bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a comprehensive infection control program for a short‐term shelter serving trafficked women
Authors: Jones Erin , Loomis Mallory , Mealey Shalise , Newman Meagan , Schroder Holly , Smith Ashlynn , Wickline Mihkaila
Published: October 2018

A shelter for trafficked women has unique infection control needs that require a comprehensive infection control plan, balancing the needs of infection prevention with respect for the vulnerable population served. Using a trauma‐informed model and evidence from infection control in other shelter settings, a group of senior baccalaureate students developed a program in a short‐term shelter for commercially sexually exploited individuals that included a written infection control manual, policies and procedures, and staff training. This partnership between academia and a nonprofit agency was an experiential service learning project in the domain of public health nursing, allowing students the opportunity to apply evidence toward a sustainable intervention for the agency.
Melatonin treatments reduce the pathogenicity and inhibit the growth of Xanthomonas oryzae pv. oryzicola
Authors: Chen X. , Sun C. , Laborda P. , He Y. , Zhao Y. , Li C. , Liu F.
Published: October 2018

Rice bacterial leaf streak (BLS), caused by Xanthomonas oryzae pv. oryzicola (Xoc), is a prevalent disease worldwide. Melatonin, an indoleamine with the chemical name N‐acetyl‐5‐methoxytryptamine, is known to inhibit the growth of human pathogenic bacteria. However, the impact of melatonin on agricultural pathogenic bacteria remains poorly understood. In this study, the effect of melatonin on Xoc was investigated. Exogenous melatonin (200 μg mL−1) significantly inhibited the growth of Xoc and reduced the mRNA expression level of seven cell division‐related genes. Melatonin reduced the pathogenicity of Xoc towards the susceptible rice IR24. The lesion length in IR24 infected by Xoc pretreated with melatonin (200 μg mL−1) was more than 23% smaller than the lesion length of the control group. Similarly, infection of IR24 leaves by Xoc pretreated with melatonin (200 μg mL−1) reduced the bacterial population by 45%. The biofilm formation, swimming motility and extracellular protease activities of Xoc also decreased under melatonin treatment. Melatonin only slightly changed the morphology of Xoc but significantly reduced the mRNA expression of toxin genes. Furthermore, treating leaves with exogenous melatonin reduced the incidence of BLS by 17%. It is reported for the first time that melatonin reduces pathogenicity and may serve as a bactericide for controlling BLS disease.
Concern about threatened species and ecosystem disservices underpin public willingness to pay for ecological restoration
Authors: Wilson Kerrie A. , Davis Katrina J. , Matzek Virginia , Kragt Marit E.
Published: October 2018

Public preferences for ecological restoration can be revealed through environmental valuation studies that aim to measure willingness to pay. However, respondents' environmental views will often influence the conclusions drawn from such studies. We conducted a national survey of perceptions of the benefits and perverse outcomes arising from ecological restoration using a dichotomous choice payment card. Using interval regression to estimate willingness to pay, we find that there are respondents who will perceive mostly biodiversity benefits from restoration, with a particular interest in threatened species recovery. We find that this eco‐centric view of the benefits of restoration also increases the dollar amount that respondents are willing to pay to support restoration activities. A proportion of respondents also perceive restoration as having negative impacts, with concerns orientated towards increased fire, decreased farmland productivity, and groundwater availability. Perceptions of the potential effects of restoration on land productivity had a significant negative influence on the amount of money respondents were willing to pay. These findings are useful for targeting outreach in order to garner public support for ecological restoration.
Suicide Risk and Emotional Responses to Thoughts of Death: The Response to Morbid Ideations Questionnaire
Authors: Yaseen Zimri S. , Molina Nicolette , Hawes Mariah , Barzilay Shira , Galynker Igor
Published: October 2018

Background

There is need for deeper understanding of the processes by which suicidal thoughts lead to action. Examination of morbid ideation and the emotional sequelae of such ideation that may feed suicide ideation (SI) and attempts (SA) have been limited.

Method

Adult psychiatric outpatients (N = 385) were administered the Response to Morbid Ideation Questionnaire (RMI‐Q) and measures of SI, suicidal thoughts and behaviors (STB), and other psychiatric symptom severity. We examined (1) incidence and prevalence in mentation of morbid ideations and emotional responses to these ideations, (2) differences in emotional responses between individuals of varying levels of suicide history, and (3) the relationships of different types of morbid ideations and emotional responses with concurrent SI and symptom severity.

Results

Morbid ideation was reported by 87.5% of participants and associated with lifetime and concurrent levels of SI/STB. Calm/relieved emotional responses were associated with lifetime and concurrent levels of SI/STB, while negative‐valence responses to morbid ideations were associated with concurrent severity of psychopathology.

