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Biomedical subjects

P E Verweij

Publications and source records attributed to P E Verweij.

At least 19 recordsLinked to original sources
PubMed2006

Primary hepatic invasive aspergillosis with progression after rituximab therapy for a post transplantation lymphoproliferative disorder.

We present a case of primary hepatic and possible splenic invasive aspergillosis (IA), which progressed under anti-CD20 B cell treatment for posttransplantation lymphoproliferative disease following allogeneic stem cell transplantation, to highlight the clinical value of a positive galactomannan-antigen test, an intestinal portal of entry of Aspergillus, and the detrimental effect of B lymphocyte depletion in IA.

Antibodies, Monoclonal↗
PubMed2006

Successful treatment of liposomal amphotericin B refractory Candida glabrata fungaemia in a patient undergoing a stem cell transplantation.

Blood stream infections caused by Candida glabrata are difficult to manage. We describe a patient who underwent an allogeneic peripheral stem cell transplantation for acute myeloid leukaemia. The patient developed C. glabrata fungaemia that was refractory to liposomal amphotericin B therapy. After changing the therapy to caspofungin, blood cultures became sterile within two days and the patient recovered clinically. The patient died shortly after due to graft-versus-host disease and at autopsy there was no evidence of residual or persistent Candida infection. Caspofungin was effective in liposomal amphotericin-B refractory C. glabrata fungaemia and proved to rapidly clear the infection. Treatment options for candidaemia are discussed.

Amphotericin B↗
PubMed2005

[Improved diagnostics in invasive aspergillosis and systematic monitoring in patients at high risk of infection].

Invasive aspergillosis remains an important cause of morbidity and mortality in patients with prolonged and severe immune suppression such as following haematopoietic stem-cell transplantation. Consensus definitions, which allow categorisation of patients based on diagnostic criteria, are an important improvement in uniform registration of invasive mycoses in clinical trials. Prospective monitoring of high-risk patients for the circulating aspergillus cell-wall component galactomannan, results in earlier diagnosis in two-thirds of patients when compared with conventional diagnostic methods. High-resolution CT (HRCT) enables the lesions characteristic of invasive mycoses to be detected earlier and better than by chest radiograph. In addition, invasive mycoses cause characteristic lesions on the HRCT scan including the halo-sign and the air-crescent sign. The pre-emptive management strategy which combines monitoring of patients for surrogate markers with a HRCT scan appears to be a promising approach to the early identification and treatment of patients with invasive aspergillosis.

Aspergillosis↗
PubMed2005

Advances in diagnostic testing.

Within the past decade surrogate markers have become important and reliable tools for the early diagnosis of invasive aspergillosis. Surrogate markers include the antigens galactomannan and (1 --> 3)-beta-D-glucan for which commercial assays are available, as well as fungal DNA for which experimental PCR assays have been developed. Although many clinical validation studies have been performed, the kinetics of these markers are still largely unknown. Recent studies have addressed several issues related to variables that interact with the performance of the assays, including exposure to mould-active antifungal agents and the interpretive cut-off levels. Insights gained as a result of these studies will help us to further optimize management strategies and to determine the optimal test sequence.

Aspergillosis↗
PubMed2005

Clinical implications of environmental sources for Aspergillus.

Invasive aspergillosis presents a formidable problem for both diagnosis and therapy. Therefore, prevention is a very important strategy in controlling this disease. Preventing invasive aspergillosis demands a clear understanding of the environmental sources of Aspergillus spp. and how this mould is transmitted to patients. Insight into the sources of exposure, mechanisms of transmission, and host susceptibility to infection are vital to appropriately direct preventive strategies to those settings where the risk of infection is the highest and consequently the impact of prevention the greatest.

Aspergillosis↗
PubMed2005

Efficacy and pharmacodynamics of flucytosine monotherapy in a nonneutropenic murine model of invasive aspergillosis.

The therapeutic efficacy of flucytosine (5FC) monotherapy and the pharmacodynamic index predictive of efficacy were evaluated in a nonneutropenic mouse model of acute invasive aspergillosis. Mice were infected intravenously with an Aspergillus fumigatus isolate (the median MICs of 5FC were 128 mug/ml under the standard condition, 0.5 microg/ml at pH 6.0, and 0.031 microg/ml at pH 5.0) 2 h prior to the start of therapy and were treated for 7 days with different 5FC dosing regimens. The total doses ranged from 50 to 800 mg/kg of body weight/day and were administered at 6-, 12-, and 24-h intervals. The efficacy was assessed by means of survival. The survival rates of the treatment groups ranged from 40 to 90%, while the survival rate of the control group was 20%. The efficacy found depended primarily on the total daily dose. However, the power of our sample size may have been too low to exclude an effect of dose fractionation. The pharmacodynamic index that most strongly correlated with the efficacy was the area under the serum concentration-time curve and MIC ratio (R(2) = 0.86). We conclude that 5FC monotherapy is efficacious in a murine Aspergillus fumigatus infection model.

