Diminished in vitro antibacterial activity of oxacillin against clinical isolates of borderline oxacillin-resistant Staphylococcus aureus

Since it is unknown whether β-lactam antimicrobial agents can be used effectively against borderline oxacillin-resistant Staphylococcus aureus (BORSA) with oxacillin MICs ≥4 mg/L, the in vitro bactericidal activity and pharmacodynamic effect of oxacillin against clinical BORSA isolates was evaluated. Time-kill experiments with oxacillin were performed and the results compared with those obtained with vancomycin, daptomycin and linezolid against BORSA with oxacillin MICs ≥4 mg/L and BORSA with oxacillin MICs ≤2 mg/L. Furthermore, the effect of β-lactamase production and plasmid profile analysis were taken into account to clarify responses to oxacillin. Oxacillin killing activity was attenuated against BORSA compared with ATCC 29213 since the pharmacodynamic parameters revealed that the potency of oxacillin was markedly reduced (c. ten-fold) against BORSA with oxacillin MICs ≥4 mg/L. pBORa53-like plasmid-containing BORSA with oxacillin MICs ≤2 mg/L showed markedly more regrowth. In conclusion, oxacillin was non-effective in the eradication of either (i) BORSA with oxacillin MICs ≥4 mg/L or (ii) β-lactamase-hyperproducing BORSA (MICs ≤2 mg/L). Further investigation into β-lactam dosing strategies against different BORSA strains is warranted in order to avoid possible therapy failure.     

Prevalence of Antibiotic Resistance of the Commensal Flora in Dutch Nursing Homes

ObjectivesTo determine the prevalence of antibiotic resistance and multiresistance of Escherichia coli and Staphylococcus aureus in nursing homes and to determine which factors are associated with this prevalence.DesignCohort study.SettingNursing homes.ParticipantsResidents of long-stay somatic care wards and rehabilitation patients were recruited from five nursing homes and two rehabilitation wards in hospitals in the central region of the Netherlands.MeasurementsFrom each included patient, an anal swab was analyzed for E. coli and its antibiotic susceptibility and extended spectrum β-lactamase-producing Enterobacteriaceae. Nasal swabs were analyzed for S. aureus and its susceptibility, including methicillin-resistant S. aureus (MRSA). Associations were determined between resistance of E. coli to amoxicillin/co-amoxiclav and recent use (previous 6 months) of these antibiotics, hospital admission (previous 3 months), and presence of a urinary catheter.ResultsA total of 125 patients were included in the study. The resistance and intermediate susceptibility of E. coli varied from 4% (ceftriaxone) to 43% (amoxicillin). Extended spectrum β-lactamase-producing Enterobacteriaceae were found in 6% of the patients. Amoxicillin and/or co-amoxiclav users were significantly more resistant to these antibiotics (69%) than nonusers (38%). No associations were found between amoxicillin and/or co-amoxiclav resistance and hospital admission or presence of a urine catheter. The resistance of S. aureus varied from 0% to 69% (penicillin). No MRSA was found. The ciprofloxacin resistance in E. coli and S. aureus was 14% and 39%, respectively.ConclusionThe prevalence of antibiotic-resistant E. coli and S. aureus in nursing homes was considerably high in this study, although no MRSA was found. This may lead to failing of empiric therapy of infections in patients in nursing homes. In particular, the high resistance to ciprofloxacin may make empiric quinolone therapy unreliable. Antibiotic use was associated with antibiotic resistance of E. coli. Therefore, antibiotic use should be restricted as much as possible. Analysis of risk factors for antibiotic resistance should be extended to be able to prevent further development of antibiotic resistance in nursing homes.     

Healthy Living with Persuasive Technologies: Framework, Issues, and Challenges

While our Y2K worries about old computers “retiring” at midnight captured the television and news media attention, a more significant “old age” phenomenon snuck onto the scene with hardly a headline: the dawn of the age of the aged.¹ The over burdened health care system will face a worldwide wave of retirees who will live longer, cost more to treat, and demand new goods and services to help them stay healthy, active, and independent. Research in persuasive technologies and the associated usage of a computing system, device, or application intentionally designed to change a person's attitude or behavior in a predetermined way is showing the potential to assist in improving healthy living, reduce the costs on the health care system, and allow the aged to maintain a more independent life. This article gives a deeper insight into the evolution of persuasive technologies and presents a framework that can guide a researcher or practitioner in comprehending more effectively the work being done in this novel research field. It also provides categories of domains within health care in which these technologies are used and surveys exemplars from published literature. The article's goal is to provide greater understanding by addressing the challenges that lie ahead for all key stakeholders that design and/or use persuasive technologies in health care.     

