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J N Galgiani

Publications and source records attributed to J N Galgiani.

At least 55 records · Page 3Linked to original sources
PubMed1994

Evaluation of 80% inhibition standards for the determination of fluconazole minimum inhibitory concentrations in three laboratories.

The purpose of this study was to evaluate 1:5 growth control dilutions (80% inhibition standards) to determine fluconazole minimum inhibitory concentration (MIC) end points in three laboratories. We tested 39 selected Candida species (in vitro susceptible: fluconazole MIC of < or = 1 microgram/ml, and resistant: fluconazole MIC of > or = 8 micrograms/ml) and Cryptococcus neoformans isolates by broth macro- and microdilution procedures following the National Committee for Clinical Laboratory Standards proposed reference method for yeasts (M27-P). Macrodilution MIC80% were the lowest drug concentrations with turbidity (growth) less than or equal to that of specific 1:5 dilutions of the growth control. Microdilution MICs-2 were the lowest drug concentrations in which there was prominent decrease of growth. A total of 1608 MICs were evaluated. C. krusei, C. parapsilosis, and C. tropicalis strains had reproducible fluconazole MICs by both tests (24 and 48 h). Fluconazole MIC80% and MIC-2 end points were consistent at 24 h (with C. albicans) and more variable at 48 h. MICs of C. neoformans were more reproducible at 72 h than at 48 h by both tests. This study suggests that the determination of fluconazole MICs is dependent on the length of incubation and the yeast being tested, and that antifungal testing of the yeasts may be performed by either test.

Candida↗
PubMed1994

Cavitary coccidioidomycosis with fungus ball formation. Diagnosis by fiberoptic bronchoscopy with coexistence of hyphae and spherules.

Pulmonary cavitary coccidioidomycosis with fungus ball formation was observed in two individuals with hemoptysis. The first patient had no overt compromise; the second was an insulin-dependent diabetic. In both, fiberoptic bronchoscopy was performed and cultures yielded Coccidioides immitis. The coexistence of spherules and hyphae of C immitis was seen histologically on bronchoscopic biopsy specimen of one cavitary lesion. Specific antifungal therapy and surgical excision were withheld and each patient has done well. This report provides for the first time nonsurgical confirmation that C immitis can produce an intracavitary fungus ball.

Adult↗
PubMed1993

Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group.

OBJECTIVE: To determine the efficacy and safety of fluconazole treatment of coccidioidal meningitis. DESIGN: Uncontrolled clinical trial. SETTING: Four university-based treatment centers in California, Arizona, and Texas. Most therapy was conducted without hospitalization. PATIENTS: Fifty consecutive patients with active coccidioidal meningitis, of which 47 (94%) were evaluable. Twenty-five patients had received no previous treatment for their meningitis, and nine had coinfection with human immunodeficiency virus (HIV). INTERVENTION: Fluconazole was administered in an oral dose of 400 mg once per day for up to 4 years (median, 37 months) in responding patients. Concurrent therapy with another antifungal agent was prohibited. MEASUREMENTS: Predefined assessment of infection-related abnormalities was done at the time of enrollment and was repeated at least every 4 months during treatment. Elimination of 40% or more of baseline abnormalities was considered a response. RESULTS: Thirty-seven of 47 (79%; 95% CI, 61% to 90%) evaluable patients responded to treatment. Response rates were similar for patients with and without previous therapy, for patients with and without concomitant HIV infection, and for patients with and without pre-existing hydrocephalus. Most improvement occurred within 4 to 8 months after starting treatment. Patient symptoms resolved more quickly than did cerebrospinal fluid abnormalities. In 15 of 20 responding patients followed for 20 months or more, residual low-level cerebrospinal fluid abnormalities remained throughout therapy. No patient discontinued therapy because of drug-related side effects, although confusion developed in two patients that resolved when the dose of fluconazole was reduced. CONCLUSION: Fluconazole therapy is often effective in suppressing coccidioidal meningitis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Coccidioidomycosis during human immunodeficiency virus infection: results of a prospective study in a coccidioidal endemic area.

