Antimicrobial Stewardship Programs (ASPs) have become an essential pillar for optimizing antimicrobial use, improving patient care, and reducing antimicrobial resistance (AMR).Here, we assessed the impact of ASP on antimicrobial consumption and AMR in Colombia.
We designed a retrospective observational study and measured trends in antibiotic consumption and AMR before and after ASP implementation over a 4-year period (24 months before and 24 months after ASP implementation) using interrupted time-series analysis.
ASPs are implemented based on each institution’s available resources.Prior to the implementation of ASP, there was a trend toward increased antibiotic consumption for all selected measures of antimicrobials.After that, an overall decrease in antibiotic consumption was observed.Ertapenem and meropenem use decreased in hospital wards, while ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, and vancomycin decreased in intensive care units.The trend of increases in oxacillin-resistant Staphylococcus aureus, ceftriaxone-resistant Escherichia coli, and meropenem-resistant Pseudomonas aeruginosa was reversed after ASP implementation.
In our study, we show that ASP is a key strategy in addressing the emerging threat of AMR and positively impacts antibiotic depletion and resistance.
Antimicrobial resistance (AMR) is considered a global threat to public health [1, 2], causing more than 700,000 deaths annually.By 2050, the number of deaths could be as high as 10 million per year [3] and could damage the gross domestic product of countries, especially low- and middle-income countries (LMICs) [4].
The high adaptability of microorganisms and the relationship between antimicrobial misuse and AMR have been known for decades [5].In 1996, McGowan and Gerding called for “antimicrobial use stewardship,” including optimization of antimicrobial selection, dose, and treatment duration, to address the emerging threat of AMR [6].Over the past few years, antimicrobial stewardship programs (ASPs) have become a fundamental pillar in optimizing antimicrobial use by improving adherence to antimicrobial guidelines and are known to improve patient care while having a favorable impact on AMR [7, 8].
Low- and middle-income countries typically have a high incidence of AMR due to a lack of rapid diagnostic tests, last-generation antimicrobials, and epidemiological surveillance [9], so ASP-oriented strategies such as online training, mentoring programs, national guidelines, and The use of social media platforms has become a priority [8].However, integration of these ASPs is challenging due to the frequent lack of healthcare professionals trained in antimicrobial stewardship, the lack of electronic medical records, and the lack of a national public health policy to address AMR [9].
Several hospital studies of hospitalized patients have shown that ASP can improve adherence to antimicrobial treatment guidelines and reduce unnecessary antibiotic consumption, while having favorable effects on AMR rates, hospital-acquired infections, and patient outcomes [8, 10, 11] , 12].The most effective interventions include prospective review and feedback, preauthorization, and facility-specific treatment recommendations [13].Although the success of ASP has been published in Latin America, there are few reports on the clinical, microbiological, and economic impact of these interventions [14,15,16,17,18].
The aim of this study was to evaluate the impact of ASP on antibiotic consumption and AMR in four high-complexity hospitals in Colombia using an interrupted time series analysis.
A retrospective observational study of four homes in two Colombian cities (Cali and Barranquilla) over a 48-month period from 2009 to 2012 (24 months before and 24 months after ASP implementation) Performed in highly complex hospitals (institutions AD).Antibiotic consumption and meropenem-resistant Acinetobacter baumannii (MEM-R Aba), ceftriaxone-resistant E. coli (CRO-R Eco), ertapenem-resistant Klebsiella pneumoniae (ETP-R Kpn), The incidence of Ropenem Pseudomonas aeruginosa (MEM-R Pae) and oxacillin-resistant Staphylococcus aureus (OXA-R Sau) were measured during the study.A baseline ASP assessment was performed at the beginning of the study period, followed by monitoring of ASP progression over the next six months using the Indicative Compound Antimicrobial (ICATB) Antimicrobial Stewardship Index [19].Average ICATB scores were calculated.General wards and intensive care units (ICUs) were included in the analysis.Emergency rooms and pediatric wards were excluded from the study.
Common characteristics of participating institutional ASPs include: (1) Multidisciplinary ASP teams: infectious disease physicians, pharmacists, microbiologists, nurse managers, infection control and prevention committees; (2) Antimicrobial guidelines for the most prevalent infections, updated by the ASP team and based on the epidemiology of the institution; (3) consensus among different experts on antimicrobial guidelines after discussion and before implementation; (4) prospective audit and feedback is a strategy for all but one institution (institution D implemented restrictive prescribing (5) After antibiotic treatment begins, the ASP team (mainly by a GP reporting to an infectious disease physician) reviews the prescription of the selected vetted antibiotic and provides direct feedback and recommendations to continue, adjust, change or discontinue treatment; (6) regular (every 4-6 months) educational interventions to remind physicians of antimicrobial guidelines; (7) hospital management support for ASM team interventions.
