Experience of rigorous practice of antimicrobial stewardship program and its impact on antibiotic consumption

INTRODUCTION

Antimicrobial resistance (AMR) has emerged as a global public health and development threat. The urgency of addressing AMR demands immediate collaborative efforts across various sectors to achieve the objectives outlined in the Sustainable Development Goals 2023 by the United Nations.^[1] According to the Institute for Health Metrics and Evaluation, drug-resistant illnesses were directly responsible for 1.27 million fatalities in 2019, with most of the fatalities from sub-Saharan Africa and South Asia.^[2] Even under optimistic scenarios, AMR could lead to an annual decline in the economy, amounting to 1.1% of global gross domestic product by the year 2050. However, this is projected to escalate up to 3.8% annually if decisive measures are not taken.^[2]

Antimicrobial stewardship program (AMSP) is a healthcare strategy that has been advocated as the most efficient process indicator for tackling AMR in an organization or state. Many low- and middle-income countries are in the process of developing and implementing various forms of AMSP for curtailment of AMR. The success of AMSP is based on the judicious use of antimicrobials through evidence-based interventions.^[3-5] Multiple studies have demonstrated the positive impact of AMSP in monitoring AMR and its subsequent curtailment.^[6,7] Monitoring quantitative antibiotic consumption is one of the core components of ASMP. It facilitates comparison over the time frame within a healthcare facility in larger districts or even countries. Commonly used metrics are the defined daily dose (DDD) index and days of therapy (DOT). The anatomical therapeutic chemical/DDD (ATC/DDD) index is developed and maintained by the World Health Organization (WHO). ATC/DDD is a standardized method for evaluating in-hospital antibiotic use. It categorizes drugs, including antibiotics, based on their therapeutic or chemical properties and defines a standardized DDD for each drug. The WHO Collaborating Centre for Drug Statistics Methodology updates and maintains this index, making it a valuable tool for monitoring drug utilization trends, promoting responsible antibiotic use, and addressing antibiotic resistance.^[8] DDD represents the quantity of drug a typical patient might receive on any given day for therapeutic purposes. Another approach to evaluating antibiotic usage involves directly measuring the number of DOT. This encompasses summing up the total days of exposure to antibiotics. DDD metrics provide insights into the average quantity of antimicrobials consumed. DOT, on the other hand, offers greater clinical relevance for healthcare providers. DOT may be calculated from various sources, such as dispensing from the pharmacy, nursing dispense charts, or actual consumption by the patient at the bedside. Among these various ways of calculating DOT, the data generated by actual consumption is the most accurate and relevant measure. These consumption measures of drugs (DDD and DOT) are presented as rates within a time frame. For antibiotic usage, these measurements involve expressing DDD or DOT per 1000 or 100 patient days for different population sizes.^[9]

The present study was conceived to document the baseline antibiotic consumption rate in DDD and DOT metrics and subsequent improvement, if any, after the initiation of AMSP in selected areas of the hospital.

MATERIALS AND METHODS

RESULTS

Antibiotic consumption rates

DDD

The detailed quarter-wise consumption of the ICMR priority antibiotics is provided in Table 2. The average DDD/100 patient days in decreasing order of the various ICMR priority antibiotics in high priority areas were as follows: Meropenem (77.9), colistin (41.4), piperacillintazobactam (13.5), vancomycin (7.5), and cefoperazone (4.2). The average DDD/100 patient days in decreasing order of the various ICMR priority antibiotics in low-priority areas were as follows: Meropenem (45.4), piperacillin-tazobactam (22.6), cefoperazone (5.0), vancomycin (2.3), and colistin (1.8) as mentioned in Table 2.

Table 2: Area-specific antibiotic consumption rate (DDD/100 patient days).

