Clarithromycin treatment selects for persistent macrolide-resistant bacteria in throat commensal flora

https://doi.org/10.1016/j.ijantimicag.2004.08.011Get rights and content

Abstract

The aim of the study was to determine the effect of clarithromycin treatment on resistance development in the commensal throat flora. Alpha-haemolytic streptococci and Neisseria spp. were isolated from patients receiving clarithromycin for eradication of Helicobacter pylori. The treatment resulted in an immediate increase in the number of macrolide-resistant streptococci, which remained for one year after treatment, but declined to background level three years later. The most prevalent resistance gene was mef(A). Neisseria spp. were less affected by the treatment: the number of resistant isolates increased in only in one case during treatment. In conclusion, a one-week standard therapy with clarithromycin selects for an increased prevalence of macrolide-resistant streptococci that persisted for more than one year.

Introduction

Antibiotic treatment affects not only the pathogen that is the target of treatment, but all bacteria of the body flora. The selective pressure for development of antibiotic resistance will, thus, be as great among the commensal flora as among pathogens. Some commensal bacteria are genetically related to pathogenic bacteria and can, thus, serve as resistance reservoirs from where resistance genes may be transferred to pathogenic bacteria during an infection.

Helicobacter pylori colonizes the human gastric mucosa and has emerged as an important pathogen in the field of gastroenterology [1]. About half of the population in the western world currently carries H. pylori (1), but only 15% of these will develop symptoms requiring treatment. A common treatment consists of a one-week therapy with omeprazole, clarithromycin and metronidazole [2], [3]. The two antibiotic components are standard drugs against other serious infections: clarithromycin, for the treatment of upper respiratory tract infections and metronidazole for infections caused by anaerobic bacteria and protozoal parasites. If use of these antibiotics selects for drug resistance in the commensal flora, more protracted use could result in a reduction of the ability to treat other serious infections using standard drug therapy.

In order to determine the long-term effects of H. pylori eradication on the commensal flora, a study was performed on dyspeptic patients in Sweden. As representatives for the commensal throat flora, α-haemolytic Streptococcus spp. and Neisseria spp. were chosen, since these genera have closely related pathogenic species (Streptococcus pyogenes, Streptococcus pneumoniae and Neisseria meningitidis).

Individual bacterial isolates from throat specimens collected at different time points were compared to detect possible effects of the treatment, regarding the level of clarithromycin resistance, the presence of macrolide resistance determinants and any changes in the presence of specific clones of bacteria.

Section snippets

Patients and strains

The throat specimens originated from a clinical study in Sweden concerning the development of antibiotic resistance during treatment of H. pylori infections. It was ensured that none of the patients enrolled had received antibiotics within four weeks prior to the study, and that they did not consume any additional antibiotics during the study period.

The treatment consisted of omeprazole (20 mg), metronidazole (400 mg), and clarithromycin (250 mg), twice daily for one week. The full study covered

Effect of clarithromycin treatment on the level of macrolide resistance in throat streptococci

The general study outline is presented in Section 2. From the full study, 12 treated patients and 2 untreated controls were selected based on the results from the initial screening. The rationale was to have a distribution from susceptible to highly resistant isolates in the samples collected one year after treatment. Seven to ten individual colonies of streptococci were isolated from each throat swab and tested for clarithromycin resistance by disc diffusion test (Fig. 1). The general trend

Discussion

This study was designed to record the long-term effects of a one-week antibiotic treatment on the commensal throat flora of bacteria. A previous Swedish study has recorded the general effect on the commensal microbial flora after standard H. pylori treatment [11], and reported a substantial increase in resistant bacteria directly after treatment and continuing presence of resistant microorganisms 35 days after treatment. This is in agreement with our results on throat streptococci, although we

Acknowledgements

We thank Karin Wreiber for keeping track of all samples and help with retrieving samples for this investigation. Thanks also to the students Adriano Atterman, Elisabeth Bobek, Laila Bucht, Andreas Dahlgren, Björn Eklund and Jordi Font Cot for all help in performing the experimental work. This work was supported by a grant from the AFA Health Fund.

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