| 1. |
- Holmbom, Martin, 1984-
(författare)
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Clinical Impact of Bloodstream Infections – Characterization, Risk factors and Outcome
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bloodstream infection (blood poisoning) and antibiotic resistance are increasing worldwide, and already cause the loss of millions of human lives each year. According to the World Health Organisation (WHO), bloodstream infections (BSIs) represent 20% of global mortality on a par with cardiac infarct, stroke, and major trauma. BSI may occur when bacteria from a focus of infection gain access to the circulation (bacteraemia). BSIs are usually divided into two subclasses: community- and hospital-onset infections, since disease this involves different patient groups, types of bacteria, and reasons for infection. Compared to other countries, Sweden has been fortunate in having a relatively low death rate from BSI and low antibiotic resistance. However, as our lifestyle changes, the age of the population increases with more disease as a result, and as the healthcare system responds, death from infection and antibiotic resistance are on the increase. It is important that we recognise ”warning symptoms” if we are to manage BSIs correctly and initiate effective treatment. It is difficult to design individualised empirical treatment, so it is very important to be aware of risk factors for BSI and local resistance patterns, and to have an effective management programme. Bacterial resistance to antibiotics is an increasing problem, especially in bowel organisms that can cause infections that are very difficult to treat. In short, antibiotic resistance arises as a result of evolutionary processes where bacteria protect themselves by developing resistance genes. These genes can be exchanged between similar organisms or transmitted to others that in turn cause resistant infection. The use of antibiotics leads to an evolutionary/selection process leading to resistance in bacteria, both normal and pathogenic, enabling resistant organisms to survive, thrive, and go on to cause infection. Antibiotic resistance is a threat to global health. This thesis aims to increase our awareness of a large group of patients who suffer bloodstream infection. BSIs are increasing globally, and the death toll is high. Antibiotic resistance is an increasing threat to the health of the population, and we are inundated by alarming reports of resistance getting out of control. What is the situation in Sweden, and can we identify risk factors for BSI and mortality? In Study I, our aim was to study the incidence and mortality of BSI in Östergötland. To be able to do this, a large patient population stretching over several years was required. The study design was thus population-based in the form of an observational cohort study where all blood culture results from 2000 to 2013 were analysed, and evaluated from clinical data. A total of 109,938 results were analysed resulting in 11,480 BSIs. We saw that the incidence of BSI increased by 64% (mostly community-onset BSIs). We also saw that mortality increased by 45%. These results illustrate the importance of nationwide cooperation to combat the increasing problem of BSI and its mortality, and the establishment of a nationwide BSI register. The aim of Study II was to assess resistance development in Östergötland and its relationship to mortality. A total of 9,587 microorganisms were analysed between 2008 and 2016. We observed an increase in quinolone resistance (3.7-7.7%) and cephalosporin resistance (2.5-5.2%) amongst Enterobacteriaceae. We then looked at BSIs caused by multiresistant bacteria showing a total of 245 cases (2.6%); an increase of 300%. Despite this, we did not see an increased mortality in this group. There are several possible explanations for the increase in BSI mortality of which antibiotic resistance is a predominant factor globally. We were unable to show this in our study, even so mortality is increasing and is currently at a high level. In Study III we therefore analysed risk factors associated with death during a community-acquired BSI, focusing on preliminary prehospital and hospital management. In a retrospective case-control study on 195 deaths matched 1:1 regarding age, gender, and microorganism, with 195 survivors (controls). Results showed that many patients had contacted the primary healthcare system because of infection before they became severely ill, and that the strongest affectable risk factor for death was delay (>24h) between primary healthcare visit and admission to hospital. This shows the need for increased awareness in society and amongst the medical profession of those patients at risk and symptoms that should raise the alarm, leading to more rapid treatment. In Studies I and II we found an increase in both BSIs and mortality, we also saw an increase in antibiotic resistance and multiresistant bacteria, mainly ESBL-producing E. coli. On the other hand, we did not see any coupling between multiresistance and mortality in this Swedish population. E. coli is a gram-negative bacteria that causes most BSIs. Since E. coli is predominantly a urine tract pathogen, Study IV aimed to study BSIs caused by ESBL-producing E. coli originating from the urinary tract. We studied the prevalence of E. coli clones, resistance genes and risk factors, as well as any signs of increased mortality from ESBL-producing E. coli compared to sensitive E. coli. Our main finding was a surprisingly low mortality from ESBL-producing E. coli (3%). Most patients in the ESBL-producing E. coli group received inadequate antibiotic treatment for at least 48h, but we did not see any sign of increased mortality or risk for serious sepsis with circulatory failure in this group. This finding is interesting and opens up for new studies on virulence factors and immunological factors that govern the immune response to BSI. The implementation of cost-effective monitoring systems including clinical microbiological epidemiology and early identification of BSI, together with information campaigns aimed at the public as well as healthcare personnel regarding patients at risk and symptoms giving cause for alarm, should lead to a radical reduction in morbidity and mortality from BSI. This requires new diagnostic tools to individualise both antibiotic treatment and targeted management based on microorganism virulence factors. Modernisation of the medical journal system with algorithms aimed at early identification of risk patients and automated suggestions for empirical antibiotic treatment based on antibiotic resistance seen in previous cultures and local resistance patterns, would certainly improve management. Furthermore, new immunological tests showing the type of immunological reaction to a serious BSI will lead to individualised immunotherapy that, together with antibiotic treatment, will further improve patient care in this important group.
