Study to Assess Management and Outcomes of Hospitalised Patients With Complicated UTI (RESCUING)

Urinary Tract Infections Clinical Trial

— RESCUING  

Official title:

A Retrospective Observational Study to Assess the Clinical Management and Outcomes of Hospitalised Patients With Complicated Urinary Tract Infection in Countries With High Prevalence of Multidrug Resistant Gram-negative Bacteria.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02641015
• Other study ID #: PR 223/15
• Status: Completed
• Phase: N/A
• First received: December 23, 2015
• Last updated: January 16, 2017
• Start date: December 2015
• Est. completion date: August 2016

Study information

• Verified date: January 2017
• Source: Institut d'Investigació Biomèdica de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

A retrospective observational study to assess the clinical management and outcomes of hospitalised patients with complicated urinary tract infection in countries with high prevalence of multidrug resistant gram-negative bacteria (COMBACTE-MAGNET,WP5)

Description:

Bacterial resistance to antimicrobial drugs is a major public health problem. Of greatest concern is the rapid emergence and dissemination of resistance to third generation cephalosporins in Enterobacteriaceae, especially Escherichia coli and Klebsiella pneumoniae. This is frequently seen in association with resistance to other classes of antibiotics leading to a multidrug resistance (MDR) profile. These MDR isolates are often involved in complicated urinary tract infection (cUTI), and are associated with poor clinical outcomes. In addition, in the last decade there has been an emergence of carbapenemase-producing Enterobacteriaceae, which are also resistant to other antibiotics than carbapenems, leaving few therapeutic options.

The overall aim of this study is to provide information about the epidemiology, clinical management and outcome of patients hospitalised with cUTI, including pyelonephritis. To achieve this aim, the investigators will perform a multicentre retrospective observational study in patients with hospitalised cUTI. The study will be conducted in several European countries plus Israel, which have a high prevalence of MDR Gram-negative bacteria (GNB), including Pseudomonas aeruginosa. The study will seek to identify possible modifiable risk factors for treatment failure, especially those related to antibiotic therapy.

On completion of this study, the investigators will develop a better understanding of the clinical management of hospitalised patients with cUTI due to MDR GNB in European countries. The investigators will identify the modifiable risk factors for treatment failure. This information will be used to inform better clinical and antibiotic management of cUTI to improve patient outcomes. The study will also be used in the development of hypothesis for future randomised controlled trials in cUTI with new antibiotics. Dissemination of results will take place through peer-reviewed publications and conference presentations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1028
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients with UTI and at least one of the following underlying conditions:

• Indwelling urinary catheter

• Urinary retention (at least 100ml of residual urine after voiding)

• Neurogenic bladder

• Obstructive uropathy (e.g. nephrolithiasis, fibrosis)

• Renal impairment caused by intrinsic renal disease: Estimated glomerular filtration rate (eGFR) <60 mL/min

• Renal transplantation

• Urinary tract modifications, such as an ileal loop or pouch

• Pyelonephritis and normal urinary tract anatomy

and at least one of the following signs or symptoms:

• Chills or rigors associated with fever or hypothermia (temperature greater than 38ºC or below 36ºC)

• Flank pain (pyelonephritis) or pelvic pain (cUTI)

• Dysuria, urinary frequency, or urinary urgency

• Costo-vertebral angle tenderness on physical examination

• UTI-related altered mental state

and at least one of the following microbiological results:

• Urine culture with at least 105 CFU/mL or greater of a uropathogen (no more than 2 species)

• At least one blood culture growing possible uropathogens (no more than 2 species) with no other evident site of infection

Exclusion Criteria:

• Patients less than 18 years of age

• Prostatitis

• Polymicrobial infections that include Candida spp.

• Polymicrobial infections that include more than 2 bacterial species

• cUTI with Candida spp. as sole uropathogen

Related Conditions & MeSH terms

• Bacterial Resistance
• Infection
• Urinary Tract Infections

Locations

Country	Name	City	State
Bulgaria	Emergency Hospital Pirogov	Sofia
Bulgaria	University Hospital Queen Joanna	Sofia
Greece	Attikon University Hospital	Athens
Greece	Hippokration Hospital	Thessaloniki
Hungary	Kenezy University Hospital	Debrecen
Hungary	Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház (SZSZBMK)	Nyíregyháza
Hungary	Soproni Erzsébet Oktató Kórház és Rehabilitációs Intézet	Sopron
Israel	Rambam Health Care Campus	Haifa
Israel	Beilinson Hospital, Rabin Medical Center	Petah-Tiqva
Israel	Tel Aviv Medical Center	Tel Aviv
Italy	Azienda Ospedaliero-Universitaria Policlinico Di Modena	Modena
Italy	AORN dei Colli Monaldi	Napoli
Italy	National Institute for Infectious Diseases L. Spallanzani, IRCCS	Rome
Romania	"Spitalul Clinic de Urgenta Bucuresti. Popular unoficial name ""Floreasca "" Hospital"	Bucharest
Romania	National Institute for Infectious Diseases Prof Dr Matei Bals	Bucharest
Romania	Infectious Diseases Hospital Sfanta Parascheva Iasi	Iasi
Spain	Hospital Universitari de Bellvitge	L'Hospitalet del Llobregat	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla
Turkey	Ankara Numune Egitim ve Arastırma Hastanesi	Ankara
Turkey	Istanbul University Cerrahpasa Medical School	Istanbul

Sponsors (5)

Lead Sponsor	Collaborator
Institut d'Investigació Biomèdica de Bellvitge	AiCuris Anti-infective Cures GmbH, Tel Aviv University, UMC Utrecht, University of Bristol

