Biomedical subjects

M Trautmann

Publications and source records attributed to M Trautmann.

At least 37 records · Page 2Linked to original sources

PubMed1997

In vitro activities of voriconazole (UK-109,496) against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients with human immunodeficiency virus infection.

The susceptibility of Candida albicans to a new antifungal triazole, voriconazole (UK-109,496), was investigated in 105 isolates obtained from the oral cavities of patients with human immunodeficiency virus (HIV) infection to study this drug's activity against fluconazole-susceptible and -resistant isolates. MICs were determined by a broth microdilution technique according to document M27-T from the National Committee for Clinical Laboratory Standards and by using a broth microdilution technique and a synthetic high-resolution medium. These antifungal susceptibility testing methods showed high levels of agreement (93% for fluconazole and 86% for voriconazole). Data from in vitro studies showed that voriconazole has good activity against fluconazole-susceptible and -resistant C. albicans isolates; the MICs at which 90% of all isolates were inhibited were 0.19 to 0.39 microgram/ml. We found that for isolates for which fluconazole MICs were high, voriconazole MICs were proportionally higher than those for fluconazole-susceptible C.albicans (P < 0.001). Pretreatment isolates from six patients with fluconazole-refractory esophageal candidiasis were included in the study. For these isolates the MICs were < or = 0.39 microgram/ml, and all patients responded to voriconazole. These results suggest that voriconazole is effective even in the treatment of fluconazole-refractory esophageal candidiasis and should be studied further to determine its clinical relevance in patients with HIV infection.

Antifungal Agents↗

PubMed1997

O-antigen seroepidemiology of Klebsiella clinical isolates and implications for immunoprophylaxis of Klebsiella infections.

To provide a database for the development of an O-antigen-polysaccharide-containing vaccine against Klebsiella spp., we examined the O-antigen seroepidemiology of 378 Klebsiella clinical isolates collected prospectively in two university centers. Strains were typed by competitive enzyme-linked immunosorbent assay with rabbit antisera specific for serogroups O1 to O12 and monoclonal antibodies (MAbs) specific for serogroups O1, O2ab, O2ac, and the genus-specific core antigen. The numbers of isolates (percentages) of individual O serogroups were as follows: 148 (39.2) for serogroup O1, 40 (10.6) for serogroup O2ab, 4 (1.1) for serogroup O2ac, 89 (23.6) for serogroup O3, 2 (0.5) for serogroup O4, 32 (8.5) for serogroup O5, none for serogroups O7, O9, and O12, and 21 (5.6) for serogroup O11. Forty-two (11.1) of the strains were non-O-typeable. O-serogroup distributions were virtually identical between isolates from invasive infections and those from noninvasive infections or colonizations. A vaccine containing the O-specific polysaccharides of serogroups O1, O2ab, O3, and O5 would cover 82% of clinically occurring O-antigen specificities. Three hundred thirty-eight of 378 isolates (89.4%) reacted with the genus-specific MAb V/9-5, which recognizes an epitope of the outer core region of Klebsiella lipopolysaccharide. Antibodies directed against this epitope may represent a further alternative for O-antigen-targeted immunoprophylaxis of Klebsiella infections. These data support further experimental investigations on the protective potential of O-antigen-based vaccines and/or hyperimmune globulins in Klebsiella infection.

Antibodies, Bacterial↗

PubMed1997

Protective effect of antilipopolysaccharide monoclonal antibody in experimental Klebsiella infection.

