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. 2019 Sep 6;75(1):14–29. doi: 10.1093/jac/dkz348

Table 3.

Study characteristics

Authors Country Title Intervention Study design Year Outcome measure Risk of bias Outcome
1 Krcmery and Gould (1999)8 Slovakia Antibiotic policies in Central/Eastern Europe (CEE) after 1990 Institution of regulation (antibiotic committees) Time series analysis 1994–7 Antibiotic consumption (number of antibiotic packages/year) Moderate Overall decrease of antibiotic consumption: ∼11 000 packages/year in 1994 to ∼ 9000 packages/year in 1997
2 Altunsoy et al. (2011)10 Turkey The impact of a nationwide antibiotic restriction programme on antibiotic usage and resistance against nosocomial pathogens in Turkey Institution of regulation (antibiotic committees) Pre–post study 2001–5

  • Antibiotic consumption (g)

  • Sales volume and value

  • Resistance rates

 Moderate 11.3% decrease in antibiotic consumption (g) and cost

  • 60 074 g in 2001/2 to 38 129 g in 2003/4

  • 47 million USD in 2001/2 to 42 million USD in 2003/4
Negative correlation between ceftriaxone consumption (−36.8%) and the prevalence of ceftriaxone-resistant Escherichia coli and Klebsiella spp. (ρ −0.395, P=0.332 and ρ −0.627, P=0.037); all non-significant
Decreased use of carbapenems was correlated with decreased carbapenems-resistant Pseudomonas spp. and Acinetobacter spp (ρ 0.155, P=0.712; ρ 0.180, P=0.668)
Methicillin resistance rates of S. aureus decreased from 44% to 41%
3 Nathwani et al. (2011)9 Scotland, UK Scottish Antimicrobial Prescribing Group (SAPG): development and impact of the Scottish National Antimicrobial Stewardship Programme Institution of regulation (antibiotic committees) Time series analysis 2005–9

  • Antibiotic consumption (items per 1000 population/day)

  • Compliance with national antibiotic prescribing indicators

 Moderate 44 500 fewer prescriptions in 2009 compared with 2008

  • Penicillin combinations (co-amoxiclav): 14.7% decrease in items per 1000 population/day

  • Fluoroquinolones: 7.1% decrease in items per 1000 population/day; ≤5% seasonal variation in fluoroquinolone use

  • Cephalosporins: 21.2% decrease in items per 1000 population/day
Increased number of NHS boards achieving ≥95% compliance with the empirical prescribing policy (range: 65%–89%)
4 Tao et al. (2013)11 China Analysis of the current situation of antibiotics use in China: a hospital-based perspective Institution of regulation (antibiotic committees) Time series analysis 2008–11

  • Percentage of overall drug sales

  • Sales volume and value

 Moderate Percentage of drug sales for antimicrobials decreased from 23.8% (2009) to 19.4% (2011)
Sales volume for second- (24.51% to 9.46%) and third-line (21.54% to 4.78%) antibiotics decreased from 2010 to 2011, while sales volume for first-line antibiotics increased from 2010 to 2011 (7.96% to 13.94%)
5 Xiao et al. (2013)12 China Changes in Chinese policies to promote the rational use of antibiotics Institution of regulation (antibiotic committees) Time series analysis 2009–12

  • Antibiotic consumption (percentage of antimicrobial prescriptions)

  • Percentage of overall drug sales

 Moderate Percentage of drug sales for antimicrobials decreased from 25% (2011) to 17% (2012)
Percentage of antimicrobial prescriptions decreased in both inpatient settings (68% versus 58%) and outpatient settings (25% versus 15%)
6 Malmvall et al. (2007)17 Sweden Reduction of antibiotics sales and sustained low incidence of bacterial resistance: report on a broad approach during 10 years to implement evidence-based indications for antibiotic prescribing in Jönköping County, Sweden Institution of regulation (antibiotic committees) Time series analysis 1993–2005

