bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic Properties of Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis
Authors: Boonstra J. M. , van der Elst K. C. , Veringa A. , Jongedijk E. M. , Brüggemann R. J. , Koster R. A. , Kampinga G. A. , Kosterink J. G. , van der Werf T. S. , Zijlstra J. G. , Touw D. J. , Alffenaar J. W. C. 
Published: October 2017

ABSTRACT

The estimated attributable mortality rate for invasive candidiasis (IC) in the intensive care unit (ICU) setting varies from 30 to 40%. Physiological changes in critically ill patients may affect the distribution and elimination of micafungin, and therefore, dosing adjustments might be mandatory. The objective of this study was to determine the pharmacokinetic parameters of micafungin in critically ill patients and assess the probability of target attainment. Micafungin plasma concentrations were measured to estimate the pharmacokinetic properties of micafungin. MIC values for
Candida
isolates were determined to assess the probability of target attainment for patients. Data from 19 patients with suspected or proven invasive candidiasis were available for analysis. The median area under the concentration-time curve from 0 to 24 h at steady state (AUC
0–24
) was 89.6 mg · h/liter (interquartile range [IQR], 75.4 to 113.6 mg · h/liter); this was significantly lower than the median micafungin AUC
0–24
values of 152.0 mg · h/liter (IQR, 136.0 to 162.0 mg · h/liter) and 134.0 mg · h/liter (IQR, 118.0 to 148.6 mg · h/liter) in healthy volunteers (
P
= <0.0001 and
P
= <0.001, respectively). All
Candida
isolates were susceptible to micafungin, with a median MIC of 0.016 mg/liter (IQR, 0.012 to 0.023 mg/liter). The median AUC
0–24
/MIC ratio was 5,684 (IQR, 4,325 to 7,578), and 3 of the 17 evaluable patients (17.6%) diagnosed with proven invasive candidiasis did not meet the AUC/MIC ratio target of 5,000. Micafungin exposure was lower in critically ill patients than in healthy volunteers. The variability in micafungin exposure in this ICU population could be explained by the patients' body weight. Our findings suggest that healthier patients (sequential organ failure assessment [SOFA] score of <10) weighing more than 100 kg and receiving 100 mg micafungin daily are at risk for inappropriate micafungin exposure and potentially inadequate antifungal treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT01716988.)
Multicenter Study of the Risk Factors for Colonization or Infection with Carbapenem-Resistant Enterobacteriaceae in Children
Authors: Chiotos Kathleen , Tamma Pranita D. , Flett Kelly B. , Naumann Matthew , Karandikar Manjiree V. , Bilker Warren B. , Zaoutis Theoklis , Han Jennifer H. 
Published: October 2017

ABSTRACT

Carbapenem-resistant
Enterobacteriaceae
(CRE) are increasingly identified in children in the United States, but data on the epidemiology of CRE in this population are limited. The objectives of this study were to characterize the risk factors for colonization or infection with CRE and describe the microbiologic characteristics of pediatric CRE isolates. We performed a multicenter matched case-control study from January 2011 to October 2015 at three tertiary care pediatric centers. Case patients were hospitalized children with CRE isolated from clinical cultures and were matched in a 2:1 ratio to control patients with carbapenem-susceptible
Enterobacteriaceae
(CSE). Risk factors for colonization or infection with CRE were then evaluated using a multivariable conditional logistic regression. Additionally, we comprehensively reported the antimicrobial susceptibility pattern for CRE isolates. Sixty-three case patients were identified and matched to 126 control patients. On multivariable analysis, antipseudomonal antibiotic exposure within the previous 3 months (odds ratio [OR], 5.20; 95% confidence interval [CI], 1.71 to 15.9;
P
= 0.004), prior surgery (OR, 6.30; 95% CI, 1.83 to 21.6;
P
= 0.003), and mechanical ventilation (OR, 12.4; 95% CI, 1.26 to 122;
P
= 0.031) were identified as risk factors for colonization or infection with CRE. Pediatric CRE isolates demonstrated relatively low rates of resistance to amikacin (5%) and ciprofloxacin (25%). Our findings support an important role for antibiotic stewardship interventions limiting the unnecessary use of antipseudomonal antibiotics as a strategy to prevent widespread emergence of CRE in children. Future studies should further characterize molecular determinants of antibiotic resistance among pediatric CRE isolates.
Diversity of Mosaic
pbp2x
Families in Penicillin-Resistant Streptococcus pneumoniae from Iran and Romania
Authors: Mousavi Seyed Fazlollah , Pana Marina , Feizabadi Mohammad , Jalali Pantea , Ghita Maria , Denapaite Dalia , Hakenbeck Regine 
Published: October 2017

