Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18–24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).

We examined the response to hepatitis B vaccination in dialysis patients, and evaluated our vaccination program to hepatitis B virus. No new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards. Sera were analyzed for anti-HBs in 25 dialysis patients vaccinated at least three times against hepatitis B and 53 health care staff vaccinated three times. The IgG subclass distribution of antibodies to hepatitis B surface antigen (anti-HBs) was determined in 11 dialysis patients and in 45 healthy controls. The antibody response to pneumococci was determined in 29 vaccinated patients.

Results: Ten of 25 (40%) of the dialysis patients had anti-HBs when both tests after the third and/or fourth injections were considered. In four patients a fourth injection was cancelled due to transplantation or bad health, while such data were lacking in 8 cases. In staff 49/53 (93%) of the persons responded with anti-HBs production. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG 1 (p<0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with lgGI as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registred in 25 out of 29 dialysis patients (in all 86 %).Dialysis patients respond poorly to hepatitis B vaccine. An anti-HBs subclass response mainly restricted to IgG I was observed in healthy adults, while dialysis patients had low or negative test results affecting all subclasses.

The findings suggest a general deficit in the ability to produce anti-HBs rather than a deficit in the production of a specific subclass of this antibody. Moreover, RBV-vaccination schedules in renal transplant recipients should be started early, as some patients otherwise, due to transplantation or bad health, may not receive a fourth injection.

The antibody response to pneumococcal vaccination indicates that the antigen involved is important in vaccination responses in dialysis patients.

Introduction: There is little information available on the effects of problem-based undergraduate curricula on doctors and their performances after graduation. Therefore, we conducted a questionnaire study of all graduates of the new medical programme at the Faculty of Health Sciences, Link÷ping University. Methods: All 446 medical students who had graduated from the new programme were asked to fill in a questionnaire about selected activities during their studies and their careers after graduation. They were also asked to evaluate the quality of their undergraduate education retrospectively. Statistical analysis was performed using descriptive, multivariate and bivariate approaches. Results: A total of 77% of the graduates responded. They showed a high degree of overall contentment with their undergraduate education and felt well prepared for professional life during their preregistration period and specialist education (mean = 4.0 on a 6-point Likert scale ranging from 0 to 5). They felt especially well prepared in terms of skills for communication with patients, collaboration with other health professionals and development of critical thinking/scientific attitudes. The students' age at the beginning of their studies correlated positively with their contentment as graduates, especially in terms of preparation for patient communication and collaboration with other health professionals. No differences between students originally admitted via a local admission procedure and those admitted via a national procedure were detected concerning retrospective evaluation of undergraduate medical education. Conclusion: Graduates of the new curriculum showed a high degree of satisfaction with their undergraduate education and its preparation of them for medical practice. Specifically, they were very content with the particular emphases of the new curriculum.

This study focuses on the interaction of Staphylococcus epidermis isolated from granulation tissue covering infected hip prostheses and neutrophil granulocytes. Bacterial strains isolated from normal flora were used as controls. The bacteria were well characterized with routine methods and further characterized with random amplified polymorphic DNA analyses and slime tests. Phagocytosis and chemiluminescence (CL) assays were used in the neutrophil interaction studies. The prostheses strains were ingested to a lesser extent than strains from normal flora (p ≤ 0.001). There was no significant difference between the prostheses strains and the normal flora strains in terms of total CL response. However, the extracellular CL response from the neutrophils was lower in comparison with the normal flora when interacting with the prostheses strains. The results of this study support the notion that S. epidermidis strains isolated from infected hip prostheses have an enhanced capacity to resist phagocytosis and that most of these strains elicit a reduced inflammatory response, measured as the production of extracellular oxidative metabolites from the neutrophils, compared to normal flora.

Health care workers at risk for hepatitis B virus infection are recommended for vaccination. Low-dose intradermal (i.d.) administration of vaccine has been suggested as a less expensive alternative to intramuscular (i.m.) inoculation. To evaluate the i.d. vaccination route, health care workers were included in a prospective study. The subjects were vaccinated with 0.1 ml (= 2 microg) recombinant vaccine (Engerix B, SmithKline Beecham) i.d. at 0, 1 and 6 months. Two months after the third vaccination, measurement of the anti-HBs level was conducted. An anti-HBs level > or =10 IU/l was considered protective. Those with an anti-HBs level <10 IU/l were given a fourth dose with new serological control after another 2 months. The results are based on the 1406 subjects that it was possible to evaluate. The seroconversion rate to protective anti-HBs level after 3 doses was 68% and after 3 or 4 doses 89%. Factors associated with a lower response rate were increasing age (p<0.05) and smoking (p<0.001). Sex or body mass index had no influence on the results. Vaccination technique seems to be of utmost importance when the i.d. route is used. Well instructed and experienced nurses are required and quality control with follow-up of overall seroconversion rate within each centre is needed.

