Publications by authors named "Leif Percival Andersen"

31 Publications

A case report of polymicrobial bacteremia with and comparison of previous treatment for successful recovery with a review of the literature.

Access Microbiol 2020 26;2(5):acmi000119. Epub 2020 Mar 26.

Department of Clinical Microbiology, Copenhagen University Hospital (Rigshospitalet), Henrik Harpestrengs Vej, Copenhagen 2100, Denmark.

is a Gram-positive coccus and a commensal bacterium of the human gastrointestinal tract with a potential to cause invasive infections. We report the presence of in the blood of a 25-year-old male patient with Crohn's disease, short bowel syndrome treated with home parenteral nutrition, and a history of recurrent bloodstream infections, admitted to our hospital with fever and malaise. A polymicrobial culture of and was identified from blood, for which treatment with meropenem and metronidazole was initiated. The literature was searched for previous cases of infection with . In total, 14 reports describing infection of 28 patients were found, most cases presenting with bacteremia. The previous reports have described variable susceptibility to antibiotics; however, all were reported to be vancomycin resistant. Because of its similarities to other vancomycin-resistant cocci, isolates of might be difficult to identify with traditional methods. Infection may be facilitated by its natural vancomycin resistance, leading to severe infection in hosts with underlying diseases. We describe the treatment of previous cases of infection and suggest treatment methods shown effective in other cases. Vancomycin is often used as treatment of infection with Gram-positive organisms, but this may need to be reevaluated, as several pathogenic bacteria are intrinsically vancomycin resistant. A review on reported treatments of bacteremia by suggests the use of daptomycin, amoxicillin-clavulanate or piperacillin/tazobactam as recommendable antibiotic regimens.
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http://dx.doi.org/10.1099/acmi.0.000119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494186PMC
March 2020

bacteraemia in a patient with multiple haematological malignancies.

Access Microbiol 2019 7;1(8):e000048. Epub 2019 Aug 7.

Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.

We present a case of sepsis in a woman suffering from multiple myeloma and myelodysplastic syndrome. , a Gram-positive coccus and a gut commensal, has been described in nine cases of infection in the literature, with most infections having occurred in patients with either gastrointestinal symptoms or prosthesis infections. In this case, was identified by mass spectrometry, and showed susceptibility to penicillin, meropenem, tetracycline, metronidazole and clindamycin. The patient was successfully treated initially with intravenous piperacillin/tazobactam and metronidazole, and then switched to oral penicillin and metronidazole. The cause of infection is hypothesized to have been a shift in the gut microbiota towards an excess growth of caused by immunosuppression, and bacterial translocation across a vulnerable mucosal barrier due to prednisolone treatment and severe thrombocytopenia.
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http://dx.doi.org/10.1099/acmi.0.000048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470407PMC
August 2019

CRHP Finder, a webtool for the detection of clarithromycin resistance in Helicobacter pylori from whole-genome sequencing data.

Helicobacter 2020 Dec 26;25(6):e12752. Epub 2020 Aug 26.

Department of Clinical Microbiology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.

Background: Resistance to clarithromycin in Helicobacter pylori (H pylori) is mediated by mutations in the domain V of the 23S rRNA gene (A2142G, A2143G, A2142C). Other polymorphisms in the 23S rRNA gene have been reported to cause low-level clarithromycin resistance but their importance is still under debate. In this study, we aimed to develop and evaluate the CRHP Finder webtool for detection of the most common mutations mediating clarithromycin resistance from whole-genome sequencing (WGS) data. Moreover, we included an analysis of 23 H pylori strains from Danish patients between January 2017 and September 2019 in Copenhagen, Denmark.

Materials And Methods: The CRHP Finder detects the fraction of each of the four nucleotides in nucleotide positions 2142, 2143, 2182, 2244 and 2712 of the 23S rRNA gene in H pylori (E coli numbering) by aligning raw sequencing reads (fastq format) with k-mer alignment (KMA). The nucleotide distribution in each position is compared to previously described point mutations mediating clarithromycin resistance in H pylori, and a genotypic prediction of the clarithromycin resistance phenotype is presented as output. For validation of the CRHP webtool, 137 fastq paired-end sequencing datasets originating from a well-characterized strain collection of H pylori were analyzed.

Results: The CRHP Finder correctly identified all resistance mutations reported in the sequencing data of 137 H pylori strains. In the 23 Danish H pylori strains, CRHP Finder detected A2143G (13%) in all resistant strains, and T2182C (13%) and C2244T (4,3%) nucleotide exchanges in only susceptible strains.

Conclusion: In this study, we present the validation of the first webtool for H pylori resistance prediction based on the detection of 23S rRNA mutations (A2142C, A2142G, A2143G, T2182C, C2244T, T2712C) from WGS data of H pylori.
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http://dx.doi.org/10.1111/hel.12752DOI Listing
December 2020

Molecular characterization of Danish ESBL/AmpC-producing Klebsiella pneumoniae from bloodstream infections, 2018.