An O-antigen-specific murine monoclonal antibody (MAb) directed against an immunodominant epitope expressed on Klebsiella O1, O6, and O8 lipopolysaccharides (LPS) was examined with respect to its binding to nonencapsulated and encapsulated bacterial cells and its ability to protect against lethal murine Klebsiella sepsis. While the MAb (clone Ru-O1, mouse immunoglobulin G2b) bound well to nonencapsulated organisms of the O1 serogroup, binding was significantly, but not completely, abolished by the presence of the K2 capsule. In a model of experimental Klebsiella peritonitis and sepsis induced by a virulent O1:K2 serogroup strain, higher doses of anti-LPS MAb Ru-O1 than of a previously described anticapsular MAb specific for the K2 capsular polysaccharide were needed to provide protection. However, high-dose (40 microg/g of body weight) pretreatment with anti-LPS MAb Ru-O1 significantly reduced bacterial dissemination to various organs as well as macroscopic and histologic pulmonary alterations. Thus, since the number of Klebsiella capsular antigens occurring in clinical material is too large to be completely "covered" by a K-antigen-specific hyperimmunoglobulin preparation, O-antigen-specific antibodies may supplement K-antigen-specific immunoprophylaxis and -therapy of clinical Klebsiella infection.

Animals↗

PubMed1996

Kinetics and dose dependence of macrophage colony-stimulating factor-induced proliferation and activation of murine mononuclear phagocytes in situ: differences between lungs, liver, and spleen.

Alveolar macrophages (AM) play an important role in antimicrobial defense mechanisms of the lung. It therefore seems reasonable to use macrophage colony-stimulating factor (M-CSF) to enhance local resistance mechanisms. However, little is known about the in vivo activity of M-CSF on macrophages in various organs. We determined the effect of a single subcutaneous dose of M-CSF (10, 50, 100, and 500 ng, respectively) on the number and functional status of AM as well as of macrophages in liver and spleen of mice. Organs were investigated immunohistochemically on days 1 and 3 after injection using monoclonal antibodies specific for F4/80, Ia antigen, and MAC-1. We found a significant increase in the number of F4/80+ AM, Kupffer cells, and splenic macrophages reaching its maximum 24 h after injection of low doses (10 and 50 ng per mouse, respectively) of M-CSF and decreasing to a level seen in untreated mice at 72 h after M-CSF in liver and spleen, whereas at a dose of 50 ng per mouse the number of AM remained high. In contrast, the numbers of AM, Kupffer cells, and splenic macrophages did not increase significantly when high doses were used (500 ng). The expression of Ia antigen and MAC-1 was increased on macrophages in the spleen but not on AM or Kupffer cells. TNF-alpha was elevated in bronchoalveolar (BAL) fluid after 3 h and IL-6 at 6, 12, and 24 h after M-CSF injection in dose-dependent manner. Nitric oxide production was not increased after injection of M-CSF. Our results point to regional differences in the response of macrophages to M-CSF. These may caused by differences in the M-CSF-induced production of TNF-alpha and IL-6. These findings may be important for the therapeutic use of M-CSF in microbial infections.

Animals↗

PubMed1996

Evaluation of a competitive ELISA method for the determination of Klebsiella O antigens.

Strains of Klebsiella spp. are often inagglutinable by O-specific antisera because of the copious capsule produced by most isolates. A competitive ELISA method based on the observation that bacterial supernates containing homologous O antigen specifically inhibited the reaction of type-specific antisera with purified LPS coated on ELISA plates was used to examine the O antigen of 82 isolates of different Klebsiella species and subspecies. The O antigens O1/2ab (19 isolates), O2ab (13 isolates), O2ac (11 isolates) and O3 (16 isolates) were found to account for > 70% of the O antigenic types. Overall, 65 (79%) of the strains could be assigned to a specific O serogroup. The method is suitable for examining the role of individual O antigens in systemic klebsiella infections such as nosocomial septicaemia and pneumonia.

Animals↗

PubMed1996

[Comparison of three antifungal susceptibility testing methods for the in vitro testing of Candida isolates from patients with HIV infection].

