Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections: a randomized, placebo-controlled study
| Autor: | Malhotra-Kumar, Surbhi, Van Heirstraeten, Liesbet, Coenen, Samuel, Lammens, Christine, Adriaenssens, Niels, Kowalczyk, Anna, Godycki-Cwirko, Maciek, Bielicka, Zuzana, Hupkova, Helena, Lannering, Christina, Mölstad, Sigvard, Fernandez-Vandellos, Patricia, Torres, Antoni, Parizel, Maxim, Ieven, Margareta, Butler, Chris C., Verheij, Theo, Little, Paul, Goossens, Hermanon, Frimodt-Møller, Niels, Bruno, Pascale, Hering, Iris, Lemiengre, Marieke, Loens, Katherine, Malmvall, Bo Eric, Muras, Magdalena, Romano, Nuria Sanchez, Prat, Matteu Serra, Svab, Igor, Swain, Jackie, Tarsia, Paolo, Leus, Frank, Veen, Robert, Worby, Tricia |
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| Přispěvatelé: | GRACE Study Grp |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Antibiotics Placebo-controlled study medicine.disease_cause Gastroenterology law.invention Placebos Randomized controlled trial law Pharmacology (medical) Prospective Studies Prospective cohort study Aged 80 and over Respiratory tract infections Streptococcus Pharmacology. Therapy Middle Aged Anti-Bacterial Agents 3. Good health Community-Acquired Infections Infectious Diseases Randomized Controlled Trial Female medicine.drug Adult Microbiology (medical) medicine.medical_specialty Adolescent medicine.drug_class 030106 microbiology Observational Study Microbial Sensitivity Tests Placebo beta-Lactam Resistance Young Adult 03 medical and health sciences Streptococcal Infections Internal medicine Pneumonia Bacterial medicine Journal Article Humans Selection Genetic Biology Aged Pharmacology business.industry Amoxicillin Surgery Human medicine business |
| Zdroj: | Journal of Antimicrobial Chemotherapy, 71(11), 3258. Oxford University Press The journal of antimicrobial chemotherapy |
| ISSN: | 0305-7453 |
| DOI: | 10.1093/jac/dkw234 |
| Popis: | 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. Patients were prescribed amoxicillin 1 g, three times daily (naEuroS=aEuroS52) or placebo (naEuroS=aEuroS50) 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 a parts per thousand yen2 mg/L) and -non-susceptible (ANS; MIC a parts per thousand yen0.5 mg/L) streptococci. Alterations in amoxicillin MICs and in penicillin-binding-proteins were also investigated. ITT and PP analyses were conducted. 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; PaEuroS < aEuroS0.0001 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; PaEuroS > aEuroS0.1588). 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; PaEuroS < aEuroS0.0001). 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%; PaEuroS=aEuroS0.0004). 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. |
| Databáze: | OpenAIRE |
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