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M Trautmann

Publications and source records attributed to M Trautmann.

At least 19 recordsLinked to original sources

Genetic variability determinants of Helicobacter pylori: influence of clinical background and geographic origin of isolates.

Helicobacter pylori has an unusual pattern of genetic variation, which complicates research on this organism. To gain a better understanding of the forces behind this phenomenon, the extent to which recombination and single point mutations affect genetic variability in H. pylori was quantified and the influence of both geographical distance and clinical background were assessed. Site-directed restriction-endonuclease digestion of 2 gene fragments was performed on 168 isolates from Montreal and Berlin. Allelic diversity was found to be much higher for H. pylori than for other bacterial species. This finding is consistent with those of previous studies on H. pylori that were conducted using other techniques. However, nucleotide diversity was within the range reported for other bacterial species. Phylogenetic analysis found no grouping of strains with clinical background or geographical origin. Recombination at a rate that resulted in linkage equilibrium within genes can explain these observations.

Alleles↗

Binding to and opsonophagocytic activity of O-antigen-specific monoclonal antibodies against encapsulated and nonencapsulated Klebsiella pneumoniae serotype O1 strains.

The high mortality of nosocomial infections caused by Klebsiella spp. has acted as a stimulus to develop immunotherapeutic approaches targeted against surface molecules of these bacteria. Since O-antigen-specific antibodies may add to the protective effect of K antisera, we tested the functional and binding capacity of O-antigen-specific monoclonal antibodies (MAbs) raised against different Klebsiella O antigens. The MAbs tested were specific for the O-polysaccharide partial antigens D-galactan II (MAb Ru-O1), D-galactan I (MAb IV/4-5), or core oligosaccharide (MAb V/9-5) of the Klebsiella serogroup O1 antigen. In enzyme-linked immunosorbent assay binding experiments, we found that all MAbs recognized their epitopes on intact capsule-free bacteria; however, binding to encapsulated wild-type strains belonging to different K-antigen serotypes was significantly reduced. The K2 antigen acted as the strongest penetration barrier, while the K7 and K21 antigens allowed some, though diminished, antibody binding. In vitro phagocytic killing experiments showed that MAb Ru-O1 possessed significant opsonizing activity for nonencapsulated O1 serogroup strains and also, to a much lesser extent, for encapsulated strains belonging to the O1:K7 and O1:K21 serotypes. MAbs or antisera specific for the D-galactan II antigen may thus be the most promising agents for further efforts to develop a second-generation Klebsiella hyperimmune globulin comprising both K- and O-antigen specificities.

Animals↗

[Community-acquired respiratory tract infections. Current data on the efficacy of various classes of antibiotics and antibiotic resistance of the main prevalent bacteria species].

BACKGROUND: The American Thoracic Society regards fluoroquinolones together with macrolides and doxycycline as first choice antibiotics in the empirical treatment of community acquired pneumoniae in non-hospitalized patients, while the Deutsche Gesellschaft für Pneumology only recommends macrolides and doxycycline for these patients. MATERIAL AND METHODS: In order to find out if the German recommendations still adequately reflect the local resistance situation, we analyzed antibiotic resistance of clinically relevant isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in a multicenter study with special reference to sparfloxacine and ciprofloxacin according to DIN recommendations. RESULTS: In contrast to other European countries and the USA the prevalence of antibiotic resistance in Germany is low. Betalactam antibiotics were effective against more than 95% of strains of Haemophilus influenzae and Streptococcus pneumoniae. However, 10% of the strains of Streptococcus pneumoniae were resistant to tetracycline and 7% resistant to erythromycin. Resistances against ciprofloxacin and sparfloxacine were not detectable. Of both quinolone antibiotics, sparfloxacine was always more active than ciprofloxacin. CONCLUSIONS: These susceptibility data and the known prevalence of other respiratory tract pathogens such as Chlamydia pneumoniae and Mycoplasma pneumoniae which are sensitive to erythromycin and tetracycline therefore support the recommendations of the Deutsche Gesellschaft für Pneumology. However, newer fluoroquinolones with increased activity against pneumococci may be a helpful alternative for patients with persistent and recurrent exacerbations of respiratory infections and patients with relevant underlying diseases or relevant risk factors.