Defined daily doses (DDDs) based on the World Health Organization (WHO) calculation system were used to measure antibiotic consumption. DDD per 100 bed-days before and after intervention with ceftriaxone, cefepime, piperacillin/tazobactam, ertapenem, meropenem, and vancomycin was recorded monthly at each hospital.Global metrics for all hospitals are generated each month during the assessment period.
To measure the incidence of MEM-R Aba, CRO-R Eco, ETP-R Kpn, MEM-R Pae, and OXA-R Sau, the number of patients with hospital-acquired infections (according to CDC and microbial culture-positive prophylaxis [ CDC] Surveillance System Standards) divided by the number of admissions per hospital (in 6 months) × 1000 patient admissions.Only one isolate of the same species was included per patient.On the other hand, there were no major changes in hand hygiene, isolation precautions, cleaning and disinfection strategies in the four hospitals.During the evaluation period, the protocol implemented by the Infection Control and Prevention Committee remained unchanged.
The 2009 and 2010 Clinical and Laboratory Standards Institute (CLSI) guidelines were used to determine trends in resistance, taking into account the sensitivity breakpoints of each isolate at the time of study, to ensure comparability of results.
Interrupted time series analysis to compare global monthly DDD antibiotic use and six-month cumulative incidence of MEM-R Aba, CRO-R Eco, ETP-R Kpn, MEM-R Pae, and OXA-R Sau in hospital wards and intensive care units.Antibiotic consumption, coefficients and incidence of pre-intervention infections, trends before and after intervention, and changes in absolute levels after intervention were recorded.The following definitions are used: β0 is a constant, β1 is the coefficient of the pre-intervention trend, β2 is the trend change, and β3 is the post-intervention trend [20].Statistical analysis was performed in STATA® 15th Edition.A p-value < 0.05 was considered statistically significant.
Four hospitals were included during the 48-month follow-up; their characteristics are shown in Table 1.
Although all programs were led by epidemiologists or infectious disease physicians (Table 2), the distribution of human resources for ASPs varied across hospitals.The average cost of ASP was $1,143 per 100 beds.Institutions D and B spent the longest time for ASP intervention, working 122.93 and 120.67 hours per 100 beds per month, respectively.Infectious disease physicians, epidemiologists and hospital pharmacists at both institutions have historically had higher hours.Institution D’s ASP averaged $2,158 per 100 beds per month, and was the most expensive item among the 4 institutions because of more dedicated specialists.
Prior to the implementation of ASP, the four institutions had the highest prevalence of broad-spectrum antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, ertapenem, meropenem, and vancomycin) in general wards and ICUs. There is an increasing trend in usage (Figure 1).Following the implementation of the ASP, antibiotic use decreased across institutions; institution B (45%) saw the largest reduction, followed by institutions A (29%), D (28%), and C (20%).Institution C reversed the trend in antibiotic consumption, with levels even lower than in the first study period compared to the third post-implementation period (p < 0.001).After the implementation of ASP, the consumption of meropenem, cefepime, and ceftriaxone decreased significantly to 49%, 16%, and 7% in institutions C, D, and B, respectively (p < 0.001).Consumption of vancomycin, piperacillin/tazobactam, and ertapenem was not statistically different.In the case of facility A, reduced consumption of meropenem, piperacillin/tazobactam, and ceftriaxone was observed in the first year after ASP implementation, although the behavior did not show any decreasing trend in the following year (p > 0.05).
DDD trends in consumption of broad-spectrum antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, ertapenem, meropenem, and vancomycin) in ICU and general wards
A statistically significant upward trend was observed across all antibiotics evaluated before ASP was implemented in hospital wards.The consumption of ertapenem and meropenem decreased statistically significantly after ASP was implemented.However, no statistically significant decrease was observed in the consumption of other antibiotics (Table 3).Regarding the ICU, prior to ASP implementation, a statistically significant upward trend was observed for all antibiotics evaluated, except ertapenem and vancomycin.Following ASP implementation, the use of ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, and vancomycin decreased.
As for multidrug-resistant bacteria, there was a statistically significant upward trend in OXA-R Sau, MEM-R Pae, and CRO-R Eco before the implementation of ASPs.In contrast, the trends for ETP-R Kpn and MEM-R Aba were not statistically significant.The trends for CRO-R Eco, MEM-R Pae, and OXA-R Sau changed after ASP was implemented, while the trends for MEM-R Aba and ETP-R Kpn were not statistically significant (Table 4).
Implementation of ASP and optimal use of antibiotics are critical to suppress AMR [8, 21].In our study, we observed reductions in the use of certain antimicrobials in three of the four institutions studied.Several strategies implemented by hospitals may contribute to the success of these hospitals’ ASPs.The fact that the ASP is made up of an interdisciplinary team of professionals is critical as they are responsible for socializing, implementing, and measuring compliance with antimicrobial guidelines.Other successful strategies include discussing antibacterial guidelines with prescribing specialists before implementing ASP and introducing tools to monitor antibiotic consumption, which can help keep tabs on any changes in antibacterial prescribing.
