| 1. |
- Östholm Balkhed, Åse, 1972-
(författare)
-
Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae : Antibiotic consumption, Detection and Resistance Epidemiology
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ESBL-producing Enterobacteriaceae are emerging worldwide and they are frequently multi-drug resistant, thus limiting treatment options for infections caused by these pathogens.The overall aim of the thesis was to investigate ESBL-producing Enterobacteriaceae in a Swedish county.First, we developed a molecular method, a multiplex PCR assay for identification of SHV, TEM and CTX-M genes in clinical isolates of Enterobacteriaceae with an ESBL phenotype.From 2002 until the end of 2007 all isolates of ESBL-producing Enterobacteriaceae in Östergötland, Sweden were further investigated. The prevalence of ESBL-producing Enterobacteriaceae was low, <1%, but increasing,while the antibiotic consumption remained unchanged. CTX-M enzymes, particularly CTX-M group 1, dominate in our region as well as in the rest of Europe.Furthermore, we have investigated antimicrobial susceptibility by performing MIC-testing in a large, well-characterized population of CTX-M-producing E. coli. Only three oral antimicrobial agents (fosfomycin, nitrofurantoin and mecillinam) demonstrated susceptibility above 90%. High susceptibility, >90%, was also demonstrated for carbapenems, colistin, tigecycline and amikacin. Sixty-eight per cent of ESBL-producing E. coli was multi-resistant, and the most common multi-resistance pattern was the ESBL phenotype with decreased susceptibility to trimethoprim, trimethoprim-sulfamethoxazole, ciprofloxacin, gentamicin and tobramycin. Isolates belonging to CTX-M group 9 are generally more susceptible to antibiotics than the CTX-M group 1-producing E. coli. Finally, a prospective multicentre case-control study examined the prevalence of ESBL-producing Enterobacteriaceae in faecal samples before and after travel abroad and the risk factors of acquisition. Sixty-eight of 226 travellers (30%) had ESBL-producing Enterobacteriaceae in the faecal flora. The geographical area visited had the highest impact on acquisition, with highest the risk for travellers visiting the Indian subcontinent, followed by Asia and Africa north of the equator. Also, acquisition of ESBL-producing Enterobacteriaceae during travel is associated with abdominal symptoms such as diarrhoea. Age also seemed to affect the risk of acquiring ESBL-producing Enterobacteriaceae, the highest risks were found among travellers ≥ 65 years.This thesis has contributed to increased understanding of the epidemiology of ESBL-producing Enterobacteriaceae and their susceptibility to both beta-lactam and non-beta-lactam agents.
|
|
| 2. |
- Claesson, Carina, 1970-
(författare)
-
Staphylococci and Enterococci : Studies on activity of antimicrobial agents and detection of genes involved in biofilm formation
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Gram-positive cocci, Staphylococcus aureus, coagulase negative staphylococci (CoNS), Enterococcus faecalis and Enterococcus faecium, are the bacteria most often isolated from patients with hospital acquired infections. S. aureus is one of the most important pathogens and have a variety of virulence mechanisms which help it to infect the patient and cause tissue damage. CoNS and enterococci are low virulent bacteria and predominantly cause infections in individuals with underlying illness, individuals that have undergone surgery or with suppressed immune-system. The aims of this thesis were i) to investigate the susceptibility to different antimicrobial agents among S. aureus, CoNS, E. faecium and E. faecalis isolates from primary care centres, general hospital wards and intensive care units in Denmark, Finland, Norway and Sweden and ii) to study the prevalence of the cytolysin genes and genes involved in biofilm formation among CoNS, E. faecium and E. faecalis. The results in this thesis show that the resistance rates among S. aureus and E. faecalis is still rather low in the north European countries. Among CoNS and E. faecium resistance rates are higher and comparable with rates in other European countries and US. CoNS had statistically significant differences in susceptibility rates between the ward levels with the lower susceptibility rates found at ICUs. Continued surveillance of resistance rates to antimicrobial agents among both staphylococci and enterococci are important internationally, nationally and locally. The results in this thesis also show that all multidrug resistant and 96% of the susceptible CoNS isolates carried at least one of the atlE and aap genes or the ica operon. Among E. faecalis isolates with HLGR, belonging to a cluster of genetically related isolates, both the esp and asa1 genes were carried in a high degree while the cyl operon was less frequently found. In addition, about 30% of unique E. faecalis isolates carried two or more of the virulence genes. Among E. faecium isolates the esp gene was common but asa1 and the cyl operon was not found in any of the isolates. Both CoNS and E. faecalis isolates from hospitalised patients are well equipped with genes involved in biofilm formation. These genes, when expressed and even more in combination with resistance to antimicrobial agents, might give these isolates an advantage compared to other isolates when it comes to adhesion to artificial surfaces, persistence in the hospital environment, colonisation of hospitalised patients and to cause nosocomial infections. Further studies are needed to be able to determine which isolates that causes hospital acquired infections and to evaluate the importance of the genes involved in biofilm formation as virulence factors and about how to prevent biofilm related infections from emerging
