Abdul Haseeb,Zikria Saleem,Aseel Fayk Maqadmi,Roaa Abdulrahman Allehyani,Ahmad J. Mahrous,Mahmoud E. Elrggal,Sairah Hafeez Kamran,Manal AlGethamy,Asem Saleh Naji,Abdullmoin AlQarni,Khalid W. Alhariqi,Muhammad Arslan Khan,Kiran Ibrahim,Fahad Raees,Aisha Azmat,Aislinn Cook,Stephen M. Campbell,Giulia Lorenzetti,Johanna C. Meyer,Brian Godman,Catrin E. Moore
Ongoing Strategies to Improve Antimicrobial Utilization in Hospitals across the Middle East and North Africa (MENA): Findings and Implications
antimicrobials,antimicrobial stewardship programs,antimicrobial resistance,Middle East,quality indicators,strategies,surgical site infections,utilization patterns
Antimicrobial resistance (AMR) is an increasing global concern, increasing costs, morbidity, and mortality. National action plans (NAPs) to minimize AMR are one of several global and national initiatives to slow down rising AMR rates. NAPs are also helping key stakeholders understand current antimicrobial utilization patterns and resistance rates. The Middle East is no exception, with high AMR rates. Antibiotic point prevalence surveys (PPS) provide a better understanding of existing antimicrobial consumption trends in hospitals and assist with the subsequent implementation of antimicrobial stewardship programs (ASPs). These are important NAP activities. We examined current hospital consumption trends across the Middle East along with documented ASPs. A narrative assessment of 24 PPS studies in the region found that, on average, more than 50% of in-patients received antibiotics, with Jordan having the highest rate of 98.1%. Published studies ranged in size from a single to 18 hospitals. The most prescribed antibiotics were ceftriaxone, metronidazole, and penicillin. In addition, significant postoperative antibiotic prescribing lasting up to five days or longer was common to avoid surgical site infections. These findings have resulted in a variety of suggested short-, medium-, and long-term actions among key stakeholders, including governments and healthcare workers, to improve and sustain future antibiotic prescribing in order to decrease AMR throughout the Middle East.
Ongoing Strategies to Improve Antimicrobial Utilization in Hospitals across the Middle East and North Africa (MENA): Findings and Implications

Antimicrobial resistance (AMR) is an increasing global concern, increasing costs, morbidity, and mortality. National action plans (NAPs) to minimize AMR are one of several global and national initiatives to slow down rising AMR rates. NAPs are also helping key stakeholders understand current antimicrobial utilization patterns and resistance rates. The Middle East is no exception, with high AMR rates. Antibiotic point prevalence surveys (PPS) provide a better understanding of existing antimicrobial consumption trends in hospitals and assist with the subsequent implementation of antimicrobial stewardship programs (ASPs). These are important NAP activities. We examined current hospital consumption trends across the Middle East along with documented ASPs. A narrative assessment of 24 PPS studies in the region found that, on average, more than 50% of in-patients received antibiotics, with Jordan having the highest rate of 98.1%. Published studies ranged in size from a single to 18 hospitals. The most prescribed antibiotics were ceftriaxone, metronidazole, and penicillin. In addition, significant postoperative antibiotic prescribing lasting up to five days or longer was common to avoid surgical site infections. These findings have resulted in a variety of suggested short-, medium-, and long-term actions among key stakeholders, including governments and healthcare workers, to improve and sustain future antibiotic prescribing in order to decrease AMR throughout the Middle East.