Countries where clinical trial is conducted

Bulgaria,  Greece,  Hungary,  Israel,  Italy,  Romania,  Spain,  Turkey, 

References & Publications (14)

Barber J, Thompson S. Multiple regression of cost data: use of generalised linear models. J Health Serv Res Policy. 2004 Oct;9(4):197-204. — View Citation

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. — View Citation

Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002 Jul 8;113 Suppl 1A:5S-13S. Review. — View Citation

Ha YE, Kang CI, Cha MK, Park SY, Wi YM, Chung DR, Peck KR, Lee NY, Song JH. Epidemiology and clinical outcomes of bloodstream infections caused by extended-spectrum ß-lactamase-producing Escherichia coli in patients with cancer. Int J Antimicrob Agents. 2013 Nov;42(5):403-9. doi: 10.1016/j.ijantimicag.2013.07.018. — View Citation

Hoban DJ, Lascols C, Nicolle LE, Badal R, Bouchillon S, Hackel M, Hawser S. Antimicrobial susceptibility of Enterobacteriaceae, including molecular characterization of extended-spectrum beta-lactamase-producing species, in urinary tract isolates from hospitalized patients in North America and Europe: results from the SMART study 2009-2010. Diagn Microbiol Infect Dis. 2012 Sep;74(1):62-7. doi: 10.1016/j.diagmicrobio.2012.05.024. — View Citation

Karnofsky DA, Burchenal JH: The clinical evaluation of chemotherapeutic agents in cancer. In Evaluation of chemotherapeutic agents. Edited by MacLeod CM. New York: Columbia University Press; 1949:191-205.

Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Kumar A, Simon D, Peters C, Ahsan M, Chateau D; Cooperative Antimicrobial Therapy of Septic Shock Database Research Group.. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009 Nov;136(5):1237-48. doi: 10.1378/chest.09-0087. — View Citation

Levison ME, Kaye D. Treatment of complicated urinary tract infections with an emphasis on drug-resistant gram-negative uropathogens. Curr Infect Dis Rep. 2013 Apr;15(2):109-15. doi: 10.1007/s11908-013-0315-7. — View Citation

Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012 Mar;18(3):268-81. doi: 10.1111/j.1469-0691.2011.03570.x. — View Citation

Morrissey I, Hackel M, Badal R, Bouchillon S, Hawser S, Biedenbach D. A Review of Ten Years of the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 2002 to 2011. Pharmaceuticals (Basel). 2013 Nov 1;6(11):1335-46. doi: 10.3390/ph6111335. — View Citation

Nicolle LE. A practical guide to the management of complicated urinary tract infection. Drugs. 1997 Apr;53(4):583-92. Review. — View Citation

Spoorenberg V, Hulscher ME, Akkermans RP, Prins JM, Geerlings SE. Appropriate antibiotic use for patients with urinary tract infections reduces length of hospital stay. Clin Infect Dis. 2014 Jan;58(2):164-9. doi: 10.1093/cid/cit688. — View Citation

Trecarichi EM, Tumbarello M. Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer: current epidemiology and clinical impact. Curr Opin Infect Dis. 2014 Apr;27(2):200-10. doi: 10.1097/QCO.0000000000000038. Review. — View Citation

Yang YS, Ku CH, Lin JC, Shang ST, Chiu CH, Yeh KM, Lin CC, Chang FY. Impact of Extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae on the outcome of community-onset bacteremic urinary tract infections. J Microbiol Immunol Infect. 2010 Jun;43(3):194-9. doi: 10.1016/S1684-1182(10)60031-X. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Failure	Treatment failure will be assessed as number of participants with evidence of treatment failure or mortality within 30 days from initial cUTI diagnosis	30 days
Secondary	Time to clinical response	Time to clinical response (in days), since initiation of antibiotic treatment	30 days
Secondary	Time to urological intervention for source control	Time to urological intervention for source control (in days) since initial cUTI diagnosis	30 days
Secondary	Time to death	Time to death (in days) since original cUTI diagnosis	30 days
Secondary	Duration of antibiotic therapy	Duration of antibiotic therapy (in days)	30 days
Secondary	Length of hospital stay	Length of hospital stay (in days)	30 days
Secondary	Hospital mortality	Hospital mortality during admission	30 days
Secondary	All cause mortality within 30 days of the original cUTI diagnosis	All cause mortality within 30 days of the original cUTI diagnosis	30 days
Secondary	All cause of mortality for two months after hospital discharge	All cause of mortality for two months after hospital discharge	60 days
Secondary	Cost per case of cUTI	Cost per case of cUTI	30 days
Secondary	Readmissions to the hospital within 60 days of hospital discharge	Readmissions to the hospital within 60 days of hospital discharge	60 days
Secondary	Adverse events related to antibiotic treatment including: moderate or severe allergic reactions, severe renal impairment, Clostridium difficile infection	Adverse events related to antibiotic treatment including: moderate or severe allergic reactions, severe renal impairment, Clostridium difficile infection	30 days

External Links

•   Complicated Urinary Tract Infections: Developing Drugs for Treatment. Guidance for Industry (2015). U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER).
•   Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data
•   European Medicines Agency (EMA). Guideline on the evaluation of medicinal products indicated for treatment of bacterial infections. December 2011. Committee for Medical Products for Human Use (CHMP).
•   Guidelines on urological infections. European Association of Urology 2014
•   International Classification of Diseases ICD-9 Data.
•   International Statistical Classification of diseases and related Health Problems 10th Revision. ICD-10. Version 2015.
•   Kidney Disease: Improving global outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney inter. Int Suppl. 2013; 3: 1-150.
•   The European Union Summary Report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2012
•   UK Five Year Antimicrobial Resistance Strategy 2013-2018, September 2013.
•   University of Maryland Medical Center. Urinary tract Infection