A variant of the Southern German clone of methicillin-resistant Staphylococcus aureus is predominant in Croatia

The aim of the present study was to investigate the antibiotic susceptibility patterns and molecular epidemiology of clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered in 24 hospitals in 20 cities in Croatia from October to December 2004. A total of 1815 consecutive S. aureus isolates were recovered, 248 of which were MRSA. The MRSA isolates were analysed using spa typing, multilocus sequence typing and SCCmec typing. Furthermore, the presence of Panton–Valentine leukocidin (PVL) genes was determined as a genetic marker for community-associated MRSA. The MRSA prevalence was 14%. Ninety-six per cent of the MRSA isolates were resistant to ciprofloxacin, 95% to clindamycin and azithromycin, 94% to gentamicin, and 93% to erythromycin. The majority of the MRSA isolates (78%) was associated with the ST111-MRSA-I clone. In addition, various other endemic MRSA clones were observed, such as the ST247-MRSA-I (4%), the ST45-MRSA-IV (2%), the ST5-MRSA-I (2%), the ST239-MRSA-III (2%), the ST5-MRSA-II (1%), the ST8-MRSA-IV (1%) and the ST5-MRSA-IV (<1%) clones. Furthermore, we observed one PVL-negative ST80-MRSA-IV isolate. Four PVL-positive MRSA isolates were found, associated with ST8-MRSA-IV, ST80-MRSA-IV and ST80-MRSA-I. The ST111-MRSA-I clone was predominant in Croatia. Future surveillance studies of MRSA are important to elucidate whether changes in the clonal distribution of MRSA will occur, and if the minor endemic MRSA clones observed in the present study will replace the ST111-MRSA-I clone on a large scale.     

Ataxin-3 is transported into the nucleus and associates with the nuclear matrix

It has been reported that the ataxin-3 protein containing a polyglutamine sequence in the pathological range (61-84Q) is localized within the nucleus of neuronal cells, whereas ataxin-3 with a normal repeat length (12-37Q) is predominantly a cytoplasmic protein. In this study, the subcellular localization of the full-length ataxin-3 protein with a glutamine sequence in the normal range (Q3KQ22) was analysed in two mammalian cell lines. Using two affinity-purified polyclonal antibodies raised against the N- or C-terminal portion of ataxin-3, the protein was detected predominantly, but not exclusively, in the nucleus of COS-7 as well as neuroblastoma cells by immunofluorescence and confocal laser scanning microscopy (CLSM). The distribution of the protein in these cellular compartments was confirmed by biochemical subcellular fractionations. Furthermore, CLSM revealed that the ataxin- 3 protein present in the nucleus of neuroblastoma cells is associated with the inner nuclear matrix. Our results taken together with the finding of a nuclear localization signal in ataxin-3 indicate that the ataxin-3 protein per se translocates to the nucleus and that an expanded glutamine repeat is not essential for this transport.      

Application of Different Genotyping Methods for Pseudomonas aeruginosa in a Setting of Endemicity in an Intensive Care Unit

Colonization with Pseudomonas aeruginosa was studied by taking serial swab specimens from the oropharynges and anuses and tracheal and gastric aspirates from patients in an intensive care unit during a 10-month period in a setting of endemicity. Nineteen (10%) of the 192 patients included in the study were colonized on admission, while another 30 (16%) patients acquired P. aeruginosa while in the hospital. Typing of 353 isolates was performed by random amplified polymorphic DNA (RAPD) analysis, and 56 strains were selected for further typing by RAPD analysis, pulsed-field gel electrophoresis (PFGE), and amplified fragment length polymorphism (AFLP) analysis. By these methods, 42, 44, and 44 genotypes were found, respectively. Computer-aided cluster analysis indicated that similar groups of related isolates were obtained by each method. By taking admission periods into account, analysis of the typing results suggested cross-acquisition of P. aeruginosa for five patient pairs. The small number of transfers and the large number of genotypes found indicate that most P. aeruginosa strains were derived from the patients themselves. The numbers of observed typing patterns and band differences between related isolates were counted for each typing method. AFLP analysis with primers without a selective base proved to be the most discriminatory method, followed by PFGE, AFLP analysis (with one selective base), and RAPD analysis. On the basis of a comparison with established strain differentiation criteria for PFGE, the criteria for differentiation of P. aeruginosa by AFLP analysis are presented.