Antimicrobial Stewardship: Fighting Antimicrobial Resistance and Protecting Global Public Health

Figures & data

Box 1 Glass Report – Highlights of Reported Resistance

1. High rates of AMR observed against common bacterial infections

2. Median frequency of resistance in pathogens isolated from patients with bloodstream infections

i. Methicillin-resistant S. aureus (MRSA): 12.11% (IQR 6.4–26.4)

ii. E. coli resistant to third-generation cephalosporins: 36.0% (IQR 15.2–63.0)

iii. K. pneumoniae resistant to third-generation cephalosporins 57.6% (IQR 33.4–77.8), with 12 countries reporting 80–100% resistance

iv. Acinetobacter spp.: aminoglycosides 41.2% (IQR 5.20–83.31); carbapenems 63.2% (IQR 19.78 −81.63)

3. Median resistance to ciprofloxacin in urinary tract infections

i. 43.29% (IQR 23.8–46.4) for E. coli in 33 reporting countries, territories and areas

ii. 38.1% (IQR 8.41–63.53) for K. pneumoniae in 34 reporting countries, territories and areas

Note: Data from World Health Organization.11

Table 1 Impact of Antimicrobial Resistance in Health Care Systems

Organisms	Threat Level	Estimated Cases in Hospitalized Patients (2017)	Estimated Deaths (2017)	Estimated Attributable Healthcare Costs (2017) US
Carbapenem-resistant Acinetobacter	Urgent	8,500	700	$281M
Clostridioides difficile	Urgent	223,900	12,800	$1B
Carbapenem-Resistant Enterobacteriaceae	Urgent	13,100	1,100	$130M
Drug-Resistant Neisseria gonorrhoeae	Urgent	550,000	1.14M	$133.4M
Vancomycin-Resistant Enterococci (VRE)	Serious	54,500	5,400	$539M
Multidrug-Resistant Pseudomonas aeruginosa	Serious	32,600	2,700	$767M
Methicillin-Resistant Staphylococcus aureus	Serious	323,700	10,600	$1.7B
Extended-Spectrum Beta-Lactamase (ESBL) Producing Enterobacteriaceae	Serious	197,400	9,100	$1.2B
Drug-Resistant Tuberculosis (Tb)	Serious	847	62	$164,000 Per MDR case $526,000 Per XDR case

Note: Data from Centers for Disease Control and Prevention.19

Box 2 Core Elements of the Antibiotic Stewardship Program

Leadership commitment towards necessary human, financial, and information technology resources.

Accountability through a single physician/pharmacist leader for program management and outcomes.

Drug expertise through an only pharmacy leader to help lead implementation efforts to improve antibiotic use.

Action to implement interventions, such as prospective audit and feedback or preauthorization, to improve antibiotic use.

Tracking prescription, the impact of interventions, resistance patterns, and other important outcomes.

Reporting prescription and resistance information directly to prescribers, pharmacists, nurses, and hospital leadership.

Education for health care professionals (prescribers, pharmacists, nurses) and patients about adverse reactions from antibiotics, antibiotic resistance, and optimal prescribing.

Note: Data from Centers for Disease Control and Prevention.⁷¹

Box 3 Antimicrobial Stewardship Aligns with the 10 Essential Services of Public Health

Antimicrobial susceptibility patterns and antimicrobial utilization trends monitor and detect at the national, state, regional, and community levels.

Surveillance of antimicrobial susceptibility across nations, states, regions, and communities.

The provision of information through education empowers patients, healthcare providers, and other agencies on appropriate antimicrobial use.

Collaborate with the community’s organization, such as non-governmental and governmental organizations geared towards patient safety regionally and nationally, hospitals, long-term care facilities, and healthcare systems in promoting antimicrobial stewardship strategies across regions, particularly with shared patient populations.

Identify and share best practices and policies in AMS widely.

