Methods of detecting multi-drug resistant organisms

Abstract

The present invention provide methods using genes associated with multi-drug resistance for rapidly detecting a patient colonized or infected with an multi-drug resistant organism and administrating the appropriate precautions and/or treatment.

We claim: 
     
         1 . A method of screening a patient for multi-drug resistant bacterial colonization or infection comprising:
 a. isolating a nucleic acid sample from a biological sample obtained from the patient;   b. amplifying the antibiotic resistant genes KPC, NDM, OXA, VIM, IMP, CTX-M and VanA by contacting the nucleic acid sample with one or more amplification primers that specifically hybridize with the each of the antibiotic resistant genes to provide an enriched nucleic acid sample;   c. detecting the presence of the antibiotic gene by contacting the nucleic acid sample with one or more detection primers that specifically hybridize with the each of the antibiotic resistant genes to in the enriched nucleic acid sample;   d. classifying the patient as having a multi-drug resistant bacterial colonization or infection when one or more of the antibiotic resistant genes are identified in the enriched nucleic acid sample;   e. providing a contact precautions recommendation for the patient having a multi-drug resistant bacterial colonization or infection.   
     
     
         2 . The method of  claim 1 , wherein the antibiotic resistant genes of step (b) further comprise one or more of IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE. 
     
     
         3 . The method of  claim 1 , wherein the contact precaution includes one or more of the following: isolating the patient to a quarantine area or ward, providing a private room for said patient, donning personal protective apparel upon entering the patient's room, limiting patient mobility, limiting or restricting access of non-colonized or non-infected patients or medical personnel to the patient, or providing dedicated patient care equipment. 
     
     
         4 . The method of  claim 1 , wherein the biological sample is an anal swab, a rectal swab, a skin swab, nasal swab, wound swab, stool, blood, plasma, serum, urine, sputum, respiratory lavage, cerebrospinal fluid, bacteria culture, bacteria isolate, fungal culture, fungal isolate, virus culture or virus isolate. 
     
     
         5 . The method of  claim 1 , wherein said patient is at high risk for having a multi-drug resistant bacteria colonization or infection. 
     
     
         6 . The method of  claim 1 , further providing a treatment recommendation for said patient wherein
 a. when KPC, NDM, OXA, VIM, IMP is detected recommending that the patient does not receive a carbapenem antibiotic;   b. when CTM-X is detected recommending that the patient does not receive a cephalosporin antibiotic; or   c. when VanA is detected recommending that the patient does not receive vancomycin.   
     
     
         7 . The method of  claim 2 , further providing a treatment recommendation for said patient wherein
 a. when KPC, NDM, OXA, VIM, IMP, SME, SFC, IMI, NMC, or CcrA is detected recommending that the patient does not receive a carbapenem antibiotic;   b. when CTM-X, PER, VEB, GES, BES, SFO, TLA, TEM with amino acid substitutions E104K, R164H, R164S, R164C, G238S or E240K, SHV with amino acid substitutions G156D, G238S or E240K, is detected recommending that the patient does not receive a cephalosporin antibiotic; or   c. when ACC, MOX, CMY, CFE, ACT, DHA or FOX is detected recommending that the patient does not receive a beta-lactamase inhibitor-beta-lactam combination; or   d. when VanA is detected recommending that the patient does not receive vancomycin.   
     
     
         8 . The method of  claim 1 , further comprising testing the biological sample to identify the phenotype of the multi-drug resistant organism. 
     
     
         9 . The method of  claim 1  further comprising culturing the biological sample and confirming drug resistance. 
     
     
         10 . A method of making a treatment recommendation for a subject known to or suspected of being colonized with or having a bacterial infection comprising:
 a. isolating a nucleic acid sample from a biological sample obtained from the patient;   b. amplifying the antibiotic resistant genes KPC, NDM, OXA, VIM, IMP, CTX-M and VanA by contacting the nucleic acid sample with one or more amplification primers that specifically hybridize with the each of the antibiotic resistant genes to provide an enriched nucleic acid sample;   c. detecting the presence of the antibiotic gene by contacting the nucleic acid sample with one or more detection primers that specifically hybridize with the each of the antibiotic resistant genes to in the enriched nucleic acid sample;   d. recommending that the patient does not receive a carbapenem antibiotic when KPC, NDM, OXA, VIM, IMP is detected;   e. recommending that the patient does not receive a cephalosporin antibiotic when CTM-X is detected; or   f. recommending that the patient does not receive vancomycin when VanA is detected.   
     
