| 1. |
- Kjellander, Christian, et al.
(författare)
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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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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 88:5, s. 422-430
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Frontiers in Microbiology. - : FRONTIERS MEDIA SA. - 1664-302X. ; 10
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 44:9, s. 641-649
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: INTERNATIONAL JOURNAL OF MYCOBACTERIOLOGY. - : WOLTERS KLUWER MEDKNOW PUBLICATIONS. - 2212-5531 .- 2212-554X. ; 12:3, s. 211-225
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Forskningsöversikt (refereegranskat)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.
(författare)
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Mycoplasma pneumoniae infections, 11 countries in Europe and Israel, 2011 to 2016
- 2020
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Ingår i: Eurosurveillance. - : EUR CENTRE DIS PREVENTION & CONTROL. - 1025-496X .- 1560-7917. ; 25:2, s. 39-51
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Risk for Endocarditis in Bacteremia with Streptococcus-Like Bacteria : A Retrospective Population-Based Cohort Study
- 2019
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:10
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Journal of Controlled Release. - : ELSEVIER. - 0168-3659 .- 1873-4995. ; 361, s. 260-269
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Journal of Microbiological Methods. - : Elsevier BV. - 1872-8359 .- 0167-7012. ; 82:3, s. 229-233
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Dynamics of Resistance Plasmids in Extended-Spectrum-beta-Lactamase-Producing Enterobacteriaceae during Postinfection Colonization
- 2019
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 63:4
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Eurosurveillance. - 1025-496X .- 1560-7917. ; 24:20, s. 6-12
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Tidskriftsartikel (refereegranskat)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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| 11. |
- Davies Forsman, Lina, et al.
(författare)
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Minimum Inhibitory Concentrations of Fluoroquinolones and Pyrazinamide Susceptibility Correlate to Clinical Improvement in Multidrug-resistant Tuberculosis Patients: A Nationwide Swedish Cohort Study Over 2 Decades
- 2019
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Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 69:8, s. 1394-1402
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Tidskriftsartikel (refereegranskat)abstract
- Background. Minimum inhibitory concentration (MIC) testing, unlike routine drug susceptibility testing (DST) at a single critical concentration, quantifies drug resistance. The association of MICs and treatment outcome in multidrug-resistant (MDR)-tuberculosis patients is unclear. Therefore, we correlated MICs of first- and second-line tuberculosis drugs with time to sputum culture conversion (tSCC) and treatment outcome in MDR-tuberculosis patients. Methods. Clinical and demographic data of MDR-tuberculosis patients in Sweden, including DST results, were retrieved from medical records from 1992 to 2014. MIC determinations were performed retrospectively for the stored individual Mycobacterium tuberculosis (Mtb) isolates using broth microdilution in Middlebrook 7H9. We fitted Cox proportional hazard models correlating MICs, DST results, and clinical variables to tSCC and treatment outcome. Results. Successful treatment outcome was observed in 83.5% (132/158) of MDR-tuberculosis patients. Increasing MICs of fluoroquinolones, diabetes, and age amp;gt;40 years were significantly associated with unsuccessful treatment outcome. Patients treated with pyrazinamide (PZA) had a significantly shorter tSCC compared to patients who were not (median difference, 27 days). Conclusions. Increasing MICs of fluoroquinolones were correlated with unsuccessful treatment outcome in MDR-tuberculosis patients. Further studies, including MIC testing and clinical outcome data to define clinical Mtb breakpoints, are warranted. PZA treatment was associated with shorter tSCC, highlighting the importance of PZA DST.
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| 12. |
- Edlund, Charlotta, et al.