J Glob Antimicrob Resist 2020 09 5;22:562-567. Epub 2020 Jun 5.

Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen S, Denmark. Electronic address:

Objectives: The aim of the study was to molecularly characterize third-generation cephalosporin-resistant Klebsiella pneumoniae isolated from bloodstream infections in Denmark in 2018 using whole-genome sequencing (WGS) data, and to compare these isolates to the most common clones detected in 2006 and 2008.

Methods: Sixty-two extended-spectrum beta-lactamase (ESBL)/AmpC-producing K. pneumoniae isolates from Danish blood cultures from 2018 were analysed using WGS to obtain multilocus sequence typing (MLST), core genome MLST (cgMLST), resistance profile and phylogeny. These were compared to the most common ESBL K. pneumoniae clones detected in 2006 and 2008.

Results: The most common ESBL clone was ST15 CTX-M-15, the DHA-1 enzyme was the most common in AmpC isolates, and the OXA-48-like group was the most common carbapenemase. Thirty-nine different sequence types (STs) were found, with the most frequent being ST14, ST15 and ST37, accounting for 24% of the isolates. The isolates were subdivided into 55 complex types (CTs) of which 49 were singletons, with the most frequent being ST14-CT2080. Two of the CTX-M-15-producing isolates from 2018 belonged to the ST15-CT105/CT3078 clone, which was first detected in 2006.

Conclusions: The ESBL/AmpC K. pneumoniae isolates detected in Danish blood cultures belonged to many different types. No dominant clones were circulating in Danish hospitals, but the ST15-CT105/CT3078 CTX-M-15 K. pneumoniae clone was seen 13 years after its first detection.
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http://dx.doi.org/10.1016/j.jgar.2020.05.014DOI Listing
September 2020

Astaxanthin from Shrimp Cephalothorax Stimulates the Immune Response by Enhancing IFN-γ, IL-10, and IL-2 Secretion in Splenocytes of -Infected Mice.

Mar Drugs 2019 Jun 26;17(7). Epub 2019 Jun 26.

Department of Research and Development, FB Dermatology Ltd., Borupvang 5C, 2750 Ballerup, Denmark.

Infection with is a critical cause of gastrointestinal diseases. A crucial host response associated with infection includes gastric inflammation, which is characterized by a sustained recruitment of T-helper (Th) cells to the site of infection and distinct patterns of cytokine production. Adequate nutritional status, especially frequent consumption of dietary antioxidants, appears to protect against infection with . The aim of the present study was to investigate whether astaxanthin (AXT) from shrimp cephalothorax may modulate cytokine release of splenocytes in -infected mice ( = 60). Six- to eight-week-old female mice were divided into three groups (n = 20 per group) to receive a daily oral dose of 10 or 40 mg of AXT for six weeks. After six weeks, a trend toward interferon gamma (IFN-γ) upregulation was found (40 mg; < 0.05) and a significant dose-dependent increase of interleukin 2 (IL-2) and IL-10 (both < 0.05) was observed. These results suggest that AXT induces higher levels of IL-2 and a shift to a balanced Th1/Th2 response by increasing IFN-γ and augmenting IL-10. We concluded that AXT may influence the pattern of cytokines during infection.
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http://dx.doi.org/10.3390/md17070382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669458PMC
June 2019

Leclercia adecarboxylata: a case report and literature review of 74 cases demonstrating its pathogenicity in immunocompromised patients.

Infect Dis (Lond) 2019 Mar 29;51(3):179-188. Epub 2018 Nov 29.

a Department of Clinical Microbiology , Copenhagen University Hospital (Rigshospitalet) , Copenhagen , Denmark.

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the family Enterobacteriaceae. It has been described as an emerging human pathogen with the potential to cause severe infection in immunocompromised patients. The aim of this study was to describe a clinical case of infection with L. adecarboxylata and give a review of previous reports on infection. We report the presence of L. adecarboxylata in a patient initially admitted to our hospital for a lung transplant. She had diarrhoea, urinary tract infection and pneumonia caused by L. adecarboxylata. The isolate was resistant to trimethoprim-sulfamethoxazole and susceptible to 15 other antibiotics tested. The literature search for previous reports of infection with L. adecarboxylata resulted in 61 publications describing 74 cases. Bacteremia and wound infections were most often described, and only a few cases were fatal. L. adecarboxylata was most often found as a monomicrobial infection in immunocompromised patients, and as part of a polymicrobial infection in immunocompetent patients. The previously described isolates showed a high susceptibility to antibiotics, and treatment was efficient in most cases. Due to similarities in metabolic products, L. adecarboxylata might have been mistaken as Escherichia spp., but with new identification methods such as MALDI-TOF MS, it is possible to obtain a certain identification.
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http://dx.doi.org/10.1080/23744235.2018.1536830DOI Listing
March 2019

Laribacter hongkongensis: clinical presentation, epidemiology and treatment. A review of the literature and report of the first case in Denmark.