     
         11 . The method of  claim 10 , wherein the antibiotic resistant genes of step (b) further comprise one or more of IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE wherein
 g. recommending that the patient does not receive a carbapenem antibiotic when SME, SFC, IMI, NMC, or CcrA is detected   h. recommending that the patient does not receive a cephalosporin antibiotic when PER, VEB, GES, BES, SFO, TLA, TEM with amino acid substitutions E104K, R164H, R164S, R164C, G238S or E240K, SHV with amino acid substitutions G156D, G238S or E240K is detected; or   i. recommending that the patient does not receive a beta-lactamase inhibitor-beta-lactam combination when ACC, MOX, CMY, CFE, ACT, DHA or FOX is detected.   
     
     
         12 . A method of making a treatment recommendation for a healthy subject comprising:
 a. isolating a nucleic acid sample from a biological sample obtained from the patient;   b. amplifying the antibiotic resistant genes KPC, NDM, OXA, VIM, IMP, CTX-M and VanA by contacting the nucleic acid sample with one or more amplification primers that specifically hybridize with the each of the antibiotic resistant genes to provide an enriched nucleic acid sample;   c. detecting the presence of the antibiotic gene by contacting the nucleic acid sample with one or more detection primers that specifically hybridize with the each of the antibiotic resistant genes to in the enriched nucleic acid sample;   d. recommending that the patient does not receive a carbapenem antibiotic when KPC, NDM, OXA, VIM, or IMP is detected;   e. recommending that the patient does not receive a beta-lactam antibiotic when CTM-X is detected; or   f. recommending that the patient does not receive vancomycin when VanA is detected.   
     
     
         13 . The method of  claim 12 , wherein the antibiotic resistant genes of step (b) further comprise one or more of IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE wherein
 j. recommending that the patient does not receive a carbapenem antibiotic when SME, SFC.IMI, NMC, or CcrA is detected   k. recommending that the patient does not receive a cephalosporin antibiotic when PER, VEB, GES, BES, SFO, TLA, TEM with amino acid substitutions E104K, R164H, R164S, R164C, G238S or E240K, SHV with amino acid substitutions G156D, G238S or E240K is detected; or   l. recommending that the patient does not receive a beta-lactamase inhibitor-beta-lactam combination when ACC, MOX, CMY, CFE, ACT, DHA or FOX is detected.   
     
     
         14 . The method of  claim 12 , wherein the biological sample is an anal swab, a rectal swab, a skin swab, nasal swab, wound swab, stool, blood, plasma, serum, urine, sputum, respiratory lavage, cerebrospinal fluid, bacteria culture, bacteria isolate, fungal culture, fungal isolate, virus culture or virus isolate. 
     
     
         15 . A method of identifying the emergence of a multi-drug resistant organism in a population of subjects comprising
 a. identifying one or more antibiotic resistant genes selected from KPC, NDM, OXA, VIM, IMP, CTX-M and VanA in a plurality of subject samples wherein identification of an antibiotic resistant genes in the plurality of subject samples indicates the emergence of a multi-drug resistant organism in a population.   
     
     
         16 . The method of  claim 15 , further comprising identifying one or more of IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE. 
     
     
         17 . A method of screening a patient for multi-drug resistant bacterial colonization or infection comprising:
 a. isolating a nucleic acid sample from a biological sample obtained from the patient such that the sample is substantially free of protein, cellular debris and or PCR inhibitors   b. identifying one or more antibiotic resistant genes selected from KPC, NDM, OXA, VIM, IMP, CTX-M and VanA in said sample   wherein identification of an antibiotic resistant genes indicates the subject is colonized or infected with a multi-drug resistant bacterial organism.   
     
     
         18 . The method of  claim 17 , further comprising identifying one or more of IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE. 
     
     
         19 . The method of  claim 17 , wherein further comprising
 a. recommending that the patient does not receive a carbapenem antibiotic when KPC, NDM, OXA, VIM, or IMP is detected;   b. recommending that the patient does not receive a beta-lactam antibiotic when CTM-X is detected; or   c. recommending that the patient does not receive vancomycin when VanA is detected.   
     
