Percentage of susceptibility per year of <i>S</i>. <i>maltophilia</i> to ceftazidime, levofloxacin, and trimethoprim-sulfamethoxazole.

Percentage of susceptibility per year of S. maltophilia to ceftazidime, levofloxacin, and trimethoprim-sulfamethoxazole.</p

Heatmap of pairwise comparison among 16S rRNA sequences.

Degraded panel on the right side reflects the visual representation of identity percentage from the lowest value (0% in blue) to the highest value (100% in dark red). Numbers into the boxes represent the numerical value of the identity percentages. (PPTX)</p

Presence/absence plot of Genes Associated to Cefiderocol Resistance (GACR) detected in the genome of Cefiderocol-Resistant <i>Stenotrophomonas</i> Strains (CRSS).

The panel on the right rise represents the functional type of the GACR. Legends on the x-axis represent the proteins annotated. Legends of the y-axis represents the strain ID. Colored boxes represented the GACR detected in the strains. White boxes represent the GACR absents.</p

Isolates selection algorithm.

BackgroundInfections caused by Stenotrophomonas maltophilia and related species are increasing worldwide. Unfortunately, treatment options are limited, whereas the antimicrobial resistance is increasing.MethodsWe included clinical isolates identified as S. maltophilia by VITEK 2 Compact. Ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. Minimum inhibitory concentrations (MICs) were reported for all antibiotics. We sequenced the Whole Genome of cefiderocol resistant strains (CRSs) and annotated their genes associated with cefiderocol resistance (GACR). Presumptive phylogenetic identification employing the 16S marker was performed.ResultsOne hundred and one clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to cefiderocol exhibiting MIC values ≥ 2 μg/mL (4.95%). The β-lactamase inhibitors meropenem/vaborbactam and imipenem/relebactam, failed to inhibit S. maltophilia, preserving both MIC50 and MIC90 ≥64 μg/mL. Ceftazidime/avibactam restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC90. Phylogeny based on 16S rRNA allowed to identify to cefiderocol resistant strains as putative species clustered into Stenotrophomonas maltophilia complex (Smc). In these strains, we detected GARCs such as Mutiple Drug Resistance (MDR) efflux pumps, L1-type β-lactamases, iron transporters and type-1 fimbriae.ConclusionAntimicrobial resistance to first-line treatment is low. The in vitro activity of new β-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. Cefiderocol could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated.</div

Strains included in the study with isolation date and type of microbiological sample.

Strains included in the study with isolation date and type of microbiological sample.</p

ML phylogenetic tree of the 16S rRNA sequences.

The ID of the sequences from type strains are displayed into the brackets. The CRSS position in marked in bold and pink color into the tree. Numbers on the nodes and branches represent the Ultrafast Bootstrap values of 2000 replicates. Scale bar represents the number of nucleotide differences between branches.</p

MIC₅₀, MIC₉₀, ranges of MIC and susceptibilities of selected agents for <i>S</i>. <i>maltophilia</i> isolates from clinical specimens.

MIC50, MIC90, ranges of MIC and susceptibilities of selected agents for S. maltophilia isolates from clinical specimens.</p

<i>In vitro</i> activities to other antibiotics of cefiderocol resistant <i>S</i>. <i>maltophilia</i> isolates.

In vitro activities to other antibiotics of cefiderocol resistant S. maltophilia isolates.</p

<i>In vitro</i> activities of selected agents against clinical <i>S</i>. <i>maltophilia</i> isolates.

In vitro activities of selected agents against clinical S. maltophilia isolates.</p