(författare)
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The clinical and microbiological efficacy of temocillin versus cefotaxime in adults with febrile urinary tract infection, and its effects on the intestinal microbiota : a randomised multicentre clinical trial in Sweden
- 2022
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Ingår i: The Lancet - Infectious diseases. - : Elsevier. - 1473-3099 .- 1474-4457. ; 22:3, s. 390-400
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Use of third-generation cephalosporins, such as cefotaxime, is associated with an increased risk of selection for antimicrobial resistance, so alternative antibiotics need to be considered. The aim of the present study was to evaluate intestinal colonisation with third-generation cephalosporin-resistant pathogens following use of temocillin-an alternative antibiotic to cefotaxime that is potentially less prone to disturbing the intestinal microbiota-in empirical treatment of febrile urinary tract infection (UTI).METHODS: We did a randomised, multicentre, superiority, open-label phase 4 trial in patients who had been admitted to inpatient care in 12 Swedish hospitals with suspected or diagnosed febrile UTI (complicated or uncomplicated). To meet inclusion criteria, a patient was required to have at least one sign or symptom of pyelonephritis (ie, flank pain; costovertebral angle tenderness; and changes to urinary frequency or urgency or dysuria), a fever of 38·0°C or higher, and a positive urine dipstick (for nitrites, white blood cells, or both). Participants were also required to have an indication for intravenous antibiotic treatment. Participants were randomly assigned (1:1) to receive either 2 g temocillin or 1-2 g cefotaxime, by local investigators opening consecutive sealed randomisation envelopes that were generated centrally in advance. Both drugs were administered intravenously every 8 h. The trial was open label for investigators and patients, but those doing the microbiological analyses were masked to the groups. Participants were treated with antibiotics for 7-10 days (or up to 14 days if they had bacteraemia), at least 3 days of which were on the study drug; at day 4 and later, participants who were showing improvement could be given an oral antibiotic (ciprofloxacin, ceftibuten, cefixime, or co-trimoxazole). Patients not showing improvement were regarded as having treatment failures. Rectal swabs were collected at three timepoints: at baseline (before the first dose), after the last dose of study drug, and 7-10 days after treatment stopped. The composite primary outcome was colonisation with Enterobacterales with reduced susceptibility to third-generation cephalosporins, or colonisation with toxin-producing Clostridioides difficile, or both, to evaluate disturbance of the intestinal microbiota. The study is registered in the EU Clinical Trials Register (EudraCT 2015-003898-15).FINDINGS: Between May 20, 2016, and July 31, 2019, 207 patients were screened for eligibility, of whom 55 patients were excluded. 152 participants were randomly assigned to groups: 77 (51%) patients received temocillin, 75 (49%) patients received cefotaxime. The composite primary endpoint was met by 18 (26%) of 68 participants receiving temocillin versus 30 (48%) of 62 patients receiving cefotaxime (risk difference -22% [95% CI -42% to -3%]), showing superiority of temocillin versus cefotaxime (ie, less disturbance of the intestinal microbiota). 43 adverse events were reported in 40 (52%) of 77 patients in the temocillin group, versus 46 adverse events in 34 (45%) of 75 patients in the cefotaxime group. Most events were of mild to moderate severity. 21 (27%) patients in the temocillin and 17 (23%) patients in the cefotaxime group had an adverse event that was considered to be associated with the study drug.INTERPRETATION: Temocillin was found to be less selective than cefotaxime of Enterobacterales with reduced susceptibility to third-generation cephalosporins, and it could therefore be a favourable alternative in the empirical treatment of febrile UTI. Use of this antibiotic could reduce hospital transmission and health-care-associated infections by these pathogens.
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| 13. |
- Eriksson, Harald, 1977-, et al.
(författare)
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A novel phage cocktail inhibiting the growth of 99 β-lactamase carrying Klebsiella pneumoniae clinical isolates in vitro
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Klebsiella pneumoniae is a gram-negative bacterial pathogen, accountable for a variety of nosocomial infections in immunocompromised patients, open-wound infections and community-acquired pneumonia in elderly. K. pneumoniae strains harboring plasmid-mediated extended spectrum β-lactamase enzymes (ESBL) are resistant to all penicillin and cephalosoprins, whereas bacteria capable of producing carbapenemase enzymes (e.g. NDM, KPC and VIM) are resistant to virtually all β-lactam group antibiotics. The use of bacterial viruses lysing bacterial hosts (phage therapy) has been suggested as an alternative in fighting bacterial infections resistant to known antibiotics. In this study, we assembled a phage cocktail consisting of 6 novel lytic bacteriophages infecting K. pneumoniae. The phage cocktail was tested against 125 β-lactamase producing clinical isolates of K. pneumoniae and we found that at high titres, the cocktail was able to lyse 99 of these isolates in vitro.
