Whole-genome sequencing reveals two prolonged simultaneous outbreaks involving Pseudomonas aeruginosa high-risk strains ST111 and ST235 with resistance to quaternary ammonium compounds.

OBJECTIVE: Water-bearing systems are known as frequent Pseudomonas aeruginosa (PA) outbreak sources. However, many older buildings continue to have sanitary facilities in high-risk departments such as the ICU. We present two simultaneous prolonged multi-drug-resistant (MDR) PA outbreaks detected at the ICU of a pulmonology hospital, which were resolved by whole-genome sequencing (WGS). METHODS: Outbreak management and investigations were initiated in August 2019 after detecting two patients with nosocomial VIM-2-positive MDR PA. The investigations involved weekly patient screenings for four months and extensive environmental sampling for 15 months. All patient and environmental isolates were collected and analysed by WGS. RESULTS: From April to September 2019, we identified 10 patients with nosocomial MDR PA, including five VIM-2-positive strains. VIM-2-positive strains were also detected in nine sink drains, two toilets, and a cleaning bucket. WGS revealed that of 16 VIM-2-positive isolates, 14 were ST111 that carried qacE, or qacEΔ1 genes, whereas 13 isolates clustered (difference of ≤11 alleles by cgMLST). OXA-2 (two toilets), and OXA-2, OXA-74, PER-1 (two patients, three toilets) qacEΔ1-positive ST235 isolates dominated among VIM-2-negative isolates. The remaining seven PA strains were ST17, ST233, ST273, ST309 and ST446. Outbreak containment was achieved by replacing U-bends, and cleaning buckets, and switching from quaternary ammonium compounds (QUATs) to oxygen-releasing disinfectant products. CONCLUSION: Comprehension and management of two simultaneous MDR PA outbreaks involving the high-risk strains ST111 and ST235 were facilitated by precise control due to identification of different outbreak sources per strain, and by the in-silico detection of high-level QUATs resistance in all isolates.

Concerning emergence of a new vancomycin-resistant Enterococcus faecium strain ST1299/CT1903/vanA at a tertiary university centre in South Germany.

BACKGROUND: vanB-carrying vancomycin-resistant Enterococcus faecium (VREfm) of the sequence types 80 (ST80) and ST117 have dominated Germany in the past. In 2020, our hospital witnessed a sharp increase in the proportion of vanA-positive VREfm. AIM: To attempt to understand these dynamics through whole-genome sequencing (WGS) and analysis of nosocomial transmissions. METHODS: At our hospital, the first VREfm isolate per patient, treated during 2020, was analysed retrospectively using specific vanA/vanB PCR, WGS, multi-locus sequence typing (MLST), and core-genome (cg) MLST. Epidemiologic links between VRE-positive patients were assessed using hospital occupancy data. FINDINGS: Isolates from 319 out of 356 VREfm patients were available for WGS, of which 181 (56.7%) fulfilled the ECDC definition for nosocomial transmission. The high load of nosocomial cases is reflected in the overall high clonality rate with only three dominating sequence (ST) and complex types (CT), respectively: the new emerging strain ST1299 (100% vanA, 77.4% CT1903), and the well-known ST80 (90.0% vanB, 81.0% CT1065) and ST117 (78.0% vanB, 65.0% CT71). The ST1299 isolates overall, and the subtype CT1903 in particular, showed high isolate clonality, which demonstrates impressively high spreading potential. Overall, 152 out of 319 isolates had an allelic cgMLST difference of ≤3 to another, including 91 (59.6%) ST1299. Occupancy data identified shared rooms (3.7%), shared departments (6.2%), and VRE-colonized prior room occupants (0.6%) within 30 days before diagnosis as solid epidemiological links. CONCLUSION: A new emerging VREfm clone, ST1299/CT1903/vanA, dominated our institution in 2020 and has been an important driver of the increasing VREfm rates.

Examining outpatients' hand hygiene behaviour and its relation to COVID-19 infection prevention measures.

