No abstract

During a period of 11 yr (1983-1993) 137 clinical isolates of Mycobacterium simiae obtained from 75 patients were identified in a University hospital in San Antonio, Texas. One hundred twenty-eight isolates (93%) were from a pulmonary source, four (3%) from blood, and five from other sites including skin, urine, lymph node, bone marrow, and brain. Of 62 evaluable patients, six (10%) had definite infection, nine (14%) had probable disease, and 48 (76%) were thought to be colonized. During the last 2 yr of the study (1992 and 1993), M. simiae became the second most frequently isolated nontuberculous mycobacterium at this institution surpassed only by Mycobacterium avium complex. There are limited data about effective treatment for this multidrug-resistant organism. New macrolides, quinolones, ethambutol, clofazimine, and aminoglycosides are promising therapeutic agents.

We describe a case of coccidioidomycosis in which several unusual morphologic forms of Coccidioides immitis occurred in biopsy tissue from the right lower lung of a patient. To our knowledge, this is the first case where so many diverse morphologic forms were manifested in a single patient in the absence of typical endosporulating spherules. Immature spherules demonstrating segmentation mimicked morula forms of Prototheca spp. Certain elements resembled budding cells of Blastomyces dermatitidis. These consisted of juxtaposed immature spherules without endospores, a germinating endospore, or thick-walled hyphal cells. Branched, septate hyphae and moniliform hyphae consisting of chains of thick-walled arthroconidia or immature spherules were also present. Complement fixation and immunodiffusion tests performed on the patient’s serum were negative for C. immitis, B. dermatitidis, and Histoplasma capsulatum antibodies. Fluorescent-antibody studies were carried out with a specificC. immitis conjugate. All of the diverse fungal tissue elements stained positive with a moderate to strong (2 to 3+) intensity.

After 2 weeks of intravenous challenge with Mycobacterium simiae, ICR outbred mice were treated with clarithromycin, ofloxacin, or clarithromycin plus ethambutol for 4 weeks. All three therapy groups demonstrated a decrease in the level of infection in both the lungs and the spleen. There were no significant differences among the three treated groups in decreasing mycobacterial counts in the lungs; however, both ofloxacin and clarithromycin plus ethambutol were superior to clarithromycin alone in reducing the level of infection in the spleen. Results of the study suggest a potential role for these agents in the treatment of human M. simiae infection.Mycobacterium simiae was originally isolated from Macacus rhesus monkeys in 1965 (3) and later recovered from humans with lung disease (1, 9). Although this organism is rarely isolated in most areas of the world, it accounted for 30% of isolates of nontuberculous mycobacteria in a hospital in Israel (4) and was recovered from 75 patients during an 11-year period in University Hospital in San Antonio, Texas, where this organism became the second most commonly isolated nontuberculous mycobacterium, surpassed only by Mycobacterium avium (data not shown). However, only a small percentage of these patients had proven or suspected clinical disease.In recent years, M. simiae has emerged as a rare pathogen in human immunodeficiency virus-infected patients (2, 5, 10, 11). M. simiae is resistant in vitro to conventional antituberculous drugs, which complicates the choice of optimal therapy. Agents with in vitro activity include ethionamide, cycloserine, clofazimine, and amikacin. In vivo data are limited to a single study of a murine model of infection in which combination therapy with rifampin, clofazimine, and amikacin demonstrated activity against two M simiae strains (12). Currently, there are limited data about the in vitro or in vivo activities of newer antimycobacterial agents such as macrolides and quinolones. We decided to test clarithromycin and ofloxacin because we recently used them successfully to treat a heart transplant patient with proven M simiae pulmonary infection. We also tested the combination of clarithromycin and ethambutol, since the addition of the latter has enhanced the activity of the macrolide in other models of multiresistant mycobacterial infection such as M avium and Mycobacterium paratuberculosis (6-8).Eighty male ICR outbred mice (Harlan Sprague-Dawley, Indianapolis, Ind.) 6 weeks old and weighing approximate 30 g each were held in groups of five and given free access to food pellets and water. An M simiae isolate obtained from a brain biopsy of a human immunodeficiency virus-infected patient (University Hospital) was subcultured at 37°C in Middlebrook 7H9 broth (Difco Laboratories, Detroit, Mich.). A disseminated model of infection was achieved by inoculation of 0.1 ml . Antibiotics were dissolved by sonication in 0.3% Noble agar (Difco Laboratories) mixed with sterile water. Clarithromycin and ethambutol doses were prepared in 0.2-ml volumes...

Four patients with cryptococcal meningitis were treated with amphotericin B colloidal dispersion because of nephrotoxicity from prior treatment with conventional amphotericin B. The limited experience presented here suggests that amphotericin B colloidal dispersion is efficacious for the treatment of cryptococcal meningitis, despite being undetectable in cerebrospinal fluid, and offers a potential therapeutic alternative for patients who cannot tolerate conventional amphotericin B.Conventional amphotericin B alone or in combination with flucytosine has a well-defined role in the treatment of most systemic fungal infections, including cryptococcal meningitis (1, 2). However, nephrotoxicity remains one of the main adverse effects of prolonged therapy. In an attempt to overcome this problem, newer amphotericin B preparations with different lipid vehicles have been created, such as amphotericin B lipid complex, AmBisome, and amphotericin B colloidal dispersion (ABCD). Although these lipid-associated amphotericin B preparations can be given at higher doses than conventional preparations (1 to 6 mg/kg of body weight/day) (1, 4, 5, 7), their therapeutic ratios, unlike that for conventional amphotericin B, have not been established. In addition, the central nervous system pharmacokinetics of these lipid-associated amphotericin B preparations have not been systematically studied. Although human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis have been reported to respond favorably to treatment with both amphotericin B lipid complex (10 of 13 evaluable patients had cerebrospinal fluid [CSF] culture conversion) (3) and AmBisome (12 of 18 patients had CSF culture conversion in a median of 11 days) (4), two treatment failures with ABCD were described, raising concern about the use of the latter preparation for HIV infection (5). We describe the outcomes for four patients with cryptococcal meningitis who were treated with ABCD or Amphocil (Liposome Technology, Inc., Menlo Park, Calif.). In addition, we also present the results of measurements of the levels of amphotericin B in the sera and CSF of three of these patients (Table 1). Patient 1. A 52-year-old man with diabetes mellitus type II and heart transplantation (day 90) was admitted because of pneumonia. He was receiving cyclosporine, azathioprine, and prednisone. A chest radiograph demonstrated bilateral interstitial infiltrates. Bronchoalveolar lavage specimens grew out both Cryptococcus neoformans and Aspergillus fumigatus. A 50-year-old man with chronic liver disease with portal hypertension (positive hepatitis C serology) was admitted because of headache. His sensorium was normal, and there was no papilledema. Examination of the CSF revealed a WBC of 59 ϫ 10 6 cells per liter, a glucose level of 4 mg/dl, a protein level of 0.61 g/liter, a CA titer of 1:8,940, and a positive India ink result. Fungal culture grew C. neoformans. Amphotericin B at a dosage of 0.3 mg/kg/day in combination with flucytosine at 150 mg/kg/day was started. Six days ...