The incidence of antimicrobial resistance is on the increase and is attributable to antibiotic misuse in communities and healthcare settings. Government policies to arrest this menace require scientific data from the health system and support from stakeholders for implementation. However, there is a paucity of data on antibiotic consumption in some health facilities in Ghana such as Tamale Teaching Hospital (TTH). This study was to assess the pattern of antibiotic consumption in inpatients and outpatients at the TTH, using the Defined Daily Dose (DDD) methodology. A retrospective cross-sectional study was therefore conducted. Data on antibiotic consumption was obtained using antibiotics issued to outpatients and inpatients at TTH from January to December 2021. The data were entered into Microsoft Excel® software, analyzed, and presented as frequencies, percentages, figures, and tables. The commonly available antibiotics are the cephalosporins (28%) and penicillins (20%) with most of them being in the Watch group (46%). Inpatients used more Access group antibiotics whilst outpatients used more Watch group antibiotics with no Reserve group antibiotics being used in all patient groups. The total antibiotic consumption in 2021 in DDD, was 323,764.4 corresponding to a DDD of 930.6 per 100 patients. A DDD of 629.9 per 100 inpatient admissions and 110 per 100 outpatients seen at the hospital were obtained. The ratio of antibiotic consumption in outpatients versus inpatients was 1:3, with intravenous antibiotics accounting for 16.3% of consumption in DDD among patients on admission. Similarly, oral antibiotics constituted 83.6% of total antibiotic use in DDD. The total DDD/100 patients increased from January to August 2021, overlapping with the initial 3 months of Foundation for Innovative New Diagnostics (FIND) antimicrobial stewardship intervention activities. Thereafter, there was a consistent reduction in antibiotic use through December 2021, which coincided with the last 3 months of FIND intervention activities. Antibiotics that witnessed a reduction in consumption were the penicillins, penicillin/inhibitor antibiotics, carbapenems, quinolones, and macrolides. The introduction of the antibiotic stewardship programme with FIND which is in line with Ghana’s Antimicrobial Resistance (AMR) policy was impactful and must be sustained.

Keywords: antimicrobial resistance; antimicrobial stewardship; defined daily doses; AWaRe; Anatomical Therapeutic Chemical (ATC) Classification

Most medications maintain their efficacy even when used by a lot of patients over time. Antibiotics are an important exception as they can become ineffective due to the bacteria developing resistance against them (Brunton et al., 2011; Ghana National Action Plan on Antimicrobial Resistance 2017). The misuse of antibiotics coupled with a lack of infection prevention and control measures has contributed to antimicrobial resistance which is currently a major challenge to global healthcare (Sekowska et al., 2002; WHO, 2019). Globally, antimicrobial resistance (AMR) is currently estimated to account for about 700,000 deaths per year and is projected to cost roughly 10 million lives and US$100 trillion per year by 2050 if no actions are taken to slow its progression (O’Neill, 2016; Tagliabue and Rappuoli, 2018; CDC, 2022).

The impact of AMR has become significant on healthcare costs and this is due to inappropriate consumption, which has been noted to be the main cause (Klein et al., 2018; Kallen, 2019). A retrospective assessment of antibiotics consumption globally has noted an increase of 65% from 2000 to 2015 and that is from 21.1 billion to 34.8 billion DDD. Due to this hike in consumption, World Health Organization’s (WHO) global action plan has been initiated to help reduce the supply and demand for antibiotics (Klein et al., 2018).

Several tools have been developed to monitor antibiotic utilisation to improve the quality of use. A Point Prevalence Survey (PPS) of antimicrobial consumption and resistance in adult hospital inpatients in 53 countries found that the top three antibiotics prescribed globally were penicillins with lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were the most frequently prescribed in Latin America and West and Central Asia (Versporten et al., 2018). Arute et al. (2011) also reported on the antibiotic prescription pattern in the pediatric ward of a tertiary healthcare facility in southern Nigeria using Drug Utilization 90% (DU 90%) (which is the number of drugs constituting 90% of the volume of prescribed drugs use in defined daily doses) and Defined Daily Dose (DDD), which is the assumed average maintenance dose daily of antimicrobial substances used for its main indication in adults. In Ghana, a study on antibacterial use at the Accident and Emergency Department of Komfo Anokye Teaching Hospital in Kumasi reported the DDD/100-bed days of cefuroxime oral and parenteral to be 75.85 and 36.12 respectively (Appiah, 2015). Also, a multicentre PPS across seven hospitals in Ghana found an overall prevalence of antibiotic use as 54.9%, with the five most commonly prescribed antibiotics being metronidazole (20.6%), cefuroxime (12.9%), ceftriaxone (11.8%), amoxicillin/clavulanic acid (8.8%), and ciprofloxacin (7.8%) (Larbi et al, 2021).