ABSTRACT

Penicillin-resistant
Streptococcus pneumoniae
strains are found at high rates in Romania and Iran. The mosaic structure of PBP2x was investigated in 9 strains from Iran and in 15 strains from Romania to understand their evolutionary history. Mutations potentially important for β-lactam resistance were identified by comparison of the PBP2x sequences with the sequence of the related PBP2x of reference penicillin-sensitive
S. mitis
strains. Two main PBP2x mosaic gene families were recognized. Eight Iranian strains expressed PBP2x variants in group 1, which had a mosaic block highly related to PBP2x of the Spain
23F
-1 clone, which is widespread among international penicillin-resistant
S. pneumoniae
clones. A second unique PBP2x group was observed in Romanian strains; furthermore, three PBP2x single mosaic variants were found. Sequence blocks of penicillin-sensitive strain
S. mitis
658 were common among PBP2x variants from strains from both countries. Each PBP2x group contained specific signature mutations within the transpeptidase domain, documenting the existence of distinct mutational pathways for the development of penicillin resistance.
Kinetics of Sulbactam Hydrolysis by β-Lactamases, and Kinetics of β-Lactamase Inhibition by Sulbactam
Authors: Shapiro Adam B. 
Published: October 2017

ABSTRACT

Sulbactam is one of four β-lactamase inhibitors in current clinical use to counteract drug resistance caused by degradation of β-lactam antibiotics by these bacterial enzymes. As a β-lactam itself, sulbactam is susceptible to degradation by β-lactamases. I investigated the Michaelis-Menten kinetics of sulbactam hydrolysis by 14 β-lactamases, representing clinically widespread groups within all four Ambler classes, i.e., CTX-M-15, KPC-2, SHV-5, and TEM-1 for class A; IMP-1, NDM-1, and VIM-1 for class B;
Acinetobacter baumannii
ADC-7,
Pseudomonas aeruginosa
AmpC, and
Enterobacter cloacae
P99 for class C; and OXA-10, OXA-23, OXA-24, and OXA-48 for class D. All of the β-lactamases were able to hydrolyze sulbactam, although they varied widely in their kinetic constants for the reaction, even within each class. I also investigated the inactivation kinetics of the inhibition of these enzymes by sulbactam. The class A β-lactamases varied widely in their susceptibility to inhibition, the class C and D enzymes were very weakly inhibited, and the class B enzymes were essentially or completely unaffected. In addition, we measured the sulbactam turnover number, the sulbactam/enzyme molar ratio required for complete inhibition of each enzyme. Class C enzymes had the lowest turnover numbers, class A enzymes varied widely, and class D enzymes had very high turnover numbers. These results are valuable for understanding which β-lactamases ought to be well inhibited by sulbactam. Moreover, since sulbactam has intrinsic antibacterial activity against
Acinetobacter
species pathogens, these results contribute to understanding β-lactamase-mediated sulbactam resistance in
Acinetobacter
, especially due to the action of the widespread class D enzymes.
Concentration and Variety of Carbapenemase Producers in Recreational Coastal Waters Showing Distinct Levels of Pollution
Authors: Paschoal Raphael P. , Campana Eloiza H. , Corrêa Laís L. , Montezzi Lara F. , Barrueto Lina R. L. , da Silva Isadora R. , Bonelli Raquel R. , Castro Laura de S. , Picão Renata C. 
Published: October 2017

ABSTRACT
Carbapenemase-producing bacteria cause difficult-to-treat infections related to increased mortality in health care settings. Their occurrence has been reported in raw sewage, sewage-impacted rivers, and polluted coastal waters, which may indicate their spread to the community. We assessed the variety and concentration of carbapenemase producers in coastal waters with distinct pollution levels for 1 year. We describe various bacterial species producing distinct carbapenemases not only in unsuitable waters but also in waters considered suitable for primary contact.
Disruption of a Transcriptional Repressor by an Insertion Sequence Element Integration Leads to Activation of a Novel Silent Cellobiose Transporter in Lactococcus lactis MG1363
Authors: Solopova Ana , Kok Jan , Kuipers Oscar P. 
Published: October 2017

