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Biomedical subjects

J N Galgiani

Publications and source records attributed to J N Galgiani.

140 records · Page 8Linked to original sources
PubMed1978

Chemotaxigenic activity of extracts from the mycelial and spherule phases of Coccidioides immitis for human polymorphonuclear leukocytes.

In order to further characterize human host defenses against Coccidioides immitis, extracts of this fungus were tested in vitro for their ability to attract polymorphonuclear leukocytes derived from peripheral blood of uninfected subjects. Soluble substances prepared from the mycelial (saprophytic) and spherule (tissue) phases exhibited, in the presence of serum, dose-dependent chemotactic activity. The dose-response correlations were different. The spherule-derived preparation showed decreased activity at the high concentrations, a diminution not observed with equivalent concentrations of the mycelial filtrate. Chemotactic activity was not observed with either substance in the absence of serum or if heat-inactivated serum was substituted. Because the response of human polymorphonuclear leukocytes to these fungal substances appears complement mediated, a selective cellular defect in this function which antedates exposure to C. immitis seems unlikely.

Chemotaxis, Leukocyte↗
PubMed1978

Paracoccidioidomycosis (South American blastomycosis): treatment with miconazole.

Six patients with multisystem paracoccidioidomycosis proven by serology and culture or smear were treated with relatively brief courses of intravenous miconazole. Two had relapsed following prior therapy; 6 had active pulmonary, 4 laryngeal, 2 oropharyngeal, 2 lymphoid, and 1 abdominal disease. Paracoccidioides brasiliensis was highly susceptible to miconazole in vitro; minimal inhibitory concentration was less than or equal to 0.001 microgram/ml. Clinical examination showed a prompt and objective response in all patients, confirmed by smear or culture and X-rays; in 4/6 serological response was shown. Side effects were minor. Two patients relapsed 3--5 mo after therapy; another had a rise in antibody 6 mo after therapy and was given maintenance oral sulfa. One remains in remission 7 mo after treatment; two given oral sulfa after response to miconazole remain in remission 4--6 mo after treatment. Paracoccidioidomycosis responds well to miconazole, but longer courses may be needed to prevent relapse.

Adolescent↗
PubMed1977

Fungal endocarditis: need for guidelines in evaluating therapy. Experience with two patients previously reported.

Successful treatment of fungal endocarditis is being described with increasing frequency. Two patients, previously reported as free of disease by two different groups of investigators, subsequently died in our institutions with evidence of continued disease. Both patients had been receiving antifungal chemotherapy at the time their case histories were reported. The lack of clinical signs and symptoms in fungal endocarditis, the suppression of manifestations of infection by chemotherapy, and the uncertain reliability of laboratory aids led us to suggest guidelines in reporting results of therapuetic regimens. These include avoidance of terms implying cure in patients who are concurrently maintained on chemotherapy, indication of attempts to evaluate fungemia, and minimum follow-up of 1-2 years' duration. The potential utility of serologic studies is illustrated by the course of one of these patients.

Adult↗
PubMed1977

Treatment of fungal meningitis with miconazole.

Twelve patients with fungal meningitis (ten cases were due to Coccidioides immitis, two were from Cryptococcus neoformans) were treated with brief courses of intravenous (IV) miconazole. Eleven patients, including patients with severe, chronic disease, had been treated unsuccessfully with amphotericin B. Four patients also received miconazole injected directly into the CSF. The drug was well tolerated by any route, with mild reversible side effects. After IV administration the miconazole concentration in the CSF rarely exceeded the minimal inhibitory concentration (MIC) of the infecting organism. Intra-CSF administration of 20 mg generally produced levels above the MIC for 24 hours. Five of ten patients with coccidiodial meningitis responded clinically. Of these five, four received only IV miconazole; three relapsed after therapy was stopped. Miconazole appears promising as a treatment of fungal meningitis, but trials of longer duration might prevent relapse.

Adolescent↗
PubMed1976

Visceral fungal infections due to Petriellidium boydii (allescheria boydii). In vitro drug sensitivity studies.

