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

Abstract

Objectives: To determine the effect of amoxicillin treatment on resistance selection in patients with communityacquired lower respiratory tract infections in a randomized, placebo-controlled trial.Methods: Patients were prescribed amoxicillin 1 g, three times daily (n ¼ 52) or placebo (n ¼ 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 23.06, 95% CI 27.34 to 1.21; ANS MI 4.91, 95% CI 24.79 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%; P¼0.0004).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.

Resistance decay in individuals after antibiotic exposure in primary care: a systematic review and meta-analysis

“…Table 1 shows study characteristics. All but three [ 26 , 29 , 39 ] were conducted in one of the Organisation for Economic Co-operation and Development countries: 16 investigated children (total of 16,353) [ 26 , 29 – 34 , 36 – 41 , 44 , 45 , 48 – 50 ] and 8 studied adults (total of 1461) [ 25 , 27 , 28 , 35 , 42 , 43 , 46 , 47 ] 14 investigated symptomatic patients (12 with respiratory infections [ 28 , 30 – 34 , 36 – 38 , 48 – 50 ], 1 with a urinary infection [ 42 ] and 1 with acute febrile illness [ 47 ]) 6 involved asymptomatic participants [ 25 , 27 , 29 , 35 , 43 , 46 ] 5 studies included both symptomatic and asymptomatic participants [ 26 , 39 , 41 , 44 , 45 ] …”

Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis by bacterial and viral aetiology

“…Neither symptom duration nor symptom severity were clearly affected by amoxicillin treatment, and the odds of illness deterioration was influenced by amoxicillin treatment only in a very specific subgroup. The potential benefits of amoxicillin treatment should therefore be balanced against side effects, such as diarrhoea, nausea, or skin rash and the long-term risk of antibiotic resistance [20]. Thus, most of these patients should probably not be prescribed an antibiotic, and/or clinicians could consider using a delayed antibiotic prescription to avoid inappropriate use of antibiotics [21].…”

Microbiome as a tool and a target in the effort to address antimicrobial resistance

“…In either case, the entire microbiome, insofar as it is exposed to concentrations of antibiotics capable of selecting for resistance, is subject to such selection. Antimicrobial treatment, whatever the indication, may lead to increases in the prevalence of resistance within potentially pathogenic microbiome members such as oral streptococci (72), Streptococcus pneumoniae (73,74), Haemophilus influenzae (75), Enterobacteriaceae (76), Staphylococcus spp. (77,78), and even concurrently infecting strains of Neisseria gonorrhoeae (79).…”