Search PubMed⌕ Search

Biomedical subjects

J N Galgiani

Publications and source records attributed to J N Galgiani.

At least 73 records · Page 4Linked to original sources
PubMed1992

Collaborative comparison of broth macrodilution and microdilution antifungal susceptibility tests.

A collaborative comparison of macro- and microdilution antifungal susceptibility tests was performed in five laboratories. MICs of amphotericin B, fluconazole, flucytosine, and ketoconazole were determined in all five centers against 95 coded isolates of Candida spp., Cryptococcus neoformans, and Torulopsis glabrata. A standard protocol with the following National Committee for Clinical Laboratory Standards Subcommittee on Antifungal Susceptibility Testing recommendations was used: an inoculum standardized by spectrophotometer, buffered (RPMI 1640) medium (pH 7.0), incubation at 35 degrees C, and an additive drug dilution procedure. Two inoculum sizes were tested (1 x 10(4) to 5 x 10(3) to 2.5 x 10(3) CFU/ml) and three scoring criteria were evaluated for MIC endpoint determinations, which were scored as 0 (optically clear), < or = 1 (slightly hazy turbidity), and < or = 2 (prominent decrease in turbidity compared with that of the growth control). Overall intra- and interlaboratory reproducibility was optimal with the low-density inoculum, the second-day readings, and MICs scored as either 1 or 2. The microdilution MICs demonstrated interlaboratory agreement with most of the four drugs higher than or similar to that of the macrodilution MICs. In general, there was good interlaboratory agreement with amphotericin B, fluconazole, and flucytosine; ketoconazole gave more variable results.

Antifungal Agents↗
PubMed1991

Interaction of human peripheral blood mononuclear cells with Coccidioides immitis arthroconidia.

We explored the in vitro interaction of human peripheral blood mononuclear cells with the arthroconidial stage of the fungus Coccidioides immitis. Fresh peripheral blood monocytes in an adherent monolayer were capable of ingesting C. immitis. Further, peripheral blood monocytes from either skin-test-positive or skin-test-negative donors significantly decreased the in vitro growth of C. immitis when coccidioidal arthroconidia were incubated with monocytes. Peripheral blood mononuclear cells also reduced fungal incorporation of the chitin precursor N-acetyl glucosamine. Cell fractions consisting predominantly of monocytes were significantly more active in this regard than fractions containing predominantly lymphocytes. Moreover, this activity was independent of the coccidioidal skin-test status of the donor. We conclude that human fresh peripheral blood mononuclear cells are able to phagocytize C. immitis arthroconidia and have the ability to inhibit its growth in vitro. That these abilities are independent of the immune status of the donor supports the possibility that the peripheral blood monocyte may contribute to the early defense against initial coccidioidal infection.

Acetylglucosamine↗
PubMed1991

New serologic tests for early detection of coccidioidomycosis.

Arizona college students suspected of having recently acquired coccidioidomycosis were tested for anticoccidioidal antibodies and circulating fungal antigens using conventional antibody detection methods and new ELISA procedures. Of 233 patients with compatible symptoms, 26 had anticoccidioidal antibodies detected by conventional tests. ELISA detected antibodies in sera from 20 of these patients and also from another 25 patients. Patients with antibodies detected by either conventional or ELISA procedures were significantly more likely to have abnormal chest radiographs, elevated erythrocyte sedimentation rates, or absent upper respiratory symptoms than were other patients. Circulating antigen was found in sera from 35 patients, 33 of whom had no detectable anticoccidioidal antibodies at that time. Detectable antigen was noted frequently in sera obtained within the first month after the onset of symptoms and was infrequently detected later when more patients exhibited antibodies. These results indicate the feasibility of developing ELISA procedures using spherule-derived antigens for earlier detection of coccidioidal infections.

Antigens, Fungal↗
PubMed1991

An immunoreactive apoglycoprotein purified from Coccidioides immitis.