Conclusions

Our results suggest that the role of morbid ideation and its emotional sequelae in the development of suicidal motivation and action deserves further attention and may be a treatment target for suicide risk reduction.
Species delimitation in Neotropical fishes of the genus Characidium (Teleostei, Characiformes)
Authors: Serrano Érica A. , Melo Bruno F. , Freitas‐Souza Diogo , Oliveira Maria L. M. , Utsunomia Ricardo , Oliveira Claudio , Foresti Fausto
Published: October 2018

Neotropical darters of the genus Characidium have a complex systematic history with several examples of sympatry throughout their distribution range in Neotropical freshwaters. Although various species within the genus have been used as models to investigate chromosomal evolution and biogeography, species boundaries and relationships still remain uncertain. Here, we use mitochondrial DNA sequences to perform species delimitation analyses within Characidium and test previous hypotheses of species richness within the Characidium zebra complex and among sympatric morphotypes of C. alipioi. Results indicate high genetic distances within tested species complexes and revealed the presence of strongly supported lineages such as the large C. lauroi group from southeastern Brazil. This suggests that the evolutionary history of these groups may be correlated with biogeographic history. Analyses also reveal that three geographically isolated populations of C. zebra represent a single species, leading us to reject prior hypothesis of multiple species. Species delimitation using mitochondrial data strongly supports the presence of two sympatric species within C. alipioi in southeastern Brazil despite limited morphological variation and conserved chromosomal patterns. These results provide a framework to further the study of systematics and evolution within Characidium.
Usage of Ulvi Cemal Erkin’s ‘Duyuşlar’ Compositions in Music Education Departments, According to the Opinions of Piano Educators
Authors: Turan Hamza Serdar , Demirci Sirin Akbulut
Published: October 2018

Piano lessons which take place in music education departments involve example works of Turkish and world composers, education music examples, piano literature and learning-teaching techniques. Within this context, Ulvi Cemal Erkin, who is a member of The Turkish Five, wrote a composition called Duyuşlar, which consists of 11 pieces and is used in piano training. In this study, it was aimed to determine the usage of the composition Duyuşlar in the programs of institutions teaching music education in piano lessons in terms of technique, musical, and style characteristics. In accordance with this purpose, interviews are carried out by asking semi-structured interview questions to piano instructors who are using this work in their education process and working in Music Education Departments. The results of the interviews are determined into themes and codes using the qualitative research analysis program NVivo11. As a result, it is observed that the usage frequency in the direction of the themes and the recommended levels to use in the students vary, but the works contribute to piano education in terms of piano techniques, aksak measures, nuances, expressions, tempo and polyphonic techniques. It has also been proposed to increase the frequency of usage of Duyuşlar. It is thought that this study will contribute to the field of piano education in terms of the limited literature about this composition.
Contemporary Nutrition Interventions to Optimize Performance in Middle-Distance Runners
Authors: Stellingwerff Trent , Bovim Ingvill Måkestad , Whitfield Jamie
Published: October 2018

Middle-distance runners utilize the full continuum of energy systems throughout training, and given the infinite competition tactical scenarios, this event group is highly complex from a performance intervention point of view. However, this complexity results in numerous potential periodized nutrition interventions to optimize middle-distance training adaptation and competition performance. Middle-distance race intensity is extreme, with 800- to 5,000-m races being at ∼95% to 130% of VO2max. Accordingly, elite middle-distance runners have primarily Type IIa/IIx fiber morphology and rely almost exclusively on carbohydrate (primarily muscle glycogen) metabolic pathways for producing adenosine triphosphate. Consequently, the principle nutritional interventions that should be emphasized are those that optimize muscle glycogen contents to support high glycolytic flux (resulting in very high lactate values, of >20 mmol/L in some athletes) with appropriate buffering capabilities, while optimizing power to weight ratios, all in a macro- and microperiodized manner. From youth to elite level, middle-distance athletes have arduous racing schedules (10–25 races/year), coupled with excessive global travel, which can take a physical and emotional toll. Accordingly, proactive and integrated nutrition planning can have a profound recovery effect over a long race season, as well as optimizing recovery during rounds of championship racing. Finally, with evidence-based implementation and an appropriate risk/reward assessment, several ergogenic aids may have an adaptive and/or performance-enhancing effect in the middle-distance athlete. Given that elite middle-distance athletes undertake ∼400 to 800 training sessions with 10–25 races/year, there are countless opportunities to implement various periodized acute and chronic nutrition-based interventions to optimize performance.
“Someone to Talk to”: Influence of Player Welfare Provision on Mental Health in Professional Rugby League Players
Authors: Kola-Palmer Susanna , Buckley Samantha , Kingston Gabrielle , Stephen Jonathan , Rodriguez Alison , Sherretts Nicole , Lewis Kiara
Published: October 2018

Player welfare is an important development in supporting elite athletes during their professional careers. Little is known about how player engagement with player welfare provision impact on mental health. Over two consecutive years, professional rugby football league (RFL) players were invited to complete an anonymous online survey assessing psychological stress, athletic identity, and attitudes to player welfare provision. Findings indicate that nearly half of respondents experienced symptoms of anxiety and depression. Multivariate analyses suggest that higher psychological stress and athletic identity and less knowledge and less positive attitudes to RFL mental health support is associated with worse mental health, whereas older age is associated with better mental health. The study has identified some key variables to focus on in developing player care and support management, and also suggest directions for future research guiding player welfare support, especially regarding increasing positive attitudes to mental health supports.
Functional Hip Characteristics and Their Relationship With Ball Velocity in College Baseball Pitchers
Authors: Yanagisawa Osamu , Wakamatsu Kenta , Taniguchi Hidenori
Published: October 2018

