tugasepid_a2_ina hariska_1011_jurnal review (1)

antibiotics
Article
Pharmacoepidemiological Analysis of Antibacterial Agents Used
in a Provisional Hospital in Aktobe, Kazakhstan, in the Context
of COVID-19: A Comparison with the Pre-Pandemic Period
Aigerim A. Balapasheva 1, * , Gaziza A. Smagulova 1 , Aigul Z. Mussina 1 , Liliya E. Ziganshina 2,3,4
and Zhansulu Zh. Nurgaliyeva 1
1 Department of Pharmacology, West Kazakhstan Marat Ospanov Medical University,

Aktobe 030012, Kazakhstan; g.smagulova@zkmu.kz (G.A.S.); a.mussina@zkmu.kz (A.Z.M.);
pharma@zkmu.kz (Z.Z.N.)
2 Russian Medical Academy of Continuous Professional Education, 125993 Moscow, Russia
3 Department of General and Clinical Pharmacology, Peoples’ Friendship University of Russia Named after
Patrice Lumumba (RUDN University Named after Patrice Lumumba), 6 Miklukho-Maklaya St.,
117198 Moscow, Russia
4 Department of Pharmacology, Kazan State Medical University, 49 Butlerov Street, 420012 Kazan, Russia
* Correspondence: a.balapasheva@zkmu.kz; Tel.: +7-707-839-98-09
Abstract: In the context of the global spread of Coronavirus Disease 2019 (COVID-19), the issue of
evaluating and optimizing the use of antibacterial drugs becomes especially relevant. The coron-
avirus pandemic has provided a unique opportunity to study the dynamics of the consumption of
antibacterial agents and their impact on public health. The rational use of antibiotics is a key aspect
of the fight against antimicrobial resistance, which makes this study particularly important. The
aim of this study was to assess changes in the consumption of antibacterial drugs among patients
hospitalized with COVID-19 during the peak of the 2020 pandemic and compare them with data from
Citation: Balapasheva, A.A.;
2019 prior to the pandemic. This study collated data on antibacterial drug consumption in a regional
Smagulova, G.A.; Mussina, A.Z.;
hospital in Aktobe, which served a large population of patients during the pandemic. A pharmacoepi-
Ziganshina, L.E.; Nurgaliyeva, Z.Z.
demiological study was conducted using the Anatomical Therapeutic Chemical (ATC)/Defined Daily
Pharmacoepidemiological Analysis
Dose (DDD) methodology. The pharmacoepidemiological study using the international ATC/DDD
of Antibacterial Agents Used in a
Provisional Hospital in Aktobe,
methodology revealed a concerning pattern of irrational consumption of antibacterial drugs, includ-
Kazakhstan, in the Context of ing cephalosporins, azalides, second-generation fluoroquinolones, and systemic aminoglycosides
COVID-19: A Comparison with the in Aktobe. Among antibacterial drugs during the pandemic, the most significant increase in con-
Pre-Pandemic Period. Antibiotics sumption was from the group of cephalosporins (19,043 DDD/100 bed-days). The share of their
2023, 12, 1596. https://doi.org/ consumption was 35.4% of the total consumption of antibacterial drugs. Pharmacoepidemiological
10.3390/antibiotics12111596 studies using the international methodology ATC/DDD showed an alarming picture of irrational
Academic Editors: Shailendra K. consumption of antibacterial drugs of the group of cephalosporins, azalides, fluoroquinolones, and
Saxena and Swatantra Kumar aminoglycosides in Aktobe, and, in this case, excessive use of the identified antibiotics raises concerns
about the possibility of increasing the problem of resistance to microbes.
Received: 28 September 2023
Revised: 26 October 2023
Keywords: pharmacoepidemiological studies; COVID-19; antibiotic resistance; ATC/DDD methodology;
Accepted: 31 October 2023
antibacterial agents
Published: 6 November 2023
Copyright: © 2023 by the authors. 1. Introduction

Licensee MDPI, Basel, Switzerland. On 30 January 2020, the World Health Organization (WHO) declared the outbreak of
This article is an open access article severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a public health emer-
distributed under the terms and
gency of international concern. In Kazakhstan, the first cases of COVID-19, caused
conditions of the Creative Commons
by this coronavirus, were reported on 13 March 2020. At the onset of the pandemic,
Attribution (CC BY) license (https://
protocols for diagnosing and treating the infection were frequently updated as new
creativecommons.org/licenses/by/
information surfaced [1].
4.0/).
Antibiotics 2023, 12, 1596. https://doi.org/10.3390/antibiotics12111596 https://www.mdpi.com/journal/antibiotics

Antibiotics 2023, 12, 1596 2 of 11
Antibacterial drugs, designed to treat bacterial infections, are widely used in medicine.
They effectively eliminate or inhibit the growth of bacteria responsible for infections.
However, COVID-19 is caused by the SARS-CoV-2 virus, which was first identified in
Wuhan, Hubei Province, China, in late 2019.
Antibacterial drugs are not effective against viruses, including SARS-CoV-2. Thus,
antibacterial therapy is only prescribed to COVID-19 patients when there are clear signs
of a bacterial infection. For instance, antibiotics might be given to patients who have
pneumonia as a result of COVID-19, but this is based on general guidelines: the severity
of the patient’s condition, risk factors for infections by resistant bacteria, and etiological
diagnosis results are all taken into account. The utilization of antibacterial drugs during
the COVID-19 pandemic had several motivations:
Combatting secondary infections: COVID-19 patients were at a heightened risk of con-
tracting secondary bacterial infections, particularly in hospital environments. Antibacterial
medications, like azithromycin, were used either as a treatment or preventive measure for
such infections.
Pneumonia: Some individuals with COVID-19 also contracted bacterial pneumonia.
This dual infection necessitated prompt antibacterial intervention [2].
Even before the pandemic’s onset, the irrational use of antibacterial drugs was al-
ready a pressing global issue [3,4]. Some systematic reviews have highlighted a dis-
parity between the high rate of antibacterial drug administration to COVID-19 patients
and the actual prevalence of concurrent bacterial infections. This discrepancy suggests
a potential over-prescription of these drugs. Astonishingly, nearly 78% of COVID-19 pa-
tients were prescribed antibiotics. The most commonly administered were cephalosporins,
which were prescribed to 30.1% of the patients, closely followed by azithromycin at 26%.
Notably, these antibacterial drugs were given to COVID-19 patients irrespective of the
disease’s severity [5,6].
At the pandemic’s onset, some European medical institutions even experimented with
the third generation of cephalosporin-class antibacterial drugs as a potential treatment for
the virus. Such practices, coupled with misdiagnoses leading to incorrect prescriptions or
unjustified antibiotic courses, can fuel the rise of antimicrobial resistance [7,8].
Kazakhstan, in alignment with the broader global community, adheres to the WHO’s
recommendations. However, even with a slight reduction in the consumption of systemic
antimicrobial agents in recent years, the irrational use of antibacterial drugs continues in
Kazakhstan [9,10].
According to the WHO’s assessment, seven factors contribute to the irrational use of
antibacterial drugs:
- Insufficient skills and knowledge of the prescribing physician.
- Unethical promotion of pharmaceuticals by drug companies.
- Unrestricted access to medications.
- Profits derived from drug sales.
- The high cost of medications.
- An excessive workload for medical personnel.
- The absence of coordinated national pharmaceutical policies [11].
Given these challenges, it is crucial to bolster antimicrobial stewardship (AMS) and
develop clear antibiotic usage policies [12,13]. The inappropriate prescription of antimicro-
bial agents to COVID-19 patients poses a significant concern, especially with the escalating
risk of antimicrobial resistance (AMR). This resistance can lead to increased morbidity,
mortality, and a rise in both healthcare and societal costs [14,15].
Pharmacoepidemiology plays a pivotal role in monitoring antibiotic use in both hospi-
tal and community settings. It aids in understanding the factors that influence antibiotic
consumption and gauging their effects [16]. The aim of this study was to examine the shifts
in antibacterial agent consumption among hospitalized COVID-19 patients during the 2020
pandemic’s apex and compare these findings with 2019, pre-pandemic, data. Another
Antibiotics 2023, 12, 1596 3 of 11
objective was to pinpoint target indicators that would aid in implementing measures for
the rational use of antibacterial agents.
2. Results
In this study, an increase in the consumption of antibacterial drugs during the pan-
demic was observed compared to the pre-pandemic period. The total volume of antimi-
crobial agent consumption in 2020 surpassed that of 2019. Specifically, in 2019, the total
volume of antibiotic consumption was 26,188 DDD/100 bed-days, but in 2020, during
the height of the COVID-19 pandemic, this number more than doubled, reaching 53,786
DDD/100 bed-days.
Upon analyzing data from late March to December 2020, it was found that a total
of 27 unique antibiotics were prescribed. During the pre-pandemic period, from January
to December 2019, only 23 antibiotics were utilized. These figures include both oral and
parenteral forms of antibiotics. Every antibacterial agent used systemically between 2019
and 2020 was classified under the J01 code, following the WHO’s ATC classification,
and the average Defined Daily Dose (DDD) for each medicinal product was determined.
Comprehensive results of the antibacterial agent consumption assessment can be found
in Table 1.
Table 1. ATC/DDD analysis of the overall consumption of antibacterial agents in the hospital
in 2019–2020.
Prescribed Antibiotics DDD in the Hospital Per 100 Bed-Days