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| 14. |
- Erlandsson, Marcus, et al.
(författare)
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Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs
- 2008
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 40:6-7, s. 487-494
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Tidskriftsartikel (refereegranskat)abstract
- Pseudomonas aeruginosa is 1 of the bacteria most adaptive to anti-bacterial treatment. Previous studies have shown nosocomial spread and transmission of clonal strains of P. aeruginosa in European hospitals. In this study we investigated antibiotic susceptibility and clonality in 101 P. aeruginosa isolates from 88 patients admitted to 8 Swedish ICUs during 2002. We also compared phenotypes and genotypes of P. aeruginosa and carried out cluster analysis to determine if phenotypic data can be used for surveillance of clonal spread. All isolates were collected on clinical indication as part of the NPRS II study in Sweden and were subjected to AFLP analysis for genotyping. 68 isolates with unique genotypes were found. Phenotyping was performed using MIC values for 5 anti-pseudomonal agents. Almost 6% of the isolates were multi-drug resistant (MDR), and this figure rose to almost 8% when intermediate isolates were also included. We found probable clonal spread in 9 cases, but none of them was found to be an MDR strain. Phenotypical cluster analysis produced 40 clusters. Comparing partitions did not demonstrate any significant concordance between the typing methods. The conclusion of our study is that cross-transmission and clonal spread of MDR P. aeruginosa does not present a clinical problem in Swedish ICUs, but probable cross-transmission of non-MDR clones indicate a need for improved hygiene routines bedside. The phenotype clusters were not concordant with genotype clusters, and genotyping is still recommended for epidemiological tracking.
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| 15. |
- Farzana, Refath, et al.
(författare)
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Molecular and genetic characterization of emerging carbapenemase-producing Acinetobacter baumannii strains from patients and hospital environments in Bangladesh
- 2022
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Ingår i: Infection Prevention in Practice. - : Elsevier. - 2590-0889. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carbapenemase-producing multidrug-resistant (MDR) Acinetobacter bau-mannii is a global health care problem. MDR A. baumannii has emerged as an important nosocomial pathogen, costing many lives worldwide including Bangladesh.Aim: To investigate the detailed molecular epidemiology of carbapenem-resistant A. baumannii (CRAB) both from patients and the hospital environment, to shed light on genetic characteristics and transmission dynamics.Methods: A set of 49 clinical A. baumannii strains collected during early 2015 was received from the clinical microbiology laboratory of Dhaka Medical College Hospital (DMCH) in Bangladesh. Additionaly, 100 environmental samples were also collected from the hospital surfaces of Dhaka Medical College Hospital and analyzed for carbapenamase-producing A. baumannii. CRAB were identified by culture on selective plates, biochemical testing and MALDI-TOF. All isolates were characterized by susceptibility testing, realtime-PCRs, conventional PCR, MLST and sequencing.Findings: Clinical A. baumannii were resistant to ciprofloxacin (100%), imipenem (91.8%), meropenem (91.8%), gentamicin (91.8%), amikacin (87.7%), and trimethoprim-sulfamethoxazole (61.2%). The majority (59%) of the isolates were MDR. All environ-mental A. baumannii (n1/410) were resistant to imipenem, meropenem, gentamicin, ami-kacin, and ciprofloxacin. Strains carried the following antibiotic resistant genes; blaOXA-23, blaOXA-58, blaPER-7, qnrB1, qnrC1, aac(60)1b-cr and armA. A total of 36 different clones were identified by rep-PCR and common clonal clusters were found both in patients and hospital environments. MLST analysis revealed different sequence types (ST2, ST10, ST149, ST575, ST1063 and ST1065). In clinical and environmental settings. A. baumannii ST2 dominated in both clinical and environmental settings. Both clinical and environmental A. baumannii strains with known STs carried several biofilm-related genes; bap, csuE, and pgaB. Conclusion: Widespread dissemination of MDR A. baumannii in the DMC hospital of Ban-gladesh is a serious problem.
