University of Ghana http://ugspace.ug.edu.gh SCHOOL OF PUBLIC HEALTH COLLEGE OF HEALTH SCIENCES UNIVERSITY OF GHANA, LEGON PRESCRIPTION PRACTICES AND PATTERNS OF ANTIBIOTICS USED IN CHILDREN ATTENDING THE PRINCESS MARIE LOUISE CHILDREN’S HOSPITAL BY NYARKO AGYEMANG DUAH (10599570) THIS DISSERTATION IS SUBMITTED TO THE UNIVERSITY OF GHANA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF A MASTER OF SCIENCE IN CLINICAL TRIALS DEGREE JULY, 2018 University of Ghana http://ugspace.ug.edu.gh DECLARATION This dissertation is the result of my own independent work under the supervision of Dr. Anthony Danso-Appiah with due acknowledgement paid to all reference sources. I declare that this work either in whole or in part has not been presented for the award of any degree. Signed ……………………………… Date ………………………………. Nyarko Agyemang Duah STUDENT Signed ……………………………… Date ...................................................... Dr. Anthony Danso-Appiah SUPERVISOR i University of Ghana http://ugspace.ug.edu.gh DEDICATION This work is dedicated to my lovely daughter Sunny Sika Koranteng. ii University of Ghana http://ugspace.ug.edu.gh ACKNOWLEDGEMENT First and foremost, I would like to thank the Almighty God for his abundant grace, guidance and protection through the years. I sincerely express my gratitude to my academic supervisor, Dr. Anthony Danso-Appaih for his guidance, support, advice and encouragement during the conduct of the study and writing of the dissertation. And also, to Miss Delia Bandoh for her immense help. I would like to thank the administration of Princess Marie Louise Children’s Hospital granting me the permission to conduct the research in their facility. Finally, I would like to thank the Dean and all lecturers of the School of Public Health, University of Ghana, Legon, for their direct and indirect contributions towards the completion of this research work. iii University of Ghana http://ugspace.ug.edu.gh Contents DECLARATION.......................................................................................................................i DEDICATION..........................................................................................................................ii ACKNOWLEDGEMENT..................................................................................................... iii LIST OF FIGURES ...............................................................................................................vii ABSTRACT.............................................................................................................................ix CHAPTER ONE ......................................................................................................................1 1.0 INTRODUCTION ..........................................................................................................1 1.1.1 Distribution of antibiotic usage ...................................................................................... 1 1.1.2 Antibiotics ....................................................................................................................... 1 1.1.3 Antibiotic practices.........................................................................................................2 1.1.4 Antibiotic Resistance ......................................................................................................3 1.1.5 Antibiotics use in children.............................................................................................. 4 1.1.6 Drug Use Evaluation studies (DUEs).............................................................................5 1.2 Problem Statement ...............................................................................................................6 1.3 Justification ..........................................................................................................................7 1.4 Conceptual Framework........................................................................................................8 1.5 RESEARCH QUESTIONS ...............................................................................................9 1.6 OBJECTIVES ....................................................................................................................10 1.6.1 General objective..........................................................................................................10 1.6.2 Specific objectives........................................................................................................10 CHAPTER TWO ................................................................................................................... 11 2.0 LITERATURE REVIEW...................................................................................................11 2.1 ASSESSMENT OF DRUG USE .......................................................................................11 2.1.1 WHO Core Drug Indicators...........................................................................................12 2.2 FACTORS INFLUENCING ANTIBIOTIC PRESCRIPTION .........................................13 2.2.1 Prescribers Characteristics..........................................................................................13 2.2.3 Non Clinical Factors .....................................................................................................15 2.2.4 Patients Clinical Factors...............................................................................................16 2.2.5. Trends of Antibiotic Prescription in Children ............................................................17 2.2.6 Respiratory Tract Infection in Children.......................................................................18 2.2.5 Policy Factors ...............................................................................................................19 2.3 ANTIBIOTICS...................................................................................................................19 2.3.1 Common Antibiotic and Common Indications ..............................................................20 2.3.2 Commonly Used Antibiotics .........................................................................................22 2.3.3 Side Effects of Antibiotics............................................................................................22 2.3.4 Antibiotic resistance .....................................................................................................24 2.3.5 Effects of Antibiotic Resistance...................................................................................25 iv University of Ghana http://ugspace.ug.edu.gh 2.4 Rational Prescribing...........................................................................................................26 CHAPTER THREE ...............................................................................................................27 3.0 METHODS ........................................................................................................................27 3.1 Study Design......................................................................................................................27 3.2 Type of Study .....................................................................................................................27 3.3 Study area...........................................................................................................................28 3.4 Variables.............................................................................................................................29 3.5 Study population ................................................................................................................30 3.5.1 Inclusion criteria ...........................................................................................................30 3.5.2 Exclusion criteria..........................................................................................................30 3.6 Sampling ............................................................................................................................30 3.7 Data Collection Techniques ...............................................................................................31 3.7.1 Research assistants Training .......................................................................................31 3.7.2 Data Collection..............................................................................................................31 3.8 Quality control ...................................................................................................................32 3.9 Data processing and Analysis ............................................................................................32 3.10 Ethical Consideration.......................................................................................................33 CHAPTER FOUR..................................................................................................................34 4.0 RESULTS...........................................................................................................................34 4.7 Standard Treatment Guideline ...........................................................................................39 CHAPTER FIVE ...................................................................................................................41 5.0 DISCUSSION....................................................................................................................41 CHAPTER SIX ......................................................................................................................47 6.0 CONCLUSION AND RECOMMENDATIONS ...............................................................47 6.1 Conclusion .........................................................................................................................47 6.2 Limitation..........................................................................................................................47 6.3 Recommendation ...............................................................................................................47 7.0 REFERENCES.................................................................................................................49 8.0 APPENDICES ..................................................................................................................60 8.1 QUESTIONNAIRE FOR INVESTIGATOR.....................................................................60 8.2.1 A TEMPLATE FOR DATA ENTRY ..............................................................................64 8.2.1 TEMPLATE FOR DATA ENTRY FOR STANDARD TREATMENT GUIDELINES .....65 8.3 Informed Consent...............................................................................................................66 8.4 FIGURES AND TABLES..................................................................................................68 v University of Ghana http://ugspace.ug.edu.gh LIST OF TABLES Table 1 WHO Core Drug indicator..........................................................................28 Table 2 Description of Study variables.....................................................................29 Table 3 Age categories of participants......................................................................34 Table 4 Type of antibiotic prescribed .......................................................................34 Table 5 Types and classes of Antibiotics prescribed...................................................35 