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H A Gallis

Publications and source records attributed to H A Gallis.

9 recordsLinked to original sources

Evaluation of new antifungal drugs for the treatment of systemic fungal infections. Infectious Diseases Society of America and the Food and Drug Administration.

These guidelines are applicable to all fungal pathogens that produce systemic infections in humans. Specific examples are provided whenever they might clarify special issues. Systemic fungal infections usually are divided into two broad categories: endemic systemic fungal diseases, which occur classically in healthy hosts, and opportunistic fungal diseases, which occur almost exclusively in patients with impaired host defenses. Both the increasing frequency of disseminated histoplasmosis and coccidioidomycosis in patients with AIDS and the occurrence of candidemia due to vascular-line infections have begun to blur this distinction. The fungi included in these guidelines are Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Candida species, Cryptococcus neoformans, Aspergillus species, and Sporothrix schenckii. Diagnosis of infections caused by these fungi should be based on culture of infected body fluids or tissues whenever possible. Cryptococcal and coccidioidal meningitis are exceptions. Amphotericin B remains the standard comparative agent for most new agents. Further studies of the efficacy of new oral agents used alone or after a hospital course of amphotericin B are needed. The agents currently available are usually inadequate for eradication of fungal infections in patients with AIDS, who may need prolonged treatment. Final assessment for these patients may need to be classified as clinical cure with presumed microbiologic persistence.

Antifungal Agents

Azithromycin--spectrum of activity, pharmacokinetics, and clinical applications.

Azithromycin is an azalide antimicrobial agent. Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit. Although slightly less potent than erythromycin against gram-positive organisms, azithromycin demonstrates superior activity in vitro against a wide variety of gram-negative bacilli, including Haemophilus influenzae. Absorption is approximately 37% after a 500-mg oral dose. The large volume of distribution (23 L/kg) and low peak serum level (0.4 micrograms/ml) are consistent with data demonstrating extensive tissue distribution and intracellular accumulation. Metabolism is predominantly hepatic (to inactive metabolites), with biliary excretion a major pathway of elimination. Drug elimination is biphasic, with a terminal half-life of up to 5 days. Published trials have examined the efficacy and safety of azithromycin in the treatment of adults with upper and lower respiratory tract infections, skin and skin structure infections, streptococcal pharyngitis, and sexually transmitted diseases. Many used a 5-day course of 250 mg once daily, supplemented with a 250-mg dose on the first day of therapy. Selected trials in sexually transmitted diseases examined single 1-g doses. Promising results also were obtained with oral daily doses of 500 mg in patients with human immunoviral infection who also had Mycobacterium avium complex infection and in animals with toxoplasmosis. Adverse reactions are primarily gastrointestinal (nausea, diarrhea, abdominal pain), with minimal laboratory abnormalities reported. Gastrointestinal tolerance is better than that of erythromycin. Drug interactions have not been observed to date, although coadministration of azithromycin with a large meal may reduce absorption by up to 50%.

Azithromycin

Pericarditis: differential diagnostic considerations.

A retrospective analysis of 133 patients was performed to define the factors identifying those individuals at risk for the more serious causes of pericardial disease. In 90% of the cases, the initial assessment from data obtained without pericardiocentesis or pericardiectomy proved correct. Underlying tuberculous or maligant pericarditis were the most common sources of error on initial assessment. Hemodynamic compromise exclusive of anticoagulants, roentgenographic cardiomegaly, pleural effusion, low voltage on ECG, and large pericardial effusion by echocardiography were more common (P less than .05) in tuberculous pericarditis than in acute idiopathic pericarditis. We discuss similar risk factors in patients with chronic idiopathic, rheumatologic, and uremic pericarditis. Anterior pericardiectomy is favored as the diagnostic procedure of choice in patients at risk for the more serious causes of pericarditis because of greater safety, diagnostic sensitivity, and potential therapeutic benefit.

Adult

Partial purification and characterization of a bacteriolytic enzyme secreted by Tetrahymena.

