ABSTRACT

Background: The over-the-counter availability of antibiotics and the absence of clearly defined protocols guiding antibiotic use in the Buea municipality may have encouraged the overuse and abuse of antibiotics.

These factors could account for  the circulation of drug resistant Salmonella species in the community.

The main objective of this work was to identify overused and misused antibiotics in the Buea municipality and also determine their effect on the antibiogram of  Salmonella typhi isolates circulating within communities of the Buea municipality.

Methods: A cross sectional study to investigate antibiotic consumption patterns and abuses were carried out by the administration of questionnaires to antibiotic purchasers  infront of  pharmacies and 10 drug stores in Buea.

A total of 186 stool samples were collected from 8 communities in the Buea municipality and processed for the isolation of Salmonella typhi using standard microbiological and biochemical tests.

Isolates were subjected to an antibiotic susceptibility test choosing antibiotics from previously identified abused and non abused groups of antibiotics from questionnaire administration. Frequency distribution of parameters of dry g abuse (source of prescription, duration of therapy, reason for consumtion of antibiotic) and antibiotic overuse was carried out using SPSS version 25 (AMONK, NY) and the Mann-Whitney sum rank test was used to compare the antimicrobial activity of abused drugs used in treatment of typhoid and unabused drugs for the same purpose

Results: Amoxicillin (26.7%), Ciprofloxacin(11.6%), and Cotrimoxazole (7.4%) are the most overused  used antibiotics in the Buea Municipality which recorded the highest resistance values of Cotrimoxazole (100), Amoxicillin (91.7%) and   Ciprofloxacin (8.30%) among the least. Respiratory tract infections(19.7%) and skin infections(15.1) were the most drugs for which the Penicillins(51.1%) Tetracyclines (39.3%) and Sulbactam antibiotics (27,3%) (p= 0.022 and X²= 14.775) were most abused without diagnosis(p= 0.000 and X²=583.630).

A (5.8%) of Salmonella typhi was reported in communities in the Buea Municipality and multidrug resistance was identified in (20%) of the isolates. The difference in the antibiotic resistance between antibiotics that were not  abused and abused was not significant  (U= 3603.0, p = .492).

Conclusion: The overuse and misuse of specific antibiotics does not account for the circulation of resistant strains Salmonella typhi to these particular antibiotics in the Buea municipality.Although antibiotic abuse does not significantly influence antibiotic resistance in Buea, if practices of abuse continue to abound it will tip off the scale to the negative. Multidrug resistant strains of salmonella typhi are circulating in the Buea Municipality.

CHAPTER ONE

INTRODUCTION

1.1 Background

The effective use of antibiotics is a significant measure promoted by the World Health Organisation (WHO) to protect their intrinsic antimicrobial activity and tackle Antibiotic resistance (ABR), a global public health threat [1].

This is due to the emergence, spread and persistence of multidrug-resistant (MDR) bacteria or “superbugs” that challenge antibiotic therapy [2]. Infections caused by MDR bacteria are associated with increased mortality compared to those caused by susceptible bacteria and are accompanied by an increased economic burden [3].

The plausible causes of antibiotic resistance include indiscriminate use of antibiotics in animals (food, pets, aquatic) and  humans, antibiotics sold over the counter, availability of substandard antibiotics, increased international travel to endemic areas, poor sanitation and hygiene, a host of environmental factors like the release of non-metabolised residues in the environment through manure or faeces and scientific factors such as genetic jugglery, intrinsic resistance, existence or resistome and subsitome among others [4].

These factors contribute to genetic selection pressure for the emergence of MDR bacterial infections [4, 5] and all these factors abound in the Buea Municipality.

The Centers for Disease Control (CDC) and Prevention threat Report 2013 [6] portrays antibiotic overuse as the single most important factor leading antibiotic resistance in both clinical and non clinical settings.

The overuse of antibiotics in clinical settings is caused by the use of new and potent antibiotics meant for severe cases, continuous overuse of the same set of antibiotics to treat common infections in the community, unnecessary prescription of broad spectrum agents, use of broad spectrum agents where there exists little or no duration of bacterial infection, excess duration for chemotherapy and failure to discontinue  existing therapy despite proof of antibiotic resistance among others [7].

All these violations abound in the Buea municipality where auto-medication is a common practice. In recent years antibiotics have been among the top 10 therapeutic classes in global pharmaceutical sales generated 40.6 billion US dollars in 2018 alone [8] yet the CDC stressed that at least 30% of the antibiotic courses prescribed were unnecessary, meaning no antibiotics were needed at all [6].

Prescription and utilization of antibiotics in Cameroon is suboptimal  with reported antibiotic resistance frequently identified in amoxicillin and cotrimoxazole [9].

The prescription of antibiotics in Cameroon is not always governed by standardized protocols due to the limited availability and use of culture and sensitivity, many antibiotics are used inappropriately. In the Buea Health District, antibiotics alone constituted 40.4% of drugs prescribed, 14.6% of the prescriptions had no clearly written indication and 6.4% had no information related to the prescriber [10]. Due to the absence of clearly defined working protocols for antibiotic prescription in the Buea Health District, antibiotic use was termed irrational and innapropriate [10].