A multicentre susceptibility study was performed on staphylococci and enterococci isolated from patients at 3 different ward levels: primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs), in Denmark, Finland, Norway and Sweden. There was a markedly higher incidence of resistance among CoNS in ICUs compared to GHWs and PCCs. Resistance rates were low among S. aureus isolates and no differences were found between the ward levels. Oxacillin resistance was found among 1.6% of S. aureus and 47% of CoNS isolates. 14% of CoNS and 0.9% of S. aureus isolates were glycopeptide intermediate. The prevalence of E. faecium isolates in this study differed significantly between the ward levels with the lowest prevalence found at PCCs. High level gentamicin resistant (HLGR) enterococci occurred in 11-25% of E. faecium and 6-20% of E. faecalis isolates. The HLGR rate was significantly higher among E. faecalis from hospitalized patients (GHWs and ICUs) compared to patients at PCCs. For enterococcal isolates, no other significant differences in antimicrobial resistance were found between the ward levels. All enterococci were teicoplanin susceptible, but decreased susceptibility to vancomycin was found among 2.0% and 0.6% of the E. faecium and E. faecalis isolates, respectively.

Problem-based learning, combined with early patient contact, integration between different subject areas, elements of multiprofessional education, and special emphasis on the development of communications skills has become the basis for the medical curriculum at the Faculty of Health Sciences in Linköping. Critics have questioned the depth of the scientific and theoretical aspects of the curriculum. Through a series of specific measures in the organization of the curriculum and examinations, and due to the pedagogical principles involved per se, our claim is that students graduating at Linköping do possess the required theoretical knowledge and a scientific attitude to the practice of medicine, at least equivalent to that obtained in a more conventional medical curriculum. One such specific measure is that all students perform one field study and two scientific studies during the course of the curriculum. An investigation of student opinions regarding the value of performing scientific projects of their own have shown that these projects have had a positive impact on the students' general scientific attitude and their willingness to engage in future scientific work. The specific skills acquired, as confirmed by oral examinations, were largely determined by the scientific nature of the chosen field of study. Our graduates have not yet progressed far enough in their careers for comparisons to be made on the basis of the Swedish Licensing Board Internship Examinations, but continuing evaluations of students, graduates and licensed doctors emerging from the curriculum will provide future evi-dence as to whether our present evaluation is correct.

The first nosocomial legionella outbreak in a Scandinavian general district hospital was identified in an epidemiological investigation of a cluster of pneumonia cases in Värnamo in 1991. During 3 months, 28 patients and 3 staff fell ill and 3 died. Legionella pneumophila serogroup (sg) 1, was found in high counts throughout the hospital hot water system and was probably spread by aerosolisation via shower nozzles. The outbreak was arrested when the circulating hot water temperature was raised from <45°C to >55°C.

The nosocomial infections proved to be part of a wider legionella outbreak and 10 cases contracted outside the hospital were also detected. Legionellae were cultured from 7 of 15 community buildings and 31% (109/354) of subjects living in the Värnamo area had an elevated titre (≥6) to L. pneumophila sg 1 in 1991, indicating a temporary spread of legionella in the community. Subclinical infection was demonstrated and it was estimated that only 10% of all infections had been clinically identified. Nosocomial legionnaires' disease should alert physicians to possible legionella transmission in the community.

In 21 patients from the nosocomial outbreak, the median L. pneumophila sg 1 antibody titre fell from 1:256 to 1:16 in 3 years. After 10 years, the titre level in this clinical cohort had reached the same level as observed in the background population 5 years earlier. Current international serological criteria (a fourfold or greater rise in antibody titre to ≥1:128) identified only 40% (21/52) of pneumonia cases caused by L. pneumophila sg 1 in a Swedish population in 1991-2001. When the antibody response was related to the antibody titre in local residents, the sensitivity rose to 87% (45/52).

Keeping the circulating hospital hot water temperature above 55°C, and vigilant clinical surveillance of nosocomial pneumonia as a method for control of nosocomial legionnaires' disease was evaluated after 10 years of practice. Infection with L. pneumophila sg 1 was diagnosed in 4 out of 366 (1.1 %) patients treated for nosocomial pneumonia, representing 1 case per 26,000 admissions. All patients were cured without complications. L. pneumophila sg 1 was isolated in 30 of 251 (12%) cultured hospital water samples during the monitoring period. It was concluded that this approach was safe and effective for long term control of nosocomial legionnaires' disease in a primary referral hospital.

