Antibiotics Potentiation With Plant Products – A Review A Research Project

ABSTRACT

Antibiotic resistance has continued to present unprecedented public health problems to mankind. Microorganisms have continued to develop various forms of resistance to virtually all the agents used against them. Scientists have continuously sought for ways of keeping these disease causing agents in check. The discovery that some plant chemical substances which may or may not have antimicrobial properties have the ability to potentiate the effects of some antibiotics which have lost potency due to resistance, has opened a new lead to tackling antibiotic resistance. This work reviews some efforts made so far to combine antibiotics and plant chemical products for a potentiation and possible restoration effect.

 

 

CHAPTER ONE

INTRODUCTION

Antimicrobial resistance is the ability of a microorganism to prevail against the effects of an antibiotic that it was once susceptible to (Nordberg et al., 2017). It canalso be referred to as the ability of microbes to grow in the presence of a drug that would normally kill them or limit their growth, it is a major global public health concern. The rapid emergence of resistant bacteria is occurring worldwide. Internationally, there is a growing concern over antimicrobial resistance (AMR) which is currently estimated to account for more than 700,000 deaths per year worldwide(Neil, 2016)A number of  reviews have summarized AMR data in Africa. Most recently the work of Leopold et al.,  (2014) which focused on Sub-Saharan Africa, reported a high level of resistance to the commonly used antibiotics in the Sub-Saharan African region. In it 90% of Gram negatives organism was resistant to chloramphenicol, a commonly used antibiotic. In contrast, resistance to third-generation cephalosporins (like ceftriaxone) was low, recommending this group for use. Antimicrobial resistance affects all age group and sex that can be infected with microorganism.

The extensive use of antibiotics over the last 50 years has led to the emergence of bacterial resistance and to the dissemination of resistance genes among pathogenic microorganisms. This resistance can be caused byincorrectly prescribed antibiotics which contribute to the promotion of resistant bacteria. Studies have shown that treatment indication, choice of agent, or duration of antibiotic therapy is incorrect in 30% to 50% of cases (Luyt et al., 2011). This emergence is endangering the efficacy of antibiotics, which have transformed medicine and saved millions of lives. (James and Anthony, 2014). The antibiotic resistance crisis has been attributed to the overuse and misuse of these medications, as well as a lack of new drug development by the pharmaceutical industry due to reduced economic incentives and challenging regulatory requirements. (Viswanathan et al., 2014). These Antibiotic abuses contributing to the emergence of antimicrobial resistance differ depending upon geographical Location. (Prestinaci et al., 2015). Practices such as Over-the-counter use of antibiotics and their use as “folk” remedies have contributed to antibiotic resistance in developing countries.(Morgan et al.,2011) In other areas, antibiotic abuse in prophylactic and empiric therapy, and misuse of the newest drugs for questionable indications in the community have been major contributors to antimicrobial resistance. Incorrerrectly prescribed antibiotics has led to questionable therapeutic benefit and expose patient to potential complications of antibiotic therapy.

Bacteria has developed various mechanism of resistance. Consequently, infectiousdiseases remain one of the leading causes of morbidity worldwide.In Nigeria, tuberculosis, respiratory infections and diarrheal disease are leading causes of infectious disease morbidity and mortality. The spread of Methicillin-resistant Staphylococcus aureus (MRSA). An emerging pathogen and public health threats result from the spread of hospital-acquired as well as community-acquired MRSA and livestock associated MRSA. (Ayliffe et al., 1997).

