Outbreak of methicillin-resistant Staphylococcus aureus in two nursing homes in Central Norway.

Until recently, infections with methicillin-resistant Staphylococcus aureus (MRSA) have mainly been associated with hospital outbreaks in Norway. However, increasingly cases are contracted outside hospitals. This paper reports the first two outbreaks of MRSA in two nursing homes in central Norway, affecting 23 residents and five staff members. Pulsed-field gel electrophoresis analysis showed that all strains from nursing home A were identical and that the strains from nursing home B were genotypically similar with one or two band differences. Multi-locus sequence typing (MLST) showed that the strains from the two nursing homes belong to clonal complex 45, with each strain being a single-locus variant of sequence type 45 (ST 45), a well-known European epidemic strain. No evident source of the two outbreaks was found, and there was no obvious connection between the two outbreaks. The latter is also supported by the minor differences observed by MLST, suggesting a connection at some time in the past. The outbreaks led to a heavier workload and economic strain on both nursing homes. The outbreak in nursing home A was brought to an end, whereas two residents remained colonized in nursing home B despite several eradication attempts. These outbreaks show the potential for MRSA spread in a nursing home. If the prevalence of MRSA in Norway continues to increase, nursing home staff and residents may have to be included in the groups to be screened for MRSA upon hospital admission.

The role of membrane-bound LBP, endotoxin aggregates, and the MaxiK channel in LPS-induced cell activation.

We have previously shown in patch-clamp experiments on excised outside-out cytoplasmic membrane patches from human macrophages that the activation of a high-conductance Ca(2+)- and voltage-dependent potassium channel, the MaxiK channel, is an early step in LPS-induced transmembrane signal transduction in macrophages. MaxiK can be activated by agonistically active LPS, and activation can be completely inhibited by LPS antagonists (e.g. synthetic compound 406) and by anti-CD14 antibodies. Furthermore, by inhibiting MaxiK with the specific MaxiK blocker paxilline, we could show that activation of MaxiK is essential for LPS-induced cytokine production. As shown by RT-PCR, blockade of MaxiK by paxilline also inhibits induction of the mRNA of TNF-alpha and IL-6. This observation together with the fact that all patch-clamp experiments were done on excised outside-out patches reveal that MaxiK activation is an early step in cell activation by endotoxins. Thus, since cells lacking TLR4 on their surface can also not be activated to produce cytokines, these data allow the conclusion that TLR4 and MaxiK are both essential for activation by LPS and may form a co-operative signaling complex. We have also shown that LBP not only exists as a soluble acute-phase serum protein, but is also incorporated as a transmembrane protein (mLBP) in the cytoplasmic membrane of MNC; in this configuration, it is obviously involved in the binding of endotoxin and its transfer to the transmembrane signaling proteins finally triggering cell activation. Complexation of soluble LBP and LPS in the serum prior to binding of LPS to mLBP, in contrast, leads to neutralization of LPS. Here, we provide evidence from fluorescence resonance energy transfer spectroscopy that endotoxin aggregates are intercalated into reconstituted membranes by mLBP. In addition, cell culture assays and patch-clamp experiments demonstrate that endotoxin activates macrophages and the MaxiK channel in the aggregated, but not in the monomeric, state at similar concentrations.

A K+ channel is involved in LPS signaling.

We previously showed a clear correlation between the molecular conformation of the lipid A moiety of endotoxin molecules and their cytokine-inducing capacity in mononuclear cells. While conically shaped lipid A moieties exhibit a high agonistic activity, a shift to a more cylindrically shaped lipid A leads to a decrease in agonistic and increase in antagonistic activity of the endotoxin molecules. Here, we show the involvement of a high-conductance Ca2+-activated potassium (MaxiK) channel in LPS signaling in macrophages. Corresponding to their biological activity, endotoxins activate a MaxiK channel as shown in outside-out patch-clamp experiments. LPS antagonists and anti-CD14 antibodies inhibit the LPS-induced activation of the channel. Blocking of the channel by specific channel blockers in macrophage cultures leads to inhibition of cytokine mRNA production. In particular, this result implies that there is no other independent transmembrane signaling pathway operative in macrophages. A shift of the molecular conformation of an a priori antagonistic lipid A from a cylindrical to a conical shape by adding the membrane-active compound chlorpromazine increases the activity of the MaxiK channel and the biological activity of the lipid A. We conclude that the activation of the MaxiK channel is a very early step in LPS-induced signaling in macrophages.

Outbreak of methicillin-resistant Staphylococcus aureus in a Norwegian hospital.