  • Antibiotic consumption (DDD per 1000 inhabitants/day in primary care)

  • Resistance rates

 Moderate 31% decrease in overall antibiotic consumption: 15.9 DDD in 1993 to 11.0 DDD in 2005

  • Decrease most evident in children 5 to 14 years (number of antibiotic prescriptions decreased 52% (from 23 352 to 11 127)
No increase in the prevalence of resistant pneumococci or Haemophilus influenzae in the county
7 Zhang et al. (2017)13 Tianjin, China Effectiveness of antibiotic use management in Tianjin (2011–2013): a quasi-experimental study Institution of regulation (antibiotic committees) Quai-experimental study 2011–13 Antibiotic consumption (percentage of antibiotic use in inpatients; DDD per 100 patient days) Moderate Decrease in percentage of antibiotic use by inpatients (%): 60.38% in 2011 to 46.88% in 2013, P<0.000
Decrease in DDD/100 patient days: 51.60 DDD in 2011 to 35.37 DDD in 2013, P<0.000
8 Mölstad et al. (1999)14 Sweden Major change in the use of antibiotics following a national programme: Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance (STRAMA) Institution of regulation (antibiotic committees) Time series analysis 1980–97 Antibiotic consumption (DDD per 1000 inhabitants/day) Moderate Decrease in DDD per 1000 inhabitants/day: 16.3 DDD in 1993 to 13.0 DDD in 1997

  • Reduction was most pronounced for children (0–6 years old): 15.7 DDD in 1993 to 9.7 DDD in 1997 per 1000 children/day
9 Mölstad et al. (2008)15 Sweden Sustained reduction of antibiotic use and low bacterial resistance: 10-year follow-up of the Swedish STRAMA programme Institution of regulation (antibiotic committees) Time series analysis 1987–2004

  • Antibiotic consumption (DDD per 1000 inhabitants/day; number of prescriptions per 1000 inhabitants per year)

  • Resistance rates

 Moderate Decrease in DDD per 1000 inhabitants/day: 15.7 DDD in 1995 to 12.6 DDD in 2004
Decrease in number of prescriptions per 1000 inhabitants per year: 536 prescriptions in 1995 to 410 prescriptions in 2004

  • Reduction most prominent for children aged 5–14 years and macrolides

National frequency of penicillin-resistant S. pneumoniae increased from 4% to 6% despite decrease in antibiotic use among children
Resistance in S. pneumoniae also increased to erythromycin, tetracyclines and co-trimoxazole between 1994 and 2004
Rate of ampicillin-resistant E. coli in urinary cultures increased from 17% to 24%, trimethoprim-resistant E. coli increased from 8% to 15% from 1997–2004
10 Zou et al. (2014)16 China Is nationwide special campaign on antibiotic stewardship programme effective on ameliorating irrational antibiotic use in China? Study on the antibiotic use of specialized hospitals in China in 2011–2012 Institution of regulation (antibiotic committees) Pre–post study 2011–12 Antibiotic consumption (DDD per 100 inpatient days; percentage of antibiotic use in outpatient and inpatient cases) High Decrease in DDD per 100 patient days: 39.37 DDD in 2011 to 26.54 DDD in 2012, P<0.001
Decrease in percentage of antibiotic use in outpatient cases: 24.12% in 2011 to 18.71% in 2012, P=0.109
Decrease in percentage of antibiotic use in inpatient cases: 64.85% in 2011 to 60.10% in 2012, P=0.006
11 Allouch et al. (2016)7 Lebanon Antibiotic use, cost, and consumption in tertiary hospitals in Lebanon: a comparative study before and after an implementation of antibiotic-restriction program (ARP) Institution of regulation (clinical guidelines) Retrospective cohort study March–June 2013

  • Antibiotic consumption (proportion of subjects’ antibiotic consumption pre and post implementation of antibiotic-restriction programme)

  • Hospital antibiotic expenditure

 Moderate Decreases in proportional consumption of third-generation cephalosporins (19% to 12%, P<0.001), increase in the consumption of penicillin derivatives (24% to 28%, P<0.001).
Decrease in rate of restricted antibiotic use: 37.1% versus 26.1%, P<0.0001
22.3% decrease in the expenditure on all antibiotics (P<0.001).
12 Goosens et al. (2008)19 Belgium Achievements of the Belgian Antibiotic Policy coordination committee (BAPCOC) Institution of regulation (clinical guidelines); public education campaigns Time series analysis 1999–present

  • Antibiotic consumption (number of reimbursed packages per 1000 inhabitants per day)

  • Hospitals with key structural resources and tools in place for effective antibiotic management and infection control

  • Incidence of nosocomial acquisition of MRSA among patients admitted to acute care hospitals

  • Resistance rate

  • Compliance with hand hygiene

 High 90% of hospitals had key structural resources and tools in place for effective antibiotic management and infection control
35% relative reduction from 2004 to 2008 in the incidence of nosocomial acquisition of MRSA among patients admitted to acute care hospitals
36% decrease in number of reimbursed packages per 1000 inhabitants per day
Increased compliance with hand hygiene: 49% to 69% in 2005; 53% to 69% in 2007
Decrease in resistance rates from 2000 to 2007

  • Penicillin resistance in S. pneumoniae decreased from ∼16% to ∼10%

  • Tetracycline resistance in S. pneumoniae decreased from 32% to 22%

  • Erythromycin resistance in S. pneumoniae decreased from 37% to 25%

  • Macrolide resistance in Streptococcus pyogenes decreased from 17% in 2001 to 2% in 2007

13 Tambić-Andršević (2009)20 Croatia Antibiotic resistance control in Croatia Prescribing restrictions Time series analysis 2003–8 Antibiotic consumption (DDD per 1000 inhabitants/day) High Decrease in DDD per 1000 inhabitants/day (outpatient): 23.6 DDD in 2003 to 22.6 DDD in 2008
Decrease in DDD per 1000 inhabitants/day (inpatient): 2.5 DDD in 2002 to 1.5 DDD in 2008
14 Conly (2012)18 Canada Antimicrobial resistance programs in Canada 1995–2010: a critical evaluation Prescribing restrictions; public education campaigns Time series analysis 1995–2010 Antibiotic consumption (oral antimicrobial prescriptions per 1000 inhabitants) High Decrease in oral antimicrobial prescriptions per 1000 inhabitants: 25.3% decrease in prescriptions, driven by decreases in β-lactams, sulphonamides and tetracyclines
15 Sørensen and Monnet (2000)21 Denmark Control of antibiotic use in the community: the Danish experience Prescribing restrictions Time series analysis 1995–6 Antibiotic consumption (DDD per 1000 inhabitants; percentage of antimicrobial use) High Decrease in DDD per 1000 inhabitants: 4620 DDD per 1000 inhabitants in 1995 to 4122 DDD in 1996
Decrease in tetracycline use: 578 DDD in 1995 to 391 DDD in 1996
Decrease in percentage of antimicrobial use: 4.5% reduction in the use of antimicrobials in the primary healthcare sector in 1998 to 1999
16 Fürst et al. (2015)22 Slovenia The influence of a sustained multifaceted approach to improve antibiotic prescribing in Slovenia during the past decade: findings and implications Prescribing restrictions; public education campaigns Time series analysis 1995–2012

  • Antibiotic consumption (DDD per 1000 inhabitants/day; prescriptions per 1000 inhabitants)

  • Resistance rates

 Moderate Decrease in prescriptions per 1000 inhabitants: 791.29 prescriptions in 1999 to 525.97 prescriptions in 2012
Decrease in DDD per 1000 inhabitants/day 20.38 DDD in 1999 to 14.01 DDD in 2012 (P<0.0001); driven by significant decreases in tetracyclines, phenoxymethylpenicillin, cephalosporins and macrolides
S. pneumoniae resistance to penicillin decreased from 14.5% to 10%.
S. pneumoniae resistance to macrolides increased from 5.4% to 21%
17 Liou et al. (2015)23 Taiwan, China The primary resistance of Helicobacter pylori in Taiwan after the national policy to restrict antibiotic consumption and its relation to virulence factors—a nationwide study Prescribing restrictions Time series analysis 1997–2008

