MODIFICATION OF ANTIBIOTIC TREATMENT THROUGH POTENTIATION OF ITS EFFECT

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CHAPTER ONE

INTRODUCTION

Antimicrobial resistance is the ability of a microorganism to prevail against the effects of anantibiotic 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 limittheir 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 were 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. (Spellberget 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).

Anadditional 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.

  1. Statement of problem

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.

MODIFICATION OF ANTIBIOTIC TREATMENT THROUGH POTENTIATION OF ITS EFFECT