Animals↗
PubMed2005

Relationship between in vitro activities of amphotericin B and flucytosine and pH for clinical yeast and mold isolates.

In this study, we investigated the pH dependency of the in vitro activities of amphotericin B (AMB) and flucytosine (5FC) against Candida spp., Cryptococcus neoformans, Aspergillus fumigatus, Rhizopus spp., and Scedosporium prolificans in RPMI 1640 buffered with citrate buffer (pH 4.0, 5.0, 5.4, and 6.0), citrate-phosphate buffer (pH 5.4, 6.0, 6.4, and 7.0), and 3-[N-morpholino]propanesulfonic acid (MOPS) (pH 6.4, 7.0, 7.4, and 7.9). For 5FC, no significant differences were found between MICs obtained with the different buffers, while for AMB, significant differences were found. The MICs obtained with citrate-phosphate buffer were approximately 1 twofold-dilution step higher than the MICs obtained with MOPS. We demonstrated that the in vitro activities of AMB and 5FC against yeast and mold isolates were pH dependent. The in vitro activity of AMB decreased when the pH was lowered, while the in vitro activity of 5FC increased. The effect of the pH on the in vitro activities was dependent not only on the antifungal agent tested but also on the microorganism. For AMB, there was a nonlinear relationship (median r(2), 0.864) for Candida spp., C. neoformans, A. fumigatus, and Rhizopus spp. over the pH range tested. The mean MICs ranged from 0.5 to 2.52 microg/ml at pH 7.0 and from 20.16 to 32 microg/ml at pH 5.0. For S. prolificans, there was no relationship. For 5FC, there was a linear relationship for Candida spp. (median r(2), 0.767) and a nonlinear relationship for C. neoformans and A. fumigatus (median r(2), 0.882) over the pH range tested. The mean MIC values ranged from 0.125 to 1,024 microg/ml at pH 7.0 and from 0.02 to 4 microg/ml at pH 5.0. For Rhizopus spp. and S. prolificans, the relationship could not be determined, since the MIC was >1,024 microg/ml over a pH range of 4.0 to 7.9.

Amphotericin B↗
PubMed2005

International and multicenter comparison of EUCAST and CLSI M27-A2 broth microdilution methods for testing susceptibilities of Candida spp. to fluconazole, itraconazole, posaconazole, and voriconazole.

The aim of this study was to compare MICs of fluconazole, itraconazole, posaconazole, and voriconazole obtained by the European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI (formerly NCCLS) methods in each of six centers for 15 Candida albicans (5 fluconazole-resistant and 4 susceptible-dose-dependent [S-DD] isolates), 10 C. dubliniensis, 7 C. glabrata (2 fluconazole-resistant isolates), 5 C. guilliermondii (2 fluconazole-resistant isolates), 10 C. krusei, 9 C. lusitaniae, 10 C. parapsilosis, and 5 C. tropicalis (1 fluconazole-resistant isolate) isolates. CLSI MICs were obtained visually at 24 and 48 h and spectrophotometric EUCAST MICs at 24 h. The agreement (within a 3-dilution range) between the methods was species, drug, and incubation time dependent and due to lower EUCAST than CLSI MICs: overall, 94 to 95% with fluconazole and voriconazole and 90 to 91% with posaconazole and itraconazole when EUCAST MICs were compared against 24-h CLSI results. The agreement was lower (85 to 94%) against 48-h CLSI endpoints. The overall interlaboratory reproducibility by each method was > or =92%. When the comparison was based on CLSI breakpoint categorization, the agreement was 68 to 76% for three of the four species that included fluconazole-resistant and S-DD isolates; 9% very major discrepancies (< or =8 microg/ml versus > or =64 microg/ml) were observed among fluconazole-resistant isolates and 50% with voriconazole (< or =1 microg/ml versus > or =4 microg/ml). Similar results were observed with itraconazole for seven of the eight species evaluated (28 to 77% categorical agreement). Posaconazole EUCAST MICs were also substantially lower than CLSI MIC modes (0.008 to 1 microg/ml versus 1 to > or =8 microg/ml) for some of these isolates. Therefore, the CLSI breakpoints should not be used to interpret EUCAST MIC data.

Antifungal Agents↗
PubMed2005

Comparison of visual 24-hour and spectrophotometric 48-hour MICs to CLSI reference microdilution MICs of fluconazole, itraconazole, posaconazole, and voriconazole for Candida spp.: a collaborative study.

