The burden of nosocomial staphylococcus aureus bloodstream infection in South Korea: a prospective hospital-based nationwide study

The population for this study consisted of all patients admitted to South Korean hospitals with over 500 beds during the June-September, 2011 study period. In 2011, there were 317 tertiary and general hospitals in South Korea, with 132,585 beds. Of these, 92 had over 500 beds, with a total number of 72,025 beds. We included 22 of a possible 92 hospitals, based on bed numbers and regional distributions (Figure?1). We considered the population of each region, and the proportion of selected hospitals in each region reflected the national proportion of the regional population. The 22 study hospitals had a total of 18,689 beds, which accounted for 25.9% of all hospitals with over 500 beds. All hospitals were acute-care hospitals.

We obtained patient-day data for the general population and the study hospitals from the claims data of the Health Insurance Review and Assessment Service, a mandatory medical insurance system that covers the entire population of South Korea [14]. Because the study was performed in 2011 and the claims data for that year were not yet complete, the data were extrapolated using the data for the previous 5?years. Data on medical costs were obtained from the administrative database of each study hospital.

Nosocomial SA-BSI was defined as S. aureus infection which occurred after 48?hours of hospitalization, and in which S. aureus was isolated from blood culture. Cases of SA-BSI occurring within 48?hours of hospitalization, but for which the association between the BSI and the current hospitalization was clear were taken to be nosocomial. Exclusion criteria were as follows: 1) community-associated infection, 2) healthcare-associated community-onset infection, and 3) transfer to a study hospital after developing SA-BSI in another hospital.

Mortality associated with SA-BSI was classified as 1) definitely associated or 2) possibly associated. The former was defined as described previously [15]: 1) positive SA-BSI at the time of death or 2) death within 14?days of the documentation of SA-BSI without any other explanation. The latter was defined as: 1) death within 30?days of the documentation of SA-BSI without another explanation. Catheter-associated infection was defined according to the definition proposed by National Nosocomial Infections Surveillance System [16]; in brief, positive blood culture drawn from a central venous catheter used within 48?hours of the onset of infection, with no other apparent source of the infection identified.

Hospital charges were defined as the amount hospitals billed for healthcare services to patients. Hospital costs were defined as the sum of hospital charges and the amount that hospitals received from the Reimbursement Service, a National Health Insurance Service in South Korea. Costs were expressed in US dollars ($) at the exchange rate of 1100 Won per $ (as of 1st June, 2011).

We conducted a matched case?control study to estimate the additional cost and length of hospitalization. In that study, nosocomial SA-BSI cases meeting the following conditions were excluded: 1) age under 18?years, 2) bloodstream infection that developed more than 30?days after admission. The latter criterion was adopted because of the difficulty of selecting control patients who were free of any nosocomial infections after 30?days of hospitalization. The control patients were selected according to the following criteria: 1) age (?5?years compared to the matched case), 2) date of admission (?2?weeks relative to the matched case), 3) confinement in the same ward as the case, and 4) underlying medical conditions similar to those of the matched case, and free of nosocomial infections. If two or more controls were identified, Charlson?s comorbidity index was used. Case?control pairs were classified into survivor and non-survivor pairs, according to whether the case patient was alive after 12?weeks of follow-up, irrespective of the outcome of the control patient.

Baseline demographic variables, such as age, gender, and underlying diseases were collected from the SA-BSI and control patients. Data on variables related to clinical outcomes, including length of hospitalization, mortality, and intensive care unit use were also collected.

During 4?months of the study period, 617 cases of SA-BSI were reported, of which 368 (59.6%) were cases of MRSA-BSI and 249 (40.4%) of MSSA-BSI. Community-associated infections consisted of 43 cases of MRSA-BSI and 109 cases of MSSA-BSI; 71 of the MRSA-BSI and 55 of the MSSA-BSI were healthcare-associated community-onset infections. After excluding these cases, 254 cases of MRSA-BSI and 85 cases of MSSA-BSI were included in the analysis. The baseline characteristics of the patients with nosocomial SA-BSI are shown in Table?1.

Of the 254 cases of MRSA-BSI, 104 (40.9%) occurred in the ICU, compared with 18 (21.2%) of the 85 cases of MSSA-BSI. While 163 cases (64.2%) of MRSA-BSI occurred within 30?days of hospitalisation, only 77 cases (90.6%) of MSSA-BSI occurred within this time period (Table?1).

Catheters were the most frequent primary site of infection for both MRSA-BSI and MSSA-BSI. Pneumonia and surgical site infection were frequently related to MRSA-BSI, while peripheral vein phlebitis and pneumonia were frequently related to MSSA-BSI.

Deaths associated with BSI occurred in 81 cases (31.9%) of MRSA-BSI. Of these, 64 were definitely associated with BSI, and 17 were probably associated with BSI. For MSSA-BSI, 12 deaths (14.1%) were definitely associated with BSI. In a subgroup analysis of central-line associated bloodstream infections (CLABSI), 30 of 94 (31.9%) MRSA-BSI patients died, and 27 out of the 30 deaths were definitely associated with SA-BSI.

Of the 254 MRSA-BSI cases, 121 were excluded from matching with control patients for the following reasons: 91 developed BSI after more than 30?days of hospitalization, 16 were under 18?years of age (two patients were both below 18 and developed BSI after more than a month of hospitalization), and 16 could not be matched with appropriate control patients. Of the 85 MSSA-BSI cases, 28 were excluded from the control patient matching: 8 patients developed BSI after more than a month of hospitalization, 9 were under 18 (one patient was both under 18 and developed BSI after more than a month of hospitalization), and 12 patients could not be matched with appropriate controls. At the end of this matching process, 56.0% of the cases were matched with controls. Baseline characteristics, including gender, age (excluding pediatric patients), proportions of CLABSI, and mortality between included and excluded cases were similar in the MRSA and MSSA-BSI groups. The clinical and economic outcomes of the cases and controls shown in Table?2 indicate that the median medical cost of MRSA-BSI was $19,318, about 2.5 times that of controls ($7,092). For the patients with MSSA-BSI, the median medical cost was $8,030 US dollars, almost double the $4,475 US dollars for the control patients.

The estimated annual incidence of nosocomial SA-BSI per 1,000 patient-days is shown in Table?3. The estimated annual incidence of MRSA-BSI was 0.12/1,000 patient-days, and that of MSSA-BSI was 0.04/1,000 patient-days. The estimated annual number of nosocomial SA-BSI cases was 2,946 for MRSA and 986 for MSSA. The estimated annual number of deaths was 943 for MRSA-BSI and 139 for MSSA-BSI.