Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients.

BACKGROUND: Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients. METHODS: A total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined. RESULTS: Genotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14-4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029). CONCLUSION: This study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea.

Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function.

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

Human granulocytic anaplasmosis combined with rhabdomyolysis: a case report.

BACKGROUND: Human granulocytic anaplasmosis (HGA) is a systemic inflammatory response caused by the rickettsial bacterium Anaplasma phagocytophilum. Rhabdomyolysis and acute kidney injury (AKI) are rare complications of HGA. Here, we report a case of HGA concurrent with rhabdomyolysis and AKI in an elderly patient. CASE PRESENTATION: An 84-year old woman with a medical history of hypertension was hospitalised after two days of fever, dizziness, whole body pain, and general weakness. Laboratory investigations showed severe thrombocytopenia, leukopenia, impaired renal function, and elevated cardiac enzyme and myoglobin levels. On the day after admission, peripheral blood smear revealed morula inclusions in neutrophils, a suggestive finding of HGA. Real-time polymerase chain reaction (PCR) results indicated the presence of A. phagocytophilum. Antibiotics were de-escalated to doxycycline monotherapy. After 10 days of antibiotic treatment, laboratory tests showed complete recovery from HGA complicated with rhabdomyolysis and AKI. CONCLUSIONS: HGA can lead to serious complications in patients with associated risk factors. Therefore, in patients with HGA accompanied by rhabdomyolysis, management with antibiotics and hydration should be initiated immediately, and not delayed until diagnostic confirmation.

Dual respiratory virus detection in adult patients with acute respiratory illness.

BACKGROUND: Nonrandom multiple respiratory virus (RV) detection provides evidence for viral interference among respiratory viruses. However, little is known as to whether it occurs randomly. METHODS: The prevalence of dual RV detection (DRVD) in patients with acute respiratory illnesses (ARIs) at 4 academic medical centers was investigated; data about the prevalence of 8 RVs were collected from the Korean national RV surveillance dataset. Linear regression analysis was performed to assess the correlation between observed and estimated prevalence of each type of DRVD. RESULTS: In total, 108 patients with ARIs showing DRVD were included in this study between 2011 and 2017. In several types of regression analysis, a strong correlation was observed between the observed and estimated prevalence of each type of DRVD. Excluding three DRVD types (influenza/picornavirus, influenza/human metapneumovirus, and adenovirus/respiratory syncytial virus), the slope of the regression line was higher than that of the line of random occurrence (1.231 > 1.000) and the 95% confidence interval of the regression line was located above the line of random occurrence. CONCLUSIONS: Contrary to the results of previous epidemiologic studies, most types of DRVD occur more frequently than expected from the prevalence rates of individual RV, except for three underrepresented pairs above.

Increasing Malaria Parasite Clearance Time after Chloroquine Therapy, South Korea, 2000-2016.

We reviewed the clinical efficacy of chloroquine for Plasmodium vivax malaria, the changing trend of parasite clearance time, and fever clearance time during 2000-2016 in South Korea. Median parasite clearance time and fever clearance time increased significantly over the study period. Chloroquine was mostly underdosed when used to treat P. vivax malaria.

A Nationwide Survey on the Hospital Vaccination Policies in Korea.

BACKGROUND: Healthcare personnel (HCP) are at risk of being exposed to or transmitting infections in hospitals, and vaccination against vaccine-preventable diseases (VPDs) is a well-known preventive strategy. Vaccination against influenza, hepatitis B virus, measles-mumps-rubella, varicella, and pertussis is recommended for HCP. However, there is no information on the current status of hospitals' vaccination policies for HCP in Korea. METHODS: We conducted a nationwide survey on hospital vaccination policies and barriers to implementing recommended vaccination programs in 2018. The online survey questionnaire was distributed to 652 hospitals, and 200 of them responded. RESULTS: Of the 200 surveyed hospitals, 151 (75.5%) conducted a pre-employment screening program for at least one VPD, and 196 (98%) had vaccination programs that included at least one vaccine. Influenza vaccine was most commonly included in their programs (97.5%, n = 195), followed by hepatitis B vaccines (69%, n = 138). However, < 25% of the hospitals included other vaccines in their policies (measles-mumps-rubella, 24.5%; varicella, 18.5%; pertussis, 11%). Only 13 hospitals (6.5%) included the five recommended vaccines for HCP in their policies. Influenza vaccination coverage had a mean of 89.9% and was significantly higher in hospitals fully funding the vaccination cost (91.8% vs. 80.4%, P < 0.001). Among hospitals funding influenza vaccines, the coverage was lower in hospitals with ≥ 700 beds (-6.5%, P = 0.003). Hospitals' financial burden was the most important barrier to implementing vaccination polices as recommended (78.6%, 121/154), followed by lack of awareness (21%) or campaign (21%) and lack of leadership (17%). CONCLUSION: Despite the recommendations on vaccination for HCP, the vaccination policies for HCP differ in hospitals and appear to be insufficient to protect HCP and prevent nosocomial transmission. Strong leadership of each hospital to protect HCP and financial support from the government are required to implement appropriate vaccination policies in hospitals.

