bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial Resistance in Salmonella in the United States from 1948 to 1995
Authors: Tadesse Daniel A. , Singh Aparna , Zhao Shaohua , Bartholomew Mary , Womack Niketta , Ayers Sherry , Fields Patricia I. , McDermott Patrick F. 
Published: February 2016

ABSTRACT

We conducted a retrospective study of 2,149 clinical
Salmonella
strains to help document the historical emergence of antimicrobial resistance. There were significant increases in resistance to older drugs, including ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline, which were most common in
Salmonella enterica
serotype Typhimurium. An increase in multidrug resistance was observed for each decade since the 1950s. These data help show how
Salmonella
evolved over the past 6 decades, after the introduction of new antimicrobial agents.
Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B
Authors: Rigatto Maria Helena , Oliveira Maura S. , Perdigão-Neto Lauro V. , Levin Anna S. , Carrilho Claudia M. , Tanita Marcos Toshiyuki , Tuon Felipe F. , Cardoso Douglas E. , Lopes Natane T. , Falci Diego R. , Zavascki Alexandre P. 
Published: February 2016

ABSTRACT

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (
P
< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;
P
< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.
Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwide Isolates of Viral Genotypes 1 to 6
Authors: Patiño-Galindo Juan Ángel , Salvatierra Karina , González-Candelas Fernando , López-Labrador F. Xavier 
Published: February 2016

ABSTRACTThere is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. In addition, we found a low genetic barrier for the generation of new RAVs, irrespective of the viral genotype. Furthermore, in 1,126 HCV genomes, including sequences spanning the three genes, haplotype analysis revealed a remarkably high frequency of viruses carrying more than one natural RAV to DAAs (53% of HCV-1a, 28.5% of HCV-1b, 67.1% of HCV-6, and 100% of genotype 2, 3, 4, and 5 haplotypes). With the exception of HCV-1a, the most prevalent haplotypes showed RAVs in at least two different viral genes. Finally, evolutionary analyses revealed that, while most natural RAVs appeared recently, others have been efficiently transmitted over time and cluster in well-supported clades. In summary, and despite the observed high efficacy of DAA-based regimens, we show that naturally occurring RAVs are common in all HCV genotypes and that there is an overall low genetic barrier for the selection of resistance mutations. There is a need for natural DAA resistance profiling specific for each HCV genotype.
Antimicrobial Activities of Ceftaroline and Comparator Agents against Bacterial Organisms Causing Bacteremia in Patients with Skin and Skin Structure Infections in U.S. Medical Centers, 2008 to 2014
Authors: Sader Helio S. , Flamm Robert K. , Mendes Rodrigo E. , Farrell David J. , Jones Ronald N. 
Published: February 2016

ABSTRACT

We evaluated the antimicrobial susceptibility of 1,454 organisms consecutively collected from patients with bacteremia associated with skin and skin structure infections. The most common organisms obtained were
Staphylococcus aureus
(670 organisms [46.1%]),
Escherichia coli
(200 organisms [13.8%]), β-hemolytic streptococci (βHS) (138 organisms [9.5%]), and
Klebsiella pneumoniae
(109 organisms [7.5%]). The susceptibility rates for ceftaroline were 97.9% for
S. aureus
(95.9% among methicillin-resistant
S. aureus
[MRSA]), 100.0% for βHS, 86.5% for
E. coli
, and 89.0% for
K. pneumoniae
. Ceftaroline and tigecycline provided the best overall coverage.
Novel Engineered Peptides of a Phage Lysin as Effective Antimicrobials against Multidrug-Resistant Acinetobacter baumannii
Authors: Thandar Mya , Lood Rolf , Winer Benjamin Y. , Deutsch Douglas R. , Euler Chad W. , Fischetti Vincent A. 
Published: February 2016

ABSTRACT

Acinetobacter baumannii
is a Gram-negative bacterial pathogen responsible for a range of nosocomial infections. The recent rise and spread of multidrug-resistant
A. baumannii
clones has fueled a search for alternative therapies, including bacteriophage endolysins with potent antibacterial activities. A common feature of these lysins is the presence of a highly positively charged C-terminal domain with a likely role in promoting outer membrane penetration. In the present study, we show that the C-terminal amino acids 108 to 138 of phage lysin PlyF307, named P307, alone were sufficient to kill
A. baumannii
(>3 logs). Furthermore, P307 could be engineered for improved activity, the most active derivative being P307
SQ-8C
(>5-log kill). Both P307 and P307
SQ-8C
showed high
in vitro
activity against
A. baumannii
in biofilms. Moreover, P307
SQ-8C
exhibited MICs comparable to those of levofloxacin and ceftazidime and acted synergistically with polymyxin B. Although the peptides were shown to kill by disrupting the bacterial cytoplasmic membrane, they did not lyse human red blood cells or B cells; however, serum was found to be inhibitory to lytic activity. In a murine model of
A. baumannii
skin infection, P307
SQ-8C
reduced the bacterial burden by ∼2 logs in 2 h. This study demonstrates the prospect of using peptide derivatives from bacteriophage lysins to treat topical infections and remove biofilms caused by Gram-negative pathogens.
Molecular Characterization of Escherichia coli Strains Isolated from Retail Meat That Harbor
bla
CTX-M
and
fosA3
Genes
Authors: Xie Miaomiao , Lin Dachuan , Chen Kaichao , Chan Edward Wai Chi , Yao Wen , Chen Sheng 
Published: February 2016

