To the best of our knowledge, this is the first study from Nigeria assessing both implementation of ASM among tertiary hospitals and predictors of good KAP of APR and AMR among physicians practicing in all six geopolitical zones of Nigeria.
Our results suggest significant gaps in the implementation of antimicrobial stewardship (AMS). None of the hospitals surveyed had a formal ASP program, while majority of participating hospitals were not routinely implementing one or more of the ASM-related interventions and there was poor awareness of ASM. Poor compliance with AMS was reported by another study from Nigeria where only six (35%) of 17 tertiary hospitals surveyed had a formal ASP and less than 23.5% of these hospitals implemented AMS-related interventions and policies . A nationwide survey of pharmacist’s involvement in ASP in Nigeria, revealed that only 5 (13.5%) of 37 hospitals had a formal ASP. In a study evaluating physicians’ knowledge and perception of AMS and AMR in six hospitals in three geopolitical zones of Nigeria, only 28.2% of respondents had ever heard of ASP and more respondents had good knowledge of AMR than ASP (82.7% vs 36.5%) . In line with our finding of poor implementation of AMS-related interventions, an international survey of ASP in 660 hospitals across the globe, revealed that only 14% of 43 hospitals in Africa had an ASP in place as compared to 53% (26/49), 66% (230/348) and 66% (45/67) of hospitals in Asia, Europe, and North America, respectively . This international survey reported lack of funding and personnel, a lack of information technology, prescriber opposition and lack of awareness on the part of the hospital administration as perceived barriers to the implementation of ASP among countries surveyed. Other identified challenges to implementation of ASP in developing countries include, limited diagnostic infrastructure, poor access to quality-assured antimicrobials, and gaps in antibiotic prescribing and AMR-related knowledge and attitude among prescribers [27, 28]. Although, the outcomes and impact of implementation of ASP have not been widely studied in Africa, few studies from this region suggest that African countries can successfully implement these programmes . To overcome these barriers and challenges, Nigeria ought to strengthen its antimicrobial stewardship through advocacy for institutional buy-in, training and education and appropriate funding of AMS activities.
Our study respondents had better knowledge of AMR (median score of 72.7%) than knowledge of rational APR (median score of 62.5%). Most respondents agreed that AMR is a serious problem in their various hospitals and Nigeria as a whole. However, over half of our respondents did not know that AMR could arise from antibiotic use in animal husbandry and farming. About 78% of farms in Nigeria are using antimicrobials for animal production, and 20% of these livestock have been shown to have multi-drug resistant isolates . Our results support the need to improve awareness on the association between antimicrobial use in animals and emergence of AMR in humans, and to institutionalize national antimicrobial use and resistance surveillance system in animals in Nigeria.
The gap in knowledge of the link between poor practice of IPC and AMR as observed in our study may partly explain why 79% of respondents disagreed that routine hand washing could prevent AMR and 36% were neutral or disagreed that AMR could be transmitted from healthcare worker to patient. About 83% of physicians in another study from Nigeria identified poor infection control as a possible cause of emergence of AMR in hospital settings . However, this study did not specifically evaluate hand hygiene-related knowledge and attitude. Garba et al. reported that 54.1% of healthcare workers in primary healthcare centers in Kaduna North local government area of northern Nigeria wrongly believed that practice of hand hygiene for prevention of AMR is overrated . A study from Europe reported that junior doctors rarely perceived poor hand hygiene practices as important drivers of AMR . The slogan 'Fight antibiotic resistance—it's in your hands' was formulated in 2017 by the WHO to emphasize the central role of hand hygiene in the prevention of AMR . Our study findings suggest that there is need to improve awareness among physicians in Nigeria about the importance of practice of hand hygiene and other components of IPC in reducing the transmission of AMRO in hospital settings.
