Biomedical subjects
Publications and source records attributed to N Khardori.
Blastomycosis is an uncommon cause of infection in the hand. Fungal infection should be suspected in any case when expected improvement does not occur with appropriate antibiotic therapy and wound care. We describe a rare case of primary blastomycosis of the hand that progressed to severe soft tissue destruction and significant loss of hand function.
Gene therapy is a way to treat disease by transfer of genetic material into the cells of a diseased organism. Generally it is transferred in the form of one or few genes. There is a tremendous potential for application of this technique to the treatment of human hereditary diseases, particularly single gene disorders. Due to ethical and practical reasons, it is currently being used only as somatic cell therapy but it could be achieved by germline also. The major problem in gene therapy is achieving an efficient gene transfer and a persistent gene expression in appropriate somatic cells.
Septicemia, often due to Staphylococcus epidermidis, is a life-threatening complication associated with indwelling vascular catheters. An important factor in the development of such infections is glycocalix, or slime. An in vitro model that mimics intravenous delivery systems in humans was developed. It consisted of a modified Robbins device containing slices of silicone catheters in the removable ports, through which S. epidermidis diluted in 5% dextrose-normal saline with 10% heat-inactivated normal human serum was run, with and without clindamycin and trospectomycin. S. epidermidis was recovered from all catheters in the absence of antibiotics; no growth was detected with antibiotics. Scanning electron microscopy demonstrated significant reduction in glycocalix and no visible organisms with all concentrations except 0.5 micrograms/ml trospectomycin and 1 microgram/ml clindamycin; for those, a moderate amount of glycocalix and a few bacteria were seen. Thus, subinhibitory levels of trospectomycin and clindamycin may have a role in the prevention of microbial adherence to vascular catheters.
A total of 535 evaluable febrile episodes in neutropenic patients were randomly assigned to treatment with ticarcillin-clavulanate plus vancomycin (TV), ceftazidime plus vancomycin (CV), or all three antibiotics (TCV). The TCV regimen was significantly more effective than TV, considering all evaluable episodes, documented infections, gram-negative infections, and infections in patients with persistent severe neutropenia (less than 100 neutrophils/mm3). The results with CV were intermediate between TV and TCV. The toxicities were similar with all three regimens and consisted primarily of skin rashes. The TCV regimen is effective for empiric therapy of fever in neutropenic patients and probably should be utilized in preference to CV or TV, although its superiority over CV in this study was inconclusive.
We have developed an indirect sandwich enzyme-lined immunosorbent assay (ELISA) for the detection of antibodies to Histoplasma ribosomes and histoplasmin; we used this test for demonstration of these antibodies in sera from proven cases of histoplasmosis and other infections. Serum dilutions from five negative controls used in each experiment were normalized against 50 normal sera, and a factor of the mean absorbance was used to establish a positive reaction. Antiribosomal antibodies were detected in 97% of the known histoplasmosis patients with ELISA titers ranging from 1:100 to over 1:12,800. In contrast, antibodies to histoplasmin were detected in only 75% of these sera; titers ranged from 1:100 to 1:12,800. Cross-reactions with sera from other fungal infections (blastomycosis, coccidioidomycosis, paracoccidioidomycosis, cryptococcosis, candidiasis, and aspergillosis) were seen in 46% of the cases with ribosomes and 37% with histoplasmin. Fifty percent of the sera from tuberculosis patients gave positive reactions with ribosomes and 29% with histoplasmin. These results warrant further studies on the significance of antibodies to ribosomes and histoplasmin in immunity to histoplasmosis.
Factors predisposing to clinically significant nosocomial infection with Xanthomonas maltophilia were examined in a matched case-control study using multivariate techniques. Sixteen cases occurred among cancer patients in a six-month period, including an apparent cluster of three cases in an intensive care unit. These infections were unusually serious; eight patients had disseminated infection caused by X maltophilia and six died as a result of their infections. Among the 64 factors that were examined, therapy with broad-spectrum antibiotics and central venous catheterization were found to significantly increase susceptibility to infection. Therapy with imipenem was more than ten times more frequent among cases than among controls (p less than .001). All fatal infections occurred in patients who had received imipenem, including two patients who died before the organism could be identified and appropriate therapy instituted. Infection with X maltophilia should be suspected in patients who develop superinfection while receiving imipenem, and prompt therapy should be instituted to improve chances of survival. Because a common environmental source of X maltophilia was not identified, further study is necessary to determine specific preventive measures.