Four patients with visceral infections due to the fungus Petriellidium boydii, who were recently hospitalized in our institutions, are described. Three of the patients were compromised hosts; in the fourth patient, infection occurred after trauma. All had received prior steroid and antibiotic therapy. Studies of patients with mycetoma or secondary infection of a pulmonary cavity due to this organism and of patients with visceral infections are reviewed. Because of histologic similarities to Aspergillus species, infections due to P. boydii may have been misdiagnosed in the past if the infecting fungus was not isolated in culture. The fungus has been shown to be resistant in vitro to currently available antifungal agents. Resistance to amphotericin and 5-fluorocytosine is demonstrated in our studies. There are few reports of successful chemotherapy of any manifestation of this infection, and no such reports of visceral disease. We demonstrate in vitro sensitivity of isolates in our cases and in others to micronazole, a new antimicrobial agent; this drug may be indicated for treatment of disease due to P. boydii.

Adult↗
PubMed1976

Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size.

The current development of potent antifungal drugs necessitates reliable methods of in vitro susceptibility testing of clinical isolates. Other laboratories have noted with some antimicrobials that conventional tube dilution visual end points for determining minimal inhibitory concentrations (MIC) vary markedly with the inoculum. With seven isolates (four species) we compared the conventional method with one developed with a spectrophotometer. Yeasts were diluted to inocula of 10(2) to 10(5) cells/ml and incubated at 37 degrees C with 5-fluorocytosine or miconazole or without drug in a synthetic defined medium. At frequent intervals MICs were determined by the lowest drug concentration without visible turbidity. Concurrently, the percent transmission of each tube was measured and an inhibitory concentration (IC((1/2))) was calculated from the turbidimetric measurements. MICs of both drugs for all strains varied with the inoculum. Intrastrain differences averaged 128-fold for miconazole and greater than 8-fold with 5-fluorocytosine. This variability in MIC occurred when readings were made after 12 to 48 h of incubation. In contrast, IC((1/2)) values of all isolates varied less than two-fold with the same range of inocula. Most isolates showed this independence when measured at 48 h. Fast-growing yeasts showed greater IC((1/2)) variability unless the turbidimetric measurements were taken earlier while the drug-free growth was still in a rapid growth phase. This method is reproducible, inoculum independent, rapid, free from subjectivity and observer variability, and suitable for adaptation to a clinical setting.

Methods↗
PubMedDate not supplied

Neutrophil killing of single microorganisms as measured by a new method.

A new method of measuring polymorphonuclear leukocyte (PMN) microbicidal activity was developed in which single colony forming units of Staphylococcus aureus were isolated in microtiter wells with or without PMN, centrifuged, and incubated overnight. The percentage of bacteria killed was determined by comparing the number of PMN-containing wells showing bacterial growth to PMN-free controls. This percentage was positively correlated with the number of PMN in each well and was reduced if plates were not centrifuged or if cytochalasin B was added. Killing of either S. aureus or Escherichia coli was enhanced using fresh serum activated by prior exposure to large numbers of E. coli. There was no enhancement using heated serum that had been exposed to E. coli, nor was there enhancement when S. aureus was preopsonized by exposure to fresh serum. This assay circumvents problems in assessing microbicidal activity where aggregation of organisms might otherwise be an issue.

Blood Bactericidal Activity↗
PubMedDate not supplied

Coccidioidomycosis: clinical update.

Over the last decade coccidioidomycosis, a fungal infection endemic to the desert Southwest of the United States, has gained national prominence. This review summarizes recent advances in the clinical understanding of this disease. Immunosuppressive therapy and infection with the human immunodeficiency virus are recognized risk factors for the development of severe, progressive disease. Although relatively uncommon, extrapulmonary dissemination of Coccidioides immitis can lead to chronic infection of the skin, bones, and meninges. Culture and histologic examination are important in establishment of the diagnosis, but serologic tests remain both diagnostically and prognostically useful. Treatment is problematic. Coccidioidomycosis is an unpredictable disease, and assessments of drug efficacy are difficult. Ketoconazole is challenging amphotericin B as the preferred treatment for some manifestations. However, many of the adverse effects of ketoconazole have only recently been recognized. Newer antifungal agents, such as fluconazole and itraconazole, hold promise for the future.

Coccidioidomycosis↗
PubMedDate not supplied

Susceptibility of Candida albicans and other yeasts to fluconazole: relation between in vitro and in vivo studies.

In vitro studies of fluconazole have demonstrated that test results can be influenced by several test conditions, including medium composition, pH, and size of the starting fungal inoculum. In studies with Candida albicans, a few isolates have been identified that are markedly more resistant than other strains of the same species; in several in vivo studies of experimental infections, the more resistant isolates have caused infections less susceptible to fluconazole treatment. These findings corroborate a relation between in vitro and in vivo results. With further work it should be possible to define standard methods for use by clinical laboratories in determining fungal susceptibility to fluconazole.