Adult↗

[Does sleep apnea increase the risk of myocardial infarct during sleep?].

Myocardial infarction shows a circadian pattern with a maximum in the early morning hours. In patients with sleep-related breathing disorders (SRBD), it is assumed that apnea-associated changes of hemodynamics, blood gases, and rheology lead to a higher frequency of myocardial infarction during sleep. This investigation analyzes the circadian pattern of myocardial infarction in patients with and without SRBD. Within a time period of 20 months, 89 male patients with acute myocardial infarction were consecutively admitted to the intensive care unit. A nocturnal long-term registration of oxygen saturation, heart rate, breathing sounds, and body position by means of a 4-channel recording system (MESAM IV) was carried out in 59 of the 89 patients 6 to 10 days (evaluation I) and in 43 of 59 patients 22 to 28 days after infarction (evaluation II). Sleep apnea with a respiratory-disturbance-index (RDI > or = 10/h was found in 44.1/39.5% of the patients (evaluation I/II). In 22% of the patients, time of infarction was during a sleeping period. Patients with myocardial infarction during sleep had a clearly higher RDI in comparison to patients with a myocardial infarction during wakefulness (evaluation I: 22.7 versus 9.4/h; p = 0.08; evaluation II: 20.3 versus 7.3; p < 0.05). 53.6% of all myocardial infarctions occurred during the time period 5:00-11:00 a.m. Investigations in a larger number of patients are necessary to confirm these results as well as the relevance of sleep apnea as a cardiovascular risk factor.

Adult↗

Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Mix50 Study Group.

The objective of this 6-month, open-label, randomized, two-period crossover study was to compare glycemic control when patients were treated with (1) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation, neutral protamine lispro (NPL), and (2) 2 manufactured premixed human insulin formulations, human insulin 50/50 and human insulin 30/70. One hundred individuals, 37 with type 1 diabetes mellitus (12 females, 25 males; mean age, 39.4 years; mean body mass index [BMI], 24.8; mean duration of diabetes, 12.9 years) and 63 with type 2 diabetes mellitus (33 females, 30 males; mean age, 59.0 years; mean BMI, 28.4; mean duration of diabetes, 12.6 years), were treated with insulin lispro mixtures. Insulin lispro Mix50 (50% insulin lispro/50% NPL) and human insulin 50/50 (50% regular insulin/50% neutral protamine Hagedorn [NPH] insulin) were administered before breakfast; insulin lispro Mix25 (25% insulin lispro/75% NPL) and human insulin 30/70 (30% regular insulin/70% NPH) were administered before dinner. Blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG <3.0 mmol/L), insulin dose and timing of dose before meals, and hemoglobin A1c were measured. Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups. However, compared with human insulin mixtures, twice-daily administration of insulin lispro mixtures resulted in improved postprandial glycemic control, similar overall glycemic control, and less nocturnal hypoglycemia, as well as offering the convenience of dosing closer to meals.

Adult↗

Genotypic relatedness of yeast isolates from women infected with human immunodeficiency virus and their children.

The objective of this study was to compare polymerase chain reaction (PCR) fingerprinting with other molecular typing methods as an epidemiologic tool to investigate the transmission of Candida strains between HIV-positive mothers and their children. Forty-nine yeast strains (including Candida albicans, Candida glabrata, Rhodotorula rubra, Candida tropicalis, Candida famata, Candida dubliniensis, Saccharomyces cerevisiae) from 30 individuals (15 children and 15 HIV-infected mothers or accompanying person) were isolated. Colonization/infection with yeast was observed in 80% of all individuals in the oral cavity, and in 33% from hand cultures, respectively. Thirteen out of 15 children (86%) and 12 out of 15 adults (80%) were colonized/infected with yeasts. Candida dubliniensis strains were found in four HIV-infected women but not in children. The results with an arbitrarily primed (AP)-PCR mediated genotyping assay using phage M13 core sequence were compared with the hybridization patterns using the species-specific DNA probe CARE-2 for the C. albicans isolates. Typing of non-C. albicans strains was done using AP-PCR in comparison with pulsed-field gel electrophoresis (PFGE). Twenty-six C. albicans strains gave two different genotypes by AP-PCR but 16 genotypes by CARE-2 hybridization. The CARE-2 probe appeared to have a higher discriminatory power compared with the primer 'M13'-mediated AP-PCR in typing C. albicans isolates.