The hospital hot water system was found to be colonised with a single genotype of L. pneumophila sg 1 over a 12-year period. The same genotype, identified using amplified fragment length polymorphism (AFLP) analysis, was also demonstrated in 18/20 (90%) community isolates. The phenotypic variation was confined to the monoclonal antibody subtypes Benidorm and Bellingham. The hospital genotype was identified in 2 out of 6 Swedish hospitals, both located within 100 km of Värnamo. Obviously, an entire municipal water network may constitute a distinct ecological niche for a single legionella strain. Certain clones also seem to be widely spread in the environment. This implies that results from molecular subtyping must be interpreted cautiously in epidemiological investigations of legionnaires' disease.

The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P = .02) and 3 (P = .04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P = .03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.

The objective of this study was to examine a design for a World Wide Web-based decision-support system in use by clinically active physicians. A prototype implementation of the design concerned management of infective endocarditis patient cases. The design was based on an integration of hypertext and rule-based knowledge. In the study sessions, physicians in the field of internal medicine worked on managing authentic patient cases in a laboratory setting. Data was collected from interviews with the physicians using video recordings and stimulated recall technique. The qualitative data was analysed according to the constant comparative method in order to develop a model of the physicians' usage of the system. The resulting model describes perceived contributions and criteria for usefulness of the system. The ways the physicians used the system showed that it was able to provide patient-specific support for confirming clinical decisions, for higher-level patient management, and for preparing for and initiating expert consultations. Users also stated that new medical knowledge could be gained as a side effect of using the system.

Five commercial Borrelia serology kits available in Sweden were evaluated and compared for their diagnostic performance in sera from clinically well-characterized patient groups. With the clinically defined groups as the gold standard, i.e. without knowledge of antibody status in serum and cerebrospinal fluid, the diagnostic performance of the kits was compared and important differences in diagnostic usefulness were found. The kits from Abbot and DAKO, that often predict clinically relevant Borrelia infection and do not detect antibodies in sera from patients without strong suspicion of Borrelia infection, were considered the most useful in the population studied. This kind of validation study is an important part of good laboratory practice and should be performed by laboratories serving patient populations with varying endemicity of Borrelia.

The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-? (IFN-?), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-?. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-?-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCR?d, which both have cytolytic properties, were the main phenotypes of IFN-?-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.

To address the issue of whether Borrelia infection can be asymptomatic, blood donors with no history of borreliosis (n = 408) were screened for antibodies against Borrelia burgdorferi. Seropositive individuals (n = 17) were further investigated with respect to Borrelia-specific T-cell reactivity, using an interferon-? ELISPOT assay. Anti-Borrelia antibodies as well as Borrelia-specific T-cell responses were evident in 9 asymptomatic donors, strongly supporting a current or previous asymptomatic Borrelia infection.

Background: Malaria affects over 300 million persons in the world each year with a mortality of close to 2 million. In developing countries malaria has been endemic in the lowlands for centuries with no occurrence in the highlands above 2000 metres above sea level. This pattern has changed over the last decade whereby malaria is occurs in epidemics with a high morbidity and mortality among the inhabitants of the highlands especially children and pregnant women. Eldoret and its environs in Kenya is a highland area with an altitude of 2300 metres above sea level where malaria was rare up to the late 1980s. Since 1988 malaria occurs in epidemics in this region with a high prevalence of severe malaria especially cerebral malaria(CM). This led to the conduct of stndies that fonn the basis of this thesis with the aim of delineating aspects of pathogenesis and the clinical presentation of CM in the Western highlands of Kenya.

Materials and Methods: Cross sectional, retrospective and prospective studies were conducted to study the prevalence of malaria among inpatients at the Moi Teaching and Referral Hospital (MTRH); to describe the clinical presentation of CM in the highlands; to compare temperatures in CM and uncomplicated malaria(UM) cases and to assay the serum tumour necrosis factor alpha (TNFa) and transforming growth factor beta (TGF-13)1 levels in these patients.

A total of 4 720 children were retrospectively and prospectively studied over an 18 month period (1991-1993) to establish the top 20 diseases at the MTRH. This was followed by a prospective study of 23 CM and 12 UM cases in 1997. All the presenting features of the cases with CM were tabulated on admission and analysed so as to establish the clinical presentation of CM in this region and compare this to the standard as described by the World Health Organisation (WHO). A comparison was made between the brain, core and skin temperatures of the CM and UM cases with normal children acting as controls.