The DDD is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose, which is the prescribed dose for the main indication (in a hospital, ward, or group of hospitals). Therapeutic doses for individual patients and patient groups will often differ from the DDD as they will be based on individual characteristics (such as age, weight, ethnic differences, type and severity of disease) and pharmacokinetic considerations (Sözen et al., 2013; WHO,2017).

Only one DDD is assigned per ATC code and route of administration (e.g. oral formulation). 

Drug utilization data presented in DDDs only give a rough estimate of consumption and not an exact picture of actual use (WHO, 2017).

DDD methodology can be used to compare the antibacterial agents' consumption between countries, hospitals, or even departments within the same hospital. This method is used to determine the DDD per 100-bed days for antibacterials used within a healthcare facility during a period. For example, if the calculated DDD per 100 bed-days for cefuroxime use in a healthcare facility is 50 DDD per 100 bed-days, this implies that 50% of the patients may receive a DDD of cefuroxime every day.

In addition, the WHO has classified antibiotics into three categories as AWaRe: ‘Access’ (antibiotics used for common infections that are to be available and accessible, e.g. amoxicillin, amoxicillin/clavulanic acid, ampicillin, clindamycin, cloxacillin, etc.), ‘Watch’ (broad-spectrum antibiotics that should be used with caution due to their high potential to develop resistance, e.g. azithromycin, ceftazidime, cefuroxime, ceftriaxone, ciprofloxacin, erythromycin, vancomycin, etc) and ‘Reserve’ (antibiotics that should be reserved for the treatment of multidrug-resistant infections and to be used only when other alternatives fail, e.g. aztreonam, ceftazidime/tazobactam, linezolid, minocycline, tigecycline.) (WHO, 2019; Pauwels et al., 2021).

Understanding the utilization patterns of antimicrobials in Ghanaian hospitals is one way to check for antimicrobial use. This involves the collection of data to inform on drug utilization and its impact on health by using several means such as the DDD method proposed by WHO (WHO, 2017; Sarwar, 2017), and helps provide information to support policies such as the recent Ghana National Action Plan on Antimicrobial Use and Resistance implementation (Opintan, 2108). There is limited data on antibiotic usage patterns in health facilities, especially in northern Ghana. (Sözen et al., 2013; Yevutsey, 2017; Opintan, 2018; WHO, 2021).

JUSTIFICATION

The incidence of antibiotic resistance is on the increase, which is mainly attributable to inappropriate antimicrobial use, a common occurrence found in hospitals. Most government policies require information and support for implementation, and this applies to health-related policies such as the National Action Plan for Antimicrobial Use and Resistance (Ghana National Action Plan on Antimicrobial Resistance 2017-2021, 2017). However, there is a paucity of data on antibiotic consumption patterns of hospitals in Ghana which when well understood, can be used to achieve the objective of policies such as the National Action Plan on Antimicrobial Resistance.

Antimicrobial resistance is an extremely expensive problem, especially in developing countries such as Ghana. Some of the main causes of antibiotic drug resistance include antibiotic overuse, abuse, and in some cases, misuse, due to incorrect diagnosis (Zhang, 2007). The benefits of antibiotic therapy when indicated are enormous, but the continued use of antibiotics without any clinical evidence or microbiological justification is dangerous and could lead to adverse events (Tzialla et al., 2015).