Adult↗

Combined activity of azithromycin and lansoprazole against Helicobacter pylori.

BACKGROUND: Due to its unique pharmacokinetic properties, azithromycin may be an attractive combination partner for H. pylori eradication regimens. However, up to 15% of clinical isolates are primarily resistant to azithromycin as well as to other macrolide antibiotics. Combination therapy with lansoprazole, a proton pump inhibitor known to have intrinsic antibacterial activity against H. pylori, may be useful to counteract such resistance. We therefore evaluated the combined effects of azithromycin and lansoprazole in vitro. MATERIALS AND METHODS: Minimal inhibitory concentrations (MICs) of azithromycin and lansoprazole alone and in combination were determined for 106 clinical H. pylori isolates by means of an agar dilution technique. Killing kinetics of seven isolates were also studied in fluid medium. RESULTS: MIC values for 50 and 90% of the isolates (MIC50, MIC90) were 0.19 and 0.5 mg/l for azithromycin, and 44.5 and 104 mg/l for lansoprazole. Nine strains (8.5%) had an MIC of azithromycin > or = 16 mg/l and were regarded as resistant. An additive interaction between the two drugs was found in 72 (68%), and indifferent effects in 24 strains (23%). Three of 9 azithromycin-resistant strains regained sensitivity in the presence of lansoprazole. In fluid culture, synergism between the two drugs occurred in 6 out of 7 strains tested. CONCLUSION: In the majority of strains, lansoprazole and azithromycin interacted in an additive or synergistic manner depending on the test method employed. Addition of lansoprazole restored in vitro sensitivity to azithromycin in 3 out of 9 azithromycin-resistant strains. Such effects may enhance the elimination of H. pylori during clinical eradication therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Endotoxin release due to ciprofloxacin measured by three different methods.

Antibiotics are known to induce the release of bioactive endotoxin (LPS) from gram-negative bacterial cells. Because varying data have been published on the influence of quinolone antibiotics on LPS liberation, we studied the effect of ciprofloxacin on a culture of Escherichia coli by determining bacterial killing and free LPS concentrations in comparison with imipenem and ceftazidime. LPS levels were measured by three different methods, namely (1) the Limulus amebocyte lysate test, (2) an ELISA method based on capture of LPS by monoclonal antibodies, and (3) indirect determination by measuring the ability of antibiotic-induced LPS to trigger TNFalpha release from a monocytic cell line. With both the Limulus and ELISA tests, a low endotoxin-releasing activity of ciprofloxacin was confirmed. In contrast to previous studies, this LPS also had low bioactivity in terms of TNFalpha induction. Limulus LPS determinations correlated more precisely with LPS bioactivity than did ELISA values, an observation which underlines the crucial role of LPS determination methods in studies of antibiotic-induced LPS release.

Anti-Infective Agents↗

Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group.