BACKGROUND: The increasing demand for outpatient care is associated with a higher risk of infection transmission in these settings. However, there is limited research on infection prevention and control practices in ambulatory clinics, and none focuses on patients. AIM: To examine outpatients' hand hygiene behaviours, their determinants, and their associations with other infection prevention measures during the COVID-19 pandemic. METHODS: We observed the hand hygiene behaviour of one cohort of patients in one outpatient clinic and surveyed a separate sample in five clinics about their hand hygiene practice in outpatient facilities. A questionnaire based on the Theoretical Domains Framework (TDF) was used to examine predictors of the behaviour. Moreover, patients indicated their compliance with COVID-19 infection prevention measures, vaccination status, disease risk perception, and vaccine hesitancy. FINDINGS: Observed hand hygiene rates among 618 patients were low (12.8%), while 67.3% of the 300 surveyed patients indicated sanitizing their hands upon entering the clinic. The TDF domains 'memory, attention, and decision processes' and 'emotions' significantly predicted both current (today's) and general hand hygiene behaviour in outpatient clinics. Hand hygiene behaviour and compliance with COVID-19 infection prevention showed a positive association; however, no significant connection was found with patients' vaccination status, suggesting different behavioural motivators. CONCLUSION: Hand hygiene among outpatients should be improved through interventions focusing on helping patients remember to clean their hands. More research on infection prevention in outpatient facilities is needed to ensure patient safety.

Nanosilver/DCOIT-containing surface coating effectively and constantly reduces microbial load in emergency room surfaces.

BACKGROUND: Colonization of near-patient surfaces in hospitals plays an important role as a source of healthcare-associated infections. Routine disinfection methods only result in short-term elimination of pathogens. AIM: To investigate the efficiency of a newly developed antimicrobial coating containing nanosilver in long-term reduction of bacterial burden in hospital surfaces to close the gap between routine disinfection cycles. METHODS: In this prospective, double-blinded trial, frequently touched surfaces of a routinely used treatment room in an emergency unit of a level-I hospital were treated with a surface coating (nanosilver/DCOIT-coated surface, NCS) containing nanosilver particles and another organic biocidal agent (4,5-dichloro-2-octyl-4-isothiazolin-3-one, DCOIT), whereas surfaces of another room were treated with a coating missing both the nanosilver- and DCOIT-containing ingredient and served as control. Bacterial contamination of the surfaces was examined using contact plates and liquid-based swabs daily for a total trial duration of 90 days. After incubation, total microbial counts and species were assessed. FINDINGS: In a total of 2880 antimicrobial samples, a significant reduction of the overall bacterial load was observed in the NCS room (median: 0.31 cfu/cm2; interquartile range: 0.00-1.13) compared with the control coated surfaces (0.69 cfu/cm2; 0.06-2.00; P < 0.001). The nanosilver- and DCOIT-containing surface coating reduced the relative risk of a critical bacterial load (defined as >5 cfu/cm2) by 60% (odds ratio 0.38, P < 0.001). No significant difference in species distribution was detected between NCS and control group. CONCLUSION: Nanosilver-/DCOIT-containing surface coating has shown efficiency for sustainable reduction of bacterial load of frequently touched surfaces in a clinical setting.

Patients with multi-drug-resistant organisms feel inadequately informed about their status: adverse effects of contact isolation.

BACKGROUND: Contact isolation of patients with multi-drug-resistant organisms (MDROs) is an essential element of infection prevention strategies in hospitals worldwide. However, this practice may be associated with adverse side effects on patients' health and well-being. AIM: This study was the first to assess mental health and well-being variables among isolated patients compared with non-isolated control patients in a German cohort. METHODS: We conducted a matched case-control study among N = 267 patients admitted to a tertiary care teaching hospital in Germany. Their levels of anxiety, depression, loneliness, and dissatisfaction with their hospital experience were assessed using a questionnaire. Additionally, among isolated patients, it was evaluated how well they felt informed about their MDRO status. FINDINGS: In our cohort, patients under contact isolation were significantly more dissatisfied than non-isolated control patients but did not show higher levels of anxiety, depression, and loneliness. A large proportion of patients felt insufficiently informed about their MDRO status. This lack of information was the strongest predictor of dissatisfaction among isolated patients. CONCLUSION: These findings underline the importance of adequate patient communication. It is essential for patients' well-being to receive timely, relevant, and understandable information about the background and consequences of their infection or colonisation with MDROs.

