bluuebunny/crossref_metadata_2025 huggingface dataset:
An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis
Authors: Pal Saumen , Wu Jing , Murray Justin K. , Gellman Samuel H. , Wozniak Michele A. , Keely Patricia J. , Boyer Meghan E. , Gomez Timothy M. , Hasso Sean M. , Fallon John F. , Bresnick Emery H.
Published: September 2006

Establishment of angiogenic circuits that orchestrate blood vessel development and remodeling requires an exquisite balance between the activities of pro- and antiangiogenic factors. However, the logic that permits complex signal integration by vascular endothelium is poorly understood. We demonstrate that a “neuropeptide,” neurokinin-B (NK-B), reversibly inhibits endothelial cell vascular network assembly and opposes angiogenesis in the chicken chorioallantoic membrane. Disruption of endogenous NK-B signaling promoted angiogenesis. Mechanistic analyses defined a multicomponent pathway in which NK-B signaling converges upon cellular processes essential for angiogenesis. NK-B−mediated ablation of Ca2+ oscillations and elevation of 3′–5′ cyclic adenosine monophosphate (cAMP) reduced cellular proliferation, migration, and vascular endothelial growth factor receptor expression and induced the antiangiogenic protein calreticulin. Whereas NK-B initiated certain responses, other activities required additional stimuli that increase cAMP. Although NK-B is a neurotransmitter/ neuromodulator and NK-B overexpression characterizes the pregnancy-associated disorder preeclampsia, NK-B had not been linked to vascular remodeling. These results establish a conserved mechanism in which NK-B instigates multiple activities that collectively oppose vascular remodeling.
Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite
Authors: O'Donnell Rebecca A. , Hackett Fiona , Howell Steven A. , Treeck Moritz , Struck Nicole , Krnajski Zita , Withers-Martinez Chrislaine , Gilberger Tim W. , Blackman Michael J.
Published: September 2006

Apicomplexan pathogens are obligate intracellular parasites. To enter cells, they must bind with high affinity to host cell receptors and then uncouple these interactions to complete invasion. Merozoites of Plasmodium falciparum, the parasite responsible for the most dangerous form of malaria, invade erythrocytes using a family of adhesins called Duffy binding ligand-erythrocyte binding proteins (DBL-EBPs). The best-characterized P. falciparum DBL-EBP is erythrocyte binding antigen 175 (EBA-175), which binds erythrocyte surface glycophorin A. We report that EBA-175 is shed from the merozoite at around the point of invasion. Shedding occurs by proteolytic cleavage within the transmembrane domain (TMD) at a site that is conserved across the DBL-EBP family. We show that EBA-175 is cleaved by PfROM4, a rhomboid protease that localizes to the merozoite plasma membrane, but not by other rhomboids tested. Mutations within the EBA-175 TMD that abolish cleavage by PfROM4 prevent parasite growth. Our results identify a crucial role for intramembrane proteolysis in the life cycle of this pathogen.
NCAM promotes assembly and activity-dependent remodeling of the postsynaptic signaling complex
Authors: Sytnyk Vladimir , Leshchyns'ka Iryna , Nikonenko Alexander G. , Schachner Melitta
Published: September 2006

The neural cell adhesion molecule (NCAM) regulates synapse formation and synaptic strength via mechanisms that have remained unknown. We show that NCAM associates with the postsynaptic spectrin-based scaffold, cross-linking NCAM with the N-methyl-d-aspartate (NMDA) receptor and Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα) in a manner not firmly or directly linked to PSD95 and α-actinin. Clustering of NCAM promotes formation of detergent-insoluble complexes enriched in postsynaptic proteins and resembling postsynaptic densities. Disruption of the NCAM–spectrin complex decreases the size of postsynaptic densities and reduces synaptic targeting of NCAM–spectrin–associated postsynaptic proteins, including spectrin, NMDA receptors, and CaMKIIα. Degeneration of the spectrin scaffold in NCAM-deficient neurons results in an inability to recruit CaMKIIα to synapses after NMDA receptor activation, which is a critical process in NMDA receptor–dependent long-term potentiation. The combined observations indicate that NCAM promotes assembly of the spectrin-based postsynaptic signaling complex, which is required for activity-associated, long-lasting changes in synaptic strength. Its abnormal function may contribute to the etiology of neuropsychiatric disorders associated with mutations in or abnormal expression of NCAM.
Exomer: a coat complex for transport of select membrane proteins from the trans-Golgi network to the plasma membrane in yeast
Authors: Wang Chao-Wen , Hamamoto Susan , Orci Lelio , Schekman Randy
Published: September 2006

Ayeast plasma membrane protein, Chs3p, transits to the mother–bud neck from a reservoir comprising the trans-Golgi network (TGN) and endosomal system. Two TGN/endosomal peripheral proteins, Chs5p and Chs6p, and three Chs6p paralogues form a complex that is required for the TGN to cell surface transport of Chs3p. The role of these peripheral proteins has not been clear, and we now provide evidence that they create a coat complex required for the capture of membrane proteins en route to the cell surface. Sec7p, a Golgi protein required for general membrane traffic and functioning as a nucleotide exchange factor for the guanosine triphosphate (GTP)–binding protein Arf1p, is required to recruit Chs5p to the TGN surface in vivo. Recombinant forms of Chs5p, Chs6p, and the Chs6p paralogues expressed in baculovirus form a complex of approximately 1 MD that binds synthetic liposomes in a reaction requiring acidic phospholipids, Arf1p, and the nonhydrolyzable GTPγS. The complex remains bound to liposomes centrifuged on a sucrose density gradient. Thin section electron microscopy reveals a spiky coat structure on liposomes incubated with the full complex, Arf1p, and GTPγS. We termed the novel coat exomer for its role in exocytosis from the TGN to the cell surface. Unlike other coats (e.g., coat protein complex I, II, and clathrin/adaptor protein complex), the exomer does not form buds or vesicles on liposomes.
Autoinhibition regulates the motility of the C. elegans intraflagellar transport motor OSM-3
Authors: Imanishi Miki , Endres Nicholas F. , Gennerich Arne , Vale Ronald D.
Published: September 2006

