Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection: NORDynamIC trial and real-life experience.

OBJECTIVE: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment. MATERIAL AND METHODS: The impact of established response predictors, e.g. age, ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients treated for 12-16 weeks in accordance with national guidelines. RESULTS: In the NORDynamIC trial, age < 40 years or achieving HCV RNA < 1000 IU/mL day 7 were highly predictive of favorable outcome following 12 weeks therapy. Among 255 Finnish real-life patients below the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12-16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR. CONCLUSIONS: Short interferon-based therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3 infected patients, and is an acceptable option given that a thorough discussion of the side effects is provided prior to initiation.

A case-control study of risk factors for urinary acquisition of Klebsiella pneumoniae producing CTX-M-15 in an outbreak situation in Sweden.

A retrospective case-control study was initiated at Uppsala University Hospital in 2006 during a major outbreak caused by a Klebsiella pneumoniae strain producing CTX-M-15. To identify risk factors associated with acquisition of the outbreak strain in the urinary tract, 52 case patients with a urine culture positive for the outbreak strain between 1 May and 31 December 2005 were enrolled. Case patients were matched 1:2 with concurrently hospitalized control patients with significant growth of susceptible Escherichia coli in a urine sample. Conditional logistic regression analyses identified hospital stay >or=9 days (odds ratio (OR) 18.8, 95% confidence interval (CI) 5.74-61.2), nasogastric feeding tube (OR 18.0, 95% CI 2.28-142) and diarrhoea (OR 9.62, 95% CI 3.30-28.1) as risk factors with high ORs. The odds of previous use of cephalosporins were 7.58 (95% CI 3.13-18.4) times higher in case patients compared with the controls. Several multivariable models were evaluated to reduce bias from confounding. These models identified prolonged period of hospitalization, diarrhoea, malignancy and antibiotic use as the most important risk factors for acquisition of the outbreak strain, factors that are often found in elderly patients with a poor functional status.

The first major extended-spectrum beta-lactamase outbreak in Scandinavia was caused by clonal spread of a multiresistant Klebsiella pneumoniae producing CTX-M-15.

Between May and December 2005, 64 multidrug-resistant isolates of Klebsiella pneumoniae were detected from patients admitted to Uppsala University Hospital. This represented a dramatic increase in ESBL-producing K. pneumoniae compared to previous years. To investigate the epidemiology and to characterize the resistance mechanisms of the isolates, a study was initiated. Antibiotic susceptibility was determined by means of the Etest and the disc diffusion method. Extended-spectrum beta-lactamase (ESBL) production was identified by clavulanic acid synergy test and confirmed with PCR amplification followed by DNA sequencing. DNA profiles of the isolates were examined with pulsed-field gel electrophoresis (PFGE). All isolates were resistant or exhibited reduced susceptibility to cefadroxil, cefuroxime, cefotaxime, ceftazidime, aztreonam, piperacillin/tazobactam, ciprofloxacin, tobramycin, and trimethoprim-sulfamethoxazole. They produced ESBL of the CTX-M-15 type, and the involvement of a single K. pneumoniae clone was shown. This is the first major clonal outbreak of multiresistant ESBL-producing K. pneumoniae in Scandinavia. The outbreak demonstrates the epidemic potential of enterobacteria containing ESBLs of the CTX-M type, even in a country with a relatively low selective pressure and a low prevalence of multiresistant bacteria.

Lemierres syndrom ­ en påminnelse om ¼den glömda sjukdomen« - God kunskap under hela vårdkedjan viktigt för att i tid väcka misstanke.

The purpose of this case report and discussion is to heighten the awareness of Lemierres syndrome (postanginal sepsis).  Affected patients present in various fields of medicine and an increased incidence of "the forgotten disease" may be expected. Fusobacterium necrophorum is the most common pathogen. The clinical course includes a primary head or neck infection with thrombosis of the internal jugular vein with subsequent septic pulmonary embolization. The syndrome bears considerable morbidity and even mortality. People aged 15-25 years are commonly affected. Early diagnosis through positive blood culture and confirmation of jugular vein thrombosis combined with prompt antibiotic treatment and source control is mandatory in the management of Lemierre's syndrome. Assessment of vital organ function is recommended across the continuum of care as this facilitates recognition and initiation of therapeutic measures to counteract a complicated clinical course.

[Quinolones--a cure which became a threat. Accelerating resistance development demands stricter indications]. / Kinoloner--bot som blivit hot. Accelererande resistensutveckling kräver skärpta indikationer.