PURPOSE: To determine the incidence of active coccidioidomycosis among subjects infected with the human immunodeficiency virus (HIV) living in an area endemic for coccidioidomycosis and to identify factors associated with the development of active coccidioidomycosis in these patients. PATIENTS AND METHODS: This was a prospective cohort analysis of HIV-infected subjects living in an area endemic for coccidioidomycosis in Arizona. On entry and at approximately 4-month intervals, subjects were interviewed and examined, and had spherulin skin testing and CD4 lymphocyte counts performed along with other tests. During each interval, it was determined whether the subject had developed active coccidioidomycosis according to established criteria. RESULTS: One hundred seventy subjects entered the study. Median follow-up was 11.3 months (range: 0 to 44 months). Thirteen subjects developed active coccidioidomycosis, with an estimated cumulative incidence of 24.6% by 41 months (95% confidence limits 8.2% and 41.1%). Risk factors associated with the development of active coccidioidomycosis in the cohort were a CD4 lymphocyte count of less than 0.250 x 10(9)/L and a diagnosis of acquired immunodeficiency syndrome. Factors associated with prior coccidioidal infection, including a positive spherulin skin test, length of residence in the endemic area for more than 25 months, and a prior history of coccidioidomycosis, were not associated with the development of active infection. CONCLUSION: Active coccidioidomycosis among individuals infected with HIV is common in the coccidioidal endemic area. Immunodeficiency appears to be the major risk factor for the development of disease. Evidence of prior coccidioidomycosis, including a positive spherulin skin test, does not appear to predict the development of active infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The natural history of coccidioidal meningitis: VA-Armed Forces cooperative studies, 1955-1958.

From records on the clinical course of 699 military and veteran patients who had coccidioidomycosis before the advent of effective antifungal therapy, we identified 25 cases in which the manifestations of meningeal dissemination were described. Of 21 patients who had an identifiable initial infection, 16 developed meningeal symptoms (most frequently headache, vomiting, and nuchal rigidity) within the next 6 months. Associated pulmonary lesions were significantly more frequent in the right than in the left lung, as was also the case among 47 matched control patients who had coccidioidomycosis but not meningitis. Of 17 patients whose meningeal symptoms developed during the period studied, all died within 31 months. However, four of eight patients whose onset of symptoms preceded the study period survived for 55-146 months. Patients whose extrapulmonary dissemination involved only the meninges survived significantly longer than did those with more extensive infections. Even without therapy, the white blood cell count in cerebrospinal fluid markedly decreased during the course of the infection. The quantitative analysis provided herein offers a basis for meaningful comparisons with patients enrolled in current and future trials of therapy for coccidioidal meningitis.

Adolescent↗
PubMed1993

Multicenter evaluation of a broth macrodilution antifungal susceptibility test for yeasts.

Thirteen laboratories collaborated to optimize interlaboratory agreement of results of a broth macrodilution procedure for testing three classes of antifungal drugs against pathogenic yeasts. The activities of amphotericin B, flucytosine, and ketoconazole were tested against 100 coded isolates of Candida albicans, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Torulopsis (Candida) glabrata, and Cryptococcus neoformans. Two starting yeast inoculum sizes (5 x 10(4) and 2.5 x 10(3) cells per ml) were compared, and readings were taken after 24 and 48 h of incubation. All other test conditions were standardized. The resultant turbidities in all tubes were estimated visually on a scale from 0 to 4+ turbidity, and MIC-0, MIC-1, and MIC-2 were defined as the lowest drug concentrations that reduced growth to 0, 1+, or 2+ turbidity, respectively. For flucytosine, agreement among laboratories varied between 57 and 87% for different inocula, times of incubation, and end point criteria. Agreement was maximized (85%) when the lower inoculum was incubated for 2 days and the MICs were defined as 1+ turbidity or less. For amphotericin B, variations in test conditions produced much smaller differences in interlaboratory agreement. For ketoconazole, interlaboratory agreement was poorer by all end point criteria. However, MIC-2 endpoints distinguished T. glabrata as resistant compared with the other species. Overall, the studies indicated that readings from the lower inoculum obtained on the second day of reading result in the greatest interlaboratory agreement. In combination with data from previous multicenter studies (National Committee for Clinical Laboratory Standards, Antifungal Susceptibility Testing: Committee Report, Vol. 5, No. 17, 1988; M. A. Pfaller, L. Burmeister, M. S. Bartlett, and M. G. Rinaldi, J. Clin. Microbiol. 26:1437-1441, 1988; M. A. Pfaller, M. G. Rinaldi, J. N. Galgiani, M. S. Bartlett, B.A. Body, A. Espinel-Ingroff, R.A. Fromtling, G.S. Hall, C.E. Hughes, F. C. Odds, and A. M. SUgar, J. Clin. Microbiol. 34:1648-1654, 1990), these findings will be used by the National Committee for Clinical Laboratory Standards to develop a standardized method for in vitro antifungal susceptibility testing for yeasts.

Antifungal Agents↗
PubMed1993

In vitro studies of a new antifungal triazole, D0870, against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts.