OSM-3 is a Kinesin-2 family member from Caenorhabditis elegans that is involved in intraflagellar transport (IFT), a process essential for the construction and maintenance of sensory cilia. In this study, using a single-molecule fluorescence assay, we show that bacterially expressed OSM-3 in solution does not move processively (multiple steps along a microtubule without dissociation) and displays low microtubule-stimulated adenosine triphosphatase (ATPase) activity. However, a point mutation (G444E) in a predicted hinge region of OSM-3's coiled-coil stalk as well as a deletion of that hinge activate ATPase activity and induce robust processive movement. These hinge mutations also cause a conformational change in OSM-3, causing it to adopt a more extended conformation. The motility of wild-type OSM-3 also can be activated by attaching the motor to beads in an optical trap, a situation that may mimic attachment to IFT cargo. Our results suggest that OSM-3 motility is repressed by an intramolecular interaction that involves folding about a central hinge and that IFT cargo binding relieves this autoinhibition in vivo. Interestingly, the G444E allele in C. elegans produces similar ciliary defects to an osm-3–null mutation, suggesting that autoinhibition is important for OSM-3's biological function.
Mechanism of transport of IFT particles in C. elegans cilia by the concerted action of kinesin-II and OSM-3 motors
Authors: Pan Xiaoyu , Ou Guangshuo , Civelekoglu-Scholey Gul , Blacque Oliver E. , Endres Nicholas F. , Tao Li , Mogilner Alex , Leroux Michel R. , Vale Ronald D. , Scholey Jonathan M.
Published: September 2006

The assembly and function of cilia on Caenorhabditis elegans neurons depends on the action of two kinesin-2 motors, heterotrimeric kinesin-II and homodimeric OSM-3–kinesin, which cooperate to move the same intraflagellar transport (IFT) particles along microtubule (MT) doublets. Using competitive in vitro MT gliding assays, we show that purified kinesin-II and OSM-3 cooperate to generate movement similar to that seen along the cilium in the absence of any additional regulatory factors. Quantitative modeling suggests that this could reflect an alternating action mechanism, in which the motors take turns to move along MTs, or a mechanical competition, in which the motors function in a concerted fashion to move along MTs with the slow motor exerting drag on the fast motor and vice versa. In vivo transport assays performed in Bardet-Biedl syndrome (BBS) protein and IFT motor mutants favor a mechanical competition model for motor coordination in which the IFT motors exert a BBS protein–dependent tension on IFT particles, which controls the IFT pathway that builds the cilium foundation.
Flow-enhanced adhesion regulated by a selectin interdomain hinge
Authors: Lou Jizhong , Yago Tadayuki , Klopocki Arkadiusz G. , Mehta Padmaja , Chen Wei , Zarnitsyna Veronika I. , Bovin Nicolai V. , Zhu Cheng , McEver Rodger P.
Published: September 2006

L-selectin requires a threshold shear to enable leukocytes to tether to and roll on vascular surfaces. Transport mechanisms govern flow-enhanced tethering, whereas force governs flow-enhanced rolling by prolonging the lifetimes of L-selectin–ligand complexes (catch bonds). Using selectin crystal structures, molecular dynamics simulations, site-directed mutagenesis, single-molecule force and kinetics experiments, Monte Carlo modeling, and flow chamber adhesion studies, we show that eliminating a hydrogen bond to increase the flexibility of an interdomain hinge in L-selectin reduced the shear threshold for adhesion via two mechanisms. One affects the on-rate by increasing tethering through greater rotational diffusion. The other affects the off-rate by strengthening rolling through augmented catch bonds with longer lifetimes at smaller forces. By forcing open the hinge angle, ligand may slide across its interface with L-selectin to promote rebinding, thereby providing a mechanism for catch bonds. Thus, allosteric changes remote from the ligand-binding interface regulate both bond formation and dissociation.
For catch bonds, it all hinges on the interdomain region
Authors: Thomas Wendy
Published: September 2006

Tensile mechanical force was long assumed to increase the detachment rates of biological adhesive bonds (Bell, 1978). However, in the last few years, several receptor–ligand pairs were shown to form “catch bonds,” whose lifetimes are enhanced by moderate amounts of force. These include the bacterial adhesive protein FimH binding to its ligand mannose (Thomas et al., 2002; Thomas et al., 2006), blood cell adhesion proteins P- and L-selectin binding to sialyl Lewis X (sLeX)–containing ligands (Marshall et al., 2003; Evans et al., 2004; Sarangapani et al., 2004), and the myosin–actin motor protein interaction (Guo and Guilford, 2006). The structural mechanism behind this counterintuitive force–enhanced catch bond behavior is of great interest.
Intra- and Intersubunit Cooperativity in Activation of BK Channels by Ca2+
Authors: Qian Xiang , Niu Xiaowei , Magleby Karl L.
Published: September 2006