An emerging Panton-Valentine leukocidin-positive CC5-meticillin-resistant Staphylococcus aureus-IVc clone recovered from hospital and community settings over a 17-year period from 12 countries investigated by whole-genome sequencing.

BACKGROUND: A novel Panton-Valentine leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA) clonal complex (CC)5-MRSA-IVc ('Sri Lankan' clone) was recently described from Sri Lanka. Similar isolates caused a recent Irish hospital outbreak. AIM: To investigate the international dissemination and diversity of PVL-positive CC5-MRSA-IVc isolates from hospital and community settings using whole-genome sequencing (WGS). METHODS: Core-genome single nucleotide polymorphism (cgSNP) analysis, core-genome multi-locus sequence typing (cgMLST) and microarray-based detection of antimicrobial-resistance and virulence genes were used to investigate PVL-positive CC5-MRSA-IVc (N = 214 including 46 'Sri Lankan' clone) from hospital and community settings in 12 countries over 17 years. Comparators included 29 PVL-positive and 23 PVL-negative CC5/ST5-MRSA-I/II/IVa/IVc/IVg/V. RESULTS: Maximum-likelihood cgSNP analysis grouped 209/214 (97.7%) CC5-MRSA-IVc into Clade I; average of 110 cgSNPs between isolates. Clade III contained the five remaining CC5-MRSA-IVc; average of 92 cgSNPs between isolates. Clade II contained seven PVL-positive CC5-MRSA-IVa comparators, whereas the remaining 45 comparators formed an outlier group. Minimum-spanning cgMLST analysis revealed a comparably low average of 57 allelic differences between all CC5/ST5-MRSA-IVc. All 214 CC5/ST5-MRSA-IVc were identified as 'Sri Lankan' clone, predominantly spa type t002 (186/214) with low population diversity and harboured a similar range of virulence genes and variable antimicrobial-resistance genes. All 214 Sri Lankan clone isolates and Clade II comparators harboured a 9616-bp chromosomal PVL-encoding phage remnant, suggesting both arose from a PVL-positive meticillin-susceptible ancestor. Over half of Sri Lankan clone isolates were from infections (142/214), and where detailed metadata were available (168/214), most were community associated (85/168). CONCLUSIONS: Stable chromosomal retention of pvl may facilitate Sri-Lankan clone dissemination.

Differences in observed and self-reported compliance with 'Five Moments for Hand Hygiene' as a function of the empathy of healthcare workers.

BACKGROUND: Hand hygiene at critical time-points (as established by the World Health Organization's model 'Five Moments for Hand Hygiene') remains the leading measure for minimizing the risk of healthcare-associated infections. While many interventions have been tested to improve hand hygiene compliance (HHC) of healthcare workers (HCWs), little is known about the relationship between HHC and empathy of HCWs. AIM: To investigate the relationship between moment-specific HHC rates and empathy of HCWs at both individual and ward levels. METHODS: HHC data were collected via observation and self-report, and empathy levels were measured using an established questionnaire. The survey was conducted on 38 wards of three tertiary care hospitals in Germany. Observation data were obtained via in-house observations conducted ≤8 months before or after the survey. FINDINGS: Evidence for the expected correlation between empathy of HCWs and moment-specific HHC was found for both observed HHC (Moment 1: r=0.483, P=0.031; Moment 2: r=588, P=0.006) and self-reported HHC (Moment 1: r=0.093, P=0.092; Moment 2: r=0.145, P=0.008). In analyses of variance, the critical interaction effect between empathy (i.e. lower vs higher empathy) and designated time-point of hand hygiene (i.e. before vs after reference task) was also significant. CONCLUSION: Empathy of HCWs should be considered as an important factor in explaining differences between moment-specific HHC rates. In consequence, empathy comes into focus not only as a crucial factor for high-quality patient care, but also as an important contributor to improving HHC.

Selective HSP90ß inhibition results in TNF and TRAIL mediated HIF1α degradation.