Methicillin-resistant Staphylococcus aureus (MRSA) occurred sporadically in Norwegian hospitals in the 1960s and 1970s, but disappeared in the late 1970s for unknown reasons. Only 1 outbreak has subsequently been reported. We describe herein a second outbreak in a different hospital, this time featuring a more resistant strain. Staff and patients were screened immediately after detection of the first MRSA isolate. Colonized and infected patients were nursed using contact precautions, and the staff were not allowed to work until 3 nose samples were MRSA-negative. We treated colonized persons with topical administration of mupirocin to the nostrils and a chlorhexidine body wash. The outbreak affected 7 patients and 5 healthcare workers. Pulsed-field gel electrophoresis proved all isolates to be of the same type, and the MRSA phage type was M3. There was no sign of transmission of MRSA after contact precautions were implemented. MRSA was eradicated in 4 of the patients and all 5 healthcare workers. One patient died and 1 was still colonized 3 y after onset of the outbreak. Contact precautions proved to be sufficient to prevent transmission of MRSA.

Measurement of the individual exposure to 50 and 16 2/3 Hz magnetic fields within the Bavarian population.

This study investigates the individual magnetic field exposures at 16 2/3 and 50 Hz of 1952 people, selected from the Bavarian population. Personal flux density meters ("Field Watcher FW2A") were worn by the participants for 24 h. Every second, the flux density was recorded for both frequencies and for the three spatial axes (dynamic range per axis: several nT up to 100 microT at 50 Hz, 150 microT at 16 2/3 Hz). For 50 Hz fields, the mean of the 1,952 individual means was 0.101 microT and that of the individual medians was 0.047 microT. High level exposures occurred mainly during working hours. Only 2.4% of the subjects showed individual medians higher than 0.2 microT. About 53% of all volunteers were working on the day of recording. Levels for craftsmen (n = 148; mean individual mean: 0.166 microT) were generally higher than those for office workers (n = 624; mean individual mean: 0.107 microT). Flux densities exceeding 100 microT at 50 Hz were measured in 31 persons. The total time with such extreme exposures amounts to nearly 21 min, less than 0.001% of the total time for all measurements (5.3 years). To our knowledge, this is the first exposure study where 16 2/3 Hz magnetic fields (caused by electrified railways) have additionally been monitored over 24 h. For persons living next to railway lines, the mean individual mean (0.156 microT) and mean individual median (0.102 microT) were calculated. Over all, the mean exposures are only 0.1% of the magnetic flux density limit for 50 Hz (100 microT) and about 0.05% of the limit (300 microT) for 16 2/3 Hz recommended by the International Commission on Non-Ionizing Radiation Protection.

New insights into endotoxin-induced activation of macrophages: involvement of a K+ channel in transmembrane signaling.

LPS (endotoxins) activate cells of the human immune system, among which are monocytes and macrophages, to produce endogenous mediators. These regulate the immune response, but may also cause severe harm leading to septic shock. The activation of monocytes/macrophages by LPS is mediated by a membrane-bound LPS receptor, mCD14. As mCD14 lacks a transmembrane domain, a further protein is required for the signal transducing step to the cell interior. Here we show, using excised outside-out membrane patches, that activation of a high-conductance Ca(2+)- and voltage-dependent potassium channel is an early step in the transmembrane signal transduction in macrophages. The channel is activated by endotoxically active LPS in a dose-dependent manner. Channel activation can be completely inhibited by LPS antagonists and by anti-CD14 Abs. Activation of the channel is essential for LPS-induced cytokine production as shown by its inhibition by selective K(+) channel blockers.

[Antibiotic resistance of blood culture isolates in Buskerud in 1994 and 1998]. / Antibiotikaresistens i blodkulturisolater i Buskerud i 1994 og 1998.

BACKGROUND: The increase of antimicrobial resistance has caused general concern world-wide. There is a high risk that this development will also occur in Norway. Several efforts have been made to prevent the emergence of antimicrobial resistance. A national surveillance programme for antimicrobial resistance has been started, and new legislation has made resistance surveillance programmes compulsory in every Norwegian hospital. Local surveillance of resistance is among the most important measures. MATERIAL AND METHODS: We have undertaken surveillance of all blood culture isolates from the County of Buskerud in 1994 and 1998. Detection of antibiotic resistance-patterns were undertaken for all blood culture isolates in the two years using disc diffusion method (Rosco diagnostics, Taastrup, Denmark). We also looked at the consumption of antimicrobial agents in Buskerud Central Hospital in 1998. A total of 628 isolates from 572 patients were included in the study, 279 isolates from 1994 and 349 from 1998. RESULTS: We still have low occurrence of resistance in Buskerud, and there has been no significant increase during the four-year period. INTERPRETATION: The low prevalence of antibiotic resistance reflects the restrictive antibiotic policy in Norway. Therefore, we find it important to continue this policy and to continue close surveillance of the development of antibiotic resistance.

The C5a receptor is expressed in normal renal proximal tubular but not in normal pulmonary or hepatic epithelial cells.

