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Biomedical subjects

John H Rex

Publications and source records attributed to John H Rex.

At least 19 recordsLinked to original sources
PubMed2005

Multicenter clinical evaluation of the (1-->3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans.

BACKGROUND: Measurement of (1-->3)-beta-D-Glucan (BG) has emerged as an adjunct diagnostic strategy for invasive fungal infections (IFI). METHODS: Subjects at 6 clinical sites in the United States were enrolled as either fungal infection-negative subjects (n = 170) or subjects with proven or probable IFI according to European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria (n = 163). A central laboratory and 4 sites performed assays. A single sample was obtained per patient and was evaluated using an assay to detect serum BG derived from fungal cell walls (range, 0 to > 7000 pg/mL). RESULTS: At a cutoff of 60 pg/mL, the sensitivity and specificity of the assay were 69.9% and 87.1%, respectively, with a positive predictive value (PPV) of 83.8% and a negative predictive value (NPV) of 75.1%. At a cutoff value of 80 pg/mL, the sensitivity and specificity were 64.4% and 92.4%, respectively, with a PPV of 89% and an NPV of 73%. Of the 107 patients with proven candidiasis, 81.3% had positive results at a cutoff value of 60 pg/mL, and 77.6% had positive results at a cutoff value of 80 pg/mL. Of the 10 patients with aspergillosis, 80% had positive results at cutoff values of 60 and 80 pg/mL. The 3 subjects diagnosed with Fusarium species had positive results at a cutoff value of 60 pg/mL. Patients infected with Mucor or Rhizopus species (both of which lack BG) had negative results at both cutoff values, and of the 12 patients with Cryptococcus infection, 3 had positive results at a cutoff value of 60 pg/mL, and 2 had positive results at a cutoff value of 80 pg/mL. Of the subjects with proven positive results who were receiving antifungal therapy (n = 118), 72.9% had results positive for BG at a cutoff value of 60 pg/mL, and 69.5% had results positive for BG at a cutoff value of 80 pg/mL. The interlaboratory sample test r2 was 0.93. CONCLUSION: Reproducible assay results with high specificity and high PPV in a multicenter setting demonstrate that use of an assay to detect serum BG derived from fungal cell walls is a useful diagnostic adjunct for IFI.

Adult↗
PubMed2005

Immunomodulation with interferon-gamma and colony-stimulating factors for refractory fungal infections in patients with leukemia.

BACKGROUND: Invasive fungal infections (IFI) in immunocompromised patients are associated with significant morbidity and mortality, despite appropriate antifungal treatment and recovery from neutropenia. The outcome of these infections depends significantly on the overall state of immunosuppression, including mainly the phagocytic system (neutrophils and macrophages). Interferon-gamma (IFN-gamma), granulocyte-colony--stimulating factor (G-CSF) and granulocyte-macrophage-colony--stimulating factor (GM-CSF) are cytokines that enhance the activity of neutrophils and macrophages. METHODS: The authors reported 4 patients with leukemia and refractory invasive candidiasis or trichosporonosis despite 1-13 months of appropriate antifungal treatment. RESULTS: Cytokines were administered for 1.5-5 months without significant toxicity. For each patient, initiation of interferon-gamma plus a colony-stimulating factor resulted in a clinical response. The contribution of cytokines to control the fungal infection in these 4 patients was suggested by the strong inflammatory reaction observed in the 2 patients who had an immediate response (within 7 days of initiation of cytokine therapy) and by the good outcome in the 2 other patients in whom antifungal agents were discontinued at the start of cytokine therapy. CONCLUSIONS: These data suggested a potential role for immunomodulation in patients with leukemia with refractory invasive fungal infections.

Adolescent↗
PubMed2005

Rules for identifying patients at increased risk for candidal infections in the surgical intensive care unit: approach to developing practical criteria for systematic use in antifungal prophylaxis trials.

The high rates of invasive candidiasis among intensive care unit (ICU) patients suggest that antifungal prophylaxis might be of value, but rules identifying patients who would best benefit are not established. Based on a retrospective study of 327 patients who stayed in a surgical ICU for > or = 4 days and had an 11.0% rate of invasive candidiasis, we sought to identify useful predictive rules. As prior work suggests that prompt initiation of prophylaxis is of value, we required our rules to be based on patient data routinely available during the week prior to ICU admission through the third day of the ICU stay. Patients with any combination of diabetes mellitus, new onset hemodialysis, use of total parenteral nutrition, or receipt of broad-spectrum antibiotics had an invasive candidiasis rate of 16.6% versus a 5.1% rate for patients lacking these characteristics (P = 0.001). Fifty-two percent of patients staying > or = 4 days in the ICU met this rule and the rule captured 78% of the patients who eventually developed invasive candidiasis. Risk-stratified antifungal prophylaxis in the ICU is possible. Validation of these results in other types of ICU is now needed.

