Antibiotics are critical in the treatment, management and prevention of infections, but inappropriate and excessive use has fuelled the emergence of antibiotic resistance – exacerbated during the pandemic, according to recent research.
A prominent driver associated with this resistance is inappropriate use or consumption, related to incorrect medical indication, antibiotic selection, dosing, route of administration and timeliness of antibiotic administration.
Some studies have shown they are incorrectly implemented in 30% to 50% of cases and that in intensive care units (ICUs), 30%-60% of antibiotics are unnecessary, inappropriate, or suboptimal. This degree of error accelerates resistance, resulting in poor patient outcomes, then coupled with the lack of antibiotic choices available.
Globally, antibiotic resistance has led to the deaths of ~700 000 people annually, which is predicted to surge to 10m by the year 2050.
Researchers from the Department of Pharmacy and Pharmacology at the University of the Witwatersrand carried out a study to compare antibiotic consumption among ICU patients admitted to a Gauteng provincial tertiary hospital during the pre-Covid-19 period and during the pandemic, and to determine the prevalence of the World Health Organisation (WHO) ‘watch’ category antibiotics before and after the emergence of Covid-10.
They found a rise in the prescribing of macrolides and penicillin classes of antibiotics transitioning from the pre-pandemic period into the Covid-19 pandemic, with the most frequently used and prescribed being azithromycin and amoxicillin in combination with clavulanate, they wrote in the SA Medical Journal.
WHO launches AWaRe
To understand the prevalence of antibiotic use, and to reduce consumption and resistance, the WHO introduced the Access, Watch, and Reserve (AWaRe) classification of antibiotics. The ‘Access’ category includes empiric first- or second-choice antibiotics with a narrow spectrum of antibacterial activity and a low potential for resistance.
Conversely, the ‘watch’ category includes antibiotics with a broader spectrum of antibacterial activity. However, antibiotics within this category are susceptible to a greater likelihood of resistance in comparison with antibiotics in the ‘access’ category.
Furthermore, ‘watch’ category antibiotics are used in patients with severe clinical manifestations that are characterised by bacterial resistance and where antibiotics within the ‘Access’ category cannot be considered for the treatment and management of infectious diseases.
The ‘Reserve’ category constitutes antibiotics with the highest potential of resistance, which are ‘last choice or last resort’. This means should are only to be prescribed and used in multidrug-resistant infections and in clinical instances where ‘access’ and ‘watch’ category agents are deemed unsuitable. The AWaRe classification of antibiotics objectifies the strengthening and monitoring of antimicrobial stewardship (AMS) programmes.
Local site
The study was conducted in the ICU of a township facility that was a National Department of Health designated Covid-19 hospital site. The hospital had a single main ICU until the year 2021, when a Covid-19 ICU was established to accommodate and quarantine infected patients.
The study authors said it was essential to include the novel Covid-19 ICU to potentially determine whether antibiotics used in those infected patients differed from antibiotics used in the non-infected individuals.
Therefore, both ICUs were considered.
Medical files of patients admitted to the ICU between January 2017 and December 2021 were reviewed. Periods before January 2020 were considered pre-pandemic, and the period during and after January 2020 was considered the pandemic period.
Eligible medical files included patients of various races and and socio-demographic statuses, and criteria also encompassed those aged ≥18 years receiving ICU-initiated antibacterial pharmacotherapy. All medical files pertaining to antibiotics prescribed between January 2017 and December2021 were considered.
Common diagnosis categories
During the pre-pandemic period, the most common diagnoses for which antibiotics were prescribed included respiratory conditions (22.1%; n=38) and neurological conditions (20.9%; n=36).
During Covid-19, the prevalence of most diagnosis categories decreased, apart from respiratory conditions, which increased to 33.7% (n=55). Furthermore, cardiovascular, dermatological, endocrinological and gynaecological conditions showed minor increases in observations.
Common diagnoses by Covid-19 status
Respiratory conditions made up the largest proportion of diagnoses, with Covid-19 -positive cases accounting for 54% (n=41). The majority of the diagnoses, not considering respiratory conditions, constituted the overall Covid-19-positive incidence (n=76).
Prescriptions in the ICUs included 21 antibiotics derived from 10 pharmacological classes, the most commonly prescribed in the pre-pandemic period including penicillins and extended beta-lactamase inhibitors, cephalosporins and macrolides.
The most commonly prescribed antibiotics within these classes were amoxicillin/clavulanate (pre-pandemic 31.99%; Covid-19 38.43%), followed by ceftriaxone (pre-pandemic 15.44%; Covid-19 14.55%), piperacillin/tazobactam (pre-pandemic 11.40%; Covid-19 8.58%) and azithromycin (pre-pandemic 7.72%; Covid-19 19.78%).
The overall trend observed was a decline in antibiotic usage in the pre-pandemic period in comparison with the Covid-19 period. This was noted within antibiotic classes as well as in individual antibiotics, particularly amoxicillin/clavulanate (access category antibiotic, penicillins and extended beta-lactamase inhibitor class).
Among the macrolides class observed, azithromycin prescribing increased across the pre-pandemic period to the Covid-19 pandemic period.
The ‘access’ group of antibiotics showed an increase in prescribing of approximately 7% after the start of Covid-10.
‘Watch’ antibiotics decreased in use by 8% from the pre-pandemic period to the Covid-19 period.