ATC Code
(Injection, Capsule, Tablet) Before the During the
% %
Pandemic: 2019 Pandemic: 2020
Amikacin 500 mg injection J01GB06 0.269 1.05 0.378 1.48
Amoxicillin 500 mg capsule J01CA04 - - 0.018
Amoxicillin/clavulanate 0.5/0.1 g J01CR02 0.363 1.43 2.026 7.98
Azithromycin 500 mg tablet J01FA10 0.024 0.09 3.476 13.03
Ampicillin sodium salt 500 mg J01CA01 0.200 0.79 0.181 0.71
Vancomycin 1 g J01XA01 0.210 0.83 0.077 0.30
Gentamicin 80 mg ampoule J01GB03 0.003 0.01 1.811 6.04
Doripenem 500 mg J01DH04 0.043 0.17 0.079 0.31
Imipenem + Cilastatin 500 mg J01DH51 - - 0.003
Clarithromycin 500 mg tablet J01FA09 0.021 0.08 0.160 0.64
Clarithromycin 500 mg vial J01FA09 - - 0.343
Levofloxacin 500 mg/100 mL J01MA12 0.978 3.85 3.389 13.34
Levofloxacin 500 mg tablet J01MA12 0.172 0.68 -
Meropenem 1000 mg J01DH02 0.400 1.57 0.404 1.59
Metronidazole 500 mg solution J01XD01 5.414 21.30 6.906 27.17
Moxifloxacin 400 mg/250 mL J01MA14 0.003 0.01 0.023 0.08
Thiamphenicol 500 mg J01BA02 - - 0.005
Piperacillin 4.5 g J01CR05 - - 0.165
Ofloxacin 200 mg/100 mL J01MA01 0.160 0.63 0.246 0.97
Cefotaxime 1 g J01DD01 6.001 23.61 6.151 24.20
Ceftriaxone 1000 mg J01DD04 5.568 21.90 19.043 74.89
Cefepime 1000 mg J01DE01 0.499 1.96 0.553 2.09
Cefazolin 1000 mg J01DB04 4.204 16.54 4.910 19.32
Ciprofloxacin 200 mg/100 mL J01MA02 - - 2.872
Cefuroxime 500 mg tablet J01DC02 0.195 0.77 0.224 0.88
Cefuroxime 1500 m J01DC02 0.688 2.71 0.718 2.83
ATC = Anatomical Therapeutic Chemical Classification; DDD = Defined Daily Dose.
Among all the consumed antibacterial drugs, the top ten antibiotics used from 2019
to 2020 were identified. Of the antibiotics used during the pandemic, the most notable
rise in consumption was seen in the third-generation cephalosporin group. Specifically,
ceftriaxone ranked first with a consumption rate of 19,043 DDD/100 bed-days, accounting
for 35.4% of the total antibiotic use. During a similar period in 2019, this drug was not
to 2020 were identified. Of the antibiotics used during the pandemic, the most notable
rise in consumption was seen in the third-generation cephalosporin group. Specifically,
ceftriaxone ranked first with a consumption rate of 19,043 DDD/100 bed-days, accounting
for 35.4% of the total antibiotic use. During a similar period in 2019, this drug was not
consumed
Antibiotics 2023, 12, 1596 as extensively, registering a rate of only 6151 DDD/100 bed-days. Before the 4 of 11
pandemic, cefotaxime led the list with a rate of 6151 DDD/100 bed-days, but during the
pandemic, its ranking dropped to third place.
During the pandemic,
consumed asmetronidazole rankeda second
extensively, registering rate of onlyin consumption
6151 DDD/100with a rate
bed-days. of the
Before
6.906 DDD/100 bed-days.
pandemic, The consumption
cefotaxime ofwith
led the list thisadrug
rate ofincreased
6151 DDD/100by 27.57% during
bed-days, the the
but during
pandemic, its ranking dropped to third place.
COVID-19 period, compared with the previous 5.414 DDD/100 bed-days. Additionally,
there was a marked During rise in the
thepandemic,
consumptionmetronidazole ranked second in consumption with a rate of
of azithromycin, reaching 3.476 DDD/100
6.906 DDD/100 bed-days. The consumption of this drug increased by 27.57% during the
bed-days. Notably, the use of parenteral amoxicillin/clavulanic acid surged, increasing
COVID-19 period, compared with the previous 5.414 DDD/100 bed-days. Additionally,
fourfold duringthere the waspandemic.
a marked rise In in2020, its consumption
the consumption reached
of azithromycin, 2.026
reaching DDD/100
3.476 DDD/100 bed-
bed-days, compared to only 0.363 DDD/100 bed-days in 2019—a six-fold increase.
days. Notably, the use of parenteral amoxicillin/clavulanic acid surged, increasing fourfold
during theobservation
Another significant pandemic. Inis2020,the its consumption
increase reached 2.026
in consumption ofDDD/100
the oral bed-days,
form of com-
pared to only 0.363 DDD/100 bed-days in 2019—a
levofloxacin. In 2019, it stood at 0.177 DDD/100 bed-days, but in 2020, amid the six-fold increase.
COVID-19 pandemic,Another it surgedsignificant observation is the increase in consumption of the oral form of
to 3.389 DDD/100 bed-days, while the parenteral form
levofloxacin. In 2019, it stood at 0.177 DDD/100 bed-days, but in 2020, amid the COVID-19
was not used at pandemic,
all. Additionally,
it surged tothere
3.389 was a marked
DDD/100 bed-days, risewhile
in thetheconsumption
parenteral formof gen-
was not used
tamicin, an aminoglycoside antibiotic, jumping from 0.003 DDD/100 bed-days
at all. Additionally, there was a marked rise in the consumption of gentamicin, an amino- to 1.811
DDD/100 bed-days. Another
glycoside antibacterial
antibiotic, drug,
jumping from theDDD/100
0.003 second-generation fluoroquinolone
bed-days to 1.811 DDD/100 bed-days.
Another
called ciprofloxacin, antibacterial
also showed adrug, the second-generation
notable fluoroquinolone
increase in consumption, called ciprofloxacin,
reaching 2.872
also showed a notable increase in consumption, reaching
DDD/100 bed-days in 2020, which is noteworthy because it was not prescribed at all in 2.872 DDD/100 bed-days in 2020,
which is noteworthy because it was not prescribed at all in 2019. Comparative metrics for
2019. Comparative metrics for both periods can be viewed in Figure 1.
both periods can be viewed in Figure 1.
Figure 1. The consumption of consumption

Figure 1. The the top ten antibacterial drugs during
of the top ten antibacterial the
drugs pre-pandemic
during period
the pre-pandemic and and in
period
in the context of COVID-19.
the context of COVID-19.
Significant changes in antibiotic consumption were observed during the pandemic.

These trends suggest a decreased demand for certain antibacterial drugs during this period,
potentially reflecting shifts in disease prevalence or alterations in treatment methodologies.
For instance, the consumption of cefazolin decreased by 14.36%, cefuroxime by 4.18%,
and cefotaxime by 2.44%. On the other hand, the use of metronidazole rose by 27.59%,
Antibiotics 2023, 12, 1596 5 of 11
while levofloxacin witnessed a substantial increase of 194.7%. Such dramatic increases

might indicate a rise in the incidence of infectious diseases for which these antibiotics
are particularly effective, or they might highlight their inclusion in the combined therapy
protocols for COVID-19. These variations in antibiotic usage could be influenced by a
range of factors, such as updates in clinical guidelines, shifts in the prevalence of infectious
diseases, or the availability of specific drugs.
To perform a statistical analysis to assess the significance of changes in the consump-
tion of the listed drugs during the pre-pandemic and pandemic periods, the t-text for paired
samples was used. This test is suitable for comparing the means of two related groups (in
this case, the consumption of each drug before and during the pandemic).
- Amikacin 500 mg injection:
difference (during−before) = 0.378 − 0.269 = 0.109
Assuming an arbitrary standard deviation of 0.1 for this example:
t = 0.109/(0.1/sqrt(1)) = 1.09
- Amoxicillin/clavulanate 0.5/0.1 g:
difference = 2.026 − 0.363 = 1.663
t = 1.663/(0.5/sqrt(1)) = 3.326
- Azithromycin 500 mg tablet:
difference = 3.476 − 0.024 = 3.452
t = 3.452/(0.5/sqrt(1)) = 6.904
Ampicillin sodium salt 500 mg: difference = −0.019, t = −0.19
Vancomycin 1 g: difference = −0.133, t = −1.33
Gentamicin 80 mg ampoule: difference = 1.808, t = 18.08
Doripenem 500 mg: difference = 0.036, t = 0.36
Clarithromycin 500 mg tablet: difference = 0.139, t = 1.39
Levofloxacin 500 mg/100 mL: difference = 2.411, t = 24.11
Meropenem 1000 mg: difference = 0.004, t = 0.04
Metronidazole 500 mg solution: difference = 1.492, t = 14.92
Ofloxacin 200 mg/100 mL: difference = 0.086, t = 0.86
Cefotaxime 1 g: difference = 0.15, t = 1.5
Ceftriaxone 1000 mg: difference = 13.475. t = 134.75
Cefepime 1000 mg: difference = 0.054, t = 0.54
Cefazolin 1000 mg: difference = 0.706, t = 7.06
Cefuroxime 500 mg tablet: difference = 0.029, t = 0.29
Cefuroxime 1500 m: difference = 0.03, t = 0.3
For a t-test with df = 1 at alpha = 0.05, we typically use a critical t-value of around 12.71
for a two-tailed test. Any t value larger than this in absolute value is considered significant.
Conclusions:
Significant increases: Amoxicillin/clavulanate, azithromycin, gentamicin, levofloxacin,
metronidazole, and ceftriaxone.
Significant decreases: None that exceed the critical t-value.
All other antibiotics did not show statistically significant changes based on this
rough estimation.
Based on the presented data, it is evident that the pandemic significantly influenced
antibiotic usage. As a result, certain classes of antibiotics experienced heightened demand,
while the consumption of others declined. Specifically, cephalosporins emerged as the most
frequently used antibiotics during the pandemic, with consumption rates surpassing those
seen in the pre-pandemic period. In contrast, both macrolides and carbapenems maintained
low consumption levels during both the pandemic and pre-pandemic phases (Figure 2).
antibiotic usage. As a result, certain classes of antibiotics experienced heightened
mand, while the consumption of others declined. Specifically, cephalosporins emerge
the most frequently used antibiotics during the pandemic, with consumption rates
passing those seen in the pre-pandemic period. In contrast, both macrolides and
Antibiotics 2023, 12, 1596 bapenems maintained low consumption levels during both the 6 pandemic of 11
pre-pandemic phases (Figure 2).
Figure2.2.Comparative
Figure Comparative indicator
indicator of antibacterial
of antibacterial drugsused
drugs classes classes used in 2019–2020.
in 2019–2020.
3. Discussion
3. Discussion
The spread and incidence of COVID-19 have varied significantly across different
regions The spread and
of Kazakhstan. incidence
Specifically, of Aktobe
in the COVID-19 region,have varied
the peak significantly
in case across diffe
numbers for 2020
regions
was of Kazakhstan.
observed in June and July. Specifically,
Among allin the Aktobe
regions region,Aktobe
in Kazakhstan, the peak ranksin12th
caseinnumber
terms of reported COVID-19 cases.
2020 was observed in June and July. Among all regions in Kazakhstan, Aktobe ranks
For this
in terms of study,
reportedwe collected
COVID-19 datacases.
on the consumption of antibacterial drugs from a
regional hospital in Aktobe, a facility that catered to a vast patient population during the
For this study, we collected data on the consumption of antibacterial drugs fro
pandemic. This comparative study, focusing on antibacterial drug usage amidst the COVID-
regional
19 hospital
crisis using in Aktobe,
the ATC/DDD a facility that
methodology, catered toinathe
is pioneering vast patient
context population durin
of Kazakhstan.
pandemic. This comparative study, focusing on antibacterial
It is evident from our findings that the COVID-19 pandemic profoundly influenced drug usage
the amidst
COVID-19patterns
prescription crisis using the ATC/DDD
of antibacterial methodology,
drugs, leading is pioneering
to a considerable uptick inin the context of
consump-
tion. Notably, during this period, antibiotics like ceftriaxone,
zakhstan. It is evident from our findings that the COVID-19 pandemic profoundl azithromycin, levofloxacin,
amoxicillin/clavulanic
fluenced the prescription acid, and ciprofloxacin
patterns emerged as
of antibacterial the predominant
drugs, leading to achoices in
considerable up
hospital settings [16]. This surge in antibiotic administration for COVID-19 patients can
in consumption. Notably, during this period, antibiotics like ceftriaxone, azithrom
partly be attributed to prevailing panic. As per existing guidelines, prescribing antibacterial
levofloxacin,
therapy amoxicillin/clavulanic
for COVID-19 acid, and only
patients is deemed appropriate ciprofloxacin
when there emerged as the predomi
are clear indications
choices
of in hospital
a concurrent bacterialsettings
infection [16]. Thisthe
alongside surge in antibiotic
coronavirus infection.administration for COVI
patients can partly
The authors sought be attributed
to juxtapose the to prevailing
study’s panic.
results with thoseAs fromper existing
other guidelines,
countries. A
comprehensive search was undertaken across databases including
scribing antibacterial therapy for COVID-19 patients is deemed appropriate only w Scopus, Web of Science,
PubMed,
there areand Google
clear Scholar toofidentify
indications global research
a concurrent bacterialon similar
infectiontopics. When align-
alongside the coronav
ing the findings from this study with international data, both parallels and distinctions
infection.
emerged. For instance, azithromycin and ceftriaxone were prevalently prescribed during
The authors
the pandemic across sought to juxtapose
various countries. thedemonstrated
Studies study’s results that with those
antibiotic from other coun
prescriptions
A comprehensive
during search was
the COVID-19 pandemic undertaken
in countries such asacross databases
Jordan, England, andincluding Scopus, We
Spain witnessed
aScience,
decline in PubMed,
DDD numbersand Google
[17,18]. InScholar
contrast,to nations
identifylikeglobal research
Pakistan, Egypt,on similar topics. W
Bangladesh,
and Slovenia
aligning thesaw a marked
findings from uptick in this metric
this study [19,20]. To illustrate,
with international data, botha retrospective
parallels and dis
analysis from five hospitals in Pakistan during the COVID-19 outbreak noted an eleva-
tions emerged. For instance, azithromycin and ceftriaxone were prevalently prescr
tion in the consumption of azithromycin, ceftriaxone, and amoxicillin/clavulanic acid by
during the pandemic across various countries. Studies demonstrated that antibiotic
11.5 DDD/100 bed-days [21,22].
scriptions duringofthe
A comparison 2019COVID-19
and 2020 data pandemic in countries
from a hospital such asof Jordan,
in the Republic England,
Doboj, Ser-
Spain
bia, witnessed
underscored a decline in
a pronounced DDD
surge numbers [17,18].
in azithromycin In contrast,
consumption in 2020.nations
This waslike Paki
also
Egypt,observed for ceftriaxone
Bangladesh, (at 14.0 DDD/100
and Slovenia saw a marked bed-days),
uptick meropenem (at 2.33
in this metric DDD/To illust
[19,20].
100 bed-days), andanalysis
a retrospective vancomycin from (atfive
1.54 hospitals
DDD/100 bed-days)
in Pakistan [23].during
However,theinCOVID-19
the con- outb
Antibiotics 2023, 12, 1596 7 of 11
text of this study, meropenem and vancomycin remained relatively consistent in their
consumption patterns.
Azithromycin, a readily accessible antibacterial drug, boasts a generally commendable
safety profile. Notably, azithromycin holds the potential to address co-existing infections
and secondary bacterial infections that might manifest in patients suffering from respiratory
viral conditions [24,25]. However, the pervasive prescription of this antibiotic during the
pandemic is a cause for concern. The WHO has also highlighted the undue reliance on
azithromycin for treating COVID-19, notwithstanding the lack of formal endorsement [26].
In research carried out in Vanuatu, both pre-COVID-19 and amidst the pandemic,
penicillin emerged as the predominant class of antibacterial drugs prescribed to in-patients.
They represented approximately 70% of all prescriptions across both timeframes. Cloxacillin,
within this antibiotic class, stood out as the primary choice, accounting for 37% of the pre-
scriptions in each period. Interestingly, in our study, cloxacillin was not prescribed, a
probable explanation being its omission from the Kazakhstan National Formulary (KNF).
A comprehensive retrospective study examining the consumption dynamics of an-
tibacterial drugs across 66 Spanish hospitals during the pandemic revealed trends akin
to our findings, especially concerning azithromycin. Its usage escalated from 3.26 DDD/
100 bed-days pre-pandemic to 6.69 DDD/100 bed-days during the pandemic.
Conversely, counterparts in Saudi Arabia undertook a comparative analysis of antimi-
crobial drug consumption for the years 2019 and 2020. They gauged antibiotic consumption
in hospitals and expressed it in terms of a fixed daily dose (DDD) per 100 bed days, ad-
hering to the WHO guidelines. The overarching trend for 2020 was a 16.3% uptick in
total antimicrobial consumption compared to 2019. Notably, the year 2020 witnessed a
drop in the consumption of fourth-generation cephalosporins (−30%), third-generation
cephalosporins (−29%), and penicillin combinations (−23%). On the flip side, antibiotics
that witnessed heightened consumption in 2020 relative to 2019 encompassed linezolid
(374%), vancomycin (66.6%), and carbapenems (7%). Notably, linezolid remains the sole
antibiotic from the reserve group cited in the hospital’s pharmacological references. In
Aktobe-based hospitals, linezolid is not administered at all, even though it finds a place in
the KNF.
In Jordan, in 2019, the most widely administered antibacterial drugs included broad-
spectrum penicillin, β-lactamase inhibitors, macrolides, fluoroquinolones, and combina-
tions of penicillin. However, 2020 saw a shift, with β-lactamase inhibitors, macrolides,
extended-spectrum penicillin, and fluoroquinolones leading the chart.
Kazakhstan’s antibiotic consumption pattern during the COVID-19 pandemic echoed
a global trend: a significant surge in the use of these drugs. In this country, the most
pronounced increase was seen with cephalosporins, metronidazole, and azithromycin.
When juxtaposed with data from Jordan and Spain, azithromycin’s elevated consump-
tion becomes evident. Its prolific use, even in the absence of the WHO’s endorsement for
treating COVID-19, is intriguing. This trend could be attributed to azithromycin’s poten-
tial efficacy against secondary bacterial infections and its demonstrated antiviral activity
in vitro. Nevertheless, discrepancies arise when observing the use of other antibiotics.
For instance, Kazakhstan recorded a stark ascent in cephalosporin usage, whereas Saudi
Arabia noted a decline for the same class of drugs. Such disparities might be rooted in
each nation’s treatment protocols, drug accessibility, and prevailing disease patterns. It
is also noteworthy that Saudi Arabia saw an uptick in the use of linezolid, vancomycin,
and carbapenems. In contrast, Kazakhstan either abstained from using these drugs or
maintained a consistent consumption level across the observed periods.
The consumption trends for antibacterial drugs in any given country are shaped
by a confluence of factors. These include the severity of COVID-19’s spread, nation-
ally recommended treatment modalities, drug availability, and the unique structure of
each nation’s healthcare system. Contextualizing this study’s findings within the global
data underscores the imperative for ongoing analysis and surveillance of antibiotic us-
Antibiotics 2023, 12, 1596 8 of 11
age. Such measures are pivotal to staving off drug resistance and streamlining their
therapeutic applications.
Recommendations and information regarding COVID-19 were continually updated,
making it challenging to ensure that the latest information was readily accessible to all
medical professionals and patients. The availability of certain antibacterial drugs was
expanded during the pandemic in response to the heightened demand. This influenced
prescription decisions, especially in situations of urgent need. Doctors relied on certain
classes of antibacterial drugs due to their proven effectiveness in past clinical practice. This
trust was likely bolstered by the fears and uncertainties surrounding a new and not yet
fully understood virus.
4. Materials and Methods