ABSTRACT

A total of 55 cefotaxime-resistant
Escherichia coli
isolates were obtained from retail meat products purchased in Shenzhen, China, during the period November 2012 to May 2013. Thirty-seven of these 55 isolates were found to harbor a
bla
CTX-M
gene, with the
bla
CTX-M-1
group being the most common type.
bla
CMY-2
was detected in 16 isolates, alone or in combination with other extended-spectrum β-lactamase (ESBL) determinants. Importantly, the
fosA3
gene, which encodes fosfomycin resistance, was detected in 12 isolates, with several being found to reside in the conjugative plasmid that harbored the
bla
CTX-M
gene. The insertion sequence IS
26
was observed upstream of some of the
bla
CTX-M-55
and
fosA3
genes. Conjugation experiments showed that
bla
CTX-M
genes from 15 isolates were transferrable, with Inc I1 and Inc FII being the most prevalent replicons. High clonal diversity was observed among the
bla
CTX-M
producers, suggesting that horizontal transfer of the
bla
CTX-M
genes among
E. coli
strains in retail meats is a common event and that such strains may constitute an important reservoir of
bla
CTX-M
genes, which may be readily disseminated to other potential human pathogens.
Removal of Dolutegravir by Hemodialysis in HIV-Infected Patients with End-Stage Renal Disease
Authors: Moltó José , Graterol Fredzzia , Miranda Cristina , Khoo Saye , Bancu Ioana , Amara Alieu , Bonjoch Anna , Clotet Bonaventura 
Published: February 2016

ABSTRACT
Data on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.)
Differences in Host Cell Invasion and Salmonella Pathogenicity Island 1 Expression between Salmonella enterica Serovar Paratyphi A and Nontyphoidal
S
. Typhimurium
Authors: Elhadad Dana , Desai Prerak , Grassl Guntram A. , McClelland Michael , Rahav Galia , Gal-Mor Ohad 
Published: February 2016

ABSTRACT

Active invasion into nonphagocytic host cells is central to
Salmonella enterica
pathogenicity and dependent on multiple genes within
Salmonella
pathogenicity island 1 (SPI-1). Here, we explored the invasion phenotype and the expression of SPI-1 in the typhoidal serovar
S
. Paratyphi A compared to that of the nontyphoidal serovar
S
. Typhimurium. We demonstrate that while
S
. Typhimurium is equally invasive under both aerobic and microaerobic conditions,
S
. Paratyphi A invades only following growth under microaerobic conditions. Transcriptome sequencing (RNA-Seq), reverse transcription-PCR (RT-PCR), Western blot, and secretome analyses established that
S
. Paratyphi A expresses much lower levels of SPI-1 genes and secretes lesser amounts of SPI-1 effector proteins than
S
. Typhimurium, especially under aerobic growth. Bypassing the native SPI-1 regulation by inducible expression of the SPI-1 activator, HilA, considerably elevated SPI-1 gene expression, host cell invasion, disruption of epithelial integrity, and induction of proinflammatory cytokine secretion by
S
. Paratyphi A but not by
S
. Typhimurium, suggesting that SPI-1 expression is naturally downregulated in
S
. Paratyphi A. Using streptomycin-treated mice, we were able to establish substantial intestinal colonization by
S
. Paratyphi A and showed moderately higher pathology and intestinal inflammation in mice infected with
S
. Paratyphi A overexpressing
hilA
. Collectively, our results reveal unexpected differences in SPI-1 expression between
S
. Paratyphi A and
S
. Typhimurium, indicate that
S
. Paratyphi A host cell invasion is suppressed under aerobic conditions, and suggest that lower invasion in aerobic sites and suppressed expression of immunogenic SPI-1 components contributes to the restrained inflammatory infection elicited by
S
. Paratyphi A.
XerC Contributes to Diverse Forms of Staphylococcus aureus Infection via
agr
-Dependent and
agr
-Independent Pathways
Authors: Atwood Danielle N. , Beenken Karen E. , Loughran Allister J. , Meeker Daniel G. , Lantz Tamara L. , Graham Justin W. , Spencer Horace J. , Smeltzer Mark S. 
Published: February 2016

