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ORIGINAL ARTICLE
Year : 2023 | Volume
: 9
| Issue : 2 | Page : 53-59
Use of a regression model and a statistical process control method to assess AWaRe classification-based antimicrobial consumption in an Indian tertiary care hospital over 5 years
Alka Bansal1, Punam Jakhar2, Kamal Kant Trivedi2, Nidhi Bansal3, Smita Jain4, Neha Sharma1
1 Department of Pharmacology, SMS Medical College, Jaipur, Rajasthan, India
2 Department of Pharmacology, RUHS-CMS, Jaipur, Rajasthan, India
3 Department of Chemistry, JECRC, Jaipur, Rajasthan, India
4 Department of Mathematics and Statistics, JECRC, Jaipur, Rajasthan, India
Correspondence Address:
Dr. Alka Bansal
Department of Pharmacology, SMS Medical College, Jaipur, Rajasthan
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ijam.ijam_77_22
Introduction: The World Health Organization (WHO) recommends quality-based “AWaRe classification of antibiotics” for the monitoring of antimicrobial consumption. It classifies commonly used antimicrobials into five main categories: Access, Watch, Reserve, Not-recommended (NR), and Others. At least 60% of total consumption should be from the Access category and <10% should be from the Reserve category to minimize the further development of resistance. However, we do not know how these recommendations compare with current trends in antimicrobial consumption in India. Hence, a study was planned to statistically evaluate the AWaRe classification-based trend of antimicrobial consumption over 5 years.
Materials and Methods: A retrospective study was conducted to retrieve the antimicrobial consumption data of SMS Hospital, Jaipur, from January 2017 to December 2021 as per AWaRe classification. Regression and statistical process control analysis was carried out separately for all five categories of antimicrobials on MATLAB 2016a (9.0.0.341360).
Results: Regression analysis revealed that the consumption of Access, NR, and Others significantly decreased while that of Watch and Reserve increased between 2017 and 2021. Statistical process control analysis showed that the use of Access, Watch, and Others was within prescribed statistical limits but that of Reserve and NR was higher than statistical thresholds at times.
Conclusion: The increased consumption of Watch and Reserve antimicrobials combined with surpassing of upper control limit by Reserve and NR antimicrobials at certain times raises concern. Hence, there is an acute need to take measures to generate awareness about the incorporation of the WHO recommendations in practice to support the antimicrobial stewardship program.
The core competencies addressed in this article are: Medical knowledge, Systems-based practice, Practice-based learning and improvement, Professionalism.
Keywords: Antimicrobial consumption, antimicrobial resistance, AWaRe classification of antimicrobials, regression model, statistical process control method
Nearly 70,000 patients die every year due to resistant infections as per the World Health Organization (WHO) report.[1] The antimicrobial stewardship program (AMSP) and Schedule H-1 (2013) were started in an attempt to tackle the problem of progressive antimicrobial resistance by regulating the sale and consumption of antimicrobials in India.[2],[3] AMSP is based on 5 Ds: right Diagnosis, right Drug (antimicrobials), right Dose, De-escalation, and Discontinuation of therapy.[4] Initially, it covered inpatients, but it has been expanded to include ambulatory patients (except surgery) also from January 1, 2020.[5] Previously, daily defined doses or days of therapy were used to assess antimicrobial consumption, but both had limitations of assessing the consumption only quantitatively and were incapable to assess it qualitatively for resistance.[6]
To overcome this limitation and make AMSP more effective and useful, the WHO put forth an additional quality-based AWaRe tool for antibiotic consumption in 2017 and revised it in 2019.