This was a follow up of a similar stndy in 1993 that compared core and skin temperatures between measles, CM and UM with normal children as controls. Serum TNF-a and TGF-131 levels were assayed and compared among the CM and UM patients in the 1997 study and included the assay of cerebrospinal (CSF) TNF-α and TGF-β1 in CM.

Results and conclusions: Malaria accounted for 3 3% of all admissions over the study period with a case fatality rate of 2.2% and a mortality rate of 10.7%. Most children with CM were aged 3-10 years and were of good nutritional status. They presented in coma, with fever, headache, convulsions and hyperparasitaemia and with a short duration of illness of less than 3 days. Severe anaemia and hypoglycaemia were not common features. Malaria is the leading cause of morbidity in the children stndied. CM in the highlands presents as that seen among non-immunes. There were no differences in brain, core and skin temperatures between the CM and UM patients. The brain temperature was however always lower than core temperature even in normal controls with brain temperature having a positive correlation with core temperature as the body temperature rises. Thus, the role of fever in the pathogenesis of CM is still unclear The serum TNF-α and TGF-β1 levels were the same in UM and CM cases with TNF-α and TGF-β1 having an inverse relationship to each other. Patients with deeper levels of coma had higher levels of TNF-α and lower levels of TGF-β1.

Forty-four children were studied to compare the pathogenesis of fever in cerebral malaria, uncomplicated malaria and measles at the Eldoret District Hospital (EDH). A control group of normal children was used. The three patient groups were studied for three consecutive days measuring skin and core temperature three-times a day using the Liquid Crystal Device (LCD) thermometer. A statistical analysis of the results within and between the groups was carried out for core and skin temperature over the study period. No statistical differences were found between the groups for either the skin or the core temperature, but a significant statistical difference was demonstrated between the core and the skin temperature for all of the groups for each of the three days. No statistical difference was found when the differences between the core and skin temperature were compared between cerebral malaria and uncomplicated malaria. The possible roles of fever in morbidity and mortality are discussed, with special reference to cerebral malaria.

A prospective study was carried out in which brain, core and skin temperatures were studied in children with cerebral malaria (n = 23), uncomplicated malaria (n = 12) and normal children (n = 9) using the zero heat flow method. Patients with cerebral or uncomplicated malaria were admitted to the paediatric wards (mean age, 6 years 8 months ± 2 years 8 months). Normal children, children of the investigators, of the same age group, served as controls. Parasitaemia levels were similar in the cerebral and uncomplicated malaria cases. Higher brain than core temperatures would have been expected in cerebral malaria but not in uncomplicated malaria but this was not the case in this study. There was no statistical difference in brain, core and skin temperature between cerebral and uncomplicated malaria patients. However, there was a highly significant difference between normal children and cerebral and uncomplicated malaria patients. Brain temperature was 0.02–0.2°C below core temperature in all the groups with larger differences during the febrile period. Mean differences of brain minus core, brain minus skin and core minus skin between the two groups of patients were not statistically significant. There was no correlation between temperature and the level of coma or parasitaemia for cerebral and uncomplicated malaria patients. There was a positive correlation between brain and core temperature in both groups of patients during the febrile phase. Brain temperature remained lower than core temperature in cerebral and uncomplicated malaria as in normal children. Normal thermoregulation appears to be maintained in cerebral malaria.

BACKGROUND:

The clinical presentation of cerebral malaria in children in the highlands has not been documented.

OBJECTIVE:

To describe the presentation of cerebral malaria in the age group one to twelve years.

DESIGN:

Prospective study conducted from May to September 1997, the rainy season during which malaria occurs in epidemics in the highlands of Kenya.

SETTING:

Paediatric wards of the Moi Teaching and Referral Hospital, Eldoret which is the Teaching Hospital for Moi University and the referral centre for surrounding districts of Western Kenya, with an altitude of over 2000 metres above sea level.

PATIENTS:

Twenty three consecutive children aged one to twelve years with cerebral malaria as defined by the WHO were studied. All children were treated with the standard quinine regimen for cerebral malaria.

RESULTS:

Majority of the children were six to ten years of age with 95.7% having a normal weight for age. 91.3%, 89.5% and 72.2% had fever, headache and convulsions respectively. 68.1% had a short duration of illness (less than three days) with only 9.5% presenting with hypoglycaemia. Severe anaemia was not observed but 72% had mild to moderate anaemia. Hyperparasitaemia (parasite counts greater than 100,000 per microlitre) was found in majority of the cases.

CONCLUSION:

Cerebral malaria presentation in the highlands is similar to that among non-immune populations and is an acute fulminant illness presenting with coma, hyperparasitaemia, fever and convulsions in children with normal nutritional status.