Antibiotic	High-priority areas				Low-priority areas
	Q1	Q2	Q3	Average	Q1	Q2	Q3	Average
Colistin	239.6	94.32	38.9	41.4	0.0	3.9	11.9	1.8
Meropenem	339.6	256.3	105.3	77.9	54.6	309.5	44.8	45.4
Vancomycin	13.1	36.7	17.6	7.5	6.3	5.1	9.1	2.3
Piperacillin-tazobactam	31.9	47.3	42.6	13.5	44.6	87.3	71.9	22.6
Cefoperazone	21.4	6.2	10.2	4.2	19.0	25.9	0.0	5.0

DDD: Defined daily dose, Q1: Quarter 1, Q2: Quarter 2, Q3: Quarter 3, Q4: Quarter 4

DOT

The average DOT/100 patient days in decreasing order of the various ICMR priority antibiotics in high priority areas were as follows: Meropenem (40.5), colistin (20.9), piperacillintazobactam (15.7), vancomycin (3.9), and cefoperazone (3.8). The average DOT/100 patient days in decreasing order of the various ICMR priority antibiotics in low-priority areas were as follows: Meropenem (45.4), cefoperazone (44.9), piperacillin-tazobactam (22.6), vancomycin (2.3), and colistin (1.8) as mentioned in Table 3.

Table 3: Area-specific antibiotic consumption rate (DOT/100 patient days).

Antibiotic	High-priority areas				Low-priority areas
	Q1	Q2	Q3	Average	Q1	Q2	Q3	Average
Colistin	104.7	46.9	36.2	20.9	0.0	3.9	11.9	1.8
Meropenem	178.7	111.2	75.0	40.5	54.6	309.5	44.8	45.4
Vancomycin	13.5	3.7	17.7	3.9	6.3	5.1	9.1	2.3
Piperacillin-tazobactam	38.7	55.5	47.3	15.7	44.6	87.3	71.9	22.6
Cefoperazone	21.3	4.7	8.3	3.8	19.0	25.9	0.0	44.9

DOT: Days of therapy, Q1: Quarter 1, Q2: Quarter 2, Q3: Quarter 3, Q4: Quarter 4

The trends of antibiotic consumption are depicted in Figure 1. There was an overall sharp decline in the consumption rate of most ICMR-priority antibiotics, as shown in Figure 1.

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Figure 1:

Quarter-wise trend in defined daily dose and days of therapy per 100 days: (a) High-priority areas (b) Low-priority areas. COL: Colistin, MEM: Meropenem, VAN: Vancomycin, PTZ: Piperacillin-tazobactam, CFM: Cefoperazone, Q1: Quarter 1, Q2: Quarter 2, Q3: Quarter 3, Q4: Quarter 4. DOT: Days of therapy, DDD: Defined daily dose

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On comparison among both the used tools, i.e., DDD and DOT as a measure of consumption of antibiotics, we observed an almost linear correlation between these two tools as depicted in Figure 2.

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Figure 2:

Correlation of antibiotics between defined daily dose/100 patient days and days of therapy/100 patient days. (a) Colistin (b) Meropenem (c) Vancomycin (d) Piperacillin/tazobactam (e) Cefoperazone. DOT: Days of therapy, DDD: Defined daily dose

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DISCUSSION

DDD and DOT have often been used as a standardized tool to measure antimicrobial consumption.^[13] Many developed nations, including the USA and European Nations, use these tools per 100 patient days to quantify and compare the consumption of antibiotics across various healthcare delivery facilities.^[14-17] Though these methods serve as benchmark tools to measure antibiotic consumption, multiple studies have brought out some shortcomings. The limitations are attributed to conditions where case-based dose adjustments are made in scenarios of varied pharmacokinetic situations (decreased hepatic or renal function or in pediatric populations). Apart from these situations, prescription writing practices in developing nations such as India are not strongly regulated and may not always follow the WHO-approved DDD.^[18-23]

