Clinical trial NCT01208519: SATURN 04 Nosocomial Acquisition Study
Official title: Impact of Specific Antibiotic Therapies on the Prevalence of Human Host Resistant Bacteria in Hospitalised Patients (SATURN 04)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bacterial Resistance
Infection Resistant to Multiple Drugs
Staph Aureus Methicillin Resistant Colonization
Infection Due to ESBL Bacteria
Keywords: Drug resistance, Microbial
Methicillin-Resistant Staphylococcus aureus
ESBL
Colonisation
Screening
Gram-negative
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
Collaborators: name: Clinical Centre of Serbia
name: National Institute of Infectious Diseases Matei Bals
name: University Hospital, Geneva
name: Canisius-Wilhelmina Hospital
name: Universiteit Antwerpen
First posted: 2010-09-24
Enrollment: 16680
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients will be screened at hospital admission and hospital discharge during the study period. Patients colonised with MRSA and/or ESBL-producing gram-negative bacteria before starting antibiotic therapy will be excluded from follow-up cultures and analysis.

Patients starting antibiotic therapy per os and/or intravenously will be sampled at antibiotic start (t0, within one hour) and at the following intervals: day 3 (t1), 7 (t2), 15 (t3), 30 (t4). Screening will be performed in outpatient clinics after patients' discharge from the hospital.

Brief summary: The study is the WP4 of the EU-funded (7th FW) project SATURN (Impact of Specific Antibiotic Therapies on the prevalence of hUman host ResistaNt bacteria). A total of 6 surgical and 6 medical wards will participate in the study. Sites of the study are located in 3 countries (Italy, Serbia, Romania). This WP will compare nosocomial acquisition rates of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria (E.coli, Klebsiella spp. and Proteus spp.) among different treatment groups and define the temporal relationship between the start of antibiotic therapy, the acquisition of new colonisation in patients previously not colonised, and the development of a bacterial infection caused by the same strain isolated in a screening sample. This goal will be achieved by completing the following primary objectives:

* To determine the rate of acquisition of target antibiotic-resistant bacteria by 1,000 antibiotic-days according to different classes of antibiotics, duration of therapy and antibiotic combination (monotherapy versus combination therapy);
* To determine genotypic relation between colonising and infecting strain in the same patient and patients' and hospital staff colonising strains (to be performed in collaboration with WP1 of the SATURN project);
* To study the virulence and fitness of the isolates (i.e. new colonising strains) causing subsequent nosocomial infections (to be performed in collaboration with WP1 of SATURN project);
* To predict the risk for nosocomial infections due to target bacteria after a single treatment therapy adjusted by length of hospitalisation and ward colonisation pressure.

Detailed description: Nasal samples for the detection of MRSA and rectal samples (stoma sample in case of colostomy) for ESBL producing gram negative bacteria will be obtained at hospital admission and discharge. Patients starting antibiotic therapy per os and/or intravenously will be sampled at antibiotic start (t0, within one hour) and at the following intervals: day 3 (t1), 7 (t2), 15 (t3), 30 (t4). Patients colonized with MRSA and/or ESBL-producing gram negative bacteria before starting antibiotic therapy (t0 sample) will be excluded from follow-up cultures and analysis. All patients included in the study will be followed to determine whether they develop clinical infections with the target ARB. Patients will be followed during the hospitalization and afterwards for a total of 30-day from the inclusion in the study. Screening will be performed in outpatient clinics after patients' discharge from the hospital within 30 days of starting antibiotic (t0 sample).

Nasal and rectal cultures will be also obtained from the ward staff at the beginning and at the end of the study. This group includes nurses and all staff including doctors having contacts with patients. These cultures will be handled in the same manner as the patients' cultures

Eligibility criteria: Inclusion Criteria:

* All hospitalized non ICU patients at hospital admission/discharge;
* Age \>18 years old;
* All patients starting intravenous and/or oral antibiotic treatments during hospitalization.

Exclusion Criteria:

* Pregnancy;
* Recent nose surgery (for nasal swabs).

Primary outcomes:
measure: Impact of different antibiotics in selecting antimicrobial resistance in in-patients
timeFrame: 5 years (January 2015)
Secondary outcomes:
measure: Colonization and infection risk according to antibiotic treatment duration
timeFrame: 5 years (January 2015)
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore; Policlinico A. Gemelli
state: Lazio
city: Bucharest
country: Romania
facility: Institute of Infectious Diseases Matei Bals
city: Beograd
country: Serbia
facility: Clinical Center of Serbia
Study officials:
affiliation: Università Cattolica del Sacro Cuore - Policlinico A. Gemelli - Roma
name: Evelina Tacconelli, MD PhD
role: STUDY_CHAIR
References:
citation: Niehus R, van Kleef E, Mo Y, Turlej-Rogacka A, Lammens C, Carmeli Y, Goossens H, Tacconelli E, Carevic B, Preotescu L, Malhotra-Kumar S, Cooper BS. Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance. Elife. 2020 May 7;9:e49206. doi: 10.7554/eLife.49206.
citation: Tacconelli E, Gorska A, De Angelis G, Lammens C, Restuccia G, Schrenzel J, Huson DH, Carevic B, Preotescu L, Carmeli Y, Kazma M, Spanu T, Carrara E, Malhotra-Kumar S, Gladstone BP. Estimating the association between antibiotic exposure and colonization with extended-spectrum beta-lactamase-producing Gram-negative bacteria using machine learning methods: a multicentre, prospective cohort study. Clin Microbiol Infect. 2020 Jan;26(1):87-94. doi: 10.1016/j.cmi.2019.05.013. Epub 2019 May 23.
citation: Meletiadis J, Turlej-Rogacka A, Lerner A, Adler A, Tacconelli E, Mouton JW; the SATURN Diagnostic Study Group. Amplification of Antimicrobial Resistance in Gut Flora of Patients Treated with Ceftriaxone. Antimicrob Agents Chemother. 2017 Oct 24;61(11):e00473-17. doi: 10.1128/AAC.00473-17. Print 2017 Nov.
citation: De Angelis G, Restuccia G, Venturiello S, Cauda R, Malhotra-Kumar S, Goossens H, Schrenzel J, Tacconelli E. Nosocomial acquisition of methicillin-resistant Staphyloccocus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae in hospitalised patients: a prospective multicenter study. BMC Infect Dis. 2012 Mar 29;12:74. doi: 10.1186/1471-2334-12-74.