Infect Dis (Lond) 2018 Jun 22;50(6):417-422. Epub 2017 Dec 22.

a Department of Clinical Microbiology , Rigshospitalet , Copenhagen , Denmark.

Background: Laribacter hongkongensis is an emerging pathogen related to gastroenteritis that can cause invasive and even fatal disease. The aim of this review is to describe the clinical presentation, epidemiology, treatment options and implications for the clinical microbiology laboratory.

Methods: We searched Pubmed using the term Laribacter hongkongensis with limitations human and language English, and identified 35 publications with eight reports on human cases.

Results: We describe our first case of prolonged, travel-related gastroenteritis where Laribacter hongkongensis was isolated as the sole pathogen. Our review suggests that L. hongkongensis causes non-bloody acute diarrhoea with potential for invasive disease, since three cases of bacteraemia and one case of dialysis related peritonitis have been described previously. L. hongkongensis has primarily been described in Asia, but reports from Europe, North America and Australia suggests a worldwide distribution. Broad culturing with subsequent identification by the MALDI-TOF is the current strategy for detection of L. hongkongensis. Phenotypic susceptibility testing is necessary to guide the treatment choice. Few resistance genes have been described in L. hongkongensis.

Conclusion: L. hongkongensis should be considered a potential cause of acute and prolonged diarrhoea. Clinicians must be aware of the test methods in the local clinical microbiology laboratory, since L. hongkongensis is difficult to detect and easily overlooked.
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http://dx.doi.org/10.1080/23744235.2017.1419373DOI Listing
June 2018

Primary antibiotic resistance of Helicobacter pylori strains among adults and children in a tertiary referral centre in Lithuania.

APMIS 2018 Jan 13;126(1):21-28. Epub 2017 Nov 13.

Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

The study evaluated primary antibiotic resistance of Helicobacter pylori within the period 2013-2015 and trends of antibiotic consumption over the last decade in Lithuania; 242 adults and 55 children were included in the study. E-tests were performed for amoxicillin, metronidazole, clarithromycin, ciprofloxacin, rifampicin and tetracycline. The presence of H. pylori and clarithromycin resistance was additionally tested by PCR. Helicobacter pylori culture was positive in 67 of 242 (28%) adult and in 12 of 55 (21.8%) children samples. Resistance rates among adults by E-tests were as follows: metronidazole - 32.8% (95% confidence interval (CI): 22.7-44.7%), ciprofloxacin - 7.5% (95% CI: 3.2-16.3%), rifampicin - 7.5% (95% CI: 3.2-16.3%), amoxicillin - 0%, whereas resistance rates in children were as follows: metronidazole - 25% (95% CI: 8.9-53.2%), rifampicin - 8.3% (CI: 1.5-35.4%), amoxicillin and ciprofloxacin - 0%. Accumulated clarithromycin resistance rates by E-tests and PCR were 8.2% (95% CI: 4.1-16.0%) in adults and 17.7% (95% CI: 6.2-41.0%) in children. Total use of macrolides and lincosamides in Lithuania increased from 1.26 to 1.86 defined daily dose (DDD)/1000 inhabitants/day among adults, while it has doubled from 1.10 to 2.22 DDD/1000/children/day in children within 2003-2015. There are no significant changes in the susceptibility of H. pylori to the most widely used antibiotics in adults over the last years in Lithuania; however, clarithromycin resistance among children exceeds 15% and mandates further larger-scale studies in paediatric population.
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http://dx.doi.org/10.1111/apm.12752DOI Listing
January 2018

Helicobacter: Inflammation, immunology and vaccines.

Helicobacter 2017 Sep;22 Suppl 1

Department of Clinical Microbiology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.

Helicobacter pylori is usually acquired in early childhood and the infection persists lifelong without causing symptoms. In a small of cases, the infection leads to gastric or duodenal ulcer disease, or gastric cancer. Why disease occurs in these individuals remains unclear, however the host response is known to play a very important part. Understanding the mechanisms involved in maintaining control over the immune and inflammatory response is therefore extremely important. Vaccines against H. pylori have remained elusive but are desperately needed for the prevention of gastric carcinogenesis. This review focuses on research findings which may prove useful in the development of prognostic tests for gastric cancer development, therapeutic agents to control immunopathology, and effective vaccines.
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http://dx.doi.org/10.1111/hel.12406DOI Listing
September 2017

WGS-based surveillance of third-generation cephalosporin-resistant Escherichia coli from bloodstream infections in Denmark.

J Antimicrob Chemother 2017 07;72(7):1922-1929

Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.

Objectives: To evaluate a genome-based surveillance of all Danish third-generation cephalosporin-resistant Escherichia coli (3GC-R Ec ) from bloodstream infections between 2014 and 2015, focusing on horizontally transferable resistance mechanisms.

