Combating Metallo-β-Lactamase-Producing <i>Pseudomonas aeruginosa</i>: The Fractional Inhibitory Concentration Index as a Tool to Evaluate Antibiotic Synergy
<b>Background</b>: Multi-drug-resistant Gram-negative bacteria producing metallo-β-lactamase are an increasing concern. Here, we described three cases of infection due to difficult-to-treat and drug-resistant <i>P. aeruginosa</i> producing metallo-β-lactamases, which were suc...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/14/2/210 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <b>Background</b>: Multi-drug-resistant Gram-negative bacteria producing metallo-β-lactamase are an increasing concern. Here, we described three cases of infection due to difficult-to-treat and drug-resistant <i>P. aeruginosa</i> producing metallo-β-lactamases, which were successfully treated with antibiotic combination of cefiderocol plus imipenem–relebactam, and reported on the molecular and epidemiological features of the isolates and the in vitro synergistic effects of different antibiotic combinations guiding antibiotic treatment. <b>Patients and methods</b>: Three <i>P. aeruginosa</i> strains were isolated from respiratory or blood cultures of three different patients. Minimum inhibitory concentrations breakpoints were interpreted according to EUCAST recommendations. Next-generation sequencing data were used for in silico identification of resistance genes and sequence types and for core genome multi-locus sequence typing analysis. The fractional inhibitory concentration index was performed as a measure of synergy of cefiderocol plus imipenem and imipenem–relebactam. <b>Results</b>: The three isolates exhibited different multi-drug-resistant and molecular profiles carrying blaIMP-13 (imipenemase metallo-β-lactamase-13) (isolates named Pse-1 and Pse-3) and blaVIM-2 (Verona integron-encoded metallo-β-lactamase-2) (isolate Pse-2). Typing showed that the isolates did not cluster and belonged to different sequence types. The E-test method showed the presence of synergy of cefiderocol in combination with imipenem–relebactam in the two <i>P. aeruginosa</i> isolates producing IMP-13 (Pse-1 and Pse-3). No synergy was observed in the isolate producing VIM-2 (Pse-2). <b>Conclusions</b>: Cefiderocol in association with imipenem–relebactam exhibited a synergistic effect against IMP-producing <i>P. aeruginosa</i> isolates. Further studies with a range of drugs and an expanded number of isolates are required to ascertain potential novel synergistic associations and the clinical utility of the fractional inhibitory concentration index. |
|---|---|
| ISSN: | 2079-6382 |