OXA-900, a Novel OXA Sub-Family Carbapenemase Identified in Citrobacter freundii, Evades Detection by Commercial Molecular Diagnostics Tests

Frenk, Sammy; Rakovitsky, Nadya; Kon, Hadas; Rov, Reut; Abramov, S. V.; Lurie-Weinberger, Mor N; Schwartz, David; Pinco, Erica; Lellouche, Jonathan; Carmeli, Yehuda

doi:10.3390/microorganisms9091898

Cited by 4 publications

(4 citation statements)

References 26 publications

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“…2023). They also have an increased propensity to take up genetic material conferring antibiotic resistance from other related or unrelated species (Frenk et al, 2021). The presence of a total of 86 naturally occurring antibiotic-resistant determinant genes identified in the reference genomes of 18 Citrobacter spp.…”

Section: Antibiotic Resistancementioning

confidence: 99%

“…The IncC plasmid-borne carbapenemresistant determinants bla OXA-900 are located in C. freundii. This gene is believed to have originated from a distinct Gram-negative bacterium Shewanella, a marine environmental extremophile (Frenk et al, 2021). In C. koseri, a single bla KPC-82 (a bla KPC-2 variant) conferring resistance to b -lactam/b -lactam inhibitor combination was carried in a transposon integrated chromosomally.…”

Section: Antibiotic Resistancementioning

confidence: 99%

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A brief insight into Citrobacter species - a growing threat to public health

Jabeen,

Islam,

Hassan

et al. 2023

Front. Antibiot.

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Citrobacter spp. are Gram-negative, non-spore forming, rod-shaped, facultative anaerobic bacteria from the Enterobacteriaceae family often found in soil, sewage, sludge, water, food, and the intestinal tracts of animals and humans. Several members of Citrobacter spp. especially C. freundii, C. koseri, C. braakii are frequently detected in newborn illnesses, urinary tract infections, and patients with severe underlying conditions, including hypertension, diabetes, cancer, and respiratory infections, or those who are immunocompromised. Strains of Citrobacter spp. can spread vertically or horizontally from carriers or other hospital sources and thus cause nosocomial infections in hospital settings. A total of 19 Citrobacter genomospecies have been recognized based on genomics. It has been noted that the Citrobacter genus acquired antimicrobial resistance and virulence, including invasion, colonization, biofilm formation, and toxin production. The recent emergence and spread of antimicrobial resistance to β-lactams, carbapenems, fluoroquinolones, aminoglycosides, and colistin in Citrobacter spp. through chromosomal and plasmid-mediated resistance limits the empiric treatment options. Therefore, combination therapy involving costly and potentially hazardous antibiotics poses significant challenges in treating Citrobacter infections. Here we summarized the nomenclature of Citrobacter spp., clinical manifestations, epidemiology, pathogenesis, antibiotic resistance mechanisms, and treatments from various clinical samples. This review will expand our knowledge of the genomics and epidemiology of Citrobacter spp., enabling improved control of infections and the spread of these organisms.

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Section: Antibiotic Resistancementioning

confidence: 99%

Section: Antibiotic Resistancementioning

confidence: 99%

A brief insight into Citrobacter species - a growing threat to public health

Jabeen,

Islam,

Hassan

et al. 2023

Front. Antibiot.

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“…Confirmation of the species was performed by molecular genotyping, as described previously [6]. OXA typing was performed by sequencing as previously described [7]. All isolates were stored at −80 • C and sub-cultured twice on blood agar (TSA + 5% blood sheep agar, HyLabs, Rehovot, Israel) at 35 ± 2 • C before further testing.…”

Section: Description Of the Isolatementioning

confidence: 99%

Colistin Dependency among Colistin-Heteroresistant Acinetobacter baumannii Isolates

et al. 2021

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Colistin dependent (CD) isolates are dependent on colistin for optimal growth. Here we aimed to systematically determine the emergence of CD among colistin-heteroresistant carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. We also examined the phenotypic characteristics of CD and the evolution of CD strains to overt resistance. Additionally, we examined whether detection of growth in blood cultures was impaired by CD. Heteroresistant isolates, as determined by population analysis profiling, were exposed to colistin; when the colony count with colistin was significantly higher than without, isolates were suspected to be CD. CD was confirmed by Etest and growth curves. CD strains with colistin minimum inhibitory concentrations > 2 mg/L after growth in colistin-free media were considered colistin-resistant. Of the 65 heteroresistant strains tested, eight became CD after colistin exposure. These strains attained higher colony counts and growth rates with colistin vs. without, and grew adjacent to the colistin Etest strip. CD strains exhibited increased susceptibilities to multiple antibiotics compared to their parent heteroresistant strains. All CD strains tested became colistin-resistant following growth without colistin. CD strains were detected in blood culture bottles, but time to detection was significantly prolonged compared with parent strains, suggesting that CD may lead to delay in detection of CRAB bacteremia.

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“…To match the kcat/Km results with biochemical validation tests, Dabos et al defined the value of 0.27 mM-1.s-1 as the cutoff above which an OXA-48 variant may be considered a carbapenem-hydrolyzing enzyme. This diversity of OXA-48 variants in terms of hydrolysis profile and amino acid sequences may also have an impact on detection with commercially available assays (either biochemical or molecular) and thus contribute to the silent spread of some variants, as observed in OXA-244 [ 13 ] and OXA-900, a novel and distinct subfamily of OXA-48 variants described by Frenk et al [ 14 ]. The IncC plasmid-mediated bla OXA-900 gene was identified in a Citrobacter freundii isolate that displayed significant carbapenem hydrolysis using β-Carba (BioRad, Marnes-la-Coquette, France) and a modified CIM test, but it was not detected using commercially available DNA-based methods.…”

mentioning

confidence: 99%