US 2017/0283862 A1 · GENETIC TESTING FOR PREDICTING RESISTANCE OF KLEBSIELLA SPECIES AGAINST ANTIMICROBIAL AGENTS

Abstract

The invention relates to a method of determining an infection of a patient with Klebsiella species potentially resistant to antimicrobial drug treatment by detecting mutations in the genes, parC, KPN 01607, gyrA, KPN 02451, baeR, aceF, ybgH, ynjE, KPN 01951, KPN 01961, KPN 02114, mhpA, KPN 02128, KPN 02144, KPN 02149, ydiJ, btuE, oppC, pth, KPN 02298, KPN 02302, dadA, yoaA, ftn, cbl, hisB, yegQ, yehY, KPN 02580, yejH, KPN 02621, yfaW, KPN 02170, KPN 02025, livG, livM, livH, fliY, yedQ, abgB, treA, baeS, KPN 02399, ydcR, anmK, ccmF, KPN 02440, KPN 02540, KPN 01752, and KPN 04195, and/or KOX 26125, KOX 13365, KOX 16735, KOX 25695, KOX 12270, and KOX 15055; a method of selecting a treatment of a patient suffering from an antibiotic resistant Klebsiella infection; and a method of determining an antibiotic resistance profile for bacterial microorganisms of Klebsiella species, as well as computer program products used in these methods. In an exemplary method, a sample is used for molecular testing and then a molecular fingerprint is taken. The result is then compared to a reference library and the result is reported.

Claims16

Dependent claims

A diagnostic method of determining an infection of a patient with Klebsiella species potentially resistant to antimicrobial drug, e.g. antibiotic, treatment, comprising the steps of:

a) obtaining or providing a sample containing or suspected of containing at least one Klebsiella species from the patient;
b) determining the presence of at least one mutation in at least two genes from the group of genes consisting of parC, KPN_01607, gyrA, KPN_02451, baeR, aceF, ybgH, ynjE, KPN_01951, KPN_01961, KPN_02114, mhpA, KPN_02128, KPN_02144, KPN_02149, ydiJ, btuE, oppC, pth, KPN_02298, KPN_02302, dadA, yoaA, ftn, cbl, hisB, yegQ, yehY, KPN_02580, yejH, KPN_02621, yfaW, KPN_02170, KPN_02025, livG, livM, livH, fliY, yedQ, abgB, treA, baeS, KPN_02399, ydcR, anmK, ccmF, KPN_02440, KPN_02540, KPN_01752, and KPN_04195, and/or KOX_26125, KOX_13365, KOX_16735, KOX_25695, KOX_12270, and KOX_15055, wherein the presence of said at least two mutations is indicative of an infection with an antimicrobial drug, e.g. antibiotic, resistant Klebsiella strain in said patient.

A method of selecting a treatment of a patient suffering from an infection with a potentially resistant Klebsiella strain, comprising the steps of:

a) obtaining or providing a sample containing or suspected of containing at least one Klebsiella species from the patient;
b) determining the presence of at least one mutation in at least two genes from the group of genes consisting of parC, KPN_01607, gyrA, KPN_02451, baeR, aceF, ybgH, ynjE, KPN_01951, KPN_01961, KPN_02114, mhpA, KPN_02128, KPN_02144, KPN_02149, ydiJ, btuE, oppC, pth, KPN_02298, KPN_02302, dadA, yoaA, ftn, cbl, hisB, yegQ, yehY, KPN_02580, yejH, KPN_02621, yfaW, KPN_02170, KPN_02025, livG, livM, livH, fliY, yedQ, abgB, treA, baeS, KPN_02399, ydcR, anmK, ccmF, KPN_02440, KPN_02540, KPN_01752, and KPN_04195, and/or KOX_26125, KOX_13365, KOX_16735, KOX_25695, KOX_12270, and KOX_15055, wherein the presence of said at least two mutations is indicative of a resistance to one or more antimicrobial, e.g. antibiotic, drugs;
c) identifying said at least one or more antimicrobial, e.g. antibiotic, drugs;
and
d) selecting one or more antimicrobial, e.g. antibiotic, drugs different from the ones identified in step c) and being suitable for the treatment of a Klebsiella infection.

2 more elements

The method of one or more of the preceding claims, wherein the Klebsiella species is Klebsiella pneumoniae and at least a mutation in parC, particularly in position 3763210 with regard to reference genome NC_009648 as annotated at the NCBI, is determined, and/or

wherein the Klebsiella species is Klebsiella oxytoca and at least a mutation in KOX_26125, particularly in position 5645611, with regard to reference genome NC_016612 as annotated at the NCBI, is determined.

The method of one or more of the preceding claims, wherein the method involves determining the resistance of Klebsiella to one or more antimicrobial, e.g. antibiotic, drugs.

The method of one or more of the preceding claims, wherein the antimicrobial drug, e.g. antibiotic drug, is selected from the group consisting of Amoxicillin/K Clavulanate (AUG), Ampicillin (AM), Aztreonam (AZT), Cefazolin (CFZ), Cefepime (CPE), Cefotaxime (CFT), Ceftazidime (CAZ), Ceftriaxone (CAX), Cefuroxime (CRM), Cephalotin (CF), Ciprofloxacin (CP), Ertapenem (ETP), Gentamicin (GM), Imipenem (IMP), Levofloxacin (LVX), Meropenem (MER), Piperacillin/Tazobactam (P/T), Ampicillin/Sulbactam (A/S), Tetracycline (TE), Tobramycin (TO), and Trimethoprim/Sulfamethoxazole (T/S).

A method of determining an antimicrobial drug, e.g. antibiotic, resistance profile for bacterial microorganisms of Klebsiella species, comprising:

obtaining or providing a first data set of gene sequences of a plurality of clinical isolates of Klebsiella species;
providing a second data set of antimicrobial drug, e.g. antibiotic, resistance of the plurality of clinical isolates of Klebsiella species;
aligning the gene sequences of the first data set to at least one, preferably one, reference genome of Klebsiella, and/or assembling the gene sequence of the first data set, at least in part;
analyzing the gene sequences of the first data set for genetic variants to obtain a third data set of genetic variants;
correlating the third data set with the second data set and statistically analyzing the correlation;
and
determining the genetic sites in the genome of Klebsiella associated with antimicrobial drug, e.g. antibiotic, resistance.

4 more elements

Dependencies are inferred from the claim text.

Genetic testing for predicting resistance of klebsiella species against antimicrobial agents

Life of this patent

Genetic testing for predicting resistance of klebsiella species against antimicrobial agents

Life of this patent

Abstract

Claims16