Table 6 Diagnosis made by prescribers for which antibiotic was prescribed over three- year period ............................................................................................................36 Table 7 Association between age and antibiotics prescribed.......................................37 Table 8 Association between sex and antibiotics prescribed .......................................37 Table 9 Association between diagnosis and antibiotics prescribed ..............................38 Table 10 WHO Core Drug indicators obtained values ...............................................39 Table 11 Availability and use of Standard Treatment Guideline .................................40 Table 12 Recommended dosing of fluoroquinolone in children ..................................68 Table 13 Antibiotic resistance range ........................................................................69 vi University of Ghana http://ugspace.ug.edu.gh LIST OF FIGURES Figure 1: Global antibiotic use according income levels between 2000 and 2015..............1 Figure 2: Global spread of antibiotic resistance Source: (WHO, 2014).............................3 Figure 3 Death Attributable to antimicrobial resistance every year by 2050.....................4 Figure 4 Conceptual framework.............................................................................................8 Figure 5 Map of Princess Marie Louise Children’s Hospital ............................................28 Figure 6 Pharmacokinetic changes of drug in neonates and young children...................70 Figure 7 Key events in antibiotic resistance ........................................................................71 vii University of Ghana http://ugspace.ug.edu.gh LIST OF ACRONYMS & ABBREVIATIONS AUGMEN Augmentin AMOXY Amoksiklav BAC. CONJI Bacterial Conjunctiva CAP Community Acquired Pneumonia CIPRO Ciprofloxacin EML Essential Medicine List GENTA Gentamycin GAS Gastroenteritis LMICs Low and Middle Income Countries MET Metronidazole URTI Upper Respiratory Tract Infection MAL Malaria VE Veneral Conjunctiva WHO World Health Organisation STG Standard Treatment Guideline viii University of Ghana http://ugspace.ug.edu.gh ABSTRACT Introduction: Globally, antibiotic use in humans increased by 36% from 2000 to 2010, of which 50% was regarded as inappropriate use. There is high prevalence of antibiotic use in Ghana which is associated with inappropriate use. Whilst antibiotics use in developed countries reduced by 4% between 2000 and 2015 there was 75% increase in low and middle income countries during the same period. This may increase the potential for resistance developing against the antibiotics which may pose a great threat to public health. Objectives: This study assessed prescription practices and pattern of antibiotics use in patients attending the Princess Marie Louise children’s hospital in Accra, Ghana. Methods: Folders of patients who had accessed care at the Princess Marie Children’s Hospital from 1st January 2013 to the 31st December 2015 were selected and reviewed. The antibiotic prescription practices and patterns in the hospital were assessed using the WHO guideline for assessing the average number of medicines prescribed per encounter, prescription by generic name, injections and prescription from the national essential medicine list. During assessment, descriptive analysis was made. Relationship between antibiotic use and indicators like diagnosis, age of patient and sex of patient were also analysed using the Pearson chi squared test. A pretested questionnaire was administered to prescribers to assess adherence to the Standard Treatment Guideline. Results: Out of the 422 folders reviewed Amoksiklav was the highest prescribed antibiotic (145) (34.7%) followed by Cefuroxime (98) (23.2%) and Augmentin (95) (22.5%). The major indication for antibiotic prescription was Upper Respiratory Tract Infection (146/422) ix University of Ghana http://ugspace.ug.edu.gh (34.6%) and fevers (102/422) (24.2%). The average drug encounter per patient was 3.2. Drugs prescribed from the Essential Medicine List was 71.4%. There were no injectables. Of the ten prescribers interviewed, 8 (80 %) had the Standard Treatment Guideline, 4 (40 %) used it regularly and 7 (70 %) prescribed an antibiotic before further investigation were done. A prescribed gave antibiotics to patients depending on the severity of presenting ailment. Conclusion The study showed that majority the study population were below 5 years and most of prescribers interviewed prescribed an antibiotic before further investigation was conducted. This has serious public health implications as some of the children whose condition will not require an antibiotic would be given antibiotic and potentially increase antibiotic resistance. The use of Who Core Drug Indicators was commendable. x University of Ghana http://ugspace.ug.edu.gh CHAPTER ONE 1.0 INTRODUCTION 1.1.1 Distribution of antibiotic usage Globally, antibiotic use in humans increased by 36% between 2000 and 2010, of which 50% was regarded as inappropriate use (Van Boeckel et al., 2014). In low and middle income countries (LMICs) up to 50% of the health budget is directed towards the acquisition and management of medicines with antibiotics forming a major proportion of the budget (Bosu & Ofori-Adjei, 1997). Antibiotics use in the developed countries reduced by 4% from 2000 to 2015 (Fig 1), but there was about 75% increase in low and middle income countries during the same period (Klein et al., 2018). Figure 1: Global antibiotic use according income levels between 2000 and 2015 (Klein et al., 2018) 1.1.2 Antibiotics Antibiotics are effective in treating many bacterial infections but are often used inappropriately to treat other infections of no clinical or pharmacological benefit. This may not only lead to an increase in side effects and costs of healthcare, but also the potential for resistance (Alumran, Hurst, 2011). 1 Yr % of Antibiotic use University of Ghana http://ugspace.ug.edu.gh 1.1.3 Antibiotic practices In low-income countries, the incidence of infectious diseases is high leading to the increase in the use of antibiotics. Bacteria tend to grow resistance due to the continuous use of antibiotics. A systematic review of facility-based studies from sub-Saharan Africa conducted between 1990 and 2006 indicated; the median percentage of upper respiratory infections treated with antibiotics was 73% and 50% of all antibiotic prescriptions were inappropriate (Holloway & Ivanovska, 2009). In addition to high infection rate, developing countries also have to deal with inadequate qualified healthcare staff, unstructured antibiotic use, widespread self-medication, inadequate information about medicines, insufficient medicines of secured quality and lack of access to newly manufactured drugs (Radyowijati & Haak, 2003). In many countries including Ghana, antibiotics can be bought without prescription and do not have underlying standard treatment guidelines (Bosu, 2000). Factors influencing prescription patterns are; specialty of the prescribers, the quality of their practice, routine in-service training and monitoring activities, motivation from pharmaceutical companies, patient preferences, policy factors and the availability of treatment guidelines. The interaction of these factors backed epidemiologic trends as well as customs and traditions, political and socioeconomic factors lead to inappropriate antibiotic use (Nordberg, 2004). Hence, providing extensive education to prescribers, dispensers, and patients in these countries must be a major focus of intervention efforts. Governments, public and private healthcare facilities, as well as medical practitioners need to enforce policies and programmes that stimulate changes in the way antibiotics are used. 2 University of Ghana http://ugspace.ug.edu.gh 1.1.4 Antibiotic Resistance Excessive clinical use of antibiotics is partly responsible for the increasing rates of resistance, especially in hospitals throughout world. The needless prescription of antibiotics seen in developed nations has also been recorded in many low income countries, specifically in cases of acute infantile diarrhoea and viral respiratory infections (Hui et al., 1997). A systematic review conducted in sub Saharan Africa to assess the extent of resistance against S. pneumoniae with various antibiotics showed median prevalence of resistance to erythromycin was consistently low (0% - 5.9%), but tetracycline was high for both S. pneumoniae (42.7%) and H. influenzae (100%) in West Africa. Tetracycline resistance was lower in East Africa (13% and 0%, respectively). Likewise, the median prevalence of resistance to co-trimoxazole appeared much higher in West Africa than in East Africa for both pathogens (Leopold & Van Leth, 2014). Figure 2: Global spread of antibiotic resistance Source: (WHO, 2014). 3 University of Ghana http://ugspace.ug.edu.gh An estimated death of 4,730,000 and 4,150,000 in Asia and Africa are likely to occur by 2050 respectively if antimicrobial resistance is not combatted (Review on Antimicrobial Resistance, 2014). Figure 3 Death Attributable to antimicrobial resistance every year by 2050. 1.1.5 Antibiotics use in children The paediatric population forms 20% - 25% of the world's population and is prone to infectious diseases which has shown high risk of misuse of antibiotics (Shankar et al., 2006). Apart from resistance, misuse of antibiotics in infants can also lead to serious adverse drug reaction, in some with long-term disability. Nevertheless, the use of antibiotics has become a routine practice for the treatment of most paediatric illnesses like fever, UTI, gastroenteritis, skin infections among others (Wachter, Joshi, & Rimal, 1999). Age is a major factor that needs to be considered when giving antimicrobials. Gastric activity and renal functions vary with age. Thus, the dosage of drugs is sometimes based on the age and 4 University of Ghana http://ugspace.ug.edu.gh weight of infants. Some drugs like Phenoxymethylpenicillin also known as Penicillin V, which is taken orally, is poorly absorbed in infants when administered. Since functions in the neonates are underdeveloped, this can result in difficulties as drugs are normally excreted or detoxify by liver. Chloramphenicol is inactivated by conjugation to the glucuronide from the liver. Administration of high levels could lead to the Gray’s syndrome, a syndrome normally found in premature babies due to the inability of their liver to produce enzymes for detoxification that can result in death (Dasgupta, 2012). Sulfonamides cause preventable brain damage when used in children with neonatal jaundice. The tetracyclines have a number of adverse effects on bones during pregnancy and after birth. Thus, when given during the latter half of the pregnancy or from birth to the age of 6 months, they may affect the formation of teeth in the child. From the age of 6 months to 8 years, damage to the permanent teeth may occur. The use of fluoroquinolone in children for indications like UTI, inhalation anthrax and cystic fibrosis exposes children to common adverse events such as dizziness, insomnia, abdominal pain, diarrhoea, dysepsia, nausea, vomiting, elevated LFT levels, fever, headache and restlessness (Taketomo & Hodding, 2011). 