Context: Compared to shoulder and elbow functions, the hip functional characteristics of baseball pitchers have not been fully investigated. Therefore, little is known about the relationship between hip function and pitching performance. Objective: The purpose of this study was to evaluate the characteristics of hip flexibility and strength, focusing on their influences on the ball velocity in baseball pitchers. Design: Descriptive laboratory study. Setting: Laboratory and university baseball facility. Participants: Twenty-three college baseball pitchers. Interventions: Passive hip range of motion (ROM) and isometric hip muscle strength were bilaterally measured. The pitchers threw 20 fastballs at an official pitching distance. Main Outcome Measures: Bilateral hip ROM and strength in flexion, extension, abduction, adduction, and external and internal rotation; the maximal ball velocity. Results: The pivot side showed smaller hip external rotation ROM (P < .01), larger hip internal rotation ROM (P = .03), and greater hip adduction strength (P = .03) than the stride side. The hip extension ROM on the stride side had a negative correlation with the maximal ball velocity (r = −.58, P < .01). The maximal ball velocity (135.3 [4.1] km/h) positively correlated with the hip extension (r = .59, P < .01), flexion (r = .57, P < .01), abduction (r = .55, P < .01), and adduction (r = .55, P < .01) strength on the pivot leg, and the hip flexion (r = .53, P = .01), abduction (r = .67, P < .01), and adduction (r = .46, P = .03) strength on the stride leg. Conclusions: These findings suggest that baseball pitchers do not have marked side-to-side differences in hip flexibility and strength, and that an important fitness factor for increasing ball velocity is not the hip flexibility but the hip muscle strength of both legs.
The Influence of Ankle Braces on Functional Performance Tests and Ankle Joint Range of Motion
Authors: Mann Brittany , Gruber Allison H. , Murphy Shane P. , Docherty Carrie L.
Published: October 2018

Context: The lateral ankle sprain is one of the most common lower-extremity injuries in sports. Previous research has found that some prophylactic ankle supports reduce the risk of recurrent ankle sprains and provide extra support to the joint. However, there is a continued concern that these supports may negatively influence performance. Objective: To determine if wearing an ankle brace influences athlete performance and ankle kinematics during functional performance tests. Design: Repeated measures. Setting: University gymnasium. Other Participants: Male and female recreational or competitive athletes (n = 20). Intervention: Participants performed 3 trials of a standing long jump, vertical jump, 40-yard sprint, and T-drill under each of the following 3 conditions: wearing traditional lace-up brace (brace 1), modified lace-up brace (brace 2), and no-brace. Main Outcome Measures: A 2-dimensional motion capture camera was used to measure ankle range of motion (ROM) in the sagittal plane during the vertical and standing long jumps and in the frontal plane during the cutting phase of the T-drill. Performance of each test and ankle ROM were compared between each of the braced conditions. Results: Ankle braces did not influence performance in speed or agility functional performance tests (P > .05). Ankle braces negatively affected performance of the standing long jump (P = .01) and vertical jump (P = .01). There was no significant difference between brace or no-brace conditions in ankle inversion ROM during the T-drill (P > .05). Both brace conditions restricted ROM in the sagittal plane during the vertical and standing long jumps (P < .05). Conclusions: Braced conditions restricted sagittal plane ROM during the vertical jump and long jump. This decrease in ROM explains the decline in functional performance also seen during these tests.
Excretion of ciprofloxacin into the large bowel of the rabbit
Authors: Ramon J , Dautrey S , Farinoti R , Carbon C , Rubinstein E
Published: October 2018

The intestinal elimination of ciprofloxacin in the large bowel was studied in a rabbit model. Segments from the cecum, colon, and sigmoid colon along with their intact blood vessels were isolated and perfused, and their contents were collected over a 90-min period following the administration of a single parenteral dose of 27 mg of ciprofloxacin per kg of body weight. The elimination rates of ciprofloxacin were 0.126 +/- 0.084 micrograms.min-1.cm-2 in the cecum and 0.264 +/- 0.126, 0.11 +/- 0.07, and 0.21 +/- 0.141 micrograms.min-1.cm-2 in the proximal colon, distal colon, and sigmoid colon, respectively. The calculated fraction of ciprofloxacin eliminated in the large bowel was 3% of the parenteral dose administered. The elimination pattern of ciprofloxacin in the large bowel may explain the unusual activity of this fluoroquinolone in modifying the colonic flora.
Clindamycin therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant Streptococcus pneumoniae
Authors: París M M , Shelton S , Trujillo M , Hickey S M , McCracken G H
Published: October 2018

Although penicillin resistance among Streptococcus pneumoniae strains is increasing in many areas, resistance to clindamycin remains low. In our well-characterized rabbit meningitis model, we conducted experiments to evaluate the bacteriologic efficacy of clindamycin after a penicillin- and cephalosporin-resistant S. pneumoniae strain was intracisternally inoculated. Animals received a loading intravenous dose of 30 mg of clindamycin per kg of body weight and then two doses of 20 mg/kg given 5 h apart. In addition to clindamycin, some animals received dexamethasone (DXM) with or without ceftriaxone. The concentrations of clindamycin in cerebrospinal fluid were from 8.9 to 12.8% of the concomitant concentrations in serum and were unaffected by DXM administration. Mean changes in CFU (log10 per milliliter) at 10 and 24 h were -3.7 and -6.1, respectively, for clindamycin-treated rabbits, -3.6 and -6.3 for clindamycin-DXM-treated rabbits, -3.9 and -5.8, respectively, for clindamycin-ceftriaxone-treated rabbits, and -5.0 and -6.7, respectively, for clindamycin-ceftriaxone-DXM-treated rabbits. By 24 h all but one of the cultures of cerebrospinal fluid (that from a clindamycin-DXM-treated rabbit) were sterile. Because of the potential risk for clindamycin-treated rabbits to develop macrolide-lincosamide resistance, we attempted, unsuccessfully, to induce clindamycin resistance in vitro in two S. pneumoniae strains. Although clindamycin therapy might be effective in selected patients with multiple-drug-resistant pneumococcal meningitis who have failed conventional treatments, clinical experience is necessary before it can be recommended.
Susceptibilities of bovine summer mastitis bacteria to antimicrobial agents
Authors: Jousimies-Somer H , Pyörälä S , Kanervo A
Published: October 2018