Animals↗
PubMedDate not supplied

Treatment of coccidioidal meningitis with fluconazole.

Fluconazole was administered at doses of 50-400 mg/d to 18 patients (15 men, three women) with coccidioidal meningitis. After a mean duration of treatment of 9.8 months, 10 (67%) of 15 assessable patients had responded, one (7%) of 15 had partially responded, and four (27%) of 15 had not responded to therapy. Five (63%) of eight assessable patients receiving fluconazole as sole therapy responded or partially responded. Two patients discontinued fluconazole after initially responding to therapy, and both experienced relapse. The toxicity of fluconazole remains minimal at doses to 400 mg/d. The penetration of fluconazole into cerebrospinal fluid is substantial at all doses studied. Thus fluconazole continues to show promise even as sole therapy against coccidioidal meningitis. Not all patients respond, however, and relapse may be a problem with the currently studied doses and durations of therapy.

Adolescent↗
PubMedDate not supplied

Treatment of systemic sporotrichosis with ketoconazole.

Infections of deep soft tissues with the dimorphic fungus Sporothrix schenckii are uncommon in humans, and therapy has often required toxic drugs. We report our experience in treating 11 patients who had deep-seated sporotrichosis with ketoconazole, a well-tolerated, orally absorbed antifungal agent. Eight infections involved one or more joints, and three involved thoracic, cervical, and widespread cutaneous sites, respectively. For eight patients all evidence of infection resolved during therapy. Sustained remissions (6 months to 5 years) were noted for six patients after the discontinuation of all therapy and for an additional patient 4 years after the initiation of ketoconazole treatment. Durable responses were associated with prolonged treatment with 400-800 mg of ketoconazole daily. Our favorable experience suggests that oral therapy with ketoconazole may benefit other patients with systemic sporotrichosis.

Adult↗
PubMedDate not supplied

Therapy of disseminated or pulmonary coccidioidomycosis with ketoconazole.

Oral therapy with ketoconazole for active disseminated or progressive pulmonary coccidioidomycosis was evaluated according to defined criteria of objective improvement for 39 patients, most of whom had received other antifungal chemotherapy. Minimal inhibitory concentrations of ketoconazole for isolates of Coccidioides immitis were below mean peak serum concentrations. Eighteen patients responded at all sites of disease, one patient failed to respond, and the others either are being evaluated or cannot be evaluated. Most patients who responded to therapy required more than three months of treatment before the response was clearly noted. Responses were seen with skin, soft tissue, skeletal, and pulmonary infection as well as other conditions. Reversions of cultures for C. immitis to negative and decreases in titers of complement-fixing antibody were common. One patient relapsed after a course of therapy of only four months. In general, patients with skin disease who responded required only 200 mg per day, whereas those with skeletal disease required 400 mg per day. Adverse effects were uncommon despite extensive monitoring and were generally limited to transient nausea (with vomiting in patients receiving 400 mg per day). The data show that ketoconazole appears to be a promising new drug for treatment of coccidioidomycosis.

Aged↗
PubMedDate not supplied

Amphotericin B and imidazole therapy for coccidioidal meningitis in children.

Coccidioidal meningitis is a fatal form of Coccidioides immitis infection. Amphotericin B (AMB) therapy has reduced mortality but is itself toxic, and experience with it in very young children is meager. We are treating six children for coccidioidal meningitis diagnosed at 19 to 74 months of age. All had acute hydrocephalus and ventriculitis. The first four patients were initially treated with AMB but were changed to imidazole therapy (miconazole and ketoconazole). In the last two patients therapy was begun with the imidazoles. Ommaya reservoirs for cisternal therapy have been of limited usefulness. AMB therapy has been limited by local and systemic toxicity and by failure in one case. All children have improved with 15 to 22 mg oral ketoconazole per kg per day and 3 to 5 mg intraventricular miconazole for instillation therapy, including those with noncommunicating hydrocephalus in whom the intraventricular drug does not reach the basilar cisterns. Peak concentrations of ketoconazole in ventricular fluid were 0.08 to 5.6 micrograms/ml. Shunt obstruction and bacterial superinfections have been the major causes of morbidity. Imidazole therapy of coccidioidal meningitis may be more effective than is AMB in young children, and it offers the advantages of fewer side effects and not requiring intrathecal or cisternal administration.

Amphotericin B↗