Incomplete doses of antibiotics lead to resistance: fact or myth?

Antibiotic resistance is a growing global problem. According to the World Health Organization (WHO) Antibiotic Resistance Monitoring System (Global Antimicrobial Resistance Monitoring and Use System), for example, E coli has 8.4-92.9% resistance to ciprofloxacin. [1]. Three mechanisms are primarily believed to drive resistance:

• Horizontal gene transfer across plasmids with genes coding for antibiotic resistance (often several resistance genes with the same plasmid)
• The proliferation of antibiotic-resistant bacteria due to the selective pressure caused by antibiotics, and
• Mutation and recombination in bacterial DNA [2].

Multiple resistant bacterial strains (eg ESBL-karba, MRSA, VRE) pose a growing challenge to health care in the treatment of infections. [1, 3]. In sub-Saharan Africa, for example, multiresistant bacterial strains have led to a high prevalence of antibiotic resistance in neonatal sepsis. [4].

The theory that incomplete antibiotic regimens contribute to the development of resistance is spreading on social media but is also being addressed by the World Health Organization [5]. The message that you must complete the full course of prescribed antibiotics is being sent by both 1177 Vårdguiden and Uppsala University. [6, 7]. A systematic review (54 studies from Europe, Asia, and North America) shows that 62 percent of study participants believed that they contributed to the development of resistance if they stopped taking antibiotics prematurely. [8]. This theory is believed to have originated in 1941, when the patient first became worse and eventually died of staphylococcal sepsis when penicillin ran out. [9]. This misconception also occurs among medical colleagues and medical students.

However, the evidence for the theory is limited: on the contrary, it is the excessive and very prolonged administration of antibiotics that drives resistance, creating selective pressure on bacteria in the body’s natural flora. This promotes the growth of resistant bacterial strains, which can lead to the spread of resistance genes [10]. Studies that have determined the effects of shorter courses of antibiotics show no results indicating increased resistance, although the results have sometimes been worse. [11, 12].

More and more randomized studies are showing that short courses do not necessarily have a worse clinical effect in conditions such as pneumonia, tonsillitis, pyelonephritis, osteomyelitis, abdominal infections, cellulite and COPD exacerbations, and in Sweden many treatment guidelines have been updated. [13-21]. However, there are cases in which a short treatment period leads to poor outcomes and more symptoms in the patient, and therefore it is important that the changing guidelines are based solely on evidence. [11].

In the UK, more than 80 per cent of antibiotic regimens for upper respiratory tract infection (OTI) and 54.6 per cent of acute cystitis in women were longer than recommended. [22] (which is remarkable, among other things, because antibiotics are only found in the exceptional cases mentioned in ÖLI), and in the United States, 67.8 percent of patients in Michigan hospitals received extended courses of antibiotics [14]. In a study from Canada, GPs with long professional experience often prescribe courses of antibiotics in excess of the recommended duration of colleagues with shorter time in the profession, which may indicate that changing guidelines may be under the radar of parts of the occupational group [23].

The focus should be shifted from “the antibiotic regimen should always end” to a more restrictive prescription. A shorter treatment time should be used when evidence provides support. There is a need for increased education and knowledge about new findings and updated treatment guidelines, better prescribing feedback in health centers and hospitals on number of prescriptions and length of courses, and clear and accessible information about changing guidelines.

Since overuse of antibiotics is primarily what drives the development of resistance, education and recommendations must be designed accordingly.

Lakartedningen 1-2 / 2021

Lakartidningen.se 2021-01-12
(Updated 2021-01-14)