Germ-free mice deficient of reactive oxygen species have increased arthritis susceptibility.

The NADPH oxidase 2 (NOX2) complex is responsible for the production of ROS in phagocytic cells. Genetic defects in NOX2 lead to opportunistic infections and inflammatory manifestations such as granulomas in humans, also known as chronic granulomatous disease (CGD). This condition is mirrored in mice with defective ROS production and interestingly both species are predisposed to autoimmune diseases. An unresolved question is whether the hyper-inflammation and tendency to develop autoimmunity are secondary to the increased infections, or whether these are parallel phenomena. We generated germ-free ROS deficient Ncf1 mutant mice that when reared in specific pathogen-free condition, are highly susceptible to collagen-induced arthritis compared with wild-type mice. Strikingly, arthritis incidence and severity was almost identical in germ-free and specific pathogen-free ROS-deficient mice. In addition, partial reduction of the microbial flora by antibiotics treatment did not alter the disease course. Taken together, this shows that ROS has a clear immune regulatory function that is decoupled from its function in host defence.

Normal gut microbiota modulates brain development and behavior.

Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.

Changes in the aerobic faecal flora of patients treated with antibiotics for acute intra-abdominal infection.

BACKGROUND: An open observational study was performed to investigate changes in the rectal flora and antibiotic susceptibility among faecal bacteria in patients treated with antibiotics for acute intra-abdominal infection. METHODS: One hundred and forty patients with acute intra-abdominal infection requiring antibiotic treatment and hospitalization were included. Eight surgical units from the southern part of Sweden participated, between January 2006 and November 2007. Antibiotic treatments were according to local guidelines. Rectal swabs were obtained on admission (sample 1) and 2-14 days after the end of antibiotic treatment (sample 2). Aerobic bacteria and yeasts were analysed. The material was divided into 2 groups: 1 group with Enterobacteriaceae and 1 group with non-fermentative Gram-negative bacteria. The susceptibility to antibiotics in each group was compared between samples 1 and 2. RESULTS: The main finding of this study on patients with severe intra-abdominal infections was a shift in the aerobic faecal flora following antibiotic treatment, from Escherichia coli to other more resistant Enterobacteriaceae, Enterococcus faecium, and yeasts. The susceptibility to cephalosporins and piperacillin-tazobactam decreased in Enterobacteriaceae. CONCLUSIONS: Following antibiotic treatment, a shift in the aerobic rectal flora to species with intrinsic antibiotic resistance was observed. This indicates that the emergence of resistance is not due to new mutations, but rather to selection of more resistant species. This should be taken into account when designing treatments for secondary intra-abdominal infections.

Direct health care costs and length of hospital stay related to health care-acquired infections in adult patients based on point prevalence measurements.

BACKGROUND: The incidence of health care-acquired infection (HAI) and the consequence for patients with HAI tend to vary from study to study. By including all patients, all medical specialties, and performing a follow-up analysis, this study contributes to previous findings in this research field. METHODS: Data from the Swedish National Point Prevalence Surveys of HAI 2010-2012 was merged with cost per patient data from the county Health Care Register (N = 6,823). Extended length of stay (LOS) and costs related to an HAI were adjusted for sex, age, intensive care unit use, and surgery. RESULTS: Patients with HAI (n = 732) had a larger proportion of readmissions compared with patients with no HAI (29.0% vs 16.5%). Of the total bed days, 9.3% was considered to be excess days attributed to the group of patients with an HAI. The excess LOS comprised 11.4% of the total costs (95% CI, 10.2-12.7). The 1-year overall mortality rate for patients with HAI in comparison to all other patients was 1.75 (95% CI, 1.45-2.11), all 5 of these differences were statistically significant (P < .001). CONCLUSIONS: Even if not all outcomes for patients with an HAI can be explained by the HAI itself, the increase in inpatient days, readmissions, associated costs, and higher mortality rates are quite notable.

A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county.

In contrast to methicillin-resistant Staphylococcus aureus (MRSA), studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. Since 2004, an increasing incidence of concomitant resistance to erythromycin, clindamycin and tobramycin (ECT) among MSSA has been detected in Ostergotland County, Sweden. The objectives of this study were to investigate the genetic relatedness among these isolates with 2 genotyping methods, pulsed-field gel electrophoresis (PFGE), and sequence-based typing of the polymorphic region X of the staphylococcal protein A gene (spa typing), and to determine the incidence of the Panton-Valentine leukocidin (PVL) gene. When genotyping 54 ECT-resistant MSSA isolates from 49 patients (1 isolate per patient per y), 91% were shown to be part of a clonal outbreak with both methods used (spa type t002). The clonal outbreak was concentrated in 8 hospital departments and 2 primary care centres, all located in the city of Linkoping. All isolates were negative for the PVL gene. In conclusion, this study demonstrates an ongoing clonal outbreak of PVL-negative ECT-resistant MSSA. This stresses the need to continuously maintain basic hygiene rules, since nosocomial transmission of pathogens is not limited to known resistant bacteria such as MRSA.

Division of the genus Enterococcus into species groups using PCR-based molecular typing methods.

Broad-range 16S rDNA PCR (BR-PCR) applied to DNA from 32 clinical enterococcal isolates and 12 other enterococci from a clinical reference collection followed by species-specific hybridization analysis identified 25 strains of Enterococcus faecalis and 19 Enterococcus species. Randomly amplified polymorphic DNA (RAPD) analysis using UPGMA clustering on the same material revealed four different clusters at a similarity level of 49%. Based on partial 16S rDNA sequence analysis of variable regions V4 and V9, it was possible to divide the 19 type strains specifying the genus Enterococcus into 12 different 16S rDNA species groups. The type strain distribution then served as a template for the analysis of the other 44 strains which were assigned to four different species groups (a-d) based on their 16S rDNA motifs. There was good agreement with the RAPD clusters. Species group a was an individual species line containing 25 strains that were identified as E. faecalis. Group b also represented an individual species line of 12 strains identified as E. faecium. The remaining seven strains that formed species groups c and d could not be fully identified to species by this analysis. It was concluded that BR-PCR of 16S rDNA followed by partial sequence analysis of the PCR products is a reliable technique for the identification and classification of enterococci. Further division of unresolved species groups should be achievable if regions other than V4 and V9 of 16S rDNA are also analysed.