Antibiotic Use Among Hospitalized Patients in Africa: A Systematic Review of Point Prevalence Studies

Background There is paucity of data describing the rate and quality indices of antibiotics used among hospitalized patients at continental level in Africa. This systematic review evaluated the pooled prevalence, indications, and types of antibiotics used in hospitals across Africa. Methods Three electronic databases, PubMed, Scopus, and African Journals Online (AJOL), were searched using search terms. Point prevalence studies of antibiotic use in inpatient settings published in English language from January 2010 to November 2022 were considered for selection. Additional articles were identified by checking the reference list of selected articles. Results Of the 7254 articles identified from the databases, 28 eligible articles involving 28 studies were selected. Most of the studies were from Nigeria (n = 9), Ghana (n = 6), and Kenya (n = 4). Overall, the prevalence of antibiotic use among hospitalized patients ranged from 27.6 to 83.5% with higher prevalence in West Africa (51.4–83.5%) and North Africa (79.1%) compared to East Africa (27.6–73.7%) and South Africa (33.6–49.7%). The ICU (64.4–100%; n = 9 studies) and the pediatric medical ward (10.6–94.6%; n = 13 studies) had the highest prevalence of antibiotic use. Community-acquired infections (27.7–61.0%; n = 19 studies) and surgical antibiotic prophylaxis (SAP) (14.6–45.3%; n = 17 studies) were the most common indications for antibiotic use. The duration of SAP was more than 1 day in 66.7 to 100% of the cases. The most commonly prescribed antibiotics included ceftriaxone (7.4–51.7%; n = 14 studies), metronidazole (14.6–44.8%; n = 12 studies), gentamicin (n = 8 studies; range: 6.6–22.3%), and ampicillin (n = 6 studies; range: 6.0–29.2%). The access, watch, and reserved group of antibiotics accounted for 46.3–97.9%, 1.8–53.5%, and 0.0–5.0% of antibiotic prescriptions, respectively. The documentation of the reason for antibiotic prescription and date for stop/review ranged from 37.3 to 100% and 19.6 to 100%, respectively. Conclusion The point prevalence of antibiotic use among hospitalized patients in Africa is relatively high and varied between the regions in the continent. The prevalence was higher in the ICU and pediatric medical ward compared to the other wards. Antibiotics were most commonly prescribed for community-acquired infections and for SAP with ceftriaxone, metronidazole, and gentamicin being the most common antibiotics prescribed. Antibiotic stewardship is recommended to address excessive use of SAP and to reduce high rate of antibiotic prescribing in the ICU and pediatric ward.


Background
Antimicrobial resistance remains a major public health challenge in the twenty-first century [1][2][3].It threatens the use of antibiotics for the prevention of infections due to surgery, dialysis, and chemotherapy [4].Infections caused by multidrug-resistant pathogens are associated with high mortality rate [5,6] and significant morbidity and healthcare costs [3].Infections caused by resistant pathogens, especially the multidrug-resistant pathogens, are difficult to treat due to limited number of effective antibiotics [6,7].Infections due to antibiotic-resistant pathogens cause an estimated 700,000 deaths per year, and this was estimated to increase to about 10 million deaths per year by the year 2050 [8].This calls for interventions to reduce the burden of antibiotic resistance in healthcare system.Inappropriate use of antibiotics contributes to the emergence and transmission of antibioticresistant pathogens [9].Evidence has shown that about 20-50% of antibiotic prescriptions are inappropriate, and this increases the risk of antibiotic resistance [10].Antimicrobial stewardship program is used as a strategy to tackle inappropriate antibiotic prescription in healthcare facilities and prevent antibiotic resistance [11].Evidence has demonstrated the effectiveness of antimicrobial stewardship in improving antibiotic prescribing practices among prescribers and improving clinical and microbial outcomes [12,13].In addition, antimicrobial stewardship has been shown to reduce healthcare cost among patients [14].
Evaluation of antibiotic prescribing pattern among patients in healthcare facilities is used to identify antimicrobial stewardship opportunities to improve appropriate use of antibiotics [15].Point prevalence studies have been found to be valid and reliable in measuring antibiotic use among hospitalized patients [16].Available evidence has shown that about 30% and 50% of hospitalized patients in Europe and the USA use at least one antibiotics per day [17,18].In Africa, several point prevalence studies have reported high rate of antibiotic use among hospitalized patients and inappropriate use of antibiotics in healthcare facilities [19][20][21][22].However, there is limited data to describe the point prevalence of antibiotic use among hospitalized patients in Africa at a regional level.Understanding the epidemiology of antibiotic use among hospitalized patients and the quality of antibiotic prescribing is important to design effective antimicrobial stewardship interventions to promote rational use of antibiotics and improve clinical outcomes among patients.The objective of this study is to evaluate the prevalence of antibiotic prescribing among hospitalized patients, the prevalence of antibiotic use in different hospital ward/unit, and the quality indicators of antibiotic prescriptions in healthcare facilities across Africa.