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| 2. |
- Östholm Balkhed, Åse, 1972-
(författare)
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Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae : Antibiotic consumption, Detection and Resistance Epidemiology
- 2014
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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.
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| 3. |
- Claesson, Carina, 1970-
(författare)
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Staphylococci and Enterococci : Studies on activity of antimicrobial agents and detection of genes involved in biofilm formation
- 2010
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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
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| 4. |
- Tärnberg, Maria, 1976-
(författare)
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Extended-spectrum beta-lactamase producing Enterobacteriaceae : aspects on detection, epidemiology and multi-drug resistance
- 2012
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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.
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| 5. |
- Hammarskjöld, Fredrik, 1966-
(författare)
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Preventing Infections Related to Central Venous and Arterial Catheters
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Central venous catheters (CVCs) are indispensable in modern medical practice. Serious complications associated with CVC use include catheter-related infection (CRI) and catheter related-bloodstream infection (CRBSI) both of which contribute to morbidity, mortality and healthcare costs. Several studies have shown that implementation of basic hygiene routines, for CVC insertion and care, can significantly reduce the number of CRBSIs. However, there are limited data on the long-term effects after such an intervention. CVC infections, in terms of incidences and microorganisms, vary between different units and countries. Studies from Scandinavian hospitals are rare and not published recently. It has been stated that arterial catheters (ACs) are less prone to be responsible for CRI and CRBSI when compared with CVCs. However, recent studies outside Scandinavia have shown that they cause infections in significant numbers. The general view has been that nosocomial Candida infections in ICU patients evolve from the patient’s endogenous flora. However, a few studies have indicated that transmission of Candida spp. can occur between patients on an ICU as is well-described for certain bacteria. Candida spp. are among the most common microorganisms responsible for CRI/CRBSI.The aim of this thesis was to study the incidences of, and microorganisms related to CVC (Study 1) and AC (Study 2) infections after implementation of evidence-based routines for insertion and care. The populations studied were patients with CVCs treated throughout the entire hospital (Studies 1 and 4) and patients with ACs treated on the ICU (Study 2). The aim was further to analyse risk factors contributing to these infections (Studies 1, 2 and 4). We also evaluated the long-term effects and endurance, of evidence-based routines, assessed as temporal variations in CVC colonisation and infections over a six-year period (Study 4). As we found that Candida spp. were common causes of CRI/CRBSI in Study 1, we decided to see if transmission of Candida spp. possibly occurred between patients on our ICU (Study 3).We found low incidence rates, compared to international studies, for CRI and CRBSI related to the 495 CVCs studied over a short period (16 months, Study 1) and the 2045 CVCs studied over long-term follow-up (six years, Study 4). We found no cases of AC-CRBSI but a low number of AC-CRI in the 600 ACs studied. The type of microorganisms responsible for infections related to CVCs and ACs were similar to those found in international studies. However, the proportion of Candida spp. was high in Studies 1 and 4 evaluating CVC infections. There was no difference in the CVC-catheterisation time for CRI/CRBSI caused by Candida spp. as compared to CRI/CRBSI caused by bacteria. Risk factors for CRI associated with CVCs were chronic haemodialysis (Study 1), all haemodialysis in general (Study 4) and CVCs inserted via the internal jugular vein as compared to the subclavian vein (Study 4). Risk factors for CRI related to ACs were colonisation or infection of a simultaneous CVC and immunosuppression. Genotypes of Candida albicans and Candida glabrata had a heterogeneous distribution between ICU patients over time. Comparison with a reference group and cluster analysis indicated that transmission of Candida spp. between ICU patients is possible.In, conclusion, we have found, after implementation of evidence-based routines for CVC and AC insertion and care, low incidences of CRI and CRBSI associated with these catheters. Furthermore, we found that transmission of Candida spp. between patients on the ICU is possible.