ABSTRACT

Lactococcus lactis
subsp.
cremoris
strains typically carry many dairy niche-specific adaptations. During adaptation to the milk environment these former plant strains have acquired various pseudogenes and insertion sequence elements indicative of ongoing genome decay and frequent transposition events in their genomes. Here we describe the reactivation of a silenced plant sugar utilization cluster in an
L. lactis
MG1363 derivative lacking the two main cellobiose transporters, PtcBA-CelB and PtcBAC, upon applying selection pressure to utilize cellobiose. A disruption of the transcriptional repressor gene
llmg_1239
by an insertion sequence (IS) element allows expression of the otherwise silent novel cellobiose transporter Llmg_1244 and leads to growth of mutant strains on cellobiose. Llmg_1239 was labeled CclR, for
c
ellobiose
cl
uster
r
epressor.

IMPORTANCE
Insertion sequences (ISs) play an important role in the evolution of lactococci and other bacteria. They facilitate DNA rearrangements and are responsible for creation of new genetic variants with selective advantages under certain environmental conditions.
L. lactis
MG1363 possesses 71 copies in a total of 11 different types of IS elements. This study describes yet another example of an IS-mediated adaptive evolution. An integration of IS
981
or IS
905
into a gene coding for a transcriptional repressor led to activation of the repressed gene cluster coding for a plant sugar utilization pathway. The expression of the gene cluster allowed assembly of a novel cellobiose-specific transporter and led to cell growth on cellobiose.
Wide but Variable Distribution of a Hypervirulent Campylobacter jejuni Clone in Beef and Dairy Cattle in the United States
Authors: Tang Yizhi , Meinersmann Richard J. , Sahin Orhan , Wu Zuowei , Dai Lei , Carlson James , Plumblee Lawrence Jodie , Genzlinger Linda , LeJeune Jeffrey T. , Zhang Qijing 
Published: October 2017

ABSTRACTCampylobacter jejuniclone SA is the major cause of sheep abortion and contributes significantly to foodborne illnesses in the United States. Clone SA is hypervirulent because of its distinct ability to produce systemic infection and its predominant role in clinical sheep abortion. Despite the importance of clone SA, little is known about its distribution and epidemiological features in cattle. Here we describe a prospective study onC. jejuniclone SA prevalence in 35 feedlots in 5 different states in the United States and a retrospective analysis of clone SA inC. jejuniisolates collected by National Animal Health Monitoring System (NAHMS) dairy studies in 2002, 2007, and 2014. In feedlot cattle feces, the overall prevalence ofCampylobacterorganisms was 72.2%, 82.1% of which wereC. jejuni. Clone SA accounted for 5.8% of the totalC. jejuniisolates, but its prevalence varied by feedlot and state. Interestingly, starlings on the feedlots harboredC. jejuniin feces, including clone SA, suggesting that these birds may play a role in the transmission ofCampylobacter. In dairy cattle, the overall prevalence of clone SA was 7.2%, but a significant decrease in the prevalence was observed from 2002 to 2014. Whole-genome sequence analysis of the dairy clone SA isolates revealed that it was genetically stable over the years and most of the isolates carried the tetracycline resistance genetet(O) in the chromosome. These findings indicate that clone SA is widely distributed in both beef and dairy cattle and provide new insights into the molecular epidemiology of clone SA in ruminants.IMPORTANCEC. jejuniclone SA is a major cause of small-ruminant abortion and an emerging threat to food safety because of its association with foodborne outbreaks. Cattle appear to serve as a major reservoir for this pathogenic organism, but there is a major gap in our knowledge about the epidemiology of clone SA in beef and dairy cattle. By taking advantage of surveillance studies conducted on a national scale, we found a wide but variable distribution of clone SA in feedlot cattle and dairy cows in the United States. Additionally, the work revealed important genomic features of clone SA isolates from cattle. These findings provide critically needed information for the development of preharvest interventions to control the transmission of this zoonotic pathogen. Control ofC. jejuniclone SA will benefit both animal health and public health, as it is a zoonotic pathogen causing disease in both ruminants and humans.
Ectomycorrhizal Fungal Communities in Urban Parks Are Similar to Those in Natural Forests but Shaped by Vegetation and Park Age
Authors: Hui Nan , Liu Xinxin , Kotze D. Johan , Jumpponen Ari , Francini Gaia , Setälä Heikki 
Published: October 2017