The activation of BK channels by Ca2+ is highly cooperative, with small changes in intracellular Ca2+ concentration having large effects on open probability (Po). Here we examine the mechanism of cooperative activation of BK channels by Ca2+. Each of the four subunits of BK channels has a large intracellular COOH terminus with two different high-affinity Ca2+ sensors: an RCK1 sensor (D362/D367) located on the RCK1 (regulator of conductance of K+) domain and a Ca-bowl sensor located on or after the RCK2 domain. To determine interactions among these Ca2+ sensors, we examine channels with eight different configurations of functional high-affinity Ca2+ sensors on the four subunits. We find that the RCK1 sensor and Ca bowl contribute about equally to Ca2+ activation of the channel when there is only one high-affinity Ca2+ sensor per subunit. We also find that an RCK1 sensor and a Ca bowl on the same subunit are much more effective in increasing Po than when they are on different subunits, indicating positive intrasubunit cooperativity. If it is assumed that BK channels have a gating ring similar to MthK channels with alternating RCK1 and RCK2 domains and that the Ca2+ sensors act at the flexible (rather than fixed) interfaces between RCK domains, then a comparison of the distribution of Ca2+ sensors with the observed responses suggest that the interface between RCK1 and RCK2 domains on the same subunit is flexible. On this basis, intrasubunit cooperativity arises because two high-affinity Ca2+ sensors acting across a flexible interface are more effective in opening the channel than when acting at separate interfaces. An allosteric model incorporating intrasubunit cooperativity nested within intersubunit cooperativity could approximate the Po vs. Ca2+ response for eight possible subunit configurations of the high-affinity Ca2+ sensors as well as for three additional configurations from a previous study.
Cyclic Nucleotide-gated Ion Channels in Rod Photoreceptors Are Protected from Retinoid Inhibition
Authors: He Quanhua , Alexeev Dmitriy , Estevez Maureen E. , McCabe Sarah L. , Calvert Peter D. , Ong David E. , Cornwall M. Carter , Zimmerman Anita L. , Makino Clint L.
Published: September 2006

In vertebrate rods, photoisomerization of the 11-cis retinal chromophore of rhodopsin to the all-trans conformation initiates a biochemical cascade that closes cGMP-gated channels and hyperpolarizes the cell. All-trans retinal is reduced to retinol and then removed to the pigment epithelium. The pigment epithelium supplies fresh 11-cis retinal to regenerate rhodopsin. The recent discovery that tens of nanomolar retinal inhibits cloned cGMP-gated channels at low [cGMP] raised the question of whether retinoid traffic across the plasma membrane of the rod might participate in the signaling of light. Native channels in excised patches from rods were very sensitive to retinoid inhibition. Perfusion of intact rods with exogenous 9- or 11-cis retinal closed cGMP-gated channels but required higher than expected concentrations. Channels reopened after perfusing the rod with cellular retinoid binding protein II. PDE activity, flash response kinetics, and relative sensitivity were unchanged, ruling out pharmacological activation of the phototransduction cascade. Bleaching of rhodopsin to create all-trans retinal and retinol inside the rod did not produce any measurable channel inhibition. Exposure of a bleached rod to 9- or 11-cis retinal did not elicit channel inhibition during the period of rhodopsin regeneration. Microspectrophotometric measurements showed that exogenous 9- or 11-cis retinal rapidly cross the plasma membrane of bleached rods and regenerate their rhodopsin. Although dark-adapted rods could also take up large quantities of 9-cis retinal, which they converted to retinol, the time course was slow. Apparently cGMP-gated channels in intact rods are protected from the inhibitory effects of retinoids that cross the plasma membrane by a large-capacity buffer. Opsin, with its chromophore binding pocket occupied (rhodopsin) or vacant, may be an important component. Exceptionally high retinoid levels, e.g., associated with some retinal degenerations, could overcome the buffer, however, and impair sensitivity or delay the recovery after exposure to bright light.
Contributions of Stretch Activation to Length-dependent Contraction in Murine Myocardium
Authors: Stelzer Julian E. , Moss Richard L.
Published: September 2006

The steep relationship between systolic force production and end diastolic volume (Frank-Starling relationship) in myocardium is a potentially important mechanism by which the work capacity of the heart varies on a beat-to-beat basis, but the molecular basis for the effects of myocardial fiber length on cardiac work are still not well understood. Recent studies have suggested that an intrinsic property of myocardium, stretch activation, contributes to force generation during systolic ejection in myocardium. To examine the role of stretch activation in length dependence of activation we recorded the force responses of murine skinned myocardium to sudden stretches of 1% of muscle length at both short (1.90 μm) and long (2.25 μm) sarcomere lengths (SL). Maximal Ca2+-activated force and Ca2+ sensitivity of force were greater at longer SL, such that more force was produced at a given Ca2+ concentration. Sudden stretch of myocardium during an otherwise isometric contraction resulted in a concomitant increase in force that quickly decayed to a minimum and was followed by a delayed development of force, i.e., stretch activation, to levels greater than prestretch force. At both maximal and submaximal activations, increased SL significantly reduced the initial rate of force decay following stretch; at submaximal activations (but not at maximal) the rate of delayed force development was accelerated. This combination of mechanical effects of increased SL would be expected to increase force generation during systolic ejection in vivo and prolong the period of ejection. These results suggest that sarcomere length dependence of stretch activation contributes to the steepness of the Frank-Starling relationship in living myocardium.
Role of Horizontal Transfer of the Transposon Tn1546in the Nosocomial Spread ofvanAVancomycin-Resistant Enterococci at a Tertiary Care Hospital in Korea
Authors: Yoo Soo Jin , Sung Heungsup , Cho Young-Uk , Kim Mi-Na , Pai Chik Hyun , Kim Yang Soo
Published: September 2006

Objective:

To investigate the epidemiologic characteristics of vancomycin-resistant enterococci (VRE) infection.