Signaling via TNF-R1 mediates pleiotropic biological outcomes ranging from inflammation and proliferation to cell death. Previous reports demonstrated that pro-survival signaling emanates from membrane resident TNF-R1 complexes (complex I) while only internalized TNF-R1 complexes are capable for DISC formation (complex II) and thus, apoptosis induction. Internalized TNF-R1 containing endosomes undergo intracellular maturation towards lysosomes, resulting in activation and release of Cathepsin D (CtsD) into the cytoplasm. We recently revealed HSP90 as target for proteolytic cleavage by CtsD, resulting in cell death amplification. In this study, we show that extrinsic cell death activation via TNF or TRAIL results in HSP90ß degradation. Co-incubation of cells with either TNF or TRAIL in combination with the HSP90ß inhibitor KUNB105 but not HSP90α selective inhibition promotes apoptosis induction. In an attempt to reveal further downstream targets of combined TNF-R1 or TRAIL-R1/-R2 activation with HSP90ß inhibition, we identify HIF1α and validate its ligand:inhibitor triggered degradation. Together, these findings suggest that selective inhibition of HSP90 isoforms together with death ligand stimulation may provide novel strategies for therapy of inflammatory diseases or cancer, in future.

[Hygiene during otorhinolaryngological examinations : Prevention of nosocomial infections]. / Hygiene bei der HNO-Untersuchung : Vermeidung nosokomialer Infektionen.

Awareness of the importance of working as aseptically as possible first emerged in the 19th century. In the meantime, there is an obligation to prevent transmission and further spread of pathogens, including adherence to the Infection Protection Act. Pathogens can also survive for a long time on inanimate surfaces, from where they can be transferred via the hands of personnel and thus lead to infections. Studies have shown that even contamination of untouched instruments after an otorhinolaryngological examination is not a rare occurrence. The Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) of the Robert Koch Institute gives recommendations for general hygiene measures (basic or standard hygiene). These must be adapted and implemented accordingly for the otorhinolaryngological examination. Due to the increasing development of resistance of nosocomial pathogens and the current pandemic, consistent implementation of these infection-prevention measures is important.

Novel photodynamic coating reduces the bioburden on near-patient surfaces thereby reducing the risk for onward pathogen transmission: a field study in two hospitals.

BACKGROUND: Near-patient surfaces are recognized as a source for hospital-acquired infections. Such surfaces act as reservoirs for microbial contamination by which pathogens can be transmitted from colonized or infected patients to susceptible patients. Routine disinfection of surfaces only results in a temporal elimination of pathogens, and recontamination inevitably occurs shortly between disinfections. AIM: A novel antimicrobial coating based on photodynamics was tested under laboratory conditions and subsequently in a field study in two hospitals under real-life conditions. METHODS: Identical surfaces received a photodynamic or control coating. Bacterial counts [colony-forming units (cfu)/cm2) were assessed regularly for up to 6 months. FINDINGS: The laboratory study revealed a mean reduction of several human pathogens of up to 4.0 ± 0.3 log10. The field study in near-patient environments demonstrated mean bacterial values of 6.1 ± 24.7 cfu/cm2 on all control coatings. Photodynamic coatings showed a significantly lower mean value of 1.9 ± 2.8 cfu/cm2 (P<0.001). When considering benchmarks of 2.5 cfu/cm2 or 5 cfu/cm2, the relative risk for high bacterial counts on surfaces was reduced by 48% (odds ratio 0.38, P<0.001) or 67% (odds ratio 0.27, P<0.001), respectively. CONCLUSION: Photodynamic coatings provide a significant and lasting reduction of bacterial counts on near-patient surfaces, particularly for high bacterial loads, in addition to routine hygiene. The promising results of this proof-of-concept study highlight the need for further studies to determine how this novel technology is correlated with the frequency of hospital-acquired infections.

[Microbiological diagnosis of periprosthetic joint infections]. / Mikrobiologische Diagnostik periprothetischer Gelenkinfektionen.

BACKGROUND: Prosthetic joint infection is a rare but serious complication after arthroplasty, leading to prolonged hospitalization and repeated surgical intervention. THEME: In this article, successful strategies for the rapid and accurate microbiological diagnosis of infection are reviewed. In the case of clinical suspicion of a prosthetic joint infection, at least a comprehensive clinical review of the patient's postoperative history, a physical examination, routine blood tests including white cell count, erythrocyte sedimentation rate, and C-reactive protein, and further investigation of the synovial-fluid leukocyte count and microbial culture are needed. Depending of the clinical signs of infection additional blood culture samples should be taken. RESULTS: The gold standard to confirm infection is a surgical procedure with at least 5-6 biopsies from suspected areas for both microbial culture and histopathological examination. Culture results may be negative because of previous antimicrobial therapy, a low number of culturable organisms in biofilm formations, inappropriate culture medium, and prolonged transport time. CONCLUSION: In any of these conditions, diagnosis with highly sensitive diagnostic techniques such as polymerase chain reaction should be considered for the identification of the causative agent in order to establish the most appropriate antimicrobial treatment options.

