Impact of Selective Reporting of Antibiotic Susceptibility Test Results in Urinary Tract Infections in the Outpatient Setting: a Protocol for a Pragmatic, Prospective Quasi-experimental Trial

Antibiotic resistance (ABR) is a serious and increasing worldwide threat to global public health. It has been estimated that multidrug-resistant bacteria affect 158.000 French persons annually, of whom 12.500 die from these infections. In France, the increase of multidrug resistance among Enterobacteriaceae is the most alarming: the prevalence of Escherichia coli resistant to third generation cephalosporins and to fluoroquinolones has dramatically increased in the last decade and has reached now 11% and 17%, respectively. More than 90% of antibiotics used in humans in France are prescribed to outpatients (70% by general practitioners) and urinary tract infections (UTIs) account for a considerable proportion of these prescriptions (15% of all outpatient prescriptions, about 10 million of prescriptions each year) with E. coli being the pathogen most frequently (70-95%) isolated in community-acquired UTIs. Antibiotic stewardship programmes aim both at limiting antibiotic therapy to proven or strongly suspected non-self-limiting bacterial infections, and at reducing broad-spectrum antibiotics' use, such as amoxicillin-clavulanate, cephalosporins and fluoroquinolones. So, two goals are pursued: to avoid unnecessary antibiotic use, and to limit inappropriate antibiotic prescribing. Several studies have shown that half of antibiotic prescriptions for UTIs in primary care are either unnecessary or inappropriate, and that general practitioners (GPs) prescribe more antibiotics than necessary. Broad-spectrum antibiotics (in particular amoxicillin-clavulanate, cephalosporins and fluoroquinolones) are frequently inappropriately prescribed in UTIs, whereas first-line and narrow-spectrum antibiotics (e.g. amoxicillin, nitrofurantoin, fosfomycin, etc.) would have been sufficient to treat the infection.

One strategy recommended by French national authorities and by international recommendations to limit the inappropriate over-prescription of broad-spectrum antibiotics is the use of selective reporting for antibiotic susceptibility test (AST) results. Selective reporting means that AST are reported back to the practitioner only for few (n=5-6) antibiotics, those that should be used first-line according to guidelines. However, the laboratory is still testing all the 20-25 antibiotics reported in the usual complete AST, and susceptibility results not mentioned in the selective reporting of AST are available at the practitioners' request to the microbiologist. Data usually used to determine which antibiotics to report for urine samples are the isolated microorganism, the patient's age and gender, and the list of antibiotics recommended in national guidelines. For example, in a wild-type E. coli isolated in urine in an adult woman, the only antibiotics to report could be amoxicillin, trimethoprim/sulfamethoxazole, nitrofurantoin, fosfomycin and pivmecillinam. To date however, even if recommended by the French authorities, selective reporting of AST is still limited to rare local initiatives. Two randomised controlled case-vignette surveys conducted among junior medical doctors and GPs in France revealed that selective reporting of AST could improve the appropriateness of antibiotic treatment for UTIs and decrease the prescription of broad-spectrum antibiotics, while being well accepted by most physicians. However, these two surveys used fictitious clinical vignettes and no study has yet been conducted in the 'real life' French health context to evaluate the impact of selective reporting of AST on antibiotic prescribing.

METHODS

Study objectives

The main objective of this study is to assess the impact of selective reporting of AST for E. coli positive urine cultures in adult outpatients on the prescription of broad-spectrum antibiotics frequently used in UTIs (amoxicillin-clavulanate, third generation cephalosporins and fluoroquinolones). These antibiotics/classes have been indeed flagged since 2013 as 'critical' antibiotics (i.e. antibiotics with a higher risk of selection of bacterial resistance) by the French Medicines Agency, in line with the recent AWaRe categorisation introduced by the WHO in its Essential Medicines List. Secondary objectives are to evaluate the feasibility of the selective reporting of AST implementation by French laboratories and their acceptability by GPs and laboratory professionals (microbiologists, technicians and secretaries).