Trospectomycin (U-63366F), a 6'-propyl analogue of spectinomycin, was tested against aminoglycoside-resistant enterococci. The MIC90 for Enterococcus faecalis was 4 mg/l and that for E. faecium was 8 mg/l. Trospectomycin alone was not bactericidal for enterococci, with MBC90 4096 mg/l for both E. faecalis and E. faecium. The addition of commercially available polyvalent immunoglobulin decreased significantly both the MICs and the MBCs and the rendered trospectomycin bactericidal for enterococci. Chequerboard titration of a combination of trospectomycin with ampicillin revealed an FIC index of 1.0 for all the isolates tested. Time-kill curves also did not show any enhancement of bactericidal activity of ampicillin when combined with trospectomycin. A combination of ampicillin and gentamicin was synergistic for enterococci under similar experimental conditions. Trospectomycin can be used as a safe alternative to aminoglycosides or beta-lactam antibiotics in enterococcal infection where bactericidal activity is not required, or in the event of serious side effects from these two classes of antibiotics.
The susceptibilities of 45 clinical and 3 environmental isolates of Xanthomonas maltophilia to 14 antimicrobial agents was determined by broth microdilution. The newer quinolones PD117596, PD117558, PD127391, A-56620, amifloxacin, and fleroxacin were the most active agents tested, with 70 to 99% of isolates being susceptible to these agents. All isolates were resistant to trospectomycin. The new aminoglycosides SCH24120 and SCH22591 were active against 12 and 1% of isolates, respectively.
At the M.D. Anderson Cancer Center (Houston), Listeria monocytogenes was cultured from 14 patients between 1980 and 1987. The case records of 11 of these patients were reviewed. Underlying malignancies included acute leukemia (three), lymphoma (two), myeloma (one), adenocarcinoma of colon (two), carcinoma of breast (one), carcinoma of lung (one), and Kaposi's sarcoma associated with the acquired immune deficiency syndrome (one). Listeria monocytogenes was cultured from blood (eight patients), cerebrospinal fluid (CSF) (two patients), and from both blood and CSF in one patient. All patients were receiving immunosuppressive therapy including corticosteroids in seven. An absolute neutrophil count of less than 1000/mm3 was noted in five. Bacteremia was the predominant type of infection and ten patients responded to antimicrobial therapy.
The outcome of host-parasite interactions in fungal infections is determined by the balance between pathogenicity of the organism and the adequacy of the host defenses. A wide variety of host defense mechanisms are involved in protection against fungal infections. These include nonspecific mechanisms such as intact skin and mucus membranes, indigenous microbial flora, and the fungicidal activity of neutrophils and monocytes. Such mechanisms constitute the major host defense against opportunistic fungal infections caused by ubiquitous organisms of low virulence. The effective role of immunoglobulins and complement as opsonins varies with the fungal pathogen involved. Specific immune responses of both the humoral and cell-mediated type develop in response to infections by pathogenic fungi. Antibodies, in general, are not of major importance in protection against these infections. Specifically sensitized T lymphocytes produce lymphokines that activate macrophages. Activated macrophages are the major line of defense against systemic fungal pathogens. The type and degree of impairment in immune responses determines the susceptibility and severity of diseases. The type of immune response also determines the tissue reactions in these diseases and sometimes may be involved in the pathogenesis of the disease process. The role of natural killer cell activity, antibody-dependent cellular cytotoxicity, and biological response modifiers in various fungal infections has been described recently. The microbial factors of importance in fungal infections are adherence, invasion, presence of an antiphagocytic capsule, and ability to grow under altered physiological states of the host. The differences in the virulence of fungal strains is of minor importance in determining the outcome in general. The seriousness of the alteration of the host state rather than the pathogenic properties of the fungus determine the severity of the disease.
The in-vitro susceptibility of Mycobacterium avium complex isolates, obtained from immunosuppressed patients with and without the Acquired Immunodeficiency Syndrome (AIDS), to various antimicrobial agents was determined. Amikacin, the 4-quinolone compounds--ciprofloxacin, temafloxacin and PD 117558--and the penem SCH 34343 were active against most of the isolates. In-vitro synergism using selected antimicrobial combinations could not be demonstrated. No differences in the susceptibility, depending upon the source of the isolates (AIDS or non-AIDS), were noted.
