Methods

  Data Sources

 
The National Health Insurance Research Dataset (NHIRD)

Taiwan National Health Insurance (NHI) was established in 1995 and includes 99% of the 23 million Taiwanese residents due to mandatory, universal enrollment. The NHIRD collects and maintains all participant demographic data and diagnoses according to the International Classification of Disease, ninth revision (ICD-9-CM), as well as all procedures and medications.

Quintiles IMS

Quintiles IMS or IMS Health is an organization that samples drug sales in each country through multiple supply routes to retail pharmacies and hospitals. Drug sales for the entire country are projected by the sampled data using patented projection methodology (1)

The Taiwan Nosocomial Infections Surveillance (TNIS)

To estimate the rate of nosocomial infections, the Taiwan CDC revised the previous surveillance system and launched the TNIS. The TNIS collects data on nosocomial infections in hospital ICUs. The detailed methodology of data collection and inclusion criteria for each year is described in annual reports issued by the Taiwan CDC.

Taiwan Surveillance of Antimicrobial Resistance (TSAR)

TSAR is a nationwide program at the National Health Research Institutes and has been conducted since 1998 (designated as TSAR period I). The isolates are recovered from clinical samples taken as part of standard care and the TSAR project has been approved by the Research Ethics Committee of National Health Research Institutes.

Since 2002, bacterial isolates have been collected biennially from July to September from 24-28 hospitals located in four regions of Taiwan. Each hospital first collects 50 outpatient isolates, 30 adult ICU and 100 non-ICU inpatient isolates, and 20 pediatric isolates. After completion of the above collection, an additional 20 (for 2002-2006) to 50 (after 2008) isolates from blood and sterile body sites are collected. All above isolates are collected sequentially without specifying species. Additional isolates of particular species are then collected. Collected isolates are stored at −80°C for subsequent species identification/confirmation and centralized antimicrobial susceptibility testing (AST). For AST, minimum inhibitory concentrations (MIC) of different antimicrobial agents are determined by reference broth microdilution method following the guidelines of the Clinical and Standard Laboratory Institute (CLSI).

  Infection Intensity

 
Incidence of Nosocomial Bacterial Infections in the ICUs.

The clinical data of patients with nosocomial infections (eg, pathogen, types of infection, age, or hospital setting) are collected from the TNIS. Types of nosocomial infections in TNIS include pneumonia, surgical site, urinary tract, bloodstream, and others. Only infections with identifiable bacterial etiology are included.

The incidence of nosocomial bacterial infections in the ICUs is calculated by dividing the total number of episodes of nosocomial bacterial infections by the number of patient-days in a given group. The number of patient-days is the sum of the number of days in the ICU of a given population (by age or hospital setting). Only participated hospitals are included in the analyses. Information of length of stay in hospitals that participated in TNIS is extracted from the NHIRD.

Percentage of Bacterial Species among Nosocomial Infections in the ICUs.

The proportion of bacterial species in each infection type is also calculated. The percentage is calculated by dividing the number of infection episodes caused by a specific bacterium by the number of total infection episode. Bacterial pathogens include Enterococcus spp. and Staphylococcus spp. as well as Acinetobacter spp., Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The sum of the percentage from each bacterium is more than 100% because one episode of infection may be caused by multiple pathogens.

Hospital settings (medical centers and regional/local hospitals) 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/local hospital.

  Antibiotic Consumption

 
Inpatient 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.

Table Designated DDD

Antibiotic DDD U Adm.R Designated ATC code
Ciclacillin 2 g O J01CA
Cephradine 2 g P J01DB09
Cefalexin 2 G P J01DB01
Cephradine 2 g O J01DB09
Sulfadiazine 1 g P J01E
Sulfamethoxazole 2 g P J01E
Sulfanilamide 4 g O J01E
Sulfathiazole 4 g O J01E
Sulfisoxazole 6 g O J01E
Sulfacarbamide 3 G O J01E
Tetroxoprim 0.2 g O J01E
Kitasamycin 2 g O J01FA
Kitasamycin 0.4 g P J01FA
Midecamycin 1 g P J01FA
Kanamycin 3 G O J01GB04
Nemonoxacin 0.5 G O J01MB08
Lomefloxacin 0.4 g O J01MA07
Gemifloxacin 0.32 g O J01MA15

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

Areas Cities
Northern Keelung, Taipei, New Taipei, Taoyuan, Yilan, Hsinchu
Central Miaoli, Taichung, Changhua, Yunlin, Nantou
Southern Chiayi, Tainan, Kaohsiung, Pingtung
Eastern Hualien, Taitung
Offshore islands Lienchiang, Kinmen, Penghu

Outpatient Consumption

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 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 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 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

 
Antimicrobial Non-Susceptibility in the ICUs.

