Clostridium difficile infections in teaching hospital in northern Finland.

BACKGROUND: The aim of this study to compare the incidence of Clostridium difficile (CD) infections in the five university hospital districts in Finland based on national register. The clinical findings of CD cases in the Oulu University Hospital (OUH) in one-year cohort were also analyzed. METHODS: The numbers of the CD cases from the national register were used for the hospital district comparison. A retrospective cohort study was conducted among all adult (> 16 years) patients treated in the OUH in 2013, who had positive CD toxin B gene test in stools. The selection of the cohort was based on the data from the OUH microbiology laboratory and the clinical characteristics were collected from hospital records. RESULTS: The incidence of CD findings in 2013 was higher in the OUH district than in the other four university hospital districts: 159 vs. 70 to 84 per 100,000 inhabitants. In 2013, 261 patients had CD infection treated in the OUH. The yearly number of CD cases treated in the OUH in 2009-2016 varied between 221 and 287, and the corresponding proportion of positive CD findings out of all samples taken varied from 10.0 to 17.8%. A recurrent infection was seen in 58 patients (22%) while the all-cause 30 day mortality was 7.3%. CONCLUSIONS: Diagnostic strategies differed nationally, which may explain the differences in CD incidence between the university hospital districts. In the OUH, no increase in the number of CD infections was seen in 2009-2016. Main characteristics of the patient cohort in the OUH were in harmony with earlier literature.

Non-tuberculous Mycobacteria can Cause Disseminated Mycobacteriosis in Cats.

Mycobacteriosis caused by non-tuberculous mycobacteria (NTM) is a rising concern in human medicine both in immunocompromised and immunocompetent patients. In cats, mycobacteriosis caused by NTM is considered mostly to be a focal or dermal infection, with disseminated disease mostly caused by Mycobacterium avium. We describe three cases of disseminated mycobacteriosis in cats, caused by Mycobacterium malmoense, Mycobacterium branderi/shimoidei and M. avium, with no identified underlying immunosuppression. In all cases, extracellular mycobacteria were seen in the pulmonary epithelium, intestinal lumen and glomerular tufts, which could affect the shedding of the organism. The present study highlights the importance of mycobacteriosis as a differential even in immunocompetent animals. Considering the close relationship of owners and pets and the potential presence of free mycobacteria in secretions, cats should be considered as a possible environmental reservoir for mycobacteria.

Increase of prostate biopsy-related bacteremic complications in southern Finland, 2005-2013: a population-based analysis.

BACKGROUND: The most severe manifestations of prostate biopsy complications are bacteremic infections. These complications are increasing alarmingly. METHODS: A retrospective cohort study of 17 183 transrectal prostate biopsies performed at the Helsinki and Uusimaa hospital district in southern Finland during 2005-2013. Biopsies were linked to a database of positive blood cultures, yielding 111 bacteremic cases, and yearly bacteremia rates were determined. By multiple regression analysis, demographic risk factors of the whole biopsy cohort for developing bacteremia or fluoroquinolone (FQ)-resistant bacteremia were studied. Clinical risk factors for bacteremia caused by an FQ-resistant organism and for serious bacteremic outcomes were studied by univariate and multivariate analyzes. RESULTS: The average bacteremia rate was 0.7% (111 of 17 183 biopsies) and an increase was observed from 0.5% in 2005 (95% confidence interval (CI): 0.3-0.9) to 1.2% in 2012 (95% CI 0.8-1.8); 53.2% were caused by an FQ-resistant organism. In univariate regression analysis, previous biopsy sessions and increasing calendar year of biopsy associated with the risk of developing bacteremia (odds ratio (OR) 1.232, 95% CI: 1.020-1.488, P=0.030 and OR 1.164, 95% CI: 1.079-1.255, P<0.001, respectively), but only increasing calendar year of biopsy remained statistically significant (OR 1.155, 95% CI: 1.070-1.247, P<0.001) in multivariate analysis. Foreign travel within 3 months was associated with FQ resistance in multivariate analysis (OR 7.158, 95% CI: 1.042 to infinite, P=0.045). The study failed to show any significant clinical risk factors for serious bacteremic outcomes (requiring intensive care, developing deep infection foci or death). CONCLUSIONS: The postbiopsy bacteremia rate doubled during the study period and half of the cases were caused by FQ-resistant organisms. Recent foreign travel increased the risk for FQ resistance. Future research efforts should be aimed at better identifying risk factors, targeted prophylaxis and reducing the need for biopsies.

