University of Ghana http://ugspace.ug.edu.gh SCHOOL OF PUBLIC HEALTH, COLLEGE OF HEALTH SCIENCES UNIVERSITY OF GHANA, LEGON ANTIMICROBIAL RESISTANCE PATTERNS AND ASSOCIATED FACTORS AMONG PATIENTS DIAGNOSED WITH URINARY TRACT INFECTION AT THE EASTERN REGIONAL HOSPITAL IN KOFORIDUA: A FIVE-YEAR RETROSPECTIVE STUDY BY FRED GBADAGO (10701899) THIS DISSERTATION IS SUBMITTED TO THE UNIVERSITY OF GHANA, LEGON IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF MASTER OF PUBLIC HEALTH DEGREE JULY, 2019 University of Ghana http://ugspace.ug.edu.gh DECLARATION I, Fred Gbadago, hereby declare that except for references to work by other persons that have been duly cited, this dissertation is the product of my own research. Signed: …………………………… Date………………………………………… MR FRED GBADAGO (Student) Signed…………………………….... Date……………………………………….. DR PRISCILLIA AWO NORTEY (Supervisor) i University of Ghana http://ugspace.ug.edu.gh DEDICATION This work is dedicated to my parents Mr & Mrs Gbadago and siblings for their immense support and motivation towards this academic achievement. ii University of Ghana http://ugspace.ug.edu.gh ACKNOWLEDGEMENT I am grateful to the God Almighty for His continuous protection and guidance in my life and towards the completion of yet another academic programme. My deepest appreciation also goes to Dr Priscillia Awo Nortey, my project supervisor, for her guidance and immense inputs towards the success of my dissertation. God Almighty bless her and her family to continue doing the good work. My appreciations also go the Head of Laboratory Department, Eastern Regional hospital, Mr Morton and Head of Bacteriology Unit, Mr Stephen Ofori for their assistance towards this project. To all the Medical Laboratory Scientists, Mr Roland Zuta, Mr Gideon Addae, Dr (Mrs) Yaa Addae, Mr. Rufai Tanko and Mr James Allotey who in many ways supported me throughout this research, debts of gratitude I owe. I am very much thankful to Mr Erasmus Tayviah, Miss Vida Ampiah, Miss Cynthia Dashie, Mr Prince Atsu-Lawluvi, Mr Dennis Bansah and Edmond. Finally, I am very much grateful to my family and friends for their support throughout the programme. iii University of Ghana http://ugspace.ug.edu.gh ABSTRACT Background: Urinary tract infections (UTI) are among the most common bacterial infections affecting people worldwide. The misuse of antibiotics used to treat UTIs has led to the development of resistance among the major uropathogens in Ghana. The local antimicrobial resistance pattern among uropathogens to help empirical decision making is not known at the Eastern Regional Hospital, Koforidua. Objective: This study examined the resistance pattern of uropathogenic bacteria over a five year period and associated factors among patients diagnosed with UTI at the Eastern Regional Hospital, Koforidua. Methods: A retrospective cross-sectional study design was used to review records of urine culture and sensitivity data to determine resistance patterns and associated factors among patients diagnosed with UTI at the Regional Hospital in Koforidua from 2014 to 2018. Results: The prevalence of UTI was 20.3% among study subjects. Out of fourteen isolates assessed, Escherichia coli (42.98%), Klebsiella spp (29.97%) and Citrobacter spp (12.51%) were the most dominant uropathogens accounting for UTI. Resistance to antibiotics was very high among uropathogens isolated with Ampicillin (90.8%), Co-trimoxazole (89.7%) and Tetracycline (88.6%) being the most resistant antibiotics and Amikacin (8.7%), Nitrofurantoin (35.9%) and Ciprofloxacin (37.5%) being the least resistant. Increasing age (AOR=2.53 CI=1.83, 3.47) and In-patient (AOR=1.26, CI=1.05, 1.53) are associated with ciprofloxacin resistance. Conclusion: This study showed that uropathogens responsible for UTI showed generally high resistance to the commonly prescribed antibiotics with few exceptions. These results could help inform empirical treatment decisions for Urinary Tract Infections locally and also contribute to AMR surveillance in general. iv University of Ghana http://ugspace.ug.edu.gh TABLE OF CONTENT DECLARATION....................................................................................................................... i DEDICATION.......................................................................................................................... ii ACKNOWLEDGEMENT ...................................................................................................... iii ABSTRACT ............................................................................................................................. iv LIST OF FIGURES ................................................................................................................ ix DEFINITION OF KEY TERMS ............................................................................................ 2 CHAPTER ONE ...................................................................................................................... 3 1.0 INTRODUCTION.............................................................................................................. 3 1.1 Background ...................................................................................................................... 3 1.2 Problem Statement ........................................................................................................... 5 1.3 Justification ...................................................................................................................... 6 1.4 Conceptual framework ..................................................................................................... 7 1.5 Research Questions .......................................................................................................... 8 1.6 General objective .............................................................................................................. 9 1.6.1 Specific objectives ......................................................................................................... 9 CHAPTER TWO ................................................................................................................... 10 2.0 LITERATURE REVIEW ............................................................................................... 10 2.1 Concept of Antimicrobial Resistance ............................................................................. 10 2.2 Global Prevalence of Antimicrobial Resistance ............................................................. 12 2.3 Prevalence of Antimicrobial Resistance in Africa ......................................................... 13 2.4 Urinary Tract Infections ................................................................................................. 14 2.4.1 Pathogenesis of UTI .................................................................................................... 15 2.4.2 Categories of urinary tract infection ............................................................................ 15 2.4.2 Epidemiology of UTI ............................................................................................... 16 2.4.3 Causative organisms of UTIs ...................................................................................... 17 2.4.4 Treatment of Urinary Tract Infections ........................................................................ 18 2.5 Prevalence of Antimicrobial Resistance among Uropathogens ..................................... 18 2.6 Factors influencing the antimicrobial resistance among patients diagnosed with UTI..21 2.6.1 Age, Sex and Residence .......................................................................................... 21 2.6.2 Hospitalization status ............................................................................................... 22 CHAPTER THREE ............................................................................................................... 24 3.0 METHODS ....................................................................................................................... 24 3.1 Research Design ............................................................................................................. 