1.1.6 Drug Use Evaluation studies (DUEs) Rational prescribing aims at giving what is needed , right dosage, duration, cost effectiveness and also monitoring, whiles taking patient’s preferences into consideration (Akhtar et al.,2012). Studies conducted to evaluate drug use are helpful in healthcare delivery systems as they provide information on drug use patterns, enhance rational use of drugs and identify expensive drugs. Drug utilisation studies can successfully be carried out in households in communities but reliably, policy makers prefer healthcare facility reviews to assess National policies and programmes related to medicines (Kristiansson & Reilly, 2008). 5 University of Ghana http://ugspace.ug.edu.gh The World Health Organization core drug indicators are essential in the monitoring of drug use. These core indicators which are average number of drugs per prescription, percentage of drugs prescribed under generic names, percentage of drugs prescribed which contained an antibiotic, percentage of drugs prescribed in an injection form and percentage of drugs from the essential drugs formulary. The use of the Essential Medicine List could limit the number of antibiotics available to clinicians. However, administration of these strategies does not ensure optimal antibiotic use by clinicians in developing countries because the inconsistencies in drug supply, availability of drugs from unofficial sources, and financial problems also affect antibiotic preferences (Gonzalez et al., 1996). 1.2 Problem Statement Antibiotic resistance is an increasing threat to public health globally. High prevalence rate of antibiotic use have been recorded in hospitals in Benin (64.6%), Vietnam (67.4) and in Ghana (59.9%) (Ahoyo et al., 2014 ; Thu et al., 2012 ; Ahiabu et al., 2015). High prevalence of antibiotic use is associated with inappropriate use. About 50% of patients given antibiotics had no need for them. This could cause high health care cost, resistance and increased mortality. The case is no different in children as long-term side effects and resistance could also occur. It is therefore expedient to assess prescription practice and pattern as it is a major route for antibiotic consumption. Majority of antibiotics consumed are in the paediatric population. Assessment of prescription practices and pattern of antibiotics in children is needed to enhance judicious use of drugs. Prescription practices and pattern is influenced by prescriber factors, policy factors and patient factors. Knowledge of prescriber is key in prescription. When, how, whom and the dosage to be given in the right amount is needed to get effective treatment outcomes. Age, gender, diagnosis and weight of the patient also affect prescription pattern. The prescriber only prescribes what is made available and accessible by policy makers. Policy makers like the government decides on what kind of antibiotics to be introduced into the health 6 University of Ghana http://ugspace.ug.edu.gh system. Hence there is the need for studies on the assessment of drug use in health facilities. These studies are prudent as they provide information on drug use trends, practices, improve appropriate use of drugs and identify expensive medicines (e.g. Antibiotics) which are of economic interests. 1.3 Justification This study is aimed at improving the use of antibiotics and preventing inappropriate prescription of antibiotics in children. Assessment of prescription practices and pattern would help reduce health care cost, duration of hospitalisation hence improving health care delivery. Taking note of facility factors could help in the implementation of strategies for the effective prescription and use of antibiotics. Studies on drug utilization serve as a form of assessment for prescribers. This would ensure that drug use indicators and treatment guidelines are well adhered to. Antibiotics are the most prescribed drug in the paediatrics, and it is important to ensure that children are given antibiotics when needed and if possible with evidence of bacterial presence. In infants there could be a long term side effect on the use of antibiotics such as adverse reaction, high cost of treatment long duration of treatment and further resistance of antibiotics. Information provided by this study would serve as an assessment for prescribers and also a guide in the utilisation of antibiotics in the paediatric population and from the basis for further studies. 7 University of Ghana http://ugspace.ug.edu.gh 1.4 Conceptual Framework Prescriber’s factors Policy factors  Qualification  Use of Standard Treatment  Insurance scheme Guideline  Availability  Accessibility Prescribing indicators  Average number of drugs per encounter  Percentage of drugs prescribed by generic name Prescription practices  Percentage of encounters with an injection prescribed and pattern  Percentage of drugs prescribed from essential drugs list (EDL) Patient’s factors Patient’s outcomes  Demographic factors  Diagnosis  Frequency of revisits  Compliance to  Adverse drug events medication  Resistance High healthcare cost Mortality Figure 4 Conceptual framework 8 University of Ghana http://ugspace.ug.edu.gh Narrative of the conceptual framework The prescriber’s factors being the qualification and specialty can inform a particular antibiotic administration and even the route of administration. For instance, the prescription pattern of specialists and clinicians attending to in-patients with special conditions is known from literature to be almost accurate. Adhering to prescribing indicators is influenced largely by the qualification of the prescriber and the use of Standard Treatment Guideline. Availability and accessibility of drugs to their patients is a factor worth considering by the Prescriber during prescription. Some policy factors like the various insurance schemes also influence prescription. Some drugs are not prescribed because the insurance scheme available does not cover. The age, weight and sex of patients to whom antibiotics are prescribed to influence the type, dosage and route of administration. Outcomes like cure, adverse drug reactions, incomplete metabolism and ultimately antibiotic resistance could be the results of the various prescriptions given. These outcomes result in high healthcare cost which can be caused by long duration of hospitalization due to complications and consequently lead to increased mortality. 1.5 RESEARCH QUESTIONS  What are the prescription practice and patterns of antibiotic used in children?  What are the factors that affect antibiotic prescription?  How is well is standard treatment guidelines adhered to? 9 University of Ghana http://ugspace.ug.edu.gh 1.6 OBJECTIVES 1.6.1 General objective To assess the prescription practices and pattern of antibiotics use in children who attended the Princess Marie Louise Children’s hospital from January 2013-December 2015. 1.6.2 Specific objectives 1. To assess prescription pattern of antibiotics using the WHO Core Drug Use indicators. 2. To assess factors that influence antibiotic prescription. 3. To assess the types and classes of antibiotics prescribed. 4. To assess adherence of prescribers to Standard treatment Guidelines. 10 University of Ghana http://ugspace.ug.edu.gh CHAPTER TWO 2.0 LITERATURE REVIEW 2.1 ASSESSMENT OF DRUG USE The basis of drug utilization involves the prescription, dispensing, marketing, distribution and the handling of drugs in a society with the ultimate aim of facilitating their rational use. Hence , the World Health Organization has put together a set of core drug use indicators that can be used to assess prescriber’s performance, patients experience at health facilities and the adherence to good healthcare delivery by the health personnel (Thiruthopu et al., 2014). The indicators used for these assessments are prescribing indicators, patient care indicators, facility indicators and complementary indicators (Akhtar et al., 2012). Prescribing indicators: These five keys listed below are essential in assessing the performance of health care providers in several key dimensions related to the appropriate use of drugs. These include,  Average number of drugs per encounter.  Percentage of drugs prescribed by generic name.  Percentage of encounters with an antibiotic prescribed.  Percentage of encounters with an injection prescribed.  Percentage of drugs prescribed from essential drugs list (EDL) or formulary. Patient care indicators: address key aspects of what patients experience at health facilities, and their compliance to dispensed drugs  Average consultation time.  Average dispensing time.  Percentage of drugs actually dispensed.  Percentage of drugs actually labelled.  Patients’ knowledge of correct dosage. 11 University of Ghana http://ugspace.ug.edu.gh Facility-specific indicators: these are measures put in place by the health care centre to facilitate and ensure prescribers are provided with the logistics and knowledge to prescribe drugs rationally.  Availability of a copy of the EDL or formulary.  Availability of key drugs in the stock. 2.1.1 WHO Core Drug Indicators The WHO prescribing indicators or the WHO core drug indicators are measurements used in the assessment of prescribers or health care providers in general in relation to the appropriate use of drugs. These indicators are in five important aspects. All aspects of these indicators are obtained from patients’ clinical encounter with the prescriber. Preferably, this encounter should include number of components such as history taking, diagnosis process; selection of non-pharmacological or pharmacological treatment, prescription of treatment; and deliberations on treatment and its adverse effects, follow-up, and prevention (Trap et al., 2002). A prescription is deemed appropriate or inappropriate based on the WHO core drugs indicators. Three or more drugs per a patient encounter is termed as poly-pharmacy which can increase the risk of adverse drug interactions, non-adherence, and antimicrobial resistance. Most studies recorded high values as compared to the standards (Babalola et al., 20 11)(Binu, Sabbu, Surendra, & Hiremath, 2013). In low-middle income countries, studies conducted in the paediatric setting reported a range of values for this indicator (average number of drug prescribed per patient encounter), in Sudan (2.0), Nigeria (2.6), and India (5.6) (Babalola et al., 2011; Binu et al., 2013). Percentage of prescription that contained antibiotic was 81.3% and 71.1% in Sudan and Nigeria respectively (Babalola et al., 2011; Binu et al., 2013). In some studies adherence to an essential drugs list was high because physicians had easy access to updated Essential Medicine List (EML) and 12 University of Ghana http://ugspace.ug.edu.gh also most insurance scheme required drugs to be prescribed from the list. A study conducted by Summoro et al, 2015 used WHO Core Drug use indicators to assess the prescription pattern in a four hospitals in Ethiopia. Prescription from the Essential Medicine List and Prescribing using the generic name of drugs were comparatively high (Summoro et al., 2015). 2.2 FACTORS INFLUENCING ANTIBIOTIC PRESCRIPTION 2.2.1 Prescribers Characteristics In Sub Saharan Africa, there is not much information about the influence of drug prescribers and dispensers which include clinicians, nurses, pharmacists, pharmacy assistants, and small- shop owners and counter staff, on the use of antibiotic. Few studies have indicated the influence of prescribers’ knowledge in different ways in the prescription or recommendation of antibiotics in practice. In a study conducted in the Southwest of Nigeria, antibiotic prescription gets better when the qualification ladder gets higher that is from community nurses, health assistants, medical doctors to pharmacists (Babalola et al., 2011). Other factors appear to influence prescription, with adequate knowledge some clinicians still prescribe antibiotics inappropriately (Kwena, Sharma, & Wamae, 2008). In-service training of prescribers is needed to broaden their knowledge to prescribe rationally. This is to be done periodically to help check irrational prescription. Lack of this training has been noticed to influence prescription pattern as the case of a study conducted in Ghana. It was found that none of the prescribers had received an in- service training for five years in a roll (Bosu, 2000). 13 University of Ghana http://ugspace.ug.edu.gh Patient to prescriber ratio is very important in the analyses of prescribing patterns. In most developing countries, there is limited health care staff hence time spent on each patient and the number of patients to be attended to are most at time quite challenging. Studies conducted in Zimbabwe and Ghana indicated that, due to time constraints most patients were attended to without any diagnostic tests being done. Also some prescribers in these developing countries also sometimes doubles up as dispensing officers. An occurrence as this, with no control mechanism can influence prescription in a negative way (Trap & Hansen., 2002 ; Polage et al., 2006). There are two basic factors considered when prescribing antibiotics. These are the patient’s information and the possible bacteria causing the particular infection. Due to uncertainties in diagnosis and inadequate or underutilized diagnostics these factors are mostly undermined and this leads to a heavy reliance on broad-spectrum antibiotics and overuse of antimicrobials (Mukonzo, Namuwenge & Okure, 2013). Essential Medicine List and Standard Treatment Guidelines (STGs) developed by the Ministry of Health is aimed at regulating prescription practices in Ghana (Ghana National Drugs Programme, 2010). The utilization of these guidelines are not mandatory. Studies conducted in Ghana (Bosu, 2000 ; Arhinful, 2009) and beyond Ghana (Abula Teferra & Desta Zeruesenay, 2002 ; Akande, 2007) have shown different degrees of inappropriate prescriptions and utilization of drugs in public health facilities. These studies were conducted in primary, secondary and tertiary health facilities. Antibiotic prescription patterns ranging from a low of 11.9% to a high of 60.7% were obtained. High level and inappropriate use of antibiotics were also recorded in primary health care facilities in the Eastern region of Ghana (Ahiabu et al., 2015). 14 University of Ghana http://ugspace.ug.edu.gh 2.2.3 Non Clinical Factors Non clinical factors like patient’s beliefs and attitudes towards the use of antibiotics is worth considering when antibiotic prescription is being discussed. A study conducted in South Africa (Hoffman, Botha, & Kleinschmidt, 2003) indicated that 83% of patients who attended a health facility were expecting an antibiotic from the clinician. About 90% from this population did not have any idea on the harm they would be exposing themselves to when an antibiotic is prescribed to them inappropriately. In a quest of sound health, some parents or caretakers tend to pressurize paediatricians into prescribing antibiotics for their ward. They feel secured and their needs met when antibiotics are prescribed for their children. In a large survey conducted in USA, 50% of paediatrics prescribed antibiotics unnecessarily to children with viral infections due to pressure from parents (Bauchner & Pelton, 1999). Several studies have indicated pressure from parents and the belief of the physician as a possible cause of overprescribing (Kutty, 2011). In a qualitative study conducted in three African countries, evidence gathered revealed that parents or guardians are likely to forget correct dosage of antibiotics due to illiteracy or absence of dosage form. Most likely antibiotic use is stopped before the full course is completed (Bedford, 2014). For financial gains, some dispensers in the private sector are likely to prescribe more antibiotics. The profit of these drugs is gained on commission basis. Trap et al (2002) found out that dispensing doctors prescribed more antibiotics than non-dispensing doctors did (Trap & Hansen, 2002). 15 University of Ghana http://ugspace.ug.edu.gh 2.2.4 Patients Clinical Factors Due to the common places like day care children find themselves in, they are susceptible to drug resistant bacteria. With lot of infections affecting this age group, children tend to be vulnerable to the use of antibiotics. Many factors affect the prescription of antibiotics in children (Woods, 2006). Prescribers tend to prescribe antibiotics based on symptoms. Drugs are administered to infants for quick relief even before further diagnosis is done. The empirical use of antibiotics is inevitable due to diagnostic challenges. The World Health Organization (WHO) among other two institutions have currently provided an outline for treatment of Community Acquired Pneumonia (CAP). Empirical antibiotic is still use due to inaccurate diagnosis and difficulty in identifying the causative organism of CAP (World Health Organisation, 2014). The age and gender of the patient have a great influence on prescription. Children most often are not included in clinical trials so information on drug effect in children is insufficient. Furthermore, non- compliance to drug therapy in children due to either multiple prescription or dosing has an influence on prescription pattern (Akhtar et al., 2012). A study conducted in Sweden revealed that the frequency at which females are given antibiotics was very high as compared to males (265.5 patients/1000 women and 191.3 patients/1000 men) (Loikas & Wettermark, 2013). Also some prescribers in quest to save money just decide to prescribe antibiotics to these children based on previous experience. Presumptive treatment is quite a common practice among prescribers. It becomes an alternative almost all the time considering the duration it takes for diagnostic test to be carried out. A study conducted in rural areas in Tanzania on the use of antimalarial indicated that 56% of patients recruited were given antimalarial without any parasitological testing (Njozi et al., 2013). 16 University of Ghana http://ugspace.ug.edu.gh 2.2.5. Trends of Antibiotic Prescription in Children Studies on the rationality of antibiotic use in children is commonly based on assessing prescriptions made by physicians to children with respiratory tract infections. This is because most respiratory tract infections are of viral etiology and when antibiotics are administered they do not prevent complication or reduce the length of day of the infection (Alves Galvao & Rocha Crispino Santos, 2014). Prescribing antibiotics to children with respiratory tract infection is a common practice. In Africa and Asia, 20-90% of children with respiratory tract infections are given antibiotics. This is the highest range as reported by Gelbrand and colleagues (2015)(Gelbrand, Miller-Petrie & Pant, 2015). Other studies conducted in Nepal, India and Vietnam reported range of 72.2% to 81.1% in Nepal (children less than 13years), India (adults) and Vietnam (children under-five) of antibiotic use (Hoan le, Chuc &Ottosson, 2009). Elsewhere in the developed countries like the U.S, 44% of children with common colds were reported to be treated with antibiotics, 46% of those with upper respiratory infections and 75% of those with bronchitis (Nyquist et al., 1999). The use of antibiotics in these cases were irrelevant. In Canada also, 74% of preschool children who were diagnosed with respiratory infections received antibiotic prescriptions. About 85% of these cases with antibiotic prescriptions were inappropriate (Nyquist et al., 1999). A global decrease in the use of antibiotics have been reported by researchers; mostly from the developed countries in the 2000s in both adults and children (McCaig & Besser, 2002). This could be backed by a cohort study conducted in Taiwan from 2000 to 2009. This decline was attributed to a restricted government policy. In this policy, antibiotics are only to be dispensed based on evidence of the presence of bacteria (Lee et al., 2016). 17 University of Ghana http://ugspace.ug.edu.gh 2.2.6 Respiratory Tract Infection in Children The possibility of the occurrence of an infection depends on age and exposure to the infection. Once the infection occurs, environmental factors and genetic factors determines the severity. A study reported that during winter and summer breaks when children were on vacation, the rate of respiratory tract infection recorded was very low (Lee et al., 2016). Globally, respiratory syncytial virus is by far the most common cause of viral lower respiratory tract infection in the paediatric population. Children by age 3 have acquired immunity against respiratory syncytial virus (Simoes, 1999). Respiratory syncytial virus accounted for 75% of all admissions for bronchiolitis in children under 5 years of age (Muller-Pebody et al.,2002). In a study conducted during winter in Netherlands, diagnostic test identified Human metapneumovirus as the cause of infection in 28 children showing symptoms of lower respiratory tract infection (Greensill et al., 2003). Influenza viruses also pose serious threat to infants. A study conducted in 2000 reported that children under the age 5 are 12-folds at risk of being admitted to the hospital due to respiratory tract infection caused by influenza virus compared with children aged 5-17 years (Izurieta et al., 2000). Most respiratory tract infections (lower, upper. acute respiratory tract, otitis media and sinusitis) are believed to be caused by virus, but various drugs such as antibiotics, Bronchodilators, Corticosteroids are used for their treatment. These drugs are used to clear air path. Streptococcus pneumoniae remains the most common bacterial cause of community- acquired Respiratory Tract Infection (Linares, Ardanuy & Pallares, 2010). 18 University of Ghana http://ugspace.ug.edu.gh 2.2.5 Policy Factors Prescribers would only prescribe based on the availability and accessibility of the antibiotics to their patients. The ability of prescribers to provide appropriate antimicrobial therapy may be limited by the unavailability of the required antibiotics. Studies conducted in Bangladesh, India and Tanzania indicated that in primary care facilities antibiotics were mostly prescribed according to availability of antibiotics not according to the needs of the clients. Overuse of antibiotics in hospitals was caused by the wider range of antibiotics available (Aryanti ,Radyowijati & Haak, 2003). A study conducted in Ghana to evaluate drug prescription also indicated that from a list of prescriptions reviewed, most drugs were from the essential drug list and 36.6% were antibiotics (Apanga et al., 2014). Most of these patients were on the health insurance scheme put in place by the Ghanaian government to make health care affordable and accessible to the general population. Based on the insurance package, prescribers prescribed from the essential drug list (Apanga et al., 2014). Rodrigues found that, though guideline for standard treatment is available for prescribers, the WHO-recommended antibiotics for children is not evenly distributed. It was reported that Nigerian guardians of children do not have easy access to antibiotics either from their health facilities or antibiotic supply agents (Rodrigues, 2017). 2.3 ANTIBIOTICS Broad-spectrum antibiotics are used to treat wide range of infections. Others are only effective against a few types of bacteria and called 'narrow-spectrum' antibiotics. Depending on the range of bacterial species susceptible to these agents, antibiotics are generally classified as either broad spectrum or narrow spectrum (Hopkins, 1997). 