The use of antibiotics in COVID-19 management: a rapid review of national treatment guidelines in 10 African countries

Abstract

Antimicrobial resistance is a hidden threat lurking behind the COVID-19 pandemic which has claimed thousands of lives prior to the emergence of the global outbreak. With a pandemic on the scale of COVID-19, antimicrobial resistance has the potential to become a double-edged sword with the overuse of antibiotics having the potential of taking us back to the pre-antibiotic era. Antimicrobial resistance is majorly attributed to widespread and unnecessary use of antibiotics, among other causes, which has facilitated the emergence and spread of resistant pathogens. Our study aimed to conduct a rapid review of national treatment guidelines for COVID-19 in 10 African countries (Ghana, Kenya, Uganda, Nigeria, South Africa, Zimbabwe, Botswana, Liberia, Ethiopia, and Rwanda) and examined its implication for antimicrobial resistance response on the continent. Our findings revealed that various antibiotics, such as azithromycin, doxycycline, clarithromycin, ceftriaxone, erythromycin, amoxicillin, amoxicillin-clavulanic acid, ampicillin, gentamicin, benzylpenicillin, piperacillin/tazobactam, ciprofloxacin, ceftazidime, cefepime, vancomycin, meropenem, and cefuroxime among others, were recommended for use in the management of COVID-19. This is worrisome in that COVID-19 is a viral disease and only a few COVID-19 patients would have bacterial co-infection. Our study highlighted the need to emphasize prudent and judicious use of antibiotics in the management of COVID-19 in Africa.

Full text

L E T T E R T O T H E E D I T O R Open Access
The use of antibiotics in COVID-19
management: a rapid review of national
treatment guidelines in 10 African
countries
Yusuff Adebayo Adebisi
1,2
, Nafisat Dasola Jimoh
3
, Isaac Olushola Ogunkola
4
, Theogene Uwizeyimana
5*
,
Alaka Hassan Olayemi
6
, Nelson Ashinedu Ukor
7
and Don Eliseo Lucero-Prisno III
8
Abstract
Antimicrobial resistance is a hidden threat lurking behind the COVID-19 pandemic which has claimed thousands of
lives prior to the emergence of the global outbreak. With a pandemic on the scale of COVID-19, antimicrobial
resistance has the potential to become a double-edged sword with the overuse of antibiotics having the potential
of taking us back to the pre-antibiotic era. Antimicrobial resistance is majorly attributed to widespread and
unnecessary use of antibiotics, among other causes, which has facilitated the emergence and spread of resistant
pathogens. Our study aimed to conduct a rapid review of national treatment guidelines for COVID-19 in 10 African
countries (Ghana, Kenya, Uganda, Nigeria, South Africa, Zimbabwe, Botswana, Liberia, Ethiopia, and Rwanda) and
examined its implication for antimicrobial resistance response on the continent. Our findings revealed that various
antibiotics, such as azithromycin, doxycycline, clarithromycin, ceftriaxone, erythromycin, amoxicillin, amoxicillin-
clavulanic acid, ampicillin, gentamicin, benzylpenicillin, piperacillin/tazobactam, ciprofloxacin, ceftazidime, cefepime,
vancomycin, meropenem, and cefuroxime among others, were recommended for use in the management of
COVID-19. This is worrisome in that COVID-19 is a viral disease and only a few COVID-19 patients would have
bacterial co-infection. Our study highlighted the need to emphasize prudent and judicious use of antibiotics in the
management of COVID-19 in Africa.
Keywords: COVID-19, Clinical case management, Antimicrobial resistance, Antibiotic resistance, Pandemic, Africa
To the editor:
COVID-19 continues to threaten health systems glo-
bally and African countries are not spared [1,2]. Prior to
the COVID-19 outbreak, antimicrobial resistance (AMR)
has been a “hidden”pandemic threatening healthcare
delivery worldwide, claiming 700,000 deaths per year [3].