Adolescent↗
PubMed2005

In vitro synergy testing of anidulafungin with itraconazole, voriconazole, and amphotericin B against Aspergillus spp. and Fusarium spp.

The in vitro interactions of anidulafungin with itraconazole, voriconazole, and amphotericin B were evaluated by using the checkerboard method. For Aspergillus spp., anidulafungin with amphotericin B showed indifference for 16/26 isolates, while anidulafungin with either azole showed a synergy trend for 18/26 isolates. All drug combinations showed indifference for 7/7 Fusarium sp. isolates.

Amphotericin B↗
PubMed2005

Syscan3, a kit for detection of anti-Candida antibodies for diagnosis of invasive candidiasis.

Sera from 76 immunocompetent and 293 immunocompromised subjects were assayed for anti-Candida antibodies. The sensitivity, specificity, positive predictive value, and negative predictive value for invasive candidiasis were 74%, 75%, 62%, and 84% in the immunocompetent group and 15%, 60%, 1.7%, and 93% in the immunocompromised group, respectively. Syscan3 has high negative predictive value.

Antibodies, Fungal↗
PubMed2004

The design of clinical trials that evaluate antifungal prophylaxis and combination therapy: introduction and overview.

On 8 February 2003, the second in a series of meetings in honor of John E. Bennett, M.D., was convened in New York City. A report from the previous meeting was published in 2003. The goal of this second meeting was to discuss the design of clinical trials in prophylaxis and combination therapy. This supplement presents 12 articles by leading clinicians who are currently active in trials in this area and presents a current view of the unmet needs and challenges.

Antifungal Agents↗
PubMed2004

Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.

The Glucatell (1-->3)- beta-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of >or=60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and >or=96% for >or=2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.

Adult↗
PubMed2004

Pharmacokinetic/pharmacodynamic modeling can help guide targeted antimicrobial therapy for nosocomial gram-negative infections in critically ill patients.

Critically ill patients have altered pharmacokinetics (PK) that need to be considered when choosing and dosing antibiotics. We conducted a prospective, observational study to assess clinical and microbiologic response rates in 19 critically ill patients with nosocomial Gram-negative infections. Antibiotics were dosed based on a mathematical pharmacodynamic (PD) model accounting for these altered kinetic parameters. The average APACHE II score +/- SE on intensive care unit admission and at the time of infection was 13.6 +/- 1.2 and 14.6 +/- 1.1, respectively. With targeted antimicrobial therapy adjusted to achieve an optimal PD profile, 17/19 (89%) patients had a clinical cure or improvement and 16/19 (84%) had either microbiologic eradication or presumed eradication. Modeling PD in these critically ill patients resulted in good clinical and microbiologic outcomes.

APACHE↗
PubMed2004

Pharmacokinetics of intravenous itraconazole in stable hemodialysis patients.

The pharmacokinetics of intravenous itraconazole (ITC) was studied in dialysis patients. Dialysis had no effect on the half-life and clearance of ITC or OH-ITC. However, dialysis allowed the clearance of hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The area under the concentration-time curve from time zero to infinity (AUC(0- infinity)) for HP-beta-CD administered before dialysis was lower than the AUC(0- infinity) when it was administered after dialysis (P < 0.01). Administration of ITC intravenously just prior to hemodialysis appears to produce adequate systemic exposures of ITC and OH-ITC while allowing dialysis clearance of HP-beta-CD. Studies of multiple administrations are warranted.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2004

Interlaboratory comparison of results of susceptibility testing with caspofungin against Candida and Aspergillus species.

Seventeen laboratories participated in a study of interlaboratory reproducibility with caspofungin microdilution susceptibility testing against panels comprising 30 isolates of Candida spp. and 20 isolates of Aspergillus spp. The laboratories used materials supplied from a single source to determine the influence of growth medium (RPMI 1640 with or without glucose additions and antibiotic medium 3 [AM3]), the same incubation times (24 h and 48 h), and the same end point definition (partial or complete inhibition of growth) for the MIC of caspofungin. All tests were run in duplicate, and end points were determined both spectrophotometrically and visually. The results from almost all of the laboratories for quality control and reference Candida and Aspergillus isolates tested with fluconazole and itraconazole matched the NCCLS published values. However, considerable interlaboratory variability was seen in the results of the caspofungin tests. For Candida spp. the most consistent MIC data were generated with visual "prominent growth reduction" (MIC(2)) end points measured at 24 h in RPMI 1640, where 73.3% of results for the 30 isolates tested fell within a mode +/- one dilution range across all 17 laboratories. MIC(2) at 24 h in RPMI 1640 or AM3 also gave the best interlaboratory separation of Candida isolates of known high and low susceptibility to caspofungin. Reproducibility of MIC data was problematic for caspofungin tests with Aspergillus spp. under all conditions, but the minimal effective concentration end point, defined as the lowest caspofungin concentration yielding conspicuously aberrant hyphal growth, gave excellent reproducibility for data from 14 of the 17 participating laboratories.

Antifungal Agents↗