Clonality behind the increase of multidrug-resistance among non-invasive pneumococci in Southern Finland.

Multidrug-resistance among Streptococcus pneumoniae isolates, especially of serotype 19A, has increased in several countries recently. Even before the introduction of the pneumococcal conjugate vaccine into the Finnish National Vaccination Programme, the proportion of multidrug-resistant (MDR) pneumococci had doubled from 2007 to 2008, when it reached 3.6% in Southern Finland. Our aim was to look for a possible association between antimicrobial susceptibility and clonality among the MDR isolates. Twelve non-invasive isolates non-susceptible to penicillin, erythromycin, clindamycin, trimethoprim/sulfamethoxazole, and doxycycline from 2008 were available for serotyping, genotyping by multilocus sequence typing (MLST), and detection of genes encoding macrolide resistance and adherence-promoting pili. Two isolates were also resistant to ceftriaxone. Five serotypes, 19F, 19A, 6B, 23F, and 14, and six genotypes from three genetic lineages were found, among which CC320 was the largest. All isolates in this study carried the erm(B) macrolide resistance gene, and the CC320 isolates additionally carried the mef(A/E) macrolide resistance gene. Eleven isolates carried pilus islet 1, while the CC320 isolates also carried the pilus islet 2 genes. The findings emphasize the importance of the careful monitoring of antimicrobial susceptibility and serotype distribution among pneumococci, especially now that antimicrobials and pneumococcal vaccines are in widespread use.

Antifungal susceptibility and virulence attributes of bloodstream isolates of Candida from Hong Kong and Finland.

Candida bloodstream infection has dramatically increased in the last decade due to the growing number of immunocompromised populations worldwide. In this study, we evaluated the antifungal susceptibility profiles and virulence attributes of Candida bloodstream isolates (CBIs) derived from Hong Kong and Finland, information which are vital for devising empirical clinical strategies. Susceptibility testing of a wide range of antifungals including fluconazole, itraconazole, voriconazole, ketoconazole, 5-fluorocytosine, amphotericin B and caspofungin was performed. Haemolytic activity and secretion of proteinase of CBIs were also examined. All CBIs derived from Hong Kong were susceptible to all the antifungals tested whilst some CBIs from Finland were resistant to azoles and caspofungin. C. albicans, C. glabrata and C. tropicalis showed higher haemolytic activity whereas C. parapsilosis and C. guilliermondii were non-haemolytic in general. Proteinase activity of the Finland C. albicans isolates was significantly higher than the Hong Kong isolates. Our data provide a glimpse of the possible evolutionary changes in pathogenic potential of Candida that may be occurring in different regions of the world. Therefore, continuous surveillance and availability of local data should be taken into consideration when treating candidemia patients.

Comparison of repetitive extragenic palindromic sequence-based PCR with PCR ribotyping and pulsed-field gel electrophoresis in studying the clonality of Clostridium difficile.

Clostridium difficile infection is most often induced by antibiotic treatment. Recently, morbidity and mortality resulting especially from C. difficile PCR ribotype 027 have increased significantly. In addition, more severe disease has been associated with C. difficile PCR ribotype 078 strains. Thus, reliable typing methods for epidemic control are needed. In the present study, we compared an automated repetitive extragenic palindromic sequence-based PCR (rep-PCR) method (DiversiLab; Bacterial Barcodes, Inc., Athens, GA, USA) to PCR ribotyping and pulsed-field gel electrophoresis (PFGE) typing using 205 isolates of C. difficile (including 24 previously characterized isolates). Among the 181 clinical isolates, a total of 31 different PCR ribotypes, 38 different PFGE types and subtypes and 28 different rep-PCR types were found. Six major rep-PCR groups (DL1-DL6) harboured 86% of the clinical isolates. All isolates belonging to PCR ribotypes 027 and 001 clustered in their own rep-PCR groups, enabling us to screen out the hypervirulent ribotype 027 strain. Within the PCR ribotype 001, four subgroups were found using rep-PCR. Overall, in 75% (135/181) of the isolates, the classification attributed following rep-PCR and PCR ribotyping was comparable. In conclusion, the automated rep-PCR-based typing method represents an option for first-line molecular typing in local clinical microbiology laboratories. The method was easy to use as well as rapid, requiring less hands-on time than PCR ribotyping or PFGE typing. The conventional PCR ribotyping or PFGE, however, are needed for confirmatory molecular epidemiology. In addition, more epidemiology-oriented studies are needed to examine the discriminatory power of automated rep-PCR with isolates collected from a larger geographical area and during a longer period of time.

