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N Lehn

Publications and source records attributed to N Lehn.

At least 19 recordsLinked to original sources
PubMed2006

Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin.

BACKGROUND: The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge. AIM: To investigate the efficacy of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome. METHODS: Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were: ERA 74% (62.4-83.6) and 78% (66.7-87.3); high-dose OA 70% (57.5-79.7) and 75% (62.5-84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non-significant trend to lower eradication rates in homozygous extensive metabolizers. CONCLUSIONS: Triple therapy with esomeprazole, rifabutin and amoxicillin and high-dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.

Adolescent↗
PubMed2006

Healing of lymphocytic gastritis after Helicobacter pylori eradication therapy--a randomized, double-blind, placebo-controlled multicentre trial.

BACKGROUND: An association between Helicobacter pylori infection and lymphocytic gastritis has been postulated. AIM: To assess the long-term effect of H. pylori eradication therapy on lymphocytic gastritis in a double-blind, placebo-controlled, multicentre trial. METHODS: Patients with lymphocytic gastritis were randomized to receive either 1-week triple therapy for eradication of H. pylori or omeprazole plus placebo. Endoscopy and histology was performed at baseline and after 3 and 12 months. Patients of the omeprazole/placebo group with persistent lymphocytic gastritis after 12 months received crossover open-label triple therapy. RESULTS: Fifty-one patients were randomized. Intention-to-treat analysis revealed a trend to a higher healing rate of lymphocytic gastritis 3 months after triple therapy compared with omeprazole/placebo (83.3% vs. 57.7%, 95% CI for RR: 0.8-2.8, P = 0.06). After 12 months, the healing rate of lymphocytic gastritis was significantly higher after triple therapy compared with omeprazole/placebo (intention-to-treat 95.8% vs. 53.8%, 95% CI for RR: 1.1-3.5, P = 0.01). All patients (n = 5) who received crossover triple therapy, showed healing of lymphocytic gastritis after further 12 months. CONCLUSION: Our study demonstrates that 1-week triple therapy aiming at eradication of H. pylori leads to a complete and long-lasting resolution of lymphocytic gastritis in the majority of patients.

Adult↗
PubMed2005

[Antibacterial photodynamic therapy. A new treatment for superficial bacterial infections?].

The basis of "antibacterial photodynamic therapy" involves the killing of bacteria by reactive oxygen species in the presence of a photosensitizer and light. Possible dermatologic indications include inactivation of bacteria in skin and wound infections and reduction in density of nosocomial multi-resistant infections. The chief advantage of antibacterial photodynamic therapy is that regardless of the resistance pattern of a bacteria, inactivation can be achieved, analogous to the use of antiseptics. The aim of the present review is to describe the physicochemical and biological mechanisms of antibacterial photodynamic therapy as well as possible clinical indications in dermatology.

Anti-Bacterial Agents↗
PubMed2005

Healthcare-associated outbreaks and community-acquired infections due to MRSA carrying the Panton-Valentine leucocidin gene in southeastern Germany.

In response to several isolations of methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leucocidin gene (PVL-MRSA), the present study was conducted to document the spread of infection in a small region of southeastern Germany. During a 9-month period, two healthcare-associated outbreaks with PVL-MRSA occurred, affecting 83 patients, personnel and contacts of personnel, and 34 additional cases were detected in the community. The clinical spectrum ranged from colonization to skin infection and necrotizing pneumonia. The findings represent the largest number of PVL-MRSA cases detected in Germany so far, and demonstrate the potential of this emerging pathogen to spread within the community and in healthcare institutions.

Adolescent↗
PubMed2005

Photodynamic effects of novel XF porphyrin derivatives on prokaryotic and eukaryotic cells.

