The Scale of Antibiotic Abuse in the Buea Municipality and the Antibiotic Resistance Profile Of Salmonella typhi in the Buea Municipality

ABSTRACT

Background: The overuse and over-the-counter availability and abuse of antibiotics are factors that could account for the circulation of drug resistant Salmonella species in the community.

The main objective of this work was to identify overused and abused 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 was carried out by the administration of questionnaires to antibiotic purchasers in front of pharmacies and 10 drug stores in Buea to identify abused and non-abused antibiotics for AST on Salmonella spp isolates.

A total of 186 stool samples were collected from 6 communities in the Buea municipality and processed for the isolation of Salmonella typhi using standard microbiological and biochemical tests.

Frequency distribution of parameters of drug abuse (source of prescription, duration of therapy, reason for consumption 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 non-abused drugs for the same purpose

Results: Amoxicillin (26.7%), Ciprofloxacin (11.6%), and Cotrimoxazole (7.4%) were the most overused antibiotics in the Buea Municipality. Antibiotic use was significantly associated with diagnosis (p= 0.000 and X²=583.630).

A (5.8%) prevalence of Salmonella spp was reported in communities in the Buea Municipality and multidrug resistance was identified in (20%) of the identified Salmonella spp.

Fluoroquinolones are the first line antibiotics for the treatment of Salmonella spp infections in the Buea municipality. Amikacin (0%) and Meropenem (8.3%) also elicited a satisfactory antimicrobial effect on Salmonella spp.

There was no significant difference in antibiotic resistance between antibiotics that were not abused and those abused (U= 3603.0, p = .492) using the Mann-Whitney test.

However, abused drugs recorded a lower mean rank sensitivity (6.33) than non-abused drugs

Conclusion: The overuse and abuse of specific antibiotics does not significantly affect the development of drug resistant strains Salmonella spp to these particular antibiotics in the Buea municipality. Multidrug resistant strains of Salmonella spp are circulating in the Buea Municipality.

There is no significant difference in antibiotic resistance between abused and non-abused antibiotics (U=17.000, p=0.567).

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 inappropriate [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, Clarithromycin 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.