| 1. |
- Kjellander, Christian, et al.
(author)
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Hematological : Low all-cause mortality and low occurrence of antimicrobial resistance in hematological patients with bacteremia receiving no antibacterial prophylaxis: a single-center study
- 2012
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 88:5, s. 422-430
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Journal article (peer-reviewed)abstract
- Background: Bacteremia is a major cause of morbidity and mortality in patients with hematological malignancies. Objectives: The aim of this study was to define temporal trends in species distribution, antimicrobial susceptibility, and all-cause mortality in bacteremic hospitalized patients receiving no antibacterial prophylaxis during chemotherapy-induced neutropenia. Methods: A total of 677 clinical episodes of bacteremia were identified in 463 patients during 2002-2008, and the results were compared with those published from the same institution during 1980-86 and 1988-2001. No major changes in patient selection were introduced during this period. Results: Between 2002 and 2008, the dominating pathogens were Escherichia coli (18%), coagulase-negative staphylococci (15%), viridans streptococci (14%), Klebsiella spp. (10%), and Enterococcus faecium (8%). The 7-d crude mortality rate was 5.2%. Polymicrobial bacteremia was seen in 25.7% of the patients who died within 7 d and in 13.1% of the survivors (P = 0.04). Acquired resistance was rarely observed, but a statistically significant increase in ciprofloxacin resistance in E. coli was observed. Comparing 2002-2008 with historical data from the same institution, the proportion of Gram-positive isolates remained stable at 53-55% from 1988. Conclusions: The avoidance of fluoroquinolone prophylaxis may have contributed to a stable proportion of Gram-positive bacteremia. The crude mortality was low in an international perspective. Acquired resistance was uncommon, but ciprofloxacin resistance in E. coli increased significantly. We believe that an indiscriminate use of antibacterial prophylaxis could be avoided in neutropenic patients without a negative impact on mortality.
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| 2. |
- Al-Farsi, Hissa M., et al.
(author)
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Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions
- 2019
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In: Frontiers in Microbiology. - : FRONTIERS MEDIA SA. - 1664-302X. ; 10
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Journal article (peer-reviewed)abstract
- Background Colistin is a polypeptide antibiotic drug that targets lipopolysaccharides in the outer membrane of Gram-negative bacteria. Inactivation of the mgrB-gene is a common mechanism behind colistin-resistance in Klebsiella pneumoniae (Kpn). Since colistin is a cyclic polypeptide, it may exhibit cross-resistance with the antimicrobial peptide LL-37, and with other innate effector mechanisms, but previous results are inconclusive. Objective To study potential cross-resistance between colistin and LL-37, as well as with other innate effector mechanisms, and to compare virulence of colistin-resistant and susceptible Kpn strains. Materials/Methods Carbapenemase-producing Kpn from Oman (n = 17) were subjected to antimicrobial susceptibility testing and whole genome sequencing. Susceptibility to colistin and LL-37 was studied. The surface charge was determined by zeta-potential measurements and the morphology of treated bacteria was analyzed with electron microscopy. Bacterial survival was assessed in human whole blood and serum, as well as in a zebrafish infection-model. Results Genome-analysis revealed insertion-sequences in the mgrB gene, as a cause of colistin resistance in 8/17 isolates. Colistin-resistant (Col-R) isolates were found to be more resistant to LL-37 compared to colistin-susceptible (Col-S) isolates, but only at concentrations >= 50 mu g/ml. There was no significant difference in surface charge between the isolates. The morphological changes were similar in both Col-R and Col-S isolates after exposure to LL-37. Finally, no survival difference between the Col-R and Col-S isolates was observed in whole blood or serum, or in zebrafish embryos. Conclusion Cross-resistance between colistin and LL-37 was observed at elevated concentrations of LL-37. However, Col-R and Col-S isolates exhibited similar survival in serum and whole blood, and in a zebrafish infection-model, suggesting that cross-resistance most likely play a limited role during physiological conditions. However, it cannot be ruled out that the observed cross-resistance could be relevant in conditions where LL-37 levels reach high concentrations, such as during infection or inflammation.
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| 3. |
- Andersson, Helene, et al.