Most old and cheap antibiotics such as the penicillin’s, the tetracyclines anderythromycin have been rendered ineffective due to the emergence of antibiotic resistance. Enterococcus strains are resistant to vancomycin, ampicillin, gentamycin and streptomycin, (Montecalvo et al., 1994). Gram negative pathogens such as Salmonella species, Pseudomonas aeruginosa, Klebsiella pneumonia have become multi-drug resistant. There are high rates of resistance to ceftriaxone, ampicillin and cotrimoxazole. Most organisms demonstrated 100% resistance to ampicillin and cotrimoxazole whichhave long been used as first line drugs in the treatment of UTI. (Federal Ministries of Agriculture, Environment and Health, 2017).The loss of clinical efficacy of this effective first-line drugs, means that treatment of infections, as a result has to be shifted to second-line or third-line antibiotics that are often more expensive with numerous side effects.(Brook et al., 2000). Antimicrobial resistance has also lead to longer hospital stays, more doctor’s visit and lengthier recuperation, higher medical costs and increased mortality. The duration of stay in hospitals as a result of antimicrobial resistance is said to be increased by 6.4 to 12.7 days. (Spellberg et al., 2014). The growing number of infections such as pneumonia, tuberculosis, gonorrhea, and salmonellosis are becoming harder to treat as the antibiotics used to treat them become less effective.

The growing misuse of antibiotics and chemotherapeutic agents leading to drug resistance is now pushing a considerable proportion of people in both developed and developing countries to the use of herbal medicines. Despite several agents being commercially available, these chemicals can alter oral microbiota and have undesirable side-effects such as vomiting, diarrhea and tooth staining  (Park et al., 2003): (Chung et al., 2006). For example, bacterial resistance to most (if not all) of the antibiotics commonly used to treat oral infections (penicillins and cephalosporins, erythromycin, tetracycline and derivatives and metronidazole) has been documented (Bidault et al., 2007).

Pharmaceutical industries no longer consider antibiotic development as a wise economic development because antibiotics are used for short terms and are curative, antibiotics are not as profitable as drugs used in chronic disease such as diabetes, psychiatric disorders, hypertension, gastroesophagal reflux etc. (Piddock. 2012), this has ledto the lack of new antibiotic development by the industries,as a result itadds considerable cost to the nations overburdened health care system.

These outbreaks of antibiotic resistance can be prevented through the urgent need for more cautious use of antibiotics inboth human and veterinary medicine, particularly in the food production. There is a great need for strengthening the curriculum of human and veterinary health care professionals in the areas of sterilization and disinfection, mechanisms of antibiotic resistance, and factors contributing to its spread, including inappropriate antibiotic usage.

Antimicrobial stewardship which is the optimal selection, dosage, and duration of antimicrobial treatment that results inthe best clinical outcome for the treatment or prevention of infection, with minimal toxicity tothe patient and minimal impact on subsequent resistance has been introduced to reduce the occurrence of antimicrobial resistance (Doron et al.,2011).

The optimal care of an infected patient meanstreating with the correct, properly dosed antibiotic and one that has the least likelikelihood ofcausing collateral damage (i.e., leading to resistance in the patient or his or her contacts).

An additional benefit of programs that aim to optimize antibiotic use is that they generally experiencecost savings because fewer doses of antibiotic are used and less expensive antibiotics are chosen. Another method which have been proposed to curb the effect of antibiotic resistance is the use of Vaccines, though there is no vaccine that specifically targets antibiotic resistant bacteria (Shinefiel  et al., 2002).

However, immunization is an effective control measure to reduce spread of certain microorganisms between individuals and reduce the number of carriers of these pathogens. Vaccines that prevent common bacterial infections where resistance has emerged, may contribute to reducing the burden of antibiotic resistance. In addition, reduced burden of bacterial infections may result in a lower antibiotic use, thus reducing the likelihood of resistance emerging. One example is the introduction of the multivalent pneumococcal conjugate vaccine to prevent invasive pneumococcal infections in young children, there is now evidence that the vaccine not only reduces the incidence of invasive pneumococcal infections, but also to some extent reduces infections caused by resistant strains in the vaccinated children. In addition, it reduces the transmission of resistant strains to their siblings and to adults. (Fattom et al., 2004).

