Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations.

BACKGROUND: Fluconazole (FLC) resistance is common in C. glabrata and echinocandins are often used as first-line therapy. Resistance to echinocandin therapy has been associated with FKS1 and FKS2 gene alterations. METHODS: We reviewed records of all patients with C. glabrata bloodstream infection at Duke Hospital over the past decade (2001-2010) and correlated treatment outcome with minimum inhibitory concentration (MIC) results and the presence of FKS gene mutations. For each isolate, MICs to FLC and echinocandins (anidulafungin, caspofungin, and micafungin) and FKS1 and FKS2 gene sequences were determined. RESULTS: Two hundred ninety-three episodes (313 isolates) of C. glabrata bloodstream infection were analyzed. Resistance to echinocandins increased from 4.9% to 12.3% and to FLC from 18% to 30% between 2001 and 2010, respectively. Among the 78 FLC resistant isolates, 14.1% were resistant to 1 or more echinocandin. Twenty-five (7.9%) isolates harbored a FKS mutation. The predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, odds ratio, 19.647 [95% confidence interval, 7.19-58.1]). Eighty percent (8/10) of patients infected with FKS mutants demonstrating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially but experienced a recurrence. CONCLUSIONS: Echinocandin resistance is increasing, including among FLC-resistant isolates. The new Clinical and Laboratory Standards Institute clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.

Diagnostic spirometry in primary care: Proposed standards for general practice compliant with American Thoracic Society and European Respiratory Society recommendations: a General Practice Airways Group (GPIAG)1 document, in association with the Association for Respiratory Technology & Physiology (ARTP)2 and Education for Health3 1 www.gpiag.org 2 www.artp.org 3 www.educationforhealth.org.uk.

Primary care spirometry services can be provided by trained primary care staff, peripatetic specialist services, or through referral to hospital-based or laboratory spirometry. The first of these options is the focus of this Standards Document. It aims to provide detailed information for clinicians, managers and healthcare commissioners on the key areas of quality required for diagnostic spirometry in primary care--including training requirements and quality assurance. These proposals and recommendations are designed to raise the standard of spirometry and respiratory diagnosis in primary care and to provide the impetus for debate, improvement and maintenance of quality for diagnostic (rather than screening) spirometry performed in primary care. This document should therefore challenge current performance and should constitute an aspirational guide for delivery of this service.

Interpretation and evaluation of pulmonary function tests.

Evaluation of pulmonary function is essential for the diagnosis and management of respiratory disease and other conditions. Various tests are available. Some, such as spirometry and pulse oximetry, are widely used in a variety of healthcare settings; others, such as those that measure diffusing capacity and static lung volumes, are performed in specialist pulmonary function laboratories. This article examines some of the pulmonary function tests available.

Simple spirometry measurement.

This article describes expiratory spirometry manoeuvres. It examines equipment care and maintenance, patient preparation, basic techniques, reproducibility and how to ensure technical acceptability and correct common errors.

Pulse oximetry.

Pulse oximetry is a widely used, non-invasive technique for assessing arterial oxygenation by measuring oxygen saturation in peripheral blood vessels. It is a simple technique, but needs to be carried out with care to obtain reliable results. This article provides guidance on the safe use of pulse oximetry and identifies some of the advantages and limitations of the procedure.

Understanding why we use spirometry: part one.

Rachel Booker discusses why spirometry is used and the interpretation of results. In part two she describes the procedure for using spirometry.

Carrying out accurate spirometry testing: part 2.

Rachel Booker describes the procedure for using spirometry.

Peak expiratory flow measurement.

Effective peak flow measurement is useful to assess patients with respiratory conditions, particularly asthma. This article describes how nurses can assist patients to achieve accurate measurements.

Chronic obstructive pulmonary disease. Part two--management.

In the second part of this two-part series, non-drug and pharmacological approaches to COPD management are explored.

Chronic obstructive pulmonary disease. Part one--diagnosis.

This two-part series covers diagnosis and management of COPD. The first part focuses on presenting symptoms, methods of diagnosis and differential diagnoses. Part two (next week) covers non-drug and pharmacological management of the condition.

Correct use of nebulisers.

Nebulisers are used to deliver bronchodilators and other medication in a variety of healthcare settings. In common with other medical equipment, healthcare professionals need an understanding of the principles of their operation to ensure they are used effectively and safely.

Chronic obstructive pulmonary disease and the NICE guideline.

This article covers the key priorities identified by the National Institute for Clinical Excellence (NICE) guideline for the management of chronic obstructive pulmonary disease (COPD) and examines the role of nurses in achieving these priorities for good care of patients with COPD.

Chronic obstructive pulmonary disease: non-pharmacological approaches.

Chronic obstructive pulmonary disease (COPD) is a progressive, smoking-related, chronic disease that eventually impacts on every area of the lives of the patient and his/her family and carers. The nature of the disease - chronic, irreversible airflow obstruction - limits the impact of drug therapy, particularly as the disease progresses. Increasing breathlessness on exertion saps confidence, reduces self-esteem and produces dependence. In addition, frequent exacerbations utilize health service resources. Non-pharmacological approaches, such as pulmonary rehabilitation, together with lifestyle advice that enables patients to help themselves manage exacerbations, maintain independence and quality of life and make the most of life with COPD can benefit both patients and the health service.

Pharmacological approaches to stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) causes disabling, slowly progressive breathlessness on exertion, chronic cough and sputum production. Its natural history is punctuated by increasingly frequent exacerbations which in turn accelerate disease progression and reduce a patient's quality of life. COPD has previously been ignored in the mistaken belief that nothing could be done. There are now a number of therapies that can be used to reduce symptoms and prevent exacerbations. In turn this reduces disability, improves the patient's health-related quality of life and has the potential to reduce costs to the health service and to society.

Causes and management of chronic breathlessness in adults.

Breathlessness is a common symptom associated with a variety of disorders. It is defined as 'an abnormal awareness or difficulty with breathing' (Bourke and Brewis, 1998). It can be acute or chronic. Acute breathlessness typically occurs within a short timeframe and may be severe. It may also be the presenting symptom of life-threatening disease. Chronic breathlessness develops over several months or years.

Chronic obstructive pulmonary disease: importance of diagnosis.

Chronic obstructive pulmonary disease is a common, smoking-related respiratory disease. It is responsible for considerable morbidity and mortality and accounts for a large amount of NHS resources. Despite this, it is underdiagnosed, often poorly managed and its impact on patients is underestimated (British Thoracic Society (BTS), 2001). The first step is to make an accurate diagnosis at as early a stage as possible. This article explores the prevalence, impact and presentation of the disease and how it can be identified and diagnosed.

The effective assessment of acute breathlessness in a patient.

Breathing is a fundamental life process that usually occurs without conscious thought and, for the healthy person, is taken for granted. It involves: The coordinated action of inspiratory and expiratory muscles; The unimpeded passage of air from the atmosphere through the upper to the lower respiratory tract; The exchange of oxygen (O2) and carbon dioxide (CO2) across the alveolar membrane.

Pharmacology of bronchodilators.

In the UK, diseases that cause airflow obstruction are common. About 5.1 million people receive treatment for asthma and about 600,000 people are diagnosed as having chronic obstructive pulmonary disease (COPD), although this is likely to be an underestimate (British Thoracic Society, 2001).