  • Antibiotic consumption (DDD per 1000 inhabitants/day)

  • Resistance rates

 Low Decrease in DDD per 1000 inhabitants/day (1997 to 2008)

  • Amoxicillin: 4.12 to 3.69

  • Tetracycline: 1.79 to 2.06

  • Macrolides: 1.12 to 0.49

  • Nitroimidazole: 0.22 to 0.15

  • Fluoroquinolone: 0.12 to 0.35
Primary H. pylori levofloxacin resistance rose from 4.9% in 2000–7 to 8.3% in 2008–10 and to 13.4% in 2011–12, P=0.001
18 Duborija-Kovačević (2006)24 Montenegro Antibiotic prescribing policy of the Republic Health Insurance Fund of Montenegro in the period 2000–2004: effects of drug utilization reform strategy Prescribing restrictions Pre–post study 2000–4 Antibiotic consumption (DDD per 1000 inhabitants/day; percentage of antibiotic prescriptions) High Decrease in percentage of antibiotic prescription: lower by 12% in 2004 compared with 2000
Decrease in DDD per 1000 inhabitants/day: 14.57 DDD in 2004 to 2.80 DDD in 2000

  • Highest increase in prescribing was established for macrolides (1.05 versus 1.64 DDD); penicillins were also prescribed more frequently (6.41 versus 6.56 DDD), but other subgroups were prescribed less frequently (cephalosporins and quinolones)

19 Cheng et al. (2012)25 Australia Control of fluoroquinolone resistance through successful regulation Prescribing restrictions Time series analysis 1992–2010 Resistance rates High Quinolone resistance rates in disease-causing isolates of E. coli increased from 0.4% in 1992 to 4.9% in 2006. Since 2006, surveillance of isolates from community-acquired infections showed a decrease in resistance rates to 4.1% in 2008.
20 Marshall et al. (2006)26 Canada Impact of administrative restrictions on antibiotic use and expenditure in Ontario: time series analysis Prescribing restrictions Time series analysis 1999–2002 Antibiotic consumption (number of prescriptions per week) Low Changes in number of antibiotic prescriptions per week

  • Fluoroquinolones: 1905 fewer prescriptions per week, P<0.0001 between 2000 and 2001; driven by decrease in ciprofloxacin prescription (2084 fewer prescriptions per week, P<0.0001

  • Nitrofurantoin: 200 more prescriptions per week, P<0.0001

  • Trimethoprim/sulfamethoxazole: 532 more prescriptions per week, P<0.0001
21 Kliemann et al. (2016)27 Brazil Socioeconomic determinants of antibiotic consumption in the state of São Paulo, Brazil: the effect of restricting over-the-counter sales Prescribing restrictions Time series analysis 2008–12 Antibiotic consumption (DDD per 1000 inhabitants/day) Moderate Decrease in DDD per 1000 inhabitants/day: 8.44 DDD in 2008 to 8.06 DDD in 2012
22 Rivas and Alonso (2011)28 Venezuela Regulation of dispensing drugs and their effect on the consumption of antibiotics in Venezuela Prescribing restrictions Retrospective study 2005–8 Antibiotic consumption (DDD per 1000 inhabitants/day) Moderate Decrease in DDD per 1000 inhabitants/day (2005 to 2008)

