Molecular Characteristics of Colistin Resistance in Acinetobacter baumannii and the Activity of Antimicrobial Combination Therapy in a Tertiary Care Medical Center in Lebanon.
Antoine G Abou FayadLouis-Patrick HaraouiAhmad SleimanHadi HusseinFrédéric GrenierGhada DerbajDana ItaniSereen IweirNour SherriWael BazziSari RasheedArax TanelianMariam MiariBassam El HafiSouha S KanjZeina A KanafaniZiad DaoudGeorge F ArajGhassan M MatarPublished in: Microorganisms (2024)
(1) Background: Infections with pan-drug-resistant (PDR) bacteria, such as A. baumannii , are becoming increasingly common, especially in healthcare facilities. In this study, we selected 15 colistin-resistant clinical A. baumannii isolates from a hospital in Beirut, Lebanon, to test combination therapies and determine their sequence types (STs) and the mechanism of colistin resistance using whole-genome sequencing (WGS). (2) Methods: Antimicrobial susceptibility testing via broth microdilution against 12 antimicrobials from different classes and growth rate assays were performed. A checkerboard assay was conducted on PDR isolates using six different antimicrobials, each in combination with colistin. Genomic DNA was extracted from all isolates and subjected to WGS. (3) Results: All isolates were resistant to all tested antimicrobials with the one exception that was susceptible to gentamicin. Combining colistin with either meropenem, ceftolozane-tazobactam, or teicoplanin showed synergistic activity. Sequencing data revealed that 67% of the isolates belonged to Pasteur ST2 and 33% to ST187. Furthermore, these isolates harbored a number of resistance genes, including bla OXA-23 . Mutations in the pmrC gene were behind colistin resistance. (4) Conclusions: With the rise in antimicrobial resistance and the absence of novel antimicrobial production, alternative treatments must be found. The combination therapy results from this study suggest treatment options for PDR ST2 A. baumannii -infected patients.
Keyphrases
- acinetobacter baumannii
- drug resistant
- combination therapy
- multidrug resistant
- gram negative
- pseudomonas aeruginosa
- klebsiella pneumoniae
- healthcare
- genetic diversity
- antimicrobial resistance
- high throughput
- tertiary care
- genome wide
- staphylococcus aureus
- cystic fibrosis
- escherichia coli
- emergency department
- electronic health record
- copy number
- machine learning
- cell free
- social media
- transcription factor
- artificial intelligence
- circulating tumor