According to the World Health Organization (WHO),
AMR occurs when pathogens such as viruses, bacteria,
parasites, and fungi undergo changes and no longer
respond to treatment making infections difficult to treat,
thus increasing the risk of disease spread, poor out-
comes, and mortality [4]. In 2019, the WHO also identi-
fied AMR as one of the major threats facing healthcare
systems [5]. AMR is a growing global health issue to
which the present COVID-19 outbreak may contribute
[3]. This situation is further complicated with the pres-
sure to repurpose drugs to treat COVID-19, deteriorat-
ing economic conditions, and the shifting of resources
away from antimicrobial stewardship programs resulting
to indiscriminate use of antibiotics in COVID-19 treat-
ment [6]. Presently, the COVID-19 is ruling all aspects
of healthcare globally, including health systems response
© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if
changes were made. The images or other third party material in this article are included in the article's Creative Commons
licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons
licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
* Correspondence: uwizeyimanatheogene@gmail.com
5
Department of Public Health, Mount Kenya University Rwanda, Kigali,
Rwanda
Full list of author information is available at the end of the article
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Adebisi et al. Tropical Medicine and Health (2021) 49:51
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to antimicrobial resistance and the impact will persist
for a while, even after the pandemic. With the alarming
increase in antibiotic resistance cases and the fact that
there are few new antimicrobial agents in the pipeline, it
is important to monitor the epidemiology of pathogens
to make informed treatment decisions.
In this paper, we conducted a rapid review of national
treatment guidelines for COVID-19 in 10 African coun-
tries and examined its implication for antimicrobial
resistance response on the continent. The 10 African
countries include Ghana, Kenya, Uganda, Nigeria, South
Africa, Zimbabwe, Botswana, Liberia, Ethiopia, and
Rwanda. The countries were selected at random with no
predetermined criterion. An online search was
conducted to retrieve the national treatment guidelines
for the management of COVID-19 in these countries
through the government/ministry of health websites.
The report guidelines were reviewed to understand the
use of antibiotics in the management of COVID-19, i.e.,
which antibiotics and in what scenario they were
recommended.
In Table 1, we summarize our findings on the use of
antibiotics in the management of COVID-19. Our find-
ings revealed that various antibiotics such as azithromy-
cin, doxycycline, clarithromycin, ceftriaxone, amoxicillin,
amoxicillin-clavulanic acid, ampicillin, gentamicin,
erythromycin, benzylpenicillin, piperacillin/tazobactam,
ciprofloxacin, ceftazidime, cefepime, vancomycin, mero-
penem, and cefuroxime were recommended for use in
the management of COVID-19, i.e., asymptomatic, mild,
moderate, and severe COVID-19 with/without complica-
tions. Most of the guidelines recommended directed and
empiric therapy with antibiotics. The WHO recom-
mended that antibiotic therapy or prophylaxis should
not be used in patients with mild/moderate COVID-19
unless it is justifiable [7]. Interestingly, according to our
findings, some countries still recommended the use of
antibiotics in the management of mild COVID-19. Most
antibiotics recommended across the African countries
were from the “watch”(antibiotics that have higher re-
sistance potential) and “reserve”(antibiotics and anti-
biotic classes that should be reserved for treatment of
confirmed or suspected infections due to multi-drug-
resistant organisms) categories of WHO AWaRe classifi-
cation, which may be further adding “fuel to the fire”of
the already fearsome antimicrobial resistance situation.
Our study reiterates the need to go revisit fundamentals
of diagnostic stewardship and practice culture-directed
therapy using narrow-spectrum antibiotics, from the “ac-
cess”category of AWaRe classification which has lower
resistance potential than antibiotics in the other groups.
Empirical use of antibiotics is a risk factor for develop-
ment of resistance [8], and in the case of COVID-19, this
situation in resource-limited settings remains worrisome
because of the weak laboratory systems, ineffective anti-
microbial stewardship, lack of human and financial
resources, prescribers’opposition, limited access to med-
icines, lack of awareness and absence of antimicrobial
stewardship committees, concerns regarding fake and
counterfeit antibiotics, limited hospital infection preven-
tion program infrastructure, and lack of effective anti-
biotic policy among others [6]. Our findings also show
that broad-spectrum antibiotics were the most recom-
mended antibiotics with the drawback of selection for
resistance [9]. The WHO has also warned against any
indiscriminate use of (broad-spectrum) antibiotics in the
management of COVID-19 [7]. Our review also revealed
that the national treatment guideline of Liberia recom-
mended the use of antibiotics in sore throat, diarrhea,
and cough that are associated with COVID-19 symp-
toms. This highlights the need to ensure prudent use of
antibiotics in COVID-19, being a viral disease.