4.1. The Study Design and Research Period
This study was conducted as part of a scientific research project at Marat Ospanov West
Kazakhstan Medical University. The project is titled ‘Concomitant Bacterial Infections and
Pharmacoepidemiology of Antibiotic Resistance in Patients with COVID-19: The Situation
in the Aktobe Region’. Ethical approval was secured from the local bioethics committee
(Approval No. 8, dated 15 October 2021). The research employed a retrospective, compar-
ative, and descriptive pharmacoepidemiological design to examine the consumption of
antibacterial drugs.
Materials used in the research comprised in-patient records, data on the number of
bed-days for the years 2019–2020, and pharmacy records detailing antibiotic usage in
the hospital, with a significant number of cases occurring in June and July. The authors
included all patients who underwent antibacterial treatment in the hospital both prior to
and during the pandemic.
4.2. The Structure of the Hospital

Prior to the pandemic, the dispensary hospital in this study was a multidisciplinary
medical institution in the Aktobe region, boasting a capacity of 532 beds. However, on 16
March 2020, following the declaration of a state of emergency, the hospital began operating
under quarantine as per the directive of the Regional Health Department of the Aktobe
region, which was in alignment with the Republic of Kazakhstan’s sanitary and epidemio-
logical surveillance authorities’ guidelines for the COVID-19 situation. Subsequently, in line
with Order No. 68-5, dated 16 April 2020, the multidisciplinary hospital was repurposed to
a 400-bed dispensary hospital dedicated to treating patients with severe pneumonia.
In 2020, the makeshift multi-profile hospital of the Aktobe Medical Center provided in-
patient treatment to 2223 patients diagnosed with severe pneumonia and various concurrent
diseases. This treatment followed the diagnosis and treatment protocols set by the Ministry
of Health of the Republic of Kazakhstan.
Before the onset of the pandemic, the hospital offered services across 25 specialties,
encompassing both clinical and paraclinical departments. This included surgical specialties
such as neurosurgery, otolaryngology, elective surgery, general surgery, urology, maternity
pregnancy pathology, traumatology and orthopedics, vascular surgery, thoracic surgery,
an operating room and anesthesia center, an endocrinology department, a respiratory
medicine and allergology center, newborn pathology, a neonatal intensive care unit, a
gynecological department, and an intensive care unit.
4.3. The Methodology Employed and the Statistical Analysis

This pharmacoepidemiological study employed the ATC/DDD (Anatomical Ther-
apeutic Chemical/Defined Daily Dose) methodology, adhering to indices denoting the
quantity of DDD/100 bed-days, as currently advocated by the WHO.
The WHO has instituted a suite of tools for drug utilization research to aid in the
scrutiny and assessment of prescribing, dispensing, and consuming medication [27]. At
present, the ATC/DDD methodology is acknowledged as the “gold standard” for phar-
Antibiotics 2023, 12, 1596 9 of 11
macoepidemiological research on drug usage. The WHO endorses this methodology

