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J Antimicrob Chemother. 2016 Nov;71(11):3258-3267. Epub 2016 Jun 26.

Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study.

Author information

1
Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium surbhi.malhotra@uantwerpen.be.
2
Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
3
Centre for General Practice, Department of Primary and Interdisciplinary care (ELIZA), University of Antwerp, Antwerp, Belgium.
4
Department of Family and Community Medicine, Medical University of Lodz, Lodz, Poland.
5
Clinical Research Associates and Consultants, Bratislava, Slovakia.
6
Institute of Microbiology, Faculty of Medicine, Comenius University Bratislava, Bratislava, Slovakia.
7
Unit of R&D, Jönköping, Sweden.
8
Department of Clinical Sciences, Lund University, Lund, Sweden.
9
Hospital Clinic of Barcelona, Barcelona, Spain.
10
Cardiff University, Cardiff, UK.
11
Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, UK.
12
University Medical Center Utrecht, Utrecht, The Netherlands.
13
University of Southampton, Southampton, UK.

Abstract

OBJECTIVES:

To determine the effect of amoxicillin treatment on resistance selection in patients with community-acquired lower respiratory tract infections in a randomized, placebo-controlled trial.

METHODS:

Patients were prescribed amoxicillin 1 g, three times daily (n = 52) or placebo (n = 50) for 7 days. Oropharyngeal swabs obtained before, within 48 h post-treatment and at 28-35 days were assessed for proportions of amoxicillin-resistant (ARS; amoxicillin MIC ≥2 mg/L) and -non-susceptible (ANS; MIC ≥0.5 mg/L) streptococci. Alterations in amoxicillin MICs and in penicillin-binding-proteins were also investigated. ITT and PP analyses were conducted.

RESULTS:

ARS and ANS proportions increased 11- and 2.5-fold, respectively, within 48 h post-amoxicillin treatment compared with placebo [ARS mean increase (MI) 9.46, 95% CI 5.57-13.35; ANS MI 39.87, 95% CI 30.96-48.78; P < 0.0001 for both]. However, these differences were no longer significant at days 28-35 (ARS MI -3.06, 95% CI -7.34 to 1.21; ANS MI 4.91, 95% CI -4.79 to 14.62; P > 0.1588). ARS/ANS were grouped by pbp mutations. Group 1 strains exhibited significantly lower amoxicillin resistance (mean MIC 2.8 mg/L, 95% CI 2.6-3.1) than group 2 (mean MIC 9.3 mg/L, 95% CI 8.1-10.5; P < 0.0001). Group 2 strains predominated immediately post-treatment (61.07%) and although decreased by days 28-35 (30.71%), proportions remained higher than baseline (18.70%; P = 0.0004).

CONCLUSIONS:

By utilizing oropharyngeal streptococci as model organisms this study provides the first prospective, experimental evidence that resistance selection in patients receiving amoxicillin is modest and short-lived, probably due to 'fitness costs' engendered by high-level resistance-conferring mutations. This evidence further supports European guidelines that recommend amoxicillin when an antibiotic is indicated for community-acquired lower respiratory tract infections.

PMID:
27353466
DOI:
10.1093/jac/dkw234
[Indexed for MEDLINE]

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