Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD). We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority). A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was -0.19 points (two-sided 90% CI, -0.33 to -0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation. CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm. (Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.).

Objectives: Human clinical isolates of Bacteroides spp. originating from patients in the UK were investigated for the presence of metronidazole resistance determinants (nim genes) and their presence was related to the MIC of metronidazole for the isolates. Methods: Isolates were screened for susceptibility to a metronidazole disc and had their MIC determined by the Etest method. They were investigated for the presence of nim genes by PCR. An experiment to determine the effect of prolonged exposure to metronidazole was applied to nim-positive isolates with MICs below the therapeutic breakpoint. Results: Fifty of 206 isolates (24%) were found to possess nim genes and these had MICs of metronidazole ranging from 1.5 to >256 mg/L with 24 (11.6%) above the therapeutic breakpoint of 16 mg/L. The remaining 26 nim-gene-positive isolates had MICs that were still below the therapeutic breakpoint, ranging from 1.5 to 6.0 mg/L. nim genes were not found in 156 (76%) isolates, and all but seven of these were susceptible to a 5 μg disc of metronidazole. Ten members of the group for which the MICs were below the therapeutic level were found to have slow-growing sub-populations with metronidazole MICs ranging from 8.0 to >256 mg/L that became evident after prolonged exposure to metronidazole in vitro. This resistance selection process was sometimes reversible after passage in the absence of metronidazole; however, seven of the 10 slow-growing mutants converted to stable high-level resistance (MIC >256 mg/L). Conclusions: Although the presence of nim genes per se does not always equate to therapeutic resistance, and other metronidazole resistance mechanisms may exist, this study has shown that prolonged exposure of nim-gene-carrying Bacteroides spp. to metronidazole can select for therapeutic resistance.

Background: Regional variations in the presentation of uncomplicated urinary tract infection (UTI) and pathogen sensitivity to antibiotics have been cited as reasons to justify differences in how the infections are managed, which includes the prescription of broad-spectrum antibiotics.Aim: To describe presentation and management of UTI in primary care settings, and explore the association with patient recovery, taking microbiological findings and case mix into account.Design and setting: Prospective observational study of females with symptoms of uncomplicated UTI presenting to primary care networks in England, Wales, the Netherlands, and Spain.Method: Clinicians recorded history, symptom severity, management, and requested mid-stream urine culture. Participants recorded, in a diary, symptom severity each day for 14 days. Time to recovery was compared between patient characteristics and between countries using two-level Cox proportional hazards models, with patients nested within practices.Results: In total, 797 females attending primary care networks in England (n = 246, 30.9% of cohort), Wales (n = 213, 26.7%), the Netherlands (n = 133, 16.7%), and Spain (n = 205, 25.7%) were included. In total, 259 (35.8%, 95% confidence interval 32.3 to 39.2) of 726 females for whom there was a result were urine culture positive for UTI. Pathogens and antibiotic sensitivities were similar. Empirical antibiotics were prescribed for 95.1% in England, 92.9% in Wales, 95.1% in Spain, and 59.4% in the Netherlands There were no meaningful differences at a country network level before and after controlling for severity, prior UTIs, and antibiotic prescribing.Conclusion: Variation in presentation and management of uncomplicated UTI at a country primary care network level is clinically unwarranted and highlights a lack of consensus concerning optimal symptom control and antibiotic prescribing.

Objectives: The aim of this study was to investigate the constitution of nim gene types, their activating insertion sequence (IS) element, their localization (plasmid or chromosome) and cfiA gene status in metronidazole-resistant Bacteroides strains (n = 26) in order to examine their interchangeability. Methods: Southern hybridization and conjugative plasmid transfer were used to localize the nimA–E genes and plasmid functions. PCR was used to detect the IS elements and the cfiA genes. PCR-mapping was applied to detect the nim gene-associated IS elements. PCR-mapping products and a nimE gene-containing plasmid fragment were sequenced. Results: Nine of the nimA genes (12) were activated by IS1168 and nine were carried on plasmids, four of which were pIP417-like. The five nimB genes were chromosomal, and two of them were associated with IS1168 and one with IS612. Of the three nimC genes, two were activated by IS1170, and one was carried on a pIP419-like plasmid. The only nimD gene was chromosomal. The five nimE strains harboured the resistance genes on plasmids: one plasmid, pBF388c, 8.3 kb, was characterized, and a novel IS-like element was demonstrated upstream of all the nimE genes. The insertion events of some of these IS elements were restricted to certain nim gene-specific positions. The 11 chromosomal nim genes displayed a positive association with the cfiA gene-specific background. Conclusions: Fourteen strains harboured the well-known genetic elements: pIP417- and pIP419-like plasmids, chromosomal nimB genes and a common nimE plasmid. However, a rate of interchangeability was also demonstrated, mostly due to combinations of nim genes and their associated IS elements harboured on different replicons.