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      Elizabethkingia Intra-Abdominal Infection and Related Trimethoprim-Sulfamethoxazole Resistance: A Clinical-Genomic Study

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          Abstract

          (1) Background: Elizabethkingia spp. is an emerging nosocomial pathogen which causes mostly blood stream infection and nosocomial pneumonia. Among Elizabethkingia species, Elizabethkingia anophelis is the major pathogen, but misidentification as Elizabethkingia meningoseptica is a common problem. Elizabethkingia also possesses broad antibiotic resistance, resulting in high morbidity and mortality of the infection. The aim of our study was to review Elizabethkingia intra-abdominal infections and investigate resistance mechanisms against TMP/SMX in Elizabethkingia anophelis by whole genome sequencing. (2) Methods: We retrospectively searched records of patients with Elizabethkingia intra-abdominal infection between 1990 and 2019. We also conducted whole genome sequencing for a TMP/SMX-resistant Elizabethkingia anophelis to identify possible mechanisms of resistance. (3) Results: We identified a total of nine cases of Elizabethkingia intra-abdominal infection in a review of the literature, including our own case. The cases included three biliary tract infections, three CAPD-related infection, two with infected ascites, and two postoperation infections. Host factor, indwelling-catheter, and previous invasive procedure, including surgery, play important roles in Elizabethkingia infection. Removal of the catheter is crucial for successful treatment. Genomic analysis revealed accumulated mutations leading to TMP/SMX-resistance in folP. (4) Conclusions: Patients with underlying disease and indwelling catheter are more susceptible to Elizabethkingia intra-abdominal infection, and successful treatment requires removal of the catheter. The emerging resistance to TMP/SMX may be related to accumulated mutations in folP.

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          Most cited references28

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          Mechanisms of quinolone action and resistance: where do we stand?

          Quinolone antibiotics represent one of the most important classes of anti-infective agents and, although still clinically valuable, their use has been compromised by the increasing emergence of resistant strains, which has become a prevalent clinical problem. Quinolones act by inhibiting the activity of DNA gyrase and topoisomerase IV - two essential bacterial enzymes that modulate the chromosomal supercoiling required for critical nucleic acid processes. The acquisition of quinolone resistance is recognized to be multifactorial and complex. The main resistance mechanism consists of one or a combination of target-site gene mutations that alter the drug-binding affinity of target enzymes. However, other mechanisms such as mutations that lead to reduced intracellular drug concentrations, by either decreased uptake or increased efflux, and plasmid-encoded resistance genes producing either target protection proteins, drug-modifying enzymes or multidrug efflux pumps are known to contribute additively to quinolone resistance. The understanding of these different resistance mechanisms has improved significantly in recent years; however, many details remain to be clarified and the contribution of less-studied mechanisms still needs to be better elucidated in order to fully understand this phenotype.
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            Elizabethkingia anophelis sp. nov., isolated from the midgut of the mosquito Anopheles gambiae.

            The taxonomic position, growth characteristics and antibiotic resistance properties of a slightly yellow-pigmented bacterial strain, designated R26(T), isolated from the midgut of the mosquito Anopheles gambiae, were studied. The isolate produced rod-shaped cells, which stained Gram-negative. The bacterium had two growth optima at 30-31 °C and 37 °C. Strain R26(T) demonstrated natural antibiotic resistance to ampicillin, chloramphenicol, kanamycin, streptomycin and tetracycline. 16S rRNA gene sequence analysis revealed that the isolate showed 98.6 % sequence similarity to that of Elizabethkingia meningoseptica ATCC 13253(T) and 98.2 % similarity to that of Elizabethkingia miricola GTC 862(T). The major fatty acids of strain R26(T) were iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 4 (iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c/t). Strain R26(T) contained only menaquinone MK-6 and showed a complex polar lipid profile consisting of diphosphatidylglycerol, phosphatidylinositol, an unknown phospholipid and unknown polar lipids and glycolipids. DNA-DNA hybridization experiments with E. meningoseptica CCUG 214(T) ( = ATCC 13253(T)) and E. miricola KCTC 12492(T) ( = GTC 862(T)) gave relatedness values of 34.5 % (reciprocal 41.5 %) and 35.0 % (reciprocal 25.7 %), respectively. DNA-DNA hybridization results and some differentiating biochemical properties indicate that strain R26(T) represents a novel species, for which the name Elizabethkingia anophelis sp. nov. is proposed. The type strain is R26(T) ( = CCUG 60038(T) = CCM 7804(T)).
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              Transfer of Chryseobacterium meningosepticum and Chryseobacterium miricola to Elizabethkingia gen. nov. as Elizabethkingia meningoseptica comb. nov. and Elizabethkingia miricola comb. nov.

              The taxonomic positions of six strains (including the type strain) of Chryseobacterium meningosepticum (King 1959) Vandamme et al. 1994 and the type strain of Chryseobacterium miricola Li et al. 2004 were re-evaluated by using a polyphasic taxonomic approach. Phylogenetic analysis, based on 16S rRNA gene sequencing, showed that the strains represent a separate lineage from the type strains of the Chryseobacterium-Bergeyella-Riemerella branch within the family Flavobacteriaceae (90.7-93.9 % similarities), which was supported by phenotypic differences. Combined phylogenetic and phenotypic data showed that C. meningosepticum and C. miricola should be transferred to a new genus, Elizabethkingia gen. nov., with the names Elizabethkingia meningoseptica comb. nov. (type strain, ATCC 13253(T) = NCTC 10016(T) = LMG 12279(T) = CCUG 214(T)) and Elizabethkingia miricola comb. nov. (type strain, DSM 14571(T) = JCM 11413(T) = GTC 862(T)) proposed.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                09 February 2021
                February 2021
                : 10
                : 2
                : 173
                Affiliations
                [1 ]Section of Infectious Disease, Taichung Veterans General Hospital, Taichung 40705, Taiwan; ricecake1771@ 123456gmail.com (L.-C.T.); tedi3tedi3@ 123456hotmail.com (C.-H.T.)
                [2 ]Routine Laboratory, Taichung Veterans General Hospital, Taichung 40705, Taiwan; jmwang@ 123456vghtc.gov.tw
                [3 ]Department of Computer Science and Information Engineering, National Chung Cheng University, Taichung 62102, Taiwan; mrfish2468@ 123456gmail.com
                [4 ]Department of Emergency Medicine, Division of Clinical Toxicology, Taichung Veterans General Hospital, Taichung 40705, Taiwan; doc1385e@ 123456gmail.com
                [5 ]National Defense Medical Center, School of Medicine, Taipei 11490, Taiwan
                [6 ]Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan; kllaichiayi@ 123456yahoo.com.tw
                [7 ]Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan
                [8 ]Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan
                Author notes
                [* ]Correspondence: ythuang@ 123456cs.ccu.edu.tw (Y.-T.H.); pyliu@ 123456vghtc.gov.tw (P.-Y.L.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8561-0582
                https://orcid.org/0000-0003-2098-8872
                https://orcid.org/0000-0001-9253-2394
                Article
                antibiotics-10-00173
                10.3390/antibiotics10020173
                7915159
                33572268
                88b3d03f-492a-453c-a9ae-a490a4f0374a
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 13 January 2021
                : 05 February 2021
                Categories
                Article

                elizabethkingia anopheles,trimethoprim-sulfamethoxazole,sequence alignment,whole genome sequencing

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