Methods: A collection of 552 3GC-R Ec isolates were whole-genome sequenced and characterized by using the batch uploader from the Center for Genomic Epidemiology (CGE) and automatically analysed using the CGE tools according to resistance profile, MLST, serotype and fimH subtype. Additionally, the phylogenetic relationship of the isolates was analysed by SNP analysis.

Results: The majority of the 552 isolates were ESBL producers (89%), with bla CTX-M-15 being the most prevalent (50%) gene, followed by bla CTX-M-14 (14%), bla CTX-M-27 (11%) and bla CTX-M-101 (5%). ST131 was detected in 50% of the E. coli isolates, with the remaining isolates belonging to 73 other STs, including globally disseminated STs (e.g. ST10, ST38, ST58, ST69 and ST410). Five of the bloodstream isolates were carbapenemase producers, carrying bla OXA-181 (3) and bla OXA-48 (2). Phylogenetic analysis revealed 15 possible national outbreaks during the 2 year period, one caused by a novel ST131/ bla CTX-M-101 clone, here observed for the first time in Denmark. Additionally, the analysis revealed three individual cases with possible persistence of closely related clones collected more than 13 months apart.

Conclusions: Continuous WGS-based national surveillance of 3GC-R Ec , in combination with more detailed epidemiological information, can improve the ability to follow the population dynamics of 3GC-R Ec , thus allowing for the detection of potential outbreaks and the effects of changing treatment regimens in the future.
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http://dx.doi.org/10.1093/jac/dkx092DOI Listing
July 2017

[How much should we screen for MRSA?].

Ugeskr Laeger 2016 05;178(18)

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May 2016

Presence of Pathogenic Bacteria and Viruses in the Daycare Environment.

J Environ Health 2015 Oct;78(3):24-9

The number of children in daycare centers (DCCs) is rising. This increases exposure to microorganisms and infectious diseases. Little is known about which bacteria and viruses are present in the DCC environment and where they are located. In the study described in this article, the authors set out to determine the prevalence of pathogenic bacteria and viruses and to find the most contaminated fomites in DCCs. Fifteen locations in each DCC were sampled for bacteria, respiratory viruses, and gastrointestinal viruses. The locations were in the toilet, kitchen, and playroom areas and included nursery pillows, toys, and tables, among other things. Coliform bacteria were primarily found in the toilet and kitchen areas whereas nasopharyngeal bacteria were found mostly on toys and fabric surfaces in the playroom. Respiratory viruses were omnipresent in the DCC environment, especially on the toys.
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October 2015

Methicillin-resistant Staphylococcus aureus transmission: unrecognised patient MRSA carriage.

Dan Med J 2015 Apr;62(4):A5047

Infektionshygiejnisk Enhed, Rigshospitalet, Juliane Maries Vej 28, 2100 København Ø, Denmark.

Introduction: Even though methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of nosocomial infections, it may often be difficult to evaluate the exact route of transmission.

Methods: In this study, we describe four cases of nosocomial transmission of MRSA in a hospital with a low MRSA incidence.

Results: In one case, a multi-traumatic patient arrived from a hospital in a foreign country and the primary surveillance swaps were negative for MRSA. The second case was a child with burn wounds who was referred from a Danish hospital. The third case was a multi-traumatic patient from Denmark. The fourth case was a new-born child in the neonate unit.

Conclusion: In none of the cases, the index patient was known to have MRSA on admission and no specific precautions were taken to prevent transmission. In all cases there was intensive contact between the patient and the staff which may increase the risk of contaminating hands, arms and the front of the uniform. Hand hygiene is therefore essential, but the use of protection gowns with long sleeves is also important in order to prevent transmission of MRSA. After culture of MRSA and implementation of specific precautions to prevent transmission of MRSA, no further transmissions were observed.

Funding: not relevant.

Trial Registration: The data in this study are included in the routine surveillance of MRSA at Rigshospitalet and do not form part of a trial.
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April 2015

Comparing whole-genome sequencing with Sanger sequencing for spa typing of methicillin-resistant Staphylococcus aureus.

J Clin Microbiol 2014 Dec 8;52(12):4305-8. Epub 2014 Oct 8.

Department of Clinical Microbiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark MRSA Knowledge Center, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

spa typing of methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been done by PCR amplification and Sanger sequencing of the spa repeat region. At Hvidovre Hospital, Denmark, whole-genome sequencing (WGS) of all MRSA isolates has been performed routinely since January 2013, and an in-house analysis pipeline determines the spa types. Due to national surveillance, all MRSA isolates are sent to Statens Serum Institut, where the spa type is determined by PCR and Sanger sequencing. The purpose of this study was to evaluate the reliability of the spa types obtained by 150-bp paired-end Illumina WGS. MRSA isolates from new MRSA patients in 2013 (n = 699) in the capital region of Denmark were included. We found a 97% agreement between spa types obtained by the two methods. All isolates achieved a spa type by both methods. Nineteen isolates differed in spa types by the two methods, in most cases due to the lack of 24-bp repeats in the whole-genome-sequenced isolates. These related but incorrect spa types should have no consequence in outbreak investigations, since all epidemiologically linked isolates, regardless of spa type, will be included in the single nucleotide polymorphism (SNP) analysis. This will reveal the close relatedness of the spa types. In conclusion, our data show that WGS is a reliable method to determine the spa type of MRSA.
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http://dx.doi.org/10.1128/JCM.01979-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313303PMC
December 2014

Comparative genomic analysis of rapid evolution of an extreme-drug-resistant Acinetobacter baumannii clone.