(author)
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Prevalence of antibiotic-resistant bacteria in residents of nursing homes in a Swedish municipality : healthcare staff knowledge of and adherence to principles of basic infection prevention
- 2012
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In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 44:9, s. 641-649
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Journal article (peer-reviewed)abstract
- Abstract Background: The aims of this study were to investigate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in residents living in Swedish nursing homes, and if carriage of resistant bacteria was related to antibiotic treatment, other risk factors, and/or staff's adherence to guidelines for infection control. Methods: Five hundred and sixty residents from 9 nursing homes on a total of 67 wards participated in the study and had microbiological cultures taken. Faecal samples were obtained from 495 residents (88.3%). ESBL-positive residents were followed for 2 y with repeated sampling. Two hundred and ninety-six staff members were interviewed and observed regarding familiarity with and adherence to infection control guidelines. Results: No resident was positive for MRSA or VRE. Fifteen of the residents were found to be ESBL-positive. Residents living on wards where ESBL-positive residents were identified had been treated more frequently with antibiotics (42%), compared to those on wards where no residents with ESBL were found (28%; p = 0.02). ESBL-positive Escherichia coli isolates from residents living in adjacent rooms were found to be closely genetically related when analysed by pulsed-field gel electrophoresis, indicating transmission between residents. Staff adherence to infection control guidelines sometimes revealed shortcomings, but no significant differences regarding compliance to the guidelines could be found. Conclusion: Carriage of resistant bacteria was uncommon and only ESBL-producing Enterobacteriaceae were identified in Swedish nursing homes. Usage of antibiotics was higher on wards where ESBL-positive residents were detected and there was an indication of transmission of ESBL between residents.
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| 4. |
- Andersson, Viktoria, et al.
(author)
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The In vitro Activity of Carbapenems Alone and in Combination with β-lactamase Inhibitors against Difficult-to-treat Mycobacteria; Mycobacterium tuberculosis, Mycobacterium abscessus, and Mycobacterium avium Complex: A Systematic Review
- 2023
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In: INTERNATIONAL JOURNAL OF MYCOBACTERIOLOGY. - : WOLTERS KLUWER MEDKNOW PUBLICATIONS. - 2212-5531 .- 2212-554X. ; 12:3, s. 211-225
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Research review (peer-reviewed)abstract
- Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with beta-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a beta-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC50, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without beta-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the beta-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.
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| 5. |
- Beeton, Michael L., et al.
(author)
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Mycoplasma pneumoniae infections, 11 countries in Europe and Israel, 2011 to 2016
- 2020
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In: Eurosurveillance. - : EUR CENTRE DIS PREVENTION & CONTROL. - 1025-496X .- 1560-7917. ; 25:2, s. 39-51
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Journal article (peer-reviewed)abstract
- Background: Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia, with large epidemics previously described to occur every 4 to 7 years.Aim: To better understand the diagnostic methods used to detect M. pneumoniae; to better understand M. pneumoniae testing and surveillance in use; to identify epidemics; to determine detection number per age group, age demographics for positive detections, concurrence of epidemics and annual peaks across geographical areas; and to determine the effect of geographical location on the timing of epidemics.Methods: A questionnaire was sent in May 2016 to Mycoplasma experts with national or regional responsibility within the ESCMID Study Group for Mycoplasma and Chlamydia Infections in 17 countries across Europe and Israel, retrospectively requesting details on M. pneumoniae-positive samples from January 2011 to April 2016. The Moving Epidemic Method was used to determine epidemic periods and effect of country latitude across the countries for the five periods under investigation.Results: Representatives from 12 countries provided data on M. pneumoniae infections, accounting for 95,666 positive samples. Two laboratories initiated routine macrolide resistance testing since 2013. Between 2011 and 2016, three epidemics were identified: 2011/12, 2014/15 and 2015/16. The distribution of patient ages for M. pneumoniae-positive samples showed three patterns. During epidemic years, an association between country latitude and calendar week when epidemic periods began was noted.Conclusions: An association between epidemics and latitude was observed. Differences were noted in the age distribution of positive cases and detection methods used and practice. A lack of macrolide resistance monitoring was noted.
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| 6. |
- Berge, Andreas, et al.