The MIC values of fluconazole were determined for 96 Candida isolates (56 C. albicans, 15 C. glabrata, 9 C. krusei and 10 C. tropicalis). The methods employed for antifungal susceptibility testing were: microdilution according to the protocol M27-P of the NCCLS (M 27-Pmicro) using RPMI 1640 medium or HR medium following Troke & Pye (HRmicro) as well as the agar diffusion method by means of the Etest (YNB agar). The in vitro results were compared with the clinical outcome of patients. All C. albicans isolates received from AIDS patients with fluconazole-refractory candidosis showed MICs of > or = 6.25 mg/ml (M27-Pmicro) or > or = 25 mg/ml (MRmicro) and Etest). On the other hand some MICs of C. albicans isolates from AIDS patients with fluconazole-sensitive candidosis were also beyond these breakpoints. Therefore, a possible success of a fluconazole therapy cannot unequivocally be predicted from the MIC value determined in vitro.

AIDS-Related Opportunistic Infections↗

PubMed1996

Pharmacokinetics of sparfloxacin and serum bactericidal activity against pneumococci.

Sparfloxacin, a new fluorinated quinolone, exhibits higher in vitro activity against pneumococci than do ciprofloxacin and ofloxacin. Since up to 30% of cases of pneumococcal pneumonia are associated with bacteremia, and since an increasing percentage of pneumococci are resistant against penicillin, we studied the serum bactericidal activity of sparfloxacin against pneumococci in eight healthy, middle-aged volunteers. Pharmacokinetics in serum and urine after a 400-mg oral dose of sparfloxacin were comparable to those described by other authors. Inhibitory and bactericidal activities in serum were measured for four pneumococcal isolates representing penicillin-susceptible (one isolate), intermediately resistant (two isolates), and highly resistant (one isolate) strains. Geometric mean inhibitory titers ranged between 1:2.4 and 1:6.3 and bactericidal titers ranged between 1:1.3 and 1:3.6 during a time period of 1 to 6 h after drug intake. Although such titers were not sufficient to predict a clinical response based on previous pharmacodynamic studies using quinolone antibiotics, data obtained with volunteers may only partially reflect the clinical situation in which a rise of humoral antibodies directed against pneumococcal antigens may help to reinforce the bactericidal action of the antibiotic.

Adult↗

PubMed1996

Comparative evaluation of three antifungal susceptibility test methods for Candida albicans isolates and correlation with response to fluconazole therapy.

In vitro susceptibilities were determined for 56 Candida albicans isolates obtained from the oral cavities of 41 patients with human immunodeficiency virus infection. The agents tested included fluconazole, itraconazole, ketoconazole, flucytosine, and amphotericin B. MICs were determined by the broth microdilution technique following National Committee for Clinical Laboratory Standards document M27-P (M27-P micro), a broth microdilution technique using high-resolution medium (HR micro), and the Etest with solidified yeast-nitrogen base agar. The in vitro findings were correlated with in vivo response to fluconazole therapy for oropharyngeal candidiasis. For all C. albicans isolates from patients with oropharyngeal candidiasis not responding to fluconazole MICs were found to be > or = 6.25 micrograms/ml by the M27-P micro method and > or = 25 micrograms/ml by the HR micro method as well as the Etest. However, for several C. albicans isolates from patients who responded to fluconazole therapy MICs found to be above the suggested breakpoints of resistance. The appropriate rank order of best agreement between the M27-P micro method and HR micro method was amphotericin B > fluconazole > flucytosine > ketoconazole > itraconazole. The appropriate rank order with best agreement between the M27-P micro method and the Etest was flucytosine > amphotericin B > fluconazole > ketoconazole > or = itraconazole. It could be concluded that a good correlation between in vitro resistance and clinical failure was found with all methods. However, the test methods used in this study did not necessarily predict clinical response to therapy with fluconazole.

AIDS-Related Opportunistic Infections↗

PubMed1995

Single-dose pharmacokinetics of fluconazole in patients with liver cirrhosis.

