PubMed Health⌕ Search

Biomedical subjects

T R Rogers

Publications and source records attributed to T R Rogers.

At least 19 recordsLinked to original sources
PubMed2004

Voriconazole for serious fungal infections.

Voriconazole is a new second generation triazole effective against a wide spectrum of fungal pathogens. A randomised, controlled trial has shown it to be superior to amphotericin B in invasive aspergillosis, and it is a potential alternative to amphotericin B in neutropenic sepsis and to fluconazole in oesophageal candidiasis. Early clinical reports and in vitro susceptibility data suggest that it may also be a valuable antifungal against fluconazole-resistant Candida species and certain emerging fungal pathogens, which cause infections that are often refractory to conventional therapies. There is limited evidence of azole cross-resistance of clinical importance. Voriconazole is available as intravenous and oral formulations and has excellent tissue penetration and a good safety profile, the main problems being transient visual impairment and hepatotoxicity in patients with liver disease. It is metabolised by cytochrome P-450 isoenzymes causing important drug interactions but, in contrast to amphotericin B, is safe in renal failure and rarely causes infusion-related reactions. This review outlines the pharmacology of voriconazole and focuses on its clinical applications and safety profile.

Antifungal Agents↗
PubMed2003

Disseminated Aspergillus terreus infection arising from cutaneous inoculation treated with caspofungin.

A case of disseminated Aspergillus terreus infection in a patient with prolonged neutropenia after stem cell transplant for myeloma is reported. The isolate was resistant to amphotericin B in vitro, and the patient was successfully managed with surgical debridement and the recently licensed antifungal agent caspofungin. There are many challenges associated with treating invasive aspergillosis, particularly that due to A. terreus, and the early use of caspofungin should be considered.

Amphotericin B↗
PubMed2001

Optimal use of existing and new antifungal drugs.

Clinicians are increasingly aware that fungal pathogens are a significant cause of morbidity and mortality in hospitalized patients. Historically, these infections occurred in severely immunocompromised patients who were undergoing treatment for hematological malignancy or solid organ transplantation. Currently, however, systemic fungal infections are commonly seen in debilitated patients who are being nursed in intensive care or high-dependency units. These infections are mostly caused by Candida albicans but there is a growing proportion of strains of non- albicans Candida spp, some with reduced susceptibility to commonly used antifungals. The limited armamentarium of antifungal agents to date has meant that amphotericin B continues to be considered the most effective therapeutic agent albeit with a poor record of treatment-limiting side effects. The past decade has seen some encouraging developments in antifungal therapy. Three lipid formulations of amphotericin B showing reduced toxicity compared with the desoxycholate formulation are now licensed. There are three investigational triazoles currently undergoing evaluation that should prove important additions to existing members of this class. The echinocandin caspofungin is the first of a new class of antifungal agents with a novel mode of action, which has recently been approved for use in the United States.

Antifungal Agents↗
PubMed1998

Multi-centre evaluation of the Etest method for antifungal drug susceptibility testing of Candida spp. and Cryptococcus neoformans. BSAC Working Party on Antifungal Chemotherapy.

Ten laboratories tested 18 isolates of Candida spp. and two of Cryptococcus neoformans against amphotericin B, flucytosine, fluconazole and itraconazole on two occasions by the Etest method. Two individuals read each set of results. Of the 18 isolates of Candida spp., five were duplicated, but the participants were not told this. In 40 of the 60 drug-organism combinations studied, at least 80% of the Etest MICs fell within a five-concentration range corresponding to the modal MIC +/- 1 log2 dilution. In five combinations, >50% of the Etest MICs fell outside this five-concentration range. In 17 (85%) of the 20 drug-organism combinations tested in duplicate, at least 80% of the paired Etest results fell within two concentrations of each other (corresponding to one log2 dilution). Overall, 88.5% of the paired Etest results for amphotericin B agreed to within two concentrations, as did 94% of results for flucytosine, 92% for fluconazole and 79% for itraconazole. The broth microdilution MICs of the four antifungal agents for the 15 isolates were measured on five occasions in the Mycology Reference Laboratory, Bristol. In each case, the results fell within a three log2 concentration range. In 24 (40%) of the 60 drug-organism combinations tested, at least 80% of the Etest results fell within the broth microdilution test MIC range, but 27 (45%) showed <50% exact agreement. In 33 (73%) of 45 drug-organism combinations involving flucytosine, fluconazole or itraconazole, at least 80% of the Etest results fell within the same class (susceptible, resistant, or susceptible dependent upon dose) as the broth microdilution results. With fluconazole, the Etest method misclassified three susceptible isolates of Candida spp. as resistant in 1.5-15% of tests. With itraconazole, the Etest misclassified seven susceptible isolates of Candida spp. as resistant in 5-62.5% of tests. The Etest also misclassified both C. neoformans isolates as resistant to flucytosine, fluconazole and itraconazole in 7.5-65% of tests. Our results suggest that the Etest is suitable for routine use with Candida spp. and amphotericin B or flucytosine. It is less reliable for the azoles, and isolates that appear to demonstrate acquired resistance should be retested with well-established reference methods.

Amphotericin B↗
PubMed1997

Hospital-acquired Clostridium difficile diarrhoea and herd immunity.