‘Reserve’ antibiotics were not prescribed among the study cohort in either pre-pandemic or Covid-19 periods. The ‘watch’ category (pre-pandemic 54.8%, n=149; Covid-19 51.1%, n=137) exceeded the ‘access’ category (pre-pandemic 45.2%, n=123; Covid-19 48.9%, n=131) across both periods.
Assessment
During the pre-pandemic period, over-use occurred in 17 out of the 21 antibiotics assessed, with nine of these antibiotics prescribed more than once. The drug that showed the greatest extent of overuse in the pre-pandemic period was amoxicillin/clavulanate.
The sub-use category reported 14 antibiotics out of the 21 antibiotics in the sample, which further indicated that nine out of 21 antibiotics were prescribed more than once during the pre-pandemic period.
Amoxicillin/clavulanate represented the higher proportion of sub-use.
Optimal use was reported in 14 out of the 21 antibiotics assessed, and eight out of 21 antibiotics were prescribed more than once during the pre-pandemic period.
Antibiotics optimally used across both periods of the study included ceftriaxone, azithromycin and metronidazole. During the pandemic, overuse occurred in 11 out of the 21 antibiotics assessed, with six of 21 antibiotics being prescribed more than once.
Amoxicillin/clavulanate, as in the pre-pandemic period, showed the greatest extent of use in the Covid-19 period. Azithromycin, ceftriaxone and metronidazole, similarly to the pre-pandemic period, constituted the higher proportions of optimal use. A relatively lower measure of sub-use was reported in eight out of the 21 antibiotics assessed in comparison
Conclusion
Findings concluded that overall, the ‘watch’ category prescription volume exceeded that of the ‘access’ category, deviating from the prospects of the WHO AWaRe system that advocates the availability and use of access category antibiotics as first-line agents for global health coverage.
Moreover, a decrease in ‘watch’ category antibiotics was seen transitioning into the Covid-19 period, with the adverse incline of azithromycin prescriptions within the category, indicating the need for improved AMS practices and stricter prescribing practices across both ‘access’ and ‘watch’ categories.
The authors said their findings could be used as an initiation point in the implementation, strengthening and adaptation of antibiotic stewardship programmes that should be built to include pandemic factors, such as drug repurposing.
They suggested that furthermore, a sustainable reporting antibiotic surveillance framework built around the operational characteristics and resource parameters of a healthcare setting was necessary to achieve improved antibiotic review and feedback systems.
This study was conducted in just one facility, but even with this inherent limitation of the study, the methodology adopted is adequate to provide insight to potential antibiotic prescribing and usage trends between the pre-Covid-19 period and the Covid-19 pandemic in the SA public healthcare system, they said.
Future studies should focus on factors associated with inappropriate prescribing during the pandemic in the public healthcare system and the consumption of antibiotics in all hospital wards, across various hospital levels (district, regional, tertiary, and quaternary), and inter-provincially, which would be critical in establishing a national antibiotic consumption baseline
Study details
The pattern of antibiotic utilisation among intensive care unit patients hospitalised in a Gauteng (South African) provincial tertiary hospital: Comparing findings before and during Covid-19
L Spinickum, Z Booth, S Leigh.
Published in the SA Medical Journal in July 2024
Background
Various mechanisms may contribute to and direct the progression of antibiotic resistance. A prominent driver associated with antibiotic resistance is inappropriate use or consumption. The sudden emergence of coronavirus disease 2019 (Covid-19 ) changed the conventional practices related to antibiotic utilisation through repurposing the use of antibiotics. Apart from the implementation of antibiotic stewardship programmes, the pressure Covid-19 placed on healthcare systems resulted in poor prescribing and medication review practices, potentially exacerbating antibiotic resistance. Furthermore, the public health system has issues that make it difficult to routinely monitor, quantify antibiotic consumption, and offer evaluation, feedback and intervention, particularly in low- and middle-income countries such as South Africa. This study aimed to determine antibiotic utilisation before and during the pandemic in a Gauteng provincial tertiary hospital (GPTH).
Objective
To determine, examine, and compare antibiotic consumption among intensive care unit (ICU) patients admitted to a GPTH during the pre-Covid-19 period and during the pandemic, in addition to determining the prevalence of the World Health Organisation (WHO) ‘watch’ category antibiotics before and following the emergence of Covid-19 .
Methods
A retrospective cross-sectional data analysis was undertaken of 335 medical files of ICU patients hospitalised in a GPTH between January 2017 and December 2021. Descriptive statistics were used to examine patient characteristics and antibiotic prescribing variables (antibiotic selection, dosage, route of administration, frequency, duration of course and indication for which antibiotic was prescribed).
Results
The study found that the most frequently prescribed antibiotics were amoxicillin in combination with clavulanate (pre-pandemic 31.99%; amid-Covid-19 38.43%), followed by ceftriaxone (pre-pandemic 15.44%; amid-Covid-19 14.55%), piperacillin in combination with tazobactam (pre-pandemic 11.40%; amid-Covid-19 8.58%) and azithromycin (pre-pandemic 7.725%; amid-Covid-19 19.78%).
Conclusion
The macrolide and penicillin (in combination with a beta-lactamase inhibitor) classes demonstrated an increase in consumption from the pre-pandemic period moving into the pandemic. This highlights the need for improved antibiotic stewardship programmes and policies to combat inappropriate and unnecessary antibiotic usage.
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