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Biomedical subjects

D W Warnock

Publications and source records attributed to D W Warnock.

At least 37 records · Page 2Linked to original sources
PubMed2000

Report of the first human case of lobomycosis in the United States.

We describe the first human case of lobomycosis caused by Lacazia loboi in a 42-year-old white male resident of Georgia. The patient had traveled to Venezuela 7 years earlier, where he had planned to rappel down Angel Falls in Canaima. Although he never actually rappelled the falls, he did walk under the falls at least three times, exposing himself to the high water pressures of the falls. He noticed a small pustule with surrounding erythema developing on the skin of his right chest wall. The lesion gradually increased in size and had an appearance of a keloid. For cosmetic reasons, the patient sought medical treatment to remove the lesion. After an uncomplicated excision of the lesion, the patient recovered completely. The excised tissue was fixed in formalin for pathologic examination. Tissue sections stained by hematoxylin and eosin, periodic acid-Schiff stain, and Gomori methenamine silver stain procedures showed numerous histiocytes, multinucleated giant cells, and numerous globose or subglobose, lemon-shaped cells producing multiple blastoconidia connected by narrow tube-like connectors and catenate chains of various lengths characteristic of L. loboi.

Adult↗
PubMed2000

Comparative evaluation of PASCO and national committee for clinical laboratory standards M27-A broth microdilution methods for antifungal drug susceptibility testing of yeasts.

The PASCO antifungal susceptibility test system, developed in collaboration with a commercial company, is a broth microdilution assay which is faster and easier to use than the reference broth microdilution test performed according to the National Committee for Clinical Laboratory Standards (NCCLS) document M27-A guidelines. Advantages of the PASCO system include the system's inclusion of quality-controlled, premade antifungal panels containing 10, twofold serial dilutions of drugs and a one-step inoculation system whereby all wells are simultaneously inoculated in a single step. For the prototype panel, we chose eight antifungal agents for in vitro testing (amphotericin B, flucytosine, fluconazole, ketoconazole, itraconazole, clotrimazole, miconazole, and terconazole) and compared the results with those of the NCCLS method for testing 74 yeast isolates (14 Candida albicans, 10 Candida glabrata, 10 Candida tropicalis, 10 Candida krusei, 10 Candida dubliniensis, 10 Candida parapsilosis, and 10 Cryptococcus neoformans isolates). The overall agreements between the methods were 91% for fluconazole, 89% for amphotericin B and ketoconazole, 85% for itraconazole, 80% for flucytosine, 77% for terconazole, 66% for miconazole, and 53% for clotrimazole. In contrast to the M27-A reference method, the PASCO method classified as resistant seven itraconazole-susceptible isolates (9%), two fluconazole-susceptible isolates (3%), and three flucytosine-susceptible isolates (4%), representing 12 major errors. In addition, it classified two fluconazole-resistant isolates (3%) and one flucytosine-resistant isolate (1%) as susceptible, representing three very major errors. Overall, the agreement between the methods was greater than or equal to 80% for four of the seven species tested (C. dubliniensis, C. glabrata, C. krusei, and C. neoformans). The lowest agreement between methods was observed for miconazole and clotrimazole and for C. krusei isolates tested against terconazole. When the data for miconazole and clotrimazole were removed from the analysis, agreement was >/=80% for all seven species tested. Therefore, the PASCO method is a suitable alternative procedure for the testing of the antifungal susceptibilities of the medically important Candida spp. and C. neoformans against a range of antifungal agents with the exceptions only of miconazole and clotrimazole and of terconazole against C. krusei isolates.

Antifungal Agents↗
PubMed2000

Aspergillus antigen testing in bone marrow transplant recipients.