The median KAP scores of respondents in our study were 71%, 75% and 77% respectively. However, only 22.3%, 40.3%, and 31.6 had good KAP (defined as score of 80% or above) of APR and AMR, respectively. In a systematic review of KAP of APR and AMR among healthcare practitioners from developing countries involving 15 studies (none from Nigeria) an average of 80.9% of respondents correctly answered questions relating to APR, whereas only 39.6% were aware of the local resistance patterns in their health facilities . About 83% of physicians working in tertiary hospitals in four geopolitical zones of Nigeria were reported to have good knowledge of AMR (defined as knowledge score of 80% or above) . Among healthcare practitioners from primary health facilities in northern Nigeria, 73% had good knowledge of AMR (defined as knowledge score between 50 and 74%), while less than 5% had very good knowledge of AMR (defined as knowledge score of 75% and above) . The variability in the proportions of respondents with good knowledge from Nigeria could be related to differences in study design. It is our view that our study findings are representative of physicians working in tertiary hospitals in Nigeria as we included hospitals and physicians across all six geopolitical zones of the country.
Excessive and inappropriate prescription of antibiotics are established drivers of AMR [35, 36]. Our results reveal that an average of 15 (83.3%) of 18 antibiotics were prescribed by each respondent in the prior 6 months. About 69% of respondents were classified as having poor prescription practice, meaning they prescribed antibiotics inappropriately. Some indicators of inappropriate APR in our study included 43% of respondents ever prescribing antibiotics for malaria and 28% sometimes prescribing antibiotics for common cold. Our results also reveal some attitudes and drivers of irrational APR including influence of pharmaceutical companies, lack of trust in laboratory test results, attempting to satisfy patient expectations, prohibitive costs of some antibiotics, and limited access to appropriate antibiotic. Penicillins with β-lactamase inhibitors, fluoroquinolones and third generation cephalosporins were the most common classes of antibiotics frequently prescribed by respondents in our study. While most respondents had prescribed antibiotics from the WHO Access and Watch categories, it is remarkable that about 63% of respondents had prescribed antibiotics in the Reserve group of the WHO AWaRe categories. The high rates of prescription of the Reserve antibiotics Cefepime without recourse to culture results could ultimately lead to high burden of ESBL.
Many studies from Nigeria have also reported overuse and irrational prescription of antibiotics among physicians, with prevalence of self-reported APR ranging from 26.8 to 97% [19, 20, 37] and point prevalence surveys (PPS) reporting APR rates of 59.6–80.1% among in-patients [38,39,40,41]. The global PPS reported a higher prevalence of antibiotic prescribing among Africa hospitals (average of 50%) compared to 27.4% among European hospitals . Most of these studies also reported Penicillins with β-lactamase inhibitors, third generation cephalosporins and fluoroquinolones as the commonest classes of antibiotics prescribed.
The determinants of inappropriate prescriptions of antibiotics have been reviewed by various authors [42, 43]. A systematic review of physicians practicing in different settings across the globe identified patients’ expectations, severity and duration of infections, uncertainty over diagnosis, potentially losing patients, and influence of pharmaceutical companies as drivers of irrational APR among physicians . A study of physicians from a tertiary hospital in Lagos, Nigeria reported factors of cost, drug availability and pressure from pharmaceutical representatives as the major drivers of irrational APR among study participants .
Educational programmes have been shown to improve awareness and knowledge of AMR among healthcare workers, as well as foster appropriate prescription behaviour [44, 45]. We found that good knowledge of AMR and APR was associated with prior training on antibiotic use and resistance. However, the lack of association between prior training and good attitude, practice, and prescription, as well as the weak positive correlations between KAP, support the role of multiplicity of factors in determining attitudes and practices regarding APR and AMR [37, 46, 47]. Additional predictive factors observed in our study were professional rank, hospital and department of practice of physicians.
Independent of other variables, more senior physicians (consultants and resident doctors) in our study had better knowledge and attitudes, and prescribed antibiotics less frequently than recently qualified medical interns. Medical interns have limited experience of clinical practice, and it is not surprising they had the lowest KAPPr scores in our study. Besides poor knowledge, the more frequent prescriptions of antibiotics among these interns compared to other physicians could be related to the hierarchical nature of medical practice in Nigeria where medical interns are in most cases required to write out prescriptions based on instructions of their supervising residents or consultants. The rotation of interns through all major medical specialties has been shown to influence their prescription practice as they are made to transcribe prescriptions from a wide variety of their supervisors in the various departments . Studies from Ghana , USA , Malaysia  and China  have also reported higher knowledge and less frequent prescriptions of antibiotic among senior physicians compared to junior physicians. Other studies have shown that prescription errors are more frequent among medical interns in hospital settings [52, 53].