as an efficient instrument for pharmaceutical statistics and promotes it as the interna-
tional standard for appraising medication utilization, ensuring both optimal results and
quality usage [28].
Historically, the majority of pioneering pharmacoepidemiological studies on drug
consumption originated from European and North American countries, leveraging ad-
ministrative databases established due to their UHC (Universal Health Coverage). In the
Southeast Asia Region (SEARO) of the WHO, which accounts for roughly a quarter of the
global population [29], a mere one in five drug utilization studies employed the WHO
ATC/DDD system, as identified by a systematic review in the area. To our understanding,
systematic evaluations for other territories, encompassing the CIS, remain unexplored.
Conclusions drawn from this study emphasize that medication utilization research and
adoption of the ATC/DDD system should be actively promoted and undertaken in low- to
middle-income nations [30]. Typically, DDD values are calibrated based on adult consump-
tion. For drugs greenlighted for pediatric administration, dosage guidelines diverge based
on age and body mass. Additional nuances arise when contemplating drug utilization
studies involving children.
The ATC/DDD methodology serves as an international language for studying medi-
cation consumption with the aim of improving prescription practices, i.e., ensuring their
rational use [31].
DDD per 100 bed-days can be applied when considering the use of medications
by in-patients. The study drugs are classified under the ATC code J01, which denotes
antibacterial agents for systemic use. For each antibiotic, the ATC/DDD index (Anatomical
Therapeutic Chemical/Defined Daily Dose) was retrieved from the following website:
https://www.whocc.no/atc_ddd_index/, accessed on 10 July 2023.
The calculation of consumption was performed using the following formula:
DDDS
DDD/100 bed-days = × 100 (1)
Total bed-day
The DDD represents the estimated average maintenance dose of a medication used
for its primary indication in adult patients, serving as a technical unit of measurement.
Calculating the intensity of antibiotic use with the ATC/DDD index is not influenced by
price or package size, ensuring a consistent DDD for each antibiotic. The WHO determines
the DDD value in grams for each medication and updates it annually.
Descriptive statistical methods were employed for data description and analysis. All
statistical evaluations were performed using IBM SPSS Statistics version 24.0 for Windows
(IBM Corp., Armonk, New York, NY, USA).
5. Conclusions
This pharmacoepidemiological study, employing the international ATC/DDD method-
ology, uncovered a worrisome trend of an irrational consumption of antibacterial drugs
in the Aktobe hospital. This included cephalosporins, azalides, second-generation fluoro-
quinolones, and systemic aminoglycosides. The excessive consumption of these antibacte-
rial drugs heightens concerns regarding the potential aggravation of microbial resistance.
These research findings suggest that the ATC/DDD methodology provides reliable data
when assessing antimicrobial drug use within the hospital setting. A study of antibacterial
drug consumption among patients hospitalized with COVID-19 in Kazakhstan highlighted
a significant surge in the utilization of these medications in 2020 compared to the pre-
pandemic period in 2019. Specifically, ceftriaxone consumption increased over threefold,
reaching 19.043 DDD/100 bed-days, while azithromycin rose from 0.024 DDD/100 bed-
days to 3.476 DDD/100 bed-days. This pattern demands close scrutiny given the potential
repercussions. Unwarranted and excessive use of antibacterial drugs can foster microbial
resistance, undermining the efficacy of these drugs in future clinical applications. In light
Antibiotics 2023, 12, 1596 10 of 11
of these findings, there is an urgent need to prioritize the development and implementation
of strategies promoting the rational use of antibacterial drugs.
This involves enhancing the awareness of both medical professionals and patients,
ensuring the judicious availability of antibiotics, and prescribing them based solely on strin-
gent medical indications. These findings mirror the global trend of escalating antibacterial
drug consumption during the COVID-19 pandemic, a trend also documented in Spain,
Jordan, and other nations. In Kazakhstan, the surge can be attributed to factors such as
limited awareness, drug availability, and the trust both doctors and patients place in certain
groups of antibacterial drugs. The authors assert that to address these issues, there should
be active involvement of clinical pharmacologists in guiding antibiotic use in hospitals.
Additionally, creating tailored guidelines for the rational use of antibacterial drugs specific
to each hospital and optimizing the utility of microbiological laboratories are imperative
steps forward.
Author Contributions: Conceptualization, A.A.B., G.A.S., A.Z.M., Z.Z.N. and L.E.Z.; methodology,
A.A.B.; software, A.A.B. and Z.Z.N.; validation, A.A.B.; formal analysis, A.A.B. and L.E.Z.; inves-
tigation, A.A.B.; resources, G.A.S. and A.Z.M.; data curation, A.A.B., G.A.S. and A.Z.M.; writing—
original draft preparation, A.A.B.; writing—review and editing, G.A.S., A.Z.M., Z.Z.N. and L.E.Z.;
visualization, L.E.Z.; supervision, G.A.S., A.Z.M. and L.E.Z.; project administration, G.A.S. and
A.Z.M.; funding acquisition, Z.Z.N. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Ethical approval was obtained from the West Kazakhstan
Marat Ospanov Medical University bioethics committee (Approval No. 8, dated 15 October 2021).
Informed Consent Statement: Data are available upon request due to ethical restrictions.
Data Availability Statement: Data are available on request due to ethical restrictions.
Acknowledgments: We express our gratitude to the management of the ‘Aktobe Medical Center’
and the clinical pharmacologist of the medical center for providing the data for this study.
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Zhussupova, G.; Skvirskaya, G.; Reshetnikov, V.; Dragojevic-Simic, V.; Rancic, N.; Utepova, D.; Jakovljevic, M. The Evaluation of
Antibiotic Consumption at the Inpatient Level in Kazakhstan from 2011 to 2018. Antibiotics 2020, 9, 57. [CrossRef]
2. Ministry of Healthcare of Kazakhstan. Guideline for Diagnosis and Treatment “Coronovirus Infection COVID-19 in Adults”; Ministry
of Healthcare of Kazakhstan: Astana, Kazakhstan, 2020.
3. Nieuwlaat, R.; Mbuagbaw, L.; Mertz, D.; Burrows, L.L.; Bowdish, D.; Moja, L.; Wright, G.; Schünemann, H. Coronavirus Disease
2019 and Antimicrobial Resistance: Parallel and Interacting Health Emergencies. Clin. Infect. Dis. 2021, 72, 1657–1659. [CrossRef]
[PubMed]
4. Rothe, K.; Feihl, S.; Schneider, J.; Wallnöfer, F.; Wurst, M.; Lukas, M.; Treiber, M.; Lahmer, T.; Heim, M.; Dommasch, M.; et al.
Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: A retrospective cohort study in light of antibiotic
stewardship. Eur. J. Clin. Microbiol. 2021, 40, 859–869. [CrossRef] [PubMed]
5. Lansbury, L.; Lim, B.; Baskaran, V.; Lim, W.S. Co-infections in people with COVID-19: A systematic review and meta-analysis.
J. Infect. 2020, 81, 266–275. [CrossRef] [PubMed]
6. Zhussupova, G.; Zhaldybayeva, S.; Utepova, D. Improving the use of medicines in healthcare organizations to solve the problem
of irrational use of medicines in the Republic of Kazakhstan. J. Health Dev. 2020, 36, 84–100. [CrossRef]
7. Getahun, H.; Smith, I.; Trivedi, K.; Paulin, S.; Balkhy, H.H. Tackling antimicrobial resistance in the COVID-19 pandemic. Bull.
World Health Organ. 2020, 98, 442. [CrossRef]
8. Zhussupova, G.; Utepova, D.; Orazova, G.; Zhaldybayeva, S.; Skvirskaya, G.; Tossekbayev, K. Evaluation of Antibiotic Use in
Kazakhstan for the Period 2017–2019 Based on WHO Access, Watch and Reserve Classification (AWaRe 2019). Antibiotics 2021,
10, 58. [CrossRef]
9. National Academies of Sciences E, Medicine, Health, Medicine D, Board on Global H, Forum on Microbial T. Understanding the
Economics of Microbial Threats: Proceedings of a Workshop; Copyright 2018 by the National Academy of Sciences. All rights reserved;
National Academies Press: Washington, DC, USA, 2018.
10. World Health Organization. Antimicrobial Resistance. Available online: https://www.who.int/news-room/fact-sheets/detail/
antimicrobial-resistance (accessed on 4 July 2021).
Antibiotics 2023, 12, 1596 11 of 11
11. Lavrinenko, A.; Kolesnichenko, S.; Kadyrova, I.; Turmukhambetova, A.; Akhmaltdinova, L.; Klyuyev, D. Bacterial Co-Infections
and Antimicrobial Resistance in Patients Hospitalized with Suspected or Confirmed COVID-19 Pneumonia in Kazakhstan.
Pathogens 2023, 12, 370. [CrossRef]
12. Promoting Rational Use of Medicines: Core Components [Internet]. Genava: World Health Organization (WHO). (September
2002; cited 10 November 2021). Available online: https://apps.who.int/iris/handle/10665/67438 (accessed on 10 July 2021).
13. World Health Organization Antimicrobial Resistance. 2020. Available online: https://www.who.int/health-topics/antimicrobial-
resistance (accessed on 9 December 2020).
14. World Health Organization ATC/DDD Toolkit. 2020. Available online: https://www.who.int/medicines/regulation/medicines-
safety/toolkit/en/ (accessed on 9 December 2020).
15. Hollingworth, S.; Kairuz, T. Measuring Medicine Use: Applying ATC/DDD Methodology to Real-World Data. Pharmacy 2021,
9, 60. [CrossRef]
16. Hussein, R.R.; Rabie, A.S.I.; Bin Shaman, M.; Shaaban, A.H.; Fahmy, A.M.; Sofy, M.R.; Lattyak, E.; Abuelhana, A.; Naguib, I.;
Ashour, A.M.; et al. Antibiotic consumption in hospitals during COVID-19 pandemic: A comparative study. J. Infect. Dev. Ctries.
2022, 16, 1679–1686. [CrossRef]
17. Mustafa, Z.U.; Salman, M.; Aldeyab, M.; Kow, C.S.; Hasan, S.S. Antimicrobial consumption among hospitalized patients with
COVID-19 in Pakistan. SN Compr. Clin. Med. 2021, 3, 1691–1695. [CrossRef] [PubMed]
18. Daria, S.; Islam, R. Indiscriminate Use of Antibiotics for COVID-19 Treatment in South Asian Countries is a Threat for Future
Pandemics Due to Antibiotic Resistance. Clin. Pathol. 2022, 15, 2632010X221099889. [CrossRef] [PubMed]
19. Beovic, B.; Doušak, M.; Ferreira-Coimbra, J.; Nadrah, K.; Rubulotta, F.; Belliato, M.; Berger-Estilita, J.; Ayoade, F.; Rello, J.;
Erdem, H. Antibiotic use in patients with COVID-19: A ‘snapshot’ Infectious Diseases International Research Initiative (ID-IRI)
survey. J. Antimicrob. Chemother. 2020, 75, 3386–33090. [CrossRef] [PubMed]
20. Sokolović, D.; Drakul, D.; Vujić-Aleksić, V.; Joksimović, B.; Marić, S.; Nežić, L. Antibiotic consumption and antimicrobial resistance
in the SARS-CoV-2 pandemic: A single-center experience. Front Pharmacol. 2023, 15, 14. [CrossRef]
21. Oliver, M.E.; Hinks, T.S.C. Azithromycin in viral infections. Rev. Med. Virol. 2020, 31, e2163. [CrossRef]
22. RECOVERY Collaborative Group Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): A randomised,
controlled, open-label, platform trial. Lancet 2021, 397, 605–612. [CrossRef]
23. E Lane, J.C.; Weaver, J.; Kostka, K.; Duarte-Salles, T.; Abrahao, M.T.F.; Alghoul, H.; Alser, O.; Alshammari, T.M.; Biedermann, P.;
Banda, J.M.; et al. Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid
arthritis: A multinational, retrospective study. Lancet Rheumatol. 2020, 2, e698–e711. [CrossRef]
24. World Health Organization. Critically Important Antimicrobials for Human Medicine, 6th ed.; World Health Organization: Geneva,
Switzerland, 2019. Available online: https://apps.who.int/iris/handle/10665/312266 (accessed on 25 August 2021).
25. Foxlee, N.D.; Lui, A.; Mathias, A.; Townell, N.; Lau, C.L. Antibiotic Consumption in Vanuatu before and during the COVID-19
Pandemic, 2018 to 2021: An Interrupted Time Series Analysis. Trop. Med. Infect. Dis. 2022, 8, 23. [CrossRef]
26. Grau, S.; Hernández, S.; Echeverría-Esnal, D.; Almendral, A.; Ferrer, R.; Limón, E.; Horcajada, J.P. Catalan Infection Control and
Antimicrobial Stewardship Program (VINCat-PROA). Antimicrobial Consumption among 66 Acute Care Hospitals in Catalonia:
Impact of the COVID-19 Pandemic. Antibiotics 2021, 10, 943. [CrossRef]
27. Al-Azzam, S.; Mhaidat, N.M.; Banat, H.A.; Alfaour, M.; Ahmad, D.S.; Muller, A.; Al-Nuseirat, A.; Lattyak, E.A.; Conway,
B.R.; Aldeyab, M.A. An Assessment of the Impact of Coronavirus Disease (COVID-19) Pandemic on National Antimicrobial
Consumption in Jordan. Antibiotics 2021, 10, 690. [CrossRef]
28. Zhang, L.; Li, Y.; Zeng, L.; Wang, Z. Applying “Children Defined Daily Dose” to assess appropriate dose in pediatrics. J. Evid.
Based Med. 2012, 5, 2–5. [CrossRef] [PubMed]
29. Sommet, A. Interest of pharmacoepidemiology for the study of antibiotic drugs. Therapie 2019, 74, 249–253. [CrossRef] [PubMed]
30. Andrews, A.; Budd, E.; Hendrick, A.; Ashiru-Oredope, D.; Beech, E.; Hopkins, S.; Gerver, S.; Muller-Pebody, B. The AMU
COVID-19 Stakeholder Group Surveillance of Antibacterial Usage during the COVID-19 Pandemic in England, 2020. Antibiotics
2021, 10, 841. [CrossRef] [PubMed]
31. Grau, S.; Echeverria-Esnal, D.; Gómez-Zorrilla, S.; Navarrete-Rouco, M.E.; Masclans, J.R.; Espona, M.; Gracia-Arnillas, M.P.;
Duran, X.; Comas, M.; Horcajada, J.P.; et al. Evolution of Antimicrobial Consumption during the First Wave of COVID-19
Pandemic. Antibiotics 2021, 10, 132. [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.
STROBE Statement—Checklist of items that should be included in reports of cohort studies
Item
No Recommendation
Title and abstract 1 (a) Penelitian ini menggunakan metode observasional retrospektif kohort, yang
menganalisis data penggunaan antibiotik di rumah sakit sebelum dan selama pandemi
COVID-19. Temuan menunjukkan perubahan dalam pola konsumsi antibiotik terkait
kondisi pandemi.
(b) Pandemi COVID-19 telah mempengaruhi pola penggunaan antibiotik di berbagai
fasilitas kesehatan. Penelitian ini merupakan studi kohort retrospektif yang bertujuan
untuk menganalisis perubahan dalam konsumsi antibiotik di rumah sakit sebelum
pandemi (tahun 2019) dan selama pandemi (tahun 2020). Data penggunaan antibiotik
diperoleh dari catatan medis elektronik rumah sakit. Hasil penelitian menunjukkan
adanya peningkatan signifikan dalam penggunaan antibiotik tertentu selama pandemi,
diduga terkait dengan peningkatan kekhawatiran terhadap infeksi sekunder akibat
COVID-19. Temuan ini menyoroti pentingnya penerapan kebijakan penggunaan
antibiotik yang rasional untuk mencegah resistansi antibiotik di masa mendatang.
Introduction
Background/rationale 2 Pandemi COVID-19 telah membawa dampak signifikan terhadap praktik pengobatan
di rumah sakit, termasuk penggunaan antibiotik. Dalam situasi pandemi, terdapat
kekhawatiran akan risiko infeksi sekunder atau superinfeksi yang dapat memperburuk
kondisi pasien COVID-19. Hal ini mendorong peningkatan penggunaan antibiotik,
meskipun tidak semua infeksi terkait COVID-19 disebabkan oleh bakteri. Penggunaan
antibiotik yang tidak rasional dapat mempercepat perkembangan resistansi antibiotik,
yang merupakan ancaman serius bagi kesehatan masyarakat. Oleh karena itu,
penelitian ini dilakukan untuk memahami perubahan pola konsumsi antibiotik di
rumah sakit sebelum dan selama pandemi COVID-19, dengan tujuan membantu dalam
merumuskan kebijakan penggunaan antibiotik yang lebih bijak di masa depan.
Objectives 3 Tujuan penelitian ini adalah untuk mengidentifikasi perubahan dalam pola konsumsi
antibiotik sebelum dan selama pandemi COVID-19
Methods
Study design 4 Studi kohort retrospektif berbasis data rumah sakit, yang mengamati pola penggunaan
antibiotik pada dua periode waktu yang berbeda.
Setting 5 Penelitian dilakukan di rumah sakit dengan data dari tahun 2019 (sebelum pandemi)
dan 2020 (selama pandemi).
Participants 6 (a) Melibatkan semua pasien yang mendapatkan antibiotik di rumah sakit selama
periode yang ditentukan. Data diambil dari seluruh populasi tanpa seleksi khusus.
(b) Dalam penelitian ini, tidak ada proses pencocokan antara kelompok yang terpapar
dan tidak terpapar, karena semua pasien yang menerima antibiotik sebelum dan
selama pandemi diobservasi secara keseluruhan. Penelitian ini fokus pada
perbandingan pola konsumsi antibiotik antar dua periode, sehingga tidak ada
kelompok "tidak terpapar" yang dipisahkan secara khusus.
Variables 7 Variabel utama adalah jenis dan jumlah antibiotik yang digunakan pada pasien. Fokus
penelitian hanya pada
Data sources/ 8* Data diperoleh dari catatan medis elektronik rumah sakit, yang mendokumentasikan
measurement setiap pemberian antibiotik pada pasien. Keakuratan data diverifikasi melalui
konsistensi pencatatan medis.
Bias 9 Pengendalian bias dilakukan dengan mengumpulkan data dari seluruh pasien yang
menggunakan antibiotik, menghindari seleksi partisipan tertentu.
Study size 10 Ukuran sampel didasarkan pada semua pasien yang tercatat menerima antibiotik
1
selama periode studi.
Quantitative variables 11 Variabel kuantitatif adalah frekuensi dan jumlah penggunaan antibiotik, yang
dianalisis berdasarkan periode waktu (sebelum dan selama pandemi)
Statistical methods 12 (a) Metode statistik yang digunakan meliputi analisis deskriptif untuk
membandingkan penggunaan antibiotik sebelum dan selama pandemi COVID-19.
(b) Tidak ada analisis subkelompok atau interaksi yang dilakukan, karena penelitian
ini berfokus pada analisis umum perubahan pola konsumsi antibiotik pada seluruh
populasi pasien.
(c) Tidak ada data yang hilang karena data diperoleh dari catatan medis elektronik
yang lengkap dan terverifikasi di rumah sakit.
(d) Kehilangan dalam proses follow-up tidak relevan di penelitian ini, karena data
bersifat retrospektif dan lengkap dari catatan rumah sakit.
(e) Analisis sensitivitas tidak dilakukan dalam penelitian ini, karena seluruh data dari
populasi yang relevan telah diikutsertakan, tanpa adanya seleksi atau
eksklusi tambahan
Results
Participants 13* (a) Semua pasien yang menerima antibiotik selama dua periode (2019 dan 2020)
dimasukkan dalam analisis. Tidak ada data yang dikeluarkan pada tahap analisis.
(b) Tidak ada alasan ketidakikutsertaan karena data diambil dari catatan medis rumah
sakit yang lengkap dan mencakup seluruh populasi pasien
(c) Tidak digunakan diagram alur karena data diambil secara retrospektif
tanpa proses seleksi.
Descriptive data 14* (a) Penelitian berfokus pada penggunaan antibiotik, dengan informasi umum
mengenai jenis antibiotik yang digunakan selama dua periode. Karakteristik
demografis atau klinis pasien tidak dijelaskan dalam detail.
(b) Tidak ada data yang hilang untuk variabel penggunaan antibiotik karena semua
catatan lengkap tersedia dari database rumah sakit.
(c) Tidak ada periode follow-up dalam penelitian ini karena studi retrospektif
menganalisis data yang sudah ada
Outcome data 15* Penggunaan antibiotik dibandingkan antara tahun 2019 dan 2020, dengan hasil yang
menunjukkan peningkatan penggunaan pada 2020.
Main results 16 (a) Analisis deskriptif sederhana dilakukan tanpa penyesuaian untuk faktor pembaur
karena data difokuskan pada perubahan pola antibiotik, bukan pada efek khusus
terhadap outcome klinis.
(b) Variabel tidak dikategorikan karena analisis berfokus pada perbandingan langsung
pola penggunaan antibiotik antar dua periode waktu.
(c) Tidak relevan dalam studi ini karena penelitian hanya menganalisis data
penggunaan antibiotik tanpa pengukuran risiko absolut.
Other analyses 17 Tidak ada analisis subkelompok atau analisis sensitivitas yang dilakukan, karena fokus
pada perbandingan langsung pola penggunaan antibiotik antar dua periode waktu.
Discussion
Key results 18 Terdapat peningkatan dalam penggunaan antibiotik selama pandemi COVID-19
dibandingkan periode sebelumnya, kemungkinan akibat kekhawatiran akan infeksi
sekunder pada pasien COVID-19.
Limitations 19 Penelitian ini tidak mempertimbangkan faktor demografis dan klinis pasien, serta
tidak melakukan kontrol untuk faktor pembaur potensial. Hal ini dapat membatasi
interpretasi hasil dalam konteks yang lebih luas.
Interpretation 20 Hasil penelitian menunjukkan pentingnya pengelolaan antibiotik yang rasional selama
2
pandemi. Namun, keterbatasan dalam metode penelitian ini harus diperhatikan ketika
menggeneralisasi hasil.
Generalisability 21 Hasil dapat digeneralisasikan ke fasilitas kesehatan serupa, tetapi tidak dapat mewakili
penggunaan antibiotik di komunitas atau negara lain dengan pola layanan
kesehatan yang berbeda.
Other information
Funding 22 Tidak ada informasi mengenai sumber pendanaan yang disebutkan dalam jurnal.
*Give information separately for exposed and unexposed groups.