24 v University of Ghana http://ugspace.ug.edu.gh 3.2 Study Area ...................................................................................................................... 24 3.3 Study Population ............................................................................................................ 26 3.4 Study Variables .............................................................................................................. 26 3.5 Sampling Method ........................................................................................................... 27 3.6 Inclusion and Exclusion Criteria .................................................................................... 27 3.6.1 Inclusion Criteria ..................................................................................................... 27 3.6.2 Exclusion Criteria .................................................................................................... 27 3.7 Source of Data and Data Collection ............................................................................... 27 3.8 Quality Control ............................................................................................................... 28 3.8.1 Pre- Data collection ..................................................................................................... 28 3.9.2 Post- Data collection ................................................................................................ 28 3.10 Data processing and Analysis ...................................................................................... 28 3.11 Ethical Consideration ................................................................................................... 29 CHAPTER FOUR .................................................................................................................. 30 4.0 RESULTS ......................................................................................................................... 30 4.1 Distribution of variables at study site ............................................................................. 30 4.2 Distribution of reported cases of UTI ............................................................................ 32 4.2.1 Overall reported cases of UTI from 2014 to 2018 ...................................................... 32 4.2.2 Distribution of UTI by sex .......................................................................................... 32 4.2.3 Distribution of UTI by age categories. ........................................................................ 33 4.2.4 Distribution of UTI by hospitalization status and hospital units ................................. 33 4.3 Distribution of Uropathogens ......................................................................................... 34 4.4 Antimicrobial Resistance Pattern ................................................................................... 39 4.5.1 Association between the three most resistant antibiotics and study characteristics .... 42 4.5.2 Association between the three least resistant antibiotics and study characteristics .... 44 CHAPTER FIVE ................................................................................................................... 46 5.0 DISCUSSION ................................................................................................................... 46 5.1 Prevalence of Urinary Tract Infections .......................................................................... 46 5.2 Distribution of Uropathogens ......................................................................................... 47 5.3 Antimicrobial Resistance Pattern and associated factors ............................................... 48 5.5 Limitations ..................................................................................................................... 50 CHAPTER SIX ...................................................................................................................... 51 6.0 CONCLUSION AND RECOMMENDATION ............................................................. 51 6.1 CONCLUSION .............................................................................................................. 51 6.2 RECOMMENDATIONS ............................................................................................... 52 vi University of Ghana http://ugspace.ug.edu.gh REFERENCES ....................................................................................................................... 53 APPENDICES ........................................................................................................................ 58 APPENDIX I: SAMPLE OF DATA EXTRACTION FORM ............................................. 58 APPENDIX II: ETHICAL CLEARANCE .......................................................................... 59 vii University of Ghana http://ugspace.ug.edu.gh LIST OF TABLES Table 3.1: Summary of Variables used in the Study................................................................ 26 Table 4.1: Distribution of study characteristics ....................................................................... 31 Table 4.2 Distribution of UTI cases by study characteristics .................................................. 34 Table 4.3.1 Distribution of uropathogens by sex ..................................................................... 37 Table 4.3.2 Distribution of uropathogens by age categories .................................................... 38 Table 4.3.3 Distribution of uropathogens by hospitalization status ......................................... 39 Table 4.4.1 Frequency and percentage distribution of antimicrobial resistance of uropathogens among antibiotics used in the study .................................................................. 40 Table 4.5.1 Association between the three most resistant antibiotics with study variables ..... 43 Table 4.5.2 Association between the three least resistant antibiotics and study variables ...... 45 viii University of Ghana http://ugspace.ug.edu.gh LIST OF FIGURES Figure 1.4: Conceptual framework of risk factors and uropathogens causing UTI and their inter-relationship with antibiotic resistance ............................................................................... 7 Figure 3.2 Map of Ghana, Eastern Region and the New Juabeng Municipality showing the location of the Eastern Regional Hospital................................................................................ 25 Figure 4.3a Percentage distribution of Uropathogens .............................................................. 35 Figure 4.3bTrendline of three main uropathogens from 2014 to 2018 .................................... 36 Figure 4.4.1 Cumulative resistance pattern of antibiotics used in the study ............................ 41 ix University of Ghana http://ugspace.ug.edu.gh LIST OF ABBREVIATIONS AMR - Antimicrobial Resistance AOR - Adjusted Odds Ratio AMC - Amoxicllin/Clavulanic Acid APUA - Alliance for the Prudent Use of Antibiotics BSI - Blood Stream Infection CI - Confidence Interval CIP - Ciprofloxacin COR - Crude Odds Ratio ERHK - Eastern Regional Hospital Koforidua NIT - Nitrofurantoin SMART - Study for Monitoring Antimicrobial Resistance Trends SXT - Trimethoprim-Sulfamethoxazole USD - United State Dollar UTI - Urinary Tract Infection WHAIF - Word Health-Care Associated Infections Forum WHO - World Health Organization 1 University of Ghana http://ugspace.ug.edu.gh DEFINITION OF KEY TERMS Antimicrobial Resistance: The ability of microbes to grow in the presence of a chemicals (drugs) that would normally kill them or limit their growth. Culture: Method of multiplying microbial organisms to determine type of organism and its abundance in a sample Sensitivity Testing: Laboratory techniques that help to determine which antibiotics are effective against a microbe. Urinary Tract Infection: Urinary tract infection is an infection in any part of your urinary system. Uropathogen: Any pathogen of the urinary tract. 