Fluoroquinolones are important antibiotics for treatment of serious infections. Increased usage has, in many countries, resulted in rapid development of resistance towards this class of antibiotics. Moreover, it has been shown that use of fluoroquinolones is associated with selection of multi-resistant bacteria, such as methicillin-resistant S. aureus and vancomycin-resistant enterococci. The risks related to overuse of fluoroquinolones among both humans and animals are reviewed and strict indications for use are suggested.

[STRAMA questionnaire on general practitioners' knowledge concerning antibiotics and resistance. Lack of time impedes exchange of information]. / STRAMA-enkät om allmänläkares kunskaper om antibiotika och resistens. Tidsbrist hindrar informationsutbytet.

The Uppsala county regional group of the Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance (STRAMA) sent a questionnaire to all the general practitioners in the county concerning their knowledge of antibiotics and bacterial resistance. The questionnaire also asked which sources were used for information on these topics, and inquired as to their views concerning the services provided by the local clinical microbiological laboratory. A third part of the questionnaire contained descriptions of three patients with infectious diseases, and each general practitioner was asked to indicate appropriate diagnostic tests and/or antibiotic treatment. The questionnaire was completed by 70% (100/145). The general awareness of which antibiotics to use for empirical treatment of urinary tract infection was good. Awareness of antibiotic resistance in S. pyogenes, H. influenzae, S. pneumoniae and MRSA was moderately good (59-80%). About 60% thought it was difficult to find information concerning resistance and use of antibiotics. Lack of time was the main reason for not being able to seek such information actively. The regional STRAMA-group believes that this kind of survey followed by reporting back of results with informative comments on the topics concerned is a useful model for education.

Bacteria with increased mutation frequency and antibiotic resistance are enriched in the commensal flora of patients with high antibiotic usage.

BACKGROUND: We examined how prolonged antibiotic treatment affected the resistance and mutation frequency of human microflora isolated from intestine (Escherichia coli, enterococci spp.), pharynx (alpha-streptococci) and nostril (coagulase-negative staphylococci, CoNS). METHODS: Samples were collected from patients at the Center of Cystic Fibrosis (n=18) and the haematology ward (n=18) of the University Hospital, Uppsala, Sweden. The individually used amount of antibiotics for 1 year was recorded as the defined daily dose (DDD). Primary health care patients (n=30), with no antibiotic treatment for 1 year before sampling, were used as controls. Three isolates of each bacterium from each patient were examined. Antibiotic susceptibilities were determined by disc diffusion. Mutation frequencies to rifampicin resistance were measured on 30 independent cultures of each bacterial species from each individual by plating on rifampicin agar plates. For alpha-streptococci the mutation frequency to streptomycin resistance was also determined. RESULTS: Isolates from patients with high antibiotic use showed a pronounced shift towards increased resistance and a small but significant increase in the mutation frequency compared with isolates from the controls. For E. coli, enterococci and CoNS the increase in geometric mean mutation frequency in the patient group was 3-, 1.8- and 1.5-fold, respectively (P values 0.0001, 0.016 and 0.012). For alpha-streptococci there was a significant difference in geometric mean mutation frequency between patient and control groups for streptomycin resistance (P=0.024) but not for rifampicin resistance (P=0.74). CONCLUSIONS: High antibiotic use selected for commensals with highly increased resistance and a slight increase in mutation frequency.

Evidence for transmission between humans and the environment of a nosocomial strain of Enterococcus faecium.

An ampicillin- and ciprofloxacin-resistant Enterococcus faecium (ARE) strain, named FMSE1, with a characteristic biochemical phenotype, was in a recent study found to dominate among faecal ARE isolates from patients in several Swedish hospitals. In the present study, the prevalence of this strain among 9676 enterococcal isolates from healthy children, hospital sewage, urban sewage, surface water, slaughtered animals (broilers, pigs and cattle) and pig faeces and manure was investigated. Enterococcal isolates having the same biochemical phenotype as the FMSE1 were most common in samples of hospital sewage (50%), surface water (35%), treated sewage (28%) and untreated sewage (17%), but rare in samples from healthy children (0.8%) and animals (2%). PFGE typing of FMSE1-like isolates from hospital sewage indicated that they were closely related to the nosocomial FMSE1 strain. Thus, this study indicated a possible transmission route for nosocomial E. faecium from patients in hospitals to hospital sewage and urban sewage, and further via treatment plants to surface water and possibly back to humans. This proposed route of circulation of drug-resistant enterococci might be further amplified by antibiotic usage in human medicine. In contrast, such transmission from food animals seems to play a negligible role in Sweden.