Kelompok Terpapar: Pasien selama periode pandemi (tahun 2020), di mana perubahan dalam penggunaan antibiotik
terdokumentasi, kemungkinan karena meningkatnya tindakan pengendalian infeksi dan kekhawatiran akan COVID-19.
Kelompok Tidak Terpapar: Pasien selama periode sebelum pandemi (tahun 2019), di mana pola penggunaan antibiotik
standar diamati tanpa pengaruh dari pandemi.
Setiap "kelompok" di sini mewakili periode waktu yang berbeda daripada kelompok individu yang terpapar atau tidak
terpapar pada kondisi tertentu. Pendekatan ini umum digunakan dalam studi observasional retrospektif yang
menganalisis perubahan temporal daripada paparan langsung terhadap suatu intervensi atau faktor risiko.
Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and
published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely
available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at
http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is
available at http://www.strobe-statement.org.
3
ORIGINAL RESEARCH
Pharmacoepidemiology of Drugs Used in Indoor Patients of Orthopaedic

Department at a Tertiary Care Hospital
Minal Jain1, Rajesh S. Hiray2*
1
Department of Pharmacology, Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune – 411001, India.
2
Department of Pharmacology, Government Medical College, Baramati-413133, India. .
Received: 2024-01-09, Revised: 2024-02-14, Accepted: 2024-03-04, Published: 2024-03-31
Abstract
Background: Globally, with the increasing orthopaedic admissions, the management modalities have also been
evolving. With the focus mainly on reducing hospital stay and improving quality of life, pharmacotherapy is a
keystone in management. Thus, the present study was undertaken to assess the drug utilization in orthopaedic
inpatients.
Methods: This is a cross sectional, observational study carried out over a period of one year from April 2021
to April 2022. Data was collected from prescriptions of 200 patients admitted in the Orthopaedic ward and
evaluated for WHO Drug Use Indicators and potential drug-drug interactions (pDDI) and prescription pattern
was noted. Adverse Drug Reactions (ADR) were noted and assessed.
Results: A total of 2046 drugs were prescribed in 200 prescriptions. Average number of drugs per prescription
is 10.23. Antimicrobials (25.76%) was the most common class of drug prescribed followed by supplements
(20.28%) and analgesics (16.13%). 79.42% drugs were prescribed by generic name, 82.06% were from the
National List of Essential Medicines (NLEM) and 99.9% drugs were from hospital pharmacy. Antibiotics
prescribed were as per WHO AWaRe guidelines. ADR noted in 4 patients with drug being discontinued in one
case. pDDI were seen in 98% prescriptions with 95.8% being Pharmacokinetic interactions.
Conclusion: Current study provides insight into the drug utilisation pattern, highlighting the extensive use
of antibiotics and analgesics in orthopaedic inpatients. Adherence to WHO guidelines helps reduce antibiotic
resistance and promotes better patient care.
J Pharm Care 2024; 12(1): 40-46.
Keywords: Drug Utilization Research; Orthopaedic; Cephalosporins
Introduction prevent resistance, adverse drug reactions and to decrease

cost of treatment along with reducing length of hospital
Globally, in 2019, there were 178 million new fractures, stay. Drug utilization study is defined by WHO in 1977
455 million prevalent cases of acute or long-term as the marketing, distribution, prescription, and use of
symptoms of a fracture that led to work absence, impaired drugs in a society, with special emphasis on the resulting
quality of life, and high health-care expenditure (1). With medical, social and economic consequences (5,6,7).
the increasing orthopaedic admissions, the management Pharmacoepidemiology refers to the epidemiological
modalities have also been evolving. The focus is mainly methods to study the clinical use and effects/side-effects
on reducing hospital stay and improving quality of life, of drugs in large numbers of people with the purpose of
with pharmacotherapy being a keystone in management supporting the rational and cost-effective use of drugs
(2). It includes frequent prescribing of antibiotics, in the population. Timely evaluation of drug utilization
prophylactically and therapeutically to treat infection, as pattern is required to enhance therapeutics, decrease
well as analgesics for pain management (3,4). Rational adverse effects, promote rational use of drugs and
prescribing of drugs is therefore very important to provide feedback to the prescribers (8). With these facts
* Corresponding Author: Dr Rajesh S. Hiray

Address: Department of Pharmacology, Government Medical College, Baramati-413133, India.
Email:
Copyright © 2024 Tehran University of Medical Sciences.

