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.

How do general practitioners implement decision-making regarding COPD patients with exacerbations? An international focus group study.

PURPOSE: To explore the decision-making of general practitioners (GPs) concerning treatment with antibiotics and/or oral corticosteroids and hospitalization for COPD patients with exacerbations. METHODS: Thematic analysis of seven focus groups with 53 GPs from urban and rural areas in Norway, Germany, Wales, Poland, Russia, the Netherlands, and Hong Kong. RESULTS: Four main themes were identified. 1) Dealing with medical uncertainty: the GPs aimed to make clear medical decisions and avoid unnecessary prescriptions and hospitalizations, yet this was challenged by uncertainty regarding the severity of the exacerbations and concerns about overlooking comorbidities. 2) Knowing the patient: contextual knowledge about the individual patient provided a supplementary framework to biomedical knowledge, allowing for more differentiated decision-making. 3) Balancing the patients' perspective: the GPs considered patients' experiential knowledge about their own body and illness as valuable in assisting their decision-making, yet felt that dealing with disagreements between their own and their patients' perceptions concerning the need for treatment or hospitalization could be difficult. 4) Outpatient support and collaboration: both formal and informal caregivers and organizational aspects of the health systems influenced the decision-making, particularly in terms of mitigating potentially severe consequences of "wrong decisions" and concerning the negotiation of responsibilities. CONCLUSION: Fear of overlooking severe comorbidity and of further deteriorating symptoms emerged as a main driver of GPs' management decisions. GPs consider a holistic understanding of illness and the patients' own judgment crucial to making reasonable decisions under medical uncertainty. Moreover, GPs' decisions depend on the availability and reliability of other formal and informal carers, and the health care systems' organizational and cultural code of conduct. Strengthening the collaboration between GPs, other outpatient care facilities and the patients' social network can ensure ongoing monitoring and prompt intervention if necessary and may help to improve primary care for COPD patients with exacerbations.

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.

Uric acid but not apple polyphenols is responsible for the rise of plasma antioxidant activity after apple juice consumption in healthy subjects.

OBJECTIVE: To determine whether (1) rapid consumption of 1 L of apple juice increases blood antioxidant capacity, measured as ferric-reducing ability of plasma (FRAP) and serum 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, and (2) apple polyphenols or fructose-induced elevation of plasma uric acid contributes to post-juice increase of blood antioxidant activity. METHODS: The study involved 12 (mean age 32 ± 5 years, mean body weight 73 ± 7 kg) healthy nonsmoking subjects. Tested subjects consumed 1 L of clear apple juice and then FRAP; serum DPPH-scavenging activity, serum uric acid, and total plasma phenolics and quercetin levels were measured just before juice ingestion and 1, 2.5, and 4 hours after ingestion. This was repeated 3 times with 4-day intervals, but volunteers drank either 1 L of clear apple juice without polyphenols (placebo), or 1 L of cloudy apple juice (positive control), or 1 L of water (negative control) at the time. All juices had similar content of sugars (i.e., saccharose, glucose, and fructose) and precisely defined composition of phenolics and antioxidant activity. RESULTS: Consumption of all 3 juices transiently increased FRAP and serum DPPH-scavenging activity, with peak values at 1 hour post-juice ingestion. This was paralleled by the rise of serum uric acid, but no significant changes in plasma total phenolics and quercetin levels were observed after all dietary interventions. At the same time, no substantial differences were found between juices (especially between clear apple juice and clear apple juice without polyphenols) concerning the measured variables. A strong significant correlation was noted instead between serum uric acid and plasma antioxidant activity at all analyzed time points, before and after juice ingestion. Plasma total phenolics and quercetin levels were not associated with FRAP and serum DPPH radical-scavenging activity. CONCLUSIONS: We have demonstrated that rapid consumption of apple juice increased plasma antioxidant activity in healthy subjects; this was caused by the fructose-induced rise of serum uric acid levels, but was not due to the presence of antioxidant polyphenols in juice. Thus, short-term consumption of apple juice seems not to be the effective dietary intervention to augment plasma antioxidant activity due to the concomitant possibility for uric acid to be a risk factor for several diseases, as verified by other authors.