The pharmacokinetics of a single 100 mg i.v. dose of fluconazole were studied in parallel groups of ten normal subjects and nine patients with liver cirrhosis, a condition with a high risk of life-threatening fungal infection. The following mean pharmacokinetic parameters were found for the patient group: terminal elimination constant 0.0101/h (normal 0.0214/h); mean residence time 134 h (normal 46.7h); area under the curve 200 h.mg/L(normal 69.4 h.mg/L); plasma clearance 0.96 L/h.kg(normal 2.16 L/h.kg). All these differences were statistically significant (P < 0.05). The majority of the patients were being concomitantly treated with duretics (frusemide and spironolactone). It is suggested that the known slight interaction between such drugs and fluconazole was intensified by the disease state. These results emphasize the need for caution in the treatment with fluconazole of patients with severe liver disease. Nevertheless, in view of the wide range of values found in the patients, and low toxicity of fluconazole, a dosage reduction in cirrhosis does not seem to be justified in the present state of knowledge.

Adult↗

PubMed1995

Effects of MICs and sub-MICs of antibiotics on production of capsular polysaccharide of Klebsiella pneumoniae.

In the present study, we examined whether MICs and sub-MICs of antimicrobial agents belonging to two different classes, ciprofloxacin and ceftazidime, were able to influence the production and release of cell-associated and soluble (extracellular) capsular polysaccharide (CPS), respectively, in a heavily encapsulated strain of Klebsiella pneumoniae (B5055). Using a CPS-specific enzyme-linked immunosorbent assay, we found that the amount of cell-associated CPS increased in a dose-dependent manner by more than 10-fold under the influence of the MIC of ceftazidime and by more than 100-fold under the influence of the MIC of ciprofloxacin. The largest amounts of CPS were measured by using the MIC of either antibiotic substance. Electron microscopic studies showed that the diameter of the capsule was significantly increased compared with the diameter for untreated controls. Thus, both antimicrobial agents genuinely stimulated CPS production.

Anti-Bacterial Agents↗

PubMed1995

Comparison of fosfomycin and teicoplanin in serum bactericidal activity against staphylococci.

A serum bactericidal test was established employing human sera of volunteers after intravenous administration of fosfomycin (CAS 23155-02-4) and teicoplanin (CAS 61036-62-2) against 40 staphylococcal strains (20 Staphylococcus aureus and 20 coagulase-negative staphylococci, 10 of each group being susceptible and 10 being resistant to oxacillin). Median serum inhibitory titres were highest for fosfomycin against oxacillin-susceptible Staphylococcus aureus. In the three other groups of strains, the activity of fosfomycin was comparable to that of teicoplanin. The killing curves showed over 99% killing within 24 h for both antibiotics. Here, fosfomycin exerted a rapid killing activity within 4-6 h and was more effective in bacterial growth reduction. It can be concluded that fosfomycin and teicoplanin exerted comparable serum bactericidal antibacterial activity against staphylococci.

Adult↗

PubMed1994

An investigation on the role of vacuolar-type proton pumps and luminal acidity in calcium sequestration by nonmitochondrial and inositol-1,4,5-trisphosphate-sensitive intracellular calcium stores in clonal insulin-secreting cells.

To test whether in RINm5F rat insulinoma cells luminal acidity and the activity of a vacuolar-type proton pump are involved in calcium sequestration by intracellular calcium stores sensitive to inositol 1,4,5-trisphosphate (InsP3) we examined the effects of various proton-conducting ionophores and ammonium chloride, and of bafilomycin, a specific inhibitor of vacuolar proton pumps, on this parameter. Bafilomycin in concentrations up to 1 microM did not affect calcium sequestration by nonmitochondrial, InsP3-sensitive stores at all; 50 microM carbonylcyanide m-chlorophenylhydrazone, 50 microM monensin and 30 mM NH4Cl, which are diverse ways to dissipate transmembrane pH gradients, did not inhibit calcium sequestration. This argues against signficant involvement of internal acidity and vacuolar proton pumps in calcium sequestration by InsP3-sensitive stores in RINm5F cells. The proton-potassium-exchanging ionophore nigericin (20-100 microM), however, inhibited calcium sequestration by nonmitochondrial and InsP3-sensitive stores. This effect was dependent on the presence of potassium and could be reversed by inclusion of carbonylcyanide m-chlorophenylhydrazone or acetate in the incubation medium. Thus, the inhibitory effect of nigericin appears to be based on proton extrusion coupled to potassium influx across the membrane of calcium stores in RINm5F cells, creating an internal alkalinization of these stores. The effect of nigericin implies the continuous maintenance of an outside-to-inside potassium concentration gradient by nonmitochondrial calcium stores in RINm5F cells. This feature will be of potential interest in the identification of InsP3-sensitive calcium-storing organelles.