Tetrahymena pyriformis strain HSM secretes large quantities of acid hydrolases into the culture medium. An enzyme secreted by the ciliate and capable of degrading walls of streptococci was identified and purified to a considerable degree. The pH optimum of this enzyme was 3--4, and it was eluted after cytochrome c from Sephadex G-75 columns. Unlike lysozyme, the enzyme was thermolabile at pH 2.9, but relatively thermostable at pH 8.1. It degraded 14C-labeled cell walls of streptococci releasing reducing groups. Cell walls prepared from different strains of streptococci differed in susceptibility to this enzyme, the most sensitive strain tested being of group A, type T12. It was shown in immunologic studies that this hydrolase released the group-specific carbohydrate from the walls. Secretions of Tetrahymena from early stationary-phase cultures had more bacteriolytic activity than those from cells from late stationary-phase cultures. Further, cells from cultures grown in glucose-supplemented medium secreted less of the enzyme than ciliates of comparable age grown in unsupplemented proteose-peptone. The newly isolated bacteriolytic enzyme, presumably of lysosomal origin, may be helpful in characterizing streptococcal cell walls.

Animals

Two-dimensional echocardiographic assessment of vegetative endocarditis.

Real-time, two-dimensional echocardiography was used to document the presence and assess the size and location of vegetative lesions of the cardiac valves and chambers in seven patients with bacterial endocarditis. Anatomic correlation (surgical or autopsy) was accurate in all patients. Two-dimensional echocardiography was shown to be of particular value in determining morphologic characteristics of the lesions since this technique provides spatial information concerning moving cardiac structures. The results of two-dimensional echocardiography were most helpful in determining selected aspects of the clinical care provided for each patient. These data demonstrate that real-time, two-dimensional echocardiography, in combination with M-mode imaging techniques, may be of great potential value in the detection of vegetative endocarditis. Furthermore, reliable assessment of lesion size and location may, in time, become a valuable method for following the morphologic changes that occur in vegetative lesions, and thus determine the efficacy of antibiotic therapy. This information may also provide a means for evaluating certain patients for surgical intervention.

Adolescent

Degradation of 14C-labeled streptococcal cell walls by egg white lysozyme and lysosomal enzymes.

The resistance of native and trypsin-treated [14C] glucose-labeled cell walls to degradation by lysozyme and human lysosomal enzymes was confirmed. In contrast, chemically N-acetylated cell walls undergo significant degradation by these enzymes in the pH range of 4.5 to 5.5 without prior removal of the group-specific carbohydrate. N-acetylation after removal of the group A carbohydrate by formamide extraction renders the cell walls considerably more susceptible to these enzymes than by formamaide extraction alone. It appears, therefore, that unless N-acetylation can occur in vivo, streptococcal cell walls are minimally degraded, if at all, by human peripheral blood leukocytes or lysozyme. Examination of leukocyte extracts from normal subjects and patients with post-streptococcal syndromes revealed no qualitative differences in ability to dissolve streptococcal cell walls.

Carbon Radioisotopes

Subacute staphylococcal pneumonia in a renal transplant recipient.

A patient is reported who developed subacute staphylococcal pneumonia 17 months after renal transplantation. Although the illness was modified by oral antimicrobial drugs, a remarkably benign course was observed, leading to a presumptive diagnosis of opportunistic fungal infection. Thus, staphylococcal pneumonia may complicate the differential diagnosis of pulmonary infection in transplant recipients.

Administration, Oral

Fungal infection following renal transplantation.

Twenty-seven deep fungal infections developed in 22 of 171 patients following renal transplantation. These infections included cryptococcosis (ten), nocardiosis (seven), candidiasis (four), aspergillosis (two), phycomycosis (two), chromomycosis (one), and subcutaneous infection with Phialophora gougeroti (one). Twelve infections occurred in living-related and ten in cadaveric recipients. Nineteen of the 22 patients were male. Infections occurred from 0 to 61 months after transplantation. Complicating non-fungal infections were present concomitantly in 15 patients. Thirteen patients died, eight probably as a result of fungal infection. Appropriate diagnostic procedures yielded a diagnosis in 20 of 27 infections, and therapy was begun in 18 patients. Serologic, culture, and biopsy procedures useful in making rapid diagnoses are advocated in the hope of increasing survival.

Adolescent