(author)
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Risk for Endocarditis in Bacteremia with Streptococcus-Like Bacteria : A Retrospective Population-Based Cohort Study
- 2019
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In: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:10
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Journal article (peer-reviewed)abstract
- Background: Many genera and species of Streptococcus-like bacteria (SLB) can cause infective endocarditis (IE), but little is known about the epidemiology of and the risk factors for IE in SLB-bacteremia. The aim of the study was to analyze this in a cohort of patients with SLB-bacteremia, focusing on Abiotrophia, Aerococcus, Gemella, and Granulicatella. We also evaluated whether published scoring systems generated for other Gram-positive bacteria known to cause IE (HANDOC for streptococci and NOVA and DENOVA for enterococci) could be used in SLB bacteremia to decide whether transesophageal echocardiography (TEE) could be omitted. Methods: Positive blood cultures with SLB were retrieved from population-based registries in Sweden (3.2 million inhabitants), from January 2012 to December 2017. Clinical data were collected from medical records. Risk factors for IE were analyzed and the performances of the scoring systems were calculated. Results: The incidence of bacteremia with the 4 SLB genera was 30 episodes/1 000 000 population per year, of which Aerococcus contributed with 18. Among 568 episodes of bacteremia, 32 cases of IE were identified (5.6%). Infective endocarditis was most common in bacteremia with Abiotrophia (4 of 19) followed by Granulicatella (9 of 124), Gemella (6 of 87), and Aerococcus (13 of 338). NOVA had 100% sensitivity to identify IE but a low specificity (15%). For HANDOC and DENOVA, the sensitivities were 97% and 91%, respectively, whereas specificities were 85% and 90%, respectively, and numbers needed to screen were 3.6 and 2.8, respectively. Conclusions: Bacteremia with these SLB is relatively rare, and the decision whether TEE should be performed or not could be based on either HANDOC or DENOVA.
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| 7. |
- Borsa, Baris Ata, First Research Engineer, et al.
(author)
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Therapeutic-oligonucleotides activated by nucleases (TOUCAN) : A nanocarrier system for the specific delivery of clinical nucleoside analogues.
- 2023
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In: Journal of Controlled Release. - : ELSEVIER. - 0168-3659 .- 1873-4995. ; 361, s. 260-269
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Journal article (peer-reviewed)abstract
- Nucleoside analogues have been in clinical use since 1960s and they are still used as the first therapeutic option for several cancers and viral infections, due to their high therapeutic efficacy. However, their wide clinical acceptance has been limited due to their high toxicity and severe side effects to patients. Herein, we report on a nanocarrier system that delivers nucleosides analogues in a target-specific manner, making nucleoside-based therapeutics safer and with the possibility to be used in other human conditions. This system, named, Therapeutic OligonUCleotides Activated by Nucleases" (TOUCAN) combines: i) the recognition power of oligonucleotides as substrates, ii) the use of nucleases as enzymatic biomarkers and iii) the clinical efficacy of nucleoside analogues, in a single approach. As a proof-of-concept, we report on a TOUCAN that is activated by a specific nuclease produced by bacteria and releases a therapeutic nucleoside, floxuridine. We demonstrate, for the first time, that, by incorporating a therapeutic nucleoside analogue into oligonucleotide probes, we can specifically inhibit bacterial growth in cultures. In this study, Staphylococcus aureus was selected as the targeted bacteria and the TOUCAN strategy successfully inhibited its growth with minimal inhibitory concentration (MIC) values ranging from 0.62 to 40 mg/L across all tested strains. Moreover, our results indicate that the intravenous administration of TOUCANs at a dose of 20 mg/kg over a 24-h period is a highly effective method for treating bacterial infections in a mouse model of pyomyositis. Importantly, no signs of toxicity were observed in our in vitro and in vivo studies. This work can significantly impact the current management of bacterial infections, laying the grounds for the development of a different class of antibiotics. Furthermore, it can provide a safer delivery platform for clinical nucleoside therapeutics in any human conditions, such as cancer and viral infection, where specific nuclease activity has been reported.
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| 8. |
- Brolund, Alma, et al.
(author)
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Development of a real-time SYBRGreen PCR assay for rapid detection of acquired AmpC in Enterobacteriaceae
- 2010
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In: Journal of Microbiological Methods. - : Elsevier BV. - 1872-8359 .- 0167-7012. ; 82:3, s. 229-233
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Journal article (peer-reviewed)abstract
- Introduction: Acquired AmpC enzymes, classified as miscellaneous extended-spectrum beta-lactamase (ESBLM) enzymes according to a recently proposed beta-lactamase classification, are increasing according to several publications. Simple and rapid methods for detection of ESBLM are needed for appropriate infection control. A gel-based multiplex PCR method for acquired bla(AmpC) detection and subtype classification has been available for several years. Here, we describe a modification of the protocol to suit real-time PCR platforms and to include novel genotypes. Material and methods: Clinical isolates with clavulanic acid non-reversible non-susceptibility to extended-spectrum cephalosporins were subjected to combination disk testing with cefoxitin +/- cloxacillin at Malmo University Hospital. Phenotypical AmpC production was defined as cloxacillin reversible cefoxitin resistance. In this study 51 phenotypical AmpC-producing isolates, were subjected to the acquired bla(AmpC) real-time PCR assay. The acquired blaAmpC positive isolates were further characterized by DNA sequencing of the acquired AmpC encoding gene, Pulsed-Field Gel Electrophoresis (PFGE) and PCR-based replicon typing. Results and discussion: The real-time PCR assay was able to detect and sub-classify all acquired bla(AmpC) genes described to date. The assay can be performed in less than 3 h, including pre-PCR preparations. Analysis of the isolate collection resulted in 18 of 51 phenotypical AmpC-producing isolates being positive in the acquired bla(AmpC) real-time multiplex PCR assay; 17 of subtype CIT and one DHA. Sequence analysis identified 16 isolates as blaCMY-2, one as blaCMY-16 and one as blaDHA-1. Detected plasmid replicon types were I1 and B/O. Two of the E. coli isolates were identical according to PFGE and the others were unrelated. (C) 2010 Elsevier B.V. All rights reserved.