A Prospective Cohort Study of Durations of Staphylococcus aureus Bacteremia According to Different Phenotypes and a New Concept of Persistent Bacteremia.

The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n = 995) than in patients with methicillin-susceptible SAB (MSSAB; n = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P < 0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P < 0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality.

Impact of health care-associated community-onset cellulitis in Korea: a multicenter study.

We conducted a multicenter study to determine the clinical and microbiological characteristics of health care-associated (HCA) cellulitis in Korea. We retrospectively reviewed the medical records of patients who had been diagnosed with community-onset cellulitis. Of the 2208 cellulitis patients, 232 (10.5%) had HCA cellulitis, 1243 (56.3%) patients were hospitalized, and 15 (0.7%) died in hospital. Compared with community-acquired (CA) cellulitis, patients with HCA cellulitis were older and more frequently presented with comorbidity and septic shock. A total of 355 microorganisms were isolated from 314 patients (14.2%). Staphylococcus aureus (134 isolates) was the most common organism, followed by Streptococcus spp. (86 isolates) and Gram-negative fermenters (58 isolates). Methicillin-resistant S. aureus (MRSA) accounted for 29.1% (39/134) of S. aureus infections. None of the Gram-negative fermenters were resistant to carbapenem. The antibiotic susceptibility pattern of isolated microorganisms was not different between HCA and CA cellulitis. In patients with HCA cellulitis, S. aureus (11.2% [26/232] vs. 5.5% [108/1976], p = 0.001), including MRSA (4.3% [10/232] vs. 1.5% [29/1976], p = 0.003) and Gram-negative fermenters (6.0% [14/232] vs. 2.3% [44/1976], p = 0.002), were more common causative organisms than in CA-cellulitis patients. Age ≥ 65 years, septic shock, and HCA infection were statistically significant factors associated with in-hospital mortality.

Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics.

Scarce information concerning the inoculum effect (InE) of methicillin-susceptible Staphylococcus aureus (MSSA) against broad-spectrum ß-lactam antibiotics is available. We investigated the InE of MSSA against ceftriaxone, cefepime, meropenem, ampicillin/sulbactam and piperacillin/tazobactam. The bacteraemic MSSA isolates were collected at ten Korean general hospitals from Sep 2013 to Mar 2015. The InE was defined if MICs of antibiotics at high inoculum (HI, ~5 × 107 CFU/ml) increased beyond the susceptible range compared to those at standard inoculum (SI, ~5 × 105 CFU/ml). All isolates were sequenced for blaZ gene typing. Among 302 MSSA isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively. Mean HI MICs of all tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs. SI, 2.04 ± 0.08 mg/L, p < 0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p < 0.001) were most prominent. No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively. About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p < 0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p < 0.001). A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.