The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to the killing of gram-positive antibiotic-resistant bacteria of the skin uses light in combination with a photosensitizer to induce a phototoxic reaction. Different concentrations (0 to 100 microM) of porphyrin-based photosensitizers (CTP1, XF70, and XF73) and different incubation times (5 min, 1 h, and 4 h) were used to determine phototoxicity against two methicillin-resistant Staphylococcus aureus strains, one methicillin-sensitive S. aureus strain, one methicillin-resistant Staphylococcus epidermidis strain, one Escherichia coli strain, and human keratinocytes and fibroblasts. Incubation with 0.005 microM XF70 or XF73, followed by illumination, yielded a 3-log10 (> or = 99.9%) decrease in the viable cell numbers of all staphylococcal strains, indicating that the XF drugs have high degrees of potency against gram-positive bacteria and also that the activities of these novel drugs are independent of the antibiotic resistance pattern of the staphylococci examined. CTP1 was less potent against the staphylococci under the same conditions. At 0.005 microM, XF70 and XF73 demonstrated no toxicity toward fibroblasts or keratinocytes. No inactivation of E. coli was detected at this concentration. XF73 was confirmed to act via a reactive oxygen species from the results of studies with sodium azide (a quencher of singlet oxygen), which reduced the killing of both eukaryotic and prokaryotic cells. When a quencher of superoxide anion and the hydroxyl radical was used, cell killing was not inhibited. These results demonstrate that the porphyrin-based photosensitizers had concentration-dependent differences in their efficacies of killing of methicillin-resistant staphylococcal strains via reactive oxygen species without harming eukaryotic cells at the same concentrations.

Anti-Bacterial Agents↗
PubMed2003

Esomeprazole-based one-week triple therapy with clarithromycin and metronidazole is effective in eradicating Helicobacter pylori in the absence of antimicrobial resistance.

AIM: This study aimed to investigate the effectiveness of a one-week triple therapy with esomeprazole, clarithromycin and metronidazole for eradication of Helicobacter pylori infection in the absence of antimicrobial resistance. METHODS: Patients testing positive for H. pylori susceptible to metronidazole and clarithromycin (E-test) were randomized to receive a one-week regimen with either esomeprazole 2 x 20 mg or omeprazole 2 x 20 mg in combination with clarithromycin 2 x 250 mg and metronidazole 2 x 400 mg. Follow-up endoscopy with histology and culture and/or rapid urease test was performed 4-8 weeks after the end of treatment. RESULTS: Eighty patients were randomized. Helicobacter pylori infection was cured in 38/39 patients of the esomeprazole group and 31/33 patients of the omeprazole group (per protocol 97.4% (95% confidence interval [CI], 86.2-99.9), 93.7% (95% CI, 79.2-99.2), P=0.59); intention-to-treat 90.4% (95% CI: 77.4-97.3), 81.6% (95% CI: 65.7-92.3), respectively. No major side effects occurred. Minor side effects occurred in eight (20%) and six (23%) patients during esomeprazole and omeprazole therapy, respectively. Post-treatment susceptibility testing revealed resistance to both metronidazole and clarithromycin in two of the three patients who failed. CONCLUSION: We conclude that esomeprazole, clarithromycin and metronidazole as one-week triple therapy is effective for eradication of H. pylori in the absence of antimicrobial resistance.

Adult↗
PubMed2003

Rapid and standardized detection of Chlamydia pneumoniae using LightCycler real-time fluorescence PCR.

In order to meet the need of many microbiological laboratories for a standardized system for detecting Chlamydia pneumoniae in respiratory specimens, a hybridization probe-based LightCycler (Roche Diagnostics, Germany) PCR assay was developed. The assay's analytical sensitivity and specificity were evaluated according to the recommendations of the Centers for Disease Control and Prevention (USA) and Laboratory Centre for Disease Control (Canada). Seventy-four bacterial species other than Chlamydia pneumoniae, including strains of Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pecorum, tested negative. Six of six representative Chlamydia pneumoniae strains tested positive. An analytical sensitivity of 1 inclusion forming unit per ml of bronchoalveolar lavage fluid, corresponding to 0.02 inclusion forming units per PCR reaction, was observed. The assay showed 100% specificity and sensitivity for Chlamydia pneumoniae when testing DNA preparations from 12 specimens of patients with known pulmonary Chlamydia pneumoniae infection and from 78 specimens of patients with respiratory tract disease of other origin. The newly developed LightCycler assay may contribute to the urgently needed standardization of laboratory diagnosis of Chlamydia pneumoniae.

Bacteriological Techniques↗
PubMed2003

Pericarditis as primary manifestation of Mycobacterium bovis SSP. caprae infection.

A 76-year-old white male presented with progressive malaise, weight loss and dyspnea at rest. Echocardiography revealed a circular pericardial effusion and global hypokinesia. Pericardiocentesis showed a purulent exudate and microbiologic examination revealed Mycobacterium bovis fully sensitive to isoniazid, streptomycin, ethambutol, rifampin, and pyrazinamide. By spoligotyping the isolate could be further differentiated to M. bovis ssp. caprae. Antimycobacterial therapy was initiated but 3 weeks later the patient's circulation and renal function deteriorated and he died with clinical signs of sepsis despite intensive care treatment. Pericarditis is a rare manifestation of tuberculosis and can be fatal even when diagnosed and treated appropriately. In low incidence countries diagnosis is often delayed and even overlooked.