19 University of Ghana http://ugspace.ug.edu.gh Broad spectrum antibiotics are active against both Gram-positive and Gram-negative microorganisms. Examples include Tetracyclines, third and second generation Cephalosporins, and Fluoroquinolones. Tetracycline is effective against gram-positive, gram- negative, anaerobic, acid-fast (atypical), and Rickettsia bacteria. They are recommended for the treatment of respiratory infections, community-acquired methicillin-resistant Staphylococcus aureus, and acne in patients aged 8 years and older (Smith, Unkel & Fenton , 2001). Tetracyclines were first introduced in 1948. In 1956, an adverse reaction of tooth discoloration in children was reported (Sánchez & Rogers III, 2004). Nalidixic acid was the first fluoroquinolone to be introduced. Even though it is not commonly used, it has been the recommended drug for children above 3 months who have Urinary Tract Infections (UTIs) from 1964. Ciprofloxacin and levofloxacin are the frequently used fluoroquinolone. They were approved for use in children solely for the post exposure treatment of inhalation anthrax prior to 2004 (American Academy of Pediatrics Committee on Infectious Diseases, 2006). On the other hand, narrow spectrum antibiotics have limited activity against bacteria and are primarily effective against particular species of microorganisms. For example, bacitracin and glycopeptides and are only effective against Gram-positive bacteria, whereas polymixins are usually only effective against Gram negative bacteria. Aminoglycosides and sulfonamides are only effective against aerobic organisms, while nitroimidazoles are generally effective against anaerobic bacteria (Edson et al., 2011). 2.3.1 Common Antibiotic and Common Indications Penicillins are broad-spectrum antibiotics used to treat infections. The penicillins are bactericidal and act by interfering with bacterial cell wall synthesis. They diffuse well into body tissues and fluids. Amoxicillin, ampicillin, bacampicillin, oxacillin are examples of 20 University of Ghana http://ugspace.ug.edu.gh Penicillin. Penicillins and Cephalosporins were the highest consumed antibiotic about 60 percent of total consumption in 2010 (Van Boeckel et al., 2014). This was because of an increase of 41 percent from 2000. Among the oldest antibiotics on the market, these are still the most common first-line antibiotics and the primary treatment for common infections around the world (Van Boeckel et al., 2014). The Cephalosporins are broad-spectrum antibiotics which are used for the treatment of septicaemia, pneumonia, meningitis, biliary-tract infections, peritonitis, and urinary tract infections. The macrolides are used for patients who have an allergic reaction to penicillin. They are used to treat infections like campylobacter enteritis, respiratory infections (including pneumonia, whooping cough, Legionella, chlamydia, and mycoplasma infection), and skin infections. Erythromycin, clarithromycin, azithromycin and roxithromycin are examples of macrolides. For the past decades due to their long half-life and short duration of therapy, macrolides have been an attractive antibiotic class and in some cases to target pathogens as Mycoplasma Pneumoniae as a cause of pneumonia (Hersh, Shapiro & Pavia, 2011). Tetracyclines are broad-spectrum antibiotics used to treat mild acne, Rocky Mountain spotted fever, Lyme disease, upper respiratory tract infections, urinary tract infections and sexually transmitted diseases. The most commonly prescribed tetracyclines are tetracycline, doxycycline and minocycline (Sánchez & Rogers III, 2004). However, the efficacy of macrolides against this pathogen has not been definitively established and resistance to this class has been reported among patients infected with community acquired pneumonia (Daneman, McGeer & Green, 2006). 21 University of Ghana http://ugspace.ug.edu.gh 2.3.2 Commonly Used Antibiotics In a study conducted by Ahiabu et al (2015) in the eastern region of Ghana indicated amoxicillin (26.7%) followed by metronidazole (18.2%), as the most prescribed antibiotics. Common diagnosis from the study were malaria and respiratory tract infections (Ahiabu et al., 2015). In Western Nepal, a study conducted among paediatric in-patient indicated neonatal sepsis and neonatal hyperbilirubinaemia as the common conditions in Neonates and Acute gastroenteritis and lower respiratory tract infections in the older age groups. Ampicillin, cefotaxime and gentamicin were the most commonly prescribed antibiotics (Shankar et al., 2006). Another study in Eastern Nepal found gentamicin, ampicillin, crystalline penicillin and cefotaxime as the common antibiotics prescribed (Rauniar, Naga Rani & Das, 2003). Ampicillin, gentamicin, amoxicillin, cloxacillin and ceftriaxone were also among the common antibiotics prescribed in a study conducted in a teaching hospital in Bangladesh (Akter, Heller, & Smith, 2004). 2.3.3 Side Effects of Antibiotics When not taken in the right amount for the right infection, antibiotic like any other drug could pose side effects. Diarrhoea, nausea, vomiting, fungal infections of the mouth, digestive tract infections are some side effects of antibiotics. When taken in excess, antibiotics can change the normal flora of the body causing the fungal infections. Antibiotics are known to be linked with adverse reactions so care needs to be taken when administering them (Dodoo et al., 2009). 22 University of Ghana http://ugspace.ug.edu.gh Fluoroquinolone, a broad spectrum antibiotic have a great tissue penetration ability and it is gradually becoming the go to drug for adults. The use of fluoroquinolones have shown adverse effects on cartilage development in juvenile animals through the inflammation and destruction of weight-bearing joints. Levofloxacin is ideally used in the absence of Ciprofloxacin. The recommended doses for these fluoroquinolones ; 18-40mg/kg/day for Ciprofloxacin and 10mg/kg/dose (IV only) for Levofloxacin (Table 12 Recommended dosing of fluoroquinolone in children in Appendix) (Taketomo & Hodding , 2011). A likely occurrence can happen in humans hence the moderated use of fluoroquinolones in the paediatric population. Ciprofloxacin recorded a 3.3% (9.3% vs. 6.0%) absolute risk increase in musculoskeletal events in 6 weeks of treatment compared with control agents used to treat complicated UTIs in a study conducted in children (American Academy of Pediatrics Committee on Infectious Diseases, 2006). The routine use of tetracycline in children under 8 years causes tooth discoloration. This is because at this age, calcification has not been completed. This broad-spectrum antibiotic form tetracycline complex and attach themselves to developing bones and teeth. Light hypersensitivity, gastrointestinal effects, and rare hepatotoxicity are known adverse events caused by tetracylines (Tan, Magill & Parise, 2011). The pharmacokinetics and pharmacodynamics processes (figure 6, Appendix) of many drugs in the paediatric population is different from that of adults. In children the benefits and side effects should be weighed before administering drugs (Mulla, 2010). 23 University of Ghana http://ugspace.ug.edu.gh 2.3.4 Antibiotic resistance The inappropriate use of medications could be practiced in the form of overuse, underuse, and misuse of prescription or over-the-counter drugs. Poor quality of antibiotic prescription, use of antibiotics in nonbacterial diseases, poor adherence to guidelines can cause antibiotic resistance (Ahmad et al., 2012). From data collected from published and those submitted by countries, the WHO antibiotic resistance shows : 0-87 and 0-98 resistance of E. coli to third-generation cephalosporins and fluoroquinolones respectively, 8-77 and 0-4 resistance of K. pneumonia to third-generation cephalosporins and carbapenems, 0-100 resistance of S. aureus to methicillin, 1-100 resistance of penicillin to S. pneumonia and 0-35 resistance of non-typhoidal Salmonella to fluoroquinilones (Table 13, Appendix) (Word Health Organization, 2014). Following the resistance ranges in recent times, neonatal sepsis caused by E. coli, K. pneumoniae and S. aureus is not effectively managed with drugs like ampicillin, aminoglycosides and cephalosporins. The high levels of resistance to amoxicillin and penicillin in S. pneumoniae and H. influenzae are also concerning given that pneumonia is a leading cause of death in children (Woldu, 2016). Furthermore, due to antibiotic resistance, patients are more likely to stay infectious for a longer time, increasing the risk of spreading the infection to others and increasing cost of treatment. Ensuring the appropriateness of antibiotic prescription is needed to promote the rational use of antibiotics (Jha et al, 2010). When bacteria are exposed to the same antibiotics over and over, the bacteria can change or adapt and are no longer affected by the drug. Bacteria gain resistance by modifying their target sites, inactivation and also inhibiting the entry of the antibiotic. Resistance can also occur when antibiotics which is effective against bacterial infection is used to treat other infections like viral or fungal infections. This reduces the efficacy of the antibiotic. Resistance to antibiotics poses a serious and growing problem, because some infectious diseases are becoming more difficult to treat. 24 University of Ghana http://ugspace.ug.edu.gh Key events in antibiotic resistance (Figure 7, Appendix) has been reported by Centre for Disease Control and Prevention (CDC) (Centers for Disease Control and Prevention, 2013). 2.3.5 Effects of Antibiotic Resistance It is quite obvious that there is a decline in the effectiveness of antibiotics across the globe. First line antibiotics are gradually losing their potency and at an alarming rate. Ways in which bacteria show resistance to specific antibiotics differ regionally and by country and this shows the burden of infectious diseases and antibiotic use in that environment (Gelbrand, Miller- Petrie & Pant, 2015). Over 2 million infections and 23,000 deaths each year in the United States have been attributed to antibiotic resistance (Centers for Disease Control and Prevention , 2013). Economically, $20 and $35 billion have been lost as direct and productivity cost of antibiotic resistance respectively in the U.S. (Centers for Disease Control and Prevention , 2013).In Europe, an estimated 25,000 deaths are attributable to antibiotic-resistant infections, costing €1.5 billion annually in direct and indirect costs (European Medicines Agency (EMA) and European Centre for Disease Prevention and Control (ECDC), 2009). The developing world has had its own ordeal in association with antibiotic resistance. Although there is no substantial evidence of antibiotic resistance on the economy, it was estimated that 58,000 neonatal sepsis deaths were as a result of drug-resistant infections in India alone (Laxminarayan et al., 2013). In Africa, further studies conducted in Tanzania and Mozambique showed that resistant infections result in increased mortality in neonates and children under five (Kayange et al., 2010; Roca et al., 2008). 