Antimicrobial resistance (AMR) is a growing priority globally, increasing morbidity, mortality, and costs [1,2,3,4,5]. According to a recent study, up to 4.95 million (95% uncertainty intervals (UI) 3.62–6.57) deaths globally were associated with bacterial AMR in 2019, with 1.27 million (95% UI 0.911–1.71) deaths directly attributable to AMR [1]. This has prompted global, regional, and national initiatives to try and address the situation [6,7,8,9,10,11], including the development of national action plans (NAPs) to reduce AMR, with countries in the Middle East and North Africa (MENA) being no exception [10,11,12,13,14]. These plans acknowledge that the MENA region contains multiple heterogenic countries with different-sized populations and economic differences [15]. A concern is that AMR rates continue to increase in the MENA region, enhanced by high rates of purchasing antibiotics without a prescription and inappropriate prescribing of antibiotics across all sectors [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]; this includes inappropriate prescribing in both hospital and ambulatory care in the MENA region [27,33,34,35,36,37,38,39,40]. Current concerns also include the high rate of prescribing of “Watch” and “Reserve” antibiotics among hospital inpatients, potentially increasing AMR, as well as appreciable prescribing of antibiotics in ambulatory care for self-limiting conditions, including acute respiratory tract infections [36,41,42,43,44,45]. Antibiotics from the “Access” list are considered first-line or second-line treatments for a range of infections and should be routinely available across countries [46,47,48]. There should be limited prescribing of antibiotics in the “Watch” group, as these are considered to have greater resistance potential and toxicity, with very limited prescribing of antibiotics in the “Reserve” antibiotics as these are considered antibiotics of last resort [47,49,50]. The target is at least 60% of antibiotics prescribed should be from the “Access” list [49,51]. However, this is not always the case among countries in the MENA Region [52,53,54]. Inappropriate prescribing of antibiotics in hospitals increased during the COVID-19 pandemic, with high utilization rates across countries in the first COVID-19 wave, including those in the MENA region [55], despite limited evidence of bacterial infections or co-infections in these patients [56,57,58,59]. There are also concerns with high rates of extended prophylaxis postoperatively to prevent surgical site infections (SSIs) among LMICs, with the prevention of SSIs with antibiotics a priority across hospitals and countries, given the increasing prevalence of AMR [60,61,62,63]. However, extended prophylaxis and the use of inappropriate “Watch” antibiotics increase adverse reactions, costs, and AMR, with limited or no improvement in patient outcomes [64,65,66,67,68]. We are now seeing a growth in antimicrobial stewardship programs (ASPs) in hospitals across countries and continents to address concerns with inappropriate prescribing [63,69,70]. These include addressing concerns with extended prophylaxis beyond the first day to prevent SSIs and reducing excessive prescribing of antibiotics generally within hospitals [63,69,71,72]. However, low- and middle-income countries (LMICs) have had barriers to successfully implementing ASPs [73], including having the necessary infrastructure, knowledge, and training in place, together with agreed guidelines, antimicrobial susceptibility testing (AST) data, and champions for ASPs [73,74,75,76,77,78,79]. Nevertheless, this is now changing with ASPs successfully being introduced in hospitals across LMICs, including the MENA region, which will improve future antibiotic prescribing, with the numbers growing over time as healthcare workers increasingly understand their importance [63,70,72,80,81,82]. A range of prescribing and quality indicators have been developed across countries to assess the impact of ASPs [63,70,83,84,85]. There are three main types of indicators (Figure 1), with a clear a priori purpose necessary for developing, collecting, and using these across sectors, including countries in MENA, to improve future antimicrobial prescribing. While different indicators have been used to improve antimicrobial prescribing in hospitals across countries [63,86,87,88,89], any proposed indicator must have clarity, be feasible to implement, and must have easy-to-use, consistent, and reliable tools for valid data collection and management [63,90,91,92]. It is recognized that this is a challenge for many MENA countries, particularly among those with a lower income. Countries are at different stages in their availability of data collection tools, and some still have extensive use of paper-based systems for data collection; however, there is an imperative need for NAPs for AMR to drive down AMR rates through improved antibiotic use [93,94,95,96]. Consequently, routine data collection, and the usefulness of collected data, is likely to change in order to reduce unnecessary prescribing [10,11,13]. In addition, there is increasing use of the WHO Essential Medicines List and the AWaRe book to improve empiric prescribing, as well as the monitoring of antibiotic prescribing for a range of infections, alongside pertinent quality indicators [48,49,51]. These are based on key prescribing considerations associated with the guidance (Supplementary Table S1) [48,49,97,98]. The first step in improving antibiotic utilization, starting in hospitals across the MENA region, is to describe current utilization patterns. This includes current utilization patterns to prevent SSIs as well as prescribing and quality indications used in practice as part of ASPs alongside other programs to improve future prescribing. Consequently, we sought to comprehensively describe current antimicrobial consumption patterns among hospitals throughout the MENA region using published point-prevalence surveys (PPS). We also sought to document the prescribing and quality indicators currently being applied across hospitals throughout the MENA region to enhance future antibiotic prescribing. Additionally, we wanted to list ASPs that have been successfully implemented among MENA countries to offer future direction. Since there is currently greater knowledge regarding the prescribing of antibiotics in hospitals compared with ambulatory care across the MENA region, we began the search in hospitals. As a result, this study attempts to describe the current antimicrobial consumption patterns in hospitals throughout the MENA region using published PPS studies to ascertain the extent to which antibiotics are improperly prescribed postoperatively to avoid SSIs. SSIs account for a significant portion of hospital-acquired infections, enhancing morbidity, mortality, and expenditures [65,99,100,101]; consequently, it is crucial that antibiotic prophylaxis is delivered following correct guidelines to reduce the burden of infections due to SSIs. However, as mentioned, continued administration of antibiotics postoperatively increases adverse reactions and AMR, with little to no effect on further lowering the rate of SSIs [65]. Based on published studies, we also identify potential prescribing and quality indicators that could be applied across hospitals throughout the MENA region to enhance future antibiotic prescribing. In addition, we document ASPs that have been successfully introduced across a range of hospitals in the MENA to offer a future direction, building on recent qualitative studies and reviews [80,81,102]. We will not cover possible programs to address the reluctance among patients in MENA, including those in Jordan and Kuwait, to receive COVID-19 vaccines [103,104,105,106]. Programs to limit the unwarranted use of antibiotics in farming and agriculture in MENA are also ongoing, given AMR concerns [107,108,109,110]. Whilst both areas are very important from a One Health perspective to reduce AMR among patients, both are outside the scope of this study.