2 University of Ghana http://ugspace.ug.edu.gh CHAPTER ONE 1.0 INTRODUCTION 1.1 Background The emergence of Antimicrobial Resistance (AMR) poses significant threat to improving on the health outcomes of populations across the globe (Bernabé et al., 2017). AMR arises when microbes such as bacteria, viruses, fungi and parasites change in ways that render the drugs used to treat the infections they cause ineffective (WHO, 2017). Since the 1940s, the prevention and control of major infectious diseases of public health concern like tuberculosis, HIV, malaria, gonorrhea and urinary tract infections (UTIs) have increasingly been affected by antimicrobial resistance. AMR has the potential of significantly reversing the progress that has already been made in the control of these diseases (Jindal, 2015). The lack of new antibiotics to replace old ones to which resistance has been developed further increases the challenges posed by AMR (Ventola, 2015). The global increase in human population coupled with an increasing disease burden has made dependence on antibiotics inevitable. The absence of a proper monitoring and regulatory framework in the use of antimicrobial agents, inadequate infection control practices and limited resources in the diagnosis of infectious diseases have contributed to the worldwide development of AMR (World Health Organization, 2016). In low and middle-income countries especially in sub-Saharan Africa, inadequate policies have resulted in the irrational use and abuse of antibiotics in almost all settings where they are needed (Jindal et al., 2015). The World Health Organization (WHO), in 2014, provided a comprehensive report on the global situation of AMR. The report focused on microbes causing diseases of public health concern. It also assessed the health and economic implications of AMR, surveillance 3 University of Ghana http://ugspace.ug.edu.gh challenges and provided future directions for its prevention and control (World Health Organization, 2014). In 2015, global leaders at the World Health Assembly authorized a global action plan to tackle AMR in the world (World Health Organization, 2015). This culminated into the first ever “African Conference on Antibiotic Use and Resistance” held in Ghana in March 2015 to publicize research information on AMR within the African sub-region. Several studies in Ghana suggests the development of AMR and the need for containment (Christian et al., 2014; Newman, 2011; Tadesse et al., 2017). The first policy on AMR titled “Policy on Antimicrobial Use and Resistance for Ghana” was developed to provide direction and guidance for all stakeholders who are affected by or use antimicrobial agents. One of the key policy statements is to increase knowledge and evidence of AMR through surveillance and research. This is to be achieved through creating national monitoring systems for the use of antibiotics and surveillance of antimicrobial resistance to update policies (Ministry of Health, 2017). The preliminary implementation period of the policy is from 2017 to 2021 through the Ghana National Action Plan on Antimicrobial Resistance. The action plan defines specific roles for all the major stakeholders (Ghana National Action Plan for Antimicrobial Use and Resistance Republic of Ghana, 2017). As part of the implementation of the National Action Plan on AMR, a laboratory-based surveillance system has been set up to monitor the development and spread of AMR in the country. The surveillance system also aims to coordinate individual research findings into the national data management system on AMR to influence future actions in managing AMR in Ghana (Policy on Antimicrobial Use and Resistance, 2017). Continuous research on AMR 4 University of Ghana http://ugspace.ug.edu.gh therefore contributes to the national pool of data and also updates information on AMR patterns at the local level for decision making on treatment strategies. 1.2 Problem Statement UTIs are among the most common bacterial infections affecting about 150 million people worldwide every year (Khoshnood et al., 2017; Kibret & Abera, 2014). Complications such as pyelonephritis with sepsis, renal damage in children and frequent recurrences could arise from UTIs (Flores-Mireles, 2015). UTIs are normally treated with commonly available antibiotics and patients are expected to be cured within days of receiving treatment. The misuse of antibiotics used to treat UTIs has led to the development of resistance among the major uropathogens in Ghana (Newman et al., 2011). Data from the Eastern regional hospital show a continuous increase in UTI cases over the past three years. Out-patient UTI cases rose from 3,757 in 2016 to 10,565 in 2018 whereas that of in-patients increased from 343 to 640 cases within the same period. Antibiotic resistance among uropathogens puts the increasing number of people with UTIs at risk of treatment failures. Failure in treatment results in an increase in morbidity, complicated forms of UTIs and UTI associated mortality. The affected patient(s) may be put on treatment for longer duration with a rise in healthcare expenditure and loss of productive time. Generally, there is a negative impact on economic activity of people affected with huge social, public health and economic implications in the country. In spite of a laboratory based surveillance programme of AMR in Ghana, the local resistance pattern of antibiotics used to treat UTIs at the Eastern Regional Hospital is not known hence underscores the need for this study to inform empirical therapy. This study therefore sought to examine the sensitivity pattern over the past five years in order to update knowledge for empirical therapy decision making at the hospital. 5 University of Ghana http://ugspace.ug.edu.gh 1.3 Justification Urinary tract infections are one of the main reasons for the prescription and use of antibiotics. Patients suffering from drug resistant UTIs may be on treatment for longer duration with huge socio-economic consequences if an effective antibiotic is not selected for treatment. Knowledge on the various pathogens and their resistance profile is necessary to guide clinicians to accurately prescribe effective antibiotics locally. It will also help policy makers to have enough information for AMR policy formulation and implementation. While several studies have focused on antibiotic resistance among various pathogens in Ghana, few have reported how resistance among uropathogens have changed over the years as hence the need for this study. In the absence of this study, the amount of data available for national AMR surveillance would be limited. If this study is conducted however, clinicians in Ghana specifically in the Eastern Region will have better understanding of the spectrum and resistance patterns of antibiotics available for treating UTIs locally. This is likely to result in better choice of antibiotics for empirical therapy, reduction in treatment failures and economic burden on patients. 6 University of Ghana http://ugspace.ug.edu.gh 1.4 Conceptual framework Institutional Factors Risk Factors Age - AMR Policy - Health service Sex delivery Residence Pregnancy Sexual activity Diabetes Uropathogens UTI Antibiotic use E. coli Cystitis Amikacin Klebsiella spp Urethritis Gentamicin Citrobacter spp Pyelonephritis Ciprofloxacin Antimicrobial Morganella spp Glomerulonep- Cefuroxime Resistance S. aureus hritis Ampicillin Pseudomonas spp Augmentin Hospitalisation Enterococcus spp Nitrofurantoin Status In- Patient Out-Patient Figure 1.4: Conceptual framework of risk factors and uropathogens causing UTI and their inter-relationship with antibiotic resistance. 7 University of Ghana http://ugspace.ug.edu.gh 1.5 Narrative of Conceptual Framework The prevalence of UTI is influenced by several factors including age, sex, pregnancy, hospitalization and exposure to urological procedures. These factors expose persons to particular uropathogens that cause UTI. UTIs are one of the major reasons for the prescription and use of antibiotics globally. The use of antibiotics largely influences the susceptibility pattern of the various uropathogens. In an environment where antibiotics are overused or abused, there is high resistance developed by bacteria to the antibiotics. Institutional factors such as access to drugs, presence of an AMR policy, proper diagnostic tools and availability of adequate prescribing staff also contribute to the way antibiotics are used. The presence and implementation of an AMR policy helps to monitor and regulate the use of antibiotics by consumers and healthcare delivery staff. The interrelationship of these factors generally affects antibiotic susceptibility patterns of disease causing bacteria including uropathogens in countries and across the world. 