25 University of Ghana http://ugspace.ug.edu.gh 2.4 Rational Prescribing The use of drugs in all stages (prescribing, dispensing, marketing, distribution and client use) aim at ensuring their rational use. Proper prescribing, dispensing and administration of drugs is needed among the prescribers to ensure correct and effective use of medicines, with deviations in any or all of these resulting in medication error (Al Balushi & Al-Shibli, 2014). Frequent assessment of the effects of drugs, re-evaluation of the risk-benefit ratio and if harmful taking the drug off the market or readjusting the dosage becomes important to enhance rational prescription of drugs (Sachdeo et al., 2013). The rational use of antibiotics prevents resistance and improves adherence. With the judicious use of the existing antibiotics, policy makers need not to introduce new set of antibiotics. This helps to reduce cost or money spent on drugs. Patients are relieved from long hospital stays and also adverse drug events if any (Risk, Naismith & Burnett, 2013). 26 University of Ghana http://ugspace.ug.edu.gh CHAPTER THREE 3.0 METHODS 3.1 Study Design Medical records of children under 12 years who attended the out-patient department of the Princess Marie Louise Children’s Hospital and were given at least one antibiotic between the1st January 2013 to 31st December 2015 were reviewed using a structured and pre-tested data abstraction form. Pretested structured questionnaire were also administered to prescribers in the health facility. 3.2 Type of Study A retrospective study was carried out in the Princess Marie Louise Children’s Hospital. Data from outpatients from day 1 to 12 years of either sex who attended the Princess Marie Louise Children’s Hospital from 1st January 2013 to 31st December 2015 was used for the study. Data was extracted from patients’ folders and nurses’ notes. The data included diagnosis, age, sex, total number of drugs prescribed per patient, dosage, frequency, duration, prescriber’s information and route of administration. A pretested structured questionnaire on Standard treatment Guideline was administered to prescribers. 27 University of Ghana http://ugspace.ug.edu.gh Table 1 WHO Core Drug indicator Core drug indicator WHO Optimal value Average number of drugs per prescription <2.0 Percentage of drugs prescribed under generic names 100% Percentage of drugs prescribed which contained an <30% antibiotic Percentage of drugs prescribed in an injection form <20% Percentage of drugs from the essential drugs formulary 100% Source: Isah et al. 1997. 3.3 Study area Figure 5 Map of Princess Marie Louise Children’s Hospital (Google, 2018) 28 University of Ghana http://ugspace.ug.edu.gh Medical care and child health, family planning and nutrition services are healthcare services provided at The Princess Marie Louise Children’s Hospital. The institution which is located at the heart of Accra the Capital of Ghana, West Africa is a 74-bed hospital admitting children from the ages of 1day to 18years. As at the year 2012, the outpatient record of the hospital was 73000. 3.4 Variables The outcome variable is the prescription pattern of antibiotics of outpatients at the Princess Marie Louise Children’s Hospital. The Independent Variables include:  Demographic Characteristics (age and sex) and prescriber’s information  Types of antibiotics prescribed  Doses, frequency, route of administration and duration of antibiotics prescribed Table 2 Description of Study variables Variable Definition Scale Type of Variable Age Age in years at the time the patient Binary Independent attended the hospital Sex Being a male or Female Binary Independent Doses, Dose = ml/mg per body weight of Categorical Independent frequency, route antibiotic to be taken at a time of Frequency = time interval antibiotic is administration to be taken within 24 hours and duration Duration of therapy = For how many days antibiotic is to be taken Type of Antibiotics used in the management of Categorical Independent Antibiotic infections Prescribed 29 University of Ghana http://ugspace.ug.edu.gh 3.5 Study population Records of all outpatient who attended the Princess Marie Louise Children’s hospital from the 1st of January 2013 to the 31st of December 2015 were qualified for the study. These outpatients were between the ages of day 1 to 12 years and had been given at least one antibiotic during their visit to the hospital. Prescribers were given the questionnaires. 3.5.1 Inclusion criteria Data from out-patients who attended PML from 1st of January to the 31st December 2015 who were between day 1 and 12 years of either sex and prescribed at least one antibiotic during their visit were extracted and used for the study. 3.5.2 Exclusion criteria Records from inpatients who were admitted from the 1st of January 2013 to the 31st December 2015 as well as patients who are currently clients in the hospital were excluded from the study. Outpatients above the age of twelve were also excluded. Folders with incomplete information about prescription were also excluded. 3.6 Sampling Sample size determination was done using the Cochran’s formula : Where:  d is the desired level of precision (i.e. the margin of error),  p is the (estimated) proportion of the population which has the attribute in question, p was assumed to be 50%  q is 1 – p. 30 University of Ghana http://ugspace.ug.edu.gh . ∗ .. ∗^ . ∗ .Sample size = = 384 Adding 10% for incomplete data gives 422 patient folders. The prescribers in the consulting rooms attending to outpatients were those interviewed there were 5 consulting rooms with 2 doctors each. 3.7 Data Collection Techniques A total of 422 out-patient folders of children aged day 1to 12 years who attended Princess Marie Louise Children’s Hospital from 1st January 2013 to 31st December 2015 who were prescribed an antibiotic, were selected for this study. Microsoft Excel was used to generate 422 folder numbers. Pretested questionnaires were administered to the doctors. 3.7.1 Research assistants Training Two research assistants including a records officer from the Princess Marie Children’s Hospital were trained. They were trained on ethical considerations and extraction of information on demographic data, diagnosis, prescriber’s information and treatment from patients’ medical records or folders and administration of questionnaires to doctors. 3.7.2 Data Collection The list of folder numbers was used to select the folders for data extraction. The principal investigator together with the trained research assistants extracted the data with the prescribing Indicator Forms. Data extracted were entered into an excel template. Patient’s demographic characteristics such as age and sex, diagnosis, antibiotics used, dosages, frequency, duration of treatment and WHO core drug indicators were extracted from the folders of the study population. Data on the from the administered questionnaires were also extracted. 31 University of Ghana http://ugspace.ug.edu.gh 3.8 Quality control The research assistants were selected based on their knowledge on the names of medicines, medical abbreviations and medical diagnosis. They were trained on the use of the data collecting tools, what information to look for and how to handle ethical considerations and security of data. Data were entered twice per patient and doctor both written and electronically. 3.9 Data processing and Analysis All statistical analysis were performed using Microsoft Excel 2013 and STATA Version 14.1 (College Station Texas, USA). The overall core indicators were computed then compared against the standard given values. The WHO drug core indicators were calculated as follows and compared to the standard to check for appropriateness: 1. Average number of drugs per encounter = total number of drugs prescribed / total number of encounters surveyed 2. Percentage of drugs prescribed by generic name = (number of drugs prescribed by generic name / total number of drugs prescribed) X 100 3. Percentage of encounters with an antibiotic prescribed = (number of patient encounters during which an antibiotic was prescribed / total number of encounters surveyed) X 100 4. Percentage of encounters with an injection prescribed = (number of patient encounters during which an injection was prescribed / total number of encounters surveyed) X 100 5. Percentage of drugs prescribed from essential drugs list = (number of drugs prescribed from essential drugs list / total number of prescribed drugs) X 100. Descriptive analysis was done to obtain frequencies and percentages. 32 University of Ghana http://ugspace.ug.edu.gh Means were computed for continuous variables like age and weight. The measures of association between antibiotic prescription and patient’s age, sex, and diagnosis were done using the Pearson’s Chi squared test. 3.10 Ethical Consideration Ethical clearance from the Ethics and Review Committee of the Ghana Health Service was obtained (61/12/2016) and permission was sought from the Princess Marie Louise children's hospital. To maintain confidentiality, names were not extracted. Folders were coded. Patients’ information was kept confidential and identity of patients was not disclosed. Data collected was password protected and kept on the computer of the Principal Investigator. 33 University of Ghana http://ugspace.ug.edu.gh CHAPTER FOUR 4.0 RESULTS The minimum age was two months and the maximum was 12 years with a mean age of 34.39 and a standard deviation of 33.20 months. Majority of the study population (76.1 %) (321/422) were children below 5 years. Table 3 Age categories of participants Age (years) Male* Female* Total* n(n/t) n(n/t) n(n/t) <5 167 (52.0) 154 (48.0) 321 (76.1) 5-10 40 (50.6) 39 (49.4) 79 (18.7) 10-12 11 (50) 11 (50) 22 (5.2) Total 218 (51.7) 204 (48.3) 422 (100) * Figures in brackets are in percentages Table 4 Type of antibiotic prescribed Antibiotic prescribed Male* Female* Total* Amosiklav 73 (50.4) 72 (49.6) 145 (34.7) Cefuroxime 55 (56.1) 43 (43.9) 98 (23.2) Augmentin 49 (51.6) 46 (48.4) 95 (22.5) Epicrom 6 (50.0) 6 (50.0) 12 (2.8) Ciprofloxacin 2 (50.0) 2 (50.0) 4 (0.9) Metronidazole 4 (100.0) 0 (0.0) 4 (0.9) Gentamicin 0 (0.0) 1 (100.0) 1 (0.2) Others 29 (46.0) 34 (54.0) 63 (15.0) Total 218 (51.7) 204 (48.3) 422 (100.0) * Figures in brackets are in percentages 34 University of Ghana http://ugspace.ug.edu.gh Out of the total of 422 patients, 34.7% (145/422) of them were prescribed Amoksiklav, penicillin class (72 females 73 males), making it the highest prescribed antibiotic. Cefuroxime a cephalosporin class of antibiotic was the next frequently prescribed antibiotic with 23.2% (98/422). Augmentin the third highest prescribed antibiotic was prescribed to 95(22.5%) patients (46 females and 49 males). Gentamicin was the least prescribed antibiotic. There were no sex variation in prescribing antibiotics, except for Cefuroxime where males were slightly prescribed compared females (56.1%) (55/98) versus 43.9% (43/98). Table 5 Types and classes of Antibiotics prescribed Antibiotic prescribed Type Class Number of Prescriptions Amoksiklav Broad spectrum Penicillin 145 Cefuroxime Broad spectrum Cephalosporin 98 Augmentin Broad spectrum penicillin 95 Epicrom Broad spectrum Mast cell stabilizer 12 Ciprofloxacin Broad spectrum Quinolone 4 Metronidazole Broad spectrum Antiprotozoal 4 Gentamicin Broad spectrum Aminoglycoside 1 Upper Respiratory Tract Infection was the highest diagnosed with 34.60%, followed by Fevers 24.17% then Wax 10.43% and Gastroenteritis 7.3%. Viral Conjunctiva was the least diagnosed among the 422 reviewed folders. 