Healthcare facilities implementing ASPs must adapt their interventions to the available human resources and payroll support of the antimicrobial stewardship team.Our experience is similar to that reported by Perozziello and colleagues in a French hospital [22].Another key factor was the support of the hospital administration in the research facility, which facilitated the governance of the ASP work team.Furthermore, allocating work time to infectious disease specialists, hospital pharmacists, general practitioners and paramedics is an essential element of the successful implementation of ASP [23].In Institutions B and C, GPs’ devotion of significant work time to implementing ASP may have contributed to their high compliance with antimicrobial guidelines, similar to that reported by Goff and colleagues [24].At facility C, the head nurse was responsible for monitoring antimicrobial adherence and use and providing daily feedback to physicians.When there were few or only one infectious disease specialist across 800 beds, the excellent results obtained with the nurse-run ASP were similar to those of the study published by Monsees [25].
Following the implementation of ASP in the general wards of four healthcare facilities in Colombia, a decreasing trend in the consumption of all antibiotics studied was observed, but only statistically significant for carbapenems.The use of carbapenems has previously been associated with collateral damage that selects for multidrug-resistant bacteria [26,27,28,29].Therefore, reducing its consumption will have an impact on the incidence of drug-resistant flora in hospitals as well as cost savings.
In this study, the implementation of ASP showed a decrease in the incidence of CRO-R Eco, OXA-R Sau, MEM-R Pae, and MEM-R Aba.Other studies in Colombia have also demonstrated a reduction in extended-spectrum beta-lactamase (ESBL)-producing E. coli and increased resistance to third-generation cephalosporins [15, 16].Studies have also reported a reduction in the incidence of MEM-R Pae following administration of ASP [16, 18] and other antibiotics such as piperacillin/tazobactam and cefepime [15, 16].The design of this study cannot demonstrate that the results of bacterial resistance are entirely attributable to the implementation of ASP.Other factors influencing the reduction of resistant bacteria may include increased adherence to hand hygiene and cleaning and disinfection practices, and general awareness of AMR, which may or may not be relevant to the conduct of this study.
The value of hospital ASPs can vary widely from country to country.However, in a systematic review, Dilip et al.[30] showed that after implementing ASP, the average cost savings varied by hospital size and region.The average cost savings in the US study was $732 per patient (range 2.50-2640), with a similar trend in the European study.In our study, the average monthly cost of the most expensive items was $2,158 per 100 beds and 122.93 hours of work per 100 beds per month due to time invested by healthcare professionals.
We are aware that research on ASP interventions has several limitations.Measured variables such as favorable clinical outcomes or long-term reductions in bacterial resistance were difficult to relate to the ASP strategy used, in part because of the relatively short measurement time since each ASP was implemented.On the other hand, changes in local AMR epidemiology over the years may affect the results of any study.Furthermore, statistical analysis failed to capture the effects that occurred prior to ASP intervention [31].
In our study, however, we used a discontinuous time series analysis with levels and trends in the pre-intervention segment as controls for the post-intervention segment, providing a methodically acceptable design for measuring intervention effects.Since breaks in the time series refer to specific points in time at which the intervention was implemented, the inference that the intervention directly affects outcomes in the post-intervention period is reinforced by the presence of a control group that never had the intervention, and thus, from the pre-intervention to the post-intervention period no change.Furthermore, time series designs can control for time-related confounding effects such as seasonality [32, 33].Evaluation of ASP for interrupted time series analysis is increasingly necessary due to the need for standardized strategies, outcome measures, and standardized measures, and the need for time models to be more robust in assessing ASP.Despite all the advantages of this approach, there are some limitations.The number of observations, the symmetry of the data before and after the intervention, and the high autocorrelation of the data all affect the power of the study.Therefore, if statistically significant reductions in antibiotic consumption and reductions in bacterial resistance are reported over time, the statistical model does not allow us to know which of the multiple strategies implemented during ASP is the most effective because All ASP policies are implemented simultaneously.
Antimicrobial stewardship is critical to addressing emerging AMR threats.Assessments of ASP are increasingly reported in the literature, but methodological flaws in the design, analysis, and reporting of these interventions hinder the interpretation and wider implementation of apparently successful interventions.Although the number of large ASPs has grown rapidly internationally, it has been difficult for the LMIC to demonstrate the success of such programs.Despite some inherent limitations, high-quality interrupted time-series analysis studies may be useful in analyzing ASP interventions.In our study comparing the ASPs of four hospitals, we were able to demonstrate that it is possible to implement such a program in an LMIC hospital setting.We further demonstrate that ASP plays a key role in reducing antibiotic consumption and resistance.We believe that, as a public health policy, ASPs must receive national regulatory support, bearing in mind that they are also currently part of the measurable elements of hospital accreditation related to patient safety.
Post time: May-18-2022