Antimicrobial activity of fosfomycin and tobramycin in combination against cystic fibrosis pathogens under aerobic and anaerobic conditions

BackgroundThere is a need for new antibiotics or combination of antibiotics that possess activity against increasingly resistant cystic fibrosis (CF) respiratory pathogens such as Pseudomonas aeruginosa and MRSA.MethodsThe antimicrobial activity of a novel 4:1 (w/w) fosfomycin:tobramycin (F:T) combination against CF respiratory pathogens under both aerobic and anaerobic conditions was determined by MIC, time-kill and biofilm studies, and compared with activity of fosfomycin and tobramycin, individually.ResultsF:T and fosfomycin had excellent activity against P. aeruginosa and were more active than tobramycin against P. aeruginosa under anaerobic conditions with lower MIC₅₀, MIC₉₀ and geometric mean values. F:T (p < 0.001) and fosfomycin (p < 0.001) MICs for P. aeruginosa were significantly lower under anaerobic conditions with tobramycin MICs significantly higher (p < 0.001). F:T and fosfomycin also had high activity against MRSA with both being more active than tobramycin. In time–kill studies, F:T was rapidly bactericidal against all 15 P. aeruginosa and 3/5 MRSA isolates tested. F:T also demonstrated bactericidal activity against P. aeruginosa grown in biofilm under both aerobic and anaerobic conditions.ConclusionsF:T has promising in vitro antimicrobial activity against MRSA and P. aeruginosa with greater activity under anaerobic conditions similar to those found in the CF lung.     

Geriatric trauma: resource use and patient outcomes.

INTRODUCTION: Elderly patients who suffer trauma have a higher mortality and use disproportionately more trauma resources than younger patients. To compare these 2 groups and determine the outcomes and characteristics of elderly patients, we reviewed patients in these 2 groups admitted and treated in our tertiary care provincial trauma centre. METHODS: From the provincial trauma registry we selected a cohort of 40 geriatric patients (group 1) (> or = 65 yr of age) with an ISS of 16 or more who were admitted to and spent time in our trauma service for more than 48 hours and compared them with a similar randomly selected cohort of 44 patients (group 2) aged 20-30 years. Family physicians were contacted for follow-up of these patients 2 years after discharge. We considered length of hospital stay, complications, disposition of the patients and use of consultation services. RESULTS: Patients in group 1 had a mean age of 72.1 years (range from 65-98 yr) and a mean ISS of 27.3 (range from 17-50). Patients in group 2 had a mean age of 26.3 years (range from 22-29 yr) and a mean ISS of 26.3 (range from 17-54). Hospital stay was significantly longer in the group 1: 34.5 days (95% confidence interval [CI]: 24-44 d) versus 21.6 days (95% CI: 15-28 d). More elderly patients experienced complications (35 v. 13, p < 0.001) and required medical consultations (35 v. 26, p < 0.001). In-hospital death rates were 8% (3 of 40) and 4% (2 of 44) respectively (p = 0.3). Fewer geriatric patients could be discharged home (35% [14 of 40] v. 27% [22 of 44], p = 0.056) or to rehabilitation facilities (28% [11 of 40] v. 34% [15 of 44], p = 0.3). Five geriatric patients were discharged to nursing homes (p = 0.007). Of the geriatric patients discharged to rehabilitation facilities or home, 75% were independent 2 years after discharge. CONCLUSIONS: Aggressive care for geriatric trauma patients is warranted, and resources should be directed toward rehabilitation. Based on our findings, we expect that creating a directed care pathway for these patients, targetting complications and earlier discharge, will further improve their outcomes.     

Identifying patients at risk for intracranial and extracranial blunt carotid injuries

BACKGROUND: Blunt carotid injuries are rare, often occult, and potentially devastating. Angiographic screening programs have detected this injury in up to 1% of blunt trauma patients. Implementing a liberal angiographic screening program at our hospital is impractical and we want to identify a high-risk group to target for screening. We hypothesize that intracranial and extracranial carotid injuries have different risks, presentations, and outcomes. METHODS: Patients with intracranial and extracranial carotid injuries were identified from the British Columbia trauma registry. Presentation and outcome were reviewed. To facilitate statistical modeling the analysis was done by matching cases to 5 randomly selected controls. Risk factors for injury were evaluated by univariate and multiple logistic regression. RESULTS: A total of 35 carotid injuries were identified. Thirteen intracranial injuries were identified in 10 patients. Twenty-two extracranial injuries were identified in 18 patients. Sixty-seven percent of patients with intracranial injuries and 31% of those with extracranial injuries died (P = 0.11). Eleven percent of intracranial injuries and 56% of extracranial injuries were occult (P = 0.04). Glasgow outcome scores were 2.04 intracranial and 3.12 extracranial (P = 0.18). For intracranial injuries the multiple variable predictive model had two predictors: Glasgow Coma Score or =3). CONCLUSIONS: Intracranial injuries were frequently detected on initial investigations and have very poor outcomes. Extracranial injuries were more frequently occult and stand to benefit from early detection by screening programs. As independent risk factors for these two injuries differ, limited screening resources should focus on risk factors for occult extracranial injury: namely, low GCS and significant thoracic injury.     

Effects of endogenous D-alanine synthesis and autoinhibition of Bacillus anthracis germination on in vitro and in vivo infections

Bacillus anthracis transitions from a dormant spore to a vegetative bacillus through a series of structural and biochemical changes collectively referred to as germination. The timing of germination is important during early steps in infection and may determine if B. anthracis survives or succumbs to responsive macrophages. In the current study experiments determined the contribution of endogenous D-alanine production to the efficiency and timing of B. anthracis spore germination under in vitro and in vivo conditions. Racemase-mediated production of endogenous D-alanine by B. anthracis altered the kinetics for initiation of germination over a range of spore densities and exhibited a threshold effect wherein small changes in spore number resulted in major changes in germination efficiency. This threshold effect correlated with D-alanine production, was prevented by an alanine racemase inhibitor, and required L-alanine. Interestingly, endogenous production of inhibitory levels of D-alanine was detected under experimental conditions that did not support germination and in a germination-deficient mutant of B. anthracis. Racemase-dependent production of D-alanine enhanced survival of B. anthracis during interaction with murine macrophages, suggesting a role for inhibition of germination during interaction with these cells. Finally, in vivo experiments revealed an approximately twofold decrease in the 50% lethal dose of B. anthracis spores administered in the presence of D-alanine, indicating that rates of germination may be directly influenced by the levels of this amino acid during early stages of disease.     

Dyspareunia Related