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Antibiotics (Basel). 2019 Apr 10;8(2). pii: E38. doi: 10.3390/antibiotics8020038.

Polymyxins: To Combine or Not to Combine?

Perez F1,2,3,4,5, El Chakhtoura NG6,7,8,9, Yasmin M10,11,12, Bonomo RA13,14,15,16,17,18,19,20.

Author information

1
Medicine Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. Federico.Perez@va.gov.
2
Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. Federico.Perez@va.gov.
3
Geriatrics Research, Education and Clinical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. Federico.Perez@va.gov.
4
Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA. Federico.Perez@va.gov.
5
Case VA Center for Antimicrobial Resistance and Epidemiology, Cleveland, OH 44106, USA. Federico.Perez@va.gov.
6
Medicine Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. nge11@case.edu.
7
Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. nge11@case.edu.
8
Geriatrics Research, Education and Clinical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. nge11@case.edu.
9
Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA. nge11@case.edu.
10
Medicine Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. mohamad.yasmin@uhhospitals.org.
11
Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. mohamad.yasmin@uhhospitals.org.
12
Geriatrics Research, Education and Clinical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. mohamad.yasmin@uhhospitals.org.
13
Medicine Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. Robert.Bonomo@va.gov.
14
Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. Robert.Bonomo@va.gov.
15
Geriatrics Research, Education and Clinical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA. Robert.Bonomo@va.gov.
16
Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA. Robert.Bonomo@va.gov.
17
Case VA Center for Antimicrobial Resistance and Epidemiology, Cleveland, OH 44106, USA. Robert.Bonomo@va.gov.
18
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Robert.Bonomo@va.gov.
19
Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106 USA. Robert.Bonomo@va.gov.
20
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Robert.Bonomo@va.gov.

Abstract

Polymyxins have been a mainstay for the treatment of extensively drug resistant (XDR) Gram-negative bacteria for the past two decades. Many questions regarding the clinical use of polymyxins have been answered, but whether the administration of polymyxins in combination with other antibiotics leads to better outcomes remains unknown. This review discusses the limitations of observational studies that suggest a benefit of combinations of colistin and carbapenems to treat infections caused by carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, and summarizes the results of randomized controlled trials in which treatment with colistin in combination with meropenem or rifampin does not lead to better clinical outcomes than colisitn monotherapy in infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). Although the introduction of new antibiotics makes it possible to treat certain strains of CRE and carbapenem-resistant P. aeruginosa (CRPA) with polymyxin-sparing regimens, the use of polymyxins is, for now, still necessary in CRAB and in CRE and CRPA harboring metallo-beta-lactamases. Therefore, strategies must be developed to optimize polymyxin-based treatments, informed by in vitro hollow fiber models, careful clinical observations, and high-quality evidence from appropriately designed trials.

KEYWORDS:

CRE; antibiotic-combinations; colistin; polymyxin B

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