|
|
| 3. |
- Tärnberg, Maria, 1976-
(författare)
-
Extended-spectrum beta-lactamase producing Enterobacteriaceae : aspects on detection, epidemiology and multi-drug resistance
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Beta-lactam antibiotics are the largest and most commonly used group of antimicrobial agents in Sweden as well as world-wide. They show very good tolerability and many of the drugs can be administrated orally. Bacteria expressing extended-spectrum beta-lactamases (ESBLs), enzymes hydrolysing penicillins and cephalosporins, may not respond to therapy using some of these antibiotics. The isolates are also often co-resistant to other antimicrobial agents, thus further limiting treatment options. Often parenterally administrated carbapenems is one of few safe treatment options left.In this thesis we have investigated the occurrence of ESBL producing Enterobacteriaceae in clinical isolates from Östergötland, Sweden, from 2002 until end of 2007 and the occurrence of multiresistance among ESBL producing E. coli. During these investigations we developed a simple method well suited for high-throughput analysis, for detection and sub typing of common ESBL genes.During the six year period, the prevalence of ESBL producing Enterobacteriaceae in Östergötland was very low, <1%, but increasing. The number of patients with ESBL producing E. coli increased significantly from 5 to 47 per year; K. pneumoniae remained between one and four per year. The genes found were dominated by CTX-M group 1 (67%), followed by group 9 (27%). There has been no reason to suspect an outbreak of nosocomial origin. The total consumption of antimicrobial agents was 10.7-12.1 DID per year in primary care; 1.14-1.30 DID per year in hospital care.Of eight oral agents tested, only three showed a generally high susceptibility; mecillinam (91%), nitrofurantoin (96%) and fosfomycin (99%). The corresponding figures for the fifteen tested parenterally administrated drugs were; amikacin (96%), tigecycline (99%), colistin (99%) and ≥99% susceptibility for the carbapenems.Sixty eight percent of the isolates were multiresistant. The most common multiresistance pattern was ESBL phenotype with decreased susceptibility to trimethoprim, trimethoprimsulfamethoxazole, ciprofloxacin, gentamicin and tobramycin. A significant difference in susceptibility between CTX-M groups, in favor of group 9 over group 1, was seen for many of the antibiotics tested; amoxicillin-clavulanic acid, aztreonam, cafepime, ceftibuten, ceftazidime, ciprofloxacin, gentamicin, piperacillin-tazobactam, temocillin, and tobramycin.In conclusion this thesis shows that the prevalence of ESBL producing Enterobacteriaceae in Östergötland was very low but increasing, and the total consumption of antimicrobial agents was stable. A majority of the isolates were multiresistant and a significant difference in susceptibility between CTX-M groups, in favor of group 9 over group 1, was seen for many of the antimicrobial agents tested.
|
|
| 4. |
- Storm, Martin, 1975-
(författare)
-
Identification and Characterization of Biomarkers in Bacterial Infections
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent years molecular biology has become an integral part of the clinical laboratory. With an ever increasing number of methodologies and applications being presented each year it has increased our knowledge of how bacteria cause disease as well as our ability to predict disease outcome. The main focus of this thesis has been to develop methods for identifying biomarkers and prediction methods for bacterial infectious diseases by taking advantage of the ever increasing possibilities of molecular biology. We applied cutting edge techniques in order to establish novel platforms for identifying and characterizing biomarkers of disease. In paper one we describe a novel approach to measure levels of antibiotic resistance and viability of C. trachomatis, a method that is a clear improvement over existing techniques. In the second paper we describe the development of two assays designed to type pertussis toxin subunit 1 in circulating strains, in order to facilitate multi center studies for vaccine escape surveillance. In paper three we develop a novel microarray application designed to identify a large number of bacterial traits of H. pylori simultaneously with human genetic polymorphisms in order to identify a collection of risk factors that could be used as a prediction tool for gastric cancer risk. In the last paper we define the “antigenome” of H. pylori and identified 14 promising, previously unreported antigens as well as a number of potential biomarkers.The platform technologies described in this collection of papers will hopefully help us identifying novel ways of fighting and predicting bacterial disease in future studies.
|
|