The first recognized case in Scandinavia with potential man to man transmission of viral haemorrhagic fever occurred in Linköping, Sweden, in January 1990. Following a visit to Kenya a 21-year-old male student suffered a very severe illness including extremely prolonged high grade fever, rash, disseminated intravascular coagulation with thrombocytopenia and severe bleedings. This necessitated one month of intensive care support including respirator treatment. The patient was discharged after 2 1/2 months in good condition, with a partial femoral nerve paresis. About 100 medical personnel were exposed to aerosol or blood before a strict containment regimen was established. No secondary cases occurred.

Human neutrophils are the most abundant of the white blood cells in circulation and represent the first line of defense against invading microorganisms. With a membrane-bound enzyme system (the NADPH oxidase), these cells can generate reactive oxygen metabolites that serve efficiently in antimicrobial defense. Neutrophils are normally dormant in the circulation but may become primed; in that state they can produce an enhanced respiratory burst response upon activation and thereby strengthen the immune response.

During bacterial infections, endogenous inflammatory mediators orbacterial products induce metabolic priming of neutrophils, which thenexpose an increased number of receptors to the peptide f-Meth-Leu-Phe(fMLP). There is, however, no correlation between the increased level ofrespiratory burst response and the level of receptor upregulation, indicating that post-receptor events in the activation sequence are also involved. Neutrophils isolated from an inflammatory focus were found tobe metabolically deactivated as far as the agonists NAP-1/IL 8 and C5awere concerned but primed in relation to tMLP. Further characterizationof exudated cells revealed that the mechanism of priming involves protein kinase C but not a rise in intracellular Ca2+ or a decreased inactivation rate of the oxidase. In primed cells most of the increased production of reactive oxygen species induced by fMLP is located intracellularly, whereas, an increased extracellular release of reactive oxygen species occurs during phagocytosis. The fact that primed cells can both produce and, under certain conditions, release increased amounts of hydrogen peroxide raises the question of whether the primed cell is a friend or a foe in the inflammatory reaction.

Denna klassiska lärobok kom 2011 ut i sin 5:e, omarbetade upplaga. Boken innehåller 28 kapitel, vilka täcker hela infektionspanoramat, från influensa till AIDS. Samtliga författare är läkare och flertalet universitetslärare. Den innehåller även 16 sidor färgplanscher med fotoillustrationer av olika sjukdomar. Boken är avsedd att användas i undervisningen av blivande läkare och som uppslagsbok i sjukvården

Denna klassiska lärobok kom 2011 ut i sin 5:e, omarbetade upplaga. Boken innehåller 28 kapitel, vilka täcker hela infektionspanoramat, från influensa till AIDS. Samtliga författare är läkare och flertalet universitetslärare. Den innehåller även 16 sidor färgplanscher med fotoillustrationer av olika sjukdomar. Boken är avsedd att användas i undervisningen av blivande läkare och som uppslagsbok i sjukvården.

Background and aims: Bacterial resistance to antibiotics hasemerged as an important factor influencing patient mortalityand morbidity. The overall purpose of this project is to exam-ine the impact of bacterial resistance on resource use andoutcome in the critically ill. The aims of the current report isto demonstrate that linkage of local microbiology databasesand the Swedish Intensive Care Registry (SIR) was possibleand to provide a preliminary analysis of data from a sub-group of ICU patients (chronic obstructive pulmonary dis-ease, COPD).

Methods: Admissions due to an acute exacerbation of COPDwere matched with bacteriology samples obtained 14 daysbefore ICU admission, during ICU stay and 14 days after dis-charge from ICU by linking six local microbiology databaseswith patient data in SIR. Linkage was by the patient’s uniquepersonal number and ICU admission and discharge days.

Results: We found 195 patients with median APACHE II prob-ability 0.22 (iqr 0.12–0.37), median length of stay (LOS) 46 (iqr 21–125) hours and 79% 30 day survival. Cultures from 2 weeks before (n=128), during ICU-stay (n=750) and from14 days after ICU discharge (n=228) were identified. During ICU stay airways (n=261), blood or intravascular devices (n=246) and other sites (n=243) were cultured. The totalnumber of airway cultures per patient increased linearly withlength of stay (P<0.01,r2= 0.61). Gram-negative bacteria were most common in positive airway cultures (41%) followedby Candida spp (22%), while positive blood cultures were pre-dominantly Gram-positive (71%). 30-day-mortality was 10/53 with positive and 10/29 with negative airway cultures(P=0.23).

