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In Vitro Activity of 22 Antibiotics against Achromobacter Isolates from People with Cystic Fibrosis. Are There New Therapeutic Options?

ABSTRACT: Bacteria belonging to the genus Achromobacter are increasingly isolated from respiratory samples of people with cystic fibrosis (PWCF). The management of this multidrug-resistant genus is challenging and characterised by a lack of international recommendations, therapeutic guidelines and data concerning antibiotic susceptibility, especially concerning the newer antibiotics. The objective of this study was to describe the antibiotic susceptibility of Achromobacter isolates from PWCF, including susceptibility to new antibiotics. The minimum inhibitory concentrations (MICs) of 22 antibiotics were determined for a panel of 23 Achromobacter isolates from 19 respiratory samples of PWCF. Two microdilution MIC plates were used: EUMDROXF^® plate (Sensititre) and Micronaut-S Pseudomonas MIC^® plate (Merlin) and completed by a third method if necessary (E-test^® or UMIC^®). Among usual antimicrobial agents, the most active was imipenem (70% susceptibility). Trimethoprim-sulfamethoxazole, piperacillin and tigecycline (65%, 56% and 52% susceptibility, respectively) were still useful for the treatment of Achromobacter infections. Among new therapeutic options, β-lactams combined with a β-lactamase-inhibitor did not bring benefits compared to β-lactam alone. On the other hand, cefiderocol appeared as a promising therapeutic alternative for managing Achromobacter infections in PWCF. This study provides the first results on the susceptibility of clinical Achromobacter isolates concerning new antibiotics. More microbiological and clinical data are required to establish the optimal treatment of Achromobacter infections.

SUBMITTER: Beauruelle C

PROVIDER: S-EPMC8703882 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Achromobacter species are increasingly being detected in cystic fibrosis (CF) patients, where they can establish chronic infections by adapting to the lower airway environment. To better understand the mechanisms contributing to a successful colonization by Achromobacter species, we sequenced the whole genome of 54 isolates from 26 patients with occasional and early/late chronic lung infection. We performed a phylogenetic analysis and compared virulence and resistance genes, genetic variants and mutations, and hypermutability mechanisms between chronic and occasional isolates. We identified five Achromobacter species as well as two non-affiliated genogroups (NGs). Among them were the frequently isolated Achromobacter xylosoxidans and four other species whose clinical importance is not yet clear: Achromobacter insuavis, Achromobacter dolens, Achromobacter insolitus and Achromobacter aegrifaciens. While A. insuavis and A. dolens were isolated only from chronically infected patients and A. aegrifaciens only from occasionally infected patients, the other species were found in both groups. Most of the occasional isolates lacked functional genes involved in invasiveness, chemotaxis, type 3 secretion system and anaerobic growth, whereas the great majority (>60%) of chronic isolates had these genomic features. Interestingly, almost all (n=22/23) late chronic isolates lacked functional genes involved in lipopolysaccharide production. Regarding antibiotic resistance, we observed a species-specific distribution of blaOXA genes, confirming what has been reported in the literature and additionally identifying blaOXA-2 in some A. insolitus isolates and observing no blaOXA genes in A. aegrifaciens or NGs. No significant difference in resistance genes was found between chronic and occasional isolates. The results of the mutator genes analysis showed that no occasional isolate had hypermutator characteristics, while 60% of early chronic (<1 year from first colonization) and 78% of late chronic (>1 year from first colonization) isolates were classified as hypermutators. Although all A. dolens, A. insuavis and NG isolates presented two different mutS genes, these seem to have a complementary rather than compensatory function. In conclusion, our results show that Achromobacter species can exhibit different adaptive mechanisms and some of these mechanisms might be more useful than others in establishing a chronic infection in CF patients, highlighting their importance for the clinical setting and the need for further studies on the less clinically characterized Achromobacter species.

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In Vitro Activity of 22 Antibiotics against Achromobacter Isolates from People with Cystic Fibrosis. Are There New Therapeutic Options?

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