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

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.

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 countries 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 findings revealed that various antibiotics such as azithromycin, doxycycline, clarithromycin, ceftriaxone, amoxicillin, amoxicillin-clavulanic acid, ampicillin, gentamicin, erythromycin, benzylpenicillin, piperacillin/tazobactam, ciprofloxacin, ceftazidime, cefepime, vancomycin, meropenem, and cefuroxime were recommended for use in the management of COVID-19, i.e., asymptomatic, mild, moderate, and severe COVID-19 with/without complications. Most of the guidelines recommended directed and empiric therapy with antibiotics. The WHO recommended 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 resistance potential) and "reserve" (antibiotics and antibiotic classes that should be reserved for treatment of confirmed or suspected infections due to multi-drugresistant organisms) categories of WHO AWaRe classification, 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 "access" category of AWaRe classification which has lower resistance potential than antibiotics in the other groups.
Empirical use of antibiotics is a risk factor for development 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 antimicrobial stewardship, lack of human and financial resources, prescribers' opposition, limited access to medicines, lack of awareness and absence of antimicrobial stewardship committees, concerns regarding fake and counterfeit antibiotics, limited hospital infection prevention program infrastructure, and lack of effective antibiotic policy among others [6]. Our findings also show that broad-spectrum antibiotics were the most recommended 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 recommended the use of antibiotics in sore throat, diarrhea, and cough that are associated with COVID-19 symptoms. 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 antibiotics, and broad-spectrum antibiotics are widely used [10][11][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]. Another study conducted in South Africa revealed that bacterial co-infection is rare at the time of intensive care unit admission with COVID-19 [14]. Another metaanalysis 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 diagnosed with bacterial co-infection [16]. This implies that only a few COVID-19 patients would need antibiotics for possible bacterial pneumonia and other superimposed/co-infections [17].
For patients who are critically ill and hospitalized, the diagnosis of a potential bacterial co-infection is uncertain; physicians tend to use broad-spectrum antibiotics to manage such patients [18]. An increase in usage of broad-spectrum antibiotics from the "watch" and "reserve" categories will not only make the agents ineffective 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 hydroxychloroquine in the management of COVID-19. Evidence has also shown that routine use of azithromycin for reducing time to recovery or risk of hospitalization for people with suspected COVID-19 in the community has been documented to offer no benefit [21][22][23]. In Table 1 The use of antibiotics in COVID-19 management in 10 African countries summary, antibiotics need to be used with care and should be withheld unless it is confirmed that the patient truly needs them. While lack of access to antibiotics 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 because pathogens that cause resistant infections thrive in hospitals and medical facilities, putting all patients at risk, irrespective of the severity of their medical conditions. The situation is further catalyzed in Africa by unsanitary conditions, high burden of infectious diseases, inadequate access to clean water, conflicts, poor coverage 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 antibiotics 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 antibiotic 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 specific treatment options [25,26]. This is a wakeup call to African countries to ensure investment in antimicrobial stewardship in order to optimize antibiotic use by ensuring that the appropriate antibiotic is administered 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 diagnostic 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.