ABSTRACT
Ectomycorrhizal (ECM) fungi are important mutualists for the growth and health of most boreal trees. Forest age and its host species composition can impact the composition of ECM fungal communities. Although plentiful empirical data exist for forested environments, the effects of established vegetation and its successional trajectories on ECM fungi in urban greenspaces remain poorly understood. We analyzed ECM fungi in 5 control forests and 41 urban parks of two plant functional groups (conifer and broadleaf trees) and in three age categories (10, ∼50, and >100 years old) in southern Finland. Our results show that although ECM fungal richness was marginally greater in forests than in urban parks, urban parks still hosted rich and diverse ECM fungal communities. ECM fungal community composition differed between the two habitats but was driven by taxon rank order reordering, as key ECM fungal taxa remained largely the same. In parks, the ECM communities differed between conifer and broadleaf trees. The successional trajectories of ECM fungi, as inferred in relation to the time since park construction, differed among the conifers and broadleaf trees: the ECM fungal communities changed over time under the conifers, whereas communities under broadleaf trees provided no evidence for such age-related effects. Our data show that plant-ECM fungus interactions in urban parks, in spite of being constructed environments, are surprisingly similar in richness to those in natural forests. This suggests that the presence of host trees, rather than soil characteristics or even disturbance regime of the system, determine ECM fungal community structure and diversity.

IMPORTANCE
In urban environments, soil and trees improve environmental quality and provide essential ecosystem services. ECM fungi enhance plant growth and performance, increasing plant nutrient acquisition and protecting plants against toxic compounds. Recent evidence indicates that soil-inhabiting fungal communities, including ECM and saprotrophic fungi, in urban parks are affected by plant functional type and park age. However, ECM fungal diversity and its responses to urban stress, plant functional type, or park age remain unknown. The significance of our study is in identifying, in greater detail, the responses of ECM fungi in the rhizospheres of conifer and broadleaf trees in urban parks. This will greatly enhance our knowledge of ECM fungal communities under urban stresses, and the findings can be utilized by urban planners to improve urban ecosystem services.
High-Quality Genome Sequence of Bacillus anthracis Strain 14RA5914 Isolated during an Outbreak in Germany in 2014
Authors: Elschner Mandy C. , Busch Anne , Schliephake Annette , Gaede Wolfgang , Zuchantke Eric , Tomaso Herbert 
Published: October 2017

ABSTRACT

Bacillus anthracis
is a zoonotic agent causing anthrax, a notifiable disease in animals. The last anthrax outbreak among cattle in Germany occurred in April 2014 in Saxony-Anhalt. Here we report a high-quality genome sequence of the
Bacillus anthracis
strain 14RA5914 Dobichau isolated from the spleen of a dead cow.
Complete Genome Sequence of a Novel Bastrovirus Isolated from Raw Sewage
Authors: dos Anjos Karoline , Nagata Tatsuya , Melo Fernando Lucas de 
Published: October 2017

ABSTRACT
The complete genome sequence of a novel bastrovirus was determined. The genome has 5,875 nucleotides and shares 56% nucleotide identity with a bastrovirus-like virus found in bat feces.
Fluorescence-Reported Allelic Exchange Mutagenesis Reveals a Role for Chlamydia trachomatis TmeA in Invasion That Is Independent of Host AHNAK
Authors: McKuen M. J. , Mueller K. E. , Bae Y. S. , Fields K. A. 
Published: October 2017