The susceptibility to 9 antimicrobial agents of 32 aerobic bacterial isolates and to 10 antimicrobial agents of 37 anaerobic bacterial isolates from 23 cases of bovine summer mastitis (16 Actinomyces pyogenes isolates, 8 Streptococcus dysgalactiae isolates, 3 S. uberis isolates, 3 S. acidominimus isolates, 2 Streptococcus spp., 15 Peptostreptococcus indolicus isolates, 10 Fusobacterium necrophorum isolates, and 12 isolates of anaerobic gram-negative rods) was determined by the agar dilution method. All isolates except one Bacteroides fragilis isolate (beta-lactamase producer) were susceptible to penicillin G, amoxicillin, amoxicillin-clavulanate, cefoxitin, clindamycin, and chloramphenicol (the B. fragilis strain was susceptible to the last four), which had MICs at which 90% of isolates were inhibited (MIC90s) of < or = 0.06, < or = 0.06, < or = 0.06 0.25, < or = 0.06, and 4.0 micrograms/ml, respectively. Spiramycin was active against the gram-positive aerobes (MIC90, 1.0 microgram/ml) but not against the anaerobes (MIC90, 16.0 micrograms/ml). Similar trends were noted for susceptibilities of aerobic and anaerobic bacteria to ofloxacin (MIC90s, 2.0 and 8 micrograms/ml, respectively). Occasional strains of aerobic streptococci were resistant to oxytetracycline, but all anaerobes were susceptible. Tinidazole was active against all anaerobes (MIC90, 2.0 micrograms/ml). beta-Lactamase was produced only by the B. fragilis isolate.
Treatment of experimental endocarditis due to Enterococcus faecalis using once-daily dosing regimen of gentamicin plus simulated profiles of ampicillin in human serum
Authors: Gavaldà J , Cardona P J , Almirante B , Capdevila J A , Laguarda M , Pou L , Crespo E , Pigrau C , Pahissa A
Published: October 2018

We compared the efficacy of ampicillin, both alone and in combination with gentamicin given once a day (q.d.) or three times a day (t.i.d.), in the treatment of experimental enterococcal endocarditis. Ampicillin was administered by using humanlike pharmacokinetics that simulated the profiles of this drug in human serum. An open one-compartment mathematical model developed in this study was used to estimate the decreasing doses administered with a computer-controlled infusion pump that simulated in rabbits the human serum pharmacokinetics after intravenous administration of 2 g of ampicillin every 4 h. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of Enterococcus faecalis J4 (MICs and MBCs of ampicillin and gentamicin, 2 and 128 and 16 and 64 micrograms/ml, respectively) and were treated for 3 days with ampicillin alone or in combination with gentamicin at 2 mg/kg of body weight subcutaneously t.i.d. or at 6 mg/kg subcutaneously q.d. The serum ampicillin levels and pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin in rabbits were similar to those found in humans treated with 2 g of ampicillin intravenously. The results of therapy for experimental endocarditis caused by E. faecalis J4 showed that the residual bacterial concentration in aortic valve vegetation was significantly lower in the animals treated with combinations of ampicillin plus gentamicin given q.d. or t.i.d. than in those treated with ampicillin alone (P < 0.01). The dosing interval of gentamicin did not significantly affect (q.d. versus t.i.d.; P = 0.673) the therapeutic efficacy of the combination of ampicillin plus gentamicin.
Pharmacokinetics of vancomycin in adult cystic fibrosis patients
Authors: Pleasants R A , Michalets E L , Williams D M , Samuelson W M , Rehm J R , Knowles M R
Published: October 2018

Although the depositions of many antibiotics are altered in cystic fibrosis patients, that of vancomycin has not been studied. To assess vancomycin pharmacokinetics, 10 adult cystic fibrosis patients were given a parenteral dose of vancomycin (15 mg/kg) during the first 72 h of hospitalization for acute bronchopulmonary exacerbation. Blood samples were obtained at 0, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 15, and 24 h. The mean (standard deviation) weight, measured creatinine clearance, and Taussig clinical score were 51 (13) kg, 130 (39) ml/min/1.73 m2, and 64 (13), respectively. Multicompartmental pharmacokinetic parameters were best described by a two-compartment model. The mean (standard deviation) volume of distribution, total body clearance, and terminal elimination rate constant were 0.58 (0.15) liter/kg, 91 (19) ml/min/1.73 m2, and 0.123 (0.05) h-1, respectively. These values were consistent with vancomycin pharmacokinetic parameters obtained in previous studies of healthy adult volunteers. Vancomycin dosages predicted by using a two-compartment Bayesian model were approximately 15 mg/kg every 8 to 12 h. There were poor correlations between clinical score or creatinine clearance and any pharmacokinetic parameter (r values of < 0.32). The coefficient of correlation between urine flow rate and total body clearance was 0.7 (P < 0.05). Adult cystic fibrosis patients exhibit a disposition of vancomycin similar to that exhibited by healthy adults, and thus cystic fibrosis does not alter vancomycin pharmacokinetics.
Comparative pharmacokinetics, distributions in tissue, and interactions with blood proteins of conventional and sterically stabilized liposomes containing 2',3'-dideoxyinosine
Authors: Harvie P , Désormeaux A , Bergeron M C , Tremblay M , Beauchamp D , Poulin L , Bergeron M G
Published: October 2018