1.5 Research Questions 1. What is the prevalence of Urinary Tract Infection among patients referred to the Eastern Regional Hospital Laboratory in Koforidua to diagnose UTI from 2014 to 2018? 2. What is the trend of the main bacteria isolates responsible for UTI among patients visiting the eastern regional hospital laboratory, Koforidua from 2014 to 2018? 3. What is the antimicrobial resistance pattern and associated factors among patients diagnosed with UTI at the Eastern Regional Hospital in Koforidua, Ghana? 8 University of Ghana http://ugspace.ug.edu.gh 1.6 General objective To assess the resistance pattern of uropathogenic bacteria over the past five years and associated factors among patients diagnosed with UTI at the Eastern Regional Hospital, Koforidua. 1.6.1 Specific objectives 1. To determine the proportion of Urinary Tract Infection among patients referred to the Eastern Regional Hospital laboratory in Koforidua to diagnose UTI from 2014 to 2018. 2. To assess the trend of the main bacteria isolates responsible for UTI among patients visiting the Eastern Regional Hospital laboratory, Koforidua from 2014 to 2018. 3. To determine the antimicrobial resistance pattern and associated factors among patients diagnosed with UTI from 2014 to 2018 at the Eastern Regional Hospital in Koforidua, Ghana. 9 University of Ghana http://ugspace.ug.edu.gh CHAPTER TWO 2.0 LITERATURE REVIEW 2.1 Concept of Antimicrobial Resistance Antimicrobial resistance (AMR) refers to the capacity of a microbe (bacteria, viruses and parasites) to prevent an antimicrobial agent (such as antibacterial, antivirals and anti-malarial) from destroying it. This renders standard treatments ineffective and infections may persist and be transmitted to other persons (WHO, 2017) Antimicrobial drugs have been of immense help to the global fight against infectious diseases since their discovery. Penicillin was the first antibiotic to be discovered in 1928 by Sir Alexander Fleming. The discovery of antibiotics has led to major transformations in the treatment, management and control of infectious diseases. Millions of lives have been saved over these years leading to a significant improvement in human health and the quality of life in general across the world (Ventola, 2015). Several classes of antibiotics have been developed since the first discovery was made. These new antibiotics have been used to treat various infections caused by bacteria, fungi, parasites and viruses. In less than a century of these significant achievements, the development of antimicrobial resistance (AMR) has been documented in almost all the classes of antibiotics. Much attention has been devoted to resistance in antibacterial agents due to the wide range and common nature of bacterial infections affecting humans across the globe. Bacteria develop resistance through several mechanisms. These include preventing access of the antibiotic, removal of the antibiotic, destroying the drug, modifying the antibiotic, circumventing the effects of the antibiotic and changing the targets of the antibiotic. 10 University of Ghana http://ugspace.ug.edu.gh Gram-negative bacteria have membranes that protect them from the external environment. The openings in these membranes can be adjusted to selectively prevent entry of antibiotics thereby rendering them ineffective against the bacteria. Another way bacteria develop resistance is to remove antibiotics that enter their cell by using pumps in the cell wall. Pseudomonas aeruginosa is an example of bacteria that shows resistance to several antibiotics (including beta-lactams and fluoroquinolones) using this approach (Kon & Rai, 2016). Some bacteria also destroy the antibiotics to make them ineffective by using enzymes they produce. An example of such bacteria is Klebsiella pneumoniae which produce carbapenemases to breakdown carbapenem drugs and most other beta-lactam drugs. Other bacteria utilize enzyme inactivation to render antibiotics ineffective. This is done by producing enzymes to inactivate certain antibiotics. For example Staphyloccus aureus uses enzymes to produce compounds that bind to aminoglycosides to make them ineffective. Some antibiotics are designed to interrupt metabolic processes necessary for the survival of the bacteria. Some bacteria acquire resistance to these antibiotics by developing alternate pathways to bypass these drug disruptions. Evidence suggests that Staphylococcus aureus bacteria uses this mechanism to bypass the drug effects of trimethoprim. Other antibiotics also function by targeting some specific parts of bacteria for destruction. By changing the structure of their target sites, some bacteria are able to avoid destruction by antibiotics thereby making them resistant to that particular antibiotic. For example E. coli bacteria can add a compound to the outside of the cell wall to prevent the drug colistin from recognizing and binding to it (“How Antibiotic Resistance Happens | CDC", 2019). 11 University of Ghana http://ugspace.ug.edu.gh 2.2 Global Prevalence of Antimicrobial Resistance A project titled the Global Advisory on Antibiotic Resistance was initiated by the Alliance for the Prudent Use of Antibiotics (APUA) to compile data on AMR from several surveillance programmes across the globe. The project report cited the problem of AMR as affecting the treatment of all microbial diseases with bacteria such as Staphylococcus aureus, Streptococcus pneumoniae, and some strains of Neisseria gonorrheae, Escherichia coli strains and Klebsiella species being implicated in Europe, United States and South East Asia. This contributed to the declaration by the World Health Assembly in 2005 that AMR was a problem that needed urgent attention (Levy & Brien, 2005). In a summary of key messages at the fourth biennial World Healthcare-Associated Infections Forum (WHAIF) held in June 2013 in France to address the rapid spread of AMR, the global situation on AMR was presented by several experts from over thirty countries. It was noted that about ninety percent of Staphylococcus aureus strains had developed resistance to penicillin in the United Kingdom. In the United States, almost all strains were penicillin resistant and fifty percent also resistant to methicillin (Huttner et al., 2013). Data obtained from some member states of the World Health Organization (WHO) suggests that the proportion of commonly isolated bacteria Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus showing resistance to specific antibacterial agents is more than 50% in most WHO member countries (WHO, 2014). Some studies conducted in Europe have shown that common uropathogens demonstrate varying degrees of AMR against commonly prescribed antibiotics in Portugal, Italy, England, The Netherlands, and some areas in France, Spain, and Poland (Fluit et al, 2000; Linhares et al, 2013). In the United States, a study carried out to determine trends in antimicrobial activity of some antibiotics on urine isolates of E. coli (most common cause of UTIs) from female 12 University of Ghana http://ugspace.ug.edu.gh patients over a seven year period showed resistant rates among the isolates to ampicillin, trimethoprim-sulfamethoxazole (SXT), ciprofloxacin and nitrofurantoin as (36.0-37.4% per year), (14.8-17.0%), (0.7-2.5%) and (0.4-0.8%) respectively (Karlowsky et al, 2002). Across many regions in the United States, Neisseria gonorrhoeae has developed resistance to penicillin, tetracycline and fluoroquinolones and only susceptible to ceftriazone currently (Huttner et al., 2013). Another study conducted by Phouangsouvanh and colleagues in the Lao People’s Democratic Republic to determine the antimicrobial susceptibility of Neisseria gonorrhoeae isolates revealed resistance to penicillin (by b-lactamase production), tetracycline and ciprofloxacin were 89.9%, 99.4% and 84.8%, respectively while all isolates were susceptible to ceftriaxone and spectinomycin (Phouangsouvanh, 2018). 