a 63-year - old man with diabetes and end - stage kidney failure had been receiving maintenance hemodialysis in the outpatient clinic at odense university hospital in odense , denmark , since 1997 . a femoral  femoral bridge graft was used for vascular access . in november 2013 , he was admitted to the hospital because of a fever he experienced during dialysis and inflammation around his bridge graft . the organism was also cultured from the patient s bridge graft and from a sample of joint fluid from his right shoulder . a transesophageal echocardiography revealed mitral valve endocarditis . despite relevant treatment with vancomycin and rifampin and surgical debridement of his shoulder joint on inquiry by the staff , the patient had reported no previous history of mrsa infection or colonization and no direct or household - related contact with pigs . four months before patient 1 s illness , mrsa cc398 spa type t011 had been cultivated from an infected decubitus ulcer of another patient who was receiving hemodialysis in the same outpatient clinic as patient 1 . subsequent mrsa screening revealed that patient 2 was a nasal and pharyngeal carrier . on inquiry by the staff , the patient reported no direct or household - related contact with pigs . a 74-year - old nursing home resident had hemiparesis and recurrent aspiration pneumonia after an apoplectic insult . in april 2014 , he was admitted to the hospital with severe pneumonia . on admission blood cultures grew mrsa cc398 spa type t034 , and the organism was found in a tracheal aspirate and from the area around a percutaneous gastrostoma tube . despite relevant treatment with piperacillin / tazobactam , metronidazole , and vancomycin , the patient died from respiratory failure after 1 week . on inquiry by the staff , the patient and his attending daughter reported no direct or household - related contact with pigs . in july 2010 , mrsa cc398 spa type t034 had been isolated from a bedsore of another patient living in the same nursing home as patient 3 . in november 2013 , the organism was isolated once more from the patient , this time from an indwelling urine catheter . patients 3 and 4 lived in the same wing of the nursing home and shared common facilities . after hospital staff recognized the transmission chain , all residents in this wing and all attached staff were screened for mrsa , but none tested positive . the mrsa cc398 isolates identified in the 2 transmission chains were spa types t011 and t034 , which are common among livestock - associated mrsa strains ( 12 ) . draft whole - genome sequencing was performed on 7 isolates from the 4 patients in the 2 transmission chains , and results were compared with similar data for cc398-related mrsa and methicillin - sensitive s. aureus isolates from denmark obtained during a previous study of the global dissemination of isolates belonging to this clonal complex ( 13 ) . sequence files for the individual isolates from patients are available at the european nucleotide archive ( http://www.ebi.ac.uk/ena ; accession no . a phylogenetic tree was constructed from single - nucleotide polymorphism differences in genome sequences of isolates from the 4 patients and from the isolates obtained during the previous study by using the s0385 complete genome sequence ( genbank accession no . am990992.1 ) as reference ( figure ) . this analysis showed that the patient isolates within each transmission chain were closely related but that no close relation between the 2 chains existed . in addition , the isolates from both chains clustered among isolates previously found to be animal associated ( clade iia ; 13 ) . consistent with an animal origin , all isolates carried the tet(m ) and czrc determinants ( similar to most mrsa strains from clade iia ) and lacked the sa3 phage ( typical of the human clade i ) ( 13 ) . phylogeny of methicillin - resistant staphylococcus aureus ( mrsa ) clonal complex ( cc ) 398 isolates linked to fatal septicemia in a hospital patient and a nursing home resident in denmark . draft whole - genome sequencing was performed on 7 isolates from the 4 patients identified in the 2 transmission chains , and results were compared with similar genomic data for cc398-related mrsa and methicillin - sensitive s. aureus isolates obtained in denmark during a previous study of isolates belonging to cc398 ( 13 ) . single - nucleotide polymorphism differences were identified , and a maximum - likelihood phylogeny was inferred from raw data by using the web tool csi phylogeny ( https://cge.cbs.dtu.dk//services/csiphylogeny ) . the region of bp 12252135180 was excluded from analysis because it contains the spa region and disrupts the phylogenic signal ( 13 ) . p , pig ; h , human ; met , methicillin susceptibility ; r , resistant ; s , susceptible . a 63-year - old man with diabetes and end - stage kidney failure had been receiving maintenance hemodialysis in the outpatient clinic at odense university hospital in odense , denmark , since 1997 . a femoral  femoral bridge graft was used for vascular access . in november 2013 , he was admitted to the hospital because of a fever he experienced during dialysis and inflammation around his bridge graft . the organism was also cultured from the patient s bridge graft and from a sample of joint fluid from his right shoulder . a transesophageal echocardiography revealed mitral valve endocarditis . despite