New vaccines for the prevention of bacterial infections, as well as antibodies, are in the pipeline of several companies. The genomic technique has promoted development of vaccines for bacterial infections. Many new antigens with properties that could overcome the limits of previous vaccine candidates have been identified through “reverse vaccinology”. This genome-based approach is being applied to streptococci, Chlamydiae, staphylococci and Yersinia pestis. (Rappuoli et al., 2003). These vaccines are likely to be expensive and indicated to prevent infections in selected high-risk patients.

The extensive use of antibiotics over the years has led to the development of resistance. This has lowered the efficacy of some currently used antibiotics which were previously susceptible to certain organisms, thereby hindering proper treatment of this organism in infected individuals. This therefore calls for modification of antibiotic treatment through potentiation of its effect.

1.2. Justification of Study

Due to the increased rate of antibiotics resistance, there is need to address and suggest possible solutions to this problem as this will help in reducing the rate of death caused by infectious diseases. More research should therefore be done to further ensure the total eradication of antimicrobial resistance.

In light of the serious threat of emerging antimicrobial-resistant pathogens and the realization that new drugs to effectively treat these pathogens are several years away, greater emphasis must be placed upon research related to rapid and reliable diagnostic tests vaccines for prevention and control of infectious diseases and reduction of the rate of antibiotics resistance by microorganism. Basic research is needed to more clearly delineate mechanisms of antibiotic resistance and to identify new ways of resolving this problem such as the potentiation of antibiotic with plant products. Several research have been carried out which have shown the possibility of antibiotic potentiation with plants products which will be discussed in this review. This work is aimed at reviewing available literature on the possible ways of potentiating the antimicrobial action of currently used antibiotics with plant products.

1.3 Aims and Objectives

To review available literature on the use of Plant products and antbiotics in combination for the control of resistant microorganism.

1.4    Review of Related Literature

1.4.0 Antibiotics

1.4.1 Definition of Antibiotics

Antibiotics are antimicrobial traditionally defined as natural compounds, produced by microorganisms, that kills microrganisms or stop their growth Their mechanism of action is either through killing the microbes (microbicidal effect) or by inhibiting their growth (biostatic effect). (Antimicrobial Merriam Webster online dictionary).  The discovery of antibiotics had eradicated the infections that once ravaged humankind. But their indiscriminate use has led to the development of multidrug-resistant pathogens.  (Chanda and  Rakholiya 2011) Antibiotics that work today may not work tomorrow. It is therefore essential to investigate newer drugs to which there is lesser resistance sakar et al 2003). The term antibiotic was coined from the word „antibiosis‟ which literally means „against life‟. In the past, antibiotics were considered to be organic compounds produced by one microorganism which are toxic to other microorganisms (Russell, 2004). Although antibiotic generally refers to antibacterial, antibiotic compounds are differentiated as antibacterials, antifungals and antivirals to reflect the group of microorganisms they antagonize (Brooks et al., 2004; Russell, 2004)

 

1.4.2 History of antibiotics

Louis Pasteur & Robert Koch recognized bacteria as a causative organism and recognized need to control them. It evolved to the era of plant extract use Quinine which was used for the treatment of malaria and Ipecacuanha root was used as an emetic in dysentery. Toxic metals such asMercury (against syphilis) and Arsenic  Arsenic(Atoxyl), against Trypanosoma, dyes were also used such as trypan blue and prontosil. Then Paul Ehrlich started the science of chemotherapy which works by selective toxicity. He developed the chemotherapeutic index.

Chemotherapeutic index

Alenxander Fleming who discovered penicillin from penicillium notatum a fungus which inhibited staphylococci in (1928), and was first used in a patient in 1942. The introduction of penicillin marked the beginning of the so-called “golden era” of antibiotics. Selman Waksman developed Streptomycin (1943) extracted from streptomyces,active against all Gram negatives and first active against mycobacterium tuberculosis.

1.4.3   Classification of Antibiotics

There are several ways of classifying antibiotics but the most common classification schemes are based on their molecular structures, mode of action and spectrum of activity (Calderon and Sabundayo, 2007)

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