Animals↗
PubMed2003

Clinically significant borderline resistance of sequential clinical isolates of Klebsiella pneumoniae.

Two sequential clinical isolates of Klebsiella pneumoniae (Kpn) were isolated from bronchoalveolar lavage fluid (Kpn#1) and sputum (Kpn#2) of a patient with pneumonia, complicated by anatomical and immunosuppressive problems due to Wegener's granulomatosis. Despite 4 weeks of systemic treatment with ciprofloxacin (CIP) Kpn#2 was isolated thereafter. A fluoroquinolone-resistant mutant (Kpn#1-SEL) was derived from Kpn#1 in vitro by selecting on agar plates supplemented with ofloxacin. Kpn#1, Kpn#1-SEL and Kpn#2 had an identical pattern in PFGE. CIP MICs were 0.25, 2 and 4 mg/l for Kpn#1, Kpn#2 and Kpn#1-SEL, respectively. Kpn ATCC 10031 (CIP MIC 0.002 mg/l) served as control. We analyzed mechanisms of fluoroquinolone resistance by determining antibiotic susceptibility, organic solvent tolerance, accumulation of fluoroquinolones, dominance testing with wild-type topoisomerase genes (gyrA/B, parC/E), sequencing of the quinolone resistance determining regions of gyrA/B, parC/E and marR and Northern blotting of marR and acrAB genes. Compared with Kpn ATCC 10031, elevated MICs to fluoroquinolones and unrelated antibiotics in Kpn#1 was presumably due to a primary efflux pump other than AcrAB and increased the CIP MIC 125-fold. Although Kpn#1 tested sensitive according to NCCLS breakpoints, the elevated CIP MIC of 0.25 mg/l presumably rendered this isolate clinically resistant and lead to therapeutic failure in this case. Further increase of MIC to fluoroquinolones in vivo and in vitro was distinct. Kpn#1-SEL, selected in vitro, acquired a GyrA target mutation, whereas in Kpn#2 no known resistance mechanism could be detected.

Blotting, Northern↗
PubMed2003

Prosthetic joint infections with osteomyelitis due to Candida albicans.

We report the case of a 78-year-old woman who suffered from a severe soft tissue and bone infection of her left knee 3 years after a total knee-joint replacement without loosening of her endoprosthesis. Cultures from joint aspiration and tissue specimen identified Staphylococcus aureus and Candida albicans. Direct microscopic examination of vital spongy bone and fibrous tissue revealed microabscesses and seeds of yeasts inside the fatty marrow and interface. After removal of the prosthesis several soft tissue and bone specimens were taken during planned re-operations. The histological examination showed no morphological changing, no reduction or extinction of the yeast cells under fluconazole therapy with a dosage of 6 mg kg(-1) body weight (400 mg daily). Curing of the fungal infection with eradication of the yeasts in the bony specimens was achieved with higher doses of 12 mg kg(-1) body weight (800 mg day(-1)) over a 2 month regimen in combination with repeated surgical debridements.

Aged↗
PubMed2002

[Diagnosis and therapy of necrotizing fasciitis].

Necrotizing fasciitis is a soft tissue infection with a lethality ranging up to 80%. Infection causes the activation of interleukin, tumor necrosis factor alpha, and gamma-interferon through a triggering mechanism. This results in a capillary thrombosis with necrosis of the fascia, cutis, and subcutis. The patient's history often reveals a triggering event in the form of a recent minimal trauma or operative procedure. In a fulminant necrotizing fasciitis, the development of sepsis with consecutive multiple-organ failure mainly determines the outcome of the disease. Diagnosis is made initially upon clinical findings with a rapid progression of the disease and confirmed later by histologic and microbiologic findings. Radical surgical debridement within the first 24 h with postoperative treatment in an intensive care unit represents the cornerstone of therapy. Between January 1992 and March 2001, we treated 15 patients with necrotizing fasciitis. Lethality was 33%. There was a significant correlation between risk factors (present in 86% of the patients) and morbidity. Diagnosis and therapy should be performed by an experienced surgeon. In this contribution, we discuss the most important criteria that lead to the diagnosis and the therapeutic consequences.

Adult↗