Antibiotic Treatment

Antibiotic-resistant infections are a major source of morbidity and mortality, and constitute a significant economic burden and a tangible threat to public health. The rate of development of antibiotic drugs has not kept pace with the rate of development of resistance in bacteria, which threatens the effectiveness of antibiotic treatments. According to the World Health Organization, bacterial resistance is “a problem so serious that it threatens the achievements of modern medicine. A post-antibiotic era, in which common infections and minor injuries can cause death, is not an apocalyptic fantasy but a very real possibility for the 21st century.”(1) According to the Centers for Disease Control and Prevention (CDC), the annual incidence of drug-resistant infections in the United States is approximately 2.8 million cases and the mortality burden is approximately 35,000 people (2). In Israel, mortality rates from infectious diseases are among the highest among OECD (Organization for Economic Co-operation and Development) countries. According to Ministry of Health data, in 2017-2019, sepsis was the fifth most common cause of death in Israel (4% of deaths in men and 5% in women). In contrast to other leading causes of death, such as cancer and heart disease, the mortality rate from sepsis in Israel has shown a consistent upward trend over the past decade (3).

The inappropriate use of antibiotics in both human medicine and agriculture is the most significant modifiable risk factor for the development of bacterial resistance (4,5). While attention has traditionally focused on antibiotic use in hospital settings, most antibiotic prescriptions—estimated at 80–95%—are issued in outpatient settings (6). Inappropriate antibiotic use is a widespread global concern. It is estimated that approximately 50% of outpatient antibiotic prescriptions are considered inappropriate in terms of indication, choice of agent, dosage, or duration of treatment (5). In the United States, approximately 30% of outpatient antibiotic prescriptions have been deemed inappropriate (7), with similar trends of overprescribing observed in outpatient care across the United Kingdom (8) and Europe. The most common indication for inappropriate antibiotic prescriptions is upper respiratory tract infections (7). In parallel with efforts to create incentives for the development of new antibacterial agents, vaccines, and rapid bacterial diagnostic tools, recent years have seen a growing emphasis on programs promoting the rational use of antibiotics as a crucial strategy in the fight against resistant infections. These programs were developed to monitor and improve the appropriate use of antibiotics by promoting the correct choice of the agent, dosage, duration and route of administration, with the aim of ensuring a better treatment outcome for the patient, reducing side effects, improving the bacterial susceptibility profile and optimal utilization of resources. An integral and important part of these programs is monitoring, reporting and tracking trends over time in the extent of antibiotic use, using measurement systems and quality indicators (5,9). Antibiotic consumption can be quantified using various methods, including Defined Daily Doses (DDD), the number of courses of antibiotic treatment, the number of prescriptions, the number of antibiotic drug packages, the total days of antibiotic treatment, and the proportion of prescriptions containing an antibiotic agent, among others. There is ongoing debate in the literature regarding the most appropriate measure for quantifying antibiotic consumption, as each method presents its own advantages and limitations. However, there is growing consensus that a more comprehensive reflection of consumption is achieved by utilizing multiple expressions (10–12). As part of the National Program for Quality Indicators in Community Healthcare in Israel, two methods are employed to quantify the extent of systemic antibiotic consumption in the community:

1.DDD (Defined Daily Doses) per 1,000 persons per Day. The DDD represents the estimated average daily maintenance dose for a drug when used for its primary indication in adults (1,13). This metric is utilized by the OECD and the World Health Organization to quantify the total volume of antibiotic consumption. By definition, the DDD is based on the average adult dose, even when used to quantify consumption in children. Since pediatric dosages vary by age and weight, this measure tends to underestimate antibiotic use in children compared to adults, and particularly in younger children compared to older ones. The two quality indicators of the National Program, based on DDD per 1,000 people per day, were adopted from the OECD and facilitate international comparisons among countries reporting to the organization (14).

2. The number of systemic antibiotic prescriptions issued per 1,000 persons per year. This expression is more intuitive to understand and better represents the extent of antibiotic use in children. In addition, the expression is used by the CDC to quantify antibiotic consumption in the USA, allowing for further international comparisons (15,16).

It is important to note that, alongside global efforts to reduce antibiotic use, there was a significant decline in antibiotic consumption in the community worldwide in 2020, during the COVID-19 pandemic. This reduction is attributed to the implementation of protective measures such as masks and social distancing, which led to a decrease in other respiratory infections, as well as a reduction in the accessibility and utilization of healthcare services in the community (15,17).