High Diagnostic Accuracy of Nitrite Test Paired with Urine Sediment can Reduce Unnecessary Antibiotic Therapy

Abstract: Background: Urinary tract infections (UTIs) are common bacterial infections dominated by lower UTI in women (LUTIW). Symptoms only are insufficient for diagnosis and accordingly, near patient diagnostic tests confidently confirming significant bacteriuria are desirable. The nitrite test (NIT) has low sensitivity, while bacterial and leukocyte counts disjunctively paired in urine sediment microscopy (SED) have high sensitivity. Similar symptomatic cure rates are found post antibiotic vs. placebo therapy in patients with negative cultures. Consequently, prescription on symptoms only implies unnecessary antibiotic therapy. Aims: to evaluate the diagnostic outcomes of NIT, SED and NIT disjunctively paired with SED (NIT+SED) vs. urine culture, with special focus on bladder incubation time (BIT), and to assess if NIT+SED can reduce unnecessary antibiotic therapy. Methods: A diagnostic, primary care, multicentre study including 1070 women with symptoms suggestive of lower UTI. Results: Significant bacteriuria was found in 77%. The BIT highly influenced the diagnostic outcomes and the optimal duration was 4h with sensitivity of 66, 90 and 95% for NIT, SED and NIT+SED, respectively. SED performed only in NIT negative specimens could reduce unnecessary antibiotics by 10% vs. prescription on symptoms only. The number needed to test with SED to reduce one unnecessary antibiotic course was five patients at BIT 4h and six patients at 3h or overall. Conclusion: The BIT highly influences the diagnostic outcomes with the highest accuracy of NIT+SED. Diagnosis of LUTIW with NIT+SED can reduce unnecessary antibiotic therapy and subsequently decrease antimicrobial resistance. Trial registration: The Swedish Medical Product Agency 1995 03 01:151:01783/94

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin