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Biomedical subjects

G Ackermann

Publications and source records attributed to G Ackermann.

At least 19 recordsLinked to original sources

Antecedent use of fluoroquinolones is associated with resistance to moxifloxacin in Clostridium difficile.

OBJECTIVE: Moxifloxacin is characterized by high activity against Gram-positive cocci and some Gram-positive and -negative anaerobes, including Clostridium difficile. This study investigates the role of prior quinolone use in relation to patterns of susceptibility of C. difficile to moxifloxacin. METHODS: Sixty-three clinical isolates of C. difficile were investigated for toxigenicity, susceptibility to moxifloxacin, and mutations in the DNA gyrase gene. The medical histories for 50 of these patients were available and used to identify previous fluoroquinolone use. RESULTS: Thirty-three (52.4%) strains showed resistance to moxifloxacin (MICs > or = 16 mg/L). All moxifloxacin-resistant strains harbored a mutation at amino acid codon Ser-83 of gyrA. Forty-five isolates (71.4%) were toxigenic; all moxifloxacin-resistant strains were in this group. Resistance to moxifloxacin was associated with prior use of fluoroquinolones (P-value 0.009, chi-square). CONCLUSIONS: Although the use of moxifloxacin to treat C. difficile-associated diarrhea is not likely to be common, these data show a relationship between antecedent fluoroquinolone use and resistance to moxifloxacin in C. difficile isolates, and raise questions regarding selection pressure for resistance placed on colonizing bacteria exposed to fluoroquinolones. Mutations in gyrA are involved in moxifloxacin resistance.

Anti-Infective Agents↗

Effects of Porphyromonas gingivalis on the activation of mouse macrophages by lipopolysaccharide.

Porphyromonas gingivalis (PG) is a micro-organism that is suggested to play an etiologic role in acute and chronic periodontitis. The present study was undertaken to evaluate the question whether PG is capable of inducing interleukin (IL)-1beta, IL-6, macrophage inflammatory protein (MIP)-2, and granulocyte-macrophage colony-stimulating factor (GM-CSF) production in macrophages. Furthermore, the effect of PG on the activation of macrophages by Escherichia coli-lipopolysaccharide (LPS) was studied. The cytokines were analyzed by detection of specific mRNA. The mRNA was amplified by RT-PCR and semi-quantitatively analyzed by high performance liquid chromatography and densitometrically, respectively. These studies demonstrate that LPS was more active than PG in inducing mRNA expression of IL-1beta, IL-6, MIP-2 and GM-CSF. Moreover, PG reduced the mRNA expression of the macrophages stimulated with LPS, especially the IL-1beta and IL-6 mRNA expression was decreased.

Animals↗

One-step cloning and expression of Clostridium difficile toxin B gene (tcdB).

The toxin genes of Clostridium difficile have been previously cloned by reconstructing the entire gene in a series of steps in sequence using several cloned fragments. Amplification of a 7.9 kb fragment corresponding to the toxin B gene (tcdB) was obtained with EXPAND Long Template PCR system. The amplified fragment was inserted into the E. coli expression vector pBAD and cloned into competent E. coli TOP 10 cells. tcdB gene sequences representing the complete toxin gene were detected in 3/120 (2.5%) clones analyzed. Culture filtrates of 2/3 clones were found to have cytotoxic activity in human lung fibroblasts. The recombinant protein expressed in E. coli was identified as toxin B by Western immunoblot analysis using C. sordellii antitoxin. This rapid cloning method may be useful in determining the role that individual genes in the pathogenicity locus (PaLoc) play in the virulence of C. difficile. Our results also suggest that the activity of toxin B is independent of other genes in the PaLoc.

Bacterial Proteins↗

Correlations between light penetration into skin and the therapeutic outcome following laser therapy of port-wine stains.

For several years the flashlamp-pumped pulsed dye laser (FPDL) has been the favoured method for the treatment of port-wine stains (PWS). The therapeutic outcome of FPDL laser therapy depends on the anatomical location of the PWS and is mainly attributed to morphological parameters such as size and depth of the PWS blood vessels. The aim of this study was to show a correlation between the therapeutic outcome following FPDL therapy and the optical properties of the skin overlying the PWS vessels. For this purpose the therapeutic outcome following FPDL treatment (585 nm; 0.45 ms) of 884 PWS situated on different body sites was evaluated by judging the grade of fading of PWS colour. On the other hand the light penetration into 123 skin samples (thickness 0.10-1.35 mm) was determined between 450 nm and 1030 nm and compared with the PWS laser therapy outcome for equal locations by statistical analysis. PWS on the neck, trunk, arms or legs yielded a higher mean grade of fading as compared to PWS on the head. Within the face, a wide range of fading was evident. The light penetration into skin increased linearly with increasing wavelength and location-dependent differences were found. The attenuation coefficient was 22.8+/-5.3 mm(-1) at 585 nm. No significant or strong correlation was observed between the therapeutic outcome of PWS laser therapy and the light penetration into skin. However, a correlation was obvious by plotting the respective profile plots. Therefore, among other effects, in particular morphological parameters of PWS vessels, the optical properties of the skin contribute to a small extent to the clinical outcome of PWS laser therapy.

Adolescent↗

Electroporation of DNA sequences from the pathogenicity locus (PaLoc) of toxigenic Clostridium difficile into a non-toxigenic strain.

Toxigenic Clostridium difficile is the etiologic agent of C. difficile-associated diarrhoea (CDAD), the most common cause of hospital-acquired infectious diarrhoea. The genes tcdA and tcdB, which encode for the toxin A and B proteins, are part of the pathogenicity locus (PaLoc) of toxigenic C. difficile. Genetic and virulence studies at the molecular level in C. difficile have been hindered by the lack of techniques for DNA manipulation in this species. We describe the electroporation of DNA fragments from a toxigenic isolate into a non-toxigenic strain of C. difficile. Using previously described methods of electroporation into Clostridium spp., the complete toxin B gene and polymerase chain reaction (PCR) fragments of the PaLoc were cloned and electroporated into a non-toxigenic strain of C. difficile. The resulting transformed clones were screened for the introduced gene fragments by PCR, which confirmed their presence. This is the first description of introduction of DNA into C. difficile by electroporation.

Bacterial Proteins↗

Infections caused by Stenotrophomonas maltophilia--a prospective study.

BACKGROUND: Stenotrophomonas maltophilia is an opportunistic microorganism, often highly resistant to routinely tested antibiotics. This microorganism is isolated in specimens from patients with nosocomial infections with increasing frequency. PATIENTS AND METHODS: During a 1-year period (1998/1999) S. maltophilia was isolated from 137 specimens (0.26% of all investigated specimens) from 80 patients who were treated in a 1,500 bed major tertiary care teaching hospital in Leipzig. The data of 76 patients (133 specimens) could be collected and analyzed completely. RESULTS: The pathogen was most frequently detected in specimens from the respiratory tract (54%). In five patients (six cases) S. maltophilia was isolated from blood cultures (0.3% of all positive blood cultures; 1.4% of all gram-negative isolates from blood cultures). 70 of the infected patients were inpatients and 32 (42%) of them were treated on the internal medicine wards. Of these 32 patients only six (19%) were pretreated with imipenem. The Length of stay at the hospital resulted in an independent increased risk of infection with S. maltophilia. In addition, this organism was detected in six infected outpatients. CONCLUSION: S. maltophilia is not only a nosocomial pathogen. Pretreatment with a carbapenem is no longer an unequivocal risk factor for an infection with S. maltophilia.

Adult↗

Rapidly growing tumor-like brain lesion.

Listeria monocytogenes accounts for 8-11% of the cases of bacterial meningitis which is associated with high mortality in patients with serious underlying diseases or those receiving immunosuppressive treatment. Brain abscess due to L. monocytogenes is a very rare occurrence. The case reported here concerns a 54-year-old female patient with a rapidly growing tumor-like brain lesion. L. monocytogenes type 4b could be cultured from blood and brain biopsy. Despite antimicrobial therapy with ampicillin and gentamicin, the patient died 11 days after admission to the hospital. The growing numbers of elderly and immunocompromised patients will increasingly confront physicians with patients with listeriosis. Delayed therapy in patients treated with corticosteroids may result in a fatal outcome.

Adrenal Cortex Hormones↗

Isolation of Clostridium innocuum from cases of recurrent diarrhea in patients with prior Clostridium difficile associated diarrhea.

Clostridium innocuum isolates resistant to vancomycin (MIC values of 16-24 microg/mL) were isolated from three patients with recurrent Clostridium difficile -associated diarrhea (CDAD). We discuss the clinical significance and problems associated with the identification and differentiation of these two clostridial species, which may result in misdiagnosis of patients.

Clostridioides difficile↗

Comparative in vitro activities of gemifloxacin, other quinolones, and nonquinolone antimicrobials against obligately anaerobic bacteria.

The in vitro activity of gemifloxacin was compared to that of other quinolone and nonquinolone antimicrobials against 204 anaerobes by the agar dilution technique. The data indicate that gemifloxacin has a rather selective anaerobic activity. Most Peptostreptococcus, Porphyromonas, and Fusobacterium species are susceptible, while gemifloxacin's activity against other gram-negative anaerobes appears to be variable.

Anti-Bacterial Agents↗

Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is associated with mutations in gyrA.

Clostridium difficile is the etiological agent of antibiotic-associated colitis and the most common cause of hospital-acquired infectious diarrhea. Fluoroquinolones such as ciprofloxacin are associated with lower risks of C. difficile-associated diarrhea. In this study, we have analyzed 72 C. difficile isolates obtained from patients with different clinical courses of disease, such as toxic megacolon and relapses; the hospital environment; public places; and horses. They were investigated for their susceptibilities to moxifloxacin (MXF), metronidazole (MEO), and vancomycin (VAN). Mutants highly resistant to fluoroquinolones were selected in vitro by stepwise exposure to increasing concentrations of MXF. The resulting mutants were analyzed for the presence of mutations in the quinolone resistance-determining regions of DNA gyrase (gyrA), the production of toxins A and B, and the epidemiological relationship of these isolates. These factors were also investigated using PCR-based methods. All strains tested were susceptible to MEO and VAN. Twenty-six percent of the clinical isolates (19 of 72) were highly resistant to MXF (MIC > or = 16 microg/ml). Fourteen of these 19 strains contained nucleotide changes resulting in amino acid substitutions at position 83 in the gyrA protein. Resistant strains selected in vitro did not contain mutations at that position. These findings indicate that resistance to MXF in a majority of cases may be due to amino acid substitution in the gyrA gene.

Anti-Infective Agents↗

Phototherapy of psoriasis: comparative experience of different phototherapeutic approaches.

BACKGROUND: Broad-band UVB alone or in combination with different topical drugs (anthralin, calcipotriol), systemic PUVA and bath-PUVA therapy are very effective and well-established treatment modalities for psoriasis. OBJECTIVE: The aim of this retrospective study was to assess which of these routinely applied phototherapeutic modalities might be most effective and safe for the treatment of plaque-type psoriasis. METHODS: Patients (n = 203) with moderate to severe (pretreatment Psoriasis Area and Severity Index score between 12 and 35) chronic plaque-type psoriasis treated between 1992 and 1998 at our department with either UVB (with/without anthralin or calcipotriol; n = 97), systemic PUVA (n = 19) or bath-PUVA therapy (n = 87) were evaluated for efficacy, duration of treatment, number of treatments necessary for complete remission (CR), cumulative light dose, side effects of therapy and duration of remission after therapy. RESULTS: No statistically significant difference comparing the efficacy of bath-PUVA (CR in 72.4%), PUVA (CR in 89.5%) and UVB phototherapy (CR in 69.1%) was found. Although the duration of therapy was significantly longer for bath-PUVA (66 +/- 42 days) as compared to UVB treatment (50 +/- 27 days), the mean number of treatments did not differ significantly between bath-PUVA (28 +/- 12), UVB therapy (30 +/- 12) and PUVA (26 +/- 13). Significantly fewer side effects of phototherapy were observed with bath-PUVA (14.9%) therapy compared to UVB treatment (30.9%). Also, the duration of remission after successful therapy was significantly longer for bath-PUVA (8.4 +/- 3.5 months) as compared to UVB phototherapy (5.1 +/- 4.2 months). CONCLUSION: Bath-PUVA therapy has some advantages over UVB phototherapy in the treatment of psoriasis: fewer UV-related acute side effects and a longer period of remission after therapy. However, the choice of treatment with either UVB, bath-PUVA or systemic PUVA should also be based on a history of previous response to treatment and patient considerations, including compliance and responsibility for following the precautions to avoid potential side effects.

Administration, Topical↗

[Fluorescence-assisted biopsy of basal cell carcinomas].