Study Design
This systematic review of antibiotic use among hospitalized patients in Africa was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement 2020 [23].

Information Sources
Three electronic databases including PubMed, Scopus, and African Journals Online (AJOL) were searched to identify eligible articles.The search was conducted using the search terms described under search strategy.Google Scholar search was also conducted to find eligible articles.Additional search was conducted by checking the reference lists of selected articles.

Search Strategy
The search terms used include "point-prevalence study," "antibiotic use," and "Africa" along with their synonyms.The terms were combined using Boolean operators.The search terms used for the electronic search are as follows: Antibiotic use OR Antibiotic prescribing OR Antimicrobial use OR antimicrobial prescribing AND hospitalized patients OR acute care patients AND Africa AND point prevalence survey OR point-prevalence study.

Quality Assessment
Quality assessment for the selected articles was performed using the Newcastle-Ottawa scale (NOS) [24].The NOS consists of three sections including selection, comparability, and outcomes.Quality assessment was conducted by an independent reviewer (MS), and the result was randomly checked by a second reviewer (UA).Disagreements between the reviewers were resolved through consensus.

Study Selection
The search conducted on PubMed, Scopus, and African Journal Online databases yielded 6761, 306, and 91 articles, respectively.A total of 96 articles were identified after screening the first 1000 results from Google Scholar.Overall, 7254 articles were retrieved from the databases after the search.Of the 7254 articles, 22 duplicate articles were identified and removed.The title and abstract of the remaining articles were screened to remove articles that were not relevant to this systematic review and meta-analysis.The full text of 60 articles was assessed for inclusion based on the eligibility criteria, and 28 articles from 28 studies were selected.Figure 1 illustrates the procedure used during the screening and selection process.

Characteristics of Selected Studies
Most of the selected studies were from Nigeria (n = 9), Ghana (n = 6), Kenya (n = 4), Tanzania (n = 2), and South Africa (n = 2).Most of the studies (n = 17) involved multiple centers and 9 and 2 studies conducted in single and two centers, respectively.Majority of the studies were conducted before COVID-19 pandemic with 10 studies conducted in 2019 and four each in 2016 and 2017.There were two studies conducted in 2021 and one study in 2020.The number of patients involved in the selected studies ranged from 113 to 4407 patients.Most studies (n = 24) included patients from different wards while two studies each involved only surgical and pediatric population.Table 1 summarizes the characteristics of the selected studies.

Quality Assessment of Selected Studies
Almost all the studies included a population that is either truly or somewhat representative of the target population.
Similarly, almost all the included studies had a sample size that is satisfactory and justified.The quality score among the included studies ranged from 4 to 9 with 23 studies (82.1%) scoring >7 points.Overall, 24 studies (85.7%) were found to have good quality while 3 studies had fair quality.One study was adjudged to have poor quality.Table 2 shows the quality assessment results of the studies included in this review.