Design.

An epidemiologic description by means of chromosomal DNA fingerprinting and transposon typing.

Setting.

A 2,200-bed tertiary care hospital in Korea.

Patients.

First VRE isolates were obtained from patients hospitalized from April 1997 to December 2001.

Interventions.

Thevangenotypes of isolates were identified by means of multiplex polymerase chain reaction (PCR). The macro-restriction patterns of chromosomal DNA were determined by pulsed-field gel electrophoresis (PFGE). The transposon Tn1546was typed by means of 2 sets of long PCR restriction fragment-length polymorphism analysis, which wereClaI restriction of a 10.4-kb region fromorf1tovanZandDdeI restriction of a 4.4-kb region fromvanRtovanX.

Results.

VRE isolates were recovered from 215 patients. All werevanAgenotype. PFGE analysis of the 215 isolates showed 172 types, including 21 clusters composed of 64 isolates and 151 types of as many isolates. Each type was composed of 2-10 isolates; the isolates within each PFGE cluster were detected within a 10-month period and mostly shared a transposon type. Transposon typing classified 169 strains into 15 types and 158 strains belonged to 4 major transposon clusters. Each of these 4 transposon clusters was isolated from patients treated in 5-22 different wards during a 31-52 month period and consisted of 9-80 PFGE types. Each of the other 11 types were found in only one strain.

Conclusions.

Our findings suggest that the horizontal transfer of Tn1546has a major role in the nosocomial spread ofvanAVRE. Clonal spread of VRE seemed to contribute to short-term dissemination in limited areas.
Active Surveillance for Methicillin-Resistant Staphylococcus aureus(MRSA) Decreases the Incidence of MRSA Bacteremia
Authors: Shitrit Pnina , Gottesman Bat-Sheva , Katzir Michal , Kilman Avi , Ben-Nissan Yona , Chowers Michal
Published: September 2006

Objectives.

To evaluate the influence of performance of active surveillance cultures for methicillin-resistant Staphylococcus aureus (MRSA) on the incidence of nosocomial MRSA bacteremia in an endemic hospital.

Design.

Before-after trial.

Setting.

A 700-bed hospital.

Patients.

All patients admitted to the hospital who were at high risk for MRSA bacteremia.

Intervention.

Performance of surveillance cultures for detection of MRSA were recommended for all patients at high risk, and contact isolation was implemented for patients with positive results of culture. Each MRSA-positive patient received one course of eradication treatment. We compared the total number of surveillance cultures, the percentage of surveillance cultures with positive results, and the number of MRSA bacteremia cases before the intervention (from January 2002 through February 2003) after the start of the intervention (from July 2003 through October 2004).

Results.

The number of surveillance cultures performed increased from a mean of 272.57 cultures/month before the intervention to 865.83 cultures/month after the intervention. The percentage of surveillance cultures with positive results increased from 3.13% before to 5.22% after the intervention (P<.001). The mean number of MRSA bacteremia cases per month decreased from 3.6 cases before the intervention to 1.8 cases after the intervention (P< 0.001).

Conclusions.

Active surveillance culture is important for identifying hidden reservoirs of MRSA. Contact isolation can prevent new colonization and infection and lead to a significant reduction of morbidity and healthcare costs.
Impact of Alcohol-Based, Waterless Hand Antiseptic on the Incidence of Infection and Colonization With Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci
Authors: Lai Kwan Kew , Fontecchio Sally , Melvin Zita , Baker Stephen P.
Published: September 2006

Objective:

Colonized and infected inpatients are major reservoirs for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), and transient carriage of these pathogens on the hands of healthcare workers remains the most common mechanism of patient-to-patient transmission. We hypothesized that use of alcohol-based, waterless hand antiseptic would lower the incidence of colonization and/or infection with MRSA and VRE.

Methods.

On June 19, 2001, alcohol hand antiseptic was introduced at the University campus and not the nearby Memorial campus of the University of Massachusetts Medical School (Worcester, MA), allowing us to evaluate the impact of this antiseptic on the incidence of MRSA and VRE colonization and infection. From January 1 through December 31, 2001, the incidence of MRSA colonization or infection was compared between the 2 campuses before and after the hand antiseptic was introduced. Its effect on VRE colonization and infection was only studied in the medical intensive care unit at the University campus.

Results.

At the University campus, the incidence of MRSA colonization or infection decreased from 1.26 cases/1,000 patient-days before the intervention to 0.75 cases/1,000 patient-days after the intervention, for a 1.46-fold decrease (95% confidence interval, 1.04-2.58; P = .037). At the Memorial campus, the incidence of MRSA colonization or infection remained virtually unchanged, from 0.34 cases/1,000 patient-days to 0.49 cases/1,000 patient-days during the same period. However, a separate analysis of the University campus data that controlled for proximity to prevalent cases did not show a significant improvement in the rates of infection or colonization. The incidence of nosocomial VRE colonization or infection before and after the hand antiseptic decreased from 12.0 cases/1,000 patient-days to 3.0 cases/1,000 patient-days, a 2.25-fold decrease (P = .018). Compliance with rectal surveillance for detection of VRE was 86% before and 84% after implementation of the hand antiseptic intervention. The prevalences of VRE cases during these 2 periods were 25% and 29%, respectively (P = .017).