ABSTRACT

We demonstrate that mutation of
xerC
, which reportedly encodes a homologue of an
Escherichia coli
recombinase, limits biofilm formation in the methicillin-resistant
Staphylococcus aureus
strain LAC and the methicillin-sensitive strain UAMS-1. This was not due to the decreased production of the polysaccharide intracellular adhesin (PIA) in either strain because the amount of PIA was increased in a UAMS-1
xerC
mutant and undetectable in both LAC and its isogenic
xerC
mutant. Mutation of
xerC
also resulted in the increased production of extracellular proteases and nucleases in both LAC and UAMS-1, and limiting the production of either class of enzymes increased biofilm formation in the isogenic
xerC
mutants. More importantly, the limited capacity to form a biofilm was correlated with increased antibiotic susceptibility in both strains in the context of an established biofilm
in vivo
. Mutation of
xerC
also attenuated virulence in a murine bacteremia model, as assessed on the basis of the bacterial loads in internal organs and overall lethality. It also resulted in the decreased accumulation of alpha toxin and the increased accumulation of protein A. These findings suggest that
xerC
may impact the functional status of
agr
. This was confirmed by demonstrating the reduced accumulation of RNAIII and AgrA in LAC and UAMS-1
xerC
mutants. However, this cannot account for the biofilm-deficient phenotype of
xerC
mutants because mutation of
agr
did not limit biofilm formation in either strain. These results demonstrate that
xerC
contributes to biofilm-associated infections and acute bacteremia and that this is likely due to
agr
-independent and -dependent pathways, respectively.
Distinct Contributions of Enzymic Functional Groups to the 2′,3′-Cyclic Phosphodiesterase, 3′-Phosphate Guanylylation, and 3′-ppG/5′-OH Ligation Steps of the Escherichia coli RtcB Nucleic Acid Splicing Pathway
Authors: Maughan William P. , Shuman Stewart 
Published: February 2016

ABSTRACT

Escherichia coli
RtcB is a founding member of a family of manganese-dependent RNA repair enzymes that join RNA 2′,3′-cyclic phosphate (RNA>p) or RNA 3′-phosphate (RNAp) ends to 5′-OH RNA (
HO
RNA) ends in a multistep pathway whereby RtcB (i) hydrolyzes RNA>p to RNAp, (ii) transfers GMP from GTP to RNAp to form to RNAppG, and (iii) directs the attack of 5′-OH on RNAppG to form a 3′-5′ phosphodiester splice junction. The crystal structure of the homologous archaeal RtcB enzyme revealed an active site with two closely spaced manganese ions, Mn1 and Mn2, that interact with the GTP phosphates. By studying the reactions of wild-type
E. coli
RtcB and RtcB alanine mutants with 3′-phosphate-, 2′,3′-cyclic phosphate-, and 3′-ppG-terminated substrates, we found that enzymic constituents of the two metal coordination complexes (Cys78, His185, and His281 for Mn1 and Asp75, Cys78, and His168 for Mn2 in
E. coli
RtcB) play distinct catalytic roles. For example, whereas the C78A mutation abolished all steps assayed, the D75A mutation allowed cyclic phosphodiester hydrolysis but crippled 3′-phosphate guanylylation, and the H281A mutant was impaired in overall
HO
RNAp and
HO
RNA>p ligation but was able to seal a preguanylylated substrate. The archaeal counterpart of
E. coli
RtcB Arg189 coordinates a sulfate anion construed to mimic the position of an RNA phosphate. We propose that Arg189 coordinates a phosphodiester at the 5′-OH end, based on our findings that the R189A mutation slowed the step of RNAppG/
HO
RNA sealing by a factor of 200 compared to that with wild-type RtcB while decreasing the rate of RNAppG formation by only 3-fold.

IMPORTANCE
RtcB enzymes comprise a widely distributed family of manganese- and GTP-dependent RNA repair enzymes that ligate 2′,3′-cyclic phosphate ends to 5′-OH ends via RNA 3′-phosphate and RNA(3′)pp(5′)G intermediates. The RtcB active site includes two adjacent manganese ions that engage the GTP phosphates. Alanine scanning of
Escherichia coli
RtcB reveals distinct contributions of metal-binding residues Cys78, Asp75, and His281 at different steps of the RtcB pathway. The RNA contacts of RtcB are uncharted. Mutagenesis implicates Arg189 in engaging the 5′-OH RNA end.
Lack of the H-NS Protein Results in Extended and Aberrantly Positioned DNA during Chromosome Replication and Segregation in Escherichia coli
Authors: Helgesen Emily , Fossum-Raunehaug Solveig , Skarstad Kirsten 
Published: February 2016