[Disinfection and recontamination of rigid endoscopes: improved safety using an immersion quiver system]. / Desinfektion und Rekontamination starrer Endoskope: Mehr Sicherheit durch ein Tauchköchersystem.

BACKGROUND: In Otorhinolaryngology, rigid endoscopes are used daily at a high frequency. There is no consensus for reprocessing these medical instruments. Often immersion disinfection procedures are used. The present study examined the possible risk of recontamination by this disinfection method and investigated the possibility of avoiding this risk by using a new immersion quiver system. METHODS: Using coloured markers, a possible contact of the endoscope with the top edges of quivers of different diameters during endoscope removal was tested for. In addition, it was evaluated whether Staphylococcus aureus transfer is possible via this route. The same methodology was applied to a new immersion quiver system. RESULTS: Whenever removing the rigid endoscopes from the conventional quiver, these touched the top of the quiver, regardless of its diameter. A transfer of Staphylococcus aureus from the quiver to the endoscope via this route could be detected in five out of eight attempts. During endoscope removal from the new immersion quiver system, no contact of the endoscope with the outer quiver occurred in 20 passes. In none of eight trials was a transfer of Staphylococcus aureus from previously contaminated immersion quivers to the endoscope shown; all immersion quivers were sterile after disinfection. DISCUSSION: After conventional immersion disinfection, recontamination of rigid endoscopes by a contaminated quiver edge is possible. An immersion quiver system can resolve this risk of recontamination easily, by decontaminating not only the endoscope, but also the immersion quiver (inner quiver) itself in the disinfectant solution.

Fatal anthrax infection in a heroin user from southern Germany, June 2012.

Blood cultures from a heroin user who died in June 2012, a few hours after hospital admission, due to acute septic disease, revealed the presence of Bacillus anthracis. This report describes the extended diagnosis by MALDI-TOF and real-time PCR and rapid confirmation of the anthrax infection through reference laboratories. Physicians and diagnostic laboratories were informed and alerted efficiently through the reporting channels of German public health institutions, which is essential for the prevention of further cases.

PCR detection of helicobacter pylori genome in colonic mucosa: normal and malignant.

BACKGROUND AND AIMS: The aim of this study was to detect Helicobacter pylori (H. pylori) in colorectal cancer tissue specimens and relate the possible role of this microorganism in the etiology of colorectal cancer. PATIENTS AND METHODS: From February 2002 to April 2003 83 CRC patients (55 male, 28 female) and 40 control patients (19 male, 21 female) entered the prospective study. The biopsy samples of CRC tissue and normal mucosa were obtained during open surgery on CRC patients. In the control patients biopsy samples were taken during colonoscopy. Pathology confirmed adenocarcinoma in all the CRC patients. The existence of genetic material of H. pylori was determined by detection of the ureA gene by nested PCR. K-ras PCR was also performed on all patients. RESULTS: H. pylori PCR was positive in 1 case (1.2%) of CRC in the tumour tissue and in all 5 samples (6.0%) of the normal colonic mucosa in the cancer patients. The control patients were PCR positive to H. pylori in 13 samples (32.5%). According to Chi-square test, there is no statistical correlation between H. pylori infection and CRC (x2 = 2.9395; p > 0.05) but there is a significant prevalence of H. pylori infection in controls compared to CRC (x2 = 15.5625; p < 0.01). The K-ras PCR showed gene mutations in 19 tumour tissues of CRC (31.6%) and in 2 cases (3.4%) of normal colonic mucosa of CRC patients . In controls K-ras PCR showed one gene mutation (3.0%). There is a significant statistical correlation between K-ras mutation and CRC (x2 = 16.0694; p < 0.01). CONCLUSION: Our established PCR for H. pylori is feasible for CRC tissue as well. However, H. pylori is not considered to play an important role in the pathogenesis of CRC. The identification of K-ras mutations in routine PCR analysis correlates with the presence of CRC.