35 University of Ghana http://ugspace.ug.edu.gh Table 6 Diagnosis made by prescribers for which antibiotic was prescribed over three- year period Disease condition Number diagnosed Percent Upper Respiratory Tract Infection 146 34.60 Fevers 102 24.17 Wax 44 10.43 Sepsis 35 8.29 Gastroenteritis 31 7.35 Bronchopneumonia 28 6.64 Veneral Conjunctiva 12 2.84 Malaria & Gastroenteritis 5 1.18 Bacterial Conjunctiva 4 0.94 Parotitis 4 0.95 Tonsillitis 4 0.95 Otitis Media 2 0.47 Unconjugated Malaria 2 0.47 Severe Anaemia 1 0.24 Viral Conjunctiva 1 0.24 Anaemia 1 0.24 Total 422 100.00 There was a significant measure of association between age and antibiotic use and diagnosis and antibiotic used. Between sex of study population and antibiotic, a P value of 0.365 was obtained. These measures of association were generated using the Pearson Chi Squared test. 36 University of Ghana http://ugspace.ug.edu.gh Table 7 Association between age and antibiotics prescribed Vari Antibiotics prescribed able Age Amoks Augm Cefuro Ciprofl Epic Genta Metroni Oth X² P yrs iklav entin xime oxacin rom micin dazole ers val n=146 n=95 n=98 n=4 n=11 n=1 n=4 n=6 ue 3 >5 118 74 67 3 9 1 1 42 5-9 22 13 24 0 1 0 3 19 10- 6 8 7 1 1 0 0 2 181.1 0.0 12 799 11 Table 8 Association between sex and antibiotics prescribed Vari Antibiotics prescribed able Sex Amoks Augm Cefuro Ciproflo Epicr Genta Metroni Oth X P iklav entin xime xacin om micin dazole ers ² val n=146 n=95 n=98 n=4 n=11 n=1 n=4 n=6 ue 3 F 73 47 42 2 6 1 0 35 M 73 48 56 2 5 0 4 28 7. 0.3 6 7 37 University of Ghana http://ugspace.ug.edu.gh Table 9 Association between diagnosis and antibiotics prescribed Vari Antibiotics prescribed able Diag Amoks Augm Cefuro Ciprofl Epic Genta Metroni Oth X² P nosis iklav entin xime oxacin rom micin dazole ers val n=146 n=95 n=98 n=4 n=1 n=1 n=4 n=6 ue 1 3 Anae 1 0 1 0 0 0 0 0 mia Bac. 0 0 0 4 0 0 0 0 Con Bron 6 12 9 0 0 0 0 1 co Gas 6 10 14 0 0 0 0 2 Mal 19 15 15 0 0 0 0 0 1 0 1 0 0 0 0 0 Mal/ Gas Otitis 2 0 0 0 0 0 0 2 Parot 0 1 1 0 0 0 0 0 itis 12 12 10 0 0 0 0 0 Sepsi s Tons 0 0 0 0 0 0 4 1 Un. 0 0 1 0 0 0 0 0 Mal Urti 68 34 45 0 0 0 0 0 Ve 0 0 0 0 11 0 0 0 Viral 0 0 0 0 0 1 0 0 1.90 0.0 Con E+03 01 Wax 32 11 1 0 0 0 0 0 Collected data established that, all the medicines prescribed were taken orally in an average duration of 6.3 days. An average of 3.1 drugs was prescribed per patient among the 422 outpatient (Table 10). 38 University of Ghana http://ugspace.ug.edu.gh Table 10 WHO Core Drug indicators obtained values WHO Indicator Value obtained Optimal value Total number of prescriptions 422 ≥100 Average number of drug per encounter 3.18 ≤2 Percentage of medicines prescribed by their generic 28.57 100 Percentage of encounters with an injection prescribed 0 ≤20 Percentage of medicines prescribed from Essential 71.4 100 Medicine List 4.7 Standard Treatment Guideline All prescribers prescribed antibiotic based on the severity of ailment. Eighty percent of prescribers actually had their personal Standard Treatment Guideline. 80% use the standard treatment guideline occasionally. 39 University of Ghana http://ugspace.ug.edu.gh Table 11 Availability and use of Standard Treatment Guideline Indicator Results (%) Availability of STG (Either hard or soft copy) n=10 Yes 80 No 20 Use of STG in practice Regularly 40 Occasionally 40 Do not use 20 What prompts antibiotic prescription n=10 Age 0 Sex 0 Severity of presenting ailment 100 Are patients asked to do investigation prescription n= 10 Yes 100 No 0 Before prescription 30 After prescription 70 Is prescription based on availability of the drug in the hospital n=10 Yes 20 No 80 40 University of Ghana http://ugspace.ug.edu.gh CHAPTER FIVE 5.0 DISCUSSION In this study, children under 5 was 76.1% of the study population and males were 51.7%. This can be compared to a study by Sharma, 2016 where 56.7% of the study population were male children. In the study, majority of the prescription were made to children aged 1month and up to 5 years. This could be due to high vulnerability and morbidity of children in this age group than older children (Sharma, 2016).In this study, the average number of drugs prescribed per encounter was 3.1. This finding is significantly lower than 3.7 reported in similar studies conducted in the Ghana Police Hospital (Afriyie, 2014). The difference could be attributed to the difference in the study population. Also studies conducted in Saudi Arabia, Sudan, Nigeria, Yemen and Nepal reported their average number of drugs per encounter to be ranging from 1.3 to 3.8 (Hogerzeil et al., 1993). Increase in the number of drugs could possibly lead to drug interactions and reduce patient compliance. Comparatively drugs prescribed per patient encounter was the only higher indicator of prescription obtained from the study. This indicates poly-pharmacy. This could lead to non-compliance since there are too many medicines to take. Lack of adequate knowledge differences in the health care delivery system, empirical prescribing and symptomatic treatment approaches, differences in socioeconomic status as well as morbidity and mortality characteristics of the population and training of health professionals were known to be the likely cause of poly-pharmacy in a study conducted in Ethiopia (Desalegn, 2013). Prescribers attributed the cause of poly-pharmacy to the management of multiple diseases in a systematic analysis study conducted in Africa (Ofori-Asenso & Brhlikova, 2016). 41 University of Ghana http://ugspace.ug.edu.gh The other four prescribing indicators were low as compared to the standard. There were no injectable and this is very commendable. This seems to be the trend as a study conducted on drug use indicators at primary healthcare centres in Alexandria, Egypt also recorded a low percentage of injectables that is 9.9 (Ola Akl et al., 2014). An even lower percentage (2%) was recorded in a study conducted in Saudi Arabia (El. Mahalli, 2012). An overuse of injectables when oral therapy is appropriate is deemed an irrational use of drug. It is always cost effective and safer to give oral medications than injectable. Blood borne disease can spread when unsterile injections are used. Percentage of drug prescribed by their generic names was 28.57 (Table 10). This a clear indication of high brand prescribing. Drugs were prescribed based on their brand names or prescription was based on the availability of the drug. The World Health Organization highly recommends that drugs are prescribed using their generic names as it serves as safety precaution for patients. This helps to ensure easy identification and flow of communication among health care workers (WHO, 2012). Prescribing drugs by generic name in a lot of developing country is low. An example is a study conducted in India which recorded a very low percentage of drug prescribed using the generic name (25%) as compared to this study (Singh & Dadhich, 2003). Drugs prescribed from the essential drug formulary was 71.4%. Which is lower than the expected 100% from the WHO prescribing indicator. A similar study conducted in Nigeria had a higher Essential Drug List percentage(83.3%) (Odusanya, 2004) as compared to the 71.4% obtained in this study. The low patronage of the use of Essential Medicines List can be linked with reasons such as; no or inadequate Essential Medicine List among prescribers, inadequate sensitization and enforcement techniques on the use of EML (Ofori-Asenso & Brhlikova, 2016). 42 University of Ghana http://ugspace.ug.edu.gh About 37% of diagnosis made was Upper Respiratory Tract Infection followed by Fevers with 24% then Wax with 10%. Upper Respiratory Tract Infection also known as common cold in previous studies is known to be concurrent in infants of preschool going age with an occurrence of from 3 to 8 times in a year (Woods, 2006). The World Health Organization records pneumonia and diarrhoea as leading causes of deaths in children under 5 years of age. Another study also stated diarrhoea and respiratory illness as the major causes of morbidity and mortality in developing countries (Hoan le, Chuc & Ottosson, 2009). This coincides with what was obtained in this study, about 76% of the 422 folders reviewed were from infants below 5. Common diagnosis from a study conducted in the eastern region of Ghana were malaria and respiratory tract infections similar to what was obtained in this study (Ahiabu et al., 2015). From this study, diagnosis of Fevers totalled 25.35% and antibiotics were co-prescribed. This is appreciably lower than a 30.15% of co-prescribed antibiotics in treating uncomplicated Malaria with Fevers in a study conducted in the Greater Accra region of Ghana (Dodoo et al., 2009). Amoksiklav was the highest prescribed antibiotic with 145 prescriptions. Amoksiklav is the combination of amoxicillin and clavulanic acid making the drug more effective in the fighting of broad-spectrum bacteria. From the study, it was used in the management of URTI (67 patients), Wax (32 patients), sepsis (13 patients) and others. From previous studies (STG, 2010), amoxicillin was used in the management of Upper Respiratory Tract Infection and is the first line treatment for URTI treatment. Amoxicillin/clavulanic was noted to be the highest prescribed broad-spectrum antibiotic in the treatment of URTI by emergency paediatrics for out-patient children in a study conducted in Queen Rania Al Abdullah II Children's Hospital, Jordan (Alumran & Hurst, 2011). Cefuroxime was the next highest prescribed antibiotic mostly for the management of URTI with 45 prescriptions. It is also a broad-spectrum antibiotic. This shows that paediatrics are prescribing more broad-spectrum antibiotics for diseases of viral 43 University of Ghana http://ugspace.ug.edu.gh aetiology. Upper Respiratory Tract Infection is a viral infection so more therapeutic information is needed to use this empirical treatment for it. The fact that Amoxicillin was not even prescribed raises a concern whether prescribers no longer see it’s effectiveness and its efficacy as a first line medication. In a global antibiotic consumption study (Klein et al., 2018), broad spectrum penicillin was the highest consumed antibiotic followed by cephalosporin of which 56% of the increase in consumption were from LMICs. This can be likened to this study with Amoksiklav (broad spectrum penicillin) being the most prescribed antibiotic followed by cefuroxime a cephalosporin. The measure of association between the antibiotic prescribed and the sex of the patient gave a result of a p value of 0.365. This indicated that antibiotic prescription is not influenced by the sex of the patient. This could be likened to a systematic review and meta-analysis study published in 2016 (Schröder et al,2016) . The summary estimates of incidence and prevalence suggested that the amount of antibiotics prescribed to girls is about 25% higher than that for men and that women are about 27% more likely than men to receive antibiotic prescriptions (Schröder et al.,2016) . Antibiotic prescription is influenced by age. Studies by Sundvall & Stuart (2015) have shown that antibiotic prescription increases with age. This can easily be explained by the manner in which the body responds to treatment, and higher use of antibiotics in the elderly population has already been established (Sundvall & Stuart , 2015). There was a significant association between diagnosis and prescription of antibiotic. 