AIMS: To assess the clinical usefulness of a commercial aspergillus antigen enzyme linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in bone marrow transplant recipients, and to compare it with a commercial latex agglutination (LA) test. METHODS: In total, 2026 serum samples from 104 bone marrow transplant recipients were tested. These comprised 67 sera from seven patients who had died with confirmed IA, 268 sera from nine patients who had died with suspected IA, and 1691 sera from 88 patients with no clinical, radiological, or microbiological signs of IA. RESULTS: The ELISA was more sensitive than the LA test. All patients who were ELISA positive were also LA positive, and a positive LA result never preceded a positive ELISA. Twelve of 16 patients with confirmed or suspected IA were ELISA positive on two or more occasions, compared with 10 of 15 who were LA positive. ELISA was positive before LA in five patients (range, 2-14 days), and became positive on the same day in the remainder. Aspergillus antigen was detected by ELISA a median of 15 days before death (range, 4-233). Clinical and/or radiological evidence of IA was noted in all patients, and a positive ELISA was never the sole criterion for introduction of antifungal treatment. Two samples (one from each of two patients without IA) gave false positive results. CONCLUSIONS: The aspergillus ELISA is a specific indicator of invasive aspergillosis if the criterion of two positive samples is required to confirm the diagnosis. However, the test is insufficiently sensitive to diagnose aspergillosis before other symptoms or signs are apparent, and hence is unlikely to lead to earlier initiation of antifungal treatment. It is therefore unsuitable for screening of asymptomatic patients at risk of invasive aspergillosis, but does have a useful role in confirming the diagnosis in symptomatic patients.

Adolescent↗
PubMed2000

In vitro antifungal susceptibility methods and clinical implications of antifungal resistance.

As new antifungal agents are introduced for the treatment of infections caused by yeasts and filamentous fungi (moulds), it is important that reliable methods are available for the in vitro testing of both new and established agents. The ultimate goal of in vitro testing is the prediction of the clinical outcome of therapy. The use of the M27-A procedures that were developed by the US National Committee for Clinical Laboratory Standards (NCCLS) has led to increased interlaboratory agreement of minimum inhibitory concentrations (MICs) for yeasts and has facilitated the establishment of interpretive breakpoints for fluconazole and itraconazole. The clinical relevance and limitations of these breakpoints are discussed elsewhere. The focus of this paper is to review the advantages and disadvantages of the available methods for antifungal susceptibility testing of yeasts and moulds as well as the clinical implications of in vitro antifungal resistance.

Antifungal Agents↗
PubMed1999

Infections in adults undergoing unrelated donor bone marrow transplantation.

This study retrospectively reviews infections over a 7-year period in 60 consecutive adults (median age 25 years) undergoing their first unrelated donor bone marrow transplant (UD-BMT). T-cell depletion was employed in 93%. More than half the patients had one or more severe, potentially life-threatening, infections. There was a high incidence of invasive fungal infections (Aspergillus 17, Candida four), despite the use of itraconazole or amphotericin prophylaxis. Ten Aspergillus infections occurred beyond 100 d. Two patients (11%) with invasive aspergillosis survived. Clustering of infections was noted, with invasive fungal infections significantly associated with bacteraemias (OR 3.73, P=0.06) and multiple viral infections (OR 4.25, P=0.05). There were 21 severe viral infections in 16 patients, with CMV disease occurring in four patients only; viral pneumonitis was predominantly due to 'community respiratory' viruses. Most early bacteraemias (68%) were due to Gram-positive organisms. The majority of episodes of Gram-negative sepsis were caused by non-fastidious non-fermentative bacteria, such as Pseudomonas spp. and Acinetobacter spp., historically regarded as organisms of low pathogenicity. In patients with successful engraftment and minimal graft-versus-host disease, late infections suggestive of continued immune dysfunction (shingles, recurrent lower respiratory infections, Salmonella enteritis and extensive warts) were common.

Adolescent↗
PubMed1999

A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group.