There are currently concerns with high antibiotic utilization rates among hospitals across the MENA region, exacerbated by high rates of empiric prescribing without following current guidelines. Alongside this, there are concerns with the extent of extended prophylaxis beyond the postoperative period to prevent SSIs which, as mentioned, increases adverse reactions, AMR, and costs. However, a number of prescribing and quality indicators are being used across hospitals to monitor and improve prescribing, including those that are part of ASPs. Their impact is documented to provide future guidance.

Table 1 documents current antimicrobial utilization patterns among 23 PPS studies that have recently been undertaken across the MENA countries. These incorporate PPS studies from as little as one hospital up to 26 hospitals within a country. In addition, Iskander et al. (2016) documented antimicrobial utilization patterns among 27 non-teaching hospitals in Lebanon, based on actual utilization rates, and subsequently compared these to point prevalence data. The authors found that average consumption levels excluding pediatric cases were 72.56 defined daily dose per 100 bed-days (DDD/100BD), with the most commonly used antibiotics being amoxycillin/clavulanic acid (from the “Access” group), ceftriaxone (from the “Watch” group), amoxycillin (“Access”), and cefuroxime (“Watch”) [111]. We have excluded the MENA hospitals that were part of the 27 Western and Central Asian countries enrolled in the Global PPS of Versporten et al. (2018) [86]. We also excluded the findings from the updated Global PPS analysis, which includes hospitals from Iraq, Iran, Jordan, and Saudi Arabia, and measures the extent of “Access”, “Watch”, and “Reserve” antibiotics prescribed [44], as there was insufficient data from these two consolidated publications for their inclusion in Table 1. However, a summary of their results has been included in our analysis. In total, over 50% of inpatients in the majority of the surveyed hospitals were prescribed antibiotics, which is comparable to the 42.0% recorded among hospitals from Western and Central Asia taking part in the Global PPS study [86]. Hospitals in Jordan recorded the highest antimicrobial usage rates (98.1%), with hospitals in Tunisia having overall the lowest utilization rates of 39.2–49.2% of patients among the surveyed in-patients (Table 1). Studies evaluating antibiotic utilization among in-patients in Iraq also found high utilization rates at 93.7% of those surveyed. The most commonly prescribed antibiotics among hospitals in the MENA region reporting their findings (Table 1) were the third-generation cephalosporins (“Watch” group) and the penicillins (“Access” group), followed by metronidazole (“Access” group). This compares to the high levels of “Watch” and “Reserve” antibiotics among hospitals in Iran, Iraq, and Jordan taking part in Pauwels et al.’s (2021) study, which compared with those in Saudi Arabia [44].