Conclusion: Linkage of local microbiology databases and theSwedish Intensive Care Registry is possible and can generate information that may be used to examine relationships between bacterial resistance and outcomes in the critically illpatient.

An enzyme-linked immunosorbent assay (ELISA) has been developed for the measurement of anti-gliadin antibodies (AGA), thereby providing a practical and cheap assay for use in the diagnosis of coeliac disease (CD). Since gliadin is a common food antigen for most people, a large group of apparently healthy blood donors (n=l866) was analysed, as well as children and adults with symptoms more or less suggesting CD. The effects of various cut-offvalues on the sensitivity, specificity and predictive value (PV) of the test were calculated, both alone and together with anti-endomysium antibodies (EMA). A high prevalence value, of at least 1/256 (7!1866), for gluten enteropathy (GE) was found in the blood donor population. Moreover, a high frequency of CD among fanners with diffuse symptoms, conceivably due to a high exposure to gluten by inhalation, was also observed. It was impossible to combine high sensitivity with high specificity for both IgA- and IgG AGA, and vice versa, in adults. A significant increase in the mean lgA AGA level with age was seen when the blood donors were divided into age groups. A positive PV of 18-25% was found for IgA-AGA, depending on how-the cut-off value was defined. For IgG-AGA the positive PV was 0% (0/35) among asymptomatic subjects. IgA-EMA yielded both high specificity and a high positive PV, but a lower sensitivity than IgA-AGA, especially in children younger than 2 years, with signs of CD. When screening for GE in a population with expected low prevalence, measurement of IgA-AGA is suggested as a primary test because of fairly good sensitivity, technical simplicity, and low cost. Sera found to be positive are then re tested with IgA-EMA, which gives a positive PV close to 100%. For populations with a moderate or high expected prevalence for CD, our results indicate that different tests should be used depending on the age of the population studied. In younger children ( < 2 years old) lgA-AGA yielded a high sensitivity (lOO%) and a high specificity (86%). fu older children (> 2 years old) and adults the use of IgA-EMA seems more suitable, because of the high specificity (99-100%) and positive PV (95-100% ). Since, however, the negative PV was not 100%, a negative test result does not exclude CD.

Lyme neuroborreliosis is a complex disease with different clinical outcomes and where immunopathological mechanisms are probably involved. In this study, sera and cerebrospinal fluid (CSF) from 21 neuroborreliosis patients and 26 control patients were analyzed for the Th1-inducing cytokines, interleukin (IL)-12 and IL-18, and the Th2 associated, soluble CD30 (sCD30) by ELISA. The results showed an increased number of neuroborreliosis patients expressing IL-12 (p<0.05) and IL-18 (p<0.05) in the CSF when compared with the controls, but no indication of increased levels in the sera. Nor were there any differences regarding levels of sCD30 in the sera or the CSF, indicating a local Th1-generating milieu in the target organ of neuroborreliosis.

The team of nurses that Tilda Shalof found herself working with in the intensive care unit (ICU) of a big-city hospital was known as “Laura’s Line.” They were a bit wild: smart, funny, disrespectful of authority, but also caring and incredibly committed to their jobs. Laura set the tone with her quick remarks. Frances, from Newfoundland, was famous for her improvised recipes. Justine, the union rep, wore t-shirts emblazoned with defiant slogans, like “Nurses Care But It’s Not in the Budget.” Shalof was the one who had been to university. The others accused her of being “sooo sensitive.”They depended upon one another. Working in the ICU was both emotionally grueling and physically exhausting. Many patients, quite simply, were dying, and the staff strove mightily to prolong their lives. With their skill, dedication, and the resources of modern science, they sometimes were almost too successful. Doctors and nurses alike wondered if what they did for terminally-ill patients was not, in some cases, too extreme. A number of patients were admitted when it was too late even for heroic measures. A boy struck down by a cerebral aneurysm in the middle of a little-league hockey game. A woman rescued – too late – from a burning house. It all took its toll on the staff.And yet, on good days, they thrived on what they did. Shalof describes a colleague who is managing a “crashing” patient: “I looked at her. Nicky was flushed with excitement. She was doing five different things at the same time, planning ahead for another five. She was totally focused, in her element, in control, completely at home with the chaos. There was a huge smile on her face. Nurses like to fix things. If they can.”Shalof, a veteran ICU nurse, reveals what it is really like to work behind the closed hospital curtains. The drama, the sardonic humour, the grinding workload, the cheerful camaraderie, the big issues and the small, all are brought vividly to life in this remarkable book.

