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Three Dimensional Checkerboard Synergy Analysis of Colistin, Meropenem, Tigecycline against Multidrug-Resistant Clinical Klebsiella pneumonia Isolates
- Source :
- PLoS ONE, PLoS ONE, Vol 10, Iss 6, p e0126479 (2015)
- Publication Year :
- 2015
- Publisher :
- Public Library of Science, 2015.
-
Abstract
- The spread of carbapenem-non-susceptible Klebsiella pneumoniae strains bearing different resistance determinants is a rising problem worldwide. Especially infections with KPC (Klebsiella pneumoniae carbapenemase) - producers are associated with high mortality rates due to limited treatment options. Recent clinical studies of KPC-blood stream infections revealed that colistin-based combination therapy with a carbapenem and/or tigecycline was associated with significantly decreased mortality rates when compared to colistin monotherapy. However, it remains unclear if these observations can be transferred to K. pneumoniae harboring other mechanisms of carbapenem resistance. A three-dimensional synergy analysis was performed to evaluate the benefits of a triple combination with meropenem, tigecycline and colistin against 20 K. pneumoniae isolates harboring different β-lactamases. To examine the mechanism behind the clinically observed synergistic effect, efflux properties and outer membrane porin (Omp) genes (ompK35 and ompK36) were also analyzed. Synergism was found for colistin-based double combinations for strains exhibiting high minimal inhibition concentrations against all of the three antibiotics. Adding a third antibiotic did not result in further increased synergistic effect in these strains. Antagonism did not occur. These results support the idea that colistin-based double combinations might be sufficient and the most effective combination partner for colistin should be chosen according to its MIC.
- Subjects :
- Carbapenem
Klebsiella pneumoniae
medicine.drug_class
Antibiotics
lcsh:Medicine
Porins
Minocycline
Tigecycline
Microbial Sensitivity Tests
Meropenem
Microbiology
Antibiotic resistance
Bacterial Proteins
Drug Resistance, Multiple, Bacterial
medicine
polycyclic compounds
lcsh:Science
Multidisciplinary
biology
Colistin
lcsh:R
Drug Synergism
Gene Expression Regulation, Bacterial
biochemical phenomena, metabolism, and nutrition
biology.organism_classification
medicine.disease
bacterial infections and mycoses
Anti-Bacterial Agents
bacteria
lcsh:Q
Thienamycins
Klebsiella pneumonia
medicine.drug
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....55a8d9061a33721d36cfab26e4c99d2a