methicillin - resistant staphylococcus aureus ( mrsa ) has been an important nosocomial pathogen for a long time . since mid-1990s , mrsa was not only identified in the hospital settings but also from persons without risk factors predisposing for the acquisition of mrsa . the reports of ca - mrsa infections are increasing , and many studies indicate that ca - mrsa isolates have different clinical and molecular features from healthcare - associated mrsa ( ha - mrsa ) isolates . ca - mrsa infections occur more often in previously healthy young people , and mostly cause skin and soft tissue infections such as cellulitis and abscess . they possess smaller staphylococcal cassette chromosome ( scc)mec , predominately sccmec iv or v , compared to sccmec i , ii , or iii for ha - mrsa isolates . ca - mrsa isolates more commonly carry panton  valentine leukocidin ( pvl ) genes , and they are less resistant to non--lactam classes of antimicrobials . however , various mrsa clones have spread between community and hospitals , particularly ca - mrsa transmitted in hospital settings , making the distinctions between ca - mrsa and ha - mrsa blurred . so far , 5 major epidemic clones have been identified , namely multilocus sequence type 1 ( usa400 ) , st8 ( usa300 ) in north america , st80 in europe , st59 in asia - pacific area , and st30 worldwide . the prevalence of ca - mrsa varies markedly worldwide and was relatively high in taiwan . the dominant clone of ca - mrsa in taiwan was st59 or its variants ( namely , clonal complex [ cc ] 59 ) . however , most studies regarding ca - mrsa from taiwan were collected retrospectively , and limited in children . for few studies addressing ca - mrsa in adults all recruited the cases of blood stream infection only but not the full spectrum of clinical entities . hence , we conduct a study to address the epidemiology and molecular characteristics of ca - mrsa in adults in taiwan . this study was conducted in chang gung memorial hospital ( cgmh ) , which is a university - affiliated teaching hospital in northern taiwan and provides a range of care , from primary to tertiary care , with 3700 beds . the study was approved by the institutional review board of chang gung memorial hospital . between 1 march and 30 june , 2012 , all clinical mrsa isolates were collected prospectively from both inpatients and outpatients older than 18 years old . we evaluated the medical charts first and if needed , interviewed the patients or their caregivers for detailed medical history after a written consent was obtained . we then categorized the patients into ca - mrsa or ha - mrsa infections according to the definition proposed by naimi et al . briefly , mrsa identified after 48  hours of hospitalization or isolated from a lesion absent at admission was defined as hospital - onset ( ho ) ; conversely , community - onset ( co ) was defined as mrsa isolated within 48  hours or from a lesion present at admission . patients were classified as ha - mrsa infection if they had ho isolates , a permanent indwelling catheter or percutaneous medical device , history of hospitalization , surgery , and dialysis within previous 12 months , or lived in a long - term - care facility . specimens obtained for colonization surveillance and the patients without available medical records were excluded . from a single patient , only 1 isolate was selected for further characterization , usually the first isolate or the one from sterile sites . the demographics , clinical diagnosis , source of specimen , and antibiotic susceptibility were collected . hinton agar with disk - diffusion method following the protocol of clsi and included oxacillin , teicoplanin , penicillin , trimethoprim / sulfamethoxazole ( tmp / smx ) , erythromycin , clindamycin , linezolid , fusidic acid , daptomycin , and tigecycline . for the determination of vancomycin susceptibility , if the clinical isolates were identified from blood stream specimens , minimal inhibition concentration ( mic ) was determined for each isolate by e - test . otherwise , a screening agar containing vancomycin 3  g / ml was used first and then , if growth , e - test was performed to determine mics of the isolates . pulsed - field gel electrophoresis ( pfge ) with smai digestion was used to fingerprint the isolates according to the procedure described previously . pfge genotypes were designated in alphabetical order as in our previous studies , and those have less than 4-band differences