Genome Biol Evol 2013 ;5(5):807-18

Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore.

The emergence of extreme-drug-resistant (EDR) bacterial strains in hospital and nonhospital clinical settings is a big and growing public health threat. Understanding the antibiotic resistance mechanisms at the genomic levels can facilitate the development of next-generation agents. Here, comparative genomics has been employed to analyze the rapid evolution of an EDR Acinetobacter baumannii clone from the intensive care unit (ICU) of Rigshospitalet at Copenhagen. Two resistant A. baumannii strains, 48055 and 53264, were sequentially isolated from two individuals who had been admitted to ICU within a 1-month interval. Multilocus sequence typing indicates that these two isolates belonged to ST208. The A. baumannii 53264 strain gained colistin resistance compared with the 48055 strain and became an EDR strain. Genome sequencing indicates that A. baumannii 53264 and 48055 have almost identical genomes-61 single-nucleotide polymorphisms (SNPs) were found between them. The A. baumannii 53264 strain was assembled into 130 contigs, with a total length of 3,976,592 bp with 38.93% GC content. The A. baumannii 48055 strain was assembled into 135 contigs, with a total length of 4,049,562 bp with 39.00% GC content. Genome comparisons showed that this A. baumannii clone is classified as an International clone II strain and has 94% synteny with the A. baumannii ACICU strain. The ResFinder server identified a total of 14 antibiotic resistance genes in the A. baumannii clone. Proteomic analyses revealed that a putative porin protein was down-regulated when A. baumannii 53264 was exposed to antimicrobials, which may reduce the entry of antibiotics into the bacterial cell.
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http://dx.doi.org/10.1093/gbe/evt047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673627PMC
December 2013

Etiology and epidemiology of catheter related bloodstream infections in patients receiving home parenteral nutrition in a gastromedical center at a tertiary hospital in denmark.

Open Microbiol J 2012 30;6:98-101. Epub 2012 Nov 30.

Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark ; Department of Clinical Microbiology, University Hospital of Copenhagen, Denmark.

We conducted a retrospective epidemiologic study of catheter related bloodstream infections (CRBSI) in patients receiving long-term home parenteral nutrition (HPN) from January 2002 to December 2005. Our results showed that coagulase negative staphylococci (CoNS) were the most prevalent pathogens (44.7% of all CRBSI episodes), followed by Enterobacteriaceae (33.2%). Prevalence for candidemia and Enterococcus bacteremia was relatively high (14.4% and 10.8%, respectively). Cefuroxime resistance was observed in 65.4% CoNS and 31.5% Enterobacteriaceae. Based on the results from the study, a new empiric antimicrobial treatment regiment was suggested.
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http://dx.doi.org/10.2174/1874285801206010098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520033PMC
December 2012

[Helicobacter pylori resistance].

Ugeskr Laeger 2010 May;172(20):1516-21

Neurokirugisk Afdeling, Glostrup Hospital, 2600 Glostrup, Denmark.

Helicobacter pylori (H. pylori) is recognized as the causative of several gastroduodenal disorders. The discovery of H. pylori revolutionized the treatment for ulcus pepticum. Antibiotics combined with proton pump inhibitors or bismuth have been effective in the treatment of H. pylori infections, but there is an emerging problem with H. pylori resistance against the most frequently used antibiotics, which substantially impairs the treatment of H. pylori-associated disorders. In this article the focus is on the prevalence of H. pylori resistance, its clinical implications and the molecular mechanisms behind resistance development.
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May 2010

Helicobacter pylori-coccoid forms and biofilm formation.

FEMS Immunol Med Microbiol 2009 Jul 27;56(2):112-5. Epub 2009 Apr 27.

Department of Infections Control 9101, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Electron microscopic studies have shown that Helicobacter pylori occurs in three stages: spiral forms, coccoid forms and degenerative forms. The spiral forms are viable, culturable, virulent and can colonize experimental animals and induce inflammation. The coccoid forms may also be viable but are nonculturable, less virulent and are less likely to colonize and induce inflammation in experimental animals than the spiral forms. The degenerative forms are pyknotic, nonculturable, coccoid forms of dead H. pylori. These forms cannot be cultured and the cell membrane has disintegrated but gene material can be detected by PCR in water supplies. There is no substantial evidence for viable H. pylori persisting in water supplies. Epidemiological studies suggest that environmental water is a risk factor for H. pylori infection when compared with tap water, and formation of H. pylori biofilm cannot be excluded. Helicobacter pylori does not seem to take part in biofilm formation in the oral cavity even though the bacterium may be detected.
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http://dx.doi.org/10.1111/j.1574-695X.2009.00556.xDOI Listing
July 2009

First attempt to produce experimental Campylobacter concisus infection in mice.