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| 6. |
- Lytsy, Birgitta, 1968-
(författare)
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Enterobacteriaceae Producing Extended-Spectrum Beta-Lactamases : Aspects of Detection, Epidemiology and Control
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Enterobacteriaceae belong to the normal enteric flora in humans and may cause infections. Escherichia coli is the leading urinary tract pathogen with septicaemic potential, whereas Klebsiella pneumoniae causes opportunistic infections and often outbreaks in hospital settings. Beta-lactams are the first choice for treatment of infections caused by Enterobacteriaceae, and might be destroyed by extended-spectrum beta-lactamases, ESBLs. ESBLs hydrolyse all beta-lactams except cephamycin and carbapenems, and constitute a large heterogeneous group of enzymes with different origins. The phenotypic and molecular characteristics of a K. pneumoniae strain causing a major outbreak at Uppsala University Hospital between 2005 and 2008 were described. The strain was multiresistant and produced CTM-M-15, a common ESBL type in Europe. Due to the lack of obvious epidemiological links between patients, a case-control study was performed, which identified risk factors for the acquisition of the outbreak strain in urine cultures. The complex chain of transmission facilitated by patient overcrowding and the interventions applied to curb the outbreak, was revealed in the subsequent study. In the final study, the genetic background of the observed increase in ESBL-producing E. coli isolates during the K. pneumoniae outbreak was explored. The utility of six typing methods in epidemiological investigations of a local outbreak with ESBL-producing E. coli was compared. The increase of ESBL-producing E. coli isolates was not secondary to the K. pneumoniae outbreak. Twentytwo per cent belonged to the epidemic O25b-ST131 clone and only a limited number of infections were caused by nosocomial transmission. ESBL-producing Enterobacteriaceae are a challenge to clinical microbiology laboratories and infection control teams. To investigate their dissemination, typing methods need to be continuously adapted to the current situation. Proper hand disinfection and structural key problems such as over-crowding, under-staffing, lack of single rooms and bathrooms must be adressed to limit transmission.
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| 7. |
- Samuelsson, Annika, 1964-
(författare)
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The faecal flora : a source of healthcare-associated infections and antibiotic resistance
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Healthcare-associated infections (HAI) are important causes of mortality and morbidity, and antibiotic treatment is often necessary. Development and availability of new antibiotics are closely followed by development of resistance among microorganisms. During antibiotic therapy, a fraction of the antibiotic given is found in the gut. The human gut is an important reservoir of bacteria. Microorganisms residing or passing the gut is referred to as the gut flora or microbiota. The results of this thesis showed spread of Enterococcus spp between patients on a general intensive care unit, causing septicaemia. After improved hygiene, reorganisation of rooms and thorough cleaning of the unit, together with revision of antibiotic strategy, the incidence of septicaemia with Enterococcus spp fell. Investigation of patients treated for acute intra-abdominal infections showed a shift in the aerobic faecal flora from antibiotic-susceptible Enterobacteriaceae spp towards Enterococcus faecium, yeasts and species of Enterobacteriaceae more resistant to antibiotics, after antibiotic treatment and hospital care. Investigation of recurrent outbreaks of Serratia marcescens sepsis in patients admitted to a neonatal intensive care unit showed different clones with each outbreak. Multiple hygiene interventions and revision of antibiotic strategy subsequently obviated recurrent outbreaks of sepsis, but spread of S. marcescens was not reduced until compliance with basic hygiene guidelines remained stable above 80%. We also found that low gestational age at birth, ventilator treatment and central venous or umbilical catheters are independent risk factors for late onset sepsis. Investigation of the faecal microbiota in patients with acute appendicitis or diverticulitis revealed that disturbance of the faecal microbiota already existed on admission, with higher numbers of Enterobacteriaceae and less Bacteroides, Faecalibacterium, Ruminococcus and Prevotella prior to antibiotic treatment and hospitalisation, than the control population. After treatment and hospitalisation diversity increased significantly in the diverticulitis group, approaching the healthy controls in composition.