The pharmacokinetics and distribution in tissue of 2',3'-dideoxyinosine (ddI) encapsulated in sterically stabilized liposomes have been evaluated in rats. Most of the sterically stabilized liposomes concentrated in the spleen with a peak level at 24 h after their intravenous injection. An extended half-life in plasma was observed for sterically stabilized liposomes (14.5 h) compared with that of conventional liposomes (3.9 h). The systemic clearance of ddI incorporated in sterically stabilized liposomes was 180 times lower than that of the free drug. The levels of in vitro and in vivo protein binding on both conventional and sterically stabilized liposomes were also evaluated. Results suggest that the amount of proteins associated with liposomes might not be the only factor involved in the in vivo clearance of liposomes, as this process may also be influenced by the nature of the bound blood proteins.
Effective ribavirin concentration in hamster brains for antiviral chemotherapy for subacute sclerosing panencephalitis
Authors: Ishii T , Hosoya M , Mori S , Shigeta S , Suzuki H
Published: October 2018

The ribavirin concentration in hamster brains was measured by a high-performance liquid chromatography (HPLC) system and a bioassay system. When ribavirin was administered intracranially at a dosage of 10 mg/kg of body weight per day for 10 days, a dosage which results in 100% survival of hamsters infected with subacute sclerosing panencephalitis (SSPE) virus and which inhibits the replication of SSPE virus in hamster brains, the ribavirin concentration in the brains estimated by HPLC and bioassay was kept higher than 50 micrograms/g for 10 days. The effective concentration in vivo corresponds to the concentration at which ribavirin completely inhibits the replication of SSPE virus in vitro. The maximal tolerable ribavirin concentration for hamsters was calculated to be 150 micrograms/g. Although ribavirin shows toxicity to the animals at a relatively low concentration (250 to 400 micrograms/g), intrathecal or intraventricular administration of ribavirin should be explored for potential use in the treatment of patients with SSPE, while the ribavirin concentration in cerebrospinal fluid or brain tissue should be monitored.
Generation and characterization of variants of NWS/G70C influenza virus after in vitro passage in 4-amino-Neu5Ac2en and 4-guanidino-Neu5Ac2en
Authors: McKimm-Breschkin J L , Blick T J , Sahasrabudhe A , Tiong T , Marshall D , Hart G J , Bethell R C , Penn C R
Published: October 2018

The compounds 4-amino-Neu5Ac2en (5-acetylamino-2,6-anhydro-4-amino-3,4,5- trideoxy-D-glycerol-D-galacto-non-2-enoic acid) and 4-guanidino-Neu5Ac2en (5-acetylamino-2,6-anhydro-4-guanidino-3,4,5- trideoxy-D-glycerol-D-galacto-non-2-enoic acid), which selectively inhibit the influenza virus neuraminidase, have been tested in vitro for their ability to generate drug-resistant variants. NWS/G70C virus (H1N9) was cultured in each drug by limiting-dilution passaging. After five or six passages in either compound, there emerged viruses which had a reduced sensitivity to the inhibitors in cell culture. Variant viruses were up to 1,000-fold less sensitive in plaque assays, liquid culture, and a hemagglutination-elution assay. In addition, cross-resistance to both compounds was seen in all three assays. Some isolates demonstrated drug dependence with an increase in both size and number of plaques in a plaque assay and an increase in virus yield in liquid culture in the presence of inhibitors. No significant difference in neuraminidase enzyme activity was detected in vitro, and no sequence changes in the conserved sites of the neuraminidase were found. However, changes in conserved amino acids in the hemagglutinin were detected. These amino acids were associated with either the hemagglutinin receptor binding site, Thr-155, or the left edge of the receptor binding pocket, Val-223 and Arg-229. Hence, mutations at these sites could be expected to affect the affinity or specificity of the hemagglutinin binding. Compensating mutations resulting in a weakly binding hemagglutinin thus seem to be circumventing the inhibition of the neuraminidase by allowing the virus to be released from cells with less dependence on the neuraminidase.
Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes
Authors: Healy D P , Brodbeck M C , Clendening C E
Published: October 2018