World J Gastroenterol 2008 Dec;14(45):6954-9

Department of Clinical Microbiology, National University Hospital (Rigshospitalet), Copenhagen, Denmark.

Aim: To infect mice with atypical Campylobacter concisus (C. concisus) for the first time.

Methods: Three separate experiments were conducted in order to screen the ability of five clinical C. concisus isolates of intestinal origin and the ATCC 33237 type strain of oral origin to colonize and produce infection in immunocompetent BALB/cA mice. The majority of the BALB/cA mice were treated with cyclophosphamide prior to C. concisus inoculation to suppress immune functions. Inoculation of C. concisus was performed by the gastric route.

Results: C. concisus was isolated from the liver, ileum and jejunum of cyclophosphamide-treated mice in the first experiment. No C. concisus strains were isolated in the two subsequent experiments. Mice infected with C. concisus showed a significant loss of body weight from day two through to day five of infection but this decreased at the end of the first week. Histopathological examination did not consistently find signs of inflammation in the gut, but occasionally microabscesses were found in the liver of infected animals.

Conclusion: Transient colonization with C. concisus was observed in mice with loss of body weight. Future studies should concentrate on the first few days after inoculation and in other strains of mice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773859PMC
http://dx.doi.org/10.3748/wjg.14.6954DOI Listing
December 2008

[Role of Helicobacter species in hepatobiliary diseases].

Ugeskr Laeger 2008 Jun;170(23):2010-5

Rigshospitalet, Klinisk Mikrobiologisk Afdeling 9301.

Helicobacter species have been found in extragastric tissues of humans and mice, and it has been shown that hepatic infection with H. hepaticus causes chronic hepatitis and hepatocellular carcinoma (HCC) in mice. 18 studies of humans with hepatobiliary diseases have been reviewed. In studies of patients with HCC the results imply a pathogen role of Helicobacter species. The same trend was not found in studies of humans with other hepatobiliary diseases. There is no evidence of the possible involvement of Helicobacter species in the development of diseases in the hepatobiliary system.
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June 2008

Efficacy of the natural antioxidant astaxanthin in the treatment of functional dyspepsia in patients with or without Helicobacter pylori infection: A prospective, randomized, double blind, and placebo-controlled study.

Phytomedicine 2008 Jun 7;15(6-7):391-9. Epub 2008 May 7.

Kaunas University of Medicine, 50009 Kaunas, Lithuania.

Objectives: The aim of this study was to evaluate the efficacy of the natural antioxidant astaxanthin in functional dyspepsia in different doses and compared with placebo.

Design: The study was a controlled, prospective, randomized, and double blind trial.

Participants: Patients with functional dyspepsia, divided into three groups with 44 individuals in each group (placebo, 16mg, or 40mg astaxanthin, respectively).

Interventions: Participants were asked to accept gastroscopy before treatment, together with questionnaires: GSRS and SF-36. Urea breath test (UBT) was done before the treatment.

Main Outcome: The primary objective was to test the hypothesis that the antioxidant astaxanthin at two doses regimens compared to placebo should ameliorate gastrointestinal discomfort measured as GSRS in patients with functional dyspepsia, who were either positive or negative for Helicobacter pylori, after 4 weeks of treatment.

Results: At the end of therapy (week 4) no difference between the three treatment groups was observed regarding mean Gastrointestinal Symptom Rating Scale (GSRS) scores of abdominal pain, indigestion and reflux syndromes. The same results were observed at the end of follow-up. However reduction of reflux syndrome before treatment to week 4 was significantly pronounced in the higher (40mg) dose compared to the other treatment groups (16mg and placebo, p=0.04).

Conclusion: In general, no curative effect of astaxanthin was found in functional dyspepsia patients. Significantly greater reduction of reflux symptoms were detected in patients treated with the highest dose of the natural antioxidant astaxanthin. The response was more pronounced in H. pylori-infected patients.
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http://dx.doi.org/10.1016/j.phymed.2008.04.004DOI Listing
June 2008

[The 2nd white coat revolution?].

Ugeskr Laeger 2008 Mar;170(14):1169

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March 2008

[Sterilisation methods].

Ugeskr Laeger 2007 Dec;169(49):4246-8

Rigshospitalet, Infektionshygiejnisk Enhed 9101.

