Discussion
The COVID-19 pandemic is currently a major health threat exhibiting a
chaotic and profound impact on all aspects of health care including the
steady increase in antimicrobial resistance. It is worth mentioning that
the irrational use of antibiotics in COVID-19 patients will exacerbate
the concern of AMR beyond the COVID-19 pandemic, thus the establishment
of an antibiotic stewardship program is crucial to tackle this issue
while promoting the optimization of antibiotic therapy. Currently,
studies conducted among healthcare providers on antibiotics use during
COVID-19 pandemic are scarce. In this regard, we conducted this study to
assess knowledge, attitudes, and practices regarding prescribing
patterns of antibiotics during COVID-19 pandemic among Lebanese
healthcare providers.
Presently, there are no drugs or therapeutics approved for COVID-19
disease. Recent clinical evidence has emphasized the supportive role of
nutritional supplementation in COVID-19 patients. In our study, the most
common supplements prescribed as immune system boosters were Vitamin C
(91.5%) and Zinc (89.1%). Vitamin C has antimicrobial and
immunomodulatory properties and works as scavenger of reactive oxygen
species (Mousavi et al., 2019; Meščić Macan et al., 2019). It can
counteract the cytokine storm that diminishes the host immune responses
exacerbating the acute respiratory distress syndrome (ARDS) (Härtel et
al., 2004; Jovic et al., 2020; Feyaerts et al., 2020). The prescription
of both Vitamin C and Zinc in addition to other mineral supplementation
or “immunonutrition” (Vitamins A, B, D and E) is crucial to mitigate
the COVID-19 devastating effects (Jovic et al., 2020).
Regarding the antibiotic therapy during COVID-19 pandemic, the findings
of this study showed an increase in antibiotic use during this period.
In addition, the participants reported that they administer oral
antibiotics as empiric therapy in patients with probable or definite
nosocomial COVID-19 (51.5%), or who tested positive for COVID-19
(53%). Fever was the most common symptom (77.7%) that guides the
prescription of empiric antibiotic regimen to non-hospitalized and
hospitalized patients. The increase of antibiotic use in this study is
consistent with a multi-hospital cohort study, conducted in Michigan,
which showed an increase in the prescription of early empiric
antibacterial therapy (56.6% of the hospitalized COVID-19 patients),
whilst only 3.5% were diagnosed with bacterial infection (Vaughn et
al., 2020). Similar findings were reported in other studies emphasizing
on the early empiric antibiotics prescription in patients hospitalized
with COVID-19 (Lansbury et al., 2020; Langford et al., 2020; Rawson et
al., 2020b; Guan et al., 2020).
Although two-thirds of the healthcare providers that participated in our
study declared that they follow specific guidelines in antibiotic
administration, the data showed that the prescription was not
evidence-based and designed without prior culture-proven identification
of bacterial pneumonia to differentiate it from COVID-19 pneumonia. The
widespread of antibiotics use in Lebanon and other countries may stem
from the clinicians experience that treated patients who had bacterial
coinfections during influenza pandemic (Nestler et al., 2020).
Moreover, the participants reported that azithromycin was the first most
commonly prescribed antibiotic to treat COVID-19 patients, followed by
ceftriaxone. The widespread prescription of azithromycin, worldwide, was
reported mostly during the early phase of the pandemic; however, the
evaluation of the practice patterns of the surveyed Lebanese healthcare
providers revealed continued prescribing of this antibiotic.
