Consommation et mésusage des antibiotiques - infections respiratoires

par Sally Yaacoub

Projet de thèse en Santé publique - épidémiologie

Sous la direction de Patrick Maison.

Thèses en préparation à Paris Est , dans le cadre de École doctorale Santé Publique (Le Kremlin-Bicêtre, Val-de-Marne ; 2015-...) , en partenariat avec ANSM - Direction de la Surveillance (laboratoire) depuis le 30-11-2018 .

  • Résumé

    L'utilisation irrationnelle d'antibiotiques, autrefois appelés «médicaments miracles», a entraîné une résistance accrue aux antibiotiques, un problème mondial [1]. Le taux élevé de consommation d'antibiotiques (ATB), associé à son utilisation abusive, a créé un environnement propice à l'apparition de résistance bactérienne [2]. En particulier, les antibiotiques sont fréquemment utilisés de manière irrationnelle dans les infections des voies respiratoires courantes en médecine de ville [3]. La surveillance de l'évolution et les caractéristiques de la consommation d'antibiotiques dans un pays développé ou non est particulièrement importante afin de programmer des actions efficientes de lutte contre l'antibiorésistance. Par ailleurs les études dans les pays en développement, comme le Liban, se concentrant sur l'utilisation abusive d'antibiotiques dans les infections respiratoires, et sur les prescripteurs (médecins ou pharmaciens) sont rares. Grâce à ces études, il sera plus facile de comprendre les déterminants de l'utilisation des antibiotiques dans les deux types de pays.