Conclusions.

Alcohol hand antiseptic appears to be effective in controlling the transmission of VRE. However, after controlling for proximity to prevalent cases (ie, for clustering), it does not appear to be more effective than standard methods for controlling MRSA. Further controlled studies are needed to evaluate its effectiveness.
Epidemiology of Methicillin-Resistant Staphylococcus aureus Colonization in a Surgical Intensive Care Unit
Authors: Warren David K. , Guth Rebecca M. , Coopersmith Craig M. , Merz Liana R. , Zack Jeanne E. , Fraser Victoria J.
Published: September 2006

Background.

Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of healthcare-associated infections among surgical intensive care unit (ICU) patients, though transmission dynamics are unclear.

Objective.

To determine the prevalence of MRSA nasal colonization at ICU admission, to identify associated independent risk factors, to determine the value of these factors in active surveillance, and to determine the incidence of and risk factors associated with MRSA acquisition.

Design.

Prospective cohort study.

Setting.

Surgical ICU at a teaching hospital.

Patients.

All patients admitted to the surgical ICU.

Results.

Active surveillance for MRSA by nasal culture was performed at ICU admission during a 15-month period. Patients who stayed in the ICU for more than 48 hours had nasal cultures performed weekly and at discharge from the ICU, and clinical data were collected prospectively. Of 1,469 patients, 122 (8%) were colonized with MRSA at admission; 75 (61%) were identified by surveillance alone. Among 775 patients who stayed in the ICU for more than 48 hours, risk factors for MRSA colonization at admission included the following: hospital admission in the past year (1-2 admissions: adjusted odds ratio [aOR], 2.60 [95% confidence interval {CI}, 1.47-4.60]; more than 2 admissions: aOR, 3.56 [95% CI, 1.72-7.40]), a hospital stay of 5 days or more prior to ICU admission (aOR, 2.54 [95% CI, 1.49-4.32]), chronic obstructive pulmonary disease (aOR, 2.16 [95% CI, 1.17-3.96]), diabetes mellitus (aOR, 1.87 [95% CI, 1.10-3.19]), and isolation of MRSA in the past 6 months (aOR, 8.18 [95% CI, 3.38-19.79]). Sixty-nine (10%) of 670 initially MRSA-negative patients acquired MRSA in the ICU (corresponding to 10.7 cases per 1,000 ICU-days at risk). Risk factors for MRSA acquisition included tracheostomy in the ICU (aOR, 2.18 [95% CI, 1.13-4.20]); decubitus ulcer (aOR, 1.72 [95% CI, 0.97-3.06]), and receipt of enteral nutrition via nasoenteric tube (aOR, 3.73 [95% CI, 1.86-7.51]), percutaneous tube (aOR, 2.35 [95% CI, 0.74-7.49]), or both (aOR, 3.33 [95% CI, 1.13-9.77]).

Conclusions.

Active surveillance detected a sizable proportion of MRSA-colonized patients not identified by clinical culture. MRSA colonization on admission was associated with recent healthcare contact and underlying disease. Acquisition was associated with potentially modifiable processes of care.
Molecular Characterization of Methicillin-ResistantStaphylococcus aureusDisseminated in a Home Care System
Authors: Rozenbaum R. , Silva-Carvalho M. C. , Souza R. R. , Melo M. C. N. , Gobbi C. N. , Coelho L. R. , Ferreira R. L. , Ferreira-Carvalho B. T. , Schuenck A. L. , Neves F. M. C. S. , Silva L. R. P. O. F. , Figueiredo A. M. S.
Published: September 2006

Objective.

To study colonization with methicillin-resistantStaphylococcus aureusin a home care service during a 4-month period.

Design.

Prospective study.

Setting.

A home care service located in Rio de Janeiro, Brazil.

Participants.

Patients admitted to the home care service during this period, their household contacts, and health care workers (HCWs).

Methods.

Swab specimens from the anterior nares were collected from each patient in the 3 groups at admission. Screening was repeated every 7 days. MRSA was detected using a mecA probe, and the clonality of isolates was evaluated by molecular methods, primarily pulsed-field gel electrophoresis.

Results.

Of the 59 study patients, 9 (15.3%) had MRSA colonization detected; these cases of colonization were classified as imported. Only 1 (2.0%) of the 50 patients not colonized at admission became an MRSA carrier (this case of colonization was classified as autochthonous). Two (0.9%) of 224 household contacts and 16 (7.4%) of 217 HCWs had MRSA colonization. Cross-transmission from patient to HCW could be clearly demonstrated in 8 cases. The great majority of MRSA isolates belonged to the Brazilian epidemic clone.

Conclusions.