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| 9. |
- Brolund, Alma, et al.
(author)
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Dynamics of Resistance Plasmids in Extended-Spectrum-beta-Lactamase-Producing Enterobacteriaceae during Postinfection Colonization
- 2019
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In: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 63:4
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Journal article (peer-reviewed)abstract
- Extended-spectrum beta-lactamase-producing Enterobacteriaceae (EPE) are a major cause of bloodstream infections, and the colonization rate of EPE in the gut microbiota of individuals lacking prior hospitalization or comorbidities is increasing. In this study, we performed an in-depth investigation of the temporal dynamics of EPE and their plasmids during one year by collecting fecal samples from three patients initially seeking medical care for urinary tract infections. In two of the patients, the same strain that caused the urinary tract infection ( UTI) was found at all consecutive samplings from the gut microbiota, and no other EPEs were detected, while in the third patient the UTI strain was only found in the initial UTI sample. Instead, this patient presented a complex situation where a mixed microbiota of different EPE strain types, including three different E. coli ST131 variants, as well as different bacterial species, was identified over the course of the study. Different plasmid dynamics were displayed in each of the patients, including the spread of plasmids between different strain types over time and the transposition of bla(CTX-M-15) from the chromosome to a plasmid, followed by subsequent loss through homologous recombination. Small cryptic plasmids were found in all isolates from all patients, and they appear to move frequently between different strains in the microbiota. In conclusion, we could demonstrate an extensive variation of EPE strain types, plasmid composition, rearrangements, and horizontal gene transfer of genetic material illustrating the high dynamics nature and interactive environment of the gut microbiota during post-UTI carriage.
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| 10. |
- Dahl, Viktor, et al.
(author)
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Lyme neuroborreliosis epidemiology in Sweden 2010 to 2014 : clinical microbiology laboratories are a better data source than the hospital discharge diagnosis register
- 2019
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In: Eurosurveillance. - 1025-496X .- 1560-7917. ; 24:20, s. 6-12
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Journal article (peer-reviewed)abstract
- Background:In a study from 2013 that prioritised communicable diseases for surveillance in Sweden, we identified Lyme borreliosis as one of the diseases with highest priority. In 2014, when the present study was designed, there were also plans to make neuroborreliosis notifiable within the European Union.Aim:We compared possibilities of surveillance of neuroborreliosis in Sweden through two different sources: the hospital discharge register and reporting from the clinical microbiology laboratories.Methods:We examined the validity of ICD-10 codes in the hospital discharge register by extracting personal identification numbers for all cases of neuroborreliosis, defined by a positive cerebrospinal fluid-serum anti-Borrelia antibody index, who were diagnosed at the largest clinical microbiology laboratory in Sweden during 2014. We conducted a retrospective observational study with a questionnaire sent to all clinical microbiology laboratories in Sweden requesting information on yearly number of cases, age group and sex for the period 2010 to 2014.Results:Among 150 neuroborreliosis cases, 67 (45%) had received the ICD-10 code A69.2 (Lyme borreliosis) in combination with G01.9 (meningitis in bacterial diseases classified elsewhere), the combination that the Swedish National Board of Health and Welfare recommends for neuroborreliosis. All 22 clinical laboratories replied to our questionnaire. Based on laboratory reporting, the annual incidence of neuroborreliosis in Sweden was 6.3 cases per 100,000 in 2014.Conclusion:The hospital discharge register was unsuitable for surveillance of neuroborreliosis, whereas laboratory-based reporting was a feasible alternative. In 2018, the European Commission included Lyme neuroborreliosis on the list of diseases under epidemiological surveillance.
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