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- Montelin, Hanna, 1984-, et al.
(författare)
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Treatment, outcomes and characterization of pathogens in urinary tract infections caused by ESBL-producing Enterobacterales : a prospective multicentre study
- 2024
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Treatment options for urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales are limited. Moreover, evidence to support therapeutic decisions is lacking. This study assessed current treatment strategies and patient and pathogen characteristics in relation to clinical and microbiological outcomes.Methods: Patients with UTI caused by ESBL-producing Enterobacterales were prospectively recruited by investigators at 15 infectious disease hospital departments. Data were collected on patient characteristics, treatments, clinical and microbiological cure 10–14 days after the end of treatment, and relapse within 3 months. Bacterial isolates were subjected to MIC determination and WGS.Results: In total, 235 patients (107 febrile UTI, 128 lower UTI) caused by Escherichia coli (n = 223) and Klebsiella spp. (n = 12) were included. Clinical and microbiological cure rates were 83% and 64% in febrile UTI, and 79% and 65% in lower UTI. Great variability in treatments was observed, especially in oral therapy for febrile UTI. No difference was seen in clinical outcomes with piperacillin/tazobactam (n = 28) compared with carbapenems (n = 41). Pivmecillinam was frequently used in lower UTI (n = 62), and was also associated with high clinical cure rates when used as initial therapy (10/10) or follow-up (7/8) for febrile UTI. Recurrent infection, diabetes mellitus and urogenital disease were associated (P < 0.05) with clinical failure and relapse. In E. coli, ST131 was significantly associated with relapse, and haemolysin with microbiological failure or relapse.Conclusions: Antibiotic treatments were highly variable. Patient and pathogen factors were identified as potential determinants of disease presentation and outcomes and may prove useful to guide individualized treatment and follow-up.
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| 2. |
- Vading, Malin
(författare)
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Klebsiella pneumoniae and Escherichia coli : multidrug-resistance and different aspects of invasive infections
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Klebsiella pneumoniae and Escherichia coli are pathogens belonging to the Enterobacteriaceae family. They can cause infections ranging from uncomplicated urinary tract infection to severe bloodstream infection (BSI). The prevalence of extended spectrum β- lactamase-producing Enterobacteriaceae (EPE) is increasing worldwide and carbapenemases (CPE), a subgroup of EPE where antibiotic treatment is very limited, is a major threat to patients.The aims of this thesis were to get expanded molecular and epidemiological knowledge about K. pneumoniae, its association to morbidity and mortality in BSI (II, III), to increase sensitivity in detection of carbapenemase-producers (I), to determine risk to acquire fecal colonization with EPE during traveling, and to characterize colonizing EPE in terms of virulence factors and phylogroups (IV). In paper I methods for antimicrobial susceptibility testing were evaluated for detection of K. pneumoniae carbapenemase (KPC)- and Verona integron-encoded metallo-- lactamase (VIM)-producing K. pneumoniae in order to define appropriate screening breakpoints. Strains (n=51) were tested against different carbapenems using disk diffusion, gradient test, and automated susceptibility testing. Results were interpreted with the European (EUCAST) and American (CLSI) antimicrobial susceptibility testing breakpoints. We found that clinical breakpoints cannot be used for carbapenemase screening. Meropenem was the most suited carbapenem to use for screening purposes. A breakpoint of 0.5 mg/L detected all isolates with an at the same time good separation from the wild type population. In paper II and III a cohort of patients with BSI caused by K. pneumoniae was evaluated retrospectively and compared with BSI caused by E. coli. Data on risk factors, prognostic factors and mortality was retrieved from 1251 medical charts (III). The late mortality (within 90 days) was significantly higher among patients with BSI caused by K. pneumoniae and could be explained by higher comorbidity. Contrary to European trends our study showed low antibiotic resistance among K. pneumoniae isolates supporting the hypothesis of absence of successful multidrug-resistant K. pneumoniae clones in the Stockholm area. For a subset of the patients (n=139) molecular analysis was performed on the K. pneumoniae isolates (II). Based on multilocus sequence typing, the isolates could be separated in three phylogenetic clades: KpI (n=96), KpII (n=9) and KpIII, also known as K. variicola (n=34). Patients infected with strains belonging to K. variicola had higher 30 days mortality (29.4 %), also when adjusting for age and comorbidity (OR for KpIII = 3.0 (95% CI: 1.1-8.4) compared to KpI). Only three of the isolates causing mortality within 30 days belonged to any of the virulent serotypes, had a mucoid phenotype, or harbored virulence genes. Hence, the increased mortality could not be related to any known strain factor. In general, a high level of comorbidity was observed in the K. pneumoniae cohort. Paper IV was a prospective study. Fecal samples and survey data were collected from 188 Swedes traveling to four regions of high EPE prevalence, and molecular characterization was performed on EPE. Colonization incidence varied by visited region; the Indian subcontinent 49%, northern Africa 44%, Southeast Asia 19% and Turkey 10%. Few strains harbored virulence factors connected to uropathogenicity, and most E. coli strains belonged to phylogroup A, rarely associated with extraintestinal infections. No clinical infections were seen in follow-up. No CPE was found, but one strain contained the plasmid- mediated colistin resistance gene, mcr-1. Independent risk factors for EPE acquisition were travelers ́ diarrhea and use of antibiotics during travel. EPE acquired during travel have seemingly low pathogenicity as indicated by the low frequency of virulence factors and phylogroups associated with extraintestinal infections. In summary this thesis provides new knowledge about K. pneumoniae BSI in a clinical and a molecular perspective. It also adds to the knowledge about molecular features of EPE colonizing the intestine, and appropriate breakpoints to use in detection of CPE.
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| 3. |
- Wiklund, Susanne, et al.
(författare)
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Knowledge and understanding of antibiotic resistance and the risk of becoming a carrier when travelling abroad : A qualitative study of Swedish travelers
- 2015
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 43:3, s. 302-308
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increasing globalisation, with the migration of people, animals and food across national borders increases the risk of the spread of antibiotic-resistant bacteria. To avoid becoming a carrier of antibiotic-resistant bacteria when travelling, knowledge about antibiotic resistance is important.MATERIALS AND METHODS: We aimed to describe the knowledge and understanding of antibiotic-resistant bacteria, and of the risk for becoming a carrier of such bacteria, among Swedish travellers before their travel to high-risk areas. A questionnaire with three open-ended questions was distributed to 100 individuals before departure.RESULTS: The travellers' answers were analysed using content analysis, resulting in the theme 'To be an insecure traveller who takes control over one's own journey'. Our results showed that the travellers were aware of what the term 'antimicrobial resistance' meant, but did not understand its real significance, nor the consequences for the individual nor for society. They also distanced themselves from the problem. Few thought that their travel would entail a risk of becoming a carrier of resistant bacteria. The lack of knowledge caused an uncertainty among the travellers, whom tried to master the situation by using coping strategies. They proposed a number of measures to prevent carriership. The measures were general and primarily aimed at avoiding illness abroad, particularly acute gastro-intestinal infection.CONCLUSIONS: In health care and vaccination clinics, there is a need for improved information for persons intending to travel to high-risk areas, both about the risks of contracting antibiotic-resistant bacteria and about effective preventive measures.
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