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| 16. |
- Froberg, Gabrielle, et al.
(författare)
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Towards clinical breakpoints for non-tuberculous mycobacteria-Determination of epidemiological cut off values for the Mycobacterium avium complex and Mycobacterium abscessus using broth microdilution
- 2023
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Ingår i: Clinical Microbiology and Infection. - : ELSEVIER SCI LTD. - 1198-743X .- 1469-0691. ; 29:6, s. 758-764
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Tidskriftsartikel (refereegranskat)abstract
- Objective: For non-tuberculous mycobacteria (NTM), minimum inhibitory concentration (MIC) distri-butions of wild-type isolates have not been systematically evaluated despite their importance for establishing antimicrobial susceptibility testing (AST) breakpoints.Methods: We gathered MIC distributions for drugs used against the Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) obtained by commercial broth microdilution (SLOMYCOI and RAPMYCOI) from 12 laboratories. Epidemiological cut-off values (ECOFFs) and tentative ECOFFs (TEC-OFFs) were determined by EUCAST methodology including quality control (QC) strains.Results: The clarithromycin ECOFF was 16 mg/L for M. avium (n = 1271) whereas TECOFFs were 8 mg/L for M. intracellulare (n = 415) and 1 mg/L for MAB (n = 1014) confirmed by analysing MAB subspecies without inducible macrolide resistance (n = 235). For amikacin, the ECOFFs were 64 mg/L for MAC and MAB. For moxifloxacin, the WT spanned >8 mg/L for both MAC and MAB. For linezolid, the ECOFF and TECOFF were 64 mg/L for M. avium and M. intracellulare, respectively. Current CLSI breakpoints for amikacin (16 mg/L), moxifloxacin (1 mg/L) and linezolid (8 mg/L) divided the corresponding WT dis-tributions. For QC M. avium and M. peregrinum, >= 95% of MIC values were well within recommended QC ranges.Conclusion: As a first step towards clinical breakpoints for NTM, (T)ECOFFs were defined for several antimicrobials against MAC and MAB. Broad wild-type MIC distributions indicate a need for further method refinement which is now under development within the EUCAST subcommittee for anti-mycobacterial drug susceptibility testing. In addition, we showed that several CLSI NTM breakpoints are not consistent in relation to the (T)ECOFFs. Gabrielle Froeuroberg, Clin Microbiol Infect 2023;29:758 (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
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| 17. |
- Froding, Inga, et al.
(författare)
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Extended-Spectrum-beta-Lactamase- and Plasmid AmpC-Producing Escherichia coli Causing Community-Onset Bloodstream Infection : Association of Bacterial Clones and Virulence Genes with Septic Shock, Source of Infection, and Recurrence
- 2020
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 64:8
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Tidskriftsartikel (refereegranskat)abstract
- Invasive infections due to extended-spectrum-beta-lactamase- and pAmpC-producing Escherichia coli (ESBL/pAmpC-EC) are an important cause of morbidity, often caused by the high-risk clone sequence type (ST131) and isolates classified as extraintestinal pathogenic E. coli (ExPEC). The relative influence of host immunocompetence versus microbiological virulence factors in the acquisition and outcome of bloodstream infections (BSI) is poorly understood. Herein, we used whole-genome sequencing on 278 blood culture isolates of ESBL/pAmpC-EC from 260 patients with community-onset BSI collected from 2012 to 2015 in Stockholm to study the association of virulence genes, sequence types, and antimicrobial resistance with severity of disease, infection source, ESBL/pAmpC-EC BSI low-risk patients, and patients with repeated episodes. ST131 subclade C2 comprised 29% of all patients. Factors associated with septic shock in multivariable analysis were patient host factors (hematologic cancer or transplantation and reduced daily living activity), presence of the E. coli virulence factor iss (increased serum survival), absence of phenotypic multidrug resistance, and absence of the genes pap and hsp. Adhesins, particularly pap, were associated with urinary tract infection (UTI) source, while isolates from post-prostate biopsy sepsis had a low overall number of virulence operons, including adhesins, and commonly belonged to ST131 clades A, B, and subclade C1, ST1193, and ST648. ST131 was associated with recurrent episodes. In conclusion, the most interesting finding is the association of iss with septic shock. Adhesins are important for UTI pathogenesis, while otherwise low-pathogenic isolates from the microbiota can cause post-prostate biopsy sepsis.