Twenty-six hospitalized patients participated in a randomized crossover study to evaluate the effect of enteral feedings on ciprofloxacin absorption when given orally or via gastrostomy or jejunostomy tubes. Patients in the oral group received an intact 500-mg ciprofloxacin tablet alone or ciprofloxacin plus three oral doses of Sustacal (240 ml given 8 h before, with, and 4 h after ciprofloxacin administration). Patients with gastrostomy or jejunostomy tubes received 500 mg of crushed ciprofloxacin in 60 ml water via the feeding tube. After a washout period, the patients received ciprofloxacin with a continuous enteral formula (Jevity) given at 60 to 90 ml/h beginning 6 h before drug administration and continuing for 10 h. Serial blood samples were analyzed for ciprofloxacin concentration by high-performance liquid chromatography. The maximum ciprofloxacin concentrations in serum for ciprofloxacin given and for ciprofloxacin plus enteral feeding for the oral, gastrostomy, and jejunostomy groups were (mean +/- standard deviation) 2.59 +/- 1.24 versus 1.43 +/- 0.61 micrograms/ml (P < 0.05), 3.68 +/- 1.36 versus 2.27 +/- 0.67 micrograms/ml (P < 0.05), and 3.78 +/- 1.87 versus 1.45 +/- 0.48 micrograms/ml (P < 0.05), respectively. Corresponding values for area under the concentration-time curve were 13.4 +/- 8.32 versus 9.44 +/- 4.74 micrograms/h/ml (P < 0.05) 15.9 +/- 6.62 versus 7.44 +/- 3.16 (micrograms/h/ml (P < 0.05), and 18.1 +/- 9.37 versus 5.82 +/- 2.63 micrograms.h/ml (P < 0.05). We conclude that enteral feedings given orally or via gastrostomy or jejunostomy tubes resulted in a 27 to 67% reduction in the mean bioavailability of ciprofloxacin in hospitalized patients. The decreased absorption may be clinically important, especially when the enteral feeding is coadministered with ciprofloxacin by the oral and jejunostomy tube routes. Reductions in maximum levels of ciprofloxacin in serum as a result of feedings given via a gastrostomy tube are similar to those following oral administration on an empty stomach, making a clinically important interaction by this route less likely.
Penetration of brodimoprim into human neutrophils and intracellular activity
Authors: Braga P C , Dal Sasso M , Maci S , Bondiolotti G , Fonti E , Reggio S
Published: October 2018

The entry of an antibiotic into phagocytes is a prerequisite for its intracellular bioactivity against susceptible facultative or obligatory intracellular microorganisms. Brodimoprim is a dimethoxybenzylpyrimidine that has recently entered into clinical use, and its uptake into and elimination from human polymorphonuclear neutrophils (PMNs), together with its effects on normal phagocytic and antimicrobial mechanisms, have been investigated. Brodimoprim uptake by PMNs was determined by a velocity-gradient centrifugation technique under various experimental conditions and was expressed as the ratio of the intracellular to the extracellular drug concentration (C/E) in comparison with the C/E of trimethoprim, which was used as a control drug. After incubation with 7.5 micrograms of brodimoprim per ml, PMNs accumulated brodimoprim (C/E, 74.43 +/- 12.35 at 30 min) more avidly than trimethoprim (C/E, 20.97 +/- 6.61 at 30 min). The cellular uptake of brodimoprim was not affected by temperature, 2,4-dinitrophenol, or potassium fluoride and was increased with an increase in the pH of the medium. It was reduced in formaldehyde-killed PMNs. The efflux of brodimoprim was very rapid (46% after 5 min). The liposolubility of brodimoprim was about three times that of trimethoprim, as was the uptake. Therefore, a possible passive transmembrane diffusion mechanism might be proposed. Brodimoprim did not decrease either phagocytosis or phagocyte-mediated bactericidal activity, nor did it affect oxidative burst activity, as investigated by luminol-amplified chemiluminescence. On the basis of the pharmacokinetic data for brodimoprim, the concentration of 7.5 micrograms/ml was chosen as the highest concentration attainable in serum by oral therapy, and at this concentration of brodimoprim, the amount of drug that penetrated into PMNs was able to maintain its antimicrobial activity without interfering with the functions of the PMNs.
In vitro activity of LY333328, an investigational glycopeptide antibiotic, against enterococci and staphylococci
Authors: Schwalbe R S , McIntosh A C , Qaiyumi S , Johnson J A , Johnson R J , Furness K M , Holloway W J , Steele-Moore L
Published: October 2018

The in vitro activities of LY333328 were compared with those of vancomycin, teicoplanin, and quinupristin-dalfopristin (Synercid) against 219 strains of enterococci and staphylococci, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MICs and MBCs were determined by a microtiter dilution protocol. LY333328 demonstrated superior activity against vancomycin-resistant enterococci and was the only antibiotic which was bactericidal. Its potency was comparable or superior to those of other antibiotics tested against methicillin-resistant staphylococci.
Pharmacodynamic effects of sub-MICs of benzylpenicillin against Streptococcus pyogenes in a newly developed in vitro kinetic model
Authors: Löwdin E , Odenholt I , Bengtsson S , Cars O
Published: October 2018