2.3 Prevalence of Antimicrobial Resistance in Africa In Africa, several studies have shown that AMR is on the rise. A systematic review by Tadesse and colleagues describes the general situation of AMR on data published from 2013–2016 on antibiotic drug sensitivity in Africa. They observed that the overall resistance to commonly used drugs, like amoxicillin and trimethoprim/sulfamethoxazole was 72.9% and 75% respectively. Also, a lesser level of resistance of S. aureus, Klebsiella spp., E. coli and S. pneumoniae to carbapenems and fluoroquinolones was seen in all regions of Africa as related to the other antibiotic-bacterium groupings. In the same study, it was observed that Klebsiella spp. resistance to ciprofloxacin in West Africa was higher than in other regions. Resistance to the trimethoprim (33.9%–100%), ampicillin (7.9%–100%) and penicillin (0%–75%) was mostly high in all regions (Tadesse et al., 2017). Commonly used antibiotics (ampicillin, penicillin, amoxicillin, gentamicin, ciprofloxacin, chloramphenicol and trimethoprim) for the treatment of common bacterial infections such as urinary tract infections (UTI), pneumonia, meningitis, blood stream infection (BSI) and 13 University of Ghana http://ugspace.ug.edu.gh diarrhoea have been observed to demonstrate various degrees of resistance in West Africa as demonstrated by Bernabe et al (2017) in a systematic review and meta-analysis of antimicrobial resistance in West Africa. Among studies on blood stream infections, the general rates of AMR were observed for antimicrobials among Gram-negative bacteria as follows: ampicillin, 68.4%; chloramphenicol, 52.4%; trimethoprim/sulfamethoxazole (SXT), 54.7%; amoxicillin/clavulanic acid (AMC), 41.5%; and gentamicin, 37.2%. The most active antibiotics for Gram-negative BSIs were third- generation cephalosporins for which resistance was observed in 17.7% of isolates, and fluoroquinolones, 12.1% of isolates. This increasing trend of resistance was similar in bacteria responsible for meningitis, UTIs, pneumonia and diarrhoea in their study (Bernabé et al., 2017). 2.4 Urinary Tract Infections Urinary tract infection (UTI) is a general term that describes any infection relating to any part of the urinary tract, namely the kidneys, ureters, bladder and urethra. The urinary tract can be separated into the upper (kidneys and ureters) and lower tract (bladder and urethra). Infections may include either only the lower urinary tract or both the upper and lower tracts. The infections can be caused by bacteria, fungi, virus and parasites. Some of the clinical symptoms of UTI include flank pain, fever, dysuria, urinary urgency and frequency (Tan, 2016). UTIs are one of the most common bacterial infections diagnosed in health practice around the world (Nzalie et al, 2016). They are a major cause of morbidity in infant boys, older men and females of all ages. Factors such as age, gender, pregnancy, sexual activity, prostate enlargement in men are the main determinants of its frequency (Mohammed et al, 2016). 14 University of Ghana http://ugspace.ug.edu.gh 2.4.1 Pathogenesis of UTI There are two main paths by which bacteria can enter and spread inside the urinary tract in humans. These are the ascending and hematogenous pathways. In the hematogenous route, organisms especially originating from the blood infect the parenchyma of the kidney. The kidney is mostly the site where abscesses occur in patients with bacteraemia. This is normally caused by gram positive bacteria such as Staphylococcus aureus. Gram negative bacteria do not normally infect the kidney by the haematogenous route. Most UTIs occur by the ascending route. Majority of uropathogens originate from the rectal flora and invade the bladder through the urethra. In females, the urethra is short and is situated near to the vulvar and perineal areas. This makes invasion by rectal flora more likely hence the frequent development of UTIs among females. The development of infection depends on the particular microbe, the amount of the inoculum and host defenses. When the bacteria ascend into the bladder, they may proliferate and then pass up the ureters and then to the renal parenchyma (Sobieszczyk, 2018). 2.4.2 Categories of urinary tract infection Clinically, UTIs are characterized as uncomplicated or complicated. Uncomplicated UTIs normally affect persons who are otherwise healthy and do not have any structural or neurological urinary tract abnormalities. These infections are further distinguished into lower UTIs (cystitis) and upper UTIs (pyelonephritis). Risk factors are connected with cystitis, include female gender, a previous UTI, sexual intercourse, vaginal infection, diabetes, obesity and genetic susceptibility (Lee et al., 2018). Complicated UTIs are normally linked with factors that compromise the urinary tract or host immunity. Some of these factors include urinary obstruction, urinary retention initiated by neurological disease, immunosuppression, renal failure, renal transplantation, pregnancy and 15 University of Ghana http://ugspace.ug.edu.gh the presence of foreign bodies such as calculi, indwelling catheters or other drainage instrument (Flores-Mireles et al, 2015). 2.4.2 Epidemiology of UTI UTIs affect all persons, however the distribution varies with age and sex. Persons at increased risk for morbidity include neonates, pre-pubertal girls, young women, older men, individuals with structural abnormalities of the urinary tract and immunocompromised patients. In neonates, UTIs occur more often in males; thereafter they occur more frequently in girls and women. Infections occurring in preschool boys are normally associated with serious congenital abnormalities. It has also been shown that lack of circumcision predisposes young boys and infants to UTIs (Odoki et al., 2019). UTs are rare in men less than 50 years of age and symptoms of dysuria (painful urination) are more commonly associated with sexually transmitted infection of the urethra or prostate. The incidence of UTIs in men increases after the age of 50 years and may be due to prostatic diseases and the use of instrumentation during hospitalization (Basseye et al, 2016). Among young adults, the prevalence of UTIs increases in the female population. Up to 40% of women will experience a symptomatic urinary tract infection at some time during their life and many will have recurrent episodes. Pregnant women have a 4-10% prevalence of UTI which has been shown to increase the risk of premature delivery, fetal mortality and pyelonephritis in the mother. In the hospitalized patient, urinary tract infection may account for close to 50% of hospital-acquired infections and are a major cause of Gram negative bacteremia and mortality (Tenney et al., 2018) 16 University of Ghana http://ugspace.ug.edu.gh 2.4.3 Causative organisms of UTIs The major causative bacteria for UTIs are gram negative bacteria and they account for about 80-85% of infections. The main organisms include Escherichia coli (E. coli), which is implicated in about 75.5-87% of UTI infections, Klebsiella species, Citrobacter spp, Acitenobacter spp, Enterobacter spp, Providencia spp, Pseudomonas spp, Serratia spp and Proteus species. Some gram positive bacteria that also cause UTIs are Staphylococcus and Enterococcus species (Akram, 2007; Mohammed et al., 2016). In a study by Oli and colleagues in 2017 to determine the type and antibiotic susceptibility pattern of bacteria uropathogens isolated from female patients attending a teaching hospital in Nigeria, they found the major uropathogens to be E. coli (28.5%), Staphylococcus aureus (28.0%), Salomonella spp (28.0%) and Pseudomonas aeruginosa (20.5%) (Oli et al., 2017). Among paediatric patients of a tertiary hospital in Eastern India, Mishra et al in 2016 discovered Enterococcus faecalis and Staphylococcus aureus, Citrobacter freundii, Enterobacter aerogenes, Escherichia coli, Klebsiella oxytoca, K. pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa as the main bacteria responsible for UTI among children from urine samples collected over an eighteen month period (Mishra, 2016). In another study at a Medical University in Iran, Khameneh and colleagues (2009) showed that out of 803 urine culture positive for bacteria growth, E. coli dominated with 75.83% followed by Klebsiella spp (5.83), Proteus spp and Staphylococcus spp. Other isolates responsible for UTI among the study subjects were Coagulase Negative Staphylococcus, Citrobacter spp, Enterobacter spp and Pseudomonas aeruginosa. In Ghana, Prah and colleagues demonstrated the common organisms causing UTI among out- patients of the University of Cape Coast Hospital to be E. coli, Staphyloccus saprophyticus, Enterobacter spp Klebsiella spp and Candida spp (Prah et al., 2019). In another study at a referral hospital in Accra, Gyansah-Lutterodt and colleagues showed the predominant 17 University of Ghana http://ugspace.ug.edu.gh organisms causing UTI among patients as Coliforms (44.2%) and E. coli (36.2%). Other organisms present were Pseudomonas spp (5.4%), S. aureus (4.5%), Proteus spp (1.3%), Klebsiella spp (1.3%) and Providencia spp (1.8%) (Gyansa-Lutterodt et al., 2014). 