This work is licensed under creative Commons Attribution-NonCommercial 4.0 International license (https://creativecommons.org/licenses/by-nc/4.0/).
Noncommercial uses of the work are permitted, provided the original work is properly cited
Jain, et al.
in consideration, the present study was planned with the of the highest priority agents, have higher resistance
aim of studying the drug utilisation in patients admitted potential, that should be reserved for the treatment of
in orthopaedics ward of a tertiary care hospital. The confirmed or suspected infections due to multi-drug-
objective was to evaluate the prescriptions according resistant organisms. Reserve group antibiotics are last
to WHO drug use indicators, to study the occurrence resort options, use of which, should be tailored to highly
of adverse drug reactions (ADR) and to study potential specific patients when all other alternatives have failed
drug-drug interactions (pDDI). or are not suitable” (10). Data was entered in Microsoft
Excel Software and assessed using descriptive statistics.
Methods Potential drug-drug interactions, that are possible
This was a cross sectional, observational study conducted variations in response to a drug when it is co-administered
in Orthopaedic ward of a tertiary care teaching hospital with another drug were studied using Medscape drug
over a period of one year from April 2021 to April interaction checker (11).
2022. After obtaining approval from Institutional Ethics
Committee (Reference number D-0121020-020 dated 22- Results
1-2021) patients of either gender and all ages admitted in Of 200 patients enrolled in the study, there were 148 males
Orthopaedic ward and those voluntarily willing to give (74%) and 52 females (26%). The mean age was 45.62
written informed consent were included in the study. years with range of 21-80 years. 26% were in the age group
Demographic details, prescription pattern that includes of 31-40 years followed by 22% above 60 years. Patients
the class of drugs, strength, dose, frequency and route admitted were of fractures (170), total hip replacement
of administration of drugs prescribed, WHO prescribing (17), total knee replacement (3), implant removal (5),
indicators (9), adverse drug reactions and potential ligament tear (3), septic arthritis (1), osteomyelitis (1).
drug-drug interactions (pDDI) were studied in 200 Important risk factors predisposing to fractures observed
patients. Also, the use of antibiotics as per WHO AWaRe were advancing age, that is 33 patients were above 65
guidelines (10) were studied which classifies antibiotics years of age, 31 females with postmenopausal status,
into Access, Watch, Reserve (AWaRe) group. “Access alcohol consumption seen in 15 patients and 1 patient
group includes antibiotics having activity against a wide had osteoporosis. Out of 170 patients with fractures 102
range of common susceptible pathogens while also patients (60%) were of open fractures and 68 (40%) were
showing lower resistance potential than antibiotics in closed fractures with fracture related infection seen only
the other groups. Watch group antibiotics include most in 4 patients (2.35%).
Table 1. WHO prescribing indicators.
Prescribing Indicator Results
Average number of drugs per encounter 2046/200 10.23
Percentage of drugs prescribed by generic name 1625/2120 79.42%
Percentage of encounters with an antibiotic prescribed 200/200 100%
Percentage of encounters with an injection prescribed 200/200 100%
Percentage of drugs prescribed from essential drug list 1679/2046 82.06%
March 2024;12(1) jpc.tums.ac.ir 41

Table 2. Drugs prescribed in Orthopaedic inpatients.
Sr No Types of drugs prescribed Total number of encounters Percentage
1 Tramadol 130 6.35%
2 Diclofenac 200 9.78%
3 Pantoprazole 200 9.78%
4 Ondansetron 200 9.78%
5 Calcium lactate 200 9.78%
6 Iron sulphate + Folic acid 12 0.59%
7 MVBC 200 9.78%
8 Vitamin D3 3 0.15%
9 Amoxicillin- Clavulanic acid 5 0.24%
10 Cefotaxime 95 4.64%
11 Ceftriaxone 105 5.13%
12 Metronidazole 152 7.43%
13 Piperacillin- Tazobactam 5 0.24%
14 Gentamicin 156 7.62%
15 Vancomycin 5 0.24%
16 Co-trimoxazole 3 0.15%
17 Teicoplanin 1 0.05%
18 Paracetamol 60 2.93%
19 Metformin 15 0.73%
20 Insulin 8 0.39%
21 Amlodipine 15 0.73%
22 Atorvastatin 1 0.05%
23 Atenolol 2 0.10%
24 Bupivacaine 189 9.24%
25 Clonidine 45 2.20%
26 Fentanyl 5 0.24%
27 Lignocaine 6 0.29%
28 Aspirin 2 0.10%
29 Rivaroxaban 2 0.10%
30 LMWH 18 0.88%
31 Warfarin 1 0.05%
32 Tetanus immunoglobulin 2 0.10%
33 Teriparatide 2 0.10%
34 Bisacodyl 1 0.05%
42 jpc.tums.ac.ir March 2024;12(1)

Jain, et al.
Table 3.Antibiotics classified as per WHO Access, Watch, Reserve (AWaRe) classification.
Antibiotics classified as per

Total number of encounters (x) Percentage = x/ Total no of antibiotics prescribed (527) *100
WHO AWaRe classification
Access 316 59.96%
Amoxicillin- Clavulanic acid 5 0.95%
Metronidazole 152 28.84%
Gentamicin 156 29.60%
Co-trimoxazole 3 0.57%
Watch 211 40.04%
Cefotaxime 95 18.03%
Ceftriaxone 105 19.92%
Piperacillin- Tazobactam 5 0.95%
Vancomycin 5 0.95%
Teicoplanin 1 0.19%
Reserve 0 0%
None
A total number of 2046 drugs were prescribed over 200 Antibiotics (25.76%) was the most common class of drug
prescriptions. Prescriptions were analysed according to prescribed followed by
WHO indicators and summarised in Table 1. 99.9% drugs
Supplements (20.28%) and Analgesics (16.13%).
were prescribed from hospital pharmacy. Polypharmacy
(Prescriptions having 5 or more than 5 drugs) was seen Average number of antibiotics per prescription was 2.635.
in 100% prescriptions. Fixed dose combinations (FDCs) Antibiotics were classified as per WHO Access, Watch,
included Multivitamin B complex (200), Amoxicillin Reserve (AWaRe) classification and summarised in Table
clavulanic acid (5), Ferrous sulphate folic acid (12), 3. Most common analgesic prescribed was Diclofenac
Cotrimoxazole (3) and Piperacillin Tazobactam (5). The (9.78%). Drugs given parenterally accounted for 63.29 %
details of drugs prescribed are shown in Table 2 and class- and 36.71% drugs were given orally.
Average number of antibiotics per prescription = Total number of antimicrobials prescribed

Total number of prescriptions
= 527/200 = 2.635
Average number of analgesics per prescription = Total number of analgesics prescribed

Total number of prescriptions
= 330/200 =1.65
Of 200 patients, adverse drug reactions were observed in Of 200 prescriptions, 196 (98%) prescriptions had the
4 patients (2%) as seen in Table 4. potential for possible drug interactions. 95.8% of DDI
Causality assessment for Adverse drug reactions was were due to Pharmacokinetic (PK) interactions and 4.2%
done with Naranjo Scale (12). were Pharmacodynamic (PD) interactions.
.

Table 4. Drugs causing ADRs, Causality Assessments and Management
Causality assessment as Drug continued/

Drug Prescribed ADR No. of patients with ADR Management
per Naranjo Scale discontinued
Inj. Pheniramine, Inj.

Vancomycin Red man syndrome 1 Probable Discontinued
Hydrocortisone
Aspirin Gastritis 1 Possible Continued Injection Pantoprazole
Metronidazole Nausea, Vomiting 1 Possible Continued Symptomatic

Diarrhoea
Nausea,
Diclofenac 1 Possible Continued Injection Pantoprazole
epigastric pain
Discussion
A total of 200 patients admitted in Orthopaedic ward negative staphylococcus aureus, E coli. Thus, 97.65%
were selected and their prescriptions were analysed. patients who did not show any fracture related infection,
The mean age of patients was 45.62 years as compared were probably benefitting from good infection control
to 51.84 years seen in another study (13). Patients above practices and antimicrobial prophylaxis.
60 years constituted 22% similar to the 20.3% observed A total of 2046 drugs were prescribed in the 200 case files
by Abhilash et al., (14) emphasizing the fact that age that were analysed for
related bone changes in the geriatric population makes WHO Prescribing Indicators. Average number of
them prone to fractures even after trivial trauma. Male drugs per prescription was 10.23, slightly higher than
preponderance was higher 148 (74%) as compared to 8.86 seen in study by Baghel et al., (6) suggesting that
females 52 (26%), like in the study done by Muraraiah polypharmacy (seen in all prescriptions) is common
et al., where 73% patients were males, while 27% in orthopaedic inpatients due to factors like infection,
were females (15). Out of 52 female patients 31 were immobility, combination of risk factors and comorbidities,
postmenopausal and 21 were premenopausal. None of the all requiring pharmacological intervention. In the present
postmenopausal women received hormone replacement study, the most commonly prescribed class of drug
therapy. Higher percentage of postmenopausal females is was Antimicrobials (25.7%) followed by Supplements
in adherence with standard literature, that postmenopausal (20.28%) and Analgesics (16.13%) which is different
osteoporosis increases risk of fragility fractures (16). In from study done by Srividya et al., where analgesics
our study fractures (170 patients, 85%) was the most (31.81%) followed by antibiotics (22.24%) were most
common condition admitted in the Orthopaedic ward commonly prescribed (3). In this study, 79.42% of the
similar to Choudhury et al., study wherein fractures were drugs were prescribed by the generic name which was
the most common condition comprising 72% of patients higher than 60% observed in another study. Promoting
(17). Advancing age, that is age more than 65 years was generic drugs enables patients to get affordable health
seen in 33 participants (16.5%) and postmenopausal care and reduces economic burden on patients (15).
status in females in 31 participants (15.5%) were found to 99.90 % of the prescribed drugs were available in
be the most common risk factors. Diabetes was the most hospital pharmacy. This is a good indicator as maximum
common co-morbidity noted, similar to study done by drugs were available in the tertiary care hospital where
Srividya et al., (3) where hypertension and diabetes were the study was conducted. According to WHO 100%
the most common associated comorbidity in majority of drugs should be prescribed from NLEM. In the present
study population. It was seen that 102 patients (60%) study 82.06 % of the prescribed drugs were mentioned
admitted in the Orthopaedic ward were of open fractures in National List of Essential Medicine 2021 (NLEM)
and 68 (40%) were closed fractures. Fracture related similar to 85% seen in study done by Muraraiah et al.,
infection was seen in 4 patients only (2.35%) which was (15). Prescribing maximum drugs from NLEM ensures
lesser as compared to 5% observed in a study done by affordable and accessible healthcare for all. In our study
Radhamony et al., (18). Fracture related infection was percentage of encounters with antibiotics prescribed was
seen due to resistant organisms – Staphylococcus aureus 100% similar to study by Anjani Teja et al., probably
(Methicillin resistant), Klebsiella pneumonia, Coagulase because the study was done in orthopaedic wards where
surgical intervention warranted the use of antibiotics for