Discussion
This systematic review evaluated the prevalence, indication, and types of antibiotics used among hospitalized patients in Africa, as well as the quality indicators of antibiotic prescribing.The study found that there are limited studies that reported the prevalence of antibiotics used among hospitalized patients, particularly in the central and North African regions, where there was paucity of studies.The studies used different protocols including the World Health Organization protocol, global point prevalence survey protocol, and the European Centre for Disease Prevention and Control protocol to conduct the studies reflecting absence of an African protocol for conducting point prevalence of antibiotic use in African hospitals.Most of the included studies included were found to have good quality.The results showed that the prevalence of antibiotic use in inpatient settings in Africa is higher than the prevalence reported in Europe (30.5%)[17] and the USA (49.9%) [18].This could be explained by the lack of adherence to antibiotic prescribing guidelines among prescribers [49,50], inadequate knowledge of antibiotic prescribing among prescribers, and the misuse of antibiotics for the management of viral infections [51,52].The high rate of antibiotics used in inpatient The current study also found that the most common indication for antibiotic use among inpatients in Africa was community-acquired infections.This is consistent with the finding in Europe [17], the USA [18], and the global PPS of antimicrobial use [53].This result indicates the need to promote infection control and prevention strategies among the public to reduce the burden of community-acquired infections and eventually reduce the use of antibiotics.Surgical antimicrobial prophylaxis was the second most common indication for antibiotic use in African inpatient settings.This is not in agreement with the result of the global PPS where hospital-acquired infection is the second most common indication.It is important to note that about two-thirds to 100% of surgical antibiotic prophylaxis was prolonged beyond 24 h.In a similar study, more than half of the surgical antimicrobial prophylaxis prescriptions were prolonged beyond 24 h [17].Excessive use of surgical antimicrobial prophylaxis contributes the emergence and spread of antimicrobial resistance.This result confirms the findings of previous studies that have demonstrated excessive use of surgical antimicrobial prophylaxis [22,54].Prolonged use of surgical antimicrobial prophylaxis is attributed to lack of knowledge among prescribers [55] and the use of antibiotics to augment suboptimal infection control and prevention practices.Therefore, surgical antimicrobial prophylaxis represents an important priority for the implementation of antimicrobial stewardship program in Africa.Previous studies have demonstrated the effectiveness of antimicrobial stewardship in improving the use of surgical antimicrobial prophylaxis and improving patient outcomes [12].The results also showed that a considerable amount of antibiotics are used for hospital-acquired infections.High rate of hospitalacquired infections is attributed to poor infection control and prevention practices due to lack of training, lack of infrastructure, and high workload among healthcare workers in Africa [56,57].Therefore, infection prevention and control strategies including training of healthcare workers and promoting hand hygiene practices are recommended to reduce the burden of healthcare-associated infections and subsequently reduce antibiotic use in inpatient settings.
Ceftriaxone, metronidazole, gentamicin, ampicillin, cefuroxime, and ciprofloxacin were the most common antibiotics used among hospitalized patients in Africa.This was not consistent with the finding in Europe where betalactam plus beta-lactamase inhibitor combinations including amoxicillin-clavulanate and piperacillin-tazobactam; thirdgeneration cephalosporins and fluoroquinolones were the most common antibiotics used in acute care hospitals [17].In China, third-generation cephalosporin, fluoroquinolones, and metronidazole were the most common antibiotics used among hospitalized patients [58].These variations are attributed to the differences in the burden of infectious diseases and the difference in antibiotic resistance pattern between the countries.In addition, high rate of ceftriaxone, metronidazole, gentamicin, and ampicillin usage could be attributed to the fact that they are relatively cheaper and have better safety profile than the beta-lactam beta-lactamase inhibitor combinations and fluoroquinolones.The high rate of ceftriaxone and ciprofloxacin usage in Africa is another important target for antimicrobial stewardship interventions.This is because these antibiotics are associated with increased risk of Clostridium difficile infection and the emergence of multidrug-resistant pathogens such as extended-spectrum beta-lactamase producing Enterobacteriaceae.