Deglycosylation of glycoproteins in a lysate of spherules of Coccidioides immitis has permitted purification and partial characterization of a proline-rich pronase-sensitive antigen. Moreover, soluble antigen specifically stimulated lymphocytes from persons with dermal delayed-type hypersensitivity to coccidioidal antigens. When related to reference coccidioidin by tandem two-dimensional immunoelectrophoresis, the antigen fused in the anodal region with a specific reference antigen (antigen 2). It did not show identity with coccidioidal antigens used in conventional serologic assays. Although immunoblots of the purified protein with monospecific rabbit antiserum showed a single antigen at 33 kDa, the parent spherule lysate bound the same antibody in a broad band between 70 and greater than 200 kDa, which could be explained by microheterogeneity of glycosylation. Immunoelectron microscopy using affinity-purified human antibodies localized the antigen to the cell wall and internal septa of spherules. These findings suggest that the apoglycoprotein may be important in human immune responses to coccidioidal infection.

Antigens, Fungal↗
PubMed1990

Itraconazole treatment of coccidioidomycosis. NAIAD Mycoses Study Group.

PURPOSE: The purpose of this study was to assess the tolerance and efficacy of itraconazole in the treatment of coccidioidomycosis. PATIENTS AND METHODS: Fifty-one patients with nonmeningeal coccidioidomycosis were considered for treatment with intraconazole. Forty-nine patients who met study criteria were treated with itraconazole given orally in doses of 100 to 400 mg/day for periods up to 39 months. Of these patients, 12 had osteoarticular disease, 23 had chronic pulmonary disease, and 14 had skin or soft tissue disease. Clinical response was evaluated using a scoring system accounting for lesion number and size, symptoms, culture, and serologic titer. Remission was defined as reduction of the pretreatment score by 50% or more. RESULTS: Patients with osteoarticular, chronic pulmonary, and soft tissue disease improved at similar rates. Because two patients had no scoring assessment for efficacy, they were considered inassessable for efficacy. Forty-seven patients are evaluable. Of these patients, 44 have completed therapy, and three are still receiving itraconazole. Of the 44 patients no longer receiving therapy, 25 (57%) achieved remission. Of the 25 patients achieving remission, four later experienced a relapse. Therapy failed in 19 patients (43%). Of these cases, 16 (36%) were clinical failures and three (7%) developed drug intolerance that precluded continuation of treatment. Evaluation of culture conversions was of limited value in the osteoarticular patients, fewer than half of whom had follow-up biopsies. However, culture conversions were a useful index of response in patients with chronic pulmonary disease. During the course of treatment, serologic titers declined in the two groups with extrapulmonary disease, but not in patients with pulmonary coccidioidomycosis. Possible toxicities were generally mild. CONCLUSION: Itraconazole appears efficacious and very well tolerated in patients with coccidioidomycosis.

Adolescent↗
PubMed1990

Activity of cilofungin against Coccidioides immitis: differential in vitro effects on mycelia and spherules correlated with in vivo studies.

Cilofungin, a new antifungal drug, was found to inhibit mycelial growth of Coccidioides immitis. Light and electron microscopic observations indicated delay in development of the outer hyphal wall. Cilofungin also blocked incorporation of the chitin substrate, N-acetylglucosamine, into mycelia. However, when C. immitis was grown under conditions that induced spherule development, drug effects were dramatically decreased. Furthermore, efficacy of cilofungin in treatment of murine coccidioidomycosis could not be demonstrated. These studies indicate that glucan-synthase inhibitors have activity against C. immitis, and other compounds with different pharmacologic properties or in combination with other antifungal drugs may exploit this biologic effect.

Animals↗
PubMed1990

Coccidioidomycosis in human immunodeficiency virus-infected patients.

Coccidioidomycosis is at best a complicated fungal infection; often it is life-threatening. Coccidioidomycosis is confined epidemiologically to the southwestern region of the USA, and most cases have occurred in that area, particularly in Arizona. However, we have seen several cases in San Francisco in patients with only a history of travel to endemic areas. In part because of its regional distribution, information about the clinical presentation, diagnosis, and treatment of patients with coccidioidomycosis has lagged behind information about other, more commonly encountered AIDS-associated opportunistic infections. Drs. Galgiani and Ampel have probably had the largest single experience with coccidioidomycosis in individuals infected with the human immunodeficiency virus. These specialists share their experience and make recommendations as to how these complicated conditions should be approached.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Coccidioidomycosis during human immunodeficiency virus infection. A review of 77 patients.

Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of incubation temperature, inoculum size, and medium on agreement of macro- and microdilution broth susceptibility test results for yeasts.

We examined the effects of temperature and inoculum on the agreement of macro- and microdilution broth MICs of five antifungal agents against six isolates of Candida species or Torulopsis glabrata. Incubation temperature affected results with amphotericin B, flucytosine, fluconazole, and SCH 39304, producing better agreement at 35 degrees C than at 37 degrees C. Agreement between methods was better with an inoculum size of 10(2) than with one of 10(4) yeast cells per ml in testing fluconazole or SCH 39304, and the discrepancies seen with a higher incubation temperature and a larger inoculum appeared to be additive. However, inoculum size did not seem to affect agreement between methods in testing amphotericin B, flucytosine, or ketoconazole. Regardless of test conditions, macrodilution broth MICs of amphotericin B for different isolates were strikingly higher than microdilution test MICs, with mean differences being greater than ninefold under some test conditions. We conclude that for most currently available antifungal agents, an incubation temperature of 35 degrees C and a starting yeast inoculum of less than 10(4) cells per ml improve the agreement between macro- and microdilution broth tests.

Amphotericin B↗
PubMed1990

Collaborative investigation of variables in susceptibility testing of yeasts.

A multicenter study was performed to evaluate the effect of medium, incubation time (24 and 48 h), and temperature (30 and 35 degrees C) on intra- and interlaboratory variations in MICs of flucytosine, amphotericin B, and ketoconazole for yeasts. Testing was performed on coded isolates of Candida species (11 strains) and Cryptococcus neoformans (2 strains) by using a standard macrodilution protocol 11 laboratories. Four chemically defined media buffered to pH 7.0 with morpholinepropanesulfonic acid were evaluated, including buffered yeast nitrogen base, synthetic amino acid medium-fungal, RPMI 1640 medium, and high-resolution antifungal assay medium. Intralaboratory variability was less than or equal to fourfold for 97% of the replicate sets of data. The highest level of interlaboratory agreement, irrespective of antifungal agent or incubation conditions, was observed with RPMI 1640 medium. Intralaboratory variability was less than or equal to fourfold for 93% of the determinations with ketoconazole and 100% with flucytosine tested in RPMI 1640 medium at 35 degrees C for 24 h. Variability in amphotericin B results was less than or equal to fourfold for 81% of the determinations in RPMI 1640 medium at 35 degrees C for 48 h. The rank order of MICs within each antifungal test group was similar among the various laboratories and was generally in agreement with the reference rank order regardless of the test medium that we used.

Amphotericin B↗
PubMed1990

Killing of Coccidioides immitis by hypochlorous acid or monochloramine.

To identify possible explanations for the resistance of Coccidioides immitis to killing by human neutrophils, its susceptibility to typical oxidants generated during the neutrophil respiratory burst was compared to the sensitivity of other microbes. When microbial suspensions were exposed to hypochlorous acid, arthroconidia or spherules of C. immitis were killed more slowly than yeast cells of Candida (Torulopsis) glabrata or Staphylococcus aureus. In contrast, exposure to the more lipophilic oxidant, monochloramine, produced equivalent rates of killing for spherules and yeast cells of C. glabrata, and arthroconidia were killed more rapidly. When larger microbial concentrations were used, significantly greater concentrations of hypochlorous acid were required to kill equivalent percentages of spherules as compared to yeast cells of C. glabrata. Mixing studies with either whole spherules or extracts of spherules demonstrated that these substances could also block hypochlorous acid killing of S. aureus. These studies suggest possible mechanisms whereby C. immitis might resist oxidative phagocytic killing.

Chloramines↗
PubMed1990

Coccidioides immitis in patients with human immunodeficiency virus infections.

Coccidioidomycosis in human-immunodeficiency virus-infected patients poses frequent and significant problems. Most cases are presently concentrated in regions highly endemic for the fungus. Infection most frequently involves the lungs, and diffuse reticulonodular infiltrates are typical. Disease has also been evident in extrapulmonary sites including meningitis. When progressive disease occurs, most patients already have low CD4 lymphocyte counts. In such cases, effective therapies have included amphotericin B, ketoconazole, and newer investigational agents such as itraconazole, and fluconazole. Although coccidioidal infections have developed in only a few patients away from the endemic regions, those that have suggest that reactivation is possible.