relevant treatment with vancomycin and rifampin and surgical debridement of his shoulder joint on inquiry by the staff , the patient had reported no previous history of mrsa infection or colonization and no direct or household - related contact with pigs . four months before patient 1 s illness , mrsa cc398 spa type t011 had been cultivated from an infected decubitus ulcer of another patient who was receiving hemodialysis in the same outpatient clinic as patient 1 . subsequent mrsa screening revealed that patient 2 was a nasal and pharyngeal carrier . on inquiry by the staff , the patient reported no direct or household - related contact with pigs . a 63-year - old man with diabetes and end - stage kidney failure had been receiving maintenance hemodialysis in the outpatient clinic at odense university hospital in odense , denmark , since 1997 . a femoral  femoral bridge graft was used for vascular access . in november 2013 , he was admitted to the hospital because of a fever he experienced during dialysis and inflammation around his bridge graft . the organism was also cultured from the patient s bridge graft and from a sample of joint fluid from his right shoulder . a transesophageal echocardiography revealed mitral valve endocarditis . despite relevant treatment with vancomycin and rifampin and surgical debridement of his shoulder joint on inquiry by the staff , the patient had reported no previous history of mrsa infection or colonization and no direct or household - related contact with pigs . four months before patient 1 s illness , mrsa cc398 spa type t011 had been cultivated from an infected decubitus ulcer of another patient who was receiving hemodialysis in the same outpatient clinic as patient 1 . subsequent mrsa screening revealed that patient 2 was a nasal and pharyngeal carrier . on inquiry by the staff , the patient reported no direct or household - related contact with pigs . a 74-year - old nursing home resident had hemiparesis and recurrent aspiration pneumonia after an apoplectic insult . in april 2014 , he was admitted to the hospital with severe pneumonia . on admission , he had sepsis . blood cultures grew mrsa cc398 spa type t034 , and the organism was found in a tracheal aspirate and from the area around a percutaneous gastrostoma tube . despite relevant treatment with piperacillin / tazobactam , metronidazole , and vancomycin , the patient died from respiratory failure after 1 week . on inquiry by the staff , the patient and his attending daughter reported no direct or household - related contact with pigs . in july 2010 , mrsa cc398 spa type t034 had been isolated from a bedsore of another patient living in the same nursing home as patient 3 . in november 2013 , the organism was isolated once more from the patient , this time from an indwelling urine catheter . patients 3 and 4 lived in the same wing of the nursing home and shared common facilities . after hospital staff recognized the transmission chain , all residents in this wing and all attached staff were screened for mrsa , but none tested positive . the mrsa cc398 isolates identified in the 2 transmission chains were spa types t011 and t034 , which are common among livestock - associated mrsa strains ( 12 ) . draft whole - genome sequencing was performed on 7 isolates from the 4 patients in the 2 transmission chains , and results were compared with similar data for cc398-related mrsa and methicillin - sensitive s. aureus isolates from denmark obtained during a previous study of the global dissemination of isolates belonging to this clonal complex ( 13 ) . sequence files for the individual isolates from patients are available at the european nucleotide archive ( http://www.ebi.ac.uk/ena ; accession no . a phylogenetic tree was constructed from single - nucleotide polymorphism differences in genome sequences of isolates from the 4 patients and from the isolates obtained during the previous study by using the s0385 complete genome sequence ( genbank accession no . this analysis showed that the patient isolates within each transmission chain were closely related but that no close relation between the 2 chains existed . in addition , the isolates from both chains clustered among isolates previously found to be animal associated ( clade iia ; 13 ) . consistent with an animal origin , all isolates carried the tet(m ) and czrc determinants ( similar to most mrsa strains from clade iia ) and lacked the sa3 phage ( typical of the human clade i ) ( 13 ) . phylogeny of methicillin - resistant staphylococcus aureus ( mrsa ) clonal complex ( cc ) 398 isolates linked to fatal septicemia in a hospital patient and a nursing home resident in denmark . draft whole - genome sequencing was performed on 7 isolates from the 4 patients identified in the 2 transmission chains , and results were compared with similar genomic data for cc398-related mrsa and methicillin - sensitive s. aureus isolates obtained in denmark during a previous study of isolates belonging to cc398 ( 13 ) . single - nucleotide polymorphism differences were identified , and a maximum - likelihood phylogeny was inferred from raw data by using the web tool csi phylogeny ( https://cge.cbs.dtu.dk//services/csiphylogeny ) . the region of bp 12252135180 was excluded from analysis because it contains the spa region and disrupts the phylogenic signal ( 13 ) . p , pig ; h , human ; met , methicillin susceptibility ; r , resistant ; s , susceptible . a 74-year - old nursing home resident had hemiparesis and recurrent aspiration pneumonia after an apoplectic insult . in april 2014 , he was admitted to the hospital with severe pneumonia . on admission , he had sepsis . blood cultures grew mrsa cc398 spa type t034 , and the organism was found in a tracheal aspirate and from the area around a percutaneous gastrostoma tube . despite relevant treatment with piperacillin / tazobactam , metronidazole , and vancomycin , the patient died from respiratory failure after 1 week . on inquiry by the staff , the patient and his attending daughter reported no direct or household - related contact with pigs . in july 2010 , mrsa cc398 spa type t034 had been isolated from a bedsore of another patient living in the same nursing home as patient 3 . in november 2013 , the organism was isolated once more from the patient , this time from an indwelling urine catheter . patients 3 and 4 lived in the same wing of the nursing home and shared common facilities . after hospital staff recognized the transmission chain , all residents in this wing and all attached staff were screened for mrsa , but none tested positive . the mrsa cc398 isolates identified in the 2 transmission chains were spa types t011 and t034 , which are common among livestock - associated mrsa strains ( 12 ) . draft whole - genome sequencing was performed on 7 isolates from the 4 patients in the 2 transmission chains , and results were compared with similar data for cc398-related mrsa and methicillin - sensitive s. aureus isolates from denmark obtained during a previous study of the global dissemination of isolates belonging to this clonal complex ( 13 ) . sequence files for the individual isolates from patients are available at the european nucleotide archive ( http://www.ebi.ac.uk/ena ; accession no . a phylogenetic tree was constructed from single - nucleotide polymorphism differences in genome sequences of isolates from the 4 patients and from the isolates obtained during the previous study by using the s0385 complete genome sequence ( genbank accession no . this analysis showed that the patient isolates within each transmission chain were closely related but that no close relation between the 2 chains existed . in addition , the isolates from both chains clustered among isolates previously found to be animal associated ( clade iia ; 13 ) . consistent with an animal origin , all isolates carried the tet(m ) and czrc determinants ( similar to most mrsa strains from clade iia ) and lacked the sa3 phage ( typical of the human clade i ) ( 13 ) . phylogeny of methicillin - resistant staphylococcus aureus ( mrsa ) clonal complex ( cc ) 398 isolates linked to fatal septicemia in a hospital patient and a nursing home resident in denmark . draft whole - genome sequencing was performed on 7 isolates from the 4 patients identified in the 2 transmission chains , and results were compared with similar genomic data for cc398-related mrsa and methicillin - sensitive s. aureus isolates obtained in denmark during a previous study of isolates belonging to cc398 ( 13 ) . single - nucleotide polymorphism differences were identified , and a maximum - likelihood phylogeny was inferred from raw data by using the web tool csi phylogeny ( https://cge.cbs.dtu.dk//services/csiphylogeny ) . the region of bp 12252135180 was excluded from analysis because it contains the spa region and disrupts the phylogenic signal ( 13 ) . p , pig ; h , human ; met , methicillin susceptibility ; r , resistant ; s , susceptible . we report 2 fatal mrsa cc398 infections after human - to - human transmission in institutional settings . both patients had debilitating underlying diseases but were in a stable condition until the time of their infections . the sequence of events leaves no doubt that septicemia attributable to mrsa cc398 was the cause of death in both cases . the cc and spa types of the isolates causing fatal infections were typical for mrsa isolates from pigs . phylogenetic analyses of whole - genome sequences indicated that the human isolates from the 2 transmission chains were located in different clusters that intermingled with isolates from pigs . the different spa types and the clustering of the mrsa isolates from the 2 chains clearly indicate 2 separate chains of infection . however , epidemiologic investigations and typing analyses strongly suggested that the 2 mrsa - infected patients could have acquired their infections from an asymptomatic carrier in the outpatient hemodialysis unit ( transmission chain 1 , patient 2 ) and the nursing home ( transmission chain 2 , patient 4 ) . transmission of mrsa cc398 in hospitals and institutions has been reported elsewhere , which underscores its potential to spread through person - to - person contact ( 911 ) . in conclusion , the organism implicated in these 2 fatal cases was by all accounts spread from person to person . these findings suggest that this clonal complex can be of high pathogenicity and is readily transmissible among humans .
we describe 2 fatal cases of methicillin - resistant staphylococcus aureus ( mrsa ) clonal complex 398 septicemia in persons who had no contact with livestock . 
 whole - genome sequencing of the isolated mrsa strains strongly suggest that both were of animal origin and that the patients had been infected through 2 independent person - to - person transmission chains .