MRSA colonization was common in the home care service analyzed. The fact that the majority of MRSA isolates obtained were primarily of nosocomial origin (and belonged to the so-called Brazilian epidemic clone) substantiated our findings that all but 1 patient had already been colonized before admission to the home care service. Only cross-transmission from patients to healthcare workers could be verified. On the basis of these results, we believe that a control program built on admission screening of patients for detection of MRSA carriage could contribute to the overall quality of care.
How Often Do Asymptomatic Healthcare Workers Cause Methicillin-ResistantStaphylococcus aureusOutbreaks? A Systematic Evaluation
Authors: Vonberg Ralf-Peter , Stamm-Balderjahn Sabine , Hansen Sonja , Zuschneid Irina , Rüden Henning , Behnke Michael , Gastmeier Petra
Published: September 2006

A systematic search was performed to identify outbreaks of methicillin-resistantStaphylococcus aureusinfection and colonization caused by healthcare workers (HCWs). Of 191 outbreaks identified, 11 had strong epidemiological evidence that HCWs were the source. In 3 of these outbreaks, asymptomatic carriers were the cause. The frequent practice of screening asymptomatic HCWs should be reconsidered.
Community-Associated Strains of Methicillin-ResistantStaphylococccus aureusas the Cause of Healthcare-Associated Infection
Authors: Gonzalez Blanca E. , Rueda Adriana M. , Shelburne Samuel A. , Musher Daniel M. , Hamill Richard J. , Hultén Kristina G.
Published: September 2006

Objective:

Methicillin-resistantStaphylococcus aureus(MRSA) isolates from patients with community-associated infection have been described as strains genetically distinct from the strains isolated from patients with healthcare-associated infection. This study examines the hypothesis that community-associated MRSA (CA-MRSA) strains now cause serious infections in hospitalized patients.

Methods.

Thirty-seven clinical MRSA isolates were randomly selected from blood isolates obtained from July 2003 through June 2004. Strains were tested for staphylococcal chromosomal cassettemec(SCCmec) type, pulsed-field gel electrophoresis (PFGE) type, and presence of Panton-Valentine leukocidin (PVL) genes. Medical records review and epidemiologic classification was performed by an investigator blinded to the results of the bacterial strain analysis. Episodes of bloodstream infection were independently classified as either community-associated or healthcare-associated infections, and bacterial isolates were independently classified as either CA-MRSA strains or healthcare-associated MRSA (HA-MRSA) strains, according to established definitions.

Setting.

A tertiary care Veterans Affairs Medical Center.

Results.

Twenty-four (65%) of 37 MRSA isolates were SCCmectype IV, a genetic type characteristic of CA-MRSA strains; 22 of these 24 isolates belonged to the CA-MRSA clone USA300 and carried PVL genes. Thirteen (35%) of the 37 strains were SCCmectype II, of which 12 were USA100-ST5 and 12 lacked PVL genes. Thirty patients (81%) had healthcare-associated infections; 18 (60%) of these 30 were infected with isolates carrying markers of CA-MRSA strains. Of 7 patients with CA-MRSA infections, 6 were infected with isolates belonging to the USA300 clone. Patients with healthcare-associated bloodstream infections were as likely to be infected with a CA-MRSA strain as patients with a community-associated infection (P= .38).

Conclusions.

MRSA strains with molecular characteristics of CA-MRSA strains have emerged as an important cause of serious health-care-associated infection in our hospital.
Emergence of Community-Associated Methicillin-ResistantStaphylococcus aureusInfection Among Patients With End-Stage Renal Disease
Authors: Johnson Leonard B. , Venugopal Anilrudh A. , Pawlak Joan , Saravolatz Louis D.
Published: September 2006

Objective.

To evaluate the frequency of infections due to community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) strains among our patients with end-stage renal disease.

Design.

Prospective observational clinical and laboratory study of patients in 2005. Molecular features of isolates recovered from these patients were compared with those of isolates recovered in 2000 from patients with end-stage renal disease.

Setting.

A 600-bed urban academic medical center.

Patients.

Thirty-two patients with end-stage renal disease and MRSA infection at the time of hospitalization from 2005 were evaluated. For comparison, laboratory analysis was performed for 17 MRSA isolates recovered from patients with end-stage renal disease in 2000.

Results.

The patients from 2005 were more likely than the patients from 2000 to have infection with strains that carried the staphylococcal cassette chromosome (SCC)mectype IV complex (50% vs 11.8%; relative risk, 4.25 [95% confidence interval, 1.17-25.98];P= .012) and the Panton-Valentine leukocidin toxin genes (25% vs 0%;P= .038). Eight patients from 2005 were infected with a strain that is identical to MRSA clone USA300 in terms of molecular type and presence of SCCmectype IV and Panton-Valentine leukocidin genes. Among the patients from 2005, those infected with SCCmectype IV strains (ie, CA-MRSA strains) and those infected with SCCmectype II strains (ie, healthcare-associated MRSA [HA-MRSA] strains) were similar with respect to demographic characteristics, risk factors, and outcomes.

Conclusions.

We documented an increased proportion of infections with CA-MRSA strains, including clone USA300, among our population of patients undergoing dialysis. Patients infected with CA-MRSA strains and HA-MRSA strains were similar with respect to presenting illness and outcomes.
Carriage of Multiple Subtypes of Methicillin-ResistantStaphylococcus aureusby Intensive Care Unit Patients
Authors: Lim Megan S. C. , Marshall Caroline L. , Spelman Denis
Published: September 2006

Objective:

To determine how consistently patients are colonized with methicillin-resistantStaphylococcus aureus(MRSA) at various sites and how many subtypes can be carried simultaneously by a single patient.

Setting.

A 28-bed Intensive care unit in a tertiary-care referral hospital.

