A new kind of orphan drug?
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Biomedical subjects
Publications and source records attributed to F Allerberger.
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Listeria monocytogenes is increasingly recognised as a cause of prosthetic joint infection. These infections tend to be more insidious and indolent in contrast to similar infections with Staphylococcus aureus. They can occur in patients who are immunocompromised due to malignancy or other illness or in nonimmunocompromised elderly patients. Listeria infections should not be treated with cephalosporins and prolonged antimicrobial treatment is generally advised for prosthetic joint infections. We noted a high affinity of L. monocytogenes for foreign bodies. Three of twenty-seven cases 11%) of listeriosis under the period of investigation were associated with foreign bodies (hip prosthesis, knee prosthesis and arterial graft).
An in vitro model was used to study whether and how catheter infections can be cured. Silastic catheters were "infected" with Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis KH11 and V2; these "infections" were then treated with 24, 48 and 96 h continuous infusions of various antimicrobial agents administered both as monotherapy and in combination. The Staphylococcus aureus strain was considerably more difficult to eliminate from catheters than were the Staphylococcus epidermidis strains. This experience gained in the laboratory was then applied in vivo to 16 episodes of catheter sepsis in seven children. Treatment for at least six days with imipenem/cilastatin combined with fosfomycin or an aminoglycoside successfully eliminated the pathogens isolated from 11 of the 16 episodes of infection. The broad-spectrum combination was chosen because it could not be assumed that individual pathogens would be sensitive to a single substance. Nine of the infected catheters could be retained in the patients. This experience suggests that it may be possible to successfully eliminate the colonization of central venous catheters by coagulase-negative staphylococci using the antimicrobial agents employed here.
Calcofluor white stain is widely used as a fluorescent stain in mycology. Recently, it was found that by calcofluor white staining Pneumocystis carinii cysts exert a highly characteristic staining pattern. We retested fifteen clinical specimens which were known to be positive for Pneumocystis carinii (diagnosis made by a methenamine silver stain). Calcofluor white stain proved to be a simple, rapid, and inexpensive method for detecting Pneumocystis carinii in clinical specimens.
In a recent study by the Centers for Disease Control (CDC) it was noted that there had been a resurgence of Gram-positive bacteremia together with an increase in fungemia. This reported trend is confirmed by data from the Austrian Tirol. In 1991 1,750 out of 13,679 specimens (12.8%) yielded bacterial or fungal growth, accounting for 1,248 cases of "bacteremia"; no decision was made about the clinical significance of the culture isolates. We consider laboratory reports of blood isolates to be fairly well suited to reflect the frequency of the various bacterial and fungal pathogens. The most common organisms were coagulase-negative staphylococci (41%). The proportion of Staphylococcus aureus (17%), E. coli (4%), Klebsiella-Enterobacter (4%), Pseudomonas (5%) and Candida (3%) corresponded well with the situation in the USA and the UK. Remarkably, anaerobes accounted for only 0.3%, possibly due to our use of a "single bottle"--blood-culture system. Various fastidious organisms, including Brucella melitensis and Haemophilus aphrophilus, were detected by this blood-culture system. Also 15 Haemophilus influenzae-strains, nontyphoidal salmonellae (9 strains), and meningococci (7 strains) were isolated. These data show that the microbiologic features of blood-cultured seen in Austrian Tyrol are broadly similar to those in the UK and North America.
The incidence of tuberculosis in the Austrian Tyrol and Vorarlberg has been declining over decades. In 1989 a reversal in this trend was observed. The number of initial isolates of Mycobacterium tuberculosis at the Federal Public Health Laboratory in Innsbruck increased by 2.2% in 1990 (137 strains), as compared with 1989 (134 strains). The number of cases reported to the health authorities increased by 7.6%. This increase has continued in 1991, with 162 initial isolates registered. It seems that the increase is connected with the presence of greater numbers of ethnic groups from countries with a high incidence of tuberculosis. It is unlikely that the increase is due to additional cases of tuberculosis resulting from the HIV epidemic. Nevertheless, it is recommended that patients with tuberculosis undergo HIV antibody testing. A comparison of the results of animal tests and cultures for demonstrating the presence of mycobacteria showed that the culture procedure is at least equally efficient.