The pharmacodynamic effects of benzylpenicillin against Streptococcus pyogenes were studied in a new in vitro kinetic model in which bacterial outflow was prevented by a filter membrane. Following the administration of an initial dose of antibiotic, decreasing concentrations were produced by dilution of the medium. A magnetic stirrer was placed above the filter to avoid blockage of the membrane and to ensure homogeneous mixing of the culture. Repeated samplings were easily provided through a silicon diaphragm. Streptococci were exposed to a single dose corresponding to 1.5, 10, 100, or 500 x the MIC of benzylpenicillin and also to an initial concentration of 10 x the MIC of benzylpenicillin, followed by exposure to a repeated dose after 8 h yielding 10 or 1.5 x the MIC. Experiments were also performed with 10 x the MIC of benzylpenicillin with a half-life of 3 h or an initial half-life of 1.1 h that was altered to 3 h at the time point at which the antibiotic concentrations and MIC intersected. Bacterial killing and regrowth were followed by determining viable counts. The post-MIC effect (PME) was defined as the difference in time for the numbers of CFU in the culture vessel to increase 1 log10 CFU/ml, calculated from the numbers obtained at the time when the antibiotic concentration had declined to the MIC, and the corresponding time for a control culture, grown in a glass tube without antibiotic, to increase 1 log10 CFU/ml. To determine how much of the PME was attributable to subinhibitory concentrations, penicillinase was added to a part of the culture drawn from the flask at the time when the antibiotic concentration had fallen to the MIC. The longest PME was found in the experiments in which the half-life was extended from 1.1 to 3 h at the MIC. This illustrated that sub-MICs are sufficient to prevent regrowth. However, when the half-life was 3 h during the whole experiment, the PME was shorter, indicating that when concentrations decline slowly penicillin-binding proteins will already be present in amounts sufficient for regrowth at the time when the MIC is reached. The PME may prove to be a more reliable factor than the in vitro postantibiotic effect or postantibiotic sub-MIC effect for the design of optimal dosing schedules, since the PME, like the in vivo postantibiotic effect, includes the effects of subinhibitory concentrations and therefore better reflects the clinical situation with fluctuating antibiotic concentrations.
Integration of pT181-like tetracycline resistance plasmids into large staphylococcal plasmids involves IS257
Authors: Werckenthin C , Schwarz S , Roberts M C
Published: October 2018

Four large staphylococcal plasmids ranging in size from 31 to 82 kbp have been shown to mediate tetracycline resistance via an integrated copy of the tet(K)-encoding plasmid pT181 which was flanked by copies of the insertion element IS257. In two cases, IS257 elements interrupted the repC reading frame of pT181 and an 8-bp sequence from within the repC gene was duplicated at the interrupted site. In the third plasmid, the IS257 elements interrupted the pT181 DNA immediately upstream of the repC coding sequence with an 8-bp duplication. In the fourth case, the IS257 elements flanked a pT181-like plasmid with one IS257 in the repC coding sequence and the other within the recombinase (pre) coding sequence, so that a section of the pT181 sequence was deleted. All four integration sites detected in this study differ from those previously described for the IS257-mediated integration of pT181-like plasmids into large plasmids or into the chromosomal DNA.
9-[2-(Phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques
Authors: Van Rompay K K , Cherrington J M , Marthas M L , Berardi C J , Mulato A S , Spinner A , Tarara R P , Canfield D R , Telm S , Bischofberger N , Pedersen N C
Published: October 2018

The long-term therapeutic and toxic effects of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) were evaluated in simian immunodeficiency virus (SIV)-infected newborn rhesus macaques. Four untreated SIV-infected newborn macaques developed persistently high levels of viremia, and three of the four animals had rapidly fatal disease within 3 months. In contrast, long-term PMPA treatment of four newborn macaques starting 3 weeks after virus inoculation resulted in a rapid, pronounced, and persistent reduction of viremia in three of the four animals. Emergence of virus with fivefold-decreased susceptibility to PMPA occurred in all four PMPA-treated animals and was associated with the development of a lysine-to-arginine substitution at amino acid 65 (K65R mutation) and additional mutations in the reverse transcriptase; however, the clinical implications of this low-level drug resistance are nuclear. No toxic side effects have been seen, and all PMPA-treated animals have remained disease-free for more than 13 months. Our data suggest that PMPA holds much promise for the treatment of human immunodeficiency virus-infected human infants and adults.
Effect of fluconazole on viability of Candida albicans over extended periods of time
Authors: Sohnle P G , Hahn B L , Erdmann M D
Published: October 2018

The treatment of chronic mycoses may expose the infecting organisms to antimicrobial agents for extended periods of time. It is possible that an azole antifungal drug such as fluconazole, with primarily fungistatic activity in standard in vitro susceptibility tests, might be able to damage the fungal cells and reduce their viability over prolonged incubations under nonproliferating conditions. To test this possibility, Candida albicans yeast cells were exposed to various concentrations of fluconazole in RPMI 1640 tissue culture medium for 4 h at 37 degrees C, washed free of the drug, and then incubated at 37 degrees C for a 28-day period; enumeration of the remaining CFU at various times during this period revealed no increased loss of viability for the fluconazole-exposed organisms. However, when fluconazole was added to the organisms maintained in distilled water (with or without pretreatment with the drug), a marked reduction of viability was found. At 14 days of incubation with two strains of C. albicans, negative cultures were found for 7 of 10 and 10 of 11 samples, respectively, containing 1.0 microgram of fluconazole per ml versus 0 of 10 and 1 of 11 control samples (P of < 0.01 and 0.001, respectively). The effect of fluconazole on fungal viability under these conditions became noticeable at approximately 7 days and was greater when the samples were incubated at 37 degrees C rather than 25 degrees C. These findings suggest that fluconazole may have fungicidal effects on fungal cells during prolonged exposures under conditions in which the organisms are prevented from proliferating by lack of nutrients.
Inhibitory effects of recombinant manganese superoxide dismutase on influenza virus infections in mice
Authors: Sidwell R W , Huffman J H , Bailey K W , Wong M H , Nimrod A , Panet A
Published: October 2018