from an existed genotype were defined as subtypes . polymerase chain reaction ( pcr ) assays for sccmec typing and pvl genes were performed according to the methods described previously . as our previous studies , some representative isolates from each pfge pattern were sent for multilocus sequence typing and spa typing . chi - square test and fisher exact test were used for categorical variable , and the independent t - test was used for continuous variables . during the 4 months , a total of 881 mrsa isolates from adults were identified from the bacterial laboratory of chang gung memorial hospital . after excluding isolates from colonization surveillance ( 10 isolates ) , from patients with unavailable medical charts ( 13 isolates ) or from patients refusing to participate in this study ( 1 isolate ) of the 857 isolates , 729 and 128 isolates were identified from the inpatients and the outpatients ( including those visiting emergency department ) , respectively . a total of 749 and 108 were classified as ha - mrsa and ca - mrsa , respectively . table 1 shows the distribution of specimens from which the 857 mrsa isolates were identified . compared to ha - mrsa , ca - mrsa isolates were significantly more frequently isolated from pus ( 78.7% vs 28.0% , p  <  0.001 ) , and less frequently found from sputum ( 4.6% vs 43.8% , p  <  0.001 ) and blood ( 3.7% vs 15.0% , p  =  0.002 ) . among 749 ha - mrsa isolates , a statistically significant difference was also found between co - mrsa and ho - mrsa isolates in terms of the sources from pus , blood , and sputum . furthermore , co - mrsa isolates were more significantly likely identified from the deep tissue specimen ( p  =  0.023 ) . distribution of 857 clinical methicillin - resistant staphylococcus aureus isolates , stratified by origin of specimens of the 555 patients included , 122 patients were outpatients and 433 were inpatients . a total of 202 patients ( 18.4% ) were identified as ca - mrsa infection . among these 433 hospitalized patients with mrsa infection , the mean age was 47 and 65 years for the patients with ca- and ha - mrsa infection , respectively ( p  <  0.001 ) . in ca- and ha - mrsa group , 57.8% and 62.7% of patients were male . of the 102 patients with ca - mrsa infection , 69 patients ( 67.6% ) presented with skin and soft tissue infection ( ssti ) . eight patients ( 7.8% ) presented with bone and joint infection , and 3 patients ( 2.9% ) presented with deep - seated soft - tissue infection , including necrotizing fasciitis for 2 cases and toe necrosis for 1 case . five patients ( 4.9% ) presented with pneumonia , including necrotizing pneumonia for 1 case . there were 6 patients with mrsa isolated from urine , but all of these were not considered as pathogens . two patients had bacteremia , 1 was secondary to wound infection and the other was due to prostatitis . the in - hospital case - fatality rate was 0% and 25.6% for ca- and ha - mrsa groups , respectively ( p  <  0.001 ) . nearly all the isolates were susceptible to vancomycin , teicoplanin , tigecycline , linezolid , and daptomycin . more than 80% of the isolates were resistant to erythromycin and clindamycin . however , ca - mrsa isolates were significantly more susceptible to erythromycin , clindamycin , fusidic acid , and tmp / smx ( p  <  0.05 for all ) than ha - mrsa isolates . comparing to ho - mrsa , co - mrsa isolates were significantly more susceptible to erythromycin , clindamycin , and tmp / smx ( p  <  0.05 ) . antibiotic susceptibility of 555 clinical methicillin - resistant staphylococcus aureus isolates from case patients , stratified according to the origin of acquisition further molecular analyses were performed for a total of 203 mrsa isolates , including 102 ca - mrsa and 101 ha - mrsa isolates ( table 3 ) . all of the 102 ca - mrsa isolates were included while 50 isolates from co - mrsa patients and 51 from ho - mrsa patients ( 1 per 4 and 1 per 5 consecutive isolates , respectively ) were selected for molecular characterization . twelve pfge patterns were identified for ca - mrsa and ha - mrsa isolates , respectively . pulsotype d and c were the most common patterns , accounting for 56.9% and 19.6% , respectively . six sccmec types were found with the predominant types of vt ( 57.8% ) and iv ( 33.3% ) . among the 101 ha - mrsa isolates , pulsotype f ( 22.8% ) , a ( 21.8% ) , and d ( 20.8% ) were the most common types . pvl genes were detected in fewer ha - mrsa isolates than ca - mrsa ones ( 19.8% vs 65.7% ) . a total of 23 ca - mrsa isolates and 21 ha - mrsa isolates were selected for mlst , and 10 and 8 sequence types were identified , respectively . a total of 56 isolates were selected for spa typing and 17 spa types were identified . molecular characteristics of 203 selective clinical methicillin - resistant staphylococcus aureus isolates from case patients , stratified by the origin of acquisition and pulsed - field gel electrophoresis patterns table 4 shows the comparison of 4 major clones identified among the ca- and ha - mrsa isolates . st59/pfge type d / sccmec vt / pvl(+)/t437 was significantly more commonly seen in ca - mrsa isolates ( 53.9% ) than in ha - mrsa isolates ( 18.8% ) ; st5/pfge type f / sccmec ii /pvl()/t002 ( 21.8% ) and st239/pfge type a / sccmec iii / pvl()/t037 ( 17.8% ) were significantly more detected in ha - mrsa isolates than in ca - mrsa isolates ( 2.9% and 1.0% , respectively ) ( all p  <  0.001 ) . likewise , st239/pfge type a was significantly more commonly seen in ho - mrsa isolates ( 27.5% ) than in co - mrsa isolates ( 8.0% ) ( p  =  0.022 ) . comparison of major clones from community - associated and healthcare - associated methicillin - resistant staphylococcus aureus isolates to our knowledge , this is the first study regarding molecularly characterizing all clinical mrsa isolates collected from any specimen sites in adult patients in taiwan . the results showed a significant difference between ca- and ha - mrsa isolates as well as between co- and ho - mrsa isolates in terms of the source of specimens , antibiotic susceptibility patterns , and molecular characteristics , a scenario similar to that seen in children in taiwan . clinically , the patients with ca - mrsa infection were younger and had better outcomes than those with ha - mrsa infection . these again suggest that ca - mrsa was a distinct pathogen from ha - mrsa in taiwan . in the present study , ca - mrsa isolates accounted for 12.6% of all mrsa isolates , 18.4% of patients with mrsa infection were classified as ca - mrsa infection , and only 10% of mrsa isolates from inpatients were categorized as ca isolates . the prevalence of ca - mrsa among adult mrsa - infected patients in taiwan may be underestimated , particularly inpatients , because this is a hospital - based study and performed in a tertiary hospital . similar to our previous study in children with same design , the most common source of specimens for ca - mrsa isolates in the present study was pus . however , the percentage of ssti ( 70% ) in adults was lower than that in children ( 92% ) , the ratio of bone and joint infection was higher in adults than in children ( 7.8% vs 1.9% , respectively ) . in 2000s in taiwanese children , ssti accounted for 72% to 86% of ca - mrsa infections and bone and joint infection accounted for 2% to 12% . in usa , 87% to 95.6% of ca - mrsa infections presented as sstis , and bone and joint infections accounted for up to 3% only . in addition , 12.7% of patients with ca - mrsa infections in the present study had invasive diseases , including osteomyelitis , necrotizing fasciitis , and necrotizing pneumonia , a rate higher than that reported from us ( 6% ) . however , none of the cases in the present study died . in contrast , ha - mrsa isolates were more commonly found in respiratory tract infection and bacteremia than ca - mrsa isolates , and thus contributed to a higher mortality , as shown in the present study . as known , there was significant difference in antibiotic susceptibility between ca- and ha - mrsa isolates . unlike a high susceptibility rate to erythromycin and clindamyin for ca - mrsa isolates from the usa , the susceptibility rate was only 17.7% for ca isolates in this study . similar to previous reports from taiwan , the largest susceptibility difference between ca- and ha - mrsa isolates was noted for tmp / smx , to which 93% of ca isolates were susceptible , significantly higher than ha - mrsa isolates ( 66% ) . this scenario was also seen between co- and ho - mrsa isolates in this study . however , the evidence of tmp / smx to treat invasive or severe mrsa infections was still inadequate . the molecular characteristics of ca - mrsa isolates from adults in this study were similar to those from taiwanese children . st59/pulsotype d / sccmec vt / pvl(+)/t437 , named as taiwan clone , was the most common clone and accounted for more than half of the clinical ca - mrsa isolates from