Clinical and Microbiological Outcomes of Infections Due to Carbapenem-Resistant Gram-Negative Bacteria

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.

Study Overview

• Status: Completed
• Conditions: Drug Resistance, Microbial
• Intervention / Treatment: Other: None - Observational study

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.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical success	Resolution (or improvement) of clinical symptoms and signs of infection and discontinuation of the antibiotics.	At the end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiological success	Two successive negative cultures from the same site as the original pathogen was isolated.	At the end of treatment
Recurrence rate	Recurrence of symptoms and signs of infection from the same organism and reinstituion of antibiotic therapy	During the hospital stay
Adverse effects of treatment	Adverse effects related to antibiotic administration, especially nephrotoxic and neurotoxic effects of polymyxin	During treatment with antibiotics
Hospital length of stay	Number of days hospitalized	During the hospital stay
Mortality	All cause mortality during hospital stay	During hospital stay

Collaborators and Investigators

• Sponsor: Maimonides Medical Center
• Investigators: Principal Investigator: Sriharsha Rao, M.D., Maimonides Medical Center

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: December 30, 2009
• First Submitted That Met QC Criteria: December 31, 2009
• First Posted (Estimate): January 1, 2010

Study Record Updates

• Last Update Posted (Estimate): August 19, 2011
• Last Update Submitted That Met QC Criteria: August 18, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Pseudomonas aeruginosa; Acinetobacter baumannii; Carbapenem; Klebsiella pneumoniae carbapenemase
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: 09/11VA03