We investigated the effects of various assay conditions on the activity of D0870 against seven species of fungi in the broth macrodilution testing procedure proposed by the National Committee for Clinical Laboratory Standards (NCCLS). Multivariate analysis demonstrated that endpoint definition, starting inoculum size, medium composition, type of buffer, and length of incubation, but not pH or temperature, had significant effects on results. Increasing the inoculum from 10(2) to 10(5) yeast cells/ml raised the MICs for all isolates up to > 75,000 fold. This effect was greatest when endpoints corresponded to a 90% reduction in visually determined turbidity (MIC90), was less prominent with an 80% inhibition visual endpoint (MIC80), and was nearly absent with a 50% endpoint measured by a spectrophotometer (IC1/2). Differences due to medium composition were attributable to antibiotic medium 3 with RPMI and yeast nitrogen base media performing nearly identically. Under standardized conditions as specified in NCCLS document M27-P (Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Proposed Standard, 1992), 79 strains (5 to 25 strains for each species) demonstrated median MIC80s of 0.0037 and 0.0075 microgram/ml for Candida albicans and Cryptococcus neoformans, respectively. In contrast, Candida krusei and Torulopsis glabrata had a median MIC80 of 1.0 microgram/ml. Our studies indicate that the pathogenic yeasts C. albicans and C. neoformans are more susceptible to D0870 than other pathogenic yeasts.

Antifungal Agents↗
PubMed1993

Antifungal susceptibility testing.

Unlike antibacterial susceptibility testing, reliable antifungal susceptibility testing is still largely in its infancy. Many methods have been described, but they produce widely discrepant results unless such factors as pH, inoculum size, medium formulation, incubation time, and incubation temperature are carefully controlled. Even when laboratories agree upon a common method, interlaboratory agreement may be poor. As a result of numerous collaborative projects carried out both independently and under the aegis of the Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards, the effects of varying these factors have been extensively studied and a standard method which minimizes interlaboratory variability during the testing of Candida spp. and Cryptococcus neoformans has been proposed. This review summarizes this work, reviews the strengths and weaknesses of the proposed susceptibility testing standard, and identifies directions for future work.

Animals↗
PubMed1993

Production of a murine monoclonal antibody that recognizes an epitope specific to Coccidioides immitis antigen 2.

Antigen 2 (Ag2) has been implicated as a T-cell-reactive component of the pathogenic fungus Coccidioides immitis. We report the production of a murine monoclonal antibody (MAb) of the immunoglobulin G2a isotype that recognizes an epitope specific to C. immitis Ag2. This specificity was evidenced by the finding that the MAb did not recognize other antigens present in coccidioidin or spherulin and did not show reactivity with antigenic extracts from Histoplasma capsulatum or Blastomyces dermatitidis. The epitope was labile to enzymatic digestion with pronase but resistant to treatment with glycolytic enzymes and to periodate oxidation. This peptide epitope appears to require conformational structure on the basis that it was not recognized by the MAb in immunoblots of antigen that had been electrophoresed in polyacrylamide gels under denaturing, reducing conditions. Immunoaffinity chromatography of spherulin on columns containing the MAb established that the MAb was effective as a ligand for isolating Ag2 from heterogeneous extracts. The production of a MAb which recognizes an Ag2-specific epitope and its utility as a ligand for isolating Ag2 will provide a valuable reagent for studies of this immunologically important antigen.

Animals↗
PubMed1993

Coccidioidomycosis.

Coccidioidomycosis is a systemic fungal infection endemic to the southwestern United States and other parts of the western hemisphere. Although producing a wide range of disorders in healthy persons, immunosuppression predisposes to especially severe disease. Thus, a knowledge of the pathogenesis of coccidioidal infections and its relation to the normal immune responses is useful to understand the diversity of problems that Coccidioides immitis may cause. Diagnosis usually requires laboratory studies such as fungal culture or specific serologic testing. Fortunately, many patients do not need to be treated for the infection to resolve. Therapy for the more severe forms of coccidioidal infection was once limited to amphotericin B but now includes azole antifungal agents. These expanded alternatives now require physicians to weigh many factors in determining the best management for specific patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Coccidioidomycosis: changes in clinical expression, serological diagnosis, and therapeutic options.

Coccidioidomycosis occurs in greater than 50,000 persons each year. As concurrent infections with the human immunodeficiency virus become more frequent, the spectrum of coccidioidal illness has shifted toward more extensive and life-threatening disease. This trend has intensified interest in developing more-sensitive methods for diagnosis of coccidioidal infection early in its course. ELISA procedures that detect fungal antigen and antibodies in patient sera have been devised but require more-purified antigens for clinically useful specificity. Clinical trials of new drugs have been initiated that may offer advantages in safety, efficacy, or ease of administration. Itraconazole and fluconazole show promise, especially in the treatment of coccidioidal meningitis. However, it has not yet been determined whether either antifungal agent is more effective than established agents, such as amphotericin B or ketoconazole. These changes in the clinical spectrum, methods of diagnosis, and therapeutic options will likely influence the medical approach to coccidioidal infections in coming years.