Antifungal Agents↗
PubMed1989

Coccidioidomycosis.

Coccidioidomycosis is a largely self-limited fungal respiratory illness. However, the infrequent case of progressive or disseminated disease can be devastating. As international travel to and from endemic areas increases, physicians unfamiliar with the disease may be called upon to recognize and treat serious coccidioidal infections. The major risk factors for dissemination are race and immunosuppression. The most common sites of dissemination are the skin, lymph nodes, bone and meninges. Diagnosis is aided by investigation of the patient's clinical history, delayed-type hypersensitivity skin test reaction, serologic testing, and recovery of organisms from infected tissue or secretions for direct examination and culture. Fungicidal agents are not available, fortunately, fungistatic therapy allows many patients to recover. The availability of both intravenous/intrathecal and oral agents now allows more therapeutic flexibility in the treatment of this disease.

Amphotericin B↗
PubMed1989

pH and other effects on the antifungal activity of cilofungin (LY121019).

We investigated the effects of various test conditions on broth macro- and microdilution susceptibility test results for several species of yeasts with a new antifungal agent, cilofungin. As the pH decreased from 7.4 to 3.0, 50% inhibitory concentrations (IC1/2) increased up to 64-fold. This effect was unrelated to yeast growth rate, solvent concentration, or choice of buffer. Broth microdilution results for 42 Candida albicans isolates at pH 7.4 in synthetic amino acid medium, fungal (SAAMF), showed IC1/2 results from 0.08 to 2.5 micrograms/ml, whereas at pH 3.0 the results were 5.0 or 10.0 micrograms/ml. Fungicidal concentrations were closer to MIC results at the lower pH, i.e., an average of 16-fold above the MIC at pH 3.0, compared with an average 256-fold difference at pH 7.4. Two strains that had very different IC1/2 results at pH 7.4 and identical IC1/2 results at pH 3.0 were found to be equally susceptible to cilofungin therapy in rats. In additional studies, other medium effects were demonstrable, with yeast nitrogen broth and minimal essential medium generally yielding higher results than two other synthetic media (SAAMF and RPMI 1640 medium). However, susceptibility results did not change with inoculum between 10(2) and 10(5) yeast cells per ml or temperature between 30 and 37 degrees C. These studies indicate that pH is an important influence on in vitro rank order susceptibility of pathogenic yeasts to cilofungin.

Animals↗
PubMed1989

In vitro susceptibilities of yeasts to a new antifungal triazole, SCH 39304: effects of test conditions and relation to in vivo efficacy.

We used six candidal strains (two Candida albicans and one each of four other species) to study the effects of test conditions on the activity of SCH 39304 compared with that of fluconazole in broth macro- and microdilution assays. Increasing the inoculum from 10(2) to 10(5) yeasts per ml raised the MICs for all isolates up to greater than 512-fold. In contrast, results with a 50% turbidimetric endpoint (50% inhibitory concentration; IC1/2) varied no more than twofold. Similar effects were seen with fluconazole, and both drugs were found to have an associated delay in onset of action. Acidity was found to increase both MICs and IC1/2s. Other effects were observed among four synthetic media, but a consistent pattern was not identified. Incubation temperatures of 37, 35, and 30 degrees C yielded equivalent results. Broth microdilution IC1/2s against most of 40 isolates of C. albicans were 0.31 microgram/ml +/- fourfold for SCH 39304 and 0.16 microgram/ml +/- twofold for fluconazole. Treatment of experimental candidiasis in rats with SCH 39304 and fluconazole resulted in 50% effective doses of 0.33 and 0.49 mg/kg per day, respectively. In contrast, another C. albicans isolate, previously identified as resistant to other azoles, had IC1/2s of 20 micrograms of SCH 39304 per ml and, in vivo, a 50% effective dose of 2.25 mg/kg per day. We conclude that the in vivo efficacy of SCH 39304 correlates with MIC results when broth macrodilution testing is performed with a small inoculum and with IC1/2 results which are independent of inoculum size.

Antifungal Agents↗