Manual or mechanical cleaning and disinfection should always be done prior to sterilisation. Steam under pressure sterilisation should always be preferred for items that can withstand heat and pressure variations. Heat-and pressure-sensitive medical devices can be sterilized with saturated water steam in combination with formaldehyde, plasma sterilisation or chemical sterilisation. Equipment for sterilisation should be purchased, tested, and maintained according to the manufacturer's recommendations and according to the standards covering the individual type.
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December 2007

[Disinfectants and disinfection methods].

Ugeskr Laeger 2007 Dec;169(49):4243-6

Rigshospitalet, Infektionshygiejnisk Enhed 9101.

A risk assessment should be made of the microorganisms to be eliminated and the chosen disinfection compound. It is also necessary to reduce the amount of microorganisms by manual or mechanical cleaning in order to obtain a satisfactory result from disinfection. New chemical disinfectants are often combinations of different compounds. Tests made on products are often insufficient to evaluate the full antimicrobial effect of a disinfectant and in some cases the compounds in a product have a synergistic effect on microorganisms which may result in a broader antimicrobial spectrum.
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December 2007

Colonization and infection by Helicobacter pylori in humans.

Helicobacter 2007 Nov;12 Suppl 2:12-5

Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.

When Helicobacter pylori arrives in the human stomach, it may penetrate the mucin layer and adhere to the gastric epithelial cells or it may pass through the stomach without colonizing the mucosa. In this paper, the colonization process and the ensuing immunological response will be briefly described. Urease production is necessary for H. pylori to establish a pH-neutral microenvironment around the bacteria. The flagella enable the bacteria to move and the shape of H. pylori makes it possible to penetrate the mucin layer where it comes into contact with the gastric epithelial cells. H. pylori contains several adhesins that enable it to adhere to the epithelial cells. This adherence activates IL-8 which, together with bacterial antigens, attracts polymorphs and monocytes and causes acute gastritis. Antigen-presenting cells activate lymphocytes and other mononuclear cells that are attracted to the inflamed mucosa, causing chronic superficial gastritis and initiating a cytotoxic or an antigen-producing Th response. The infection is established within a few weeks after the primary exposure to H. pylori. After this initial colonization, many chemical, biochemical, and immunologic reactions take place that are of importance in the progress of the infection and the development of disease.
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http://dx.doi.org/10.1111/j.1523-5378.2007.00574.xDOI Listing
November 2007

Combined serum IgG response to Helicobacter pylori VacA and CagA predicts gastric cancer.

FEMS Immunol Med Microbiol 2007 Jul;50(2):220-5

Department of Microbiology, University of Medicine, Kaunas, Lithuania.

Helicobacter pylori is a major factor for the development of gastric cancer. The aim of this study was to define serum antibody patterns associated with H. pylori infection in patients with gastric cancer using a Western blot technique. Serum samples collected from 115 patients with gastric cancer and 110 age- and gender-matched patients without gastrointestinal diseases were tested for IgG antibodies to H. pylori antigens (outer membrane proteins and whole cell preparations). No significant differences were found between patients with and without gastric cancer using outer membrane proteins (82% and 73%, P>0.05) or whole cell antigens (84% and 76%, P>0.05), respectively. The significant differences between patients with and without gastric cancer were associated with bands of 94 kDa (54% and 20%, P<0.001) and 30 kDa (65% and 44%, P<0.01). A combination of antibodies to 85 kDa (VacA) and 120 kDa (CagA) was significantly (P<0.01) more frequent in gastric cancer patients than in patients without gastric cancer. The detection of antibodies to 94- and 30-kDa bands, in association with the determination of serum antibodies to CagA+/VacA+, may have a prospective value in assessment of the risk of developing of gastric cancer.
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http://dx.doi.org/10.1111/j.1574-695X.2007.00268.xDOI Listing
July 2007

Gastric inflammatory markers and interleukins in patients with functional dyspepsia treated with astaxanthin.

FEMS Immunol Med Microbiol 2007 Jul 23;50(2):244-8. Epub 2007 May 23.

Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

The chronic active inflammation caused by Helicobacter pylori is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins are involved in the inflammatory process. The aim of this study was to investigate the effect of astaxanthin on gastric inflammation in patients with functional dyspepsia. Forty-four consecutive patients were included, and biopsies were examined for IL-4, IL-6, IL-8, IL-10, interferon-gamma, CD4, CD8, CD14, CD19, CD25 and CD30. Patients were randomized: 21 patients were treated with 40 mg of astaxanthin daily, and 23 patients were treated with a placebo. There was a significant decrease in gastric inflammation in H. pylori-positive patients from both groups. There were no significant changes in the density of H. pylori or in any of the interleukins during or after treatment. There was a significant up-regulation of CD4 and down-regulation of CD8 in patients with H. pylori treated with astaxanthin. Astaxanthin had an effect on the inflammation and on the density of H. pylori in mice in a study where the diet could be standardized without antioxidants (Bennedsen et al., 1999). These dietary conditions are impossible in studies involving humans, and may be due to the minor effect when the host have access to antioxidants in their diet.
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http://dx.doi.org/10.1111/j.1574-695X.2007.00257.xDOI Listing
July 2007

[Prevalence of Helicobacter pylori and Cag-A strains in patients with duodenal ulcer in Iceland.].

