bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Antibiotic Resistance in Urinary Tract Infection Patients with Prior Urine Cultures
Authors: Dickstein Yaakov , Geffen Yuval , Andreassen Steen , Leibovici Leonard , Paul Mical 
Published: May 2016

ABSTRACT

To improve antibiotic prescribing, we sought to establish the probability of a resistant organism in urine culture given a previous resistant culture in a setting endemic for multidrug-resistant (MDR) organisms. We performed a retrospective analysis of inpatients with paired positive urine cultures. We focused on ciprofloxacin-resistant (cipro
r
) Gram-negative bacteria, extended-spectrum-beta-lactamase (ESBL)-producing
Enterobacteriaceae
, carbapenem-resistant
Enterobacteriaceae
(CRE), and carbapenem-resistant nonfermenters (CRNF). Comparisons were made between the frequency of each resistance phenotype following a previous culture with the same phenotype and the overall frequency of that phenotype, and odds ratios (ORs) were calculated. We performed a regression to assess the effects of other variables on the likelihood of a repeat resistant culture. A total of 4,409 patients (52.5% women; median age, 70 years) with 19,546 paired positive urine cultures were analyzed. The frequencies of cipro
r
bacteria, ESBL-producing
Enterobacteriaceae
, CRE, and CRNF among all cultures were 47.7%, 30.6%, 1.7%, and 2.6%, respectively. ORs for repeated resistance phenotypes were 1.87, 3.19, 48.25, and 19.02 for cipro
r
bacteria, ESBL-producing
Enterobacteriaceae
, CRE, and CRNF, respectively (
P
< 0.001 for all). At 1 month, the frequencies of repeated resistance phenotypes were 77.4%, 66.4%, 57.1%, and 33.3% for cipro
r
bacteria, ESBL-producing
Enterobacteriaceae
, CRE, and CRNF, respectively. Increasing time between cultures and the presence of an intervening nonresistant culture significantly reduced the chances of a repeat resistant culture. Associations were statistically significant over the duration of follow-up (60 months) for CRE and for up to 6 months for all other pathogens. Knowledge of microbiology results in the six preceding months may assist with antibiotic stewardship and improve the appropriateness of empirical treatment for urinary tract infections (UTIs).
Antifungal Susceptibility Testing of Ascomycetous Yeasts Isolated from Animals
Authors: Álvarez-Pérez Sergio , García Marta E. , Peláez Teresa , Martínez-Nevado Eva , Blanco José L. 
Published: May 2016

ABSTRACT
Recent studies suggest that antifungal resistance in yeast isolates of veterinary origin may be an underdiagnosed threat. We tested a collection of 92 ascomycetous yeast isolates that were obtained in Spain from birds, mammals and insects for antifungal susceptibility. MICs to amphotericin B and azoles were low, and no resistant isolates were detected. Despite these results, and given the potential role of animals as reservoirs of resistant strains, continuous monitoring of antifungal susceptibility in the veterinary setting is recommended.
New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients
Authors: Cristallini Stefano , Hites Maya , Kabtouri Hakim , Roberts Jason A. , Beumier Marjorie , Cotton Frederic , Lipman Jeffrey , Jacobs Frédérique , Vincent Jean-Louis , Creteur Jacques , Taccone Fabio Silvio 
Published: May 2016

ABSTRACT
Despite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment.
Detection of the
mcr-1
Colistin Resistance Gene in Carbapenem-Resistant Enterobacteriaceae from Different Hospitals in China
Authors: Yu Hua , Qu Fen , Shan Bin , Huang Bin , Jia Wei , Chen Cha , Li Aiqing , Miao Minhui , Zhang Xin , Bao Chunmei , Xu Yunmin , Chavda Kalyan D. , Tang Yi-Wei , Kreiswirth Barry N. , Du Hong , Chen Liang 
Published: May 2016