Fluconazole is widely used as antifungal prophylaxis but it is ineffective against Aspergillus. Itraconazole has a broader spectrum of activity but the capsules give erratic bioavailability in neutropenic patients. We compared itraconazole oral solution (which has an improved pharmacokinetic profile) with fluconazole for antifungal prophylaxis. Adults with haematological malignancies receiving chemotherapy or bone marrow transplants were randomly allocated 5 mg/kg/d itraconazole (itra) solution (288 episodes) or 100 mg fluconazole suspension (flu) (293 episodes) from before the onset of neutropenia until neutrophil recovery or suspected fungal infection. Outcomes were assessed by independent reviewers unaware of the prophylaxis allocation. More proven systemic fungal infections occurred in flu (Aspergillus four, Candida tropicalis one, C. krusei one) than itra (C. albicans one) and more of these were fatal (four versus nil). This difference reached statistical significance when first study episodes were considered separately (six flu versus nil itra, P = 0.03). Significantly more deaths of presumed fungal origin occurred in flu than itra (seven versus nil, P = 0.024). There were significantly more cases of proven aspergillosis in flu than itra (six versus nil, P = 0.038, 5/6 cases were fatal) if those occurring outside the study period are included. Significantly more patients receiving flu required amphotericin B (58 v 39, P = 0.043) but this may have been affected by the fact that the study was not blinded. There were 11 proven mucosal candidal infections in flu and four in itra. Itraconazole solution and fluconazole provide effective prophylaxis against Candida but itraconazole affords greater protection against fatal aspergillosis.

Adolescent↗
PubMed1999

Bioassays for itraconazole blood levels: an interlaboratory collaborative study.

Duplicate bioassays for itraconazole and hydroxy-itraconazole were run with 30 serum samples in five laboratories, each using a different method. Both itraconazole and hydroxy-itraconazole were used as standards. Despite quantitative variations, the results of the bioassays correlated sufficiently to indicate the relative level of antifungal activity in the test samples.

Antifungal Agents↗
PubMed1999

In vitro activity of Syn-2869, a novel triazole agent, against emerging and less common mold pathogens.

The in vitro activity of Syn-2869 was compared with that of amphotericin B and itraconazole. MICs for 100 isolates of pathogenic molds belonging to 12 species were determined by a broth microdilution adaptation of the method recommended by the National Committee for Clinical Laboratory Standards. Syn-2869 and itraconazole showed comparable, good activity against the dematiaceous molds Cladophialophora bantiana, Cladophialophora carrionii, Exophiala dermatitidis, Fonsecaea pedrosoi, Phialophora parasitica, and Ramichloridium mackenziei. Neither of the azole agents was active against the hyaline molds Fusarium solani, Scedosporium prolificans, and Scopulariopsis brevicaulis, but both were more active than amphotericin B against Scedosporium apiospermum. The MICs of the three agents were comparable for the mucoraceous mold Absidia corymbifera, but Syn-2869 appeared to be the least active against the dimorphic mold Sporothrix schenckii. Our results suggest that Syn-2869 could be effective against a range of mold infections in humans.

Antifungal Agents↗
PubMed1999

Comparison of the API Candida system with the AUXACOLOR system for identification of common yeast pathogens.

Two commercial systems for the identification of yeasts were evaluated by using 159 clinical isolates that had also been identified by conventional biochemical and morphological methods. The API Candida system correctly identified 146 isolates (91.8%), and the AUXACOLOR system correctly identified 145 isolates (91.2%). However, of the 146 isolates identified by the API Candida system, 23 required supplemental biochemical tests or morphological assessment to obtain the correct identification. The AUXACOLOR system gave no identification in 13 cases (8.2%), while the API Candida system gave an unreadable profile in only one case. Incorrect identifications were more common with the API Candida system (12 isolates; 7.5%) than with the AUXACOLOR system (1 isolate; 0.6%).

Automation↗
PubMed1999

Comparison of E-test and broth microdilution methods for antifungal drug susceptibility testing of molds.

