John R. Graybill

The University of Texas Health Science Center at San Antonio

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Laura K. Najvar

The University of Texas Health Science Center at San Antonio

Rosie Bocanegra

The University of Texas Health Science Center at San Antonio

Michael G. Rinaldi

The University of Texas Health Science Center at San Antonio

Gregory M. Anstead

South Texas Veterans Health Care System

William E. Dismukes

University of Alabama at Birmingham

Thomas F. Patterson

The University of Texas Health Science Center at San Antonio

David A. Stevens

Stanford University

David J. Drutz

Murphy Oil Corporation (United States)

Philip C. Craven

Centers for Disease Control and Prevention

Joan Ahrens

Murphy Oil Corporation (United States)

Cooperative Institutions

The University of Texas Health Science Center at San Antonio

149

Centers for Disease Control and Prevention

119

Office of Infectious Diseases

Johns Hopkins University

National Institutes of Health

Harvard University

Murphy Oil Corporation (United States)

National Institute of Allergy and Infectious Diseases

The University of Texas Health Science Center at Houston

Center for Global Health

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Therapeutic efficacy of caspofungin alone and in combination with amphotericin B deoxycholate for coccidioidomycosis in a mouse model

Journal of Antimicrobial Chemotherapy (2007)

Gloria M. González Gloria M. González Laura K. Najvar John R. Graybill

The therapeutic efficacy of caspofungin alone and in combination with amphotericin B deoxycholate was evaluated in treatment of murine coccidioidomycosis.Survival and tissue burdens of the spleens and livers were used as antifungal response markers. In a monotherapy study, caspofungin was injected intraperitoneally at 0.1, 0.2, 0.5, 1 and 5 mg/kg per day on days 2 through 15. Amphotericin B deoxycholate was given at 0.1, 0.2 and 0.5 mg/kg intravenously and 1 and 5 mg/kg intraperitoneally three times per week for 2 weeks. In a combination therapy study, amphotericin B deoxycholate at 0.1 mg/kg was administered intravenously three times per week for 2 weeks, respectively, with and without caspofungin intraperitoneally given at 0.1, 0.5 and 5 mg/kg daily on days 2 through 15 post-infection.The study shows that caspofungin and amphotericin B deoxycholate at > or =0.5 and > or =0.1 mg/kg, respectively, were significant in both prolongation of survival and reduction of the tissue fungal burdens of mice compared with controls. No sterilization of either organ was observed with caspofungin doses. In combination therapy, any combination of caspofungin (0.1, 0.5 and 5 mg/kg) with amphotericin B deoxycholate (0.1 mg/kg) improved the period of survival and significantly reduced spleen and liver counts compared with controls.This study indicates that caspofungin has efficacy against systemic coccidioidomycosis in a murine model given in combination with amphotericin B deoxycholate.

Amphotericin B deoxycholate

Combination therapy

10.1093/jac/dkm383

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Citations (26)

Disseminated Histoplasmosis Followed by Disseminated Coccidioidomycosis

CHEST Journal (1977)

Peter W. Kaplan John R. Graybill Daniel E. Thor

Histoplasma

Cellular immunity

Cell mediated immunity

10.1378/chest.72.2.238

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A Comparison of Respiratory Tract Bacterial Culture Sources and Effectiveness of Chemoprophylaxis Against Bacterial Pneumonia

Charles Ellenbogen John R. Graybill P. J. Homme

Thirty-five USAF basic trainees hospitalized with nonbacterial pneumonia during an epidemic of acute respiratory disease were treated either with tetracycline or minocycline to prevent secondary bacterial pneumonia; 15 served as untreated controls. Six of 50 patients had bacterial pneumonia, two in each of the two treatment groups and the control group. Three of four patients with bacterial pneumonia being treated with tetracycline or minocycline required additional antibiotics for recovery. Five of six patients with bacterial pneumonia had adenovirus infections. Eighteen of the 44 patients with only nonbacterial pneumonia had single or multiple infections with adenovirus, parainfluenza, influenza AZ or B viruses. In this population, (1) adenoviral and bacterial pneumonia were associated, although a causal relationship was not proved; (21 tetracycline and minocycline were not efficacious either for preventing or treating bacterial pneumonia complicating adenoviral pneumonia; (3) group Y Neisseria meningitidis was a significant lower respiratory pathogen; and (4) bacterial culture of specimens from the respiratory tract obtained by transtracheal aspiration or transthoracic lung aspiration more accurately reflect the bacteriology of infection in the lower respiratory tract than do cultures of expectorated sputum.

Bacterial pneumonia

Minocycline

Sputum culture

Respiratory tract

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Treatment of Mycobacterium haemophilum infection in a murine model with clarithromycin, rifabutin, and ciprofloxacin

Antimicrobial Agents and Chemotherapy (1995)

Barbara Atkinson Rosie Bocanegra John R. Graybill

An animal model of disseminated Mycobacterium haemophilum infection was utilized to compare treatment with azithromycin, ciprofloxacin, rifabutin, and the combination of clarithromycin with rifabutin. Following subcutaneous challenge with M. haemophilum, local and disseminated infection occurred only in immunosuppressed mice. For disseminated infection, ciprofloxacin was relatively ineffective therapy. Clarithromycin and rifabutin alone significantly reduced the tissue burden in the spleen after 4 weeks of therapy. Combination therapy with rifabutin and clarithromycin was superior to 4 weeks of treatment with the individual agents. When immunosuppressed mice were treated for 20 weeks with the combination of rifabutin and clarithromycin, the tissue burden remained reduced in the spleen at 1 month following the completion of therapy. Combined rifabutin and clarithromycin provide effective treatment for M. haemophilum in this model.