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| 18. |
- Giske, Christian
(författare)
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Carbapenem resistance in Pseudomonas aeruginosa
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Carbapenem (imipenem and meropenem) resistance in Pseudomonas aeruginosa is increasing, with global resistance rates approaching 20%. The most common resistance mechanisms are down-regulation of the porin OprD, and increased activity of multi-drug efflux pumps, primarily MexAB-OprM. Down-regulation of OprD, which is the primary porin for carbapenem uptake, confers resistance to both imipenem and meropenem, although the latter is affected less. Only meropenem is a substrate for the efflux pumps, due to the absence of a heterophilic side chain in the chemical structure of imipenem. Apart from alterations of OprD and the efflux pumps, changes of penicillin-binding proteins have been suggested as a third chromosomal mechanism of carbapenem resistance. Transferable carbapenemases, conferring resistance to all â-lactams except aztreonam, have emerged during the last decade, and consist of five groups of enzymes, namely IMP, VIM, SPM, GIM and SIM. These enzymes are designated metallo-â-lactamases (MBL) due to their dependency of zinc for â-lactam hydrolysis. The genes encoding the MBLs are usually found on integrons, often embedded in functional transposons. The aim of this thesis was to study chromosomal and transferable carbapenemresistance in clinical isolates of P. aeruginosa. Totally 67 isolates with variable levels of carbapenem resistance were characterized regarding transcription of the chromosomal genes encoding OprD, and the efflux pumps MexAB-OprM, MexXY, MexCD-OprJ and MexEFOprN. Transcription of the genes encoding penicillin-binding 2 and 3 (PBP-2 and -3) was studied in some of the isolates. Quantitative reverse transcriptase PCR (qRT-PCR) was used for the quantification of mRNA for the respective resistance genes. A phenotypic efflux inhibition assay was also employed, using the inhibitor Phe-Arg-â-naphtylamide (40 mg/L). DNA sequencing of oprD, pbp-2, pbp-3 and some of the efflux pump regulatory genes was conducted in selected isolates. Transferable carbapenem-resistance was studied in 11 isolates producing MBLs belonging to the VIM-lineage, derived from four European countries. Isolates were characterized by serotyping, pulsed-field gel electrophoresis (PFGE), random amplification of polymorphic DNA (RAPD), multilocus sequence typing (MLST) and integron sequencing. Studies of isolates with decreased susceptibility to imipenem, and retained meropenem susceptibility, confirmed that down-regulation of oprD was the primary mechanism of resistance, although this was not found in all of the isolates. In isolates intermediately susceptible to meropenem and with variable susceptibility to imipenem, we found phenotypic or genotypic evidence of efflux in 5/8 isolates. These isolates are reported as susceptible according to some of the international breakpoint groups, but are regarded intermediately susceptible according to the Swedish Reference Group for Antibiotics (SRGA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). In isolates with decreased susceptibility to both carbapenems, we found evidence of concomitant downregulation of oprD and up-regulation of mexB in many of the isolates. In five isolates we found evidence of down-regulation of either pbp-2 or pbp-3, although the relative importance of this finding was difficult to ascertain. Studies of transferable carbapenem resistance showed that the serotype O11 isolates from Italy and Greece belonged to the same clonal complex, according to MLST. Also, serotype O12 isolates from Greece harboring genes encoding different VIM-variants were found to belong to the same sequence type. PFGE and RAPD did not cluster all isolates that were found to belong to the same clonal complex according to MLST, and the latter is therefore probably best suited for studies of international epidemiology.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Goyal, Gaurav, 1983, et al.