Background: Intensive care units (ICUs) are hot zones for emergence and spread of antibiotic resistance because of frequent invasive procedures, antibiotic usage and transmission of bacteria. We report prospective data on antibiotic use and bacterial resistance from 14 academic and non-academic ICUs, participating in the ICU-STRAMA programme 1999-2003. Methods: The quantity of antibiotics delivered to each ICU was calculated as defined daily doses per 1000 occupied bed days (DDD1000). Specimens for culture were taken on clinical indications and only initial isolates were considered. Species-related breakpoints according to the Swedish Reference Group for Antibiotics were used. Antibiotic resistance was defined as the sum of intermediate and resistant strains. Results: Mean antibiotic use increased from 1245 DDD1000 in 1999 to 1510 DDD1000 in 2003 (P = 0.11 for trend). Of Staphylococcus aureus, 0-1.8% were methicillin resistant (MRSA). A presumptive extended spectrum beta-lactamase (ESBL) phenotype was found in <2.4% of Escherichia coli, based on cefotaxime susceptibility, except a peak in 2002 (4.6%). Cefotaxime resistance was found in 2.6-4.9% of Klebsiella spp. Rates of resistance among Enterobacter spp. to cefotaxime (20-33%) and among Pseudomonas aeruginosa to imipenem (22-33%) and ciprofloxacin (5-21%) showed no time trend. Conclusion: MRSA and cefotaxime-resistant E. coli and Klebsiella spp strains were few despite high total antibiotic consumption. This may be the result of a slow introduction of resistant strains into the ICUs, and good infection control. The cause of imipenem and ciprofloxacin resistance in P. aeruginosa could reflect the increased consumption of these agents plus spread of resistant clones. © 2007 The Authors.

Antibiotic resistance among bacteria causing hospital-acquired infections poses a threat, particularly to patients in intensive care units (ICUs). In order to control the spread of resistant bacteria, local, regional and national resistance surveillance data must be used to develop efficient intervention strategies. In an attempt to identify national differences and the dynamics of antibiotic resistance in European ICUs, data have been merged from several networks of resistance surveillance performed during the 1990s. It should be stressed, however, that comparisons of results from different studies using different methods and different population samples must be made with caution. Antibiotic resistance across all species and drugs was, with some exceptions, highest in southern European countries and Russia, and lowest in Scandinavia. More effective strategies are needed to control the selection and spread of resistant organisms. Antibiotic intervention policies, efficient infection control measures and an overall awareness of the serious implications at public health level will contribute to the management of antibiotic resistance.

For 50 years, antibiotics have been dispensed like sweets. This must not be allowed to continue. This unique book assembles contributions from experts around the world concerned with responsible use of antibiotics and the consequences of overuse. For the first time, it provides up to the minute texts on both the theoretical aspects of antibiotic stewardship and the practical aspects of its implementation, with consideration of the key differences between developed and developing countries. All concerned with teaching, practice and administration of clinical medicine, surgery, pharmacy, public health, clinical pharmacology, microbiology, infectious diseases and clinical therapeutics will find Antibiotic Policies: Theory and Practice essential reading. Antibiotic use and resistance is not just the responsibility of specialists in the field but the responsibility of all doctors, pharmacists, nurses, healthcare administrators, patients and the general public.

The pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis ATCC 29212 and Staphylococcus aureus ATCC 25923 were investigated by studying the postantibiotic effect (PAE) and initial killing. The influence of Ca2+ and albumin on these drugs was also evaluated. The PAE was studied by use of bioluminescence assay of bacterial ATP. Daptomycin at clinically achievable concentrations produced a dose-dependent PAE on E. faecalis (0.6 to 6.7 h) and S. aureus (1.0 to 6.3 h). The long PAE of daptomycin was seen simultaneously with a potent dose-dependent initial killing assayed by viable count determination. The initial change in bacterial ATP was not as extensive as the decrease in viability. Vancomycin at corresponding concentrations produced shorter PAEs on E. faecalis (0.5 to 1.0 h) and S. aureus (1.3 to 1.8 h). This coincides with a weak non-dose-dependent initial change in viability and intracellular ATP. The MICs of vancomycin were not influenced by different Ca2+ concentrations or by the addition of albumin to the broth. The MICs of daptomycin for both strains were lowered, and the PAEs were prolonged with increasing concentrations of Ca2+ in the broth. The PAE of daptomycin was Ca2+ dependent to the same extent as the MIC was. In the presence of physiological concentrations of albumin and free Ca2+, the PAEs of daptomycin on both strains were reduced and the MICs were increased in comparison with the results obtained in pure Mueller-Hinton broth with approximately the same free Ca2+ concentration. This decrease in daptomycin activity was considered to be due to the albumin binding of daptomycin. Despite the albumin binding of daptomycin, the PAE produced on E. faecalis and S. aureus in the presence of a physiological free Ca2+ concentration was still over 6 h at clinically achievable concentrations.