A multicenter (six-center) study evaluated the performance (interlaboratory reproducibility, compatibility with reference methods, and categorical agreement) of 24-h visual and 48-h spectrophotometric MICs. MICs of fluconazole, itraconazole, voriconazole, and posaconazole were compared to reference 48-h microdilution broth visual MICs (CLSI [formerly NCCLS] M27-A2 document) for 71 isolates of Candida spp. that included 10 fluconazole-resistant strains. Twenty readings (5%) were reported as showing no growth at 24 h, mostly for Candida dubliniensis and from a single center. The overall interlaboratory agreement of 24-h visual readings and 48-h spectrophotometric MICs, as well their compatibility with reference values, were excellent with the four triazoles for most of the species (93 to 99%, within 3 dilutions). The categorical agreement between the investigational reading conditions and reference values was good with fluconazole and voriconazole (93 to 97%) but lower with itraconazole (86 to 88%), due primarily to minor errors. There were only 0 to 3% very major errors with these three triazoles; the number of substantial errors (more than three dilutions) was also low (<2%) with posaconazole. These data suggest that the performance of both investigational MIC readings gives results similar to those of reference MICs. Since spectrophotometric MICs are more objective and the 24-h time period would shorten the MIC determination of azoles, the description of either of these two reading conditions in the M27-A2 document should be considered by the CLSI subcommittee in addition to or instead of the longer, less practical, and more subjective 48-h visual MIC reading.

Antifungal Agents↗
PubMed2004

[New developments in antifungal therapy: fluconazole, itraconazole, voriconazole, caspofungin].

The azole antifungal voriconazole and the echinocandin caspofungin have recently become available for the treatment of invasive mycoses. Fluconazole remains the drug of choice for candidemia, except for infections with one of the resistent species such as Candida krusei and some strains of Candida glabrata. In these cases, as well as in patients who cannot tolerate azoles in connection with side effects or drug interactions, caspofungin is an attractive alternative. Voriconazole has become the drug of choice for severe invasive aspergillosis. Itraconazole is a good alternative for milder and chronic forms of aspergillosis. The use of conventional amphotericin B will be limited by the availability of the new drugs. In view of their high costs, the lipid-bound forms of amphotericin B will usually be given only as salvage therapy in case of failure, in patients who are unable to tolerate either conventional amphotericin or one of the newer agents, and for the treatment of zygomycosis.

Amphotericin B↗
PubMed2004

In vitro interactions between amphotericin B, itraconazole, and flucytosine against 21 clinical Aspergillus isolates determined by two drug interaction models.

Combination therapy of flucytosine (5FC) with other antifungal agents could be of use for the treatment of invasive aspergillosis. However, interpretation of the results of in vitro interactions is problematic. The fractional inhibitory concentration (FIC) index is the most commonly used method, but it has several major drawbacks in characterizing antifungal drug interaction. Alternatively, a response surface approach using the concentration-effect relationship over the whole concentration range instead of just the MIC can be used. We determined the in vitro interactions between amphotericin B (AMB), itraconazole, and 5FC against 21 Aspergillus isolates with a broth microdilution checkerboard method that employs the dye MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]. FIC indices based on three different MIC endpoints (MIC-0, MIC-1, and MIC-2) and the interaction coefficient alpha were determined, the latter by estimation from the response surface approach described by Greco et al. (W. R. Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995). The value obtained for the FIC index was found to be dependent on the MIC endpoint used and could be either synergistic, indifferent, or antagonistic. The response surface approach gave more consistent results. Of the three combinations tested, the AMB-5FC combination was the most potent in vitro against Aspergillus spp. We conclude that the use of the response surface approach for the interpretation of in vitro interaction studies of antifungals may be helpful in order to predict the nature and intensity of the drug interaction. However, the correlation of these results with clinical outcome remains difficult and needs to be further investigated.

Algorithms↗
PubMed2004

Effect of pH on the in vitro activities of amphotericin B, itraconazole, and flucytosine against Aspergillus isolates.

The in vitro susceptibilities of 21 Aspergillus isolates were tested against three antifungal agents in RPMI 1640 and yeast nitrogen base at pH 5.0 and 7.0 by a broth microdilution format of the NCCLS method. The MICs of amphotericin B and itraconazole were higher, while those of flucytosine were lower, at pH 5.0 than at pH 7.0. The poor correlation between in vitro results and clinical outcome could be due to a difference in pH between the in vitro susceptibility test and at the site of infection.

Amphotericin B↗
PubMed2004

Routine use of a commercial test, GLABRATA RTT, for rapid identification of Candida glabrata in six laboratories.

When evaluated in six clinical laboratories from six countries with 1,174 fresh isolates, including 715 Candida glabrata and 459 non-C. glabrata strains, GLABRATA RTT (Fumouze Diagnostics, Levallois Perret, France) yielded an overall sensitivity and an overall specificity of 95.8 and 98.9%, respectively. The results were consistent from one laboratory to another. The five false-positive results corresponded to C. parapsilosis (n = 2), C. tropicalis, C. guilliermondii, and C. lusitaniae. GLABRATA RTT allows a rapid, cost-effective, and reliable presumptive identification of C. glabrata.

