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.

Cost effectiveness of amoxicillin for lower respiratory tract infections in primary care: an economic evaluation accounting for the cost of antimicrobial resistance.

BACKGROUND: Lower respiratory tract infections (LRTIs) are a major disease burden and are often treated with antibiotics. Typically, studies evaluating the use of antibiotics focus on immediate costs of care, and do not account for the wider implications of antimicrobial resistance. AIM: This study sought to establish whether antibiotics (principally amoxicillin) are cost effective in patients with LRTIs, and to explore the implications of taking into account costs associated with resistance. DESIGN AND SETTING: Multinational randomised double-blinded trial in 2060 patients with acute cough/LRTIs recruited in 12 European countries. METHOD: A cost-utility analysis from a health system perspective with a time horizon of 28 days was conducted. The primary outcome measure was the quality-adjusted life year (QALY). Hierarchical modelling was used to estimate incremental cost-effectiveness ratios (ICERs). RESULTS: Amoxicillin was associated with an ICER of €8216 (£6540) per QALY gained when the cost of resistance was excluded. If the cost of resistance is greater than €11 (£9) per patient, then amoxicillin treatment is no longer cost effective. Including possible estimates of the cost of resistance resulted in ICERs ranging from €14 730 (£11 949) per QALY gained - when only multidrug resistance costs and health care costs are included - to €727 135 (£589 856) per QALY gained when broader societal costs are also included. CONCLUSION: Economic evaluation of antibiotic prescribing strategies that do not include the cost of resistance may provide misleading results that could be of questionable use to policymakers. However, further work is required to estimate robust costs of resistance.

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.

Point of care testing for urinary tract infection in primary care (POETIC): protocol for a randomised controlled trial of the clinical and cost effectiveness of FLEXICULT™ informed management of uncomplicated UTI in primary care.

BACKGROUND: Urinary tract infections (UTI) are the most frequent bacterial infection affecting women and account for about 15% of antibiotics prescribed in primary care. However, some women with a UTI are not prescribed antibiotics or are prescribed the wrong antibiotics, while many women who do not have a microbiologically confirmed UTI are prescribed antibiotics. Inappropriate antibiotic prescribing unnecessarily increases the risk of side effects and the development of antibiotic resistance, and wastes resources. METHODS/DESIGN: 614 adult female patients will be recruited from four primary care research networks (Wales, England, Spain, the Netherlands) and individually randomised to either POCT guided care or the guideline-informed 'standard care' arm. Urine and stool samples (where possible) will be obtained at presentation (day 1) and two weeks later for microbiological analysis. All participants will be followed up on the course of their illness and their quality of life, using a 2 week self-completed symptom diary. At 3 months, a primary care notes review will be conducted for evidence of further evidence of treatment failures, recurrence, complications, hospitalisations and health service costs. DISCUSSION: Although the Flexicult™ POCT is used in some countries in routine primary care, it's clinical and cost effectiveness has never been evaluated in a randomised clinical trial. If shown to be effective, the use of this POCT could benefit individual sufferers and provide evidence for health care authorities to develop evidence based policies to combat the spread and impact of the unprecedented rise of infections caused by antibiotic resistant bacteria in Europe. TRIAL REGISTRATION NUMBER: ISRCTN65200697 (Registered 10 September 2013).

How do COPD patients respond to exacerbations?

BACKGROUND: Although timely treatment of COPD exacerbations seems clinically important, nearly half of these exacerbations remain unreported and subsequently untreated. Recent studies have investigated incidence and impact of failure to seek medical treatment during exacerbations. Yet, little is known about type and timing of other self-management actions in periods of symptom deterioration. The current prospective study aims at determining the relative incidence, timing and determinants of three types of patient responses. METHODS: In a multicentre observational study, 121 patients (age 67 ± 11 years, FEV1pred. 48 ± 19) were followed for 6 weeks by daily diary symptom recording. Three types of action were assessed daily: planning periods of rest, breathing techniques and/or sputum clearing (type-A), increased bronchodilator use (type-B) and contacting a healthcare provider (type-C). RESULTS: Type-A action was taken in 70.7%, type-B in 62.7% and type C in 17.3% of exacerbations (n = 75). Smokers were less likely to take type-A and B actions. Type-C actions were associated with more severe airflow limitation and increased number of hospital admissions in the last year. CONCLUSIONS: Our study shows that most patients are willing to take timely self-management actions during exacerbations. Future research is needed to determine whether the low incidence of contacting a healthcare provider is due to a lack of self-management or healthcare accessibility.

Management of upper respiratory tract infections in Dutch general practice; antibiotic prescribing rates and incidences in 1987 and 2001.

BACKGROUND AND AIM: This study aims to assess differences in antibiotic prescribing and incidence of Upper Respiratory Tract Infections (URTIs) between 1987 and 2001, before (1987) and after (2001) publication of Dutch guidelines on URTIs. DESIGN, SETTING AND METHOD: Data were collected in two national surveys: 96 general practices (n=344,449 patients) in 1987 and 90 general practices (n=358,008 patients) in 2001. Outcome measures were: (1) antibiotic prescribing rates for acute otitis media (AOM), common cold, sinusitis and acute tonsillitis; (2) number of antibiotic prescriptions per 1000 patients per year; (3) incidence rates per 1000 patients per year. RESULTS: Antibiotic prescribing rates in AOM and common cold were increased in 2001 compared to 1987 (from 27% to 48%; from 17% to 23%, respectively), while the rates for sinusitis and acute tonsillitis were about the same (72% and 70%; 74% and 72%, respectively). Except for AOM, the number of antibiotic prescriptions per 1000 patients decreased by 30% to 50%. As incidence rates of common cold, tonsillitis and sinusitis decreased, the decline in the total volume of antibiotic prescriptions per 1000 patients for these three categories has mainly to be attributed to a fall of incidence rates. CONCLUSION: Antibiotic prescribing rates for URTIs have not declined between 1987 and 2001, but the volumes for common cold, sinusitis and tonsillitis have fallen down mainly attributable to declined incidences, which have probably been caused by a reduced inclination of patients to present respiratory illness to their GP. Prescribing antibiotics for AOM has increased.