Various studies have also shown that most bacterial
pneumonias that are diagnosed early in COVID-19
patients can be safely and effectively treated with antibi-
otics, and broad-spectrum antibiotics are widely used
[10–12]. A recent review article that pooled data from
19 studies (2834 patients) revealed that the mean rate of
antibiotic use in COVID-19 management is 74.0% and
only 17.6% of patients had secondary infections [13]. An-
other study conducted in South Africa revealed that bac-
terial co-infection is rare at the time of intensive care
unit admission with COVID-19 [14]. Another meta-
analysis revealed that only 7.0% of hospitalized COVID-
19 patients had a bacterial co-infection [15]. A recent
multi-center study showed that only 86 out of 905
(9.5%) confirmed COVID-19 patients were clinically di-
agnosed with bacterial co-infection [16]. This implies
that only a few COVID-19 patients would need antibi-
otics for possible bacterial pneumonia and other super-
imposed/co-infections [17].
For patients who are critically ill and hospitalized, the
diagnosis of a potential bacterial co-infection is uncer-
tain; physicians tend to use broad-spectrum antibiotics
to manage such patients [18]. An increase in usage of
broad-spectrum antibiotics from the “watch”and “re-
serve”categories will not only make the agents ineffect-
ive but will also create highly drug-resistant bugs which
may become clinicians’nightmare. This is a major threat
to antimicrobial stewardship. For instance, an increase
in the use of azithromycin, a broad-spectrum macrolide
antibiotic, has been documented amid the pandemic in
many African countries [19,20], usually with hydroxy-
chloroquine in the management of COVID-19. Evidence
has also shown that routine use of azithromycin for re-
ducing time to recovery or risk of hospitalization for
people with suspected COVID-19 in the community has
been documented to offer no benefit [21–23]. In
Adebisi et al. Tropical Medicine and Health (2021) 49:51 Page 2 of 5

Table 1 The use of antibiotics in COVID-19 management in 10 African countries
Country List of antibiotics
recommended in the guideline
Scenario for recommendation Compliance with WHO
guideline
Guideline references (accessed
4 June 2021)
Ghana Azithromycin, doxycycline Recommended for use in the
management of confirmed cases
(with asymptomatic, mild, or
moderate symptoms)
-WHO does not recommend
antibiotic use in suspected/
mild/moderate COVID-19.
-WHO does not recommend
azithromycin with/without
hydroxychloroquine in the
management of COVID-19.
-WHO does not encourage the
use of broad-spectrum antibi-
otics for COVID-19 especially
those on the Watch and Re-
serve List.
https://www.moh.gov.gh/wp-
content/uploads/2016/02/
COVID-19-STG-JUNE-2020-1.pdf
Kenya Amoxicillin, amoxicillin-clavulanic
acid, erythromycin, azithromycin,
clarithromycin
Recommended for use in the
management of severe COVID-19
and sepsis. Empirical use of anti-
microbials for all severe acute re-
spiratory infections and should
be de-escalated on the basis of
microbiology results and clinical
judgment
-WHO does not recommend
azithromycin with/without
hydroxychloroquine in the
management of COVID-19
- WHO does not encourage
the use of broad-spectrum
antibiotics for COVID-19 espe-
cially those on the Watch
and Reserve List.
https://kma.co.ke/Documents/
Case%20management%2
0protocol.pdf
Uganda Azithromycin and amoxicillin
(moderate COVID-19); ceftriax-
one, ampicillin, gentamicin, ben-
zylpenicillin, and azithromycin
(severe COVID-19 pneumonia);
and azithromycin, piperacillin/taz-
obactam (critically ill COVID-19
patient)
Empiric use of antibiotics is
recommended for sepsis in
COVID-19 patient as well as in
moderate, severe, and critically ill
COVID-19 patient and de-
escalated on the basis of micro-
biology results and clinical
judgment
-WHO does not recommend
antibiotic use in mild/
moderate COVID-19.
-WHO does not encourage the
use of broad-spectrum antibi-
otics for COVID-19 especially
those on the Watch and Re-
serve List.
https://covidlawlab.org/wp-
content/uploads/2020/06/
National-Guidelines-for-Clinical-
Management-of-Covid-19.pdf
Nigeria No specific antibiotic was stated
in the treatment guideline for
COVID-19. However, broad-
spectrum antibiotics based on
local epidemiology were recom-
mended for some cases
Prophylactic/empiric use of
antibiotics is not recommended
in asymptomatic and mild
COVID-19 cases. For severe
COVID-19 cases, the choice of an-
tibiotics should be based on the
clinical diagnosis, local epidemi-
ology, and antibiotic
susceptibility
The country’s guideline
complies with WHO treatment
guidelines for COVID-19 and
does not list any specific anti-
biotic for use in COVID-19
management.