Tuberculous meningitis still poses a major diagnostic problem. Recently, several new techniques for rapid diagnosis of tuberculous meningitis have been developed. One of these newer techniques is the detection of mycobacterial fatty acids, using gas chromatography--mass spectroscopy. In this study we evaluated the sensitivity and specificity of this recently reported method in a blind trial. The sensitivity was found to be 100%, specificity only 91%. The number of false positive results limits the value of this test in the primary diagnosis of tuberculous meningitis. Nonetheless, we consider this method to be a valuable tool for establishing the diagnosis in culture-negative patients presenting with signs and symptoms suggestive of tuberculous meningitis.
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During a six-year period five patients with Campylobacter fetus subspecies fetus infections were seen at the Mayo Clinic in Rochester, Minnesota. Bacteremia was observed in two patients, one presenting with aortic valve endocarditis and the other with abdominal atherosclerotic aortic aneurysm. C. fetus subsp. fetus was isolated from tibial tissue of a patient with osteomyelitis. Diarrhea was the main complaint of two further patients, and was also mentioned by the patient with the aortic aneurysm. Despite the use of incubation conditions and selective media geared to detect only Campylobacter jejuni, C. fetus subsp. fetus was isolated from stool specimens of the two patients with gastrointestinal symptoms. The fact that three of five C. fetus subsp. fetus infections observed in this study were associated with intestinal symptoms further supports the importance of the gastrointestinal tract in the pathogenesis of C. fetus subsp. fetus infections.
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We studied 41 AIDS patients in the Austrian Tyrol with respect to toxoplasma antibody titers and the presence of CNS toxoplasmosis. In no patient had primary Pneumocystis carinii pneumonia (PcP) prophylaxis with either trimethoprim/sulfamethoxazole or pyrimethamine/sulfadoxine been applied; the degree to which CNS toxoplasmosis is influenced by this kind of PcP chemoprophylaxis, widely used elsewhere, is still unclear. In this study 47.4% of toxoplasma-seropositive patients developed CNS toxoplasmosis, compared to the previously estimated risk of 12%-28% for developing CNS involvement in such patients. In view of the high risk of toxoplasma-seropositive patients with AIDS, increased efforts in developing a well-tolerated chemoprophylaxis to combat CNS toxoplasmosis are required.
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The immunomodulator ditiocarb sodium (sodium diethyldithiocarbamate, DTC, CAS 148-18-5) is finding increasing use in treating AIDS-patients. Using a macro broth dilution method the minimal inhibitory concentrations and minimal fungicidal concentrations of DTC were studied for 76 fungal strains (54 species) and a broad spectrum of direct antifungal activity was found. All 6 Candida albicans strains tested were inhibited by 1.2 micrograms DTC/ml, a concentration achievable by i.v. administration of DTC in doses as presently used for immunomodulation. All strains of Cryptococcus were inhibited by DTC in concentrations of 2.5 micrograms/ml. In combination with amphotericin B, DTC showed a synergistic mode of action for 6 out of 7 Cryptococcus neoformans strains (checkerboard technique). As far as the direct antifungal activity of DTC was tested (11 strains, 5 species), the combination with amphotericin B or flucytosine showed no antagonistic mode of action. The augmentation of host defences by the immunomodulating agent DTC could become an adjunct to conventional therapy in immunocompromised patients with systemic fungal infections.
Traditional test methods with determination of MIC values alone are not sufficient for the estimation of antimicrobial activity in tissues. Various other parameters like protein binding, the pH value of tissues and other yet unknown parameters influence bacterial killing under the influence of various antibiotics. In an in vitro model using fibrin clots kill kinetics of H. influenzae were determined. Concentrations of antibiotics were determined in fibrin clots. In these in vitro experiments the eradication of H. influenzae from fibrin clots was investigated under the influence of various antibiotics in different concentrations. The results demonstrate, that the relationship between MIC value and tissue concentration is of little value to determine the antimicrobial activity of beta lactam antibiotics and macrolide antibiotics of H. influenzae in fibrin clots. Macrolide antibiotics demonstrate a bactericidal mode of action.
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Theoretical consideration, empirical findings since 1972 and in vitro results had suggested that a combination of antibiotics for treatment of sepsis is more effective if the 2 or 3 antibiotics are not applied simultaneously but individually and sequentially at short intervals of 4 hours. Between January 1986 and March 1990 100 children were treated with spaced administration of antibiotic combinations at the University Hospital Innsbruck (Department of Paediatric). Causative agents isolated compared well to data published for other institutions; staphylococci were the dominating species. Anaerobic bacteria and fungi accounted for only 1% each, 60% of the cases were nosocomial infections. Overall, the fatality was 4%, a result significantly below the values reported in the literature for conventional therapeutic regimens.