Severe fever with thrombocytopenia syndrome: comparison with scrub typhus and clinical diagnostic prediction.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is emerging in Asian 3 countries, China, Japan and Korea, which are scrub typhus endemic areas, and its incidence is increasing. As the two infections overlap epidemiologically and clinically and the accessibility or sensitivity of diagnostic tests is limited, early clinical prediction may be useful for diagnostic and therapeutic purposes. METHODS: Patients aged ≥16 years who were clinically suspected and laboratory-confirmed to be infected with Orientia tsutsugamushi or the SFTS virus in South Korea were enrolled. Clinical and laboratory parameters were compared. Scrub typhus was further subclassified according to the status of eschar and skin rash. An SFTS prediction scoring tool was generated based on a logistic regression analysis of SFTS compared with scrub typhus. RESULTS: The analysis was performed on 255 patients with scrub typhus and 107 patients with SFTS. At initial presentation, subjective symptoms except for gastrointestinal symptoms, were more prominent in scrub typhus patients. In addition to the characteristic eschar and skin rash, headache was significantly more prominent in scrub typhus, while laboratory abnormalities were more prominent in SFTS. Leukopenia (white blood cell count < 4000/mm3; odds ratio [OR] 30.13), thrombocytopenia (platelet count < 80,000 /mm3; OR 19.73) and low C-reactive protein (< 1 mg/dL; OR 67.46) were consistent risk factors for SFTS (all P < 0.001). A prediction score was generated using these 3 variables, and a score ≥ 2 had a sensitivity of 93.1% (95% confidence interval [CI], 87.9-96.4%) and a specificity of 96.1% (95% CI, 93.8-97.6%) for SFTS. CONCLUSION: This prediction scoring tool may be useful for differentiating SFTS from eschar- or skin rash-negative scrub typhus. It is a simple and readily applicable tool with potential for use in primary care settings.

Co-Infection of Scrub Typhus and Human Granulocytic Anaplasmosis in Korea, 2006.

BACKGROUND: Scrub typhus, severe fever with thrombocytopenia syndrome (SFTS) and human granulocytic anaplasmosis (HGA) are important arthropod-borne infectious diseases in Korea and share a common point that they are transmitted by arthropod bites mostly during outdoor activities and there are considerable overlaps of epidemiologic and clinical features at presentation. We investigated the co-infection of these infections. METHODS: The study subjects were patients with laboratory-confirmed scrub typhus who were enrolled retrospectively in 2006. SFTS virus (SFTSV) infection was confirmed by a reverse transcriptase polymerase chain reaction (PCR) to amplify partial L segment of SFTSV for molecular diagnosis. HGA was confirmed by a nested PCR to amplify 16S rRNA gene of Anaplasma phagocytophilum. Direct sequencing of the positive PCR products was performed. Clinical features of co-infected subjects were described. RESULTS: One-hundred sixty-seven patients with scrub typhus were included in the analysis. Co-infection of A. phagocytophilum was identified in 4.2% of scrub typhus patients (7/167). The route of co-infection was uncertain. The co-infected patients had not different clinical manifestations compared to the patients with scrub typhus only. All the study subjects were negative for SFTSV. CONCLUSION: We found retrospective molecular evidence of the co-infection of scrub typhus and HGA in Korea. HGA may be more prevalent than expected and need to be considered as an important differential diagnosis of febrile patients in Korea.

Gender affects prognosis of methicillin-resistant Staphylococcus aureus bacteremia differently depending on the severity of underlying disease.

We aimed to elucidate the potential impact of gender on prognosis of Staphylococcus aureus bacteremia (SAB). We analyzed SAB cases prospectively collected over an 8-year period at 11 hospitals in Korea. SAB-related mortality was pre-defined as a death within 30 days from the onset of SAB without other apparent cause of death. The effect of gender on SAB-related mortality was examined in the entire cohort and in subgroups stratified according to methicillin resistance and Charlson's comorbidity-weighted index (CCWI) score. Those factors independently associated to SAB-related mortality were explored. Among 1974 eligible cases, SAB-related mortality rates in male and female were 21.2% (259/1224) and 21.9% (164/750), respectively (P = 0.786). The SAB-related mortality rate was independently higher in male than that in female in CCWI score ≤ 3 methicillin-resistant SAB (MRSAB) group (15.9 vs. 6.2%; aOR 3.65, 95% CI 1.46-9.13; P = 0.006) while the association tended to be inverse when CCWI score rises. Interaction between CCWI score and gender to MRSAB-related mortality was significant in multivariate analysis (aOR 0.85, 95% CI 0.74-0.96; P = 0.011). There was no significant interaction between gender and CCWI in entire SAB or methicillin-susceptible SAB cohorts. Gender may affect clinical outcomes of MRSAB differently depending on the severity of underlying disease.

Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections.