Emergence of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae during the years 2000 and 2004 in Helsinki, Finland.

The molecular epidemiology of 33 Escherichia coli and 81 Klebsiella pneumoniae extended-spectrum beta-lactamase-producing healthcare-associated and community-acquired isolates collected in the Helsinki district during 2000-2004 was investigated. Clonality studies, antimicrobial susceptibility and genotyping of the isolates were performed. Newly emerging CTX-M-producing E. coli and bla(SHV-12)-producing K. pneumoniae isolates were detected. Clonal clusters of both species persisted throughout the study period.

First isolations of KPC-2-carrying ST258 Klebsiella pneumoniae strains in Finland, June and August 2009.

The first two Klebsiella pneumoniae carbapenemase-producing (KPC) type 2 strains carrying ST258 were detected in Finland in June and early August 2009. They were found colonising two patients transferred from the Mediterranean; one patient referred from a hospital in Greece where isolates were first found in 2007 and another from Italy where the first isolates have been described only very recently.

Evaluation of a commercial MRSA assay when multiple MRSA strains are causing epidemics.

Rapid and reliable diagnostic methods are needed to control methicillin-resistant Staphylococcus aureus (MRSA) transmission. We studied the BD GeneOhm MRSA Assay which is based on one specific amplification product at the junction of the right extremity sequence of the staphylococcal cassette chromosome mec (SCCmec) and the chromosomal sequence of orfX of S. aureus. The test was applied on 95 clinical isolates in Finland: 83% were positive. The isolates giving negative results represented several pulsed-field gel electrophoresis (PFGE) types and harboured SCCmec types IV, V, VI or were new types with different combinations of ccr genes.

New 16-plex PCR method for rapid detection of diarrheagenic Escherichia coli directly from stool samples.

A rapid 16-plex polymerase chain reaction (PCR) suitable for routine diagnostics of diarrheagenic Escherichia coli (EHEC, EIEC, EAEC, ETEC, and EPEC) was developed, validated with control strains, and tested with 250 diarrhoeal stool samples. The specificity was 100% when tested with 289 control bacterial strains, and the analytical sensitivity of automated DNA extraction directly from stool samples was made by boiling the bacterial culture (10(4)-10(5) colony forming units/ml). The assay design starting directly from extraction of stool DNA allowed same day analysis without compromising sensitivity and specificity, which makes it superior compared to PCR after culturing the bacteria. The 16-plex PCR method demonstrated high prevalence of diarrheagenic E. coli in stool samples of patients returning from abroad (39.0%) in contrast to the patients with no travel history (8.7%; p < 0.001). The high prevalence of diarrheagenic E. coli suggests that their screening should be part of normal diarrhoea diagnostics, at least in the leading diagnostic laboratories.

Molecular characterization of methicillin-resistant Staphylococcus epidermidis strains from bacteraemic patients.

In order to study the clonality of clinical methicillin-resistant Staphylococcus epidermidis (MRSE) strains and their staphylococcal cassette chromosome mec (SCCmec) elements, 60 isolates of MRSE from bacteraemic patients in three units of the Helsinki University Hospital, Finland were selected, covering the periods 1990-1993 and 1997-1998. The MRSE strains were analysed by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing and SCCmec typing. Eleven PFGE types (FIN-SE-1-11) with sequence type ST2 (clonal complex 2; CC2) were identified. The previously established methicillin-resistant Staphylococcus aureus SCCmec criteria were applied to name the MRSE SCCmec complexes, and it was found that 7% of the isolates carried SCCmec type IA (ccrA1, class B), whereas the majority (93%) yielded six non-typeable SCCmec PCR patterns (P1-P6). Within each SCCmec PCR pattern, two ccr recombinase genes (ccrA2 and ccrA3) and two mec gene complexes (class A and class B) were detected. In addition, the ccrC gene was associated with three of the six patterns. In conclusion, the MRSE strains were genetically related to each other (ST2) but their SCCmec complexes were unique combinations of elements previously recognized among SCCmec types III and IV.

Nosocomial bloodstream infections in children: an 8-year experience at a tertiary-care hospital in Finland.