(författare)
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A simple cut and stretch assay to detect antimicrobial resistance genes on bacterial plasmids by single-molecule fluorescence microscopy
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a fast-growing threat to global health. The genes conferring AMR to bacteria are often located on plasmids, circular extrachromosomal DNA molecules that can be transferred between bacterial strains and species. Therefore, effective methods to characterize bacterial plasmids and detect the presence of resistance genes can assist in managing AMR, for example, during outbreaks in hospitals. However, existing methods for plasmid analysis either provide limited information or are expensive and challenging to implement in low-resource settings. Herein, we present a simple assay based on CRISPR/Cas9 excision and DNA combing to detect antimicrobial resistance genes on bacterial plasmids. Cas9 recognizes the gene of interest and makes a double-stranded DNA cut, causing the circular plasmid to linearize. The change in plasmid configuration from circular to linear, and hence the presence of the AMR gene, is detected by stretching the plasmids on a glass surface and visualizing by fluorescence microscopy. This single-molecule imaging based assay is inexpensive, fast, and in addition to detecting the presence of AMR genes, it provides detailed information on the number and size of plasmids in the sample. We demonstrate the detection of several beta-lactamase-encoding genes on plasmids isolated from clinical samples. Furthermore, we demonstrate that the assay can be performed using standard microbiology and clinical laboratory equipment, making it suitable for low-resource settings.
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| 23. |
- Goyal, Gaurav, 1983, et al.
(författare)
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CRISPR/CAS9 BASED DNA-COMBING ASSAY FOR DETECTING ANTIMICROBIAL RESISTANCE GENES ON PLASMIDS
- 2021
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Ingår i: MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. ; , s. 801-802
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Konferensbidrag (refereegranskat)abstract
- We present a method based on CRISPR/Cas9 excision and DNA combing to detect anti-microbial resistance (AMR) genes on bacterial plasmids. The assay is inexpensive, simple, fast, and also provides information on the number and size of plasmids in a sample. We demonstrate detection of the gene encoding for the New Delhi metallobeta-lactamase 1 (blaNDM-1) enzyme, known to make bacteria resistant to a broad range of beta-lactam antibiotics.
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| 24. |
- Hammar, Katarina Stenberg, et al.
(författare)
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Subnormal levels of vitamin D are associated with acute wheeze in young children
- 2014
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:8, s. 856-861
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study evaluated risk factors for acute wheeze in preschool children and investigated whether subnormal levels of vitamin D were associated with increased risk for acute wheeze, atopy or viral/bacterial respiratory infections. Methods: We recruited 130 children with acute wheeze, aged 6 months to 4 years, from paediatric emergency departments in Stockholm, Sweden, and 101 age-matched controls with no history of wheeze or sensitisation to airborne allergens. Parents answered standardised questionnaires, and blood samples were analysed for specific IgE to airborne and food allergens and levels of 25 hydroxyvitamin D (25(OH)D). Nasopharyngeal virus samples were collected during the emergency department visit in the group of children with wheeze, and a subset were also tested for bacteria. Results: Vitamin D insufficiency (25(OH)D < 75 nmol/L (30 ng/mL)) was associated with an odds ratio of 2.7 (95% confidence interval 1.1-6.2) for acute wheeze. However, no association was found between vitamin D insufficiency and atopy, presence of virus or bacteria or recurrent infections. Children older than 24 months were particularly at risk of subnormal vitamin D levels, irrespective of wheezing history. Conclusion: Our findings support the hypothesis that subnormal levels of vitamin D are associated with acute wheeze in young children.
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| 25. |
- Hanberger, Håkan, et al.
(författare)
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Antibiotic consumption and antibiotic stewardship in Swedish hospitals
- 2014
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Ingår i: Upsala Journal of Medical Sciences. - : Informa Healthcare / Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 119:2, s. 154-161
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Forskningsöversikt (refereegranskat)abstract
- Background. The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. Results. The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e. g. bloodstream infections and hospital-acquired pneumonia-data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Conclusions. Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels.
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