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.