ABSTRACT

The spread of the plasmid-mediated colistin resistance gene,
mcr-1
, into carbapenem-resistant
Enterobacteriaceae
(CRE) clinical isolates poses a significant threat to global health. Here we report the identification of three
mcr-1
-harboring carbapenem-resistant
Escherichia coli
strains, collected from three patients in two provinces in China. Our results show that
mcr-1
-harboring CRE strains have started to spread in different hospitals in China. In addition, this report presents the first description of chromosomal integration of
mcr-1
into a carbapenem-resistant
E. coli
strain.
Changes in the Frequencies of β-Lactamase Genes among Enterobacteriaceae Isolates in U.S. Hospitals, 2012 to 2014: Activity of Ceftazidime-Avibactam Tested against β-Lactamase-Producing Isolates
Authors: Castanheira Mariana , Mendes Rodrigo E. , Jones Ronald N. , Sader Helio S. 
Published: May 2016

ABSTRACT

Among 15,588
Enterobacteriaceae
isolates collected in 63 U.S. hospitals from 2012 to 2014, 2,129 (13.7%) displayed an extended-spectrum β-lactamase (ESBL) phenotype. These rates were similar over time (13.2 to 13.9%); however, differences among
Escherichia coli
(12.7 and 15.1% in 2012 and 2014;
P
= 0.007) and
Klebsiella pneumoniae
(18.9 and 15.5% in 2012 and 2014;
P
= 0.006) were noted when comparing 2014 and 2012. Carbapenem-resistant
Enterobacteriaceae
(CRE) (2.3 and 1.8%) and carbapenem-resistant
K. pneumoniae
(6.8 and 5.1%;
P
= 0.003) rates were lower in 2014 than in 2012. Isolates carrying
bla
CTX-M-15
-like genes were stable (42.1 to 42.4%), but a decrease among
E. coli
isolates (59.1 and 49.7%;
P
= 0.008) and an increase among
K. pneumoniae
isolates (32.7 and 41.2%;
P
= 0.022) in 2014 were observed. Isolates carrying
bla
KPC
(304) decreased over the years (16.5 and 10.9%;
P
= 0.008), mainly due to the decrease in
K. pneumoniae
isolates harboring
bla
KPC
(
n
= 285; 35.6 and 28.4%;
P
= 0.041) in hospitals in the Mid-Atlantic and South Atlantic regions, where these isolates were highly prevalent during 2012 and 2013. Isolates carrying
bla
CMY-2-
like and
bla
CTX-M-14-
like genes increased (8.2 and 11.9% and 9.1 and 12.9%, respectively;
P
= 0.04 for both), and those producing
bla
SHV
ESBL decreased (24.9 and 12.7%;
P
< 0.001) over the studied years, due to a decreased occurrence of the enzymes among
K. pneumoniae
isolates. Other enzymes were detected in smaller numbers of isolates, including four
K. pneumoniae
isolates carrying
bla
NDM-1
metallo-β-lactamase (two in 2012 and two in 2014). Ceftazidime-avibactam, a recently approved β-lactamase inhibitor combination, was very active against the ESBL phenotype isolates (MIC
50/90
, 0.12 and 1 μg/ml; 99.7% susceptible) and CRE strains (MIC
50/90
, 0.5 and 2 μg/ml; 98.5% susceptible) that displayed elevated MIC values for many comparator agents. In conclusion, significant changes were noted in the frequencies of isolates harboring various β-lactamases among U.S. hospitals between 2012 and 2014 that will require continued monitoring.
Phenotypic Screening
In Vitro
of Novel Aromatic Amidines against Trypanosoma cruzi
Authors: Simões-Silva M. R. , Nefertiti A. S. G. , De Araújo J. S. , Batista M. M. , Da Silva P. B. , Bahia M. T. , Menna-Barreto R. S. , Pavão B. P. , Green J. , Farahat A. A. , Kumar A. , Boykin D. W. , Soeiro M. N. C. 
Published: May 2016