Laboratory-based surveillance at a Finnish paediatric tertiary-care centre during the period 1999-2006 identified 739 nosocomial bloodstream infections (BSIs) (1.6 BSIs/1000 patient-days). High rates were detected among haematology patients (4.9 BSIs/1000 patient-days) and neonatology patients (3.2 BSIs/1000 patient-days). Most BSIs (95%) were primary infections, and 75% of those were associated with a central line. The most common pathogens were coagulase-negative staphylococci (52%), Staphylococcus aureus (7%) and Candida species (6%). The overall mortality rate within 7 days after the first positive blood culture was 3%. Those who died were more likely to have been admitted to an intensive-care unit or to have undergone surgery.

Costs of an outbreak of meticillin-resistant Staphylococcus aureus.

An outbreak of meticillin-resistant Staphylococcus aureus (MRSA) occurred in surgical and internal medicine units of a 1752-bed Finnish tertiary care hospital during 2003-2004. In order to analyse the costs of this 14-month outbreak, patients were categorized as follows: patients with MRSA infections; patients with MRSA colonization; patients exposed to MRSA but whose MRSA status remained inconclusive; and exposed patients who were negative for MRSA. We reviewed a sample of patients' charts to determine the types of clinical infections and interviewed staff about the practical implementation of control measures. The number of patients and patient-days involved in the outbreak were identified from the hospital's databases, with the administrative database supplying unit costs of work and materials. Loss of income due to closed beds was analysed. A total of 266 MRSA-positive patients (114 with infections and 152 colonized) and 797 patients exposed to MRSA were identified (11,744 contact isolation days). There were 1240 patients negative after screening (9880 contact isolation days). Total additional costs of MRSA were 386,062 euro (70% for screening and 25% for contact isolation). Costs due to meticillin resistance in treatment of MRSA infections were 16,000 euro. The income loss for this hospital due to closed beds was 1,183,808 euro. The high cost of MRSA screening underlines the importance of appropriate screening methods. Our model of analysing costs might be useful for other hospitals after adapting variables such as local control measures.

Postural balance in a random sample of 7,979 subjects aged 30 years and over.

BACKGROUND: Reliable normative data for force platform measurements of postural balance have not been available. METHODS: Data on postural balance were collected from a representative nationwide sample of a Finnish population aged >or=30 years (n = 7,979). As part of a comprehensive health survey (Health 2000), postural balance was measured with the help of a force platform system in four test conditions: normal standing with eyes open and closed (both for 30 s), semi-tandem (20 s) and tandem stand with eyes open (20 s). In addition, balance abilities were also evaluated by a non-instrumented field test. RESULTS: The main findings of this study indicated that the differences in balance between subjects belonging to different age categories were apparent already among young and middle-aged subjects. This is true, however, only for the more accurate force platform measurements, as the field test showed a clear ceiling effect up to 60 years of age. At higher ages both methods indicated a further, accelerating decline in balance function. In most cases, males tended to have more pronounced sway, as indicated by the speed and amplitude aspects of the movement of the center of pressure during the force platform registrations and these differences were larger in the older age groups. In contrast, in the field test a larger proportion of males were able to achieve the highest category (10 s in tandem stand) and the proportion of subjects unable to stand for a minimum of 10 s feet side by side was larger among females than males. These observations may partly be due to differences in the participation/acceptable performance in the different tests. In addition, the field test and force platform measurements may partially reflect different aspects of balance abilities. CONCLUSION: The results of the present study provide normative values for force platform balance tests at an age of 30 years and above. Deterioration in balance function clearly starts at relatively young ages and further accelerates from at about 60 years upwards. Due to systematic differences between males and females, separate normative values for both sexes are needed. Due to marked ceiling effects the field test can only be recommended for older individuals, aged >/=60. On the other hand, force platform registrations in the more demanding tests (semi-tandem and tandem stands) suffer from floor effects in the oldest age groups.

Levofloxacin does not decrease mortality in Staphylococcus aureus bacteraemia when added to the standard treatment: a prospective and randomized clinical trial of 381 patients.

