Giuseppe
Emeritus
[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections: Risk Factors for Treatment Failure
Yanina Dubrovskaya, PharmD 1, Ting-Yi Chen, MD, MPH 2, Marco R. Scipione, PharmD 1, Diana Esaian, Pharm 1, Michael S. Phillips, MD 2, John Papadopoulos, B.S, Pharm 1,2 and Sapna A. Mehta, MD 2
Author Affiliations: <SUP>1</SUP>Department of Pharmacy/Division of Pharmacotherapy, New York University Langone Medical Center, New York, NY <SUP>2</SUP>Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY
ABSTRACT
Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are non-standardized and the clinical effect of synergy remains unclear. This study describes outcomes of patients with CRKP infections treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by survival rate and 17/32 (53%) patients with follow up culture data achieved microbiological cure. End-of-treatment mortality was 10% and 30-day mortality was 28%. In multivariate analysis, baseline renal insufficiency was associated with 5.5-fold increase in clinical failure after adjusting for septic shock (OR=5.5, 95% CI 1.2-24.5). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection at a median of 23 days after initial polymyxin B treatment, and 3 of these 18 were polymyxin-resistant. Clinical cure rate in this retrospective study was achieved in 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.
FOOTNOTES
Corresponding author: Ting-Yi Chen, MD, MPH, Department of Infectious Diseases, New York University School of Medicine, 550 1st Avenue, New York, NY 10016, Phone: 626-506-4472 Email: s871060@gmail.com
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections: Risk Factors for Treatment Failure
Yanina Dubrovskaya, PharmD 1, Ting-Yi Chen, MD, MPH 2, Marco R. Scipione, PharmD 1, Diana Esaian, Pharm 1, Michael S. Phillips, MD 2, John Papadopoulos, B.S, Pharm 1,2 and Sapna A. Mehta, MD 2
Author Affiliations: <SUP>1</SUP>Department of Pharmacy/Division of Pharmacotherapy, New York University Langone Medical Center, New York, NY <SUP>2</SUP>Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY
ABSTRACT
Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are non-standardized and the clinical effect of synergy remains unclear. This study describes outcomes of patients with CRKP infections treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by survival rate and 17/32 (53%) patients with follow up culture data achieved microbiological cure. End-of-treatment mortality was 10% and 30-day mortality was 28%. In multivariate analysis, baseline renal insufficiency was associated with 5.5-fold increase in clinical failure after adjusting for septic shock (OR=5.5, 95% CI 1.2-24.5). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection at a median of 23 days after initial polymyxin B treatment, and 3 of these 18 were polymyxin-resistant. Clinical cure rate in this retrospective study was achieved in 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.
FOOTNOTES
Corresponding author: Ting-Yi Chen, MD, MPH, Department of Infectious Diseases, New York University School of Medicine, 550 1st Avenue, New York, NY 10016, Phone: 626-506-4472 Email: s871060@gmail.com
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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