ABSTRACT

The current treatment of Chagas disease (CD), based on nifurtimox and benznidazole (Bz), is unsatisfactory. In this context, we performed the phenotypic
in vitro
screening of novel mono- and diamidines and drug interaction assays with selected compounds. Ten novel amidines were tested for their activities against bloodstream trypomastigote (BT) and amastigote forms of
Trypanosoma cruzi
(Y and Tulahuen strains) and their toxicities for mammalian host cells (L929 cells and cardiac cells). Seven of 10 molecules were more active than Bz against BT, with the most active compound being the diamidine DB2267 (50% effective concentration [EC
50
] = 0.23 μM; selectivity index = 417), which was 28-fold more active and about 3 times more selective than the standard drug. Five of the six monoamidines were also more active than Bz. The combination of DB2267 and DB2236 in fixed-ratio proportions showed an additive effect (sum of fractional inhibitory concentrations < 4) on BT. Interestingly, when intracellular forms were exposed to DB2267, its activity was dependent on the parasite strain, being effective (EC
50
= 0.87 ± 0.05 μM) against a discrete typing unit (DTU) II strain (strain Y) but not against a representative DTU VI strain (strain Tulahuen) even when different vehicles (β-cyclodextrin and dimethyl sulfoxide) were used. The intrinsic fluorescence of several diamidines allowed their uptake to be studied. Testing of the uptake of DB2236 (inactive) and DB2267 (active) by amastigotes of the Y strain showed that the two compounds were localized intracellularly in different compartments: DB2236 in the cytoplasm and DB2267 in the nucleus. Our present data encourage further studies regarding the activities of amidines and provide information which will help with the identification of novel agents for the treatment of CD.
Assessment of the
In Vitro
Activity of Ceftazidime-Avibactam against Multidrug-Resistant Klebsiella spp. Collected in the INFORM Global Surveillance Study, 2012 to 2014
Authors: Hackel Meredith , Kazmierczak Krystyna M. , Hoban Daryl J. , Biedenbach Douglas J. , Bouchillon Samuel K. , de Jonge Boudewijn L. M. , Stone Gregory G. 
Published: May 2016

ABSTRACT

Increasing resistance in Gram-negative bacilli, including
Klebsiella
spp., has reduced the utility of broad-spectrum cephalosporins. Avibactam, a novel non-β-lactam β-lactamase inhibitor, protects β-lactams from hydrolysis by Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs) and serine carbapenemases, including Ambler class A and/or class C and some class D enzymes. In this analysis, we report the
in vitro
activity of ceftazidime-avibactam and comparators against multidrug-resistant (MDR)
Klebsiella
spp. from the 2012-2014 INFORM surveillance study. Isolates collected from 176 sites were sent to a central laboratory for confirmatory identification and tested for susceptibility to ceftazidime-avibactam and comparator agents, including ceftazidime alone. A total of 2,821 of 10,998 (25.7%)
Klebsiella
species isolates were classified as MDR, based on resistance to three or more classes of antimicrobials. Among the MDR isolates, 99.4% had an ESBL screen-positive phenotype, and 27.4% were not susceptible to meropenem as an example of a carbapenem. Ceftazidime-avibactam was highly active against MDR isolates, including ESBL-positive and serine carbapenemase-producing isolates, with MIC
50/90
values of 0.5/2 μg/ml and 96.6% of all MDR isolates and ESBL-positive MDR isolates inhibited at the FDA breakpoint (MIC value of ≤8 μg/ml). Ceftazidime-avibactam did not inhibit isolates producing class B enzymes (metallo-β-lactamases) either alone or in combination with other enzymes. These
in vitro
results support the continued investigation of ceftazidime-avibactam for the treatment of MDR
Klebsiella
species infections.
HtrA Is Important for Stress Resistance and Virulence in Haemophilus parasuis
Authors: Zhang Luhua , Li Ying , Wen Yiping , Lau Gee W. , Huang Xiaobo , Wu Rui , Yan Qigui , Huang Yong , Zhao Qin , Ma Xiaoping , Wen Xintian , Cao Sanjie 
Published: May 2016

ABSTRACT

Haemophilus parasuis
is an opportunistic pathogen that causes Glässer's disease in swine, with polyserositis, meningitis, and arthritis. The high-temperature requirement A (HtrA)-like protease, which is involved in protein quality control, has been reported to be a virulence factor in many pathogens. In this study, we showed that HtrA of
H. parasuis
(HpHtrA) exhibited both chaperone and protease activities. Finally, nickel import ATP-binding protein (NikE), periplasmic dipeptide transport protein (DppA), and outer membrane protein A (OmpA) were identified as proteolytic substrates for HpHtrA. The protease activity reached its maximum at 40°C in a time-dependent manner. Disruption of the
htrA
gene from strain SC1401 affected tolerance to temperature stress and resistance to complement-mediated killing. Furthermore, increased autoagglutination and biofilm formation were detected in the
htrA
mutant. In addition, the
htrA
mutant was significantly attenuated in virulence in the murine model of infection. Together, these data demonstrate that HpHtrA plays an important role in the virulence of
H. parasuis
.
Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins
Authors: Hu Yueming , Huang He , Hui Xinjie , Cheng Xi , White Aaron P. , Zhao Zhendong , Wang Yejun 
Published: May 2016