     
         20 . The method of  claim 18 , wherein the antibiotic resistant genes of step (b) further comprise one or more of IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE wherein
 m. recommending that the patient does not receive a carbapenem antibiotic when SME, SFC, IMI, NMC, or CcrA is detected   n. recommending that the patient does not receive a cephalosporin antibiotic when PER, VEB, GES, BES, SFO, TLA, TEM with amino acid substitutions E104K, R164H, R164S, R164C, G238S or E240K, SHV with amino acid substitutions G156D, G238S or E240K is detected; or   o. recommending that the patient does not receive a beta-lactamase inhibitor-beta-lactam combination when ACC, MOX, CMY, CFE, ACT, DHA or FOX is detected.   
     
     
         21 . A kit for determining whether a patient is colonized or infected with a multi-drug resistant bacteria comprising:
 a. a biological sample collection means;   b. one or more primers that specifically hybridize with one or more antibiotic resistant genes selected from KPC, NDM, OXA, VIM, IMP, CTX-M and VanA;   c. a control sample; and   d. an instruction, wherein said instruction classifies said patient as being colonized or infected with a multi-drug resistant bacteria when one or more of the antibiotic resistant genes are identified in the sample.   
     
     
         22 . The kit of  claim 21 , further comprising one or more primers that specifically hybridize with one or more antibiotic resistant genes selected from IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE. 
     
     
         23 . A method for implementation by one or more data processors forming part of at least one computing system comprising:
 a. receiving, by at least one data processor, data characterizing test results of biological specimens for a patient or group of patients, wherein the test results characterize an outcome of a nucleic acid sample contacted with one or more primers that specifically hybridize with one or more antibiotic resistant genes selected from KPC, NDM, OXA, VIM, IMP, CTX-M and VanA; and   b. generating, using at least one data processor and the received data, a database of test results for the patient or group of patients.   
     
     
         24 . The method of  claim 23 , wherein the antibiotic resistant genes of step (a) further comprise one or more of IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE. 
     
     
         25 . The method of  claim 23 , wherein the database of test results further comprises an Electronic Health Record (EHR) or Laboratory Information Management System (LIMS). 
     
     
         26 . The method of  claim 23 , further comprising aggregating the database of test results with additional individual patient health data, patient group demographic data, healthcare institution demographic data, regional, national, or global geographic healthcare data. 
     
     
         27 . The method of  claim 23 , further comprising establishing, using the database of test results, colonization or infection rates and trends. 
     
     
         28 . The method of  claim 23 , further comprising monitoring, using the database of test results, Hospital Acquired Infection (HAI) and death rates, CRE infection or death rates, ESBL infection or death rates. 
     
     
         29 . The method of  claim 23 , further comprising establishing or augmenting, using the database of test results, treatment guidelines and policies, infection control procedures, or healthcare economic and risk management policies. 
     
     
         30 . The method of  claim 23 , further comprising computing, using the database of test results, baseline MDRO infection rates for a hospital and measuring the rate against a regional or national rate. 
     
     
         31 . The method of  claim 23 , further comprising augmenting treatment procedures, using the database of test results, to lower patient Length of Stay (LOS) in a healthcare institution, to lower overall costs, to lower patient death rates due to MDRO, to lower CMS penalties for HAIs, and to lower risk of legal settlements due to wrongful death claims. 
     
     
         32 . A surveillance method to establish source of the infection or colonization, comprising:
 a. extracting a nucleic acid sample from a sample collected from the environment;   b. amplifying the antibiotic resistant genes KPC, NDM, OXA, VIM, IMP, CTX-M and VanA by contacting the nucleic acid sample with one or more amplification primers that specifically hybridize with the each of the antibiotic resistant genes to provide an enriched nucleic acid sample;   c. detecting the presence of the antibiotic gene by contacting the nucleic acid sample with one or more detection primers that specifically hybridize with the each of the antibiotic resistant genes to in the enriched nucleic acid sample;   d. wherein the presence of the antibiotic gene in the sample indicates the source of the infection or colonization.   
     
     
         33 . The method of  claim 32 , wherein the antibiotic resistant genes of step (b) further comprise one or more of IMI, SME, GIM, SPM, NMC, SFC, SHV, TEM, BEL, VEB, GES, PER, SFO, BES, TLA, ACC, CMY, MIR, ACT, DHA, MOX, FOX, or CFE.