Laeknabladid 2003 Jul-Aug;89(7-8):595-7

Landspitali University Hospital, Hringbraut, 101 Reykjavík, Iceland.

Objective: The prevalence of Helicobacter pylori infection and related gastric diseases is rapidly changing in western societies. H. pylori has been associated with gastritis, gastric and duodenal ulcer and gastric cancer. This association applies in particular to H. pylori strains which are Cag-A positive. H. pylori is naturally disappearing from western populations in particular Cag-A positive strains which are selectively eradicated due to their association with peptic ulcer. The aim of the study was to assess the prevalence of H. pylori in duodenal ulcer disease and its Cag-A status before the eradication of H. pylori was routinely applied.

Material And Methods: Antibodies for H. pylori and Cag-A were investigated by Western blot method in serum samples from 62 patients with duodenal ulcer. The samples were collected during the period 1993-1996 and should represent the Cag-A prevalence before it was changed by active eradication. No subject had received H. pylori eradication before the study.

Results: Of the 62 samples 54 (87.1%) were positive for H. pylori specific antigen and of the 54 positive samples 53 (98.1%) were positive for Cag-A.

Conclusion: H. pylori strains associated with duodenal ulcer in Iceland were predominantly (98.1%) Cag-A positive.
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October 2015

The humoral immuneresponse to Helicobacter pylori infection in children with gastrointestinal symptoms.

FEMS Immunol Med Microbiol 2005 May;44(2):205-12

Department of Microbiology, Kaunas University of Medicine, Lithuania.

The prevalence of Helicobacter pylori is high in Eastern Europe. The purpose of this study was to estimate the prevalence of H. pylori in symptomatic Lithuanian children and to identify the infection by clinicopathological and serological analyses. One hundred sixteen symptomatic children (age 8-16) with gastritis and duodenal ulcer were included. Biopsies were histologically assessed according to the Sydney-System. Serum IgG antibodies against H. pylori were detected by an enzyme-linked immunosorbent assay (ELISA), using low molecular mass antigen. The western blot technique was used to detect serum antibodies against the cytotoxin-associated protein (CagA) using whole cell antigen. Histologically the prevalence of H. pylori infection was 79% and not influenced by demographic factors. Mucosal inflammation and atrophy were associated with a H. pylori infection. Intestinal metaplasia was found in eight children, suggesting early H. pylori acquisition in life. Increased levels of IgG antibodies were detected in 57% of children. The prevalence of IgG antibodies was significantly higher in patients with duodenal ulcer compared to children with gastritis. Forty-four (67%) H. pylori-seropositive children had antibodies against CagA. Low molecular weight-ELISA and whole cell-western blot results were significantly associated with histopathology, the presence of duodenal ulcer and the CagA status. A high number of false seronegative cases were due to poor immunological responses in children and poor locally validated tests. The prevalence of H. pylori infection in Lithuanian children is higher compared to Western Europe. The infection is acquired in early life. Diagnosing H. pylori infection, serology is helpful, but endoscopy/histology remains as gold standard.
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http://dx.doi.org/10.1016/j.femsim.2005.02.005DOI Listing
May 2005

Helicobacter pylori antibodies and gastric cancer: a gender-related difference.

FEMS Immunol Med Microbiol 2005 May;44(2):191-5

Department of Microbiology, Kaunas University of Medicine, Mickeviciaus 9, LT-4430 Kaunas, Lithuania.

Helicobacter pylori has been proposed as a causative agent of gastric cancer. The aim of this study was to define serum antibodies response against different H. pylori antigens in patients with gastric cancer. Serum samples were collected from 115 Lithuanian patients with non-cardia gastric cancer and 110 age- and sex-matched controls without cancer. Heat-stable, low-molecular-mass, and outer membrane proteins were used as antigens to analyze serum IgG antibody response against H. pylori by enzyme-linked immunosorbent assay. Seroprevalence of H. pylori using low-molecular-mass antigen was significantly higher in gastric cancer patients, compared to controls (77% versus 57%, p<0.05). Significant differences in the prevalence of H. pylori infection between gastric cancer patients and controls were found in females using all three studied antigens: heat-stable (98% versus 84%, p<0.05), low-molecular-mass (88% versus 48%, p<0.05) and outer membrane proteins (78% versus 57%, p<0.05). In males, no significant differences were revealed between gastric cancer patients and controls. There may be other cofactors in addition to H. pylori that are important for the development of gastric cancer. H. pylori seems, however, to be a more important for development of gastric cancer in females than in males or males may have more confounding risk factors for gastric cancer than females.
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http://dx.doi.org/10.1016/j.femsim.2004.11.011DOI Listing
May 2005
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