Hospital of practice was independently associated with good KAPPr among physicians in our study. Physicians practicing in hospitals located in the South-West region of the country generally had better KAPPr scores than those from other hospitals. Prescriptions of Reserve antibiotic (Cefepime) were more frequently observed among physicians practicing in northern Nigeria, as all three hospitals with over 80% of physicians with prior prescriptions of Cefepime were in northern Nigeria. Among five published PPS from Nigeria [38,39,40,41, 54], the lowest prevalence of antibiotic use among inpatients of 59.5% was reported in a South-West hospital  while the highest prevalence of 80.1% was reported among three hospitals located in northern Nigeria . The reasons for the observed hospital-based and regional differences in KAPPr scores and APR are not obvious from our study data, especially as there were no remarkable differences in the implementation of AMS between hospitals surveyed.
Variabilities between hospitals in APR and knowledge of AMR have also been reported by various other studies from other parts of the world [55, 56] and they are usually fueled by contextual, cultural and behavioural factors that define the various hospitals . Differences in the burden, types, and resistance patterns of ID between hospitals could determine the frequency and type of antibiotic prescribed. Organization culture may also influence how physicians prescribe . Studies suggest that “prescribing etiquette” are usually created by senior physicians and passed on to junior physicians as part of mentorship process and to maintain the ‘culture’ of prescription within clinical groups [48, 59, 60]. Recognizing the importance of institutional context and peculiarities in the implementation of ASP, the WHO recommends institutional situational analysis and needs assessment before implementation of AMS in healthcare settings .
Our study data show that physicians practicing in paediatric department prescribed antibiotics more frequently than those from other departments, and physicians practicing in internal medicine and paediatric were more likely to prescribe the Reserve antibiotic Cefepime than those in other departments. Several PPS suggest that paediatric departments rank second only to the intensive care unit with respect to antibiotic use in hospital settings [38,39,40,41, 54]. These PPS have shown that APR are related to burden and resistance spectrum of bacterial infections among in-patients. Consequently, the observed variabilities of APR in relation to department of practice in our study could partly be due to higher burden of bacterial infections and AMR among patients in these departments. It could also be due to ‘prescription etiquette’ that favour more frequent APR in these departments.
Our study had several limitations. First, we did not evaluate all aspects of AMS in healthcare facilities as defined by the WHO . However, our results identified fundamental gaps in the implementation of AMS in Nigeria tertiary hospitals deserving corrective interventions. Second, we did not use probability sampling in selecting respondents, and we could only enroll a limited number of respondents from the north-east region of the country due to prevailing security challenges in this region. However, our study is the first on KAP of AMR to include participants from all six geopolitical zones of the country. In view of the large sample size including participants from most parts of the country, we believe our sample is largely representative of the Nigeria context. Third, the frequency of antibiotic prescription was based on a qualitative Likert’s scale which may not necessarily reflect the quantitative equivalent of antibiotic prescription among respondents. Fourth, our study was not specifically designed to evaluate predictors of institutional or regional variabilities in good KAPPr. Future studies are necessary to determine other relevant contextual, cultural and behavioural factors that could influence KAP of antibiotic prescriptions among physicians in Nigeria.
In conclusion, our study results suggest a lack of implementation of AMS among tertiary hospitals in Nigeria. Although most physicians working in these hospitals had above average KAP of APR and AMR, there were gaps in knowledge and attitude, as well as frequent and inappropriate prescriptions of antibiotics, including those in the Reserve group. Good KAPPr were associated with institutional, geographical, educational, and professional factors. Our study findings should inform interventions that optimize the use of antibiotics in healthcare facilities and improve awareness and understanding of AMR in Nigeria in line with Nigeria’s NAPAR.