Table 2 outlines the extent of extended antibiotic prophylaxis among hospitals throughout the MENA region. This is similar to the findings among hospitals from West and Central Asia in the consolidated findings of Versporten et al. (2018) [86]. However, this is not always the case, as seen in the study of Alnajjar et al. (2020), where 100% of mothers undergoing a Cesarean section were just administered a single dose of cefazolin within one hour of skin incision to prevent SSIs [62]. Third-generation cephalosporins, including ceftriaxone (“Watch” group), metronidazole (“Access” group), and the penicillins, including co-amoxiclav (usually “Access” group), were typically administered for surgical antibiotic prophylaxis (SAP). Published justifications for extended prophylaxis included healthcare professionals (HCP) resistance to change, hospital overcrowding, worries about hospital cleanliness, concerns about proper aseptic techniques not being used during operations, physician ignorance of antibiotics, worries about malnutrition in some patients, and patient expectations. Table S1 discusses some of the concerns regarding SSIs across the MENA region in addition to extended prophylaxis and potential ways forward to improve future antimicrobial prescribing. There is also a need to strengthen patient education regarding the role of preoperative antibiotics in preventing SSIs, given concerns with limited patient knowledge currently in this area [132].

A number of prescribing and quality indicators have been used among hospitals across the MENA region to improve future prescribing (Table 3). These reflect increasing activities among hospitals across MENA to improve future prescribing of antimicrobials and reduce AMR. However, a major concern across a number of countries in MENA is the current lack of electronic healthcare systems to routinely track prescribing practices against agreed indicators. This is likely to change as more applications and other electronic tools become available across MENA to document current patterns. It is essential, however, that consistent coding is agreed upon and used to enable intra- and inter-comparisons.

ASPs have been effectively implemented in the MENA region over the past few years to enhance the appropriate prescribing of antibiotics. Checklists and guidelines have also been created among hospitals in the region and beyond to enhance the creation and implementation of ASPs despite ongoing challenges (Table 4) [55,149,150]. Encouragingly, a number of ASPs have now been undertaken among middle-income countries in MENA despite previous concerns [73], with the number likely to grow as the various countries strive to reduce rising AMR rates as part of agreed AMR NAPs. Typically, the introduction of several interventions simultaneously to improve the prescribing of antibiotics appears to have a greater impact on future prescribing than single-activity interventions. In addition, antibiotic prescribing needs to be regularly monitored; otherwise, prescribing patterns will tend to revert back to pre-intervention levels exacerbated if there is a regular turnover of staff within the hospital. Besides these ASPs, we have also seen clinical pharmacists giving advice regarding antibiotic prescribing in some hospitals in the MENA region, including advice on dosage adjustments and recommending more effective antibiotics. In one hospital in Oman, such activities resulted in projected net cost savings of approximately USD 200,000 per year [148]. In addition, in Jordan, among 661 blood cultures reviewed by the ASP pharmacist in a cancer center, 26% subsequently required antimicrobial therapy modification [148]. Advice included changing to a susceptible antimicrobial and the initiation of pertinent antimicrobials, as well as the discontinuation, de-escalation, and dose modification of pertinent antimicrobials—all cost-saving interventions [147]. Overall, there was a high acceptance rate of the advice at 86% among prescribing physicians.

There are concerns with the variable knowledge of healthcare students, as well as qualified healthcare professionals, regarding their knowledge of antibiotics, AMR, and ASPs (Table 5). This matches concerns with the knowledge of antibiotics and AMR among adults in the region [163,164,165,166]. This needs to be addressed alongside other identified concerns, including prolonged prescribing of antibiotics postoperatively to prevent SSIs, to improve future prescribing, and reduce AMR among countries in the MENA region. Suggested strategies to improve future antimicrobial prescribing among hospitals in the Middle East to reduce AMR have been divided into short to medium-term and long-term (Table 6).

We believe this is the first comprehensive study to bring together all key aspects associated with the prescribing of antibiotics among hospitals in the MENA region to provide future guidance. This is important in the Region with such a heterogeneity in the country incomes, and concerns with growing AMR rates, reflected in ongoing NAPs and other activities to reduce AMR [10,11,12,13,14]. Such concerns will be exacerbated by high utilization of antibiotics, which has been seen among a number of hospitals in the MENA region, with Jordan having the highest rates, (up to 98% of patients studied, alongside concerns with resistance patterns [80,123,140]. This is higher than the proposed target of 40% of hospital in-patients [176]. We are aware that the published PPS studies included here were typically undertaken before the recent COVID-19 pandemic. This is an important consideration as there was typically appreciably increased prescribing of antimicrobials in patients admitted to hospitals with COVID-19 in the first wave of the pandemic across continents and countries in the absence of bacterial co-infections or secondary infections [56,57,58,177,178]. As such, this may potentially further increase antibiotic utilization and AMR rates, in addition to those documented in Table 1, without improving patient care [179,180]. Third-generation cephalosporins and penicillins, along with metronidazole, were among the most commonly prescribed antibiotics in the MENA region (Table 1). However, there are concerns with the extent of “Watch” and “Reserve” antibiotics being prescribed among hospitals in the MENA region, similar to other studies [44]. This needs urgent addressing where it occurs to reduce rising AMR rates. There are also concerns with the extent of antimicrobials being prescribed in the pos-operative period to reduce SSIs among Middle Eastern countries, with no obvious difference between the income levels of countries in the MENA region or with other regions, including across Africa and among a number of Asian countries [63,65]. This also needs to be addressed as excessive prescribing of antibiotics will increase adverse reactions, AMR, and costs without improving patient outcomes [65]. Where necessary, setting appropriate prescription/quality targets and monitoring subsequent hospital utilization patterns as part of ASPs will improve future prescribing (Table 3). However, as mentioned, any proposed indicator must have clarity, be feasible to implement, as well as having easy-to-use, consistent, and reliable tools for valid data collection and management [60,90,91,92]. The development of appropriate indicators based on the AWaRe book and other guidance should help in this regard and address identified key issues and risk factors (Supplementary Table S1). This will be an issue in a number of hospitals in the MENA region that still rely on paper-based systems. However, this is changing and will grow as part of NAPs to reduce AMR [181,182]. A number of ASPs have been successfully introduced among MENA countries, with multiple interventions seen to have the greatest impact. There were concerns that the introduction of ASPs among LMIC MENA countries would be a concern in view of potential resource issues [73]. However, this appears to be less of an issue currently, with ASPs successfully introduced among a range of income countries in the region, providing exemplars for the future (Table 6). This is similar to the situation that now exists across Africa, also providing direction for the future [63,72,183]. It is likely that we will continue to see growth in ASPs among hospitals in the MENA region as they attempt to reduce unnecessary antimicrobial prescribing as part of NAPs to combat AMR. As documented (Table 6), future strategies to improve the appropriateness of antimicrobial drug prescribing in the hospital sector can be divided into short-, medium-, and long-term actions. Government involvement and initiatives through NAPs are crucial to ensure sustainability, and MENA nations are currently developing and putting them into action. However, there are still several obstacles and challenges to address to undertaking agreed activities. These include available and trained staff as well as available resources and digital platforms alongside the consistent use of codes for diagnosis and other activities. We will continue to monitor the situation given rising AMR rates in the MENA region and their effects on mortality and costs. We are aware there are a number of limitations with this paper. We did not conduct comprehensive systematic reviews for each issue, including PPS and SSI studies, as well as quality indicators and ASPs, for the reasons discussed in the Methodology section. However, as seen, we have compiled a comprehensive list of PPS and SSI studies currently undertaken among hospitals in the MENA region, as well as a range of prescribing and quality indicators that have been used in practice. Alongside this, we have documented a number of ASPs that have been successfully implemented across a range of countries in the Middle East as exemplars. Consequently, despite these limitations, we believe our findings, suggestions, and conclusion are robust, given the number of examples combined with our methodology.

The principal strategy involved a narrative review of key areas to comprehensively inform current antimicrobial utilization patterns across hospitals in the MENA region, including concerns and potential ways forward to address key issues. These include the instigation of agreed prescribing and quality indicators as part of planned ASPs. The co-authors’ extensive expertise in working with patients with infectious diseases, documenting current utilization patterns, adopting policies to improve future prescribing, which includes the creation of applicable quality indicators, and researching and implementing ASPs, have added to this. We have used this approach before when debating key areas across multiple countries and continents, including key issues and challenges surrounding infectious diseases [45,63,65,184,185,186,187].