In our study in high-priority areas, the average DDD/100 patient days was highest for meropenem (77.9), followed by colistin (41.4) and piperacillin-tazobactam (13.5), as shown in Table 2 and Figure 1. The comparative DDD/100 patient days in the 1^st and 3^rd quarters revealed that there was a significant decrement for meropenem and colistin. The minor increment in usage of piperacillintazobactam is self-explanatory in view of the reduction in high-end antibiotics such as meropenem and colistin. In our study in low-priority areas, the average DDD/100 patient days was highest for meropenem (45.4), followed by piperacillintazobactam (22.6) and cefoperazone (5), as presented in Table 2 and Figure 1. In comparison to the first quarter, the DDD/100 patient days in the last quarter were significantly decreased for meropenem, piperacillin-tazobactam, and cefoperazone. However, there was an increment in the use of colistin DDD/100 patient days which may be explained by more and more sicker patients being treated in the general ward. However, this might be a situation where, in pursuit of decreasing the antibiotic exposure, we might have under-treated initially and there was a subsequent terminal knee-jerk correction.

In our study in high-priority areas, the average DOT/100 patient days were maximum for meropenem (40.5), followed by colistin (20.9) and piperacillin-tazobactam (15.7), as mentioned in Table 3 and Figure 1. While comparing the DOT from the first quarter to the third quarter, it was observed that there was a significant decrease in the usage of meropenem, colistin, and piperacillin-tazobactam. In our study in low-priority areas, the average DOT/100 patient days were maximum for meropenem (45.4), followed by cefoperazone (44.9) and piperacillin-tazobactam (22.6), as mentioned in Table 3 and Figure 1. While comparing the DOT from the first quarter to the third quarter, it was observed that there was a significant decrease in the usage of meropenem and cefoperazone and a minor increase in piperacillin-tazobactam, which is self-explanatory. However, the increment in consumption of colistin may be explained by the theory of knee-jerk correction as already explained under the section of DDD.

Our study documents a strong direct linear correlation between DDD and DOT for all the studied antibiotics. This is in contrast to similar studies earlier conducted in India by Saudi Arabia by Balkhy et al., (2018), in India by Patra et al., (2020), and in Spain by Vallès et al., (2020).^[24-26] A detailed comparison between similar studies across the globe is presented in Table 4.

In the current study, the baseline (first quarter) DDD and DOT of most antibiotics were much higher than in comparison to the developed nations such as the United Nations, European nations, and Saudi Arabia. The details of the comparative values are provided in Table 4. However, it is extremely encouraging that with the implementation of AMSP, the third quarter DDD and DOT of most antibiotics were significantly decreased, almost equivalent to the developed nations, as presented in Table 4. The present study also documents that, the baseline consumption of vancomycin was, in fact, lesser than the United States, Australia, New Zealand, and Saudi Arabia but lesser than the European Nations as in Table 4.^[27-32] This could be attributed to the lesser prevalence rates of methicillin-resistant Staphylococcus aureus in India particularly in our Institute.^[33,34]

Although there is still a chase for a gold standard tool for the measurement of antibiotic usage and subsequent comparison, the WHO-ATC DDD and DOT/100 patient days are some of the best available tools with only minor disadvantages. The present study documented that DDD and DOT can be calculated even in large public sector hospitals with huge footfalls. The study also documented the significant positive impact of a well-planned AMSP in a significant decrement in antibiotic consumption and subsequent decrease in AMR in the community.

The study had several limitations. The study was only observational and case record-based. The consultants were free to choose their drug regimen and dosage without any specific protocol-based treatment plan. The study was carried out by trained and enthusiastic personnel specifically recruited for the purpose.

CONCLUSIONS

AMSP is one of the most effective measures for the containment of AMR. Although there are many facets of AMSP, simple measures such as writing an infection-related diagnosis, sending an appropriate sample for bacterial culture before writing an antibiotic, and conducting PPS from time to time are of utmost importance to decrease antibiotic consumption at healthcare facilities. Calculating WHO ATC DDD and DOT/100 days at the baseline and post-AMSP implementation can be used as a quantitative measurement of antibiotic usage and subsequent comparison from time to time. In resource-limited settings, only DOT/100 days may be practiced as it is less labor-intensive and has a positive co-relation with DDD/100 days.