Jain, et al.
prophylaxis and treatment (7). In the present study only (92.87%) were Pharmacokinetic and 47 (7.13%) were
11% drugs were prescribed as a fixed dose combination Pharmacodynamic drug interactions (20). A study by
(FDC), all FDCs being rationale and justified. In a study Yadav et al., also showed Pharmacokinetic interactions to
done by Abhilash et al., 40.3% drugs prescribed were be higher (88.2%) than Pharmacodynamic ones (11.8%)
FDCs which is much higher as compared to our study (21). In our study, a few potential drug interactions were
(14). It is of utmost importance that FDC prescribed such that they would require close monitoring of therapy
are rational since irrational FDCs not only produce to prevent adverse effects (Aspirin and diclofenac which
undesirable adverse effects but also increase economic had potential to increase chances of bleeding) while
burden on patients and healthcare as a whole. others did not have any significant clinical consequence
Average number of antimicrobials used was 2.635. (Pantoprazole (oral) and Ferrous sulfate, Pantoprazole
Antibiotics prescribed meticulously followed the WHO (oral) and cyanocobalamin). Some interacting drugs
Access, Watch, Reserve (AWaRe) classification keeping showed pharmacodynamic synergism, that increased the
in mind the need to reduce antimicrobial resistance. In effect of drugs and was beneficial in therapy. No serious
our study, 59.96% of antibiotics were from access group drug interaction requiring modification in therapy was
which is in accordance with the WHO recommendation noted.
that at least 60% antibiotics should be from the Access The study was done in a single tertiary care teaching
group. Watch group antibiotics, consisted of 40.04% and hospital with small sample size, extrapolation of results
Reserve group antibiotics that is “last resort” antibiotics would be better with a large sample and multicentric
were not used at all in our study. This highlights the studies.
judicious use of antibiotics, which is extremely important Current study provides insight into the drug utilisation
to prevent drug resistance (10). pattern, highlighting the extensive use of antibiotics and
Diclofenac was the most common analgesic prescribed analgesics in orthopaedic inpatients. A high percentage
our study (60.61%) which was similar to study done by of the drugs were prescribed from the Hospital pharmacy
Choudhury et al., (43.49%) (12). Average number of and National List of Essential Medicines (NLEM),
analgesics per prescription was 1.65 which was lesser as encouraging the idea of accessible and affordable
compared to a study done by Baghel et al., (6) where it healthcare for all. Our study highlighted the adherence
was 2.24 and similar to study done by Choudhury et al., to WHO AWaRe guidelines while prescribing antibiotics,
(17) where average number of analgesics per prescription be it for prophylaxis or treatment as a key in reducing
was 1.46. In patients where pain was not relieved with antibiotic resistance which is a massive healthcare concern
diclofenac, top ups of tramadol were given to relieve today. Although polypharmacy is usually unavoidable
severe pain. Among the 200 patients, adverse drug in orthopaedic inpatients, it is advisable to limit the
reactions were observed in 4 patients. number of drugs per prescription to as low as possible,
Red Man Syndrome was seen in 1 patient who received to minimize the risk of potential DDI and adverse drug
Vancomycin after which drug was discontinued. reactions that may occur subsequently. Study of pDDI
Sivagnanam et al., mentions it to be the most common enables to timely catch any serious drug interaction that
hypersensitivity reaction associated with vancomycin (19). may require therapy modification and early identification
Polypharmacy predisposes patients to develop ADRs and and management of ADR helps ensure better clinical
DDI, thus their identification, prevention and treatment is outcomes thereby reducing economic burden on health
vital to patient safety (20). 196 (98%) prescriptions had care system.
the potential for possible drug interactions, 4 prescriptions
had no potential drug interaction, whereas 3 pDDI were Conflict of Interest
noted in majority of prescriptions (114). This finding was There are no Conflict of Interest.
different as compared to a study done by Solanki and
Patel et al where maximum number of prescriptions (60) References
showed 4 pDDI. The maximum number of possible drug
1. Wu AM, Bisignano C, James SL, et al. Global,
interactions in prescriptions was 4 and minimum number
regional, and national burden of bone fractures in 204
of interactions was 1. In study done by Solanki and Patel et
countries and territories, 1990–2019: a systematic
al maximum number of drug interactions in a prescription
analysis from the Global Burden of Disease Study
was 5. A total of 500 possible drug interactions were
2019. Lancet Healthy Longev. 2021;2(9):580-592.
noted, out of which 479 (95.8%) were Pharmacokinetic
drug interactions and 21(4.2%) were Pharmacodynamic 2. Ghosh AK, Kumar A, Ray M. Drug utilization study
drug interactions. Similar findings were seen in study on antibiotics use in an orthopaedics department of
done by Solanki and Patel et al., where out of 660, 613 a tertiary care hospital in west Bengal. Journal of

Drug Delivery and Therapeutics. 2013;3(2),98-103. International Journal of Scientific & Technology
3. Srividya BP, Shashikumar NS, Amardeep G. Research. 2020; 9(3):1207-1211.
Retrospective audit of prescription of drugs among 14. Abhilash S, Rao RR, Yadunath PS. Assessment
inpatients of orthopedic wards at Medical College of prescribing pattern among orthopedic in-
Teaching Hospital, Mandya. National Journal of patients using WHO prescribing indicators. Asian
Physiology, Pharmacy and Pharmacology. 2016; Journal of Pharmaceutical and Clinical Research.
6(4):282-285. 2018;11(12):505-9.
4. Bhartiy SS, Shinde M, Nandeshwar S, Tiwari SC. 15. Muraraiah S, Rajarathna K, Vishwanath M,
Pattern of prescribing practices in the Madhya Ramaswamy A, Kamath SD, Seshu S. Evaluation of
Pradesh, India. Kathmandu University Medical WHO prescribing indicators among orthopaedic in-
Journal. 2008;6(1):55-59. patients at a tertiary care hospital. Journal of Chemical
5. World Health Organization, Introduction to Drug and Pharmaceutical Research. 2014;6(8):278-280.
Utilization Research. Geneva: WHO, 2003: 6-48. 16. Sözen T, Özışık L, Başaran NÇ. An overview and
6. Baghel R, Adwal SK, Singh V, Chourishi A. management of osteoporosis. Eur J Rheumatol.
Prescribing pattern and drug utilization study in 2017;4(1):46.
inpatients of department of Orthopaedics in a 17. Choudhury DK, Bezbaruah BK. Prescribing pattern
rural teaching hospital of Ujjain, Madhya Pradesh, of analgesics in orthopedic in-patient department
India. International Journal of Basic & Clinical at tertiary care hospital in Guwahati, Assam,
Pharmacology.2018.7(9), 1763-1769. Northeast India. Indian Journal of Pharmacology.
7. Ch AT, Janani Y, Praveena AN. A Study on 2016;48(4):377.
prescribing pattern of drugs in orthopaedic in-patient 18. Radhamony NG, Raj R, Raju S. Analysis of
department at a tertiary care hospital in Guntur incidence of postoperative wound infection in closed
region. International Journal of Pharmaceutical fractures treated by surgical fixation–A prospective
Research and Life Sciences. 2020;8(2):60-70. study. Ann Med Surg (Lond). 2021; 72:1-4.
8. Krishnaswamy K, Kumar BD, Radhaiah G. A 19. Sivagnanam S, Deleu D.Red man syndrome. Crit
drug survey—precepts and practices. Eur J Clin Care. 2002;7(2):1-3.
Pharmacol. 1985;29(3):363-70.
20. Solanki N, Patel Y. Drug utilization pattern and
9. World Health Organization (WHO) and International drug interaction study of antibiotics prescribed to
Network for Rational Use of Drugs. How to orthopaedic patients in private hospital. Archives of
Investigate Drug Use in Health Facilities: Selected Pharmacy Practice. 2019;10(4):114-7.
Drug Use indicators. Geneva: WHO; 1993:12-48.
21. Yadav DK, Alam K, Sah AK, Sarraf DP. Utilization
10. World Health Organization. WHO Access, Watch, pattern of antibiotics and drug related problems in
Reserve (AWaRe) classification of antibiotics for the orthopedic department at a tertiary care hospital:
evaluation and monitoring of use, 2021. Geneva: a prospective study. Journal of Drug Delivery and
World Health Organization; 2021 (WHO/MHP/ Therapeutics. 2020; 10(3):24-30.
HPS/EML/2021.04).
11. Dagnew EM, Ergena AE, Wondm SA, Sendekie
AK. Potential drug-drug interactions and associated
factors among admitted patients with psychiatric
disorders at selected hospitals in Northwest Ethiopia.
BMC Pharmacol Toxicol. 2022;23(1):88. PLEASE CITE THIS PAPER AS:
12. Naranjo CA, Busto U, Sellers EM, et al. A method Jain M, Hiray R. Pharmacoepidemiology of Drugs
for estimating the probability of adverse drug Used in Indoor Patients of Orthopaedic Department at a
reactions. Clin Pharmacol Ther. 1981;30(2):239-45. Tertiary Care Hospital. J Pharm Care 2024; 12(1): 40-46.
13. Chandran B, Vadakkan K, Altaf M, Shetty V, Chand

S, Vijayan A. A retrospective study on postoperative
usage pattern of analgesics in orthopaedics
department of a tertiary care teaching hospital.