ABSTRACT

The architectural protein H-NS binds nonspecifically to hundreds of sites throughout the chromosome and can multimerize to stiffen segments of DNA as well as to form DNA-protein-DNA bridges. H-NS has been suggested to contribute to the orderly folding of the
Escherichia coli
chromosome in the highly compacted nucleoid. In this study, we investigated the positioning and dynamics of the origins, the replisomes, and the SeqA structures trailing the replication forks in cells lacking the H-NS protein. In H-NS mutant cells, foci of SeqA, replisomes, and origins were irregularly positioned in the cell. Further analysis showed that the average distance between the SeqA structures and the replisome was increased by ∼100 nm compared to that in wild-type cells, whereas the colocalization of SeqA-bound sister DNA behind replication forks was not affected. This result may suggest that H-NS contributes to the folding of DNA along adjacent segments. H-NS mutant cells were found to be incapable of adopting the distinct and condensed nucleoid structures characteristic of
E. coli
cells growing rapidly in rich medium. It appears as if H-NS mutant cells adopt a “slow-growth” type of chromosome organization under nutrient-rich conditions, which leads to a decreased cellular DNA content.

IMPORTANCE
It is not fully understood how and to what extent nucleoid-associated proteins contribute to chromosome folding and organization during replication and segregation in
Escherichia coli
. In this work, we find
in vivo
indications that cells lacking the nucleoid-associated protein H-NS have a lower degree of DNA condensation than wild-type cells. Our work suggests that H-NS is involved in condensing the DNA along adjacent segments on the chromosome and is not likely to tether newly replicated strands of sister DNA. We also find indications that H-NS is required for rapid growth with high DNA content and for the formation of a highly condensed nucleoid structure under such conditions.
Quality gaps identified through mortality review
Authors: Kobewka Daniel M , van Walraven Carl , Turnbull Jeffrey , Worthington James , Calder Lisa , Forster Alan 
Published: February 2016

BackgroundHospital mortality rate is a common measure of healthcare quality. Morbidity and mortality meetings are common but there are few reports of hospital-wide mortality-review processes to provide understanding of quality-of-care problems associated with patient deaths.ObjectiveTo describe the implementation and results from an institution-wide mortality-review process.DesignA nurse and a physician independently reviewed every death that occurred at our multisite teaching institution over a 3-month period. Deaths judged by either reviewer to be unanticipated or to have any opportunity for improvement were reviewed by a multidisciplinary committee. We report characteristics of patients with unanticipated death or opportunity for improved care and summarise the opportunities for improved care.ResultsOver a 3-month period, we reviewed all 427 deaths in our hospital in detail; 33 deaths (7.7%) were deemed unanticipated and 100 (23.4%) were deemed to be associated with an opportunity for improvement. We identified 97 opportunities to improve care. The most common gap in care was: ‘goals of care not discussed or the discussion was inadequate’ (n=25 (25.8%)) and ‘delay or failure to achieve a timely diagnosis’ (n=8 (8.3%)). Patients who had opportunities for improvement had longer length of stay and a lower baseline predicted risk of death in hospital. Nurse and physician reviewers spent approximately 142 h reviewing cases outside of committee meetings.ConclusionsOur institution-wide mortality review found many quality gaps among decedents, in particular inadequate discussion of goals of care.
Raising the issue of DNAR orders in vascular surgery patients
Authors: McIntosh Rachel , Webb Hannah , Hartley Matthew , Brooks Marcus 
Published: February 2016

AbstractThe Tracey Report has recently raised the status of Do Not Attempt Cardio Pulmonary Resuscitation (DNACPR) orders in the hospital setting.[1] Guidelines are in place both nationally and locally to provide advice to clinicians on when to discuss DNACPR, and the approach to be taken. There was concern that on a busy regional vascular surgery unit, discussion of resuscitation status was not regular practice. Consequently, some patients were at risk of being inappropriately resuscitated, particularly out of hours.The North Bristol Somerset and Gloucester DNAR decision tree[2] was the tool used to decide whether a patient should have a documented discussion and/or a DNACPR form completed. We correlated the outcome of the decision tree with the presence of a DNACPR form or documented resuscitation discussion. Baseline measurements from all vascular inpatients on the vascular surgery unit demonstrated that only 27% had a DNACPR form or documented discussion in concordance with the DNACPR Decision Tree outcome.The aim of this project was to increase the proportion of patients with concordance of the DNACPR decision tree outcome with documented discussion or DNACPR form.The following three simple interventions raised concordance from 27% to 64% of patients on the vascular surgery unit.1. Including resuscitation status of each patient as a column in the doctors daily handover.2. Posters in staff only areas to highlight the meaning of DNACPR and raise awareness of the DNACPR decision tree.3. Educational meeting surrounding DNACPR with the vascular surgery consultants, led by a care of the elderly consultant .This project has highlighted how raising awareness around DNACPR increases discussion amongst the clinical team surrounding resuscitation status of a patient. Consequently, this enables discussion to be had with patient and their family.