2.4.4 Treatment of Urinary Tract Infections Presently, antibiotics are the main drugs of choice in the treatment of urinary tract infections. The choice of antibiotic therapy is normally guided by urine culture and sensitivity results. However, these tests are normally completed after three days and also not readily available in all health facilities. Hence, antibiotic treatment is typically started empirically before urine culture results become available (Karimian et al., 2017). It is also recommended that the choice of antibiotic be done in reference with local antimicrobial sensitivity patterns in each area. Some of the groups of antibiotics commonly prescribed include aminoglycosides, carbapenems, cephalosporin, monobactams, nitrofurans, penicillins, quinolones, and sulfonamides (Linhares et al., 2013). In Ghana, the main recommended drugs of choice for treating complicated and uncomplicated UTIs include ciprofloxacin, nitrofurantoin and cefuroxime (Standard Treatment Guidelines, Ghana, 2017). 2.5 Prevalence of Antimicrobial Resistance among Uropathogens The development of AMR among uropathogens has been widely demonstrated in various studies across the globe. These increasing rates of resistance threatens to increase disease burden, prolong illness and increase the cost of health service delivery. In a study conducted by Karimian and colleagues to examine the antibiotic resistance of bacteria causing UTI among children in Iran, results showed that resistance to imipenem, cefotaxime and cephalexin was more dominant in persistent UTI cases as well as in patients who had used antibiotics before acquiring the UTI. Additionally, the study identified nitrofurantoin as a viable alternative for the treatment of multidrug-resistant uropathogens in 18 University of Ghana http://ugspace.ug.edu.gh children with a febrile UTI (Karimian et al., 2017). Sibi (2014) showed that Klebsiella oxytoca strains isolated from the urine of pregnant women in India were resistant to cefotaxime and ceftriaxone. The study also revealed Cephalosporins and Quinolones to be effective against UTI causing organisms in pregnant women while antibiotic sensitivity testing revealed high resistance to penicillins (beta lactam group) by uropathogens (Sibi, 2014). A study conducted by Lu et al. (2012) to monitor antimicrobial resistance trends surveyed gram negative bacteria causing UTI in Asia-Pacific region. The study showed that the level of antibacterial resistance among uropathogens was high in most countries in the region (China, Hong Kong, Taiwan, Malaysia, Philippines, Singapore and South Korea) with the exception of New Zealand. Over 85% of pathogens causing UTI were sensitive to antimicrobial agents used in testing in New Zealand (Lu et al., 2012). In Africa, several studies have been conducted to show the varying uropathogenic profile and antibiotic resistance across the continent. In Ethiopia, Bitew and colleagues showed the overall antibiotic resistance rates of the gram-negative bacterial isolates ranged from 17.7% for piperacillin/tazobactam combination and 78.3% for ampicillin. High resistance levels of bacterial uropathogens for trimethoprim/sulfamethoxazole combination (66.3%) and tetracycline (62.3%) (Bitew et al, 2017). In Libya, one study suggested a range of 10.5% to 64.5% of AMR shown by uropathogens isolated to various antibacterial agents (Kibret & Abera, 2014) while another study in Ethiopia demonstrated high resistance rates of 85.6%, 88.9%, 76.7% to erythromycin, amoxicillin and tetracycline respectively (Mohammed et al., 2016). Duffa in 2018 demonstrated in Ethiopia the susceptibility of bacteria isolated from urine to some commonly prescribed antibiotics. In their study, Acinetobacter spp. was completely resistant to gentamicin (GN), trimethoprim-sulfamethoxazole (SXM), and augmentin (AMP). 19 University of Ghana http://ugspace.ug.edu.gh Enterococcus species showed resistance of 71.4% to chloramphenicol (C) and 85.7% to both SXM and erythromycin. S. aureus was 100% sensitive to almost all antibiotics. Multidrug resistance to more than two antibiotics was seen in 73.7% of the bacterial isolates (Duffa et al, 2018). In West Africa, specifically, in low and middle income countries, Bernabé et al (2017) found after the isolation of bacteria from urine samples of both inpatients and outpatients that urinary tract pathogens in West Africa showed varying degrees of resistance to commonly prescribed antibiotics. The analysis showed AMR among in-patients with UTIs to third-generation cephalosporins. Moreover, ciprofloxacin (a fluoroquinolone) was moderately active against E.. coli, Klebsiella spp. and P. aeruginosa isolated from inpatients’ urine specimen and was extremely active in that of outpatients. Their findings suggested that fluoroquinolones were a better choice in the treatment of UTIs (Bernabé et al., 2017). In a study to determine the prevalence and antibiotic resistance patterns of UTI at the university of Port Harcourt teaching hospital in Nigeria, the commonest isolates were Escherichia coli (32.8%), Staphylococcus aureus (17.2%), and Klebsiella spp. (16.4%). About 93.8% of isolates were resistant to tetracycline, 92.2% to the Co-trimoxazole, and 86.7% to Nalidixic acid. Pseudomonas spp. isolates were also resistant to the fluoroquinolone (Wariso, 2010). Moroh et al (2014) conducted a retrospective analysis of a twelve year data on urine sample in Abidjan and results showed that Escherichia coli was the predominant species (28.7%), followed by Staphylococcus aureus (17.4%), and Klebsiella pneumoniae (14.9%), and Enterobacter aerogenes (10%). These bacteria accounted for 71% of UTI diagnoses over the study period. Resistance investigations to antibiotics showed high rates of resistance to amoxicillin (78.9%), tetracycline (76.4%), and trimethoprim/sulfamethoxazole (77.9%). Cefotaxime and netilmicin respectively demonstrated 13.9% and 3.1% of bacterial resistance. 20 University of Ghana http://ugspace.ug.edu.gh Generally, it was observed in the study that bacterial resistance increased over time for all antibiotics except chloramphenicol (Moroh et al., 2014). In Ghana, a laboratory-based surveillance on AMR conducted in the year 2015 revealed increasing trends of resistance to commonly used antimicrobial agents believed to cure various bacterial infections. According to the study, urine was the most common clinical specimen cultured in clinical laboratories in Ghana. Urine isolates formed 38.6% of pathogens isolated. Sensitivity testing revealed high levels of resistance to ciprofloxacin which is the recommended antibiotic for treating UTIs Ghana (Opintan et al., 2015). Also, Gyansa-Lutterodt et al (2014) showed antibiotic resistance in their study to determine the prevalence and antibiotic sensitivity pattern of uropathogens among patients referred to the Ghana Police Hospital’s Laboratory. Uropathogens isolated were highly sensitive to nitrofurantoin and gentamicin. The bacteria showed varying degrees of resistance to common antibiotics used in the treatment of uncomplicated UTI such as ciprofloxacin (Gyansa-Lutterodt et al., 2014). Furthermore, Boye et al. (2012) showed the high incidence of UTI among pregnant women in Cape Coast. The bacteria isolated showed variable sensitivity patterns to gentamicin, tetracycline, amikacin, ampicillin and erythromycin. The highest sensitivity was seen against gentamicin and the lowest against erythromycin. All the isolated bacteria were resistant to amikacin and penicillin. 