Despite recommendations by WHO on antibiotic use, antibiotics are  abused by both the young and the old whether consciously or unconsciously in Cameroon [11,12]. This inappropriate use is aggravated by the over-the-counter availability of antibiotics [10] which are commonly self-medicated by outpatients of the Buea Health District. A prevalence of 68.4% of outpatients in Buea self-medicated with 81.8% prevalence of self-medication being among the age group 30-49 years while 0-9 years had the lowest prevalence of 37.5% [13]. The main reasons for self-medication were cost cutting (40.9%) followed by past experience from similar symptoms (29.3%). The main source of antimicrobials was from the community drugs stores 55.1% [13].

To use a specific case to illustrate this problem, Typhoid fever is an invasive bacterial infection  caused by the bacterium Salmonella enterica serovar Typhi [9].  It is prevalent  in low and lower-middle-income countries of which three million cases occur in Africa[14, 15]  mainly due to the inadequate access to safe water and sanitation which is a major problem in developing countries like Cameroon. Salmonella infections require antimicrobial therapy for the eradication of the infection However, the human threat presented by antibiotic resistant Salmonella strains is a global concern [16]. Typhoid fever has a 21% reported prevalence in the Buea municipality and has developed resistance to first-line antibiotics it was normally susceptible to such as Ciprofloxacin, Ofloxacin and  Chloramphenicol [17]. Treatment also involves the administration  of Intravenous (IV) fluids and  Oral Rehydration therapy as supportive care. For the purpose of this study, Salmonella strains were  investigated for resistance to selected drugs. Antibiotics that were investigated for abuse were Cell wall inhibitors (Amoxicillin, Ampicillin, Cloxacillin, Cefixime, Meropenem, Amphotericin B, Bacitracin and Ceftriaxone), Protein synthesis inhibitors (Gentamicin, Amikacin, Azithromycin, Rifampicin, Streptomycin, Erythromycin, Chlarithromycin and Chloramphenicol), DNA replication inhibitors (Ciprofloxacin, Novobiocin, and Ofloxacin), Antifolate synthesis inhibitor (Cotrimoxazole).

The ineffectiveness of antibiotics selected for the treatment of Typhoid fever in the Buea municipality is now common knowledge, since residents would rather turn to traditional medicine for treatment instead of antimicrobial chemotherapy.

This study sought to compare two groups  of antibiotics which both exert  an intrinsic antimicrobial effect on S. typhi.

These groups differ in whether or not they are commonly abused in the Buea municipality.

This course gave an understanding of how drug abuse may impart development of an antibiotic resistant strain of S. typhi.

 1.2 Problem statement

The failure to pursue  antibiotic stewardship guidelines  in Cameroon  has led to the abuse of antibiotics [18,19]. Furthermore, all antibiotics well regulated in the developed world, which are only sold upon clinician’s prescription or used in severe clinically ill patients are available in Buea, Cameroon    as over the counter drugs that can be obtained without a prescription [20].

Misleading knowledge in the community on antibiotics promotes misuse and overuse of antibiotics [11,21].

This chaotic situation will definitely promote development and persistence of drug resistant pathogens in the community [20].

An updated understanding of the effect of consumption patterns and quantity of antibiotic use on the development of antibiotic resistant pathogens in the Buea municipality will permit more appropriately targeted interventions to control antibiotic resistance, relieve its economic burden and improve the quality of health care in Buea Municipality.

1.3 Justification

Antibiotic Resistance is a major public health threat due to the emergence and dissemination of multidrug resistant bacteria. Infections caused by these bacteria are associated with increased mortality and aggravated economic burden which is more devastating in developing countries like Cameroon.

In Cameroon, antibiotic stewardship is not strictly pursued as the guidelines governing the availability and use of antibiotics are consistently applied.

The general public is not well educated on antibiotic resistance and its drivers.

In Cameroon, a majority of people consume antibiotics based on self-medication, without performing a diagnostic test to confirm the presence of a pathogen  or an antibiotic susceptibility test to guide the choice of antibiotic therapy.

There is a need to update the antibiotic resistance profile of Salmonella typhi in the Buea Municipality where antibiotic abusive practices abound.

1.4 Research Questions

1. What are the commonly abused antibiotics in the Buea Municipality?

2. What is the prevalence of antibiotic use without diagnosis in the Buea Municipality?

3. What is the magnitude of antibiotic resistant Salmonella typhi in the Buea Municipality?

4. What is the relationship between antibiotic abuse and drug resistance in Salmonella typhi?

1.5 Research Hypothesis

Overuse and misuse of specific antibiotics accounts for the development and  circulation of resistant  Salmonella typhi strains to these particular antibiotics in the Buea Municipality.

1.6 Objectives

1.6.1 General Objective

The overall aim of this study is to identify and quantify overused/misused antibiotics in the Buea Municipality and also determine their effect on the antibiotic drug resistance profile  of Salmonella typhi isolates circulating within communities of the Buea Municipality.

1.6.2 Specific Objectives

1. To determine the prevalence of antibiotics used without diagnosis in the Buea Municipality.
2. To identify commonly abused antibiotics in the Buea Municipality
3. To determine the magnitude of antibiotic resistance in clinical isolates of Salmonella typhi from communities in the Buea municipality and its association with antibiotic abuse.