BACKGROUND AND OBJECTIVE: The diagnosis of precancerous and cancerous skin lessons in pretreated or scarred skin can be difficult. The determination of the right biopsy site in a suspected area depends largely on the physician's experience. PATIENTS/METHODS: The possibility of using a CCD-camera system and measuring tumor fluorescence following topical application of 5-aminolevulinic acid was employed in a single case to facilitate accurate choice of biopsy site. RESULTS: An user-independent evaluation of the induced fluorescence intensity was achieved by means of the described optical system and digital imaging. The contrast of the acquired fluorescence images can be significantly enhanced and allows the determination of a threshold. As result an initial, clinically not visible basal cell carcinoma was detected and excised by a punch biopsy in toto. CONCLUSIONS: Using the described optical system the early recognition of a superficial basal cell carcinoma and the determination of the exact biopsy site was achieved in pretreated skin. The routine employment of the system will be assessed in a prospective study.

Administration, Topical↗

Comparative activity of moxifloxacin in vitro against obligately anaerobic bacteria.

The antimicrobial activity of moxifloxacin and seven other antibiotics (four of them quinolones) against 292 strains of obligately anaerobic bacteria was assessed employing a broth microdilution technique performed in Wilkens-Chalgren broth. MIC50/MIC90 values (mg/l) for moxifloxacin were as follows: Bacteroides fragilis (n = 62) 0.25/2, Bacteroides ovatus (n = 70) 1/4, Bacteroides vulgatus (n = 29) 0.25/1, Bacteroides thetaiotaomicron (n = 17) 2/2, Bacteroides caccae (n = 11) 1/2, Prevotella spp. (n = 11) 0.25/2, Fusobacterium spp. (n = 17) 1/4, Bilophila wadsworthia (n = 29) 0.5/1, and Clostridium spp. (n = 29) 0.125/0.5, respectively. MIC50 values (mg/l) for Bacteroides distasonis (n = 8) and Peptostreptococcus spp. (n = 9) were 0.25. The results indicated that moxifloxacin was almost as active as trovafloxacin, as active as gatifloxacin, and more active than levofloxacin and ciprofloxacin against the anaerobes tested.

Anti-Bacterial Agents↗

In vitro activities of fourteen antimicrobial agents against obligately anaerobic bacteria.

The in vitro activities of fourteen antimicrobial agents were tested against 292 clinical isolates of obligately anaerobic bacteria using the broth microdilution technique. Taking all strains as a group the MIC(50/90) (mg/l) values were metronidazole and imipenem 0.25/1, meropenem 0.25/0.5, trovafloxacin 0.25/1, gatifloxacin and moxifloxacin 0.5/2, levofloxacin 2/16, ciprofloxacin 4/32, clindamycin 0.5/8, amoxycillin/clavulanate 1/4, doxycycline and chloramphenicol 2/4, erythromycin 4/>32 and penicillin G 16/>32.

Anti-Bacterial Agents↗

In vitro activity of telithromycin (HMR 3647) and seven other antimicrobial agents against anaerobic bacteria.

We assessed the in vitro activity of telithromycin (HMR 3647) and seven other antimicrobials against 292 strains of obligately anaerobic bacteria. MICs were determined with the microdilution technique and Wilkins-Chalgren broth according to DIN 58940-83. MIC50/MIC90s (mg/L) for telithromycin were 4/4 for Bacteroides fragilis, Bacteroides ovatus and Bacteroides thetaiotaomicron, 2/4 for Fusobacterium spp. and Bilophila wadsworthia, 2/2 for Bacteroides caccae, 1/4 for Bacteroides vulgatus, 0.25/4 for Prevotella spp., > or =0.03/0.5 for Clostridium spp. and 0.125/4 for Peptostreptococcus spp.

Anti-Bacterial Agents↗

In vitro activities of gatifloxacin, two other quinolones, and five nonquinolone antimicrobials against obligately anaerobic bacteria.

The activity of the new fluoroquinolone gatifloxacin was compared with those of other quinolones and antimicrobial agents of other classes against 294 anaerobes by the broth microdilution technique. For all strains tested, gatifloxacin MICs at which 50 and 90% of the isolates were inhibited were 0.5 and 2 mg/liter, respectively, and were 3 to 4 dilution steps lower than, e.g., ciprofloxacin.

Anti-Bacterial Agents↗