C5a, a 74 amino acid peptide cleaved from the complement protein C5, is an extremely potent anaphylatoxin. Expression of the receptor for the anaphylatoxin C5a (C5aR) has been thought to be restricted to cells of myeloid origin. However, recent evidence suggests that the C5aR is also expressed in hepatocytes as well as in pulmonary epithelial, endothelial and smooth muscle cells. In the present study, we investigated the tissue distribution of C5aR by immunohistochemistry in normal human lung, liver, intestine and kidney using well-defined monoclonal antibodies (mAbs) directed against the extracellular N-terminus of the receptor. In all tissues examined, macrophages displayed an abundant expression of C5aR protein. However, in the normal human lung, C5aR expression was not detectable in bronchial and alveolar epithelial cells or in vascular smooth muscle or endothelial cells. In the normal human liver, no C5aR protein was detected in hepatocytes, whereas Kupffer cells strongly expressed the C5aR. In normal human kidney, the C5aR was detectable only in proximal tubular cells. C5aR gene transcription in Kupffer cells and proximal tubular cells was confirmed by in situ hybridization. Thus, our results point to an as yet unknown role of the C5aR in normal renal physiology. In the normal lung and liver, however, previous evidence for the ubiquitous expression of C5aR in epithelial, endothelial and smooth muscle cells in situ should be re-evaluated.

National prevalence survey on hospital infections in Norway.

A nationwide prevalence survey was carried out in Norwegian hospitals (excluding mental hospitals) on 23 October 1997. The aim was to assess the magnitude of major hospital-acquired infections (HAIs) prior to the introduction of quarterly prevalence surveys in Norway as required by the new Regulations for Communicable Disease Control in Hospitals. The survey included 71 of 76 possible hospitals, and 12,775 patients. Altogether 779 HAIs were identified--a prevalence rate of 6.1%. Only the four major HAIs were included: urinary tract infection (36.4% of all HAIs); surgical wound infection (28.6%); lower respiratory tract infection (25.4%) and septicaemia (9.6%). Three thousand, three hundred and forty-nine patients had undergone surgery and the prevalence of surgical wound infection was 6.3%. The results form a baseline for the next step in Norweigan hospital infection control; the quarterly prevalence surveys.

Living with methicillin-resistant Staphylococcus aureus: a 7-year experience with endemic MRSA in a university hospital.

A review of our infection control records revealed 3,159 new isolations of methicillin-resistant Staphylococcus aureus (MRSA) from 1988 to 1994. Prior to this period, our approach to MRSA had changed from eradication to containment measures. We found a decline in MRSA rates from 11.4 to 5.2 first isolations per 1,000 deaths and discharges over the study period.

[Chlamydia pneumoniae infections in Norway]. / Chlamydia pneumoniae-infeksjoner i Norge.

During the last 5-6 years our understanding of Chlamydia pneumoniae has changed radically. C. pneumoniae is no longer considered a dangerous, obligatory pathogen. Rather, it is a common, highly contagious intracellular opportunist, inducing poor immunity and with a tendency to repeated reinfections. At present, a possible role in the formation of atheromatous plaques is being discussed. There is a significantly higher prevalence of antibodies against C. pneumoniae in coronary heart disease patients than in controls. Another unsolved problem is that of therapy, since chronic lung infection resists long-term macrolide antibiotic treatment. Should additional treatment with cortisone be given? Here we clearly need clinical trials before we move in a totally new direction.

Comparison of E-test with agar dilution for determining susceptibility of Streptococcus pneumoniae to penicillin.

Minimum inhibitory concentrations (MICs) of penicillin for Streptococcus pneumoniae were determined by the E-test and the agar dilution method. Ninety Streptococcus pneumoniae strains were tested, of which 16 were resistant, 33 intermediate, and 41 susceptible by agar dilution. By the E-test, 80 (88.9%) strains agreed with these determinations within one log2 dilution step, and no strains disagreed by more than two dilution steps. Sixty-eight of the 70 strains with discrepant MICs read lower in the E-test, resulting in 15 strains being placed in different susceptibility categories when classified by this test. Exact MICs rather than classification groups should be used to determine appropriate antibiotic therapy, since small differences in MICs determined by different methods can lead to a significant degree of misclassification.

[Homeopathy--time for official authorization?]. / Homøopati--tid for offentlig godkjenning?

The Norwegian government has recently appointed a committee to scrutinise alternative therapies and distinguish between serious and nonserious practitioners in preparation for future authorisation. Homoeopathy seems to be the most popular of alternative therapies in Norway, and counts Prime Minister Thorbjørn Jagland among contented patients. For this reason we have taken a closer look at the principles of homoeopathy, and the documentation. Just as in a recent report on documentation and the effect of selected alternative therapies, we too were unable to find studies of reasonable quality that were confirmed by others. Homoeopathists use theoretical physics to explain how water "remembers" the information from molecules no longer existing in the solution, when the liquid is shaken in a special way between every dilution. It does not matter whether the homoeopathist is serious or not as long as the remedy consists only of pure water. We conclude, therefore, that homoeopathy should not be authorised as a serious medical treatment in the Norwegian Health Service.