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| 8. |
- Erlandsson, Marcus, 1972-
(författare)
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Surveillance of Antibiotic Consumption and Antibiotic Resistance in Swedish Intensive Care Units
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Nosocomial infections remain a major cause of mortality and morbidity. The problem is most apparent in intensive care units (ICUs). Most ICU patients are compromised and vulnerable as a result of disease or severe trauma. One in ten people admitted to hospital is given an antibiotic for infection. The risk of acquiring a nosocomial infection in a European ICU is approximately 20%. It is vitally important that ways are found to prevent transmission between patients and personnel, and that local hygiene routines and antibiotic policies are developed. This thesis is a holistic work focused particularly on antimicrobial antibiotic resistance, antibiotic consumption and to some extent on hygiene in Swedish ICUs.Aims: The general aim of this thesis was to investigate bacterial resistance and antibiotic consumption in Swedish ICUs and to try to correlate ICU demographic data with antibiotic consumption and antibiotic resistance. Additional aims were to investigate on which clinical indications antibacterial drugs are prescribed in the ICU, and to investigate the emergence of resistance and transmission of Pseudomonas aeruginosa in the ICU using cluster analysis based on antibiograms and genotype data obtained by AFLP.Material and methods: In paper 1-3, antibiotic consumption data together with bacterial antibiotic resistance data and specific ICU-demographic data were collected from an increasing number of ICUs over the years 1997-2001. Data from ICUs covering up to six million out of Sweden’s nine million inhabitants were included. In paper 4, the indications for antibiotic prescribing were studied during two weeks in 2000. Paper 5 investigated Pseudomonas aeruginosa isolates in order to detect cross-transmission with genotype obtained by AFLP, and antibiogram-based cluster analysis was also performed in order to see if this could be a quicker and easier substitute for AFLP.Results: This thesis has produced three important findings. Firstly, antibiotic consumption in participating ICUs was relatively high during the study period, and every patient received on average more than one antimicrobial drug per day (I-IV). Secondly, levels of antimicrobial drug resistance seen in S. aureus, E. coli and Klebsiella spp remained low when data were pooled from all ICUs throughout the study period, despite relatively high antibiotic consumption (I-V). Thirdly, the prevalence of antibiotic resistance in CoNS and E. faecium, cefotaxime resistance in Enterobacter, and ciprofloxacin and imipenem resistance in P. aeruginosa was high enough to cause concern.Conclusion: For the period studied, multidrug resistance in Swedish ICUs was not a major problem. Signs of cross-transmission with non-multiresistant bacteria were observed, indicating a hygiene problem and identifying simple improvements that could be made in patient care guidelines and barrier precautions. A need for better follow up of prescribed antibiotics was evident. With further surveillance studies and monitoring of antibiotics and bacterial resistance patterns in the local setting as well as on a national and international level, some of the strategic goals in the prevention and control of the emergence of antimicrobial-resistant microbes may be achievable.
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| 9. |
- Taxbro, Knut, 1973-
(författare)
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Vascular access in cancer patients – clinical implications
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Central venous catheters (CVC) are vital for patients receiving chemotherapy not compatible with peripheral infusion. Thousands of centrally and peripherally inserted central venous catheters are inserted into patients with cancer each year. All types of intravascular catheters are associated with complications. These complications may be divided into infectious, thrombotic, mechanical and occlusive events. All of these events have the potential to harm patients and cause additional expense for the health-care system. Furthermore, the above-mentioned complications are largely avoidable through proper patient selection, insertion technique, hygiene precautions and catheter maintenance.Catheter-related infections and deep venous thrombosis are the two most common and feared CVC related complications. Infection in a catheter can cause lifethreatening bacteraemia, and thrombosis can lead to pulmonary embolisation, post-thrombotic syndrome and stenosis of the vessel affected. Many studies describing methods to minimise infectious complications associated with central venous catheters have been carried out. These methods appear to have been implemented in most modern advanced healthcare facilities resulting in a continual decrease in catheter-related infections over the last two decades. New implantation techniques, fewer infections and better catheter materials are likely to have contributed to the reduction in the incidence of catheter-related deep venous thrombosis (CR-DVT). Peripherally inserted central venous catheters (PICC) and subcutaneously implanted vascular access ports (PORT) are two very commonly used catheter devices for delivery of chemotherapy. International guidelines are unclear as to which device to choose due to the paucity of controlled trials.The aim of this thesis was to study complications related to central venous access devices used over long periods of time, usually for the delivery of chemotherapy. Vascular access in cancer patients – clinical implications We prospectively studied PORT complications (Study 1) over a six-month follow- up period. In Study 2, we assessed the number of common CVC-related micro- organisms that are transferred across PORT membrane contaminated by a controlled suspension of micro-organisms when a non-coring access needle is inserted using two different techniques. In the largest randomised controlled trial published on this topic (Study 3), we compared PICC with PORT regarding CRDVT and other catheter-related complications. The economic implications of using PICC or PORT were assessed from health-care system´s perspective (Study 4), using data on adverse events and clinical factors (implantation, treatments and dwell-time) from Study 3.Chemotherapy against various forms of cancer is very common. Implantation of PORT is one of the ten most common surgical procedures in Sweden according to the Swedish Perioperative Register. Hence, the topic in this thesis may be clinically relevant to many patients and their health care providers.We found that the incidence of catheter-related blood stream infection was very low in the cohorts studied. In general, PICCs are associated with significantly more CR-DVTs and adverse events than PORTs. The cost to the health-care system when using PICC is higher than for PORT when complications are included. Given the choice, patients about to commence chemotherapy appear to prefer PORT to PICC. PORT implantation is more painful than PICC insertion, but PICC appears to influence activities of daily life more than PORT.
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