OBJECTIVE: Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin. Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion (CSII) treatment were assessed in an open randomized crossover trial comparing insulin lispro and regular human insulin, both applied with insulin pumps. RESEARCH DESIGN AND METHODS: A total of 113 type 1 patients (60 male, 53 female, age [mean +/- SD] 37 +/- 12 years, duration of diabetes 19 +/- 9 years) participated in this open, randomized crossover study. Both insulins were applied for 4 months each with the appropriate intervals between the prandial insulin bolus and the meal (human insulin: 30 min; lispro: 0 min). Observation parameters were HbA1c, daily and postprandial blood glucose profiles, adverse events, rate of hypoglycemic and hyperglycemic events, number of catheter obstructions, and treatment satisfaction as assessed with an international validated questionnaire. RESULTS: The patients were well controlled with a mean HBA1c of 7.24 +/- 1.0% at baseline. HbA1c decreased in both treatment periods, but it was better during insulin lispro treatment (insulin lispro: 6.8 +/- 0.9%, regular human insulin: 6.9 +/- 1.0%, Friedman's rank-sum test: P < 0.02). In addition, the 1-h and 2-h postprandial rises in blood glucose were significantly lower (P < 0.001 for each meal) with insulin lispro, resulting in smoother daily glucose profiles as compared with regular human insulin. No significant differences were reported for the rate of hypoglycemia (mean +/- SD [median]: insulin lispro 12.4 +/- 13.9 [8], regular human insulin 11.0 +/- 11.2 [8]), for the rate of catheter obstructions (42 events in each treatment arm), and for the number and type of adverse events. No severe case of ketoacidosis was seen during insulin lispro treatment, whereas one case was reported during therapy with regular human insulin. Treatment satisfaction was better when patients were treated with insulin lispro. CONCLUSIONS: Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment. Its safety profile does not differ from that of regular human insulin.

Adult↗

Granulocyte colony-stimulating factor worsens the outcome of experimental Klebsiella pneumoniae pneumonia through direct interaction with the bacteria.

Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. We studied the effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae, an important gram-negative bacillary pulmonary pathogen. Using a highly reproducible murine model, we here show the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Binding of 125I-G-CSF to K pneumoniae was displaced by an excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1alpha, did not compete with G-CSF binding to the bacteria. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes.

Animals↗

Antibacterial activity of meropenem against Pseudomonas aeruginosa, including antibiotic-induced morphological changes and endotoxin-liberating effects.

The in vitro effects of meropenem on Pseudomonas aeruginosa were examined by studying (i) the inhibitory and bactericidal concentrations of meropenem versus those of imipenem for clinical isolates; (ii) changes in bacterial morphology during in vitro culture; and (iii) release of endotoxin induced by meropenem compared with that induced by other antipseudomonal compounds. Meropenem MIC90 and MBC90 values for 108 clinical isolates were 2 and 4.8 mg/l compared to 4.5 and 9.6 mg/l for imipenem. Morphological studies using phase-contrast and scanning electron microscopy showed that meropenem induced the formation of indeterminate bacterial cell forms at drug concentrations of 1-2.5 mg/l (0.5- to 1.25-fold the MIC), while spheroplasts predominated at drug levels exceeding 5 mg/l (2.5-fold the MIC). Determination of free and EDTA-releasable endotoxin activity by means of the Limulus lysate test showed that both meropenem and imipenem liberated significantly less endotoxin than did ceftazidime. Therefore, although meropenem binds to penicillin-binding proteins (PBPs) 2 and 3 (in contrast to imipenem, which binds to PBP2 only), endotoxin release should not be a cause of concern when treating systemic gram-negative infections with this drug.

Anti-Infective Agents↗

Bacterial lipopolysaccharide (LPS)-specific antibodies in commercial human immunoglobulin preparations: superior antibody content of an IgM-enriched product.

The anti-LPS antibody content of commercial intravenous immunoglobulins was examined by quantitative ELISA using LPS preparations from Escherichia coli, Klebsiella and Pseudomonas aeruginosa O serotypes occurring most frequently in gram-negative septicaemia. Three IgG products from different manufacturers and one IgM-enriched product were tested. Mean antibody levels were significantly higher in the IgM fraction of the IgM-enriched product compared with 'pure' IgG products, indicating that natural antibodies against bacterial LPS belong primarily to the IgM class. Immunoblotting studies showed that antibody specificities were directed mainly against O side chain epitopes. Antibodies against rough mutant LPS representing various chemotypes were detected in IgG but not in IgM products. The virtual absence of antibodies against Vibrio cholerae LPS indicated that human anti-LPS antibodies result from continuous environmental exposure to gram-negative pathogens. These data support the further development of IgM-enriched preparations for prophylaxis and treatment of gram-negative nosocomial infections.