The methodology built upon a recent systematic review of PPS studies undertaken by some of the co-authors [40], and subsequently involving studies from 2016 onwards until October 2022. 2016 was chosen as this was the launch of the WHO Global Action Plan to reduce AMR [93]. This methodology was employed since we were aware that a number of possible PPS studies would not be listed in databases, including PubMed and Web of Science, building on recent experiences [63]. However, we wanted to include them as our intention was to comprehensively document a range of PPS studies, and their findings, across the MENA countries to provide a baseline for future studies. We also purposely did not select which countries from the MENA region to include in this narrative overview in order not to bias any findings. Similar to the systematic review of Saleem et al. (2020) and the recent Pan-African study [40,63], key categories included the number of participating hospitals within the PPS study, the PPS methodology, e.g., ECDC, WHO, or Global PPS, [27,112,124,176], as well as the first, second, or third most prescribed antibiotic broken down by ATC code and the AWaRe classification [47,48,49,188]—the latter, especially with growing concerns regarding the extent of prescribing of “Watch” and “Reserve” antibiotics among a number of Western and Central Asian countries [44,47,50]. In addition, whether antibiotics were prescribed for prophylaxis or treatment and the average number of antibiotics prescribed per patient. As mentioned, we excluded the findings from the two recent Global PPS studies, e.g., Versporten et al. (2018) and Pauwels et al. (2021), since it was difficult to pull out individual hospital data to populate the respective Tables [44,86]. However, the findings from these two studies were discussed in relation to the findings from the various MENA countries. The various MENA countries were broken down by their World Bank classification, i.e., low-income, low-middle, upper-middle income, and high-income countries, building on the recent study of Adekoya et al. (2021), as well as the recent Pan-African study for consistency [63,131].

The principal approach was a narrative review, which built upon recent publications involving some of the co-authors [65,189]. This was supplemented by additional studies from 2016 onwards known to the co-authors. This is similar to the approach adopted by the authors in other studies, including the recent Pan-African study [40,63]. In addition, a narrative review of ongoing concerns with the management of SSIs among Middle Eastern countries provides a background to the importance of this area for future quality improvement initiatives. The various MENA countries were again broken down by their World Bank classification, i.e., low-, low-middle, upper-middle, and high-income countries, building on the recent study of Adekoya et al. (2021) and the Pan-African study for consistency [63,131].

The principal approach was a narrative review. This built upon recent PPS and ASP publications from across the MENA area, supplemented with additional studies known to the co-authors. This mirrors the approach for the PPS and SSI studies.

Again, the principal approach was a narrative review of recent ASPs that had been instigated among hospitals across the Middle East, as well as published papers on the knowledge, attitude, and practices among key stakeholders towards antibiotics and AMR. This includes details of the interventions undertaken from 2016 onwards as well as the outcomes against agreed indicators. The MENA countries that had instigated ASPs were again broken down by their World Bank classification, i.e., low-, low-middle, upper-middle, and high-income countries, building on the recent study of Adekoya et al. (2021) and the Pan-African study for consistency [63,131]. This is important as there have been concerns about conducting ASPs in LMICs due to issues of available and trained personnel as well as the necessary finances [73]. Possible short to medium and long-term activities to improve future antibiotic prescribing in hospitals have been based on the findings from the various narrative reviews combined with the considerable knowledge of the co-authors, building upon similar activities across Africa [63].

In conclusion, reducing AMR must be a high priority for all MENA countries, with AMR potentially developing into the next pandemic unless it is addressed. However, in order to lower AMR rates, numerous coordinated efforts need to be undertaken as part of agreed AMR NAPs. This calls for better awareness of current antimicrobial utilization patterns in hospitals, along with key targets for quality improvement programs. The study identified concerns with current antibiotic prescribing in hospitals, including prolonged administration to prevent SSIs as well as the extent of inappropriate prescribing, including “Watch” and “Reserve” antibiotics. Greater use of the AWaRe classification and guidance will help in this regard, along with other suggestions for the future. We will continue to monitor these developments to enhance future appropriate prescribing of antimicrobials in hospitals throughout the MENA region. This is crucial given the lack of novel antimicrobials being produced.