We compared the E test with a broth microdilution method, performed according to National Committee for Clinical Laboratory Standards document M27-A guidelines, for determining the in vitro susceptibilities of 90 isolates of pathogenic molds (10 Absidia corymbifera, 10 Aspergillus flavus, 10 Aspergillus fumigatus, 10 Aspergillus niger, 10 Aspergillus terreus, 10 Exophiala dermatitidis, 10 Fusarium solani, 10 Scedosporium apiospermum, 5 Scedosporium prolificans, and 5 Scopulariopsis brevicaulis). Overall, there was 71% agreement between the results of the two methods for amphotericin B (E-test MICs within +/-2 log2 dilutions of broth microdilution MICs) and 88% agreement with the results for itraconazole. The overall levels of agreement (within +/-2 log2 dilutions) were >/=80% for 5 of the 10 species tested against amphotericin B and 8 of the 10 species tested against itraconazole. The best agreement between the results was seen with A. fumigatus and A. terreus (100% of results for both agents within +/-2 log2 dilutions). The poorest agreement was seen with S. apiospermum, S. prolificans, and S. brevicaulis tested against amphotericin B (20% of results within +/-2 log2 dilutions). In every instance, this low level of agreement was due to isolates for which the broth microdilution MICs were low but for which the E-test MICs were much higher. The E test appears to be a suitable alternative procedure for testing the susceptibility of Aspergillus spp. and some other molds to amphotericin B or itraconazole.

Amphotericin B↗
PubMed1998

Rhizopus microsporus in wooden tongue depressors: a major threat or minor inconvenience?

The investigation and management of an apparent outbreak of Rhizopus spp. in a London paediatric referral centre between September 1995 and April 1996 is described. The organism was identified in microbiological surveillance samples from 23 patients nursed in four hospital areas. Investigations revealed the presence of the organism in spatulae from all ward areas investigated and from closed boxed containers held in the central hospital stores obtained from a new supplier. In contrast, culture of spatulae from the initial supplier failed to yield any fungal isolates. The incident was reported to the Medical Device Agency (MDA), the Central Public Health Laboratory Service (CPHLS) and the Birmingham PHLS. A statement was prepared for the weekly Communicable Disease Report and a hazard warning issued by the MDA. The spatulae were withdrawn from use and the contract with the original supplier was re-established. This incident resulted in contamination of samples only and no patient involvement. It highlights the problems which may follow use of equipment for unintended purposes and the need for good manufacturing practice guidelines to be applied to non-sterile equipment used in direct patient care.

Child↗
PubMed1998

Fungal infections in neutropenia: current problems and chemotherapeutic control.

Invasive fungal infection is a significant problem in neutropenic individuals. The commonest causes of infection are Aspergillus and Candida spp., although a growing number of other organisms (including species of Fusarium and Trichosporon) have been implicated. The clinical manifestations of these infections are described here, and diagnostic problems are discussed. The role of lipid-based formulations of amphotericin B, and of the triazole compounds, itraconazole and fluconazole, in the treatment and prevention of fungal infection is discussed.

Antifungal Agents↗
PubMed1998

In-vitro susceptibility of Cryptococcus neoformans isolates to fluconazole and itraconazole.

The in-vitro susceptibilities of 143 isolates of Cryptococcus neoformans, collected from British patients between 1994 and 1996, to fluconazole and itraconazole were compared with those of 36 isolates collected between 1971 and 1985, 41 isolates collected between 1986 and 1989, and 43 Ugandan isolates collected in 1996. Testing was done with a broth microdilution method in YNB medium supplemented with glucose, incubation at 30 degrees C for 72 h, and an endpoint of 50% inhibition. The results showed that the MIC ranges, MIC50s and MIC90s of fluconazole and itraconazole for C. neoformans isolates from the UK have remained unchanged despite the recent widespread use of triazoles for long-term maintenance of patients with AIDS-associated cryptococcal meningitis. The MIC ranges, MIC50s and MIC90s of the 43 isolates from untreated Ugandan patients with AIDS were similar to those of the British isolates. Examination of our records for 1994-96 revealed six cases in which a four-fold or greater rise in the MIC of fluconazole was associated with relapsed cryptococcal meningitis.

Acquired Immunodeficiency Syndrome↗
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↗
PubMed1998

Comparison of a new commercial colorimetric microdilution method with a standard method for in-vitro susceptibility testing of Candida spp. and Cryptococcus neoformans.

