
 fever and at least

 Exclusion Criteria:

 -  Sepsis due to other causes besides the urogenital tract.