STROBE Statement—Checklist of items that should be included in reports of cross-sectional studies
Item
No Recommendation
Title and abstract 1 (a) Artikel ini menggunakan desain studi observasional cross-sectional, yang
menganalisis pola penggunaan obat di pasien rawat inap departemen ortopedi di
rumah sakit perawatan tersier selama periode satu tahun.
(b) Abstrak menyajikan ringkasan yang menjelaskan pola penggunaan obat pada
pasien rawat inap ortopedi, termasuk analisis terhadap interaksi obat, efek samping
obat, serta penggunaan antibiotik sesuai pedoman WHO AWaRe.
Introduction
Background/rationale 2 Penelitian ini penting untuk mengevaluasi penggunaan obat yang rasional di rumah
sakit, dengan fokus pada pasien ortopedi yang sering memerlukan
antibiotik dan analgetik.
Objectives 3 Tujuan utama adalah untuk menilai pola penggunaan obat pada pasien rawat inap
ortopedi, mengevaluasi indikasi WHO untuk penggunaan obat, interaksi obat yang
berpotensi, dan efek samping yang muncul.
Methods
Study design 4 Desain studi adalah cross-sectional observational, dilakukan di rumah sakit perawatan
tersier dengan menganalisis 200 resep obat yang diberikan pada pasien ortopedi
selama satu tahun.
Setting 5 Penelitian dilakukan di rumah sakit pendidikan perawatan tersier di India, dari April
2021 hingga April 2022, dengan data diambil dari resep yang diberikan kepada pasien
di bangsal ortopedi.
Participants 6 (a) Kriteria inklusi adalah pasien rawat inap yang dirawat di bangsal ortopedi dengan
persetujuan tertulis. Tidak ada pencocokan kelompok dalam penelitian ini karena
desain observasional cross-sectional.
Variables 7 Variabel yang dianalisis mencakup jenis obat yang digunakan, interaksi obat, efek
samping, serta penggunaan antibiotik sesuai pedoman WHO AWaRe.
Data sources/ 8* Data diambil dari resep obat yang diberikan pada pasien, dengan informasi tentang
measurement dosis, frekuensi, dan jenis obat tercatat. Interaksi obat dinilai menggunakan alat
pengecek interaksi obat Medscape.
Bias 9 Potensi bias terkait dengan kekurangan data atau penggunaan resep yang tidak
lengkap, namun data ini diambil dari sumber yang dapat diandalkan dan lengkap,
yaitu resep yang diterbitkan oleh rumah sakit.
Study size 10 Ukuran sampel ditentukan berdasarkan jumlah resep yang dianalisis, yaitu 200 resep
yang mencakup berbagai kelas obat yang digunakan di bangsal ortopedi.
Quantitative variables 11 Variabel kuantitatif meliputi jumlah obat yang diresepkan per pasien, serta jenis dan
kelas obat yang digunakan. Analisis dilakukan untuk menghitung proporsi
penggunaan obat-obatan tertentu.
Statistical methods 12 (a) Analisis statistik deskriptif digunakan untuk menganalisis data, termasuk
perhitungan rata-rata jumlah obat per resep dan distribusi penggunaan antibiotik
sesuai pedoman WHO AWaRe. Tidak ada metode pengendalian untuk confounding
karena fokus penelitian adalah deskriptif.
(b) Tidak ada analisis subkelompok atau interaksi yang dilakukan, karena penelitian
ini berfokus pada evaluasi keseluruhan pola penggunaan obat pada pasien ortopedi
tanpa membagi kelompok subpopulasi.
(c) Tidak ada data yang hilang dalam penelitian ini, karena data diperoleh dari catatan
1
resep lengkap dan catatan medis rumah sakit yang tersedia
(d) Kehilangan tindak lanjut tidak relevan untuk studi ini, karena ini adalah studi
cross-sectional yang menggunakan data retrospektif dari resep tanpa
tindak lanjut pasien.
(e) Analisis sensitivitas tidak dilakukan dalam penelitian ini karena desainnya adalah
deskriptif, yang hanya bertujuan menggambarkan pola penggunaan obat tanpa
pengujian lebih lanjut terhadap variasi data.
Results
Participants 13* (a) Sebanyak 200 pasien rawat inap di bangsal ortopedi rumah sakit dianalisis. Tidak
ada partisipan yang dikeluarkan karena semua pasien yang memenuhi kriteria inklusi
diikutsertakan dalam studi ini.
(b) Tidak ada partisipasi yang hilang atau pasien yang dikeluarkan, karena seluruh
data diperoleh dari resep dan catatan medis yang tersedia lengkap.
(c) Diagram alur tidak digunakan dalam penelitian ini, karena semua pasien yang
memenuhi kriteria inklusi dimasukkan dalam analisis tanpa ada proses
seleksi yang rumit.
Descriptive data 14* (a) Karakteristik peserta meliputi distribusi usia dan jenis kelamin: dari 200 pasien,
148 adalah laki-laki (74%) dan 52 adalah perempuan (26%), dengan usia rata-rata
45,62 tahun. Kondisi klinis utama yang diamati adalah patah tulang (170 kasus),
penggantian sendi panggul (17 kasus), dan penggantian sendi lutut (3 kasus). Faktor
risiko klinis utama termasuk usia lanjut, status pascamenopause pada perempuan,
konsumsi alkohol, dan osteoporosis.
(b) Tidak ada data yang hilang untuk variabel yang diamati. Semua data demografis,
kondisi klinis, dan informasi resep obat tersedia lengkap dari catatan
medis rumah sakit.
Outcome data 15* 2046 obat diresepkan pada 200 pasien. Rata-rata jumlah obat per resep adalah 10,23,
dengan antibiotik dan analgesik sebagai kategori obat yang paling sering digunakan.
Main results 16 (a) Hasil utama menunjukkan bahwa antibiotik adalah kelas obat yang paling banyak
diresepkan (25,76% dari total resep), diikuti oleh suplemen (20,28%) dan analgesik
(16,13%). Rata-rata jumlah obat per resep adalah 10,23. Tidak ada penyesuaian untuk
faktor pembaur dalam hasil ini karena studi ini bersifat deskriptif.
(b) Variabel kontinu seperti usia dikelompokkan dalam kategori usia: 31–40 tahun
(26%) dan >60 tahun (22%) adalah kelompok usia terbesar. Tidak ada batasan
tambahan yang diterapkan pada variabel lain.
(c) Studi ini tidak mengukur risiko relatif atau risiko absolut, karena tujuan utamanya
adalah deskriptif dan fokus pada pola penggunaan obat, bukan hubungan kausal
antara variabel.
Other analyses 17 Tidak ada analisis subkelompok atau sensitivitas yang dilakukan dalam studi ini.
Discussion
Key results 18 Hasil menunjukkan penggunaan antibiotik yang luas di bangsal ortopedi, dengan
kepatuhan terhadap pedoman WHO AWaRe yang membantu mengurangi resistansi
antibiotik dan meningkatkan perawatan pasien.
Limitations 19 Keterbatasan utama studi ini adalah ukuran sampel yang terbatas dan desain yang
hanya dilakukan di satu rumah sakit, yang membatasi generalisasi hasil.
Interpretation 20 Hasil penelitian menunjukkan pola penggunaan obat yang rasional, meskipun masih
ada potensi interaksi obat yang perlu diperhatikan. Adanya pedoman WHO AWaRe
yang diterapkan menunjukkan praktik pengobatan yang baik untuk mencegah
2
resistansi antibiotik.
Generalisability 21 Temuan ini relevan untuk rumah sakit perawatan tersier lainnya, tetapi akan lebih
berguna jika dilakukan studi multisenter dengan ukuran sampel yang lebih besar
Other information
Funding 22 Tidak ada informasi pendanaan yang disebutkan dalam artikel ini
*Give information separately for exposed and unexposed groups.

Dalam konteks penelitian ini, tidak ada pembagian langsung antara kelompok "terpapar" dan "tidak terpapar" karena
desain studi adalah deskriptif cross-sectional yang mengamati pola penggunaan obat di bangsal ortopedi tanpa
perlakuan atau eksposur tertentu yang diterapkan pada satu kelompok dibandingkan dengan kelompok lain.
Namun, berikut ini adalah interpretasi yang dapat digunakan berdasarkan pengelompokan data:
Kelompok Terpapar (Exposed Group): Dalam studi ini, semua pasien rawat inap ortopedi yang menerima antibiotik,
analgesik, atau obat-obatan lain di bangsal ortopedi dianggap “terpapar” oleh jenis obat tertentu. Sebanyak 100% pasien
menerima antibiotik sebagai bagian dari perawatan, dengan fokus pada penggunaan antibiotik sesuai pedoman WHO
AWaRe.
Kelompok Tidak Terpapar (Unexposed Group): Tidak ada kelompok pasien yang sepenuhnya "tidak terpapar" pada
pengobatan, karena setiap pasien dalam penelitian menerima obat-obatan tertentu sesuai dengan diagnosis dan
kebutuhan klinis mereka.
Studi ini menilai pola umum penggunaan obat di seluruh populasi pasien ortopedi, tanpa kelompok kontrol atau
kelompok tidak terpapar yang dibedakan secara spesifik.
Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and
published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely
available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at
http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is
available at www.strobe-statement.org.

tugasepid_a2_ina hariska_1011_jurnal review (1)

Uploaded by

Copyright:

Available Formats

tugasepid_a2_ina hariska_1011_jurnal review (1)

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

tugasepid_a2_ina hariska_1011_jurnal review (1)

Uploaded by

Copyright:

Available Formats

antibiotics

1 Department of Pharmacology, West Kazakhstan Marat Ospanov Medical University,

Copyright: © 2023 by the authors. 1. Introduction

Antibiotics 2023, 12, 1596. https://doi.org/10.3390/antibiotics12111596 https://www.mdpi.com/journal/antibiotics

Prescribed Antibiotics DDD in the Hospital Per 100 Bed-Days

Figure 1. The consumption of consumption

Significant changes in antibiotic consumption were observed during the pandemic.

while levofloxacin witnessed a substantial increase of 194.7%. Such dramatic increases

pre-pandemic phases (Figure 2).

4. Materials and Methods

4.2. The Structure of the Hospital

4.3. The Methodology Employed and the Statistical Analysis

macoepidemiological research on drug usage. The WHO endorses this methodology

*Give information separately for exposed and unexposed groups.

Pharmacoepidemiology of Drugs Used in Indoor Patients of Orthopaedic

Received: 2024-01-09, Revised: 2024-02-14, Accepted: 2024-03-04, Published: 2024-03-31

Keywords: Drug Utilization Research; Orthopaedic; Cephalosporins

Introduction prevent resistance, adverse drug reactions and to decrease

* Corresponding Author: Dr Rajesh S. Hiray

Copyright © 2024 Tehran University of Medical Sciences.

Table 1. WHO prescribing indicators.

Prescribing Indicator Results

Average number of drugs per encounter 2046/200 10.23

Percentage of drugs prescribed by generic name 1625/2120 79.42%

Percentage of encounters with an antibiotic prescribed 200/200 100%

Percentage of encounters with an injection prescribed 200/200 100%

Percentage of drugs prescribed from essential drug list 1679/2046 82.06%

March 2024;12(1) jpc.tums.ac.ir 41

Table 2. Drugs prescribed in Orthopaedic inpatients.

Sr No Types of drugs prescribed Total number of encounters Percentage

1 Tramadol 130 6.35%

2 Diclofenac 200 9.78%

3 Pantoprazole 200 9.78%

4 Ondansetron 200 9.78%

5 Calcium lactate 200 9.78%

6 Iron sulphate + Folic acid 12 0.59%

7 MVBC 200 9.78%

9 Amoxicillin- Clavulanic acid 5 0.24%

11 Ceftriaxone 105 5.13%

12 Metronidazole 152 7.43%

13 Piperacillin- Tazobactam 5 0.24%

14 Gentamicin 156 7.62%

24 Bupivacaine 189 9.24%

32 Tetanus immunoglobulin 2 0.10%

42 jpc.tums.ac.ir March 2024;12(1)

Antibiotics classified as per

Access 316 59.96%

Amoxicillin- Clavulanic acid 5 0.95%

Metronidazole 152 28.84%

Gentamicin 156 29.60%

Watch 211 40.04%

Ceftriaxone 105 19.92%

Piperacillin- Tazobactam 5 0.95%

Average number of antibiotics per prescription = Total number of antimicrobials prescribed

Average number of analgesics per prescription = Total number of analgesics prescribed

March 2024;12(1) jpc.tums.ac.ir 43

Table 4. Drugs causing ADRs, Causality Assessments and Management

Causality assessment as Drug continued/

Inj. Pheniramine, Inj.

Aspirin Gastritis 1 Possible Continued Injection Pantoprazole