Ammonium Chloride↗

PubMed1994

Use of a receiver operating characteristic in the evaluation of two commercial enzyme immunoassays for detection of Helicobacter pylori infection.

Two novel commercial IgG enzyme immunoassay (EIA) systems based on acid-glycine-extracted (Pyloriset IgG EIA, Orion Diagnostica) or fast protein liquid chromatography-purified (Cobas Core Anti-H. pylori EIA, Roche Diagnostic Systems) Helicobacter antigens were evaluated in a prospective study involving 127 patients. All patients underwent upper endoscopy with biopsy, and biopsies were examined for the presence of Helicobacter pylori by a rapid urease test, microscopy and culture. Of the 71 patients found to be infected with Helicobacter pylori, 69 (97.2%) and 65 (91.5%) tested positive with the Cobas Core and Pyloriset test, respectively. A detailed receiver operating characteristic analysis of the two tests showed that the Cobas Core assay was more sensitive and specific at every possible cut-off level; gave a better resolution of individual results, indicating a greater fine-sensitivity; and had no grey zone compared to a large grey zone encompassing 13.4% of the serum samples tested with the Pyloriset EIA. The Cobas Core assay appears to be a valuable tool for epidemiological purposes as well as for pre-endoscopic screening of dyspeptic patients.

Antigens, Bacterial↗

PubMed1994

Complicated tuberculosis and residual disease.

Complicated and extrapulmonary manifestations of tuberculosis (TB) may cause prolonged suffering for the individual patient and represent a high economic burden for the society concerned. Complications of pulmonary TB may be the consequence of reduced individual resistance, immunosuppression or specific immune defects. In HIV patients, pulmonary TB is often associated with extrapulmonary lesions, while the radiologic appearance of lung infiltrates may be less prominent compared to HIV negative persons. The present review summarizes data obtained during a 12-year study of extrapulmonary TB in Berlin, Germany, and outlines the role of residual TB lesions for disease reactivation in later life. Indications and limitations of INH preventive chemotherapy will be discussed.

HIV Seropositivity↗

PubMed1994

The pharmacokinetics of fluconazole after a single intravenous dose in AIDS patients.

The pharmacokinetics of fluconazole after a single 100 mg i.v. dose were studied in 10 healthy subjects (5 M; 5 F) and 10 HIV-positive patients (8 M; 2 F). The mean value of plasma clearance was 25% lower in the patient groups (17 +/- 6 (s.d.) vs 23 +/- 4 ml min-1; 95% CI of difference -11 to -0.7; P < 0.05). This difference may have been related to slightly reduced kidney function in the patient group (mean creatinine clearance -18%) but is unlikely to be clinically significant. Therefore, no adjustment of the dose of intravenously administered fluconazole appears to be necessary in AIDS patients without clinical signs of enteropathy.

Acquired Immunodeficiency Syndrome↗

PubMed1994

A murine monoclonal antibody defines a unique epitope shared by Klebsiella lipopolysaccharides.