Clostridium difficile diarrhoea represents a significant health-service burden. We recently experienced an outbreak of C difficile diarrhoea associated with increased use of cefotaxime. The question we pose in this paper is how did the introduction and withdrawal of a single antibiotic so greatly affect rates of C difficile diarrhoea? Other antibiotics had nearly as high a risk of causing diarrhoea as cefotaxime, and the majority of patients never received cefotaxime. We believe that such outbreaks of C difficile diarrhoea are best understood in terms of a population model, and that taking antibiotics like cefotaxime should be thought of as a population rather than an individual risk factor. We postulate a herd-immunity model of C difficile diarrhoea, and examine the implications of this hypothesis.

Aged↗
PubMed1997

Guidelines for the investigation of invasive fungal infections in haematological malignancy and solid organ transplantation. British Society for Medical Mycology.

Invasive fungal infections are increasing in incidence and now affect as many as 50% of neutropenic/bone marrow transplant patients and 5 to 20% of solid organ transplant recipients. Unfortunately, many of the diagnostic tests available have a low sensitivity. The guidelines presented here have been produced by a working party of the British Society for Medical Mycology in an attempt to optimise the use of these tests. The yield of fungi from blood cultures can be increased by ensuring that at least 20 ml of blood are taken for aerobic culture, by using more than one method of blood culture, and by employing terminal subculture if continuous monitoring systems are used with a five-day incubation protocol. Skin lesions in febrile neutropenic patients should be biopsied and cultured for fungi. The detection of galactomannan in blood or urine is of value in diagnosing invasive aspergillosis only if tests are performed at least twice weekly in high-risk patients. Antigen detection tests for invasive candidiasis are less valuable. Computed tomography scanning is particularly valuable in diagnosing invasive pulmonary fungal infection when the chest radiograph is negative or shows only minimal changes. Bronchoalveolar lavage is most useful in patients with diffuse changes on computed tomography scan. The major advances in the diagnosis of invasive fungal infection in patients with haematological malignancy or solid organ transplantation have been in the use of imaging techniques, rather than in the development of new mycological methods in the routine laboratory.

Algorithms↗
PubMed1997

International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections.

Because of the rapidly increasing incidence of serious candidal infections, a consensus conference of 22 investigators from the United States, Europe, and Japan was held to discuss strategies for the prevention and treatment of deep-organ infections caused by Candida species. Commonly asked questions concerning the management of candidal infections were selected for discussion by the participating investigators. Possible answers to the questions were developed by the investigators, who then voted anonymously for their preferences. In certain instances, unanimity or a strong consensus was the result. In all cases, the full spectrum of responses was recorded and is presented in this report. The forms of candidal infection addressed included candidemia, candiduria, hepatosplenic candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and candidal peritonitis. Prevention and treatment strategies were considered for patients who have undergone surgery, for neutropenic and nonneutropenic patients, and for patients who have undergone bone marrow and solid organ transplantation. The therapeutic roles of amphotericin B (standard and lipid formulations) and the azoles were considered.

Animals↗
PubMed1996

Fungal infections: a survey of laboratory services for diagnosis and treatment.

A questionnaire on the services provided and the methods used for the diagnosis of fungal infections and for the support of antifungal chemotherapy was sent to members of the British Society for Medical Mycology (BSMM) and the British Society for Antimicrobial Chemotherapy (BSAC). Ninety-five responses from general microbiology laboratories in the United Kingdom were analysed, and we compared services provided by laboratories that serve a transplant unit with those offered by other laboratories. We estimate that about 150 cases of cryptococcosis, 500 to 600 of candidaemia, and 300 to 400 of invasive aspergillosis are identified by laboratories in the United Kingdom (UK) each year. The clinical laboratories are aware of the importance of fungal infection, but rely heavily on reference services. In some laboratories, however, the degree of investigation of specimens and the procedures in use are inadequate for diagnosing systemic mycoses and determining the susceptibility of isolates to antifungal agents. The balance between reference and local services requires attention and external quality assurance needs to be applied effectively. In addition, effective methods for the diagnosis of systemic mycoses, and reliable and practicable methods for determining the susceptibility of isolates to antifungal agents, are needed urgently.

Antifungal Agents↗
PubMed1995

Antifungal drug susceptibility testing. Working Party of the British Society for Antimicrobial chemotherapy.

This article describes the current situation with regard to intrinsic and acquired resistance to antifungal compounds and progress with the development of standardized methods of susceptibility testing for amphotericin B, flucytosine, and the azoles. Recommendations for testing of isolates from patients destined to receive antifungal drug treatment, or in whom therapeutic failure or relapse is suspected, are presented.

Antifungal Agents↗
PubMed1994

Retrospective evaluation of a latex agglutination test for diagnosis of invasive aspergillosis in immunocompromised patients.

A commercial latex agglutination (LA) test for the detection of circulating Aspergillus galactomannan was evaluated in sera obtained from 121 immunocompromised patients, including 19 with proven invasive pulmonary aspergillosis. Patient urine (the specimen of choice for detection of galactomannan) was not tested with the LA test as 34 of 81 specimens from controls gave false-positive results. The sensitivity (95%), specificity (90%) and negative predictive value (99%) of the LA test were similar to previously published results obtained with two EIAs. However, the positive predictive value was only 67% compared to > or = 95% obtained with the EIAs. In addition, the LA test was also of less value than the EIAs in predicting the onset of invasive pulmonary aspergillosis. It was the earliest indicator of infection in only 1 of 19 proven cases.

Antigens, Fungal↗