ICU data on antimicrobial susceptibility (resistant, intermediate or susceptible) are extracted from the TNIS. MICs are not collected in TNIS 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.

Table Pathogens-antibiotics

Pathogens Antibiotic class Antimicrobial agents
Acinetobacter baumannii complex Amikacin Amikacin
  Aminoglycosides Gentamicin, Tobramycin
  Aminopenicillins and enzyme inhibitors Ampicillin-sulbactam
  Carbapenems Imipenem, Meropenem , Doripenem
  Cephalosporins (3rd gen) Ceftazidime
  Cephalosporins (4th gen) Cefepime, Cefpirome
  Fluoroquinolones Ciprofloxacin, Levofloxacin
  Piperacillin-tazobactam Piperacillin-tazobactam
Enterobacter spp. Amikacin Amikacin
  Aminoglycosides Gentamicin, Tobramycin
  Carbapenems Imipenem, Meropenem, Doripenem
  Cephalosporins (3rd gen) Cefotaxime, Ceftriaxone, Ceftazidime
  Cephalosporins (4th gen) Cefepime, Cefpirome
  Fluoroquinolones Ciprofloxacin, Levofloxacin
  Piperacillin-tazobactam Piperacillin-tazobactam
Escherichia coli, Klebsiella pneumoniae Amikacin Amikacin
  Aminoglycosides Gentamicin, Tobramycin
  Aminopenicillins Ampicillin
  Aminopenicillin and enzyme inhibitors Amoxicillin-clavulanate, Ampicillin-sulbactam
  Carbapenems Imipenem, Meropenem, Doripenem
  Cephalosporins (3rd gen) Cefotaxime, Ceftriaxone, Ceftazidime
  Cephalosporins (4th gen) Cefepime, Cefpirome
  Fluoroquinolones Ciprofloxacin, Levofloxacin
  Piperacillin-tazobactam Piperacillin-tazobactam
Pseudomonas aeruginosa Amikacin Amikacin
  Aminoglycosides Gentamicin, Tobramycin
  Carbapenems Imipenem, Meropenem, Doripenem
  Cephalosporins (3rd gen) Ceftazidime
  Cephalosporins (4th gen) Cefepime, Cefpirome
  Fluoroquinolones Ciprofloxacin, Levofloxacin
  Piperacillin-tazobactam Piperacillin-tazobactam
Salmonella spp. Aminopenicillins Ampicillin
  Trimethoprim-sulfamethoxazole Trimethoprim-sulfamethoxazole
  Carbapenems Imipenem, Meropenem, Doripenem
  Cephalosporins (3rd gen) Cefotaxime, Ceftriaxone
  Fluoroquinolones Ciprofloxacin, Levofloxacin
  Macrolides Azithromycin
Staphylococcus aureus Penicillins Penicillin
  Oxacillin Oxacillin, Cefoxitin
  Aminoglycosides Gentamicin
  Macrolide Azithromycin, Clarithromycin, Erythromycin
  Clindamycin Clindamycin
  Fluoroquinolones Ciprofloxacin, Levofloxacin, Moxifloxacin
  Tetracyclines Minocycline, Doxycycline, Tetracycline
  Trimethoprim-sulfamethoxazole Trimethoprim-sulfamethoxazole
  Glycopeptides Vancomycin
Streptococcus pneumoniae Macrolides Erythromycin, Clarithromycin, Azithromycin
  Penicillins Penicillin
  Cephalosporins (3rd gen) Cefotaxime, Ceftriaxone
  Glycopeptides Vancomycin
  Fluoroquinolones Levofloxacin, Moxifloxacin
  Aminopenicillins Amoxicillin
  Cephalosporins (4th gen) Cefepime, Cefpirome
  Carbapenems Imipenem, Meropenem , Doripenem
Enterococcus faecalis Aminoglycosides (high-level) Gentamicin (high-level)
  Penicillins Penicillin
  Aminopenicillins Amoxicillin, Ampicillin
  Glycopeptides Vancomycin
Enterococcus faecium Aminoglycosides (high-level) Gentamicin (high-level)
  Penicillins Penicillin
  Aminopenicillins Ampicillin
  Glycopeptides Vancomycin

  Antimicrobial Resistance Data from TSAR

 
Antimicrobial Non-Susceptibility in the outpatients, hospitalized non-ICU patients, and ICU patients.

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.

Table Pathogens-antibiotics

Pathogens Antibiotic class Antimicrobial agents

Acinetobacter baumannii complex

Amikacin

Amikacin

Aminoglycosides

Gentamicin, Tobramycin

Aminopenicillin and enzyme inhibitors

Ampicillin-sulbactam

Carbapenems

Imipenem, Meropenem, Doripenem

Cephalosporins (3rd gen)

Ceftazidime

Cephalosporins (4th gen)

Cefepime

Fluoroquinolones

Ciprofloxacin, Levofloxacin

Piperacillin or ticarcillin and enzyme inhibitors

Piperacillin-tazobactam or ticarcillin/clavulanate

 Escherichia coli

Amikacin

Amikacin

Aminoglycosides

Gentamicin, Tobramycin

Aminopenicillins

Ampicillin

Aminopenicillin and enzyme inhibitors

Amoxicillin-clavulanate, Ampicillin-sulbactam

Carbapenems

Imipenem, Meropenem, doripenem, ertapenem

Cephalosporins (3rd gen)

Cefotaxime, Ceftazidime

Cephalosporins (4th gen)

Cefepime

Fluoroquinolones

Ciprofloxacin, Levofloxacin

Piperacillin or ticarcillin and enzyme inhibitors

Piperacillin-tazobactam or ticarcillin/clavulanate

Klebsiella pneumoniae

Amikacin

Amikacin

Aminoglycosides

Gentamicin, Tobramycin

Aminopenicillins

Ampicillin

Aminopenicillin and enzyme inhibitors

Amoxicillin-clavulanate, Ampicillin-sulbactam

Carbapenems

Imipenem, Meropenem, doripenem, ertapenem

Cephalosporins (3rd gen)

Cefotaxime, Ceftazidime

Cephalosporins (4th gen)

Cefepime

Fluoroquinolones

Ciprofloxacin, Levofloxacin

Piperacillin or ticarcillin and enzyme inhibitors

Piperacillin-tazobactam or ticarcillin/clavulanate

Pseudomonas aeruginosa

Amikacin

Amikacin

Aminoglycosides

Gentamicin, Tobramycin

Carbapenems

Imipenem, Meropenem, Doripenem

Cephalosporins (3rd gen)

Ceftazidime

Cephalosporins (4th gen)

Cefepime

Fluoroquinolones

Ciprofloxacin, Levofloxacin

Piperacillin or ticarcillin and enzyme inhibitors

Piperacillin-tazobactam

Staphylococcus aureus

Penicillins

Penicillin

Oxacillin

Oxacillin

Aminoglycosides

Gentamicin

Macrolide

Erythromycin

Clindamycin

Clindamycin

Fluoroquinolones

Ciprofloxacin, Levofloxacin

Tetracyclines

Tetracycline

Trimethoprim-sulfamethoxazole

Trimethoprim-sulfamethoxazole

Glycopeptides

Vancomycin

Daptomycin

Daptomycin

Linezolid

Linezolid

Tigecycline

Tigecycline

Enterococcus faecalis

Aminoglycosides (high-level)

Gentamicin (high-level)

Aminopenicillins

Ampicillin

Glycopeptides

Vancomycin

Daptomycin

Daptomycin

Linezolid

Linezolid

Tigecycline

Tigecycline

Enterococcus faecium

Aminoglycosides (high-level)

Gentamicin (high-level)

Aminopenicillins

Ampicillin

Glycopeptides

Vancomycin

Daptomycin

Daptomycin

Linezolid

Linezolid

Tigecycline

Tigecycline

 

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