Rifabutin

Combination therapy

10.1128/aac.39.10.2316

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Polymerase Chain Reaction Detection ofAspergillusDNA in Experimental Models of Invasive Aspergillosis

The Journal of Infectious Diseases (2002)

Juergen Loeffler Kerstin Kloepfer Holger Hebart Laura K. Najvar John R. Graybill

To determine the sensitivity of polymerase chain reaction (PCR) assays for the diagnosis of invasive aspergillosis, results of quantitative culture, PCR-ELISA, and a quantitative LightCycler assay (Roche Diagnostics) of blood and organ specimens of experimentally infected mice and rabbits were compared. By PCR-ELISA, 297 of 379 murine lung specimens were positive, but only 235 of 379 were culture positive. Whereas 64 culture-negative lungs were positive by PCR, Aspergillus was grown from only 2 PCR-negative samples. The PCR assay was 19.4 times more sensitive than culture. None of the 68 blood cultures from mice and rabbits were positive for Aspergillus fumigatus, whereas PCR detected Aspergillus DNA in 17 of 68 blood samples. Quantitative PCR analysis of blood samples showed a fungus load of 101-102 cfu/mL of blood. The data confirm the superior sensitivity of PCR for the diagnosis of experimental Aspergillus infections.

10.1086/339824

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Citations (85)

Randomized Trial of Itraconazole Oral Solution for Oropharyngeal Candidiasis in HIV/AIDS Patients

The American Journal of Medicine (1998)

John R. Graybill José A. Vázquez Rabih O. Darouiche R E Morhart Deborah Greenspan

Purpose: Oropharyngeal candidasis (thrush) is the most common opportunistic infection in individuals who are positive for the human immunodeficiency virus (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro spectrum of activity, including a wide variety of Candida species. Our study determined the relative efficacy of a new oral solution formulation of itraconazole and fluconazole tablets in the treatment of oropharyngeal candidiasis. Patients and Methods: This was a prospective randomized, third-party–blind, multicenter trial conducted at 12 centers in the United States. One hundred seventy-nine HIV-positive patients with mycologically documented oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on days 3, 7, 14, 21, 35, and 42. Semiquantitative cultures of mouth washings were also obtained on these days. Results: Both 14-day and 7-day regimens of itraconazole oral solution were equivalent to fluconazole for most efficacy parameters. The clinical response rate was 97% after 14 days of itraconazole and 87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was also equivalent to fluconazole treatment for 14 days. Approximately one half of patients in all three groups relapsed by 1 month after completion of treatment. There were few adverse reactions to either drug. Conclusion: Itraconazole oral solution is well tolerated and offers an alternative at least as effective as fluconazole in the treatment of oropharyngeal candidiasis.

10.1016/s0002-9343(97)00307-0

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Citations (107)

Proceedings of a symposium on new developments in therapy for the mycoses.

The American Journal of Medicine (1983)

John R. Graybill

Source

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Potentiation of Topical Voriconazole (VCZ) Ocular Penetration by Pretreatment with Topical Latanoprost (LT)

Dan Dang Randolph D. Glickman John R. Graybill W.E. Sponsel AM Miller

Penetration (warfare)

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Immunomodulation and antifungal therapy of experimental invasive candidosis, histoplasmosis and aspergillosis: recent advances and concepts

Medical Mycology (1992)

Thomas J. Walsh J. Van Cutsem Annemarie Polak John R. Graybill

10.1080/02681219280000921

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Citations (17)

Variation in fluconazole efficacy for Candida albicans strains sequentially isolated from oral cavities of patients with AIDS in an experimental murine candidiasis model

Antimicrobial Agents and Chemotherapy (1996)

Francesco Barchiesi Laura K. Najvar Michael Luther Giorgio Scalise Michael G. Rinaldi

Four strains of Candida albicans, isolated from two patients with AIDS who had undergone prolonged fluconazole therapy for oral candidiasis, were studied in a model of disseminated murine candidiasis. Pre- and posttreatment isolates from each patient were genetically related, and the fluconazole MICs for the strains had increased significantly, from 0.25 to 32 micrograms/ml for the strains isolated from patient 1 and from 1.0 to 16 micrograms/ml for the strains isolated from patient 2. Mice were infected intravenously and were treated orally with fluconazole. For survival studies, mice were treated from day 1 to day 10 postinfection and were observed through day 30. The fluconazole dosages were as follows: 0.25, 0.5, 1.0, and 5.0 mg/kg of body weight twice a day. For tissue burden studies, two groups of mice (each group received fluconazole at 0.25 or 5.0 mg/kg) were treated from day 1 to day 7 and were sacrificed 1 day later for quantitative tissue cultures of the spleen and both kidneys. For pretreatment isolates from both patients, all fluconazole dosing regimens were effective at prolonging survival compared with the survival of the control groups. For posttreatment isolates, only fluconazole at 5.0 mg/kg was effective at prolonging survival. Both fluconazole dosing regimens used in the tissue burden studies significantly reduced the counts of the pretreatment isolate from patient 1 in the spleen and kidney, while fluconazole at 5.0 mg/kg was effective at reducing the counts of the posttreatment isolate. For both isolates from patient 2, only fluconazole at 5.0 mg/kg was effective at reducing the counts in the spleen and kidney. The study indicates that C. albicans mutation to resistance to fluconazole may play a critical role in fluconazole-refractory oral candidiasis in AIDS patients.

Dose

10.1128/aac.40.5.1317

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Citations (29)