There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) infections, defined as the isolation of S. aureus from a normally sterile site. Over a 2-year period, 1,027 adult patients with ISA infections were enrolled in 10 hospitals, including 673 (66%) patients with methicillin-resistant S. aureus (MRSA) infections. There were 200 (19.5%) isolates with high VAN-MIC (≥1.5 mg/liter) by Etest and 87 (8.5%) by broth microdilution (BMD). The all-cause 30-day mortality rate was 27.4%. High VAN-MIC by either method was not associated with all-cause 30-day mortality, and this finding was consistent across MIC methodologies and methicillin susceptibilities. We conclude that high VAN-MIC is not associated with increased risk of all-cause 30-day mortality in ISA infections. Our data support the view that VAN-MIC alone is not sufficient evidence to change current clinical practice.

Health care-associated acute pyelonephritis is associated with inappropriate empiric antibiotic therapy in the ED.

BACKGROUND: Acute pyelonephritis (APN) is one of the most common bacterial infections. Because health care-associated (HCA) infections in the community setting have similar characteristics to hospital-acquired infections, HCA infections should be distinguished from community-acquired (CA) infections. However, the impact of HCA-APN on treatment outcomes has not been clearly defined. This study aimed to analyze the impact of HCA-APN on the appropriateness of empiric antibiotic therapy and outcomes in community-onset APN. METHODS: We prospectively identified women older than 18years who were hospitalized with APN via the emergency department and whose urine culture grew bacteria at 10 acute care hospitals in South Korea. RESULTS: Of the 388 APN episodes that were included, 99 (25.5%) were HCA-APN and 289 (74.5%) were CA-APN. Compared with patients with CA-APN, patients with HCA-APN had comorbid conditions and septic shock more frequently. Health care-associated APN was caused by resistant uropathogens more often. Patients with HCA-APN had poorer outcomes (ie, early/final clinical and microbiologic failures); however, this was not statistically significant. Patients with HCA-APN had significantly longer hospital stays than did patients with CA-APN. In the multivariable logistic regression analysis for inappropriate empiric therapy, HCA-APN (odds ratio, 1.96; 95% confidence interval, 1.07-3.57; P=.03) and being bed-ridden (odds ratio, 3.04; 95% confidence interval, 1.31-7.07; P=.01) were significant. CONCLUSIONS: Health care-associated APN was associated with inappropriate empiric antibiotic therapy, which might lead to worse outcomes. These HCA factors should be considered when prescribing empiric antibiotic therapy in patients with community-onset APN.

Effect of Qnr on Plasmid Gyrase Toxins CcdB and ParE.

Plasmid toxins CcdB and ParE are part of addiction systems promoting plasmid maintenance. Both target host DNA gyrase, as do quinolones and plasmid-determined Qnr proteins that protect gyrase from quinolone inhibition. We cloned qnrB4, qnrS1, ccdB, parE, and the antitoxin-encoding genes ccdA and parD on compatible plasmids and tested them in combination. CcdB and ParE had no specific effect on quinolone susceptibility or Qnr protection, and Qnr did not act as a CcdB or ParE antitoxin.

External and internal validation of healthcare-associated infection data collected by the Korean National healthcare-associated Infections Surveillance System (KONIS).

BACKGROUND: This study analyzed the validity of healthcare-associated infection (HAI) data of the Korean National healthcare-associated Infections Surveillance System. METHODS: The validation process consisted of external (EV) and internal (IV) validation phases. Of the 193 hospitals that participated from July 2016 through June 2017, EV was performed for 10 hospitals that were selected based on the HAI rate percentile. The EV team reviewed 295 medical records for 60 HAIs and 235 non-HAI control patients. IV was performed for both the 10 EV hospitals and 11 other participating hospitals that did not report any HAIs. RESULTS: In the EV, the diagnosis of urinary tract infections had a sensitivity of 72.0% and a specificity of 99.3%. The respective sensitivities of bloodstream infection and pneumonia were 63.2% and 70.6%; the respective specificities were 98.8% and 99.6%. The agreement (ĸ) between the EV and IV for 10 hospitals was 0.754 for urinary tract infections and 0.674 for bloodstream infections (P < .001, respectively). Additionally, IV found additional cases among 11 zero-report hospitals. DISCUSSION: This study demonstrates the need for ongoing validation and continuous training to maintain the accuracy of nationwide surveillance data. CONCLUSIONS: IV should be considered a validation method to supplement EV.

Induction of plasmid-carried qnrS1 in Escherichia coli by naturally occurring quinolones and quorum-sensing signal molecules.