Provide advocacy initiatives for promoting legislation to improve patient safety, reduce exposure, and develop resistant infections.

Establish linkages amongst healthcare entities to enhance AMS across regions.

Ensure effective ASP is established within healthcare facilities.

Monitor and evaluate ASP towards improvement in healthcare facilities.

The creation of innovative research solutions to obstacles in AMS implementation.

Note: Data from these studies.^74,81,82

Box 4 Types of Stewardship Interventions

Education and guidelines

Formulary restrictions

Intravenous to oral conversion

Intravenous batching

Therapeutic substitutions

Antibiotic timeout

Antimicrobial cycling

Note: Copyright © 2020. Pharmacy Times. Reproduced from Pharmacy Times. Antimicrobial Stewardship: A Primer for Hospital Pharmacists. Available from: https://www.pharmacytimes.com/publications/health-system-edition/2016/march2016/antimicrobial-stewardship-a-primer-for-hospital-pharmacists.⁷²

Figure 1 Core elements of ASP to optimize the treatment of infections and reduce adverse events associated with antibiotic use.

Notes: Copyright © 2020. Global Alliance for Infections in Surgery. Reproduced from Global Alliance for Infections in Surgery. Core elements of antibiotic stewardship. Available from: https://infectionsinsurgery.org/core-elements-of-antibiotic-stewardship/.⁶⁹

Table 2 Impact of ASPs on Antibiotic Usage, Microbiological, Clinical, and Financial Outcomes

Study Reference No.	Countries	Settings, Design, Time, and Health Personnel Involved	Interventions	Outcome Measured	Impact
Wang et al (2019)^Citation156	China	Tertiary hospital. A retrospective observational study. 2011 to 2016 Pharmacists	Multi-aspect interventions: activity program, performance management, and training.	Antibiotic prescriptions, the intensity of consumption, antibiotic prophylaxis, and resistance rates	↓Prescriptions: outpatients - 19.38% to 13.21%, inpatients −64.34% to 34.65%. ↓Intensity: 102.46 to 37.38 DDD^a/100 PD^b ↓Prophylaxis: 98.94% to 18.93%. ↓Resistance rates^c ↓MRSA^d incidence: 68.0% to 37.5% ↑Resistance rates^e
Xiao et al (2020)^Citation161	China	Secondary and tertiary hospitals A retrospective observational study. 2010 to 2016	AMS campaign	Antibiotic prescriptions, intensity of consumption, antibiotic expense, and resistance rates	↓Prescription: outpatients - 19.5% to 8.5%; surgical patients - 97.9% to 38.3%. ↓Intensity: 85.3% to 48.5% DDD/100 bed-days. ↓Antibiotic procurement costs:22.3% to12.1%. ↓Resistance rates^f: 30.8% to 22.3% ↓MRSA incidence: 54.4% to 34.4%
Mardani et al (2020)^Citation162	Iran	Tertiary teaching hospitals. An interventional quasi-experimental study. Before (2017 to 2018) and after (2018 to 2019) ASP implementation. Nurses and physicians.	AMS educational programs	Antibiotic prescriptions, the occurrence of CDI, and positive MDR cases	↓Prescription^g: 22,464 to 17,262 g. ↓CDI^h incidence: 11.2% to 2.7% cases per 10,000 patient days ↓MDR^i cases: 145 t0 75
Onorato et al (2020)^Citation163	Italy	Intensive care units (ICUs) of a teaching hospital. Prospective, interventional, Interrupted time-series study. Time: 2017–2018.		Antibiotic prescriptions, incidence of BSI, hospital mortality rate, mean LOS, and antibiotic expense.	↓Prescription: 324.8 DDD/100 PD ↓Incidence of BSI^j: 5.8 events/100 PD Hospital mortality rate: No difference Mean LOS^k: No difference
Savoldi et al (2020)^Citation164	Germany	Prospective quasi-experimental, Interrupted time-series study. Tertiary care teaching hospital. 2014 and 2017.	Non-restrictive ASP, 3 phases: 1-year pre-intervention, 2-year multifaceted intervention, and one year of post-intervention.	Antibiotic prescriptions, antibiotic expense, mean LOS, CDI incidence rate, and mortality in the patients’ group were admitted from ED to medical wards.	↓Prescription: 31.1% to 7.2% DDD/100 PD. ↓Incidence of CDI ↓Mean LOS Mortality rate: No difference ↓Antibiotic expense: 691.5 to 263.3 EUROs/100 PDs
Singh et al (2018)^Citation165	India	Tertiary teaching hospital. Quasi-experimental study. 2015 to 2017. Infection control team	Post-prescriptive audit and establishment of institutional guidelines	Antibiotic prescriptions, antibiotic expense, compliance with ASP Recommendations	↓Prescription (DDD/100 PD). ↓Mean monthly cost for restricted drugs by 14.4% ↑Compliance: 54%
Wee et al (2020)^Citation166	Singapore	Tertiary teaching hospital. A retrospective cohort studies. 2016 to 2018.	Prospective audit and feedback strategy	Adherence to ASP recommendations	↑Adherence: 81.9% (5758/7028)
Abubakar et al (2019)^Citation167	Nigeria	Tertiary hospitals. Prospective pre- and post-intervention study. May and December 2016. Pharmacists.	Development of a protocol, educational meeting and audit and feedback	Antibiotic prescriptions, the intensity of consumption, antibiotic expense, and resistance rates	↓Prescription: 19.1% ↓Prescription: third generation cephalosporin (−8.6%), ↓Intensity: (3.8 DDD/procedure) ↓Cost: $4.2/procedure ↑Compliance: Timing (14.2% to 43.3%) and duration (0% to 21.8%)
Brink et al (2017)^Citation168	South Africa	Private hospitals. Prospective pre- and post-intervention study. Pharmacist. 2013–2015.	Prospective audit and feedback for perioperative antibiotic prophylaxis	SSI and compliance.	↑Compliance: 66.8% to 83.3% (95% CI 80.8–85.8). ↓SSI^l rate 19.7%
Horikoshi et al (2017)^Citation155	Japan	Tokyo Metropolitan Children’s Medical Center. Prospective pre- and post-intervention study. Quasi-experimental study. 2010–2017.	Computerized preauthorization and a prospective audit, an electronic chart-based drug ordering system	DOT in the post-intervention period, the resistance rate, and the correlation between DOT and resistance rates, average days of hospitalization, all-cause mortality, and infection-related mortality in the pre- and post-intervention periods.	↓DOT^m in the post-intervention period: 59.3% ↓The resistance rate: 72.2% ↑positive correlation ↓Average hospitalization (days) ↓All-cause mortality rate (per 1000 patient-days) ↓Infection-related mortality rate (per 1000 patient-days)
D’Agata et al (2018)^Citation169	USA	Outpatient dialysis facilities. Quasi-experimental study. 2015–2016	ASP	Rates of antimicrobial use per 100 patient months, rates of use for specific antimicrobials or antimicrobial groups.	↓Antimicrobial doses per 100 patient months: 6%

Notes: ^cE. coli and P. aeruginosa to fluoroquinolones. ^eE. coli and K. pneumoniae to carbapenems. ^fCarbapenem-resistant Pseudomonas aeruginosa isolates. ^gMeropenem prescriptions. ^hClostridium difficile infections. ↑: Increase. ↓: Decrease.

Abbreviations: ^aPD, patient-days; ^bDDD, defined daily doses; ^dMRSA, methicillin-resistant Staphylococcus aureus; ⁱMDR, multidrug resistance; ^jBSI, bloodstream infections caused by multidrug-resistant (MDR) organisms; ^kLoS, length of stay; ^lSSI, surgical site infections; ^mDOT, day of therapy.

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