https://covid19.ncdc.gov.ng/
media/files/National_Interim_
Guidelines_for_Clinical_
Management_of_COVID-19_v3.
pdf
South
Africa
Ceftriaxone and azithromycin Empirical use of antibiotics is
recommended for co-infections
such as conventional
community-acquired pneumonia
or atypical pneumonia
WHO does not encourage the
use of broad-spectrum antibi-
otics for COVID-19 especially
those on the Watch and Re-
serve List.
https://www.nicd.ac.za/wp-
content/uploads/2020/03/
Clinical-Management-of-COVID-1
9-disease_Version-3_27March202
0.pdf
Zimbabwe Ceftriaxone and azithromycin Recommend that antimicrobial
therapy should not be delayed
just to collect blood culture.
Empiric antibiotics are
recommended
WHO does not encourage the
use of broad-spectrum antibi-
otics for COVID-19 especially
those on the Watch and Re-
serve List.
https://cquin.icap.columbia.edu/
wp-content/uploads/2020/04/
ZIMBABWE_COVID-19-CLINICAL-
GUIDELINES-APRIL-2020.pdf
Botswana Amoxicillin-clavulanic acid and
azithromycin (suspected/
confirmed COVID-19 cases)
If clinical suspicion for co-
infection exists, consider empir-
ical antimicrobials to treat co-
pathogens causing the syndrome
-WHO does not encourage the
use of broad-spectrum antibi-
otics for COVID-19 especially
those on the Watch and Re-
serve List.
-WHO does not recommend
antibiotic use in mild/
moderate/suspected COVID-19.
-WHO does not recommend
azithromycin alone or with/
without hydroxychloroquine in
the management of COVID-19.
https://covid19portal.gov.bw/
sites/default/files/2020-05/
Interim-COVID-19-Clinical-
Management-Guideline-
Botswana.pdf
Liberia Amoxicillin-clavulanic acid,
azithromycin, amoxicillin
(moderate COVID-19) and
Empiric use of antibiotic (broad
spectrum) is recommended for
severe and mild case. For COVID-
WHO does not encourage the
use of broad-spectrum antibi-
otics for COVID-19 especially
http://moh.gov.lr/wp-content/
uploads/Interim_Guidance_for_
care_of_Pts_with_Covid_19_in_
Adebisi et al. Tropical Medicine and Health (2021) 49:51 Page 3 of 5

summary, antibiotics need to be used with care and
should be withheld unless it is confirmed that the pa-
tient truly needs them. While lack of access to antibi-
otics could be dangerous in the same vein as its misuse,
it is of importance to ensure that these life-saving agents
are preserved and used with utmost care [18].
African countries are vulnerable to the looming threat
of the antimicrobial resistance. This is worrisome be-
cause pathogens that cause resistant infections thrive in
hospitals and medical facilities, putting all patients at
risk, irrespective of the severity of their medical condi-
tions. The situation is further catalyzed in Africa by un-
sanitary conditions, high burden of infectious diseases,
inadequate access to clean water, conflicts, poor cover-
age of vaccination program, and growing numbers of
immunosuppressed people, such as those living with
HIV, which facilitate both the evolution and emergence
of resistant organisms and their sporadic spread in the
community. In addition, judicious empirical use of anti-
biotics in Africa will be challenging because of the lack
of widespread data on antimicrobial resistance and ease
of purchase of antibiotics over the counter without a
prescription. Many African countries are also yet to align
with the international efforts to fight the increasing anti-
biotic resistance in that only seven African countries
have developed the national action plan on antimicrobial
resistance [24]. Our review highlighted the need to
emphasize prudent use of antibiotics in the management
of COVID-19 in Africa by strengthening antimicrobial
stewardship programs on the continent.
The COVID-19 pandemic reveals that we remain
susceptible to infections for which we have no spe-
cific treatment options [25,26]. This is a wakeup call
to African countries to ensure investment in anti-
microbial stewardship in order to optimize antibiotic
use by ensuring that the appropriate antibiotic is ad-
ministered at the right dose, for the right duration,
and in a way that ensures the maximum outcome
and reduces any untoward effect and development of
resistance. Diagnostic precision and addressing diag-
nostic insufficiency are also crucial in modifying the
current approach of widespread empirical antibiotic
use in the management of COVID-19. We also call
on national health authorities in African countries to
ensure their treatment guidelines for COVID-19 do
not encourage the injudicious use of antibiotics. All
countries should also implement measures to track
the use of antibiotics and comply with the WHO’s
guideline to promote antibiotic stewardship amid the
COVID-19 pandemic. Countries should also invest in
continuous training of their healthcare workers on
antimicrobial stewardship.