Twenty-six serotypes of Xanthomonas maltophilia were defined by using 15 antisera described by Hugh and Ryschenkow (R. Hugh and E. Ryschenkow, J. Gen. Microbiol. 26:123-132, 1961) and 11 new antisera. The antisera were prepared by immunizing rabbits with bacterial strains heated at 100 degrees C for 2 h. Twelve antisera required adsorptions with cross-reacting heterologous immunizing strains. We tested 275 clinical and environmental strains of X. maltophilia with 26 antisera by the slide agglutination technique. A total of 259 (94.2%) strains were typeable, with 137 (49.8%) strains agglutinating in three antisera.
Primary cutaneous infection with Aspergillus species and Rhizopus species was observed in five patients between October 1986 and January 1988. All patients had an underlying hematological malignancy and were neutropenic. Four patients developed skin lesions with eschars at and around the site of intravenous catheter insertion. One patient had two lesions along the course of the intravenous line. The fifth patient developed the lesion on the left side of the lower part of the back subsequent to the appearance of a rash due to excessive perspiration. A diagnosis was made in each case by histopathological studies and cultures of skin biopsy specimens. The fungal organisms cultured were Aspergillus species in three patients and Rhizopus species in two patients. All patients were treated with amphotericin B. Three patients responded to antifungal therapy and local care without surgical débridgement. Two patients died of disseminated fungal infection. The development of cutaneous lesions due to opportunistic fungal pathogens seemed to have been related to the moist and humid conditions created by occlusive dressings or excessive perspiration.
During a 10-year period, four patients with leukemia were identified who had Branhamella catarrhalis septicemia. Two patients had acute leukemia and the remaining two had chronic myelogenous leukemia with blastic transformation. All patients were febrile and neutropenic at the onset of the septicemia. After appropriate antibiotic therapy, they recovered from their infection despite persistence of neutropenia. Because beta-lactamase-producing bacteria are an increasing cause of nosocomial infections, treatment should be selected to cover them.
A 42-year-old Latin American female with acute lymphocytic leukemia in second relapse developed a small ecthymic lesion around the entrance site of a left subclavian line. This was followed by development of left-sided hemiparesis with contralateral loss of pain and temperature sensation. CT of the neck revealed a diffuse inflammatory process with soft tissue involvement and several bubbles of air in the anterior paraspinal muscles and within the spinal canal in the epidural location.
PURPOSE: Progressive disseminated histoplasmosis is now diagnosed frequently in patients with the acquired immunodeficiency syndrome (AIDS) living in the central United States. Previous review articles of AIDS have failed to mention this infection. Herein, we describe 48 AIDS patients with progressive disseminated histoplasmosis in an effort to better understand the clinical presentation and diagnosis of the condition in this setting and to assess the efficacy of antifungal chemotherapy. PATIENTS AND METHODS: In the Houston metropolitan area, there were 66 cases of progressive disseminated histoplasmosis among 1,300 confirmed cases of AIDS from January 1983 to July 1987. Of AIDS patients in East Texas with histoplasmosis, 16 patients were available for follow-up by one of us, and the histories of 32 were obtained by examination of hospital charts and physician records. RESULTS: Fever, weight loss, and splenomegaly were the most common presenting signs and symptoms, occurring in 81, 52, and 31 percent, respectively. One-third of the patients had hematologic abnormalities. Infiltrates on chest roentgenograms were observed in 52 percent. Progressive disseminated histoplasmosis was the initial manifestation of AIDS in almost three-fourths of our patients. Biopsy and culture of the bone marrow established the diagnosis of progressive disseminated histoplasmosis in 69 percent. Clinical or autopsy proof of relapse occurred in three patients despite an initial course of more than 2 g of amphotericin B chemotherapy followed by ketoconazole suppression. CONCLUSION: Progressive disseminated histoplasmosis is often the first sign of immunodeficiency in patients with AIDS, and the diagnosis of this condition is most often established by bone marrow biopsy and culture. Because of the permanence of the immunodeficient state in these patients, progressive disseminated histoplasmosis is resistant to treatment.
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