ABSTRACT

Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In
Yersinia
, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by
Yersinia
genomes or their evolution. In this study, the
Yersinia
LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 protein-encoding genes (
LRR1
genes) varied dramatically and were categorized into 4 subgroups (a to d), with the
LRR1a
to
-c
genes evolving from the same ancestor and
LRR1d
genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of
Yersinia
.
YodL and YisK Possess Shape-Modifying Activities That Are Suppressed by Mutations in Bacillus subtilis
mreB
and
mbl
Authors: Duan Yi , Sperber Anthony M. , Herman Jennifer K. 
Published: May 2016

ABSTRACT

Many bacteria utilize actin-like proteins to direct peptidoglycan (PG) synthesis. MreB and MreB-like proteins are thought to act as scaffolds, guiding the localization and activity of key PG-synthesizing proteins during cell elongation. Despite their critical role in viability and cell shape maintenance, very little is known about how the activity of MreB family proteins is regulated. Using a
Bacillus subtilis
misexpression screen, we identified two genes,
yodL
and
yisK
, that when misexpressed lead to loss of cell width control and cell lysis. Expression analysis suggested that
yodL
and
yisK
are previously uncharacterized Spo0A-regulated genes, and consistent with these observations, a Δ
yodL
Δ
yisK
mutant exhibited reduced sporulation efficiency. Suppressors resistant to YodL's killing activity occurred primarily in
mreB
mutants and resulted in amino acid substitutions at the interface between MreB and the highly conserved morphogenic protein RodZ, whereas suppressors resistant to YisK occurred primarily in
mbl
mutants and mapped to Mbl's predicted ATP-binding pocket. YodL's shape-altering activity appears to require MreB, as a Δ
mreB
mutant was resistant to the effects of YodL but not YisK. Similarly, YisK appears to require Mbl, as a Δ
mbl
mutant was resistant to the cell-widening effects of YisK but not of YodL. Collectively, our results suggest that YodL and YisK likely modulate MreB and Mbl activity, possibly during the early stages of sporulation.

IMPORTANCE
The peptidoglycan (PG) component of the cell envelope confers structural rigidity to bacteria and protects them from osmotic pressure. MreB and MreB-like proteins are thought to act as scaffolds for PG synthesis and are essential in bacteria exhibiting nonpolar growth. Despite the critical role of MreB-like proteins, we lack mechanistic insight into how their activities are regulated. Here, we describe the discovery of two
B. subtilis
proteins, YodL and YisK, which modulate MreB and Mbl activities. Our data suggest that YodL specifically targets MreB, whereas YisK targets Mbl. The apparent specificities with which YodL and YisK are able to differentially target MreB and Mbl make them potentially powerful tools for probing the mechanics of cytoskeletal function in bacteria.
Likelihood of ACL graft rupture: not meeting six clinical discharge criteria before return to sport is associated with a four times greater risk of rupture
Authors: Kyritsis Polyvios , Bahr Roald , Landreau Philippe , Miladi Riadh , Witvrouw Erik 
Published: May 2016

