Antibiotic resistance patterns in human, animal, food and environmental isolates in Ghana: a review

Many articles have been published on resistant microorganisms isolated from humans, animals, foods and the environment in Ghana. However, there are no reviews that summarize the information on the isolates and antibiotics tested so far in the country. This literature review was completed through “PubMed” and “Google Scholar” searches. We included publications from the period 1975-2015 with a laboratory-based methodology to determine antibiotic resistance of strains isolated in Ghana. In total, 60 articles were included in the analysis with 10% of the articles carrying out nationwide research on antibiotic resistance. The regions of Ghana with the highest published articles were Greater Accra (40%), Ashanti (21.7%) and Northern Region (10%). Most of the studies (86.7%) were related to isolates collected from human samples followed by environmental (5%), animal (3%) and food samples (2%). Ten different bacteria genera were observed in the studies. The most common was Escherichia coli, followed by Staphylococcus spp., Mycobacterium spp. and Streptococcus spp. The highest mean resistance rate was encountered in Escherichia coli (62.2%) followed by Klebsiella spp. (60.4%) and Pseudomonas spp. (52.1%). High resistance rates have been found in Ghana, however, the data are skewed and some regions of the country have been neglected. There is a need for higher quality research to establish and monitor resistance patterns in Upper West, Brong-Ahafo, Volta and Eastern Regions of Ghana.


Introduction
The increasing problem of antibiotic resistance remains a major global health problem and causes a huge medical burden [1]. There are significant international efforts, notably the World Health Organization (WHO) and Food and Agriculture Organizations (FAO), working towards tackling this crisis through planned programs such as antibiotic stewardship programs coordinated by the Global Action Plan on Antimicrobial Resistance of the WHO [2]. These programs promote optimal antimicrobial use [3][4][5][6], resistance surveillance [7], research into the molecular bases for resistance [8], strict regulations on antibiotic usage [9][10][11] and education of medical, public health officials and the general populace [12][13][14]. Some private organizations and individuals have made efforts to tackle the antibiotic crisis in some African countries. An example can be seen in Ghana through the sponsorship of research projects and educational programs [15][16][17][18][19][20][21][22].
Unfortunately, some of these projects may be duplicated and have narrow coverage area due to limited funding. Others may be executed successfully but their impacts are minimal. Furthermore, complex socio-economic and political conditions in developing and low-income countries [23] make antibiotic resistance a difficult problem to tackle [24]. This is further hindered by the inadequate and unpublishable data produced [25]. A systematic review of publications of these research works is important to evaluate the overall impacts of antibiotics on human, animal, food and environmental isolates. The objective of this study was to compile all the available information concerning antibiotic resistance in Ghana to assist clinicians and researchers to know the most commonly isolated microbes and their resistance patterns. This research aims to provide further information on the current antibiotic resistance problems, which may also help institutions to create programs and policies to enhance antimicrobial stewardship, reduce misuse of antibiotics by health professionals and unskilled practitioners, control drug quality, limit the spread of resistant bacteria, develop adequate surveillance systems and update the Standard Treatment Guidelines of hospitals in Ghana [26]. These will help to prevent or slow the emergence of resistance among microorganisms. Furthermore, this review aims to inspire researchers to conduct more investigations, particularly in neglected areas of the country.

A thorough search of literature was done in Medline (PubMed) and
Google Scholar electronic databases. The search was carried out in June 2015. The following keywords were used to search in both databases with no language restriction or methodological filters: Antimicrobial OR Antibiotic AND resistance AND Ghana. Abstracts of potentially relevant titles were then reviewed manually for eligibility and were selected for closer examination to be included in the study. Search on Google Scholar: the same search words were used on Google Scholar, producing over ten thousand results. Consequently, a selection was done of every 10 th page (pages 1, 10, 20,30,40,50) and articles related to antibiotics in Ghana were selected based on their titles and abstracts.
Inclusion and exclusion criteria: the inclusion criteria were: (i) abstract availability, (ii) information about antibiotic resistance of at least one bacterium, (iii) laboratory-based methodology, (iv) bacterial strains collected in Ghana. The exclusion criteria were: (i) articles already included from PubMed but found on Google Scholar (ii) articles without abstract (iii) abstracts without factual data on antibiotic resistance.
Data analysis: data were gathered from each article concerning the bacteria isolated, the origin of isolation (human, animal, food and environment), the methods of antibiotic susceptibility test and the antibiotics used for them, the most frequent antibiotics used, the most resistant bacteria to the antibiotics used. The particular regions where the researches were conducted were also recorded. Data compilation and analysis were performed using the software MS Excel ® and results were presented in percentages using tables and figures.