Most of the antibiotics used in Africa are in the access group while a considerable percentage of antibiotics belong to the watch group.However, the access group accounts for NA, not applicable less than 60% of the antibiotics in most of the studies while the watch group accounted for more than 40% of the antibiotics in most of the studies.A previous study revealed that low-income countries had the highest access (62.8%), lowest watch 36.0%), and no reserve antibiotic prescription among adults compared to the other income groups [59].
The results of the current study imply that the antibiotics in the watch group were overused and those in the access group were underused.Therefore, interventions to promote more usage of antibiotics in the access group are recommended.Antibiotics in the watch group have higher potential for antibiotic resistance compared to those in the access group [60].In addition, antibiotics in the reserve group are used for the treatment of multidrug-resistant infections.The low usage of the reserve antibiotics in Africa may be attributed to the non-availability of the antibiotics [59], and in some cases, the expensive cost of these life-saving medications may limit their use for those who pay for health services out-of-pocket.Therefore, interventions that promote accessibility, affordability, and availability of reserve antibiotics are recommended.
The general principle of antibiotic use requires taking specimen for microbiology culture and sensitive to guide definitive antibiotic therapy and minimize the risk of antibiotic resistance.The current study found that only onequarter of patients receiving antibiotic therapy had specimen taken for culture.This shows that there is a major gap in the management of infectious diseases in Africa and highlights the need to strengthen laboratory capacity through diagnostic stewardship.The documentation of the reason(s) for antibiotic prescription was observed in most of the cases, although there is still room for improvement.The results also revealed that less than one-third of patients receiving antibiotics in Africa had a review/stop date documented in their case notes.The implication of this finding is the tendency to use antibiotics inappropriately and excessively.There was also report of redundant antibiotic combinations among inpatients in African hospital.These findings highlight some important opportunities for hospital pharmacists across Africa to participate in antimicrobial stewardship program.Therefore, training of hospital pharmacists and pharmacy students on antimicrobial stewardship is recommended [11,61,62].
The COVID-19 pandemic has caused significant disruption in healthcare systems across the world, and Africa is no exemption.The pandemic has affected both antimicrobial stewardship and infection control and prevention programs across the globe.Available evidence has shown that the pandemic has increased the rate of multidrug-resistant Gram-positive and Gram-negative pathogens [63].There is paucity of data describing the impact of the pandemic on the prevalence and types of antibiotics prescribed among inpatients in Africa.Therefore, future studies should assess the impact of COVID-19 pandemic on antibiotic prescribing among inpatients in Africa.This study has a number of limitations including selection bias due to scarcity of point prevalence studies from Central African and North African regions.In addition, the exclusion of studies published in languages other than English language may have excluded relevant articles.Therefore, the findings may not be easily generalizable to the entire continent.Secondly, there was heterogeneity in the reporting of the prevalence as only a few studies reported the 95% confidence interval.This made it difficult to perform a quantitative analysis of the results.Therefore, a standardized protocol for conducting and reporting point prevalence survey of antibiotic use among inpatients in Africa is required to facilitate the performance of meta-analysis in the future.Despite these limitations, the current review provide some insights into the prevalence, indications, and types of antibiotics used among hospitalized patients in Africa as well as the quality indicators of antibiotic prescribing.

Conclusion
The prevalence of antibiotic use among hospitalized patients in Africa is relatively high compared to Europe and the USA.The prevalence of antibiotic use was higher in adult intensive care unit and pediatric medical and neonatal wards compared to other wards.Antibiotics were most commonly used for community-acquired infections, followed by surgical antibiotic prophylaxis where more than two-thirds of the prescriptions was prolonged beyond 24 h.Broad spectrum antibiotics such as ceftriaxone, gentamicin, and fluoroquinolones were among the most common antibiotics prescribed among inpatients in Africa.Antimicrobial stewardship interventions are recommended, particularly in the surgical, ICU, and pediatric wards, to improve quality use of antibiotics in African hospitals and prevent antibiotic resistance.

Fig. 1 Flow
Fig. 1 Flow chart of article screening and selection

Table 1
Characteristics of the studies included in this review

Table 2
Quality assessment of the studies included in the review

Table 3
Quality indicators of antibiotic prescribed among hospitalized patients