The purpose of this thesis was to study enterococci in Sweden, their resistance to antibiotics in general and high-level gentamicin resistance (HLGR) in particular, with a special focus on the ICU setting. Dynamics of rectal colonisation during prolonged intensive care unit (ICU) stay was assessed. In addition, enterococcal virulence factors and the ability to adhere to abiotic surfaces such as urinary catheters were studied.

We found that among prolonged-stay patients admitted to ICUs, the rectal flora was altered, with a decrease in Gram-negative rods in favour of Gram-positive bacteria, mainly Coagulase negative staphylococci and enterococci.

Among clinical enterococcal isolates from patients admitted to Swedish ICUs, although vancomycin resistant enterococci (VRE) were only sporadically found, multidrug resistance was common. This was most apparent in Enterococcus faecium, where the majority of isolates were ampicillin- and quinolone resistant. Enterococcus faecalis was still the most frequently isolated enterococcal species in clinical specimens. Among patients admitted to Swedish ICUs 1996-1998, E. faecalis with HLGR was found in higher frequency (20%) than previously reported. The majority (89%) of these isolates belonged to two dominating clusters of genetically related E. faecalis. Cluster I (69%), which was predominantly found in the eastern and central parts of southern Sweden and Cluster II (20%) in south-western Sweden.

In the County of Östergötland, the first E. faecalis with HLGR isolated from blood cultures was found in 1996. The yearly incidence of isolates with HLGR in E. faecalis bacteraemia was studied from 1996-2001, and varied between 9-22%. The majority of these isolates were genetically related and belonged to Cluster I, also found in the previous study. The first blood isolate of E. faecium with HLGR in the County of Östergötland was found in 1999. A clone of E. faecium, with HLGR and ampicillin resistance, was found to colonise 6/10 and 2/11 prolonged-stay patients admitted from November 2001 through January 2002 to the general ICU and cardio-thoracic ICU, respectively, at the University Hospital of Linköping.

All studied isolates with HLGR carried the gene aac(6')-Ie-aph(2'')-Ia encoding the bifunctional aminoglycoside modifying enzyme Aac(6')Ie-Aph(2'')Ia, which conveys resistance to all commercially available amino-glycosides except streptomycin. The location of the gene, aac(6')Ie-aph(2'')-Ia, was studied in 45 E. faecalis isolates and the gene was carried on a Tn5281-like transposon in all isolates except one. The 30 µg disc diffusion test, as recommended by the SRGA, had 100% sensitivity and specificity when compared to PCR detection of aac(6')-Ie-aph(2'')-Ia.

E. faecalis isolates with HLGR belonging to widely disseminated clusters of genetically related isolates were more likely to carry both the gene encoding enterococcal surface protein (esp) and the gene encoding aggregation substance (asa1) compared to unique isolates. Esp was the only virulence factor found among E. faecium isolates, where it was common. E. faecalis isolates adhered with higher bacterial densities to urinary tract catheters compared to E. faecium isolates. In vitro adherence to urinary tract catheters was not affected by esp.

Three hundred and twenty-two (322) clinical isolates were collected from patients admitted to intensive care units (ICUs) at eight Swedish hospitals between December 1996 and December 1998. Of the isolates, 244 (76%) were Enterococcus faecalis, 74 (23%) were Enterococcus faecium and four (1%) were other Enterococcus spp. MICs of ampicillin, imipenem, meropenem, piperacillin/tazobactam, ciprofloxacin, trovafloxacin, clinafloxacin, gentamicin, streptomycin, vancomycin, teicoplanin, quinupristin/dalfopristin, linezolid and evernimicin were determined by Etest. Susceptible and resistant isolates were defined according to the species-related MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the Swedish Reference Group for Antibiotics (SRGA). Tentative breakpoints were applied for new/experimental antibiotics. Multidrug resistance among enterococci in ICUs is not uncommon in Sweden, particularly among E. faecium, and includes ampicillin resistance and concomitant resistance to fluoroquinolones. Almost 20% of E. faecalis isolates showed high-level resistance to gentamicin and concomitant resistance to fluoroquinolones. Vancomycin-resistant enterococci were only found sporadically. Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates. There was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance. When applying the SRGA breakpoints for susceptibility, isolates were more frequently interpreted as intermediate. This might indicate earlier detection of emerging resistance using the SRGA breakpoint when the native population is considered susceptible, but with the risk that isolates belonging to the native susceptible population will be incorrectly interpreted as intermediate.