Clinical trial NCT01041716: Clinical and Microbiological Outcomes of Infections Due to Carbapenem-Resistant Gram-Negative Bacteria
Official title: Clinical and Microbiological Outcomes of Infections Due to Carbapenem-Resistant Gram-Negative Bacteria
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Drug Resistance, Microbial
Keywords: Carbapenem
Klebsiella pneumoniae carbapenemase
Acinetobacter baumannii
Pseudomonas aeruginosa
Lead sponsor: Maimonides Medical Center
Sponsor class: OTHER
First posted: 2010-01-01
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult in-patients (age≥18 years) having an infection due to CRGNB (Klebsiella pneumoniae, Acinitobacter baumanii and Pseudomonas aeruginosa only). CRGNB Infection will be defined as isolation of CRGNB from any source requiring treatment with anti-infective agents with or without manifestations of systemic inflammatory response syndrome.

Brief summary: Carbapenems are a class of antibiotic agents which kill a broad spectrum of bacteria. Infections due to gram-negative bacteria which have acquired resistance to carbapenems are increasing, especially with Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa . The optimal treatment of such infections is not known. Antibiotics like polymyxin, tigecycline and rifampin are used alone or in combination with other antibiotics. The outcome of using these new and old drugs is not well studied. This observational study aims to study the clinical and microbiological outcomes of these infections and treatment at our institution.

Detailed description: Objectives

1. To define the demographic and risk factor profile of patients acquiring CRGNB infection.
2. To define the characteristics of CRGNB infection.
3. To report the different treatments employed for CRGNB infection.
4. To report the microbiological and clinical outcomes of different treatment options

   * a. Microbiological outcomes: frequency of microbiological success. Microbiological success will be defined as two successive negative cultures from the same site as from where the CRGNB was originally isolated.
   * b. Clinical outcomes: clinical success (clinical cure), adverse effects of treatment especially the nephrotoxicity in relation to the use of polymyxin, ICU length of stay (if applicable), hospital length of stay, ICU mortality (if applicable), hospital mortality and in-hospital recurrence of infection. Clinical success will be defined as resolution or improvement of clinical symptoms and signs of infection and discontinuation of the antibiotics.

Study duration:

We plan to collect the data for a one year period. Based on the current prevalence rate at our institution, we anticipate having data for 300 patients.

Eligibility criteria: Inclusion Criteria:

* Adult in-patients (age≥18 years) having an infection due to CRGNB (Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa only). CRGNB Infection will be defined as isolation of CRGNB from any source requiring treatment with anti-infective agents with or without manifestations of systemic inflammatory response syndrome.

Exclusion Criteria:

* Patients colonized with CRGNB and not having an active infection.
* Recurrent infection in a previously included patient.

Primary outcomes:
measure: Clinical success
timeFrame: At the end of treatment
Secondary outcomes:
measure: Microbiological success
timeFrame: At the end of treatment
measure: Recurrence rate
timeFrame: During the hospital stay
measure: Adverse effects of treatment
timeFrame: During treatment with antibiotics
measure: Hospital length of stay
timeFrame: During the hospital stay
measure: Mortality
timeFrame: During hospital stay
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
Study officials:
affiliation: Maimonides Medical Center
name: Sriharsha Rao, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bradford PA, Bratu S, Urban C, Visalli M, Mariano N, Landman D, Rahal JJ, Brooks S, Cebular S, Quale J. Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactamases in New York City. Clin Infect Dis. 2004 Jul 1;39(1):55-60. doi: 10.1086/421495. Epub 2004 Jun 14.
citation: Bratu S, Landman D, Haag R, Recco R, Eramo A, Alam M, Quale J. Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. Arch Intern Med. 2005 Jun 27;165(12):1430-5. doi: 10.1001/archinte.165.12.1430.
citation: Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol. 2008 Dec;29(12):1099-106. doi: 10.1086/592412.
citation: Weisenberg SA, Morgan DJ, Espinal-Witter R, Larone DH. Clinical outcomes of patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae after treatment with imipenem or meropenem. Diagn Microbiol Infect Dis. 2009 Jun;64(2):233-5. doi: 10.1016/j.diagmicrobio.2009.02.004. Epub 2009 Apr 2.
citation: Bratu S, Tolaney P, Karumudi U, Quale J, Mooty M, Nichani S, Landman D. Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents. J Antimicrob Chemother. 2005 Jul;56(1):128-32. doi: 10.1093/jac/dki175. Epub 2005 May 25.