[7],[8] It classifies commonly used antimicrobials into three main categories: Access (A), Watch (Wa), and Reserve (Re) represented by green, amber, and red colors, respectively, based on safety and propensity to develop resistance [Table 1]. Access is the safest antibiotic category and should be primarily used if the organism is sensitive. Watch and Reserve group antimicrobials are the main targets for the surveillance program. Not-recommended (NR) and Others (O) are two additional groups of antimicrobials that lack evidence for utility and hence their use should be discouraged. The Others category was removed in the 2019 version of the WHO AWaRe tool. Many antimicrobials in each major category are common to the WHO Model List of Essential Medicines (WHO-EML) and National List of Essential Medicines, varying from country to country. Here, it is to recall that essential medicines satisfy the priority health-care needs of the population, and the EML is prepared by experts after considering the disease prevalence, efficacy, safety, and comparative cost-effectiveness of the medicines. The WHO-EML 2019 has 20, 12, and 7 antimicrobials common to the WHO list of 48, 110, and 22 antimicrobials belonging to the Access, Watch, and Reserve groups, respectively [Table 1].[9] The WHO further recommends that at least 60% of total antimicrobials used should be from the Access category and <10% should be from the Reserve category to check the further development of resistance.[10],[11]
Table 1: Category-wise list of antibiotics common to the World Health Organization Model List of Essential Medicines 2019 and World Health Organization-recommended Access, Watch, Reserve List 2019However, we do not know how these recommendations compare with current trends in antimicrobial consumption. Hence, a retrospective study was planned to evaluate the AWaRe classification-based trend of antimicrobial consumption over 5 years with the help of the regression model and statistical process control method.
Materials and MethodsThe study was conducted in a tertiary care hospital in North India after obtaining institutional ethical permission via letter no 816 MC/EC/2020 dated October 29, 2020, and in strict compliance with the EQUATOR guidelines. The individual patient's consent was not required as this was a retrospective data review.
The 5-year antimicrobial consumption data (from January 2017 to December 2021) was retrieved from the drug distribution centers and warehouses on hospital premises every month. These pharmacies supply the medicines prescribed by practitioners in the hospital and maintain a proper record of the dispensed medications. The antimicrobials consumed during the years 2017 and 2018 were classified into Access, Watch, Reserve, NR, and Others categories as per the WHO tool 2017.[7] The data from 2019 to 2021 were classified using the WHO tool 2019.[8] Trend analysis of data was then carried out separately for all five categories of antimicrobials using the regression model and statistical process control method. Microsoft Excel 2010 was used for creating the database and analysis was performed on MATLAB 2016a (9.0.0.341360).
For data analysis, the data set of each category was fitted to a linear regression model using the following equation:
Y it = ai + bit + eit
where i is the category, Y it is the volume of antibiotics consumed in category i (dependent variable), t is the time (independent variable), ai is the intercept of category i, bi is the slope for category i, and e is the error term. The sign of the slope (+/−) reflects the increase or decrease in the consumption of antibiotics during the 5 years. Finally, analysis of variance (ANOVA) was applied to test the relationship between antibiotic category and time (in months), and the results were considered statistically significant at a 0.05 level of significance.
ResultsWe first report some descriptive results and their interpretation. The three most commonly used antimicrobials from 2017 to 2021 are shown in [Table 2].
Table 2: Commonly used antimicrobials in decreasing order along with category from 2017–2021As it is clear from [Table 2], in the initial year of the study, Access dominated the commonly used antimicrobials triad. However, in later years, the Watch group started dominating.
Now, we come to statistical analysis.
[Figure 1]a shows the fitted linear regression line for the Access category. Its P value is < 0. 0001. The downward slope of the regression means the consumption of Access antimicrobials continuously decreased during the period of 5 years.
Figure 1: (a) Regression model showing the original data and the fitted trend line of consumption of Access antibiotics (b) Statistical process control method showing UCL and LCL of Access antibiotics. UCL = Upper control limits, LCL = Lower control limits[Figure 1]b shows the statistical process control method limits (upper and lower control limits represented by UCL and LCL, respectively) of the data. Except for two data points, all other data of Access antimicrobial consumption were within the range of LCL to UCL.
