Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study.
<h4>Objectives</h4> <p>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.</p> <h4>Methods</h4> <p>Patients were prescribe...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2016
|
| _version_ | 1826268357701140480 |
|---|---|
| author | Malhotra-Kumar, S Van Heirstraeten, L Coenen, S Lammens, C Adriaenssens, N Kowalczyk, A Godycki-Cwirko, M Bielicka, Z Hupkova, H Lannering, C Mölstad, S Fernandez-Vandellos, P Torres, A Parizel, M Ieven, M Butler, C Verheij, T Little, P Goossens, H |
| author_facet | Malhotra-Kumar, S Van Heirstraeten, L Coenen, S Lammens, C Adriaenssens, N Kowalczyk, A Godycki-Cwirko, M Bielicka, Z Hupkova, H Lannering, C Mölstad, S Fernandez-Vandellos, P Torres, A Parizel, M Ieven, M Butler, C Verheij, T Little, P Goossens, H |
| author_sort | Malhotra-Kumar, S |
| collection | OXFORD |
| description | <h4>Objectives</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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 MI23.06, 95% CI 27.34 to 1.21; ANS MI 4.91, 95% CI24.79 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).</p> <h4>Conclusions</h4> <p>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.</p> |
| first_indexed | 2024-03-06T21:08:29Z |
| format | Journal article |
| id | oxford-uuid:3d4e1c2c-d839-4cd9-b2a1-27a537b1198c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:08:29Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:3d4e1c2c-d839-4cd9-b2a1-27a537b1198c2022-03-26T14:18:45ZImpact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3d4e1c2c-d839-4cd9-b2a1-27a537b1198cEnglishSymplectic Elements at OxfordOxford University Press2016Malhotra-Kumar, SVan Heirstraeten, LCoenen, SLammens, CAdriaenssens, NKowalczyk, AGodycki-Cwirko, MBielicka, ZHupkova, HLannering, CMölstad, SFernandez-Vandellos, PTorres, AParizel, MIeven, MButler, CVerheij, TLittle, PGoossens, H <h4>Objectives</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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 MI23.06, 95% CI 27.34 to 1.21; ANS MI 4.91, 95% CI24.79 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).</p> <h4>Conclusions</h4> <p>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.</p> |
| spellingShingle | Malhotra-Kumar, S Van Heirstraeten, L Coenen, S Lammens, C Adriaenssens, N Kowalczyk, A Godycki-Cwirko, M Bielicka, Z Hupkova, H Lannering, C Mölstad, S Fernandez-Vandellos, P Torres, A Parizel, M Ieven, M Butler, C Verheij, T Little, P Goossens, H Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study. |
| title | Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study. |
| title_full | Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study. |
| title_fullStr | Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study. |
| title_full_unstemmed | Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study. |
| title_short | Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study. |
| title_sort | impact of amoxicillin therapy on resistance selection in patients with community acquired lower respiratory tract infections a randomized placebo controlled study |
| work_keys_str_mv | AT malhotrakumars impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT vanheirstraetenl impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT coenens impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT lammensc impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT adriaenssensn impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT kowalczyka impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT godyckicwirkom impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT bielickaz impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT hupkovah impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT lanneringc impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT molstads impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT fernandezvandellosp impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT torresa impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT parizelm impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT ievenm impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT butlerc impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT verheijt impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT littlep impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy AT goossensh impactofamoxicillintherapyonresistanceselectioninpatientswithcommunityacquiredlowerrespiratorytractinfectionsarandomizedplacebocontrolledstudy |