Naturally occurring quinolone and quinolone-like compounds, such as quinine, 2-hydroxyquinoline, 4-hydroxyquinoline, and 2-heptyl-3-hydroxy-4(1H)-quinolone, increased expression of qnrS1 in Escherichia coli 2.3- to 11.2-fold, similar to the synthetic quinolone ciprofloxacin. In contrast, chromosomal qnrVS1 of Vibrio splendidus was not induced by these compounds. Molecules associated with quorum sensing, such as N-3-hydroxybutyryl-homoserine lactone (HSL), N-hexanoyl-HSL, and N-3-(oxododecanoyl)-HSL, did not show an induction effect on either qnrS1 or qnrVS1 at the tested concentrations.

Association of norB overexpression and fluoroquinolone resistance in clinical isolates of Staphylococcus aureus from Korea.

OBJECTIVES: Although the prevalence of fluoroquinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) is known to be higher than in methicillin-susceptible S. aureus (MSSA), the reasons have never been identified. METHODS: We randomly selected 115 isolates of S. aureus collected from 10 different hospitals in Korea between June 2009 and May 2011. To investigate the difference in fluoroquinolone resistance mechanisms between MRSA and MSSA, we evaluated gyrA and parC mutations and the relative expression of the multidrug efflux pump genes norA, norB and norC. RESULTS: All 62 ciprofloxacin-resistant S. aureus had either gyrA or parC mutations. The S84L mutation of gyrA (59/62, 95.2%) and the S80F mutation of parC (61/62, 98.4%) were the most common. Fifty-eight (93.6%) strains had both the S84L mutation of gyrA and the S80F mutation of parC. Among the 115 isolates, norB overexpression was the most common, occurring in 49 (42.6%) strains. There were only two (1.7%) strains with norA overexpression and none with norC overexpression. Strains overexpressing norB were more common among ciprofloxacin-resistant S. aureus (33/62, 53.2%) than ciprofloxacin-susceptible S. aureus (16/53, 30.2%) (P = 0.013). When we analysed 62 ciprofloxacin-resistant S. aureus strains, those overexpressing norB were more common in ciprofloxacin-resistant MRSA (28/46, 60.9%) than in ciprofloxacin-resistant MSSA (5/16, 31.3%) (P = 0.041). CONCLUSIONS: Increased expression of norB can be a factor that contributes to ciprofloxacin resistance in MRSA strains.

Characteristics of invasive Staphylococcus aureus infections in three regions of Korea, 2009-2011: a multi-center cohort study.

BACKGROUND: Despite the importance of invasive Staphylococcus aureus (ISA) infection, its overall burden in non-selected populations has only been defined in a small number of studies in Europe and North America. To define the characteristics of ISA infections in Korea, we conducted a multi-center cohort study to estimate population-based incidence rates. METHODS: We conducted a multicenter prospective cohort study at nine university-affiliated active-surveillance core centers (ASCs) in three regions of Korea. To cover all available clinical microbiologic laboratories, we classified the laboratories in these regions into three groups according to their clinical environment as: 1) Nine ASCs, 2) Five major commercial laboratories and 3) Forty-four acute-care hospital-affiliated microbiology laboratories. We requested all the laboratories to report prospectively their numbers of cases of S. aureus isolated from normally sterile sites. Detailed clinical information was collected about the cases in the nine ASCs. RESULTS: From 1 July 2009 to 30 June 2011, a total of 1,198 cases of ISA infection were identified at the nine ASCs, including 748 (62%) methicillin-resistant S. aureus (MRSA) infections. Most (81%) ISA infections were healthcare-associated (HCA): 653 (55%) hospital-onset and 322 (27%) community-onset. 223 (19%) were community-associated infections. The most common primary diagnosis was catheter-associated infection (225 cases, 19%). Respiratory tract infection (160, 13%), skin & soft tissue (152, 13%) and bone & joint infections (120, 10%) were also common. 30-day and 12-week mortality rates were 25.6% (262/1,024) and 36.5% (314/860), respectively. Complications, including metastatic infection within 12 weeks, occurred in 17.8% of ISA infections. The most common site of metastatic infection was the lung (9.8%, 84/860). Based on the total of 2,806 observed cases of ISA infection, estimated annual rates of ISA and invasive MRSA infections were 43.3 and 27.7 per 100,000 populations, respectively. CONCLUSIONS: Our data provide important information about the clinical characteristics of ISA infections. We estimate that over 21,000 ISA infections and 13,000 invasive MRSA infections occurred in Korea in 2010.