Abstract
Research is lacking on the reversibility of antimicrobial resistance (AMR). Thus, we aimed to determine the influence of previous antibiotic use on the development and decay over time of third generation cephalosporin (3GC)-resistance of E. coli. Using the database of hospital laboratories of the Autonomous Province of Bolzano/Bozen (Italy), anonymously linked to the database of outpatient pharmaceutical prescriptions and the hospital discharge record database, this matched case-control study was conducted including as cases all those who have had a positive culture from any site for 3GC resistant E. coli (3GCREC) during a 2016 hospital stay. Data were analyzed by conditional logistic regression. 244 cases were matched to 1553 controls by the date of the first isolate. Male sex (OR 1.49, 95% CI 1.10–2.01), older age (OR 1.11, 95% CI 1.02–1.21), the number of different antibiotics taken in the previous five years (OR 1.20, 95% CI 1.08–1.33), at least one antibiotic prescription in the previous year (OR 1.92, 95% CI 1.36–2.71), and the diagnosis of diabetes (OR 1.57, 95% CI 1.08–2.30) were independent risk factors for 3GCREC colonization/infection. Patients who last received an antibiotic prescription two years or three to five years before hospitalization showed non-significant differences with controls (OR 0.97, 95% CI 0.68–1.38 and OR 0.85, 95% CI 0.59–1.24), compared to an OR of 1.92 (95% CI 1.36–2.71) in those receiving antibiotics in the year preceding hospitalization. The effect of previous antibiotic use on 3GC-resistance of E. coli is highest after greater cumulative exposure to any antibiotic as well as to 3GCs and in the first 12 months after antibiotics are taken and then decreases progressively.
Highlights
The introduction of penicillin in the 1930–1940s initiated the antibiotic era, which contributed significantly to the global decrease of morbidity and mortality due to communicable diseases [1]
The analysis showed that independent risk factors for being infected or colonized by 3GC resistant E. coli (3GCREC) are the following: male sex, older age, the number of different antibiotics taken in the previous five years, at least one antibiotic (J01) prescription in the previous year, and the diagnosis of diabetes
Over a 5-year period, the risk of developing a community acquired infection due to 3GCREC increases significantly in patients who were exposed to antibiotics previously, with the highest risk observed for antibiotics taken in the last 12 months and for greater cumulative exposures to any antibiotic as well as to 3GCs
Summary
The introduction of penicillin in the 1930–1940s initiated the antibiotic era, which contributed significantly to the global decrease of morbidity and mortality due to communicable diseases [1]. Antimicrobial resistance (AMR), likely due to natural selection occurring when microorganisms are exposed to antimicrobial drugs, emerged shortly afterwards [2,3]. This prompted the search and development of new effective antibiotics but, since the antibiotic pipeline is running dry, the world is facing the threat of a post-antibiotic era. In addition to AMR, the excessive use of antibiotics has been recently reported to have consequences beyond the clinical setting, the impact of which is only beginning to be appreciated [3]. Reducing unnecessary antibiotic use is a pivotal strategy to preserve the efficacy of these drugs and to reduce unintended effects [4,5]. It is estimated that every year in Europe 33,000 people die due to infections caused by antibiotic resistant bacteria with approximately one third of these deaths (namely 10,762) occurring in Italy [6]
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