Methods

  Data Sources

  Infection Intensity

  Antibiotic Consumption

Data on inpatient antibiotic consumption are derived from the NHIRD. Only systemic use (oral or intravenous form) of antibiotics is included in analyses. Consumption is measured by the Defined Daily Doses (DDD) of antibiotics divided by the number of patient-days or population-days in a given group.

The DDD of each antibiotic is calculated according the ATC codes. The DDD of an antibiotic that is not indicated by the ATC is designated based on the mechanism of action and structure of the medication (DDD Table). The number of patient-days is the sum of hospitalization duration (days) of a given population (defined by age, area, or hospital setting). The number of population-days is defined by the number of Taiwanese residents multiplied by 365 days. The number of Taiwanese residents in a given group (age or area) is based on data issued by the Interior Ministry.

Hospital settings (medical centers, and regional and local hospitals) and area (Designated Areas Table) are defined in accordance with the NHI administration and Interior Ministry, respectively. There is only one medical center in Eastern Taiwan and the NHI administration prohibits the dissemination of information on specific hospitals. Therefore, this medical center is categorized as a regional hospital.

Table Designated Areas

Outpatient antibiotic consumption comprises the drug use in community clinics and that in hospital-affiliated clinics and Emergency Room (ER). Due to the lack of data reliability from the NHIRD (2), data on community clinics are derived from the IQVIA/IMS. Data on hospital-affiliated clinics or ER are still from NHIRD. As with inpatient consumption, only systemic use (oral or intravenous form) of antibiotics is included in analyses. The IQVIA/IMS sampled the sales of drugs in outpatient clinics and pharmacies. Consumption is measured by the DDD divided by population-days. Due to a lack of clinical data in the IQVIA/IMS, further stratification (by age or area) is not possible.

As with inpatient consumption, the DDD of each antibiotic is defined by ATC codes. The DDD of an antibiotic that is not indicated by the ATC is designated based on the mechanism of action and structure of the medication (Table designated DDD). The number of population-days is the number of Taiwanese residents multiplied with 365 days. The number of Taiwanese residents is based on data issued by the Internal Ministry.

  Antimicrobial Resistance

ICU data on antimicrobial susceptibility (resistant, intermediate or susceptible) are extracted from the TNIS/THAS. MICs are not collected in TNIS/THAS dataset. Antibiotics for each bacterial species in the website are chosen in accordance with the recommendation of the Clinical & Laboratory Standards Institute (CLSI). Some antibiotics are grouped into one class. Antibiotics or antibiotic groups are listed in the Pathogens-antibiotics Table. The breakpoint of each antibiotic in a given year may vary among hospitals, depending on how quickly the hospital updates breakpoint information following annual revisions of the CLSI.

The non-susceptibility rate is measured by the number of isolates that are non-susceptible to a certain antibiotic class or a certain antibiotic, divided by the number of isolates tested. The non-susceptibility of an isolate to any member of an antibiotic class is deemed non-susceptible to that class. The numbers of isolates are not always provided due to the tight regulation of NHI, which prohibits the revelation of information of the targets if their number is limited; a range, instead of a number, is provided. The information regarding the non-susceptibility of newer agents, i.e., polymyxins, linezolid, daptomycin, and tigecycline is not provided because of variation among testing methods, non-routine testing, presence of selection bias, and/or lack of breakpoint in CLSI.

Hospital settings (medical centers and regional/local hospitals) are defined in accordance with the NHI administration. There is only one medical center in Eastern Taiwan and the NHI administration prohibits the dissemination of information on specific hospitals. Therefore, this medical center is categorized into regional/local hospitals. Types of infections are divided into 2 categories; bloodstream infections, and non-bloodstream infections.

  Antimicrobial Resistance Data from TSAR

The interpretation of the MIC of each antibiotic in accordance with the recommendation of the Clinical & Laboratory Standards Institute (CLSI). Some antibiotics are grouped into one class. Antibiotics or antibiotic groups are listed in the Pathogens-antibiotics Table. The non-susceptibility rate is measured by the number of isolates that are non-susceptible to a certain antibiotic class or a certain antibiotic, divided by the number of isolates tested. For ease of categorization, non-susceptibility of an isolate to any member of an antibiotic subclass or class listed in the Pathogen-antibiotics Table is deemed non-susceptible to all agents in that subclass or class.

Patient location refers to the location where the patient was when the specimen was obtained for culture, from which the isolate was recovered and included outpatients/emergency department, ward (hospitalized non-ICU), and ICU. The breakpoints (interpretive criteria) of CLSI’s most recent 2 years are provided to interpret the MICs.

  References

1. Kirkcaldy RD, Bartoces MG, Soge OO, Riedel S, Kubin G, Del Rio C, Papp JR, Hook EW, 3rd, and Hicks LA. 2017. Antimicrobial Drug Prescription and Neisseria gonorrhoeae Susceptibility, United States, 2005-2013. Emerg Infect Dis 23:1657-1663.
2. Kuo SC, Shih SM, Hsieh LY, Lauderdale TY, Chen YC, Hsiung CA, and Chang SC. 2017. Antibiotic restriction policy paradoxically increased private drug consumptions outside Taiwan’s National Health Insurance. J. Antimicrob. Chemother.