2.6 Factors influencing the antimicrobial resistance among patients diagnosed with UTI 2.6.1 Age, Sex and Residence A number of studies have shown the association between demographic characteristics and antimicrobial resistance among patients with urinary tract infections. Karlowsky and colleagues (2011), in a yearly Canadian National Surveillance study (CANWARD), tested 2,943 urinary culture pathogens for antimicrobial sensitivity from the 21 University of Ghana http://ugspace.ug.edu.gh year 2007 to 2009. They found out that there was a significant association between increased age and resistance to ciprofloxacin. Their study also demonstrated an association with resistance to two or more frequently recommended oral antibiotics (amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and SXT). They also showed that the percentage of isolates resistant to amoxicillin (AMC), ciprofloxacin (CIP), nitrofurantoin (NIT) and trimethoprim- sulfamthoxazole (SXT) varied by gender. Among females, the percentage resistance was AMC (4.3%), NIT (2.9), CIP (17.2), SXT (20.8) while that of males was AMC (3.3%), NIT (7.9%), CIP (27.2%), SXT (26.3%) (Karlowsky et al., 2011). These findings were consistent with a previous study conducted in the United States by Sahm et al (2001). They showed that among females, the percentage of multiple drug resistant E. coli resistant to ampicillin, cephalothin, nitrofurantoin, SXT, and ciprofloxacin were 38.6%, 14.3%, 0.8%, 18.7% and 3.2% respectively. That of males also were 39.3%, 18.5% 1.4% 20.1% and 7.6% respectively (Sahm, 2001). In a joint modelling of resistance to six antimicrobials in Canada (2019), Soucy and colleagues showed that male sex was a consistent risk factor for antibiotic resistance to Escherichia coli. They also showed that resistance trends were higher in more densely populated urban areas compared with less densely populated areas which is suggestive of increased use in densely populated areas (Soucy et al., 2019). 2.6.2 Hospitalization status The hospitalization status referring to whether a patient is an Out-patient or In-patient (on admission) is known to influence disease patterns and consequently resistant patterns among various uropathogens. While some infectious diseases such as UTIs are acquired from the community, they may also be acquired from the hospital due to some procedures such as catheterization that patients are exposed to. 22 University of Ghana http://ugspace.ug.edu.gh Some studies have examined how hospitalization status influences resistance to antibiotics used to treat uropathogens. In 2013, McGregor showed significant differences in resistance pattern of E. coli to Ciprofloxacin and Nitrofurantoin between In-patients and Out-patients (McGregor et al., 2013). In-patients are also a consistent risk factor for resistance to antibiotics (Soucy et al., 2019). In Botswana (2013), Renuart and colleagues also demonstrated that uropathogens from In-patient urine samples were more likely to exhibit resistance to co-trimoxazole compared to Outpatient samples (Renuart et al., 2013). 23 University of Ghana http://ugspace.ug.edu.gh CHAPTER THREE 3.0 METHODS 3.1 Research Design A retrospective cross-sectional study design was employed to review records of urine culture and antibacterial sensitivity results of patients referred to the bacteriology laboratory at the Eastern Regional Hospital in Koforidua, Ghana from 2014 to 2018. 3.2 Study Area The study was carried out at the Bacteriology unit of the Clinical Laboratory Department of the Eastern Regional Hospital located in Koforidua, Ghana. The Eastern Regional Hospital was established in 1926 to provide comprehensive secondary level in-patient and out-patient healthcare service. It is a secondary level referral health facility and also a referral center for the entire district hospitals in the Eastern region. The hospital also serves as the main health facility for people living in the New Juabeng municipality with over 180,000 inhabitants. It has ten (10) wards and 280 to 300 bed capacity. (Eastern Region Analytical Report, 2018). There are several departments at Eastern Regional Hospital of which the Clinical Laboratory department is included. Other departments include the Out-patient department, Surgical Wards, Prenatal and Postnatal wards, Children’s ward, Neonatal Intensive Care Unit (NICU), Dental Department, Physiotherapy and Optometry Departments. In the year 2018, the facility saw an OPD attendance of 237,870 and admitted 21,014 patients (DHMIS, 2019). The Clinical Laboratory Department provides reliable laboratory services for patients to support clinicians for diagnosis and monitoring of patients’ treatment outcomes. It is subdivided into the Bacteriology Unit, Parasitology Unit, Haematology Unit, Serology Unit, 24 University of Ghana http://ugspace.ug.edu.gh Chemical Pathology Unit and the Blood Transfusion Unit to serve specialized functions. The Bacteriology Unit also doubles as the Public Health Reference Laboratory (PHRL) of the Eastern Region. Figure 3.2 Map of Ghana, Eastern Region and the New Juabeng Municipality showing the location of the Eastern Regional Hospital. Credit: Geographic Information Systems (2019). 25 University of Ghana http://ugspace.ug.edu.gh 3.3 Study Population This was a records review. The study included all clinical laboratory records of patients suspected of UTI and referred to the Bacteriology Unit at the Eastern Regional Hospital in Koforidua, Ghana, for confirmation between the years 2014 to 2018. The period was selected in order to provide a comprehensive amount of recent laboratory data for evaluation. 3.4 Study Variables The variables in this study included dependent variable and independent variables. The dependent variable was antimicrobial resistance among patients diagnosed with UTI at the Eastern Regional Hospital in Koforidua, Ghana. The independent variables were Sex of patient, age of patient, urinary tract infection status, uropathogens isolated, type of ward and hospitalization status of patient (as shown in Table 3.1). Table 3.1: Summary of Variables used in the Study Variables Operational Indicator Variable type Source of data Definitions Dependent Variable Antimicrobial Documented Resistant or Categorical Records review resistance resistance to Sensitive to antibiotics used to antibiotics used to treat UTI treat UTI Independent variables Age Age of patient in Age at last Continuous Records review years birthday Sex Biological sex of Male or Female Categorical Records review patient Urinary Tract Bacteriologically Bacteria growth or Categorical Records review Infection status confirmed UTI No bacteria growth using culture Uropathogen Bacteria isolated Type of bacteria Categorical Records review from culture as isolated from urine cause of UTI culture Hospitalisation Location of patient In-patient or Out- Categorical Records review status in the hospital patient 26 University of Ghana http://ugspace.ug.edu.gh 3.5 Sampling Method This study utilized a census of total laboratory records available on patients tested for UTI at the Bacteriology Unit of the Eastern Regional Hospital in Koforidua, Ghana from the year January 2014 to December 2018. The sample included all laboratory data that met the inclusion criteria. 3.6 Inclusion and Exclusion Criteria 3.6.1 Inclusion Criteria 1. All records of patients in the Urine Culture and Sensitivity testing records book at the Bacteriology Unit of the Eastern Regional Hospital Laboratory. 2. All patient records of Urine Culture and Sensitivity from January 2014 to December 2018. 3.6.2 Exclusion Criteria 1. All records of UTI caused by other uropathogens apart from bacteria was excluded from the study. 2. Laboratory records of Urine culture and sensitivity tests with incomplete data was excluded from the study. 3. Urine culture results that indicated mixed bacteria growth were excluded from the study since they are considered as a contamination making the result invalid. 3.7 Source of Data and Data Collection The data collected were located in the Bacteriology Unit of the Clinical Laboratory Department of the Eastern Regional Hospital. In the Bacteriology Unit, the data were archived in a shelf containing all Culture and Sensitivity records. The data were in the upper section of the shelf designated as Urine Culture and Sensitivity result. 