This trend should be of concern because antimicrobial resistance is putting the gains of the Millennium Development Goals at risk and endangers the achievement of the Sustainable Development Goals (WHO, 2018). Consequently, antimicrobial resistance increases the cost of healthcare and the financial burden on the government and caregivers and is a disincentive to the gains made in healthcare delivery (Policy on Antimicrobial Use and Resistance for Ghana, 2017)

The Ghana National Action Plan on Antimicrobial Resistance strategic objective 1, sub-objective 2 recommends the establishment of a surveillance system for antimicrobial consumption to quickly track the development of resistance. However, this is yet to be implemented in some healthcare facilities in Ghana such as the Tamale Teaching Hospital. This research, therefore, seeks to study the pattern of antimicrobial consumption in the Tamale Teaching Hospital to understand antimicrobial consumption patterns, identify inappropriate use of antimicrobials and support the implementation of the Ghana AMR policy.

OBJECTIVE

·             To assess antibiotic consumption patterns of inpatients and outpateints at the Tamale Teaching Hospital using Defined Daily Dose methodology.

Study design

A retrospective cross-sectional study involving antibiotics issued from the Pharmacy Stores to all satellite pharmacies was conducted at TTH.   A data collection instrument was used to extract data on antibiotics issued from the electronic database of the Pharmacy Stores of TTH from January to December, 2021. The electronic database was assessed to document antibiotic stocks issued over the study period. Also, both inpatient admissions and outpatient attendance over the study period were obtained from the Biostatistics Record Unit of TTH.

Study setting

The study was conducted at TTH in the Northern Region of Ghana. It is the only tertiary health facility in the northern part of Ghana, has an 812-bed capacity, and serves over 2 million people living in the region and beyond. The hospital provides a range of specialist care services and receives referral cases from health facilities in the five regions of northern Ghana.

The Pharmacy Directorate of TTH is responsible for the supply of pharmaceutical products to patients. This includes the Pharmacy Stores from which all the 10 satellite pharmacies receive their drug requisitions. The satellite pharmacies include accident and emergency,  internal medicine, surgery, pediatric, neonatal intensive care unit, obstetrics and gynecology, urology, eye clinic, fevers unit, and Specialist pharmacy. Drug requisitions are made to the Pharmacy Stores based on the consumption pattern and stock level at the various satellite pharmacies twice weekly (i.e. Mondays and Thursdays).

Study population

The study included patients who used antibiotics over the review period.

Inclusion criteria

All parenteral and oral adult dosage forms of antibiotics dispensed were included in the study

Exclusion criteria

All oral pediatric dosage forms of antibiotics, anti-tuberculosis drugs, and topical antibiotics were not included in this study as they do not have a Defined Daily Dose.

Data analysis

Antimicrobial consumption pattern was monitored with pharmacy store records and presented per the WHO Anatomical Therapeutic Chemical (ATC) classification and DDD methodology. The collected data were computed and analyzed using Microsoft Excel (2019). The results were summarized using frequency, and percentages and presented as tables and figures.

The defined daily dose (DDD)/ 100 bed-days was calculated using the formula;

DDD/100 bed-days =          No. of units administered in a given period (mg) X 100

                                  DDD (mg) X no. of days in the period X no. of beds X occupancy index

Where the Occupancy index is the measure of actual utilization of an inpatient health facility for a given period. The occupancy index for TTH in 2021 was 87%

DDD was estimated monthly using antibiotic consumption and admissions and outpatient attendance.

Ethical approval consideration

Ethical approval was sought from the Research and Development Unit of TTH (TTH/R&D/SR/22/056).

A total number of 25 antibiotics across different classes were available in TTH from January to December 2021. Cephalosporins constituted about 24% (n=6) of antibiotics available in TTH as shown in table 1 below. Antibiotics names are the International Non-proprietary Name (INN)

Table 1: Antibiotics available in TTH and their WHO AWaRe Classification

A, Access (40%); W, Watch (46%); Re, Reserve (0); U, Unclassified (14%). 

In 2021, the total consumption of antibiotics expressed in DDD was 323,764.4 (Table 2). When the data were expressed as the DDD per patient category, the overall number of administered DDDs per 100 patients was 930.6. A DDD of 629.9 per 100 inpatient admissions and 110 per 100 outpatients seen at the hospital were obtained. Overall, the ratio of antibiotic consumption in outpatients versus inpatients was 1:3, with intravenous antibiotics accounting for 16.4% (n = 80914.2 DDD /242822.8 DDD) of the consumption among patients on admission. Similarly, oral antibiotics constituted 83.6% of total antibiotic use in DDD (n = 270697.7 DDD/ 323764.4 DDD).

