In vitro Evaluation of Antibiotic Synergy for Polymyxin B-Resistant Carbapenamase Producing Klebsiella pneumoniae.
Summary of "In vitro Evaluation of Antibiotic Synergy for Polymyxin B-Resistant Carbapenamase Producing Klebsiella pneumoniae."
Since carbapenemase producing Klebsiella pneumoniae were first reported in North Carolina, these highly resistant organisms have been isolated with increasing frequency, especially in the New York City area. Polymyxin B is one of the few antimicrobials that retain reliable activity against these organisms. However, polymyxin B minimum inhibitory concentrations (MIC) were elevated against K. pneumoniae isolates with increasing frequency, leaving clinicians with few therapeutic options. We investigated several antimicrobial agents for potential synergy with polymyxin B against twelve clinical strains of carbapenemase-producing K. pneumoniae. A broth microdilution assay using a 96-well plate was developed where graded dilutions of polymyxin B and the study drug were incubated with resistant isolates in a checkerboard pattern. Polymyxin B was studied in combination with cefazolin, ceftriaxone, cefepime, imipenem, gentamicin, tigecycline, doxycycline and rifampin. All the K. pneumoniae strains tested positive for KPC genes by real-time PCR and had an elevated polymyxin B MIC values ranging from 16 to 128 mug/mL. Synergy was observed with the combination of polymyxin B and rifampin as well as polymyxin B and doxycycline, resulting in at least a fourfold decrease in the polymyxin B MIC. For both combinations, this effect occurred at physiologically achievable concentrations. Less pronounced synergy was noted with tigecycline and polymyxin B. No synergy was observed with the other antimicrobials when studied at physiologic concentrations. These results suggest that rifampin, doxycycline, or tigecycline may be useful additions to polymyxin B in the treatment of infections caused by highly resistant carbapenemase producing K. pneumoniae. Further studies are warranted to determine if these in vitro findings translate into clinical efficacy.
Affiliation
Departments of Infectious Diseases and Pathology/Laboratories, Saint Vincent Medical Center, New York, NY 10011.
Journal Details
This article was published in the following journal.
Name: Journal of clinical microbiology
ISSN: 1098-660X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20686085
- DOI: http://dx.doi.org/10.1128/JCM.01106-10
Medical and Biotech [MESH] Definitions
Polymyxin B
A mixture of polymyxins B1 and B2, obtained from Bacillus polymyxa strains. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for infections with gram-negative organisms, but may be neurotoxic and nephrotoxic.
Colistin
Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally.
Polymyxins
Basic lipopeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter.
Cefoxitin
A semisynthetic cephamycin antibiotic resistant to beta-lactamase.
Oxacillin
An antibiotic similar to FLUCLOXACILLIN used in resistant staphylococci infections.
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