  • Titre traduit

    Antibiotics overuse and misuse - Respiratory tract infections

  • Résumé

    The irrational use of antibiotics, the once named “miracle drugs”, has led to an increased antibiotic resistance, a worldwide problem [1]. The high rate of antibiotic (ATB) consumption, coupled with its misuse created an environment for resistance to emerge [2]. In specific, antibiotics are frequently used irrationally in many cases of respiratory tract infections (RTIs) since they were dubbed among the most common and important problems in clinical medicine [3]. Study that tackles the evolution and characteristics of the consumption of antibiotics in a developed or in developing country are particularly important to determine efficient public health action against antibiotics resistance and misuse. Studies in a developing country, like Lebanon, that focus on antibiotic misuse in RTIs and prescribers are scarce. Through these studies, it will be easier to understand the trend of use of antibiotics in both types of countries. Thesis Detailed Overview Antibiotics are considered the greatest discovery of the twentieth century. In the pre-ATB era, infectious diseases accounted for significant morbidity and mortality until the discovery of antibiotics changed this reality [4]. However, the wonders of ATBs did not last long due to the emergence of resistant bacterial strains which are still increasing in prevalence [5]. The acquired ability of bacteria to avoid the antibacterial actions and effects is rising to dangerously high levels worldwide. New resistance mechanisms are emerging and spreading globally causing a serious worldwide threat to the wellbeing of patients and the quality of health care [6]. It leads to longer hospital stays and increased mortality especially that without effective antibiotics, the success of major surgeries and cancer chemotherapy would be compromised. Moreover, the cost of health care for patients with resistant infections is higher than those with non-resistant infections. This is due to longer duration of illness, additional tests and use of more expensive drugs [7]. Antibiotic-resistant infections are already widespread across the globe [8]. It is estimated that at least every 10 minutes in the United States or Europe, a patient dies from a fatal infection caused by a resistant bacterium [9]. The Centers for Disease Control (CDC) declared that the human race is now in the “post-antibiotic era”, in 2013. Moreover, in 2014, the World Health Organization (WHO) warned that the antibiotic resistance crisis is dreadful [10]. Although antibiotic resistance occurs naturally, other important factors augment this crisis. According to the WHO, the overuse of antibiotics is one of the foremost causes of the emergence of multi-drug resistant (MDR) bacteria [11]. In addition, epidemiological studies have demonstrated a direct relationship between antibiotic consumption and the emergence and dissemination of resistant bacteria strains. Despite warnings regarding overuse, antibiotics are overprescribed worldwide [12]. In Europe, some countries such as Greece and France are using three times the amount of ATBs per head of population compared to other countries like Netherlands, with similar disease profiles [13]. In 2015, the European Union/European Economic Area (EU/EEA) population-weighted mean consumption of antibiotics for systemic use in the community was 22.4 defined daily doses (DDD) per 1000 inhabitants and per day. The consumption ranged from 1.0 package per 1 000 inhabitants and per day in Sweden to 4.7 packages per 1 000 inhabitants and per day in France. In addition, the EU/EEA population-weighted mean consumption of carbapenems, a last-line group of antibiotics used to treat patients infected with multidrug-resistant bacteria, did not show any significant trend during 2011‒2015. However, in six countries, (Bulgaria, Croatia, Cyprus, Greece, Hungary and the Netherlands), there was a significant increasing trend during the same period [14]. In fact, there is a high rate of wide spectrum ATB consumption in the Mediterranean region. In Saudi Arabia, for instance, all ATBs use amounted to 25,171 standard units per 1000 population in 2000. By 2010, this number rose to 32,272. In Egypt, ATB drug intake experienced a similar hike, the consumption climbed from 16,654 standard units per 1000 population in 2000 to 24,734 by 2010 [15]. In Lebanon, a study has shown that broad spectrum antibiotics (such as 3rd generation cephalosporins and quinolones) are extensively consumed, where more than 15% of the total national consumption consisted of quinolones [16]. The high rate of ATB consumption alongside ATB misuse (improper use outside the intended purpose, scope, or guidelines for use) with regards to indication, selection, dosage, and duration of therapy, favors the emergence of resistance [2,17]. This irrational use of ATBs occurs in animals and in agriculture, as well. Unfortunately, while resistance to older ATBs is increasing, the pipeline for new generations of ATBs by the pharmaceutical industry is dried up [18]. Since the overuse and misuse of ATBs is the utter most reason for the emergence of bacterial resistance, it is worth to mention that many different factors are associated with this misuse. The major forces can be categorized as those deriving from prescribers including physicians and pharmacists (in many countries including Lebanon) [19]. The physician's role to irrational antibiotic use mainly lies in irrational prescribing. Some factors are: lack of up-to-date knowledge (of diagnosis, therapeutics, evidence-based medicine and the consequences of irrational ATB use), inadequate training and education of medical graduates, poor communication with patients and underutilization of diagnostic tools [20]. The pharmacists' major misuse is antibiotic prescribing, together with inadequate quality of prescribing and counseling. Although dispensing of antibiotics without a medical prescription, nonetheless the prescribing of antibiotics, is prohibited by laws, it is still evident in many countries, like Lebanon, especially for common infections like acute rhinosinusitis [21]. Therefore, ATB resistance, with its multifaceted contributors, constitutes a major health threat worldwide, including Lebanon. This may be due to the lack of regulation in human use, lack of surveillance of ATB use and resistance and national guidelines for the management of infectious diseases, lack of continuing medical education on ATB use for prescribers, and lack of microbiological lab capacity/lab training/diagnostic tools. Antibiotics are frequently used irrationally in many cases of respiratory tract infections since they are a frequent cause of medical consultations. In developed countries, acute respiratory infections (ARI) account for the majority of antibiotic prescriptions written, 20% of all medical consultations and over 30% of lost days from work. In developing countries, nearly 20% of mortality in children under the age of 5 years can be attributed to ARI [22]. In addition, RTIs represent the third most frequent health problem for international travelers [23]. Although the majority (>80%) of such infections are viral in etiology and thus do not require ATB treatment, they account for three-quarters of all human ATB consumption [3]. The WHO estimated that up to 60% of people with viral RTIs receive ATBs inappropriately [24]. It has been also reported that inappropriate ATB consumption has an essential role in the development of beta- lactam- resistance pneumococcal, and in the dissemination of MDR Streptococcus pneumoniae, macrolide-resistant Streptococcus pyogenes, and methicillin-resistant Staphylococcus aureus [25]. In developing and transitional countries, while only 70% of pneumonia cases receive an appropriate ATB, about half of all acute upper RTI cases receive ATBs inappropriately [13]. Thus, making RTIs a great interest to dig more into the depths of the antibiotics used for the treatment of these infections. However, national studies about ATB misuse in RTIs in an Arab country like Lebanon are lacking. Lebanon is especially essential to study since alarming resistance rates have been reported. In addition, the lack of regulation in human use, surveillance of ATB use and resistance, national guidelines for the management of infectious diseases, continuing medical education on ATB use for prescribers, and microbiological lab capacity/lab training/diagnostic tools, are all major factors of resistance present in Lebanon. Studies in a developing country, like Lebanon, that focus on antibiotic misuse in RTIs, tackling the prescribers in the society: physicians and pharmacists are scarce. In addition, a study that tackles the evolution and characteristics of the consumption of antibiotics in a developed country, like France, is almost non-existent. Through these studies, it will be easier to understand the trend of use of antibiotics in both types of countries. A study is to be conducted in Lebanon to explore ATB misuse in RTIs by prescribers (physicians and pharmacists). In addition, a study about the evolution and characteristics of the consumption of antibiotics in France over the last thirty-two years and determining if it is related to RTIs, is a must. France is of special interest since many regulations and authorities control and monitor ATB use and thus, the effect of all the measures implemented will be studied. Finally, a systematic review will be conducted to study the prevalence of antibiotic misuse and its related factors in respiratory tract infections. All of the studies aforementioned aim to identify the factors associated with this health-threatening problem in hopes of finding the proper interventions and regulations, which will hinder resistance and its consequences. The major goal of this project is not to only address ATB utilization, but to improve the worldwide practice.