OBJECTIVES: To study whether levofloxacin, added to standard treatment, could reduce the high mortality and complication rates in Staphylococcus aureus bacteraemia. DESIGN: A prospective randomized multicentre trial from January 2000 to August 2002. SETTING: Thirteen tertiary care or university hospitals in Finland. SUBJECTS: Three hundred and eighty-one adult patients with S. aureus bacteraemia. Patients with meningitis, and those with fluoroquinolone- or methicillin-resistant S. aureus were excluded. INTERVENTIONS: Standard treatment (mostly semisynthetic penicillin) (n = 190) or that combined with levofloxacin (n = 191). Supplementary rifampicin was recommended if deep infection was suspected. MAIN OUTCOME MEASURES: Primary end-points were mortality at 28 days and at 3 months. Clinical and laboratory parameters were analysed as secondary end-points. RESULTS: Adding levofloxacin to the standard treatment offered no survival benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin combination did not differ from the standard treatment in the number of complications, time to defervescence, decrease in serum C-reactive protein concentration or length of antibiotic treatment. Deep infection was found in 84% of patients within 1 week following randomization with no difference between the treatment groups. At 3 months, the case fatality rate for patients with deep infection was 17% amongst those who received rifampicin versus 38% for those without rifampicin (P < 0.001, odds ratio = 3.06, 95% confidence intervals = 1.69-5.54). CONCLUSIONS: Levofloxacin combined with standard treatment in S. aureus bacteraemia did not decrease mortality or the incidence of deep infections, nor did it speed up recovery. Interestingly, deep infections in S. aureus bacteraemia appeared to be more common than previously reported.

Effects of a 6-month exercise program on patients with multiple sclerosis: a randomized study.

OBJECTIVE: To improve walking and other aspects of physical function with a progressive 6-month exercise program in patients with multiple sclerosis (MS). METHODS: MS patients with mild to moderate disability (Expanded Disability Status Scale scores 1.0 to 5.5) were randomly assigned to an exercise or control group. The intervention consisted of strength and aerobic training initiated during 3-week inpatient rehabilitation and continued for 23 weeks at home. The groups were evaluated at baseline and at 6 months. The primary outcome was walking speed, measured by 7.62 m and 500 m walk tests. Secondary outcomes included lower extremity strength, upper extremity endurance and dexterity, peak oxygen uptake, and static balance. An intention-to-treat analysis was used. RESULTS: Ninety-one (96%) of the 95 patients entering the study completed it. Change between groups was significant in the 7.62 m (p = 0.04) and 500 m walk tests (p = 0.01). In the 7.62 m walk test, 22% of the exercising patients showed clinically meaningful improvements. The exercise group also showed increased upper extremity endurance as compared to controls. No other noteworthy exercise-induced changes were observed. Exercise adherence varied considerably among the exercisers. CONCLUSIONS: Walking speed improved in this randomized study. The results confirm that exercise is safe for multiple sclerosis patients and should be recommended for those with mild to moderate disability.

Safety of probiotics that contain lactobacilli or bifidobacteria.

Lactobacilli and bifidobacteria are extremely rare causes of infection in humans, as are probiotics based on these organisms. This lack of pathogenicity extends across all age groups and to immunocompromised individuals. Strains used for new probiotics should be chosen from the commensal flora of humans and should not carry intrinsic resistance to antibiotics that would prevent treatment of a rare probiotic infection. Vigilance regarding the detection of possible rare cases of infection due to probiotics should be maintained, and isolates should be sent to reference centers for molecular characterization and confirmation.

Clinical "pneumococcal pneumonia" due to Moraxella osloensis: case report and a review.

A previously healthy 6-y-old girl presented with a disease very similar to pneumococcal pneumonia. However, Moraxella osloensis was isolated by lung tap. The patient responded well to a course of parenteral penicillin. This is probably the first documented case of community-acquired pneumonia associated with this agent. Clinical isolates of M. osloensis are rare and its pathogenesis has not been delineated; however, a literature review suggests that the organism is more common than is generally recognized.

BRCT domain-containing protein TopBP1 functions in DNA replication and damage response.

Topoisomerase IIbeta-binding protein (TopBP1), a human protein with eight BRCT domains, is similar to Saccharomyces cerevisiae Dpb11 and Schizosaccharomyces pombe Cut5 checkpoint proteins and closely related to Drosophila Mus101. We show that human TopBP1 is required for DNA replication and that it interacts with DNA polymerase epsilon. In S phase TopBP1 colocalizes with Brca1 to foci that do not represent sites of ongoing DNA replication. Inhibition of DNA synthesis leads to relocalization of TopBP1 together with Brca1 to replication forks, suggesting a role in rescue of stalled forks. DNA damage induces formation of distinct TopBP1 foci that colocalize with Brca1 in S phase, but not in G(1) phase. We also show that TopBP1 interacts with the checkpoint protein hRad9. Thus, these results implicate TopBP1 in replication and checkpoint functions.