Characterizing the role of porin mutations in susceptibility of beta lactamase producing Klebsiella pneumoniae isolates to ceftaroline and ceftaroline-avibactam
| Autor: | Jonathan R. Iredell, Ali Khalid, Ruby C.Y. Lin, Li Ma, Alicia Fajardo Lubian |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Klebsiella pneumoniae Avibactam medicine.medical_treatment 030106 microbiology Porins Microbial Sensitivity Tests beta-Lactamases lcsh:Infectious and parasitic diseases Microbiology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Bacterial Proteins Drug Resistance Bacterial medicine Humans Potency lcsh:RC109-216 030212 general & internal medicine biology Broth microdilution General Medicine biology.organism_classification Anti-Bacterial Agents Cephalosporins Infectious Diseases chemistry Mutation Porin Beta-lactamase Bacterial outer membrane Azabicyclo Compounds Bacteria |
| Zdroj: | International Journal of Infectious Diseases, Vol 93, Iss, Pp 252-257 (2020) |
| ISSN: | 1201-9712 |
| Popis: | Objectives: Evaluate the role of porins in the susceptibility of Klebsiella pneumoniae to ceftaroline and ceftaroline-avibactam. Methods: Susceptibility to ceftaroline and ceftaroline-avibactam was tested by broth microdilution method in Klebsiella pneumoniae isolates (n = 65), including isogenic mutants (n = 30) and clinical isolates (n = 35), with different outer membrane porin defects in the presence or absence of beta lactamases. Results: Ceftaroline exhibited excellent activity against all the isogenic porin mutants with a MIC range of 0.125–0.25 μg/ml. Ceftaroline showed limited activity in the presence of extended spectrum β-lactamase enzymes in isogenic mutant constructs as expected but regained effectiveness in combination with avibactam against these isolates except those carrying metallo-carbapenemase (IMP-4) with an MIC range of 0.25–>32 μg/ml. Ceftaroline-avibactam was able to inhibit 86% of the clinical isolates (n = 35) of Klebsiella pneumoniae carrying porin defects and multiple beta lactamases with only four isolates showing raised MICs against the combination (MIC range 0.125–4 μg/ml). One clinical isolate with IMP-4 carbapenemase had an MIC value of >32 μg/ml. Conclusion: Outer membrane porins play a key role in the transport of ceftaroline inKlebsiella pneumoniae but it remains effective in isolates with altered permeability due to common porin mutations. The addition of avibactam substantially enhances the potency of ceftaroline providing an effective remedy to the problem of omnipresent beta lactamases in these bacteria. Keywords: Ceftaroline, Isogenic mutants, Porins, Klebsiella pneumoniae, β-Lactamase, Avibactam |
| Databáze: | OpenAIRE |
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