Methods.

A total of 1,181 patients were screened by culture of swab specimens obtained from the nose, throat, groin, and axilla on admission to the intensive care unit (ICU), twice weekly during their ICU stay, and at discharge.

Results.

MRSA was isolated at least once from 224 patients. Of these isolates, 359 were selected from 32 patients to be subtyped using pulsed-field gel electrophoresis. The rate of compliance with collection of swab specimens was 79.9%. The combination of sites colonized varied frequently over time for many patients. Of patients who had swab specimens obtained twice in 1 day, 8.7% had discordant results from the 2 swab sets. No patient had a clinical isolate that was not of an identical subtype to an isolate from an anatomical site that was sampled for screening. Half the patients carried multiple subtypes during their stay, with up to 4 subtypes per patient.

Conclusions.

The findings of this study may indicate that these patients have been colonized with MRSA on more than one occasion, possibly because of multiple breaches in infection control procedure. In MRSA-colonized patients, anatomical sites were intermittently colonized and carriage of multiple subtypes was common. These findings indicate that MRSA carriage is not a fixed state but may vary over time.
Surveillance for Vancomycin-Resistant Enterococci: Type, Rates, Costs, and Implications
Authors: Shadel Brooke N. , Puzniak Laura A. , Gillespie Kathleen N. , Lawrence Steven J. , Kollef Marin , Mundy Linda M.
Published: September 2006

Objective.

To evaluate 2 active surveillance strategies for detection of enteric vancomycin-resistant enterococci (VRE) in an intensive care unit (ICU).

Design.

Thirty-month prospective observational study.

Setting.

ICU at a university-affiliated referral center.

Patients.

All patients with an ICU stay of 24 hours or more were eligible for the study.

Intervention.

Clinical active surveillance (CAS), involving culture of a rectal swab specimen for detection of VRE, was performed on admission, weekly while the patient was in the ICU, and at discharge. Laboratory-based active surveillance (LAS), involving culture of a stool specimen for detection of VRE, was performed on stool samples submitted forClostridium difficiletoxin detection.

Results.

Enteric colonization with VRE was detected in 309 (17%) of 1,872 patients. The CAS method initially detected 280 (91%) of the 309 patients colonized with VRE, compared with 25 patients (8%) detected by LAS; colonization in 4 patients (1%) was initially detected by analysis of other clinical specimens. Most patients with colonization (76%) would have gone undetected by LAS alone, whereas use of the CAS method exclusively would have missed only 3 patients (1%) who were colonized. CAS cost $1,913 per month, or $57,395 for the 30-month study period. Cost savings of CAS from preventing cases of VRE colonization and bacteremia were estimated to range from $56,258 to $303,334 per month.

Conclusions.

A patient-based CAS strategy for detection of enteric colonization with VRE was superior to LAS. In this high-risk setting, CAS appeared to be the most efficient and cost-effective surveillance method. The modest costs of CAS were offset by the averted costs associated with the prevention of VRE colonization and bacteremia.
Molecular Characterization of Vancomycin-Resistant Enterococci from Clinical and Surveillance Specimens
Authors: Huh Ji Young , Lee Wee Gyo , Jin Hye Young
Published: September 2006

Objective:

To compare the molecular characteristics of infection-derived (ID) isolates and intestinal colonization–derived (ICD) isolates of vancomycin-resistant enterococci (VRE) recovered from hospitalized patients.

Design.

A 12-month prospective cohort study.

Setting.

A 1,000-bed teaching facility.

Methods.

From January through December 2004, a total of 30 pairs ofvanA-containing enterococcal isolates were collected from patients admitted to a teaching hospital in South Korea. Each pair comprised an ID and an ICD VRE isolate from the same patient. All VRE isolates were investigated on the basis ofSmaI-restricted pulsed-field gel electrophoresis (PFGE) pattern, Tn1546type, and presence of theespgene, including A and C repeat number variation.

Results.

Members of 19 pairs (63%) of VRE isolates were genetically indistinguishable from each other. The 11 patients for whom the molecular characteristics of the ID isolates differed from those of the ICD isolates had longer durations of hospitalization and intensive care unit (ICU) stay, compared with the other 19 patients.

Conclusions.

These findings suggest the longer durations of hospitalization and ICU stay may be possible risk factors for colonization with multiple clones of VRE.
Antimicrobial Use Control Measures to Prevent and Control Antimicrobial Resistance in US Hospitals
Authors: Zillich Alan J. , Sutherland Jason M. , Wilson Stephen J. , Diekema Daniel J. , Ernst Erika J. , Vaughn Thomas E. , Doebbeling Bradley N.
Published: September 2006

Objective.

Clinical practice guidelines and recommended practices to control use of antibiotics have been published, but the effect of these practices on antimicrobial resistance (AMR) rates in hospitals is unknown. The objective of this study was to examine relationships between antimicrobial use control strategies and AMR rates in a national sample of US hospitals.

Design.

Cross-sectional, stratified study of a nationally representative sample of US hospitals.

Methods.