Candida glabrata↗
PubMed2003

Antifungal activity of nonantifungal drugs.

The antifungal activity of synthetic, nonchemotherapeutic compounds, antineoplastic agents and antibacterial drugs, such as sulphonamides, has been known since the early 20th century (1932). In this context, the term "nonantifungal" is taken to include a variety of compounds that are employed in the management of pathological conditions of nonfungal infectious etiology but have been shown to exhibit broad-spectrum antifungal activity. In this review, the antifungal properties of compounds such as chlorpromazine, proton pump inhibitors, antiarrhythmic agents, cholesterol-lowering agents, antineoplastic and immunosuppressive agents, antiparasitic drugs and antibiotics are described. Since fungi are eukaryotic cells, they share many pathways with human cells, thus increasing the probability of antifungal activity of "nonfungal drugs". The potential of these drugs for treatment of fungal infections has been investigated sporadically using the drugs alone or in combination with "classic" antifungal agents. A review of the literature, supplemented with a number of more recent investigations, suggests that some of these compounds enhance the activity of conventional antifungal agents, eliminate natural resistance to specific antifungal drugs (reversal of resistance) or exhibit strong activity against certain fungal strains in vitro and in animal models. The role of these agents in the epidemiology and in the clinical manifestations of fungal infections and the potential of certain drugs for treatment of invasive fungal infections require further investigation.

Adrenergic beta-Antagonists↗
PubMed2003

In vitro activity of amphotericin B and itraconazole in combination with flucytosine, sulfadiazine and quinolones against Exophiala spinifera.

The combined effects of antifungal and antibiotic drugs against Exophiala spinifera were evaluated in vitro by the chequer-board method, calculated as a fractional inhibitory concentration (FIC) index. Amphotericin B was combined with flucytosine and ciprofloxacin, whereas itraconazole was combined with ciprofloxacin, levofloxacin, lomefloxacin and sulfadiazine. Synergic effects were observed for the combinations of itraconazole with ciprofloxacin and levofloxacin, and amphotericin B with ciprofloxacin and flucytosine. No antagonism was observed for any combination tested.

Amphotericin B↗
PubMed2003

Multicenter evaluation of the reproducibility of the proposed antifungal susceptibility testing method for fermentative yeasts of the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST).

OBJECTIVE: To evaluate the intra- and inter-laboratory reproducibility of a new standard for susceptibility testing of fermentative yeasts. This standard is based on the M27-A procedure of the National Committee for Clinical Laboratory Standards (NCCLS), but incorporates several modifications, including spectrophotometric growth-dependent endpoint reading. METHODS: Nine laboratories participated in the study. Common material lots were used to test six Candida species (one each of C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. lusitaniae), and two quality control strains (C. krusei ATCC6258 and C. parapsilosis ATCC22019). Triplicate testing on three separate days was performed in microtiter format with RPMI-2% glucose, pH 7.0. Flucytosine, fluconazole and itraconazole were tested. In total, 3888 MIC values were included in the analyses. Reproducibility was calculated by means of agreement (percentage of MICs within one two-fold dilution of the mode) and intraclass correlation coefficient (ICC, maximum value of 1). RESULTS: The average intra-laboratory agreements were 99% and 96% after 24 h and 48 h of incubation, respectively, with ICCs of 0.98 and 0.97 (P < 0.05). Two strains exhibiting a trailing effect showed intra-laboratory agreement of 92% and ICCs of < 0.91 at 48 h. The inter-laboratory agreement was 94% and 88% after 24 h and 48 h, respectively, with ICCs of 0.93 and 0.91 (P < 0.05). Lower values of agreement and ICCs were obtained for strains exhibiting trailing after 48 h of incubation. Itraconazole yielded the lowest values of reproducibility. CONCLUSION: The new procedure of EUCAST for antifungal susceptibility testing is a reproducible method within and between laboratories and offers several advantages over the NCCLS approved method.

Advisory Committees↗
PubMed2003

Two cases of subcutaneous Scedosporium apiospermum infection treated with voriconazole.

Scedosporium apiospermum is a mold that is increasingly being recognized as an opportunistic pathogen in immunocompromised patients, and treatment is complicated by intrinsic resistance to several antifungal agents. In our hospital, two cases of S. apiospermum infection occurring within 2 weeks were successfully treated with voriconazole. Since both patients were infected with an uncommon pathogen, a search for a common nosocomial source was performed. As environmental cultures yielded no S. apiospermum, and random amplified polymorphic DNA (RAPD) fingerprinting showed that the patients' strains were genotypically unrelated, we considered a common nosocomial source of S. apiospermum to be unlikely.

Aged↗