Table 2: Antibiotic consumption indicators for Tamale Teaching Hospital, 2021

*DDD, Defined daily dose; IV, intravenous

Antibiotics consumption pattern from January to December, 2021 in DDD/100 admissions

Figure 1(a) shows a clear separation in DDD/100 patients in which the consumption trend among inpatients from January through December mirrored the consumption levels for the total patient population and exceeded the outpatient consumption levels by a factor of > 3 for all the months under study. The monthly consumption of antibiotics for all patients is shown in Figure 1(b) below. The total DDD/100 patients increased from January to August 2021, overlapping with the initial 3 months of FIND intervention activities. Thereafter, there was a consistent reduction in antibiotic use through December 2021. 

Relative changes in monthly antibiotic consumption in 2021

Table 3 shows the relative increase or decrease in antibiotic consumption expressed as percentages. Before the implementation of FIND interventions, antibiotic consumption in June was 108.2 DDD/100 admissions, representing a +44.7% relative increase in consumption from January (124.4 DDD/100 patients) through the next 6 months.  In contrast, antibiotic consumption declined from 108.3 DDD/100 patients in July compared to 34.2 DDD/100 admission in December, representing a relative decrease of -53.7% from November to December of FIND intervention activities. Table 3 shows that the reduction was favored mainly by a decrease in inpatient antibiotic consumption of -36.8% from July to December, driven by a high reduction in oral antibiotic use which fell by - 40.8% in the same period.

Table 3: Relative changes in monthly antibiotic consumption in 2021

                      Change in antibiotic consumption (DDD/100 admissions) from preceding month

Months in      Patient groups                                                                    Route of administration

2021              All          %          In-         %          Out-       %         Oral       %          IV          %

                   patients   change  patients  change  patients   change              change                change

*IV, intravenous antibiotics; %, percentage; “+”, increase; “-’’, decrease; FIND interventions were implemented from July to December

Antibiotic consumption by subgroup

Antibiotic consumption by ATC level 4 between the two study periods, January-June and July-December were compared, as shown in Figure 2. Within the entire patient population, very little difference in consumption by antibiotic class was observed between the two study periods (Figure 2a). In contrast, when antibiotic utilization was split between outpatients (Figure 2b) and inpatients (Figure 2c), there was a clear separation in the latter compared to the former where considerable reduction in DDD/100 patients was observed for many antibiotic groups in July-December.  Notably, it was observed there was approximately 40% reduction in the consumption of penicillins, and a>20% reduction in the consumption of penicillin/inhibitor antibiotics, carbapenems, quinolones, and macrolides. Exceptions were the cephalosporins, aminoglycosides, and glycopeptides which showed no considerable change in consumption. Among outpatients, only cephalosporins recorded a drop in antibiotic consumption in July-December.

The study revealed a reduction in the overall consumption pattern of antibiotics in both inpatients and outpatients in DDD/100 admissions from January to December, with the interventions being introduced within the second half of the year 2021.

Based on the WHO AWaRe classification, it was observed that most (46%) of the antibiotics were under the Watch classification with none of the antibiotics in the Reserve classification. About 40% of Access group antibiotics available are lower than the WHO country-level target of at least 60% of total antibiotic consumption being Access group antibiotics (Simmons et al., 2021). The pattern of antimicrobial use is partly due to the availability of certain antibiotics in the hospital (WHO, 2021). This was in direct relation to antibiotic consumption in inpatients where cephalosporins were found to dominate and this can be found in the Watch group (table 1). This is congruent with a study conducted by Knowles et al. (2020), where it was concluded that cephalosporins are the most commonly prescribed class of antibiotics in the world. The dominance of this class of antibiotics is attributable to its wider spectrum of activity, accessibility, relatively cheaper cost, and effectiveness (Pwint, 2017).