Acquired Immunodeficiency Syndrome↗
PubMed1992

In vitro assessment of cellular immunity in human coccidioidomycosis: relationship between dermal hypersensitivity, lymphocyte transformation, and lymphokine production by peripheral blood mononuclear cells from healthy adults.

Dermal hypersensitivity in coccidioidomycosis was compared with three simultaneous measures of in vitro cellular immunity using 35 healthy donors living in an area endemic for coccidioidomycosis. Twenty donors had greater than 5 mm induration to usual-strength spherulin and were considered skin test-positive. Mononuclear cells from these individuals were more responsive by lymphocyte transformation (12,541 +/- 3746 vs. -112 +/- 260 cpm, P = .007) and produced significantly more interleukin-2 (3481 +/- 1067 vs. -5 +/- 69 cpm, P less than .001) and interferon-gamma (1831 +/- 481 vs. 75 +/- 58 pg/ml, P less than .001) than cells from skin test-negative donors in response to a coccidioidal antigen. However, the correlation between the skin test size and the magnitude of the in vitro response among skin test-positive donors was poor (R2 = 0.08, P = .24). These results indicate that healthy individuals with dermal hypersensitivity to Coccidioides immitis can be distinguished from those without hypersensitivity by their cellular in vitro response to a coccidioidal antigen.

Adult↗
PubMed1992

Killing of Coccidioides immitis by human peripheral blood mononuclear cells.

The ability of human peripheral blood mononuclear cells (MNL) obtained from healthy donors to kill the fungus Coccidioides immitis was examined in vitro with an assay that uses a single fungal particle per well. MNL killed 25.0% +/- 3.5% of a coccidioidal arthroconidial target, compared with the 4.7% +/- 2.9% killed by polymorphonuclear leukocytes obtained from the same donors (P = 0.012). Arthroconidial killing by MNL was not dependent on donor delayed dermal hypersensitivity to spherulin. Killing of another fungal target, Candida glabrata, was not significantly different between MNL and polymorphonuclear leukocytes (P = 0.783). Depletion of monocytes from MNL with Sephadex G-10 resulted in a significant reduction in arthroconidial killing (21.4% +/- 13.6% versus 2.4% +/- 3.4%; P = 0.025), while enrichment of monocytes by Percoll density gradient centrifugation or plastic adherence resulted in significantly increased arthroconidial killing compared with that by MNL (P = 0.005 and 0.001, respectively). Killing of 96-h spherules by MNL was 7.3% +/- 3.1%, significantly less than the 21.4% +/- 2.8% killing of arthroconidia in the same experiments (P = 0.016). Incubation of MNL with human recombinant gamma interferon or tumor necrosis factor alpha did not result in increased MNL killing of coccidioidal arthroconidia under various conditions. These results suggest that MNL have an inherent ability to kill coccidioidal arthroconidia in vitro which is not dependent on prior host exposure to C. immitis. This activity appears to reside in peripheral blood monocytes.

Coccidioides↗
PubMed1992

An arthroconidial-spherule antigen of Coccidioides immitis: differential expression during in vitro fungal development and evidence for humoral response in humans after infection or vaccination.

A 33-kDa protein antigen purified from spherules of Coccidioides immitis was analyzed for ultrastructural localization and for binding to serum antibodies from infected or immunized humans. By using colloidal gold detection of affinity-purified anti-33-kDa protein antibodies, electron photomicrographs showed binding to the inner cell wall of arthroconidia and spherules and to the septa and glycocalyx surrounding endospores. Enzyme immunoassay measurements also demonstrated that the antigen was most abundant in mature spherules. Of 37 patients with coccidioidomycosis but without concurrent human immunodeficiency virus infections, all but 2 demonstrated immunoglobulin M (IgM) (usually with early infection) or IgG antibodies for the 33-kDa antigen. In contrast, only one of four HIV-infected patients with active coccidioidal infections demonstrated antibody. On the other hand, 107 of 108 patients without evident coccidioidomycosis and 15 of 16 patients with histoplasmosis did not have similar antibodies, indicating a high degree of specificity. Immunization of humans with a spherule vaccine produced IgM responses to this antigen that were not evident in placebo recipients.

Acquired Immunodeficiency Syndrome↗