Table 1 The use of antibiotics in COVID-19 management in 10 African countries (Continued)
Country List of antibiotics
recommended in the guideline
Scenario for recommendation Compliance with WHO
guideline
Guideline references (accessed
4 June 2021)
amoxicillin-clavulanic, gentami-
cin, doxycycline acid, azithromy-
cin, and ampicillin (severe
COVID-19). Fluoroquinolones,
e.g., ciprofloxacin with or without
metronidazole in COVID-19-
related symptoms.
19-associated sepsis, laboratory
findings such as blood cultures,
sputum culture, chest X-ray,
examination of line sites, etc. are
recommended to guide anti-
biotic selection. Antibiotics are
also recommended for sore
throat in mild/moderate COVID-
19, as well as cough, and
diarrhea.
those on the Watch and Re-
serve List.
-WHO does not recommend
antibiotic use in mild/
moderate/suspected COVID-19.
-WHO does not recommend
azithromycin or with/without
hydroxychloroquine in the
management of COVID-19.
Liberia.pdf
Ethiopia Amoxicillin-clavulanic acid or
amoxicillin (moderate COVID-19)
and ceftazidime/cefepime and/or
vancomycin or meropenem
(other carbapenems) ± vanco-
mycin (severe/critical COVID-19).
Recommended antibiotics in
pediatrics also include gentami-
cin, ampicillin, ceftriaxone/cefo-
taxime, azithromycin, and
meropenem
Antibiotics (preferably broad
spectrum) are recommended for
empiric use based on physician
judgment after taking a sample
for blood culture, in severe
COVID-19 cases
WHO does not encourage the
use of broad-spectrum antibi-
otics for COVID-19 especially
those on the Watch and Re-
serve List.
-WHO does not recommend
antibiotic use in mild/
moderate/suspected COVID-19.
-WHO does not recommend
azithromycin or with/without
hydroxychloroquine in the
management of COVID-19.
https://www.moh.gov.et/ejcc/
sites/default/files/2020-09/
National%20Comprehensive%2
0COVID%2019%20Clinical%2
0Management%20Handbook%2
0Second%20Edition.pdf
Rwanda Doxycycline, amoxicillin,
amoxicillin-clavulanic acid (mod-
erate and mild COVID-19), clari-
thromycin, amoxicillin-clavulanic
acid, cefuroxime, ceftriaxone, or
levofloxacin [if allergy to penicil-
lin] (severe and critical COVID-19)
Recommend antibiotics for
highly suspected pneumonia
based on clinical signs in
moderate/mild COVID-19, pre-
vention of secondary bacterial in-
fection, and ventilator-associated
pneumonia in severe/critically ill
COVID-19 patient
-WHO does not recommend
the use of antibiotics in mild/
moderate COVID-19.
https://www.rbc.gov.rw/
fileadmin/user_upload/guide/
Guidelines/COVID-19%2
0Clinical%20Managment%2
0guidelines.pdf
Adebisi et al. Tropical Medicine and Health (2021) 49:51 Page 4 of 5

Abbreviations
COVID-19: Coronavirus disease; AMR: Antimicrobial resistance; WHO: World
Health Organization
Acknowledgements
Not applicable
Authors’contributions
This letter was conceptualized by YAA. YAA and NDJ led, collected the data,
and wrote the first draft of the manuscript with support from TU, IOO, and
AHO. YAA, NAU, and DELP III critically reviewed the first draft. All the authors
read and approved the final manuscript.
Authors’information
Not applicable
Funding
No external funding was used in this study.
Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated
or analyzed.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
2
Medical
Research Center, Kateb University, Kabul, Afghanistan.
3
Federal University of
Technology Minna, Minna, Nigeria.
4
Department of Public Health, University
of Calabar, Calabar, Nigeria.
5
Department of Public Health, Mount Kenya
University Rwanda, Kigali, Rwanda.
6
Department of Microbiology, Obafemi
Awolowo University, Ile-Ife, Nigeria.
7
Faculty of Pharmacy, University of Port
Harcourt, Choba, Nigeria.
8
Department of Global Health and Development,
London School of Hygiene and Tropical Medicine, London, UK.
Received: 19 May 2021 Accepted: 9 June 2021
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