Having none of the antibiotics present under the reserved category confirms similar findings of studies conducted by Labi et al. (2018) and Amponsah et al. (2021). Knowing this pattern will therefore become helpful in identifying antibiotic resistance patterns and this would be a useful guide for individualized empiric or definite treatment. The highest consumed antibiotic for inpatients was penicillins, and these were found to be in the Access category (table 1). This could be due to affordability, availability, and spectrum of activity when compared to those in the Watch and Reserve group (Knowles et al., 2020). Our findings affirmed a study conducted across 69 countries by Pauwels et al. (2021) which stated that low-income countries utilize more of the Access category antibiotics (63%), followed by the Watch category antibiotics (36%) and no Reserve category prescriptions on adult wards in those 69 countries. Once there is a spike in the consumption of the Watch category of antibiotics, it shows a high rate of resistance in patients to the Access category of antibiotics. This can be alarming since overuse of this category can influence the spread of multidrug-resistant bacteria therefore measures are to be put in place to help address the consumption of this category of medicines (Cox, 2017). Antimicrobial consumption monitoring in the hospital is considered to be an important component of antimicrobial stewardship programs (Garcell et al., 2016).

From table 2, the total number of DDD of antibiotics was 323,764.4. This constituted more oral antibiotics 83.6% (n = 80914.2 DDD /242822.8 DDD) compared to intravenous forms 16.4% (n = 270697.7 DDD/ 323764.4 DDD). Comparisons cannot be drawn from the value obtained from this study as this antibiotic consumption study is the first of its kind to be conducted in TTH. However, higher annual DDD could have been recorded in the absence of the interventions made by FIND in the last six months of the year. The DDD outcomes to be obtained in the future may decrease further if there is continuous adherence to standard guidelines and policies established by FIND, interdisciplinary education, and cooperation between pharmacists, physicians, and microbiologists, as well as modern diagnostics, provided patient characteristics do not change significantly (Kuster et al., 2008; Wojkowska-Mach et al., 2018).

The impact of FIND interventions was monitored within the last six (6) months of the year and it was found that there was still an increase in antibiotic consumption initially but this was found to overlap with the initial 3 months of intervention implementation. However, it consistently reduced in December 2021 as shown in (Figure 1). These positive outcomes were possibly realized because of how fast the healthcare team adapted to the interventions made with FIND. They could also be due to activities of World Antimicrobial Awareness Week undertaken in November, 2021. A repeat of this study will help monitor the impact of the FIND interventions implemented. The DDD/100 patients obtained in this study could serve as a baseline for future antimicrobial consumption studies to be conducted to find out whether the interventions would be sustained with time or not before adjustments in the interventions could be made. 

Data on the relative changes in monthly consumption showed a reduction within the last 3 months of the year. Before the implementation of the interventions, antibiotic consumption was 108.2 DDD/100 in June indicating a +44.7% relative rise from January. However, the decline in DDD/100 observed was from 108.3 DDD/100 in July to 34.2 DDD/100 in December indicating a decrease of -53.7% from November to December. The outcomes observed in the study have proven that the implementation Antimicrobial Stewardship Program has an impact on antimicrobial consumption reduction as recommended by several studies (Pereira et al., 2004; Storey et al., 20212; Bozkurt et al., 2013; Wu et al., 2017) A study conducted by Tan et al. (2022) also recorded a reduction in antimicrobial consumption after the initiation of Antimicrobial Stewardship Activities.

There was a reduction in the consumption of penicillins, penicillin/inhibitor antibiotics, carbapenems, quinolones, and macrolides. In contrast, there was no remarkable decrease in the consumption of cephalosporins, aminoglycosides, and glycopeptides (figure 2). The inappreciable reduction in consumption of these classes may be due to their wider spectrum of activity, relatively cheaper cost, effectiveness, and accessibility especially cephalosporins (Pwint et al., 2021). This shows that there is a need for intensification of the FIND interventions which focus more on those that did not decrease appreciably. Further studies on the assessment of the antibiotic consumption pattern in the subsequent years are needed to help determine the long-term impact of the interventions.

The commonly available antibiotics are cephalosporins and penicillins with most of them being in the Watch group. Inpatients used more Access group antibiotics whilst no Reserve group antibiotics were used in all patient groups. The total number of DDD of antibiotics was 323,764.4, which constituted more oral antibiotics (83.6%) compared to intravenous forms (16.4%). There was a significant decrease in DDD/100 patients of -53.7% between November and December. Antibiotics that witnessed a reduction in consumption were penicillins, penicillin/inhibitor antibiotics, carbapenems, quinolones, and macrolides. The introduction of the antibiotic stewardship programme at TTH was impactful and must be sustained.

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