Clinical relevance of bacterial resistance in lower respiratory tract infection in primary care: secondary analysis of a multicentre European trial.

BACKGROUND: The impact of antimicrobial resistance on clinical outcomes in patients with lower respiratory tract infection in primary care is largely unknown. AIM: To determine the illness course of infections with resistant bacteria in adults presenting to primary care with acute cough. DESIGN AND SETTING: Secondary analysis of a multicentre European trial in primary care. METHOD: A total of 2061 adults with acute cough (lasting ≤28 days) were recruited from primary care and randomised to amoxicillin or placebo. To reflect the natural course of disease, only patients in the placebo group (n = 1021) were eligible. Nasopharyngeal flocked swabs and/or sputa (when available) were analysed at baseline and Streptococcus pneumoniae and Haemophilus influenzae isolates underwent susceptibility testing. Patients recorded their symptoms in a diary every day for 4 weeks. Patients with and without resistant bacterial infection were compared with regards to symptom severity, duration of symptoms, worsening of illness, and duration of interference with normal activities or work. RESULTS: Of the 834 patients with diary records, 104 showed S. pneumoniae and/or H. influenzae infection. Of this number, 54 (52%) were resistant to antibiotics, while seven (7%) were resistant to penicillin. For the duration of symptoms rated 'moderately bad or worse' (hazard ratio 1.27, 95% confidence interval [CI] = 0.67 to 2.44), mean symptom severity (difference -0.48, 95% CI = -1.17 to 0.21), and worsening of illness (odds ratio 0.31, 95% CI = 0.07 to 1.41), there was no statistically significant difference between the antibiotic-resistant and antibiotic-sensitive groups. CONCLUSION: The illness course of antibiotic-resistant lower respiratory tract infection does not differ from that caused by antibiotic-sensitive bacteria.

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

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.