A survey instrument was sent to the person responsible for infection control at a sample of 670 US hospitals. The outcome was current prevalences of 4 epidemiologically important, drug-resistant pathogens, considered concurrently: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, ceftazidime-resistant Klebsiella species, and quinolone (ciprofloxacin)-resistant Escherichia coli Five independent variables regarding hospital practices were selected from the survey: the extent to which hospitals (1) implement practices recommended in clinical practice guidelines and ensure best practices for antimicrobial use, (2) disseminate information on clinical practice guidelines for antimicrobial use, (3) use antimicrobial-related information technology, (4) use decision support tools, and (5) communicate to prescribers about antimicrobial use. Control variables included the hospitals' number of beds, teaching status, Veterans Affairs status, geographic region, and number of long-term care beds; and the presence of an intensive care unit, a burn unit, or transplant services. A generalized estimating equation modeled all resistance rates simultaneously to identify overall predictors of AMR levels at the facility.

Results.

Completed survey instruments were returned by 448 hospitals (67%). Four antimicrobial control measures were associated with higher prevalence of AMR. Implementation of recommended practices for antimicrobial use (P< .01) and optimization of the duration of empirical antibiotic prophylaxis (P<.01) were associated with a lower prevalence of AMR. Use of restrictive formularies (P = .05) and dissemination of clinical practice guideline information (P<.01) were associated with higher prevalence of AMR. Number of beds and Veterans Affairs status were also associated with higher AMR rates overall.

Conclusions.

Implementation of guideline-recommended practices to control antimicrobial use and optimize the duration of empirical therapy appears to help control AMR rates in US hospitals. A longitudinal study would confirm the results of this cross-sectional study. These results highlight the need for systems interventions and reengineering to ensure more-consistent application of guideline-recommended measures for antimicrobial use.
Use of Germicides in the Home and the Healthcare Setting Is There a Relationship Between Germicide Use and Antibiotic Resistance?
Authors: Weber David J. , Rutala William A.
Published: September 2006

Background.

The spread of antibiotic-resistant pathogens represents an increasing threat in healthcare facilities. Concern has been expressed that the use of surface disinfectants and antiseptics may select for antibiotic-resistant pathogens.

Objective.

To review the scientific literature on whether there is a link between use of germicides (ie, disinfectants and antiseptics) and bacterial resistance to antibiotics. In addition, we will review whether antibiotic-resistant bacteria exhibit altered susceptibility to germicides that are recommended for use as disinfectants or antiseptics.

Design.

A review of the appropriate scientific literature.

Results.

In the laboratory, it has been possible to develop bacterial mutants with reduced susceptibility to disinfectants and antiseptics that also demonstrate decreased susceptibility to antibiotics. However, the antibiotic resistance described was not clinically relevant because the test organism was rarely a human pathogen, the altered level of antimicrobial susceptibility was within achievable serum levels for the antibiotic, or the antibiotic tested was not clinically used to treat the study pathogen. Similarly, wild-type strains with reduced susceptibility to disinfectants (principally, quaternary ammonium compounds) and antiseptics (principally, triclosan) have been reported. However, because the concentration of disinfectants used in the healthcare setting greatly exceeds the concentration required to kill strains with reduced susceptibility to disinfectants, the clinical relevance of these observations is questionable.

Conclusion.

To date, there is no evidence that using recommended antiseptics or disinfectants selects for antibiotic-resistant organisms in nature. Disinfectants and antiseptics should be used when there are scientific studies demonstrating benefit or when there is a strong theoretical rationale for using germicides.
Use of Gaseous Ozone for Eradication of Methicillin-ResistantStaphylococcus aureusFrom the Home Environment of a Colonized Hospital Employee
Authors: Boer Hero E. L. de , van Elzelingen-Dekker Carla M. , van Rheenen-Verberg Cora M. F. , Spanjaard Lodewijk
Published: September 2006

An intensive care nurse with eczema was repeatedly treated for methicillin-resistantStaphylococcus aureus(MRSA) carriage. Because cultures remained positive for MRSA, her house was investigated. Thirty-four percent of environmental samples yielded MRSA. Her children and cat were free of MRSA. The house was decontaminated with gaseous ozone. All subsequent cultures were negative for MRSA. This decontamination cost €2,000 (approximately $2,400).
The Decrease in Healthcare-Associated Methicillin-Resistant Staphylococcus aureus Infections and Savings From Glycopeptide Use
Authors: Coşkun Diler , Aytaç Jale
Published: September 2006

We evaluated changes in the rate of healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) infections and healthcare-associated S. aureus infections after implementation of infection control precautions and the effect of this on glycopeptide use and expenditures for glycopeptides in a private medical center in Turkey in the years 2000-2005. A striking decrease was obtained in the number of MRSA infections, and the expenditure for glycopeptide use also decreased
Incidence and Epidemiology of Methicillin-ResistantStaphylococcus aureusInfection in a Saudi Arabian Hospital, 1999-2003
Authors: Al-Tawfiq Jaffar A.
Published: September 2006

During 1999-2003 in a Saudi Arabian Hospital, methicillin-resistantStaphylococcus aureusconstituted 6% of allS. aureusisolates; the proportion had increased from 2% in 1999, to 9.7% in 2002, to 8% in 2003. Of all MRSA isolates, 62% represented community-acquired infection, 20.4% represented healthcare-associated infection, and 17.6% represented nosocomial infection. The proportion of community-acquired isolates increased from 41.7% in 1999 to 66.6% in 2002, and the proportion representing nosocomial infection decreased from 33% in 1999 to 19% in 2003. Isolates representing nosocomial infection showed higher rates of resistance to ciprofloxacin (76.6%), clindamycin (76.6%), erythromycin (68%) and trimethoprim-sulfamethoxazole (68%) than did isolates in the other categories (P<.001).