44 University of Ghana http://ugspace.ug.edu.gh Most antibiotic use that occur in the community are intended to treat respiratory tract infections. Several studies have reported that about 40 to 60 percent of these prescriptions made for outpatients with suspected respiratory tract infections are inappropriate (Barlam & Morgan, 2015). This finding can be linked to this study. Respiratory tract infections topped the diagnosis made by the prescribers and the patients were given antibiotic in this study. The Standard Treatment Guidelines (STG) serve as a guide to assist health personnel in the administration of treatment for specific clinical conditions. The consistent publishing of EML by The Ministry of Health, Ghana with treatment guideline is to aid in the appropriate use of drugs in the country (Ahiabu et al., 2015). In this study, 80% prescribers possessed the Standard Treatment Guideline. This finding can be compared to what was found in another primary health facility in Ghana (Afriyie, 2014), that found that about 77.8 % of prescribers had access to the guidelines. The findings of this study could be a reflection of the general practice of prescribers in the country even though the guidelines are free and available both online and in print. All prescribers gave prescription based on the severity of the ailment. High empirical use of antibiotics was found in this study as 70% of prescribers administered antibiotics before further investigations were done. This could be related to lack of effective, fast and reliable diagnostic mechanisms. Generally there was low adherence to Standard Treatment Guideline. In assessing the policy factor of availability, 20 % of prescribers prescribed based on what was in stock at the health care facility. A study conducted in Nigeria reported that although treatment guidelines are followed the availability and accessibility of WHO recommended antibiotics for children is challenging (Rodrigues, 2017). Majority of prescribers prescribed without checking availability. 45 University of Ghana http://ugspace.ug.edu.gh Per this study, the practices and pattern of antibiotic utilisation in the Princess Marie Louise Children’s Hospital needs to be reviewed. Prescription should be based on final diagnosis to prevent children from being exposed to antibiotics and ultimately prevent antibiotic resistance. If possible the number of drugs given the children should be minimized to promote compliance. There was low adherence to Standard Treatment Guideline due to inadequate therapeutic infrastructure. 46 University of Ghana http://ugspace.ug.edu.gh CHAPTER SIX 6.0 CONCLUSION AND RECOMMENDATIONS 6.1 Conclusion According to the approved standards obtained from WHO, only one obtained value was higher than the standard and that indicated poly-pharmacy. The remaining standards had an appreciably low values as compared to the standards with no injectable. Brand prescribing was high. Most of the drugs were prescribed from the Essential Drug Formulary. Indications such as age, sex and diagnosis affected the prescription of mainly broad spectrum antibiotics. Generally, the dosage was correctly done based on the weight of the child. 6.2 Limitation This study aimed at comparing the drug indicators to the approved WHO drug prescribing indicators, to identify indications of prescription and adherence to Standard Treatment Guidelines in the Princess Marie Louise Children’s Hospital. The study however does not establish the reason why the problems at hand exist and if the indications for prescribing the antibiotics was right or wrong. Also whether the appropriated medication was given to the right diagnosis. The number of antibiotic prescriptions given to both patients who had an antibiotic and non-antibiotic responsive diagnosis could not be stated because of the retrospective nature of this study. 6.3 Recommendation Clinical practice  Appropriate diagnosis and further therapeutic assessment should be done before the prescription of antibiotic.  Prescribers should be educated against poly-pharmacy to help increase patient compliance. 47 University of Ghana http://ugspace.ug.edu.gh Policy  The recommended antibiotics should be readily available for use in the health facility.  Standard Treatment Guideline should be made available and accessible to prescribers. Adherence to the Standard Treatment Guideline should be encouraged. Public health  To prevent resistance first line or first generation antibiotics should be used with a regular assessment to determine their efficacy against infections. 48 University of Ghana http://ugspace.ug.edu.gh 7.0 REFERENCES Abula Teferra, Desta Zeruesenay, Y. A. G. (2002). Prescribing Pattern of Drugs in Medical Wards of Three Hospitals in North-West Ethiopia. J Ethiopia Med Pract, 4(1), 8–13. Afriyie D, T. R. (2014). A description of the pattern of rational drug use in Ghana Police Hospital. Int J Pharm Pharmacol, 3, 143–148. Ahiabu, M., Tersbøl, B. P., Biritwum, R., Bygbjerg, I. C., & Magnussen, P. (2015). A retrospective audit of antibiotic prescriptions in primary health-care facilities in Eastern, 1–9. https://doi.org/10.1093/heapol/czv048 Ahmad A, Parimalakrishnan S, Patel I, Praveen Kumar NV, Balkrishnan R, M. G. (2012). Evaluation of self-medication antibiotics use pattern among patients attending community pharmacies in rural India. J Pharm Res, 5, 765–8. 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The Lancet Infectious Diseases, 14(8), 742–750. https://doi.org/10.1016/S1473-3099(14)70780-7 Wachter, D., Joshi, M., & Rimal, B. (1999). Antibiotic dispensing drug retailers in Kathumandu, Nepal. Trop Med Int Health, 782–8. Wang, E. E., Einarson, T. R., Kellner, J. D. et al. (1999). Antibiotic prescribing for Canadian preschool children: evidence of overprescribing for viral respiratory infections. Clinical Infectious Diseases, 29, 155–60. Woldu B, B. G. (2016). Rheumatic heart disease in the twenty-first century. Curr Cardiol Rep, 18(10), 96. https://doi.org/10.1007/s11886-016-0773-2.) Woods, D. (2006). Rational Use of Antibiotics in Respiratory Tract Infections. Retrieved from http://www.bpac.org.nz/resources/campaign/respiratory/bpac_respiratory_infections_po em_wv.pdf Word Health Organization. (2014). Antimicrobial Resistance Global Report on Surveillance. Geneva. World Health Organisation. (2014). Revised WHO classification and treatment of childhood pneumonia at health facilities. Geneva, Switzerland. 59 University of Ghana http://ugspace.ug.edu.gh 8.0 APPENDICES 8.1 QUESTIONNAIRE FOR INVESTIGATOR PRESCRIBING INDICATOR FORM LOCATION………………………………………………………DATE………………... INVESTIGATOR ……………………………………………….SIGNATURE Objective 1. To assess prescription pattern using WHO core drug use indicators SECTION A Sequence No of No of no of No of no medicines generics EML antoibiotics 1 2 3 4 5 6 7 8 9 10 60 University of Ghana http://ugspace.ug.edu.gh SECTION B Objective 2 To assess the factors that influence the use of antibiotics. NUMBER ANTIBIOTIC AGE SEX DIAGNOSIS DURATION ROUTE 1 2 3 4 5 6 7 8 9 61 University of Ghana http://ugspace.ug.edu.gh SECTION C Objective 3 To assess the types and classes of antibiotics used for the various diagnosed diseases. Antibiotic prescribed Type Class Number of Prescriptions SECTION D To assess adherence of prescribers to Standard treatment Guidelines. 62 University of Ghana http://ugspace.ug.edu.gh Questionaire for Prescriber Prescriber ID………………………. Indicator Response Ownership of STG (Either hard or soft copy) Yes No Use of STG in practice Regularly Occasionally Do not use What prompts antibiotic prescription Age Sex Severity of presenting ailment Are patients asked to do investigation before or after prescription before after other Yes No Is prescription based on availability of the drug in the hospital YES No 63 University of Ghana http://ugspace.ug.edu.gh 8.2.1 A TEMPLATE FOR DATA ENTRY Sequen 1 2 3 4 5 6 7 8 9 10 ce Sex DOB Weight No of med No of anti No of EML No of inject Durati on Dose Frequency Prescriber’s qualification 64 University of Ghana http://ugspace.ug.edu.gh 8.2.1 TEMPLATE FOR DATA ENTRY FOR STANDARD TREATMENT GUIDELINES Indicator Response % Availability of STG (Either hard or soft copy) Yes No Use of STG in practice Regularly Occasionally Do not use What prompts antibiotic prescription Age Sex Severity of presenting ailment Are patients asked to do investigation before or after prescription before after other Yes No Is prescription based on availability of the drug in the hospital YES No 65 University of Ghana http://ugspace.ug.edu.gh 8.3 Informed Consent Purpose My name is Nyarko Agyemang Duah a graduate student from the School of Public Health, University of Ghana, Legon. I would be conducting a study on Prescription pattern of antibiotics in children attending the Princess Marie Children’s Hospital which is located in the Greater Accra region. The purpose of the study is to find out the prescription pattern of antibiotics in children from day 1 to 12 years of age and the factors influencing the prescription and utilization of antibiotics. Patient cards/ folders of children a day old to 12 years of age would be reviewed. The information obtained would help improve the prescription of antibiotic in this vulnerable population. Procedure I would taking data from cards/folders of children from day 1 to 12 years who have been managed by your institution. I would be reviewing the demographic data, prescriptions, prescriber’s qualification and the types infections for which prescriptions were made. Allowing your institution to be used for this study is solely voluntary. During the period of study you can decide to withdraw your consent if for any reason you do not want the study to be continued in your institution. Risks and Discomforts The risks involved in this study being carried out in your institution are minimal. These include the inconvenience that the search for folders will cause your staff and space. The study would be undertaken at times, patient folders would not be in use and the staff involved will not be engaged. 66 University of Ghana http://ugspace.ug.edu.gh Benefits There are no direct benefits to the institution in the study. However, the information that would be obtained from this study would be made available to the hospital which would help you improve health care delivery in the hospital and the nation as a whole. Confidentiality Patient’s record would be treated strictly confidential and no personal identifying information concerning any person or patient will be presented in the analysis or publications of this study. The information would not be shared with anyone except your institution and authorities from the University of Ghana. Right to refuse or withdraw The decision to allow the study to be carried out in your hospital is voluntary. You will also not lose any benefits if you refuse grant of permission or decide to withdraw the permission. 67 University of Ghana http://ugspace.ug.edu.gh 8.4 FIGURES AND TABLES Table 12 Recommended dosing of fluoroquinolone in children Agent Indication(s) Dosing Common Adverse Events Ciprofloxacin Inhalation 18-40mg/kg/day Dizziness, insomnia, anthrax, cystic divided q8- abdominal pain, diarrhoea, fibrosis, 12h;specific dysepsia, nausea, complicated UTI dosing varies by vomiting, elevated route, indication LFTlevles,fever,headache, restlessness(IV only) Levofloxacin Inhalational (IV/oral) infants Dizziness, insomnia, anthrax(in ≥6 mths and less abdominal pain, diarrhoea, than 5yrs: the absence of dysepsia, nausea, 10mg/kg/dose Ciprofloxacin) vomiting, elevated LFT q12h; children levels, fever, headache, ≥5yrs: restlessness (IV only) 10mg/kg/dose q24h (Taketomo CK, Hodding JH, 2011). 68 University of Ghana http://ugspace.ug.edu.gh Table 13 Antibiotic resistance range Range (%) Antibiotic Organism 0–87 third-generation in E. coli – cephalosporins and0 98 fluoroquinolones 8–77 third-generation K. pneumonia 0– cephalosporins and4 carbapenems 0–100 methicillin S. aureus 1–100 penicillin S. pneumonia 0–35 fluoroquinolones non-typhoidal Salmonella 0–9 fluoroquinolones Shigella spp 0–12 third-generation N. gonorrhoea cephalosporins (Word Health Organization, 2014). 69 University of Ghana http://ugspace.ug.edu.gh Figure 6 Pharmacokinetic changes of drug in neonates and young children (Centers for Disease Control and Prevention, 2013) 70 University of Ghana http://ugspace.ug.edu.gh Figure 7 Key events in antibiotic resistance 71