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.

Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation.

Acidic noncaspase proteases-like cathepsins have been introduced as novel mediators of apoptosis. A clear role for these proteases and the acidic endolysosomal compartment in apoptotic signalling is not yet defined. To understand the role and significance of noncaspases in promoting and mediating cell death, it is important to determine whether an intersection of these proteases and the caspase pathway exists. We recently identified the endolysosomal aspartate protease cathepsin D (CTSD) as a target for the proapoptotic lipid ceramide. Here, we show that tumor necrosis factor (TNF)-induced CTSD activation depends on functional acid sphingomyelinase (A-SMase) expression. Ectopic expression of CTSD in CTSD-deficient fibroblasts results in an enhanced TNF-mediated apoptotic response. Intracellular colocalization of CTSD with the proapoptotic bcl-2 protein family member Bid in HeLa cells, and the ability of CTSD to cleave directly Bid in vitro as well as the lack of Bid activation in cathepsin-deficient fibroblasts indicate that Bid represents a direct downstream target of CTSD. Costaining of CTSD and Bid with Rab5 suggests that the endosomal compartments are the common 'meeting point'. Caspase-9 and -3 activation also was in part dependent on A-SMase and CTSD expression as revealed in the respective deficiency models. Our results link as novel endosomal intermediates the A-SMase and the acid aspartate protease CTSD to the mitochondrial apoptotic TNF pathway.

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.

Influence of a prophylactic single dose of ciprofloxacin on the level of resistance of Escherichia coli to fluoroquinolones in urology.

During the years 1991-1996 an increase in fluoroquinolone-resistant Escherichia coli was observed at the Urological Department of the Municipal Hospital in Straubing, Germany. A prospective study was undertaken to investigate the influence of single-dose prophylaxis (SDP) using 500 mg ciprofloxacin orally on the level of resistance to ciprofloxacin of faecal E. coli. One hundred and five patients were recruited to the study: E. coli resistance to ciprofloxacin before prophylaxis was 3% (3/91) in contrast to 12% (5/42) after prophylaxis (P = 0.052). In 31 isolates no major change in the low MIC values before and after SDP was observed. PFGE showed clonal diversity in about half of the cases. Three isolates showed low-level resistance and three isolates high-level resistance to ciprofloxacin both before and after SDP. PFGE showed clonal identity in all cases. All patients had previously been treated with fluoroquinolones (FQ). In two isolates emergence of high-level resistance to ciprofloxacin after SDP occurred. PFGE showed clonal diversity in both cases. We conclude that after SDP with 500 mg ciprofloxacin there is a shift to gram-positive bacteria in the faeces and an increase in the rate of FQ resistance. Since selection of highly resistant E. coli is possible, a careful risk-benefit evaluation of prophylaxis with FQ is indicated.

Activation of ERK1/2 and cPLA(2) by the p55 TNF receptor occurs independently of FAN.

The generation of proinflammatory eicosanoids in response to tumor necrosis factor (TNF) involves the activation of cytosolic phospholipase A(2) (cPLA(2)), presumably by phosphorylation through extracellular signal-regulated kinases (ERK). Earlier results had suggested that a pathway involving the p55 TNF receptor (TNF-R55), neutral sphingomyelinase (N-SMase), and c-Raf-1 activates ERK and cPLA(2). We have previously shown that a cytoplasmic region of TNF-R55 distinct from the death domain regulates the activation of N-SMase through binding of the adapter protein FAN. Analysis of embryonal fibroblasts from FAN knockout mice revealed that TNF-induced activation of both ERK and cPLA(2) occurs without involvement of FAN. Furthermore, we provide evidence that the TNF-dependent activation of ERK and cPLA(2) requires the intact death domain of TNF-R55. Finally, we demonstrate that in murine fibroblasts cPLA(2) is phosphorylated in response to TNF solely by ERK, but not by p38 mitogen-activated protein kinase, suggesting a signaling pathway from TNF-R55 via the death domain to ERK and cPLA(2).