Azithromycin is a semisynthetic macrolide with a broad-spectrum
bacteriostatic activity against Gram-positive bacteria and some
community-acquired Gram-negative pathogens. Beyond their antimicrobial
properties, the effectiveness of macrolides use in respiratory viral
infections is controversial. Macrolide antibiotics are reported for
their anti-inflammatory and immunomodulatory effects, they mitigate the
production of pro-inflammatory cytokines and attenuate virus-induced
exacerbations (Min et al., 2012). These striking features render them
promising drug candidates for treating the cytokine storm which is a
prominent hallmark of severe influenza A and of COVID‐19 diseases. Our
findings are consistent with other studies that showed increased use of
broad-spectrum antibiotics including azithromycin and ceftriaxone during
early phase of the pandemic (Nestler et al., 2020; Abelenda et al.,
2020). Additionally, a recent Canadian meta-analysis revealed similar
antibiotic prescribing practices to nearly three-quarters of patients
with COVID-19, whereas the prevalence of bacterial co-infections was
8.6% (Langford et al., 2020). Recent studies reported a clinical
efficacy for virus elimination of the hydroxychloroquine and
azithromycin combined treatment in addition to a decrease in mortality
in patients with severe COVID-19 (Gautret et al., 2020; Arshad et al.,
2020). Furthermore, a retrospective observational study conducted in an
American tertiary-care academic medical center reported that
approximately two-thirds of COVID-19–confirmed patients received an
antibiotic. It also demonstrated an increase in both azithromycin and
ceftriaxone use for COVID-19 patient care teams compared to
pre–COVID-19 levels, but followed by significant antimicrobial use
reduction, resulting from the implementation of clinical guidance team
who recommended the cessation of azithromycin use for COVID-19 treatment
alone, and the discontinuation of antibiotic therapy in patients with
confirmed COVID-19. However, ceftriaxone use in that study did not show
any significant change (Staub et al., 2020). Despite the fact that they
improve the clinical outcomes of hospitalized patients with severe
COVID-19, there is no significant evidence on the efficacy of including
macrolides to the treatment regimen for COVID-19 patients. A randomized
clinical trial, conducted in Brazil, showed that the use of azithromycin
in a combination therapy with hydroxychloroquine has no effect on the
clinical outcomes of patients with severe COVID-19 (Furtado et al.,
2020). Another observation study conducted in a French teaching hospital
reported a significant reduction in the prescription of the combination
of hydroxychloroquine with azithromycin from the beginning of April 2020
(Gourieux et al., 2020). Notably, studies showed that prevalence of
bacterial coinfection is very low (<5%) and antibiotics
should not be routinely used unless a bacterial coinfection is
suspected. Consequently, the WHO and Chinese guidelines discouraged
inappropriate and routine empirical antibiotic treatment, especially the
broad-spectrum antibacterial drugs, in patients without suspected or
confirmed severe COVID-19 (WHO, 2020; Zhang et al., 2020).
In this study, more than two thirds of the participants agreed that
unneeded and over-prescribed antibiotics across health care settings
will contribute to antimicrobial resistance; and described the emergence
of antibiotic resistance as an urgent healthcare issue. In response to
the pandemic, healthcare settings have rapidly implemented prophylactic
antibiotic regimen in the first-line treatment for COVID-19. This
adaptation may be explained by disease severity on admission despite few
reports of bacterial coinfection. Most of the surveyed nurses and
physicians in our study reported that they don’t perform daily
electronic audit, and nearly half of them don’t conduct a thorough
examination regarding whether a patient is in need of antibiotics and
don’t incorporate formulary restrictions into the drug ordering process.
In addition, they don’t perform culture-based revisions but the
discontinuation of antibiotics therapy is based on symptoms relief. All
these findings could be explained by the limited training and education
provided on antibiotic stewardship program, since only 11% of the
healthcare providers had participated in this program. In this regard,
antibiotic stewardship program training during COVID-19 among nurses and
physicians was significantly associated with training, restrictions on
antibiotic use, adherence to practice guidelines, and other patterns
related to monitoring of antimicrobial use. These practices were
significantly improved among nurses that had participated in ASP. Hence,
excessive antibiotics prescription may be explained by lack of attention
to the implementation and support of stewardship in healthcare settings
that could improve the rational and judicious use of antibiotics.
Engagement and education of healthcare providers is crucial to mitigate
inappropriate use of antibiotics during COVID-19 pandemic, and thus
antimicrobial resistance (Liew et al., 2020).
The present study is the first nationwide descriptive analysis that
reveals the current situation and reflects the antibiotic prescribing
practices among Lebanese healthcare providers during COVID19 pandemic.
However, the interpretation of our findings must be considered in the
context of limitations. First, the cross-sectional design of the survey
demonstrated associations with no evidence of temporal relationships.
Second, we did not have data on secondary bacterial infections that
could further explain the use of antibiotics. The implementation of
educational interventions and antibiotic stewardship programs in
Lebanese hospitals are imperative to improving antibiotic use and
consequently patient outcomes.