A hybridoma secreting a monoclonal antibody (MAb) directed against Klebsiella lipopolysaccharide (LPS) was derived from spleen cells of mice immunized a smooth, nonencapsulated Klebsiella strain (Friedländer 201; serogroup O1). The MAb, called V/9-5 (immunoglobulin G2a), cross-reacted with LPS preparations produced from reference strains for the Klebsiella O serogroups O1, O2ab, O2ac, O3, O4, O5, and O12. Furthermore, the MAb reacted with LPSs from serogroup reference strains O6/O8, O9, and O11, which are regarded as being identical to O1, O2, and O4, respectively. When testing the supernatant of clinically isolated Klebsiella strains by means of an inhibition enzyme-linked immunosorbent assay, we found that 86 (92.4%) of 93 Klebsiella pneumoniae subsp. pneumoniae isolates and 24 (96.0%) of 25 K. oxytoca isolates harbored the cross-reactive epitope. By contrast, two laboratory strains of K. pneumoniae subsp. rhinoscleromatis did not react with MAb V/9-5. The MAb proved to be specific for the genus Klebsiella, since it did not react with any of a total of 73 strains belonging to other gram-negative bacterial genera. In conjunction with other LPS-specific MAbs, MAb V/9-5 might become a useful reagent for rapid identification of klebsiellae in clinical specimens. Furthermore, the epitope recognized by MAb V/9-5 might serve as a target epitope for the production of human MAbs for immunotherapeutic purposes.

Animals↗

PubMed1994

Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection.

After repeated use of fluconazole for therapy of oropharyngeal candidosis, the emergence of in vitro fluconazole-resistant Candida albicans isolates (MIC, > or = 25 micrograms/ml) together with oral candidosis unresponsive to oral dosages of up to 400 mg of fluconazole were observed in patients with human immunodeficiency virus (HIV) infection. Antifungal susceptibility testing was done by broth microdilution and agar dilution techniques on C. albicans isolates recovered from a cohort of patients with symptomatic HIV infection who were treated repeatedly with fluconazole for oropharyngeal candidosis. In vitro findings did show a gradual increase in the MICs for C. albicans isolates recovered from selected patients with repeated episodes of oropharyngeal candidosis. Primary resistance of C. albicans to fluconazole was not seen. Cross-resistance in vitro occurred between fluconazole and other azoles (ketoconazole, itraconazole), but to a lesser extent. The results of the study suggest that the development of clinical resistance to fluconazole could be clearly correlated to in vitro resistance to fluconazole. Itraconazole may still serve as an effective antifungal agent in patients with HIV infection and oropharyngeal candidosis nonresponsive to fluconazole.

AIDS-Related Opportunistic Infections↗

PubMed1994

Malaria prophylaxis: identifying risk groups for non-compliance.

To investigate behaviour in the use of drug prophylaxis against malaria and the risk factors for non-compliance, 507 European or North American travelers returning from endemic areas were studied retrospectively at Berlin in a 11-year period from 1980 to 1990. Compliance was significantly correlated with shorter travel duration: the group with good compliance stayed 37.2 +/- 38.5 days (mean +/- SD) in contrast to 69.8 +/- 93.5 days in the group of patients with no compliance (p = 0.00001). Older patients were significantly more compliant than patients aged < 55 years (20/27 compliant at > 54 years vs. 175/476 at < 55 years; p = 0.0001). Compliance was significantly affected by travel destination (Southern and East African regions; p = 0.0054), age (< or = 15 and > or = 55 years, respectively; p = 0.0001), and reason of travel (package tours; p = 0.0001). CART analysis confirmed logistic regression analysis with respect to age and travel type, and revealed that patients using only one information source were significantly more compliant than those using two or more information sources. Travel agencies were nearly as well informed as Institutes of Tropical Medicine, but family doctors had a significant incidence of giving wrong advice. This study should enable medical personnel dealing with prophylactic advice against malaria to identify patients at high risk for non-compliance, and to educate them more carefully than other travellers regarding antimalarial drug prophylaxis.

Adolescent↗