ABSTRACT

Development of approaches to genetically manipulate
Chlamydia
is fostering important advances in understanding pathogenesis.
F
luorescence-
r
eported
a
llelic
e
xchange
m
utagenesis (FRAEM) now enables the complete deletion of specific genes in
C. trachomatis
L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to
ct694-ctl0063
t
ranslocated
m
embrane-associated
e
ffector A (TmeA). Deletion of
tmeA
did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity in both tissue culture and murine infection models. The
in vitro
defect was reflected by impaired invasion of host cells. TmeA binds human AHNAK, and we demonstrate here that AHNAK is transiently recruited by invading chlamydiae. TmeA, however, is not required for endogenous AHNAK recruitment. TmeA also impairs AHNAK-dependent actin bundling activity. This TmeA-mediated effect likely does not explain impaired invasion displayed by the
tmeA
strain of
Chlamydia
, since AHNAK-deficient cells revealed no invasion phenotype. Overall, our data indicate the efficacy of FRAEM and reveal a role of TmeA during chlamydial invasion that manifests independently of effects on AHNAK.
Inflammasome Activation by Bacterial Outer Membrane Vesicles Requires Guanylate Binding Proteins
Authors: Finethy Ryan , Luoma Sarah , Orench-Rivera Nichole , Feeley Eric M. , Haldar Arun K. , Yamamoto Masahiro , Kanneganti Thirumala-Devi , Kuehn Meta J. , Coers Jörn 
Published: October 2017

ABSTRACT

The Gram-negative bacterial cell wall component lipopolysaccharide (LPS) is recognized by the noncanonical inflammasome protein caspase-11 in the cytosol of infected host cells and thereby prompts an inflammatory immune response linked to sepsis. Host guanylate binding proteins (GBPs) promote infection-induced caspase-11 activation in tissue culture models, and yet their
in vivo
role in LPS-mediated sepsis has remained unexplored. LPS can be released from lysed bacteria as “free” LPS aggregates or actively secreted by live bacteria as a component of outer membrane vesicles (OMVs). Here, we report that GBPs control inflammation and sepsis in mice injected with either free LPS or purified OMVs derived from Gram-negative
Escherichia coli
. In agreement with our observations from
in vivo
experiments, we demonstrate that macrophages lacking GBP2 expression fail to induce pyroptotic cell death and proinflammatory interleukin-1β (IL-1β) and IL-18 secretion when exposed to OMVs. We propose that in order to activate caspase-11
in vivo
, GBPs control the processing of bacterium-derived OMVs by macrophages as well as the processing of circulating free LPS by as-yet-undetermined cell types.

IMPORTANCE
The bacterial cell wall component LPS is a strong inducer of inflammation and is responsible for much of the toxicity of Gram-negative bacteria. Bacteria shed some of their cell wall and its associated LPS in the form of outer membrane vesicles (OMVs). Recent work demonstrated that secreted OMVs deliver LPS into the host cell cytosol by an unknown mechanism, resulting in the activation of the proinflammatory LPS sensor caspase-11. Here, we show that activation of cytosolic caspase-11 by OMVs requires additional host factors, the so-called guanylate binding proteins (GBPs). The discovery of GBPs as regulators of OMV-mediated inflammation paves the way toward a mechanistic understanding of the host response toward bacterial OMVs and may lead to effective strategies to ameliorate inflammation induced by bacterial infections.
Neuroimaging and endocrine disorders in paediatric optic nerve hypoplasia
Authors: Qian Xiaoxiao , Fouzdar Jain Samksha , Morgan Linda A , Kruse Travis , Cabrera Monina , Suh Donny W 
Published: October 2017

PurposeOptic nerve hypoplasia (ONH) is one of the leading causes of blindness among children. The purpose of this retrospective study is to determine the risk factors and association between brain MRI findings, pituitary abnormalities and endocrine disorders with the presence of ONH.MethodsA retrospective review of patients seen at paediatric ophthalmology clinics from January 2006 to December 2016 at Children’s Hospital and Medical Center and the University of Nebraska Medical Center was performed. All patients with a documented diagnosis of ONH or septo-optic dysplasia were identified. MRI and endocrinology results were analysed by masked examiners.ResultsOut of 77 patients, overall incidence of abnormal pituitary on MRI was 35.1% and the incidence of endocrine abnormalities was 37.7%. Of the 57 patients with bilateral ONH, 23 (40.4%) had an abnormal pituitary while 4 of the 20 patients (20.0%) with unilateral ONH had an abnormal pituitary on MRI. The sensitivity and specific of brain MRI as signs of endocrinopathy are 67.9% and 83.3%, respectively.ConclusionThis study has determined that abnormal MRI findings do not have the sensitivity to predict endocrinopathy, nor does a normal MRI rule out possible endocrine abnormalities. When patients with ONH present with normal neurological examinations, normal endocrine workup and normal developmental milestones, a MRI of the brain may be deferred until new indications arise. Regardless of the MRI status, children with ONH should have a comprehensive endocrine evaluation and continue to have routine endocrine follow-up.