BackgroundThe decision as to whether or not an athlete is ready to return to sport (RTS) after ACL reconstruction is difficult as the commonly used RTS criteria have not been validated.PurposeTo evaluate whether a set of objective discharge criteria, including muscle strength and functional tests, are associated with risk of ACL graft rupture after RTS.Materials and methods158 male professional athletes who underwent an ACL reconstruction and returned to their previous professional level of sport were included. Before players returned to sport they underwent a battery of discharge tests (isokinetic strength testing at 60°, 180° and 300°/s, a running t test, single hop, triple hop and triple crossover hop tests). Athletes were monitored for ACL re-ruptures once they returned to sport (median follow-up 646 days, range 1–2060).ResultsOf the 158 athletes, 26 (16.5%) sustained an ACL graft rupture an average of 105 days after RTS. Two factors were associated with increased risk of ACL graft rupture: (1) not meeting all six of the discharge criteria before returning to team training (HR 4.1, 95% CI 1.9 to 9.2, p≤0.001); and (2) decreased hamstring to quadriceps ratio of the involved leg at 60°/s (HR 10.6 per 10% difference, 95% CI 10.2 to 11, p=0.005).ConclusionsAthletes who did not meet the discharge criteria before returning to professional sport had a four times greater risk of sustaining an ACL graft rupture compared with those who met all six RTS criteria. In addition, hamstring to quadriceps strength ratio deficits were associated with an increased risk of an ACL graft rupture.
Prospective cohort analysis of cellphone use and emotional and behavioural difficulties in children
Authors: Sudan Madhuri , Olsen Jorn , Arah Oyebuchi A , Obel Carsten , Kheifets Leeka 
Published: May 2016

BackgroundWe previously reported associations between cellphone exposure and emotional and behavioural difficulties in children in the Danish National Birth Cohort using cross-sectional data. To overcome the limitations of cross-sectional analysis, we re-examined these associations with prospectively collected data.MethodsBased on maternal reports, prenatal and postnatal cellphone exposures were assessed at age 7 years, and emotional and behavioural difficulties were assessed at 7 and 11 years with the Strengths and Difficulties Questionnaire. We used multivariable-adjusted logistic regression models to estimate ORs and 95% CIs relating prenatal exposure and age-7 cellphone use to emotional and behavioural difficulties at age 11 years.ResultsChildren without emotional and behavioural difficulties at age 7 years, but who had cellphone exposures, had increased odds of emotional and behavioural difficulties at age 11 years, with an OR of 1.58 (95% CI 1.34 to 1.86) for children with both prenatal and age-7 cellphone exposures, 1.41 (95% CI 1.20 to 1.66) for prenatal exposure only, and 1.36 (95% CI 1.14 to 1.63) for age-7 use only. These results did not materially change when early adopters were excluded, or when children with emotional and behavioural difficulties at age 7 years were included in the analysis.ConclusionsOur findings are consistent with patterns seen in earlier studies, and suggest that both prenatal and postnatal exposures may be associated with increased risks of emotional and behavioural difficulties in children.
The clinical dilemma of heart failure with preserved ejection fraction: an update on pathophysiology and management for physicians
Authors: Irizarry Pagán Emily E , Vargas Pedro E , López-Candales Angel 
Published: May 2016

AbstractThe prevalence of heart failure with preserved ejection fraction (HFpEF) continues to grow at alarming rates and is predicted to become the most prevalent phenotype of heart failure over the next decade. Recent data show a higher non-cardiac comorbidity burden associated with HFpEF, and similar overall hospitalisation rates when compared with patients with heart failure with reduced ejection fraction (HFrEF). Unfortunately, clinicians mainly focus their efforts in diagnosis of HFrEF despite HFpEF accounting for 50% of the cases of heart failure. Therefore, this review is intended to create awareness on the pathophysiology, risk factors, diagnosis and management of patients with HFpEF and its core mechanical abnormality left ventricular diastolic dysfunction. Clinical distinction between HFpEF and HFrEF should be of particular interest to internal medicine physicians and general practitioners as this distinction is seldom made and early diagnosis can lag if appropriate risk factors are not promptly recognised.
Running on empty: a review of nutrition and physicians' well-being
Authors: Hamidi Maryam S , Boggild Miranda K , Cheung Angela M 
Published: May 2016

AbstractResident and physician burnout is a complex issue. Adequate nutrition and hydration play important roles in the maintenance of health and well-being of all individuals. Given the high prevalence of burnout in physicians, we believe that in addition to issues related to heavy workload, structure and length of shifts, the current status of physicians' nutrition and hydration and their effects on their work performance and well-being should also be addressed. In this review, we summarise the current evidence on the potential effects of nutrition and hydration on physicians' occupational well-being and performance, identify gaps and discuss opportunities to address nutrition as one of the important means of improving physicians' well-being.