The Sensititre Yeast One method (AccuMed International Ltd, East Grinstead, UK) is a microplate-based procedure that incorporates an oxidation-reduction indicator, Alamar Blue, for the in-vitro testing of five antifungal agents (amphotericin B, fluconazole, itraconazole, ketoconazole and flucytosine). We compared this colorimetric method with a standard broth microdilution test, performed according to US National Committee for Clinical Laboratory Standards document M27-A guidelines, for determining the in-vitro susceptibilities of 180 isolates of Candida spp. (50 Candida albicans, 50 Candida glabrata, ten Candida kefyr, 20 Candida krusei, ten Candida lusitaniae, 20 Candida parapsilosis and 20 Candida tropicalis) and 20 isolates of Cryptococcus neoformans. The overall agreement between the results of the two methods (colorimetric MICs within +/- two log2 dilutions of standard MICs) were 99% for amphotericin B, 96.5% for flucytosine, 93% for itraconazole, 91.5% for fluconazole and 85.5% for ketoconazole. The overall levels of agreement between the two methods were > or = 94% for six of the eight species tested, the exceptions being C. neoformans and C. tropicalis where the overall agreement was 89% and 80% respectively. The poorest agreement between the results for individual agents was seen with C. tropicalis and the three azole agents (60-75% of colorimetric MICs within +/- two log2 dilutions of standard MICs), and C. neoformans for ketoconazole (50%). The Yeast One method appears to be a suitable alternative procedure for routine antifungal susceptibility testing of Candida spp. and C. neoformans.

Antifungal Agents↗
PubMed1998

In-vitro activity of voriconazole, itraconazole and amphotericin B against filamentous fungi.

The in-vitro fungistatic and fungicidal activities of voriconazole were compared with those of itraconazole and amphotericin B. MICs for 110 isolates belonging to 11 species of filamentous fungi were determined by a broth microdilution adaptation of the method recommended by the National Committee for Clinical Laboratory Standards. Minimum lethal concentrations (MLCs) of the three antifungal agents were also determined. The MIC ranges of the three compounds were comparable for Aspergillus flavus, Aspergillus fumigatus, Cladophialophora bantiana and Exophiala dermatitidis. Voriconazole and itraconazole were more active than amphotericin B against Fonsecaea pedrosoi, but the two azole agents were less active against Sporothrix schenckii. Voriconazole was more active than itraconazole or amphotericin B against Scedosporium apiospermum, but less active than the other two agents against two mucoraceous moulds, Absidia corymbifera and Rhizopus arrhizus. Voriconazole and amphotericin B were more active than itraconazole against Fusarium solani. With the exception of S. apiospermum, all the moulds tested had MLC50 values of < or =2 mg/L and MLC90 values of < or =4 mg/L against amphotericin B. Voriconazole and itraconazole showed fungicidal effects against five of the 1 1 moulds tested (A. flavus, A. fumigatus, C. bantiana, E. dermatitidis and F. pedrosoi) with MLC90 values of < or =2 mg/L. In addition, voriconazole was fungicidal for Phialophora parasitica. Our results suggest that voriconazole could be effective against a wide range of mould infections in humans.

Amphotericin B↗
PubMed1998

Comparison of in vitro antifungal activities of free and liposome-encapsulated nystatin with those of four amphotericin B formulations.

The in vitro activity of a multilamellar liposomal formulation of nystatin (Nyotran) was compared with those of free nystatin and four pharmaceutical preparations of amphotericin B. MICs for 200 isolates of two Aspergillus spp., seven Candida spp., and Cryptococcus neoformans were determined by a broth microdilution adaptation of the method recommended by the National Committee for Clinical Laboratory Standards. Minimum lethal concentrations (MLCs) of the six antifungal preparations were also determined. Both nystatin formulations possessed fungistatic and fungicidal activities against the 10 species tested. Liposomal nystatin appeared to be as active as free nystatin, with MICs and MLCs that were similar to, or lower than, those of the latter. Neither formulation of nystatin was as active as amphotericin B deoxycholate (Fungizone) or amphotericin B lipid complex (Abelcet), but both were more effective than liposomal amphotericin B (AmBisome). Our results suggest that further evaluation of liposomal nystatin is justified.

Amphotericin B↗