Similarly, in [Figure 2]a, it is clear that the consumption of the Watch group of antimicrobials continuously increased over 5 years. ANOVA test proved that the relationship between the volume of Watch and time (month) was statistically significant (P < 0.0001). [Figure 2]b shows that the consumption of Watch antimicrobials was within the prescribed limits.
Figure 2: (a) Regression model showing the original data and the fitted trend line of consumption of Watch antibiotics (b) Statistical process control method showing UCL and LCL of Watch antibiotics. UCL = Upper control limits, LCL = Lower control limitsIn [Figure 3]a, a positive (increasing) trend for the volume of consumption of Reserve antimicrobials is revealed by the regression model. P = 0.0001 shows that the trend is statistically significant. [Figure 3]b shows that the Reserve antimicrobials were consumed in a very high amount in 2020 as some points in this period are well above the UCL.
Figure 3: (a) Regression model showing the original data and the fitted trend line of consumption of Reserve antibiotics (b) Statistical process control method showing UCL and LCL of Reserve antibiotics. UCL = Upper control limits, LCL = Lower control limitsFor the NR group of antibiotics, the regression model and ANOVA indicated a statistically significant (P < 0.000) decrease in consumption after 2019 [Figure 4]a. [Figure 4]b shows that its consumption was a very high amount at some points between 2017 and 2019. This is an important finding as the WHO does not support the use of this group of antimicrobials due to a lack of evidence.
Figure 4: (a) Regression model showing the original data and the fitted trend line of consumption of NR antibiotics (b) Statistical process control method showing UCL and LCL of NR antibiotics. NR = Not-recommended, UCL = Upper control limits, LCL = Lower control limitsFinally, the regression model and ANOVA for Others also found a statistically significant (P = 0.002) declining trend [Figure 5]a. [Figure 5]b shows that the use of the Others group of antibiotics was recently within the prescribed limits, though it was higher in the initial years.
Figure 5: (a) Regression model showing the original data and the fitted trend line of consumption of Others antibiotics (b) Statistical process control method showing UCL and LCL of Others antibiotics. UCL = Upper control limits, LCL = Lower control limitsBased on the slopes of the five trend lines, it is inferred that the increment rate is highest for the Watch (b = 0.3030) followed by Reserved (b = 0.2336). In contrast, the decrease rate is highest for Others (b = −0.0018) followed by Access (b = −0.5591).
DiscussionWhile the WHO has come up with the recommendation to use 60% Access antimicrobials as an “optimum use” of antimicrobials, there is a need to compare this recommendation with current practice.
The use of the regression model for temporal evaluation of categorical antimicrobial consumption in our study conducted at a tertiary care hospital revealed that the consumption of Access antimicrobials has decreased continuously in India for the last 5 years with a maximum decline noticed in the year 2017–18 where it plunged from 53.3% to 41.2%. This is consistent with the data reported from Shaanxi province, where between 2015 and 2018, the consumption of the Access group decreased from 43.76% to 40.31%.[12]
On the contrary, the overall proportion of antimicrobials used in England within the Access category increased year on year from 2011 to 2016 from 60.2% to 63.3% of total prescribing (5% increase).[13] A meta-analysis to estimate the prevalence of antibiotic consumption showed that Access antimicrobials accounted for more than 60% of consumption in 12 out of 16 studies from low- and middle-income countries. However, the meta-analysis was particularly limited to the primary care level where comparatively formulary restriction is followed, especially for the Reserve and Watch groups of antimicrobials.[14]
In another study in a Swiss primary care setting based on 27,829 patients' electronic records from 2008 to 2020 on the WHO AWaRe classification scale, 57.9% of antimicrobials belonged to Access and 41.7% belonged to the Watch group.[15] As such, this confirms that developed countries show a comparatively judicious use of the Access group. In contrast, developing countries exhibit deviation from the WHO recommendations.