  • Diaminopyrimidines–sulfonamides: 1.11 to 1.01

  • Tetracyclines: 0.45 to 0.44

  • Aminoglycosides: 0.1357 to 0.1377

  • Rifampicin: 0.011 to 0.012

  • Penicillins and first-generation cephalosporins: 6.37 to 8.09

  • Macrolides and lincosamides: 2.03 to 2.85

  • Fluoroquinolones: 1.68 to 2.58

  • Third-generation cephalosporins: 0.15 to 0.34
23 Chou et al. (2003)29 Taiwan Impact of separating drug prescribing and dispensing on provider behaviour: Taiwan’s experience Separation of antibiotic prescribing from dispensing Time series with control group 1996–9 Antibiotic prescription (probability of non-prescription) Average drug dispensing expenditure per visit Low No significant difference between control and experimental cities: 7% increase in non-prescription probability in antibiotics immediately after the policy was in place, but the effect diminished over time
Non-significant changes in average drug dispensing expenditure per visit
24 Kim et al. (2016)30 South Korea Antibiotic control policies in South Korea, 2000–2013 Separation of antibiotic prescribing from dispensing Time series analysis 1998–2008 Antibiotic consumption (DDD per 1000 inhabitants/day) High Decrease in DDD per 1000 inhabitants/day: 28.8 DDD in 1998 to 22.8 DDD in 2008
25 Belongia et al. (2005)31 Wisconsin and Minnesota, USA Impact of statewide programme to promote appropriate antimicrobial drug use Campaigns for healthcare professionals; public education campaigns Pre–post study with control 1998–2003 Antibiotic prescription; annual primary care prescriptions of antibiotics per physician Low Decrease in percentage of annual primary care prescriptions of antibiotics per physician (dividing the number of new filled prescriptions by the number of prescribers per year):

  • 19.8% decrease in Minnesota

  • 20.4% decrease in Wisconsin
26 Weiss et al. (2011)32 Quebec, Canada Impact of a multipronged education strategy on antibiotic prescribing in Quebec, Canada Campaigns for healthcare professionals; public education campaigns Time series analysis 2003–7 Antibiotic consumption (number of outpatient antibiotic prescriptions per 1000 inhabitants/day) Moderate Decrease in the number of outpatient antibiotic prescriptions per 1000 inhabitants/day (2003 to 2007):

  • Cephalosporins: 70 to 58

  • Macrolides: 134 to 110

  • Penicillins: 155 to 141

  • Fluoroquinolones: 101 to 101

  • Others: 66 to 61

  • Total: 526 to 471
27 Chahwakilian et al. (2011)33 France Impact of the French campaign to reduce the inappropriate ambulatory antibiotic use on the prescription and consultation rates for respiratory tract infections Campaigns for healthcare professionals; public education campaigns Retrospective cohort study 2001–9

  • Antibiotic prescription (DDD per 1000 inhabitants/day; number of ambulatory antibiotic prescriptions per 1000 inhabitants/year; proportion of consultations resulting in antibiotic prescriptions)

  • Number of consultations for respiratory tract infections (RTIs)

 Moderate Decrease in DDD per 1000 inhabitants/day: 35.7 DDD in 2001 to 30.2 DDD in 2009
Decrease in the number of ambulatory antibiotic prescriptions per 1000 inhabitants/year

  • Pharmacy-based data: 1404 in 2001 to 1118 in 2009; 20.4% decrease

  • Physician-based data: 863 in 2001 to 577 in 2009; 33.1% decrease driven by decreased prescriptions for RTIs

23% decrease in the number of consultations for RTIs between 2001 and 2009
Decrease in the proportion of consultations resulting in antibiotic prescriptions: 58% in 2001 to 46% in 2009
28 Plachouras et al. (2014)34 Corinth, Greece Promoting prudent use of antibiotics: the experience from a multifaceted regional campaign in Greece Campaigns for healthcare professionals; public education campaigns Pre–post study with control January–February 2009 Antibiotic consumption (DDD per 1000 inhabitants/year; percentage of antibiotic use) Moderate Increase in DDD per 1000 inhabitants/year: 26 DDD (January–February 2009) to 32 DDD (March 2009)
Changes in percentage of antibiotic use, P=0.02:

  • Amoxicillin and penicillin: 34.3% increase

  • Macrolides: 21.9% decrease

  • Second-generation cephalosporins: 6.4% decrease

  • Fluoroquinolones: 21.9% decrease

  • Amoxicillin clavulanate: 9.4% decrease

29 Bernier et al. (2014)35 France Outpatient antibiotic use in France between 2000 and 2010: after the nationwide campaign, it is time to focus on the elderly Campaigns for healthcare professionals; public education campaigns Time series analysis 2000–10 Antibiotic prescription (number of weekly antibiotic prescriptions per 1000 inhabitants) Moderate 30% (95% CI −36.3 to −23.8) decrease in weekly antibiotic prescriptions during campaign period; no significant differences during non-campaign period
21% increase (95% CI 12.9%–29.6%) antibiotic consumption in seniors
30 Hemo et al. (2009)36 Israel Can a nationwide media campaign affect antibiotic use? Campaigns for healthcare professionals; public education campaigns Pre–post study 2004–5; 2005–6 Antibiotic consumption (purchasing rates for upper respiratory infection, otitis media and pharyngitis) Low Decrease in antibiotic purchasing rates for:

  • Upper RTI (OR=0.75; 95% CI 0.69–0.81)

  • Otitis media (OR = 0.65; 95% CI 0.59–0.72)

  • Pharyngitis (OR = 0.93; 95% CI 0.89–0.97)
31 Lambert et al. (2007)37 England Can mass media campaigns change antimicrobial prescribing? A regional evaluation study Public education campaigns Pre–post study 2004, 2005 Antibiotic prescription; antibiotic prescriptions per 1000 STAR-PU (Specific Therapeutic group Age-sex Related Prescribing Units) Moderate 21.7 fewer items prescribed per 1000 population (P<0.0005); 5.8% absolute reduction in prescribing
32 Sabuncu et al. (2009)38 France Significant reduction of antibiotic use in the community after a nationwide campaign in France, 2002–2007 Public education campaigns Time series analysis 2002–7 Antibiotic prescription; number of antibiotic prescriptions per 100 inhabitants Low 26.5% (95% CI −33.5 to −19.6) decrease in the number of antibiotic prescriptions per 100 inhabitants:

  • Mean number of all antibiotic prescriptions for all classes decreased (penicillins, cephalosporins, macrolides, cyclines, etc.) except for quinolones

  • Greatest decline −35.8% (95% CI−48.3% to −23.2%) observed in young children aged 6–15 years.
33 Parsons et al. (2004)40 England Did local enhancement of a national campaign to reduce high antibiotic prescribing affect public attitudes and prescribing rates? Public education campaigns Time series analysis 1995/6–99/2000

  • Antibiotic prescription; number of antibiotic prescriptions per 1000 patients dispensed between 1995/6 and 1999/2000

  • Proportion of participants who believed that children should be prescribed antibiotics for a fever

 Moderate Decrease in number of antibiotic prescriptions per 1000 patients: 686 1995/6 to 431 in 1999/2000; not significant
Decrease in the proportion of responders who believed that children should be prescribed antibiotics for a fever: 56% in 1995/6 to 49% in 1999/2000
34 Wutzke et al. (2006)39 Australia Evaluation of a national programme to reduce inappropriate use of antibiotics for upper respiratory tract infections: effects on consumer awareness, beliefs, attitudes and behaviour in Australia Public education campaigns Time series analysis 2001–4 (June to August) Antibiotic prescription (total antibiotic prescriptions dispensed in the community; total antibiotic prescriptions dispensed for upper respiratory tract infections Moderate Decrease in total antibiotic prescriptions in the community: 23.08 million antibiotic prescriptions in 1998/9 to 21.44 million in 2001/2
Decrease in total antibiotic prescriptions for upper respiratory tract infections: 216 000 fewer prescriptions for upper respiratory tract infections from 2001 to 2003