adult patients , as in pediatric patients . nearly 20% of the isolates were st59/pulsotype c / sccmec iv / pvl( ) , which was also a major community clone in taiwan but more frequently identified from colonized subjects in taiwan . the clone of st30/sccmec iv / pvl(+)/t019 , named as southwest pacific clone and rarely reported from taiwan previously , accounted for 7 ( 6.9% ) ca - mrsa isolates and deserved further observation . interestingly , 1 st9/t899 isolate , a livestock - associated mrsa in taiwan , was found in pus from a pig farmer hospitalized for skin and soft - tissue infection and subsequent osteomyelitis . for molecular characteristic of ha - mrsa isolates in the present study , there were 3 major clones identified , namely cc 59 ( 32.7% ) , cc239 ( 29.7% ) , and cc5 ( 24.8% ) , which were consistent with an islandwide study in 2010 . st239/pulsotype a / sccmec iii ( hungarian or brazilian clone ) , the previously most epidemic ha clone in taiwan , decreased year by year since 2000 ( from 73% in 2000 to 26% in 2010 ) , and accounted for less than 20% in the current study . its dominance was lost by the clone of st5 and the community clone of st59 , both of which emerged in late 1990s , increased gradually and were among the major clones of bloodstream isolates up to 2010 . in our previous study in children , st 59 also accounted for 30.7% of ha - mrsa isolates and 40% of co - mrsa . all of these findings indicated that the community clone had spread into hospital settings in taiwan . first , the clinical cases as well as the clinical isolates of mrsa were not collected all year round but for only 4 months , which limited the full epidemiologic features , since the case number was too huge to be handled . second , not every ha - mrsa isolate , but selected isolates , were molecularly characterized . third , clinical outcomes were not evaluated and correlated with ha- or ca - mrsa infections as well as genotypes of mrsa infections . in conclusion , the characteristics of ca- and ha - mrsa isolates from taiwanese adults were significantly different in terms of clinical disease spectrum , antibiotic susceptibility , and molecular characteristics . the major ca - mrsa clones were cc59/t437 and included st59/pulsotype d / sccmec vt / pvl(+ ) and st59/pulsotype c / sccmec iv / pvl( ) . further longitudinal molecular surveillance for mrsa and population - based studies are needed to provide more clinical information .
abstractmethicillin - resistant staphylococcus aureus ( mrsa ) is an important nosocomial pathogen in hospitals , and increases rapidly in the community , named as community - associated mrsa ( ca - mrsa ) . 
 we conducted a prospective / retrospective study to understand the epidemiology , antimicrobial susceptibility , and molecular characteristics of mrsa infections in adult patients in taiwan.from march to june , 2012 , all clinical mrsa isolates were prospectively collected from adult patients in a tertiary hospital in northern taiwan . 
 selective isolates were further characterized . 
 we reviewed the detailed medical record of each case retrospectively.a total of 857 clinical isolates were collected from 555 patients . 
 a total of 749 isolates from 453 patients were classified as healthcare - associated ( ha)-mrsa and 108 isolates from 102 patients as ca - mrsa by the epidemiologic criteria . compared to ha - mrsa , 
 ca - mrsa isolates were significantly more frequently identified from pus ( 78% vs 28% , p  <  0.001 ) and less frequently from sputum ( 4.6% vs 43.8% , p  <  0.001 ) and blood ( 3.7% vs 15% , p  =  0.002 ) . 
 ca - mrsa isolates were more susceptible to all antibiotics tested . 
 a total of 102 ca - mrsa and 101 ha - mrsa isolates were characterized , showing significantly different molecular characteristics between ca and ha isolates ( p  <  0.001 ) . 
 the clone of sequence type ( st ) 59/t437 complex , with 2 pulsotypes , accounted for 70% of ca isolates . 
 three major clones were identified from ha - mrsa isolates , namely clonal complex ( cc ) 59 ( 32.7% ) , cc239 ( 29.7% ) , and cc5 ( 24.8% ) . among ha isolates , a significant difference was also seen between community - onset and hospital - onset mrsa isolates in terms of the source of specimens , antibiotic susceptibility patterns , and molecular characteristics.ca-mrsa isolates from adults in northern taiwan were genetically significantly different from ha isolates . 
 the community clones , cc59 , spread into hospitals .