Our study also reported that two (amoxicillin-clavulanic acid and metronidazole) of the three most commonly consumed antimicrobials in 2017 belonged to the Access category, but from 2018 onward, cephalosporins (cefixime and ceftriaxone) from Watch were included among the three most frequently used antimicrobials except in 2020 when azithromycin (Watch) dominated. Similar studies by Patil and Agarwal and Sangeda et al. found amoxicillin, metronidazole, tetracycline, ciprofloxacin, cefalexin, and azithromycin among the top-ranking antibiotics.[16],[17]
The regression model in our study revealed a rising trend in the consumption of the Watch and Reserve groups of antimicrobials in India [Figure 2] and [Figure 3]. Regarding the same, contradictory findings have been recorded from various parts of the world.[14],[18],[19] While Budd et al. found a decrease in the Watch and Reserve categories, a global study conducted in 69 countries reported Watch antimicrobials making up 66.1% of total use in Western and Central Asian hospitals.[13],[14],[18],[19]
Cephalosporins (ceftriaxone and cefixime) were the most commonly used antimicrobials in our analysis, followed by macrolides (azithromycin), as in the majority of other similar studies. However, one survey found carbapenem (meropenem) and aminoglycoside (amikacin) to be the most often prescribed antimicrobial groups.[20]
The current investigation found a persistent upward trend for Reserve antimicrobials, and the usage was occasionally quite high in 2020 [Figure 3]. This increased use of Reserve antimicrobials in 2020 was probably due to the naive, potentially lethal COVID-19 viral pandemic at that time. Contrary to our research's findings, a few studies showed very little use of reserve antibiotics.[14],[21]
Consumption of NR and Other group antimicrobials was high in the early years of our study, but it gradually declined [Figure 4] and [Figure 5]. North Africa reported the highest percentage (2.3%) of consuming NR antimicrobials, and cefoperazone and beta-lactamase inhibitors combination accounted for 64.9% of all NR-antibiotic prescriptions worldwide.[14]
Another important conclusion from the statistical process control method in our study was that the UCL and LCL for the uses of the Access, Watch, and Others groups of antimicrobials were within the prescribed limits. On the other hand, the same statistical model divulged that the use of NR antimicrobials was very high in the years 2017–2019. Similarly, the use of Reserve antimicrobials was otherwise within the prescribed limits except in 2020 when their use was a very high amount as some points in the graph during this period are above the UCL. Such statistical results have not been reported in prior literature and future research should focus on a similar analysis of data from other settings.
The change of pattern of consumption from Access to Watch and Reserve antimicrobials can be due to either (i) an increase in drug resistance or (ii) a limited supply of Access antimicrobials (less likely as the study setting is the same).
It is also inferred from the process control method that the NR and Others whose use was notoriously higher in initial years have now decreased to be within normal limits or even lesser. This is a positive step in the direction of attaining the goal of optimum use of antibiotics.
The strengths of the study were that substantial data were collected over an extended period from the largest tertiary hospital in North India and is a retrospective observational study; the results document the actual situation in practice. However, there were a few limitations of the study. First, it was confined to antimicrobial consumption data from adult patients only. Second, it was restricted to one area of the country. Third, it did not cover any private and primary, community health centers in the government sector where considerable antibiotics are prescribed.
ConclusionThus, the study concludes that though the consumption of NR and Others has decreased markedly over the five periods of study duration as desired, the significant increase in consumption of Watch and Reserve antimicrobials along with surpassing of Reserve antimicrobials beyond the UCL at times raises concern. Hence, there is an acute need to generate awareness about the incorporation of the WHO recommendations in practice to support the AMSP. More studies at every level of patient care in different parts of the country will further help to get a better picture.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Ethical conduct of research
The authors of this manuscript declare that this scientific work complies with reporting quality, formatting, and reproducibility guidelines set forth by the EQUATOR Network. The authors also attest that Institutional Ethics Committee permission was taken via approval number 816 MC/EC/2020 dated October 29, 2020.
References
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