27 University of Ghana http://ugspace.ug.edu.gh A data extraction form (Appendix I) was designed to cover all relevant information from the lab records. It had sections on patients’ demographic characteristics, bacteria isolates responsible for UTI, source of urine specimen, culture and sensitivity result. 3.8 Quality Control 3.8.1 Pre- Data collection The principal investigator was assisted by four intern laboratory scientists who had received training in the extraction of data from the lab records. Pre-testing of the data extraction tool was done at the Bacteriology unit of the Tetteh Quarshie Memorial Hospital at Mampong as a quality control measure for the study. The data extraction forms did not permit entry of names of patients but rather specimen identification numbers to be captured to assist in data cleaning and validation processes. The extracted data sheets were reviewed on a daily basis for completeness and allocated unique serial numbers to avoid double entry. 3.8.2 Post- Data collection The extracted data were randomly checked with original records to validate entered data. Information derived from patients records were kept in secret files and made only accessible to the principal investigator. 3.9 Data processing and Analysis The data gathered from the medical records were cleaned, coded, and entered into a Microsoft excel 2010 spreadsheet and exported into STATA version 15. Statistical tools namely time graphs, percentages, frequency tables, and cross tabulations were used to describe the data. Chi-square test was used to assess the association between UTI and various independent variables. Both bivariate and multivariable logistic regression analysis was used to assess predictors of antimicrobial resistance for three most sensitive antibiotics and the most resistant antibiotics. 28 University of Ghana http://ugspace.ug.edu.gh Odds ratios were reported with their 95% Confidence Intervals. Statistical significance was determined at p-value of < 0.05. 3.10 Ethical Consideration Ethical clearance was obtained from the Ethical Review Committee of the Ghana Health Service. Ethical Approval number was GHS-ERC: 036/05/19 (Appendix II) Permission to the Eastern Regional Hospital and Laboratory Department was granted by the Eastern Regional Director of Health Services, the Medical Director of the Eastern Regional Hospital and Head of Laboratory Services before data collection. 29 University of Ghana http://ugspace.ug.edu.gh CHAPTER FOUR 4.0 RESULTS 4.1 Distribution of variables at study site Out of 14568 records of urine culture and sensitivity recorded from January 2014 to December 2018, 12655 (86.9%) met the criteria to be included in the study. Out of 12655 records used in the study, 2234(17.7%) were recorded in 2014, 2081(16.4%) in 2015, 1868(14.8%) in 2016, 3045(24.1%) in 2017 and 3427(27.0%) in 2018 (as shown in Table 4.1) 4.1.1 Distribution of participants by sex Most of the cases eligible for inclusion in the study were females 8280, (65.43%) (as shown in Table 4.1) 4.1.2 Distribution of participants by age. The ages of the cases selected into the study range from 4 weeks to 100 years with the median age being 25 years. Majority of the cases fall within 19 to 45 years of age, 5807 (45.89%) followed by those within the age bracket of 2 to 5 years, 1824 (14.41%). The least recorded age group is those within 13 to 18 years, 555 (4.39%) (As shown in Table 4.1). 4.1.3 Distribution of cases by hospital location Majority of the cases included in the study were from the Out-patient department, 8663(68.46%) followed by the kids ward which represent 12.64% of selected participants. Majority of the units that referred cases to the laboratory to test for UTI were units that catered specifically for females and children (Antenatal Clinic, Gynaecology Unit, Female Ward, Children’s Ward and Neonatal Intensive Care Unit) (as shown in Table 4.1). 30 University of Ghana http://ugspace.ug.edu.gh Table 4.1: Distribution of study characteristics Study characteristic Frequency Percentage (%) N=12,655 Sex Female 8,280 65.4 Male 4,375 34.6 Age groups <1 1,096 8.7 2-5 1,824 14.4 6-12 1,297 10.3 13-18 555 4.4 19-45 5,807 45.8 46-60 1,051 8.3 Above 60 1,025 8.1 Hospital location Out-patient Department 8,663 68.5 Antenatal clinic 796 6.3 Gynaecology unit 858 6.8 Female ward 172 1.4 Male ward 109 0.9 Children’s ward 1,600 12.6 Neonatal Intensive care 90 0.7 Emergency unit 329 2.6 Other units* 38 0.3 Year of attendance 2014 2,234 17.6 2015 2,081 16.4 2016 1,868 14.8 2017 3,045 24.1 2018 3,427 27.1 Other units*: Urology, Ant-retroviral clinic 31 University of Ghana http://ugspace.ug.edu.gh 4.2 Distribution of reported cases of UTI 4.2.1 Overall reported cases of UTI from 2014 to 2018 The overall proportion of UTI from 2014 to 2018 was 2,573 (20.3%) out of 12,655 people. As seen in figure 4.2, UTI cases rose significantly from 398 (17.8%) in 2014 to 757 (28.4%) in 2018. 30 28.1 28.4 24.9 25 23.4 20 17.8 15 10 5 0 2014 2015 2016 2017 2018 YEAR OF DIAGNOSIS Figure 4.2 Pattern of UTI cases from 2014 to 2018 4.2.2 Distribution of UTI by sex. Out of 2573 cases of UTI, majority were females 2060 (80.06%). Proportions of UTI varied significantly (p<0.05) between Male and Females in the study subjects (as shown in Table 4.2). 32 PERCENTAGE OF REPORTED UTI CASES University of Ghana http://ugspace.ug.edu.gh 4.2.3 Distribution of UTI by age categories. Out of 2,573 UTI cases, 42.32% (1,089/2,573) representing the majority of cases were among the 19-45 age category. This is followed by those above 60 years of age 14.65% and then children aged 1 and below. The age group with the least number of UTI cases is those between 13 and 18 years (as shown in Table 4.2). 4.2.4 Distribution of UTI by hospitalization status and hospital units Most of the UTI cases, 74.04%, occurred from Out-patient settings though this was not statistically significant (p>0.05) when compared with number of cases occurring from In- patients. When stratified into the individual hospital units, 68.09% (1,752/2,573) being majority of the cases were Out-patients followed by Children’s’ ward 9.06% (233/2,573). The least number of UTI cases were from Male ward and other units which contributed 0.93% and 0.51% of UTI cases respectively. Variations in UTI cases among the various hospital units were statistically significant (p<0.05) (Table 4.2). 33 University of Ghana http://ugspace.ug.edu.gh Table 4.2 Distribution of UTI cases by study characteristics Study characteristics UTI No UTI Pearson Chi-square N=2573 N=10082 χ2 p-value n (%) n (%) Sex Male 513 (19.9) 3,862 (38.3) 305.75 0.0001 Female 2,060 (80.1) 6,220 (61.7) Age categories 0.05) (Table 4.5.1) 42 University of Ghana http://ugspace.ug.edu.gh Table 4.5.1 Logistic regression showing association between the three most resistant antibiotics with study variables. ANTIBIOTICS Variables AMPICILLIN COTRIMOXAZOLE TETRACYCLINE COR AOR COR AOR COR AOR Sex Female Ref Ref Ref Ref Ref Ref Male 1.01(0.72,1.42) 0.91(0.63, 1.30) 0.91(0.67, 1.25) 0.94(0.67, 1.31) 0.94(0.69, 1.27) 1.04(0.76, 1.44) Uropathogen Other uropathogens Ref Ref Ref Ref Ref Ref Escherichia coli 0.96 (0.22, 4.13) 0.93 (0.21, 4.01) 4.19 (1.69, 10.34)** 4.00(1.61, 9.94)** 5.78(2.45, 13.53)*** 5.82(2.47, 13.72)*** Klebsiella spp 0.82 (0.19, 3.56) 0.77 (0.19, 3.37) 3.77 (1.51, 9.37)** 3.73(1.49, 9.33)** 4.54(1.93, 10.67)*** 4.86(2.05, 11.50)*** Citrobacter spp 1.08 (0.24, 4.86) 1.02 (0.23, 4.60) 2.60 (1.02, 6.63)* 2.63(1.03, 6.73)* 3.89(1.60, 9.45)** 4.20(1.72, 10.26)** Proteus spp 2.82 (0.24, 33.04) 2.79 (0.24, 32.77) 6.18 (1.15, 33.15)* 6.06(1.12, 32.69)* ------ ----- Morganella spp 1.04 (0.19, 5.74) 1.02 (0.18, 5.64) 3.84 (1.14, 12.99)* 3.67(1.08, 12.43)* 8.7(2.35, 32.16)** 8.62(2.32, 32.02)** Pseudomonas spp 1.23 (0.23, 7.03) 1.29 (0.23, 7.14) 4.00 (1.24, 12.95)* 3.88(3.31, 1.12)* 3.9(1.35, 11.27)* 3.81(1.31, 11.05)* Staphylococcus aureus 0.53 (0.11, 2.47) 0.53 (0.11, 2.48) 3.41 (1.16, 10.03)* 3.31(1.12, 9.71)* 2.46(0.94, 6.43) 2.47(0.94, 6.51) Enterococcus spp 0.45 (0.09, 2.25) 0.44 (0.09, 2.18) 2.33 (0.75, 7.22) 2.32(0.75, 7.2) 3.40(1.14, 10.10)* 3.53(1.18, 10.54)* Enterobacter spp 0.77 (0.10, 6.06) 0.81 (0.10, 6.40) 2.20 (0.48, 9.99) 2.22(0.49, 10.14) 2.25(0.57, 8.93) 2.18(0.55, 8.70) Age categories