The oxygen free-radical scavenger recombinant human manganese superoxide dismutase (MnSOD) was studied for its effects on influenza virus infections in mice when used alone and in combination with ribavirin. Mice challenged with influenza A/NWS/33 (H1N1) virus were treated parenterally in doses of 25, 50, and 100 mg/kg of body weight per day every 8 h for 5 days beginning at 48 h post-virus exposure. An increase in mean day to death, lessened decline in arterial oxygen saturation, and reduced lung consolidation and lung virus titers occurred in the treated animals. To determine the influence of viral challenge, experiments were run in which mice were infected with a 100 or 75% lethal dose of virus and were treated intravenously once daily for 5 days beginning 96 h after virus exposure. Weak inhibition of the mortality rate was seen in mice receiving the high viral challenge, whereas significant inhibition occurred in the animals infected with the lower viral challenge, indicating that MnSOD effects are virus dose dependent. To determine if treatment with small-particle aerosol would render an antiviral effect, infected mice were treated by this route for 1 h daily for 5 days beginning 72 h after virus exposure. A dose-responsive disease inhibition was seen. An infection induced by influenza B/Hong Kong/5/72 virus in mice was mildly inhibited by intravenous MnSOD treatment as seen by increased mean day to death, lessened arterial oxygen saturation decline, and lowered lung consolidation. MnSOD was well tolerated in all experiments. A combination of MnSOD and ribavirin, each administered with small-particle aerosol, resulted in a generally mild improvement of the disease induced by the influenza A virus compared with use of either material alone.
In vivo activities of ceftriaxone and vancomycin against Borrelia spp. in the mouse brain and other sites
Authors: Kazragis R J , Dever L L , Jorgensen J H , Barbour A G
Published: October 2018

Borrelia burgdorferi, the agent of Lyme disease, and B. turicatae, a neurotropic agent of relapsing fever, are susceptible to vancomycin in vitro, with an MIC of 0.5 microgram/ml. To determine the activity of vancomycin in vivo, particularly in the brain, we infected adult immunocompetent BALB/c and immunodeficient CB-17 scid mice with B. burgdorferi or B. turicatae. The mice were then treated with vancomycin, ceftriaxone as a positive control, or normal saline as a negative control. The effectiveness of treatment was assessed by cultures of blood and brain and other tissues. Ceftriaxone at a dose of 25 mg/kg of body weight administered every 12 h for 7 to 10 days eliminated cultivable B. burgdorferi or B. turicatae from all BALB/c or scid mice in the study. Vancomycin at 30 mg/kg administered every 12 h was effective in eliminating infection from immunodeficient mice if treatment was started within 3 days of the onset of infection. If treatment with vancomycin was delayed for 7 days or more, vancomycin failed to eradicate infection with B. burgdorferi or B. turicatae from immunodeficient mice. The failure of vancomycin in eradicating established infections in immunodeficient mice was associated with the persistence of viable spirochetes in the brain during antibiotic treatment.
Comparative activities of LY 333328, a new glycopeptide, against penicillin-susceptible and -resistant pneumococci
Authors: Fasola E , Spangler S K , Ednie L M , Jacobs M R , Bajaksouzian S , Appelbaum P C
Published: October 2018

Microdilution MIC testing was used to test the susceptibility of 202 pneumococci to LY 333328 and six other agents. LY 333328 was the most active glycopeptide (MIC at which 90% of the pneumococci were inhibited [MIC90], 0.008 microgram/ml), followed by teicoplanin (MIC90, 0.06 microgram/ml) and vancomycin (MIC90, 0.5 microgram/ml). Rifampin resistance was seen in some penicillin-resistant strains. The MICs of imipenem and ceftriaxone rose with those of penicillin. Time-kill testing confirmed the excellent antipneumococcal activity of LY 333328.
Development of experimental pneumonia by infection with penicillin-insensitive Streptococcus pneumoniae in guinea pigs and their treatment with amoxicillin, cefotaxime, and meropenem
Authors: Ponte C , Parra A , Nieto E , Soriano F
Published: October 2018

Acute respiratory infection with penicillin-insensitive Streptococcus pneumoniae (MIC and MBC, 1 and 2 micrograms/ml, respectively) was established in guinea pigs. Intratracheal instillation of 0.5 ml of an overnight culture of S. pneumoniae concentrated 25 times (approximately 3 x 10(9) CFU) induced a bacteremic and fatal pneumonia in > 85% of untreated animals within 46 h, with a mean +/- standard deviation bacterial count of 8.83 +/- 1.11 log10 CFU in lung homogenates. This model was used to evaluate the efficacies of two doses each of amoxicillin, cefotaxime, and meropenem given 1 h after bacterial inoculation. The antibiotics were given at 8-h intervals for up to a total of four injections. The dose of 50 mg of any antibiotic per kg of body weight gave 66.6% survival, compared with 5.05% survival for untreated control animals (P < 0.001). A dose of 200 mg/kg gave a survival rate of 77.8% for meropenem and 83.3% for amoxicillin and cefotaxime, while survival for untreated controls was 11.1% (P < 0.001). Although antibiotic treatment decreased mortality compared with that in untreated controls, the antibiotics contributed to a high early (less than 9 h after bacterial inoculation) mortality, being 53.5% compared with only 6.06% for the untreated controls (P < 0.001). Quantitative cultures of the lungs of animals that died during the 46-h observation period or that were killed after this time showed a significant reduction in the numbers of organisms among treated animals compared with numbers among the control animals (P < 0.001). The described model is an appropriate system for evaluating antibiotic efficacy in invasive pulmonary infection caused by penicillin-insensitive S. pneumoniae.