Sample collection
Geographical/regional distribution of articles: Ghana has ten different administrative regions ( Figure 2 Genus and species of bacteria isolated: the bacterial species isolated and identified in the sixty articles were from ten different genera: Escherichia coli, Staphylococcus spp., Streptococcus spp., Klebsiella spp., Salmonella spp., Pseudomonas spp., Mycobacterium spp., Neisseria spp., Proteus spp. and Shigella spp. More information about the isolation of each genus of bacteria can be found in Table 1. Antibiotic resistance patterns: the information on the most tested antibiotics and the antibiotics recording the highest resistance rates was compiled, producing a table with forty antibiotics and 3 antibiotic combinations ( Table 2). The resistance level of all the organisms isolated and their resistance patterns to forty-three antibiotic formulations and the number of bacteria tested were also included in the isolated from the environment did not have any data specifying antibiotic resistance [86]. The highest resistance rates were found in the Ashanti Region [73,80] and the Northern Region [74]. In the Ashanti Region, 100% resistance was found against the combination of Amoxicillin-Ampicillin and Ampicillin and Tetracycline [73,80]. In Northern Region, the highest resistance rates were 100% to Ampicillin, Cotrimoxazole, Erythromycin, Penicillin and Tetracycline [74]. Also, high resistance rates were found against Cotrimoxazole Antibiotic resistance is one of the biggest threats to international health nowadays; its influence goes beyond health, impacting food security and the holistic development of Ghana. Substantial evidence worldwide indicates that there has been significant increase in antibiotic resistance. Furthermore, high antibiotic resistance rates were found in different bacterial isolates in Ghana [1]. As this study  (Table 2). However, the data were skewed because some regions of the country have been totally neglected in terms of antibiotic resistance research. There is a need for higher quality research to establish and monitor resistance patterns in Ghana to contribute to the global efforts to curb antibiotic resistance.

What is known about this topic
• Antibiotic resistance is one of the biggest threats to international health, food security and development nowadays; • Antibiotic resistance occurs naturally, as a survival adaptation of the bacteria, nevertheless, antibiotics misuse in humans and animals accelerates the process; • It is crucial to improve surveillance and raise public awareness about this global crisis; enabling public knowledge will increase understanding of proper use of antibiotics and reduce misuse.

What this study adds
• Compiled available information concerning antibiotic resistance research in Ghana; • Evidenced the significantly high antibiotic resistance rates in Ghana, especially in E. coli, Klebsiella spp. and Pseudomonas spp.; • Identified some gaps about resistance in Ghana: neglected regions and low-quality research.

Competing interests
The authors declare no competing interests.

Authors' contributions
Courage Kosi Setsoafia Saba created the idea and designed the study.

Acknowledgments
The authors wish to thank Molly D. Pither from Keele University for proofreading this paper. Table 1: isolation, antibiotic susceptibility test and focus of the study Table 2: summary of resistance rates findings     (1) [63] This table has been elaborated using the general data from bacteria, with no discrimination of region or sample origin a Methodology used to test the susceptibility of bacteria to antibiotic b Exclusive: studies that were conducted exclusively on this bacterium, without including other genera   Resistance rates are expressed in percentages (%) R: some of the resistances were not included in the articles as a numeric value but as resistant or not resistant. The cases w here bacteria were resistant to antibiotics but the rate is unknown have been written as an R. This table has been elaborated using the general data from bacteria, with no discrimination of region or sample origin. Antibiotics not tested in a bacteria were not included in the calculations of the total resistance of that bacteria