Antibodies, Bacterial↗

Antibiotic-induced release of endotoxin: in-vitro comparison of meropenem and other antibiotics.

The influence of meropenem, a new carbapenem antibiotic, on cell morphology and in-vitro lipopolysaccharide (LPS) release from Escherichia coli was compared with that of imipenem, ceftazidime, tobramycin and ciprofloxacin. Free and cell-associated LPS was quantified by means of a capture ELISA method based on the recognition of E. coli LPS by monoclonal antibodies. Microscopically, meropenem was found to induce spheroplast formation similar to that seen with imipenem, while ceftazidime and ciprofloxacin induced filament formation. Free and cell-associated LPS levels were low in the presence of meropenem, imipenem, ciprofloxacin and tobramycin, but high in the presence of ceftazidime. Reduced endotoxin release appears to be a common property of carbapenem antibiotics. Morphological changes in bacteria in the presence of antibiotics do not predict their LPS-liberating effect since ciprofloxacin induced low levels of LPS despite causing filament formation.

Anti-Bacterial Agents↗

Adherence of Staphylococcus aureus isolated in peritoneal dialysis-related exit-site infections to HEp-2 cells and silicone peritoneal catheter materials.

BACKGROUND: Peritoneal catheter exit-site infections cause a relevant morbidity in peritoneal dialysis patients and are frequently caused by Staphylococcus aureus. We tested the hypothesis that adherence of exit-site-derived S. aureus to epithelial cells and peritoneal catheter silicone tubes discriminates virulent and less virulent strains. METHODS: The binding of isolated S. aureus to an epithelial cell line (HEp-2) and to silicone tubes was analyzed using light-microscopy or radioactive labeling of bacteria. RESULTS: Of 378 exit-site swabs, 99 (26%) were positive for microbial growth. S. aureus was cultured in 25 of 99 positive swabs; three of 13 swabs taken in exit-site infections grade 3 and 4 that had tested positive for S. aureus. Adherence of S. aureus from exit-site infections grade 2, 3 and 4 to Hep-2 cells did not differ from adherence of bacteria isolated from asymptomatic or moderately inflamed catheter exit sites (grade 0-2). However, binding of S. aureus to silicone tubes was enhanced in grade 0/1 compared with grade 2-4 exit-site isolates. CONCLUSIONS: Staphylococcus aureus is an important pathogen in CAPD-related exit-site infection being isolated in about 6.6% of all exit-site swabs (and in 25% of all positive swabs). Silicone-adhesive strains may be of more clinical significance in peritoneal dialysis patients since adhesion to silicone was increased in S. aureus strains isolated in more severe exit-site infections.

Bacterial Adhesion↗

Bacterial colonization and endotoxin contamination of intravenous infusion fluids.

Bacterial colonization and endotoxin contamination of intravenous infusion fluids and catheter systems were examined in a surgical intensive care unit. Nineteen consecutive patients were randomly assigned to 48 h (N = 8) or 96 h (N = 11) change of infusion systems. Fluid from infusion bottles (51), infusion bottles plus burettes (102) and catheter systems (104) was cultured quantitatively for aerobic and anaerobic bacteria. Swabs (362) were taken from three-way stopcocks before and after the in-line infusion filters. Total and free endotoxin levels in infusion fluids were measured by quantitative chromogenic Limulus assay. The overall rate of bacterial colonization of bottles/burettes was 7.8% at 48 h and 15.7% at 96 h, while colonization rates of catheter fluid were 34.0% and 24.1%, respectively (n.s.). These high rates of colonization, despite regularly reinforced hand disinfection practices, may be explained by the high frequency of manipulations of the catheter systems, during acute interventions in emergency situations. Cell-bound endotoxin was found in 8.8% of the samples, but only 2.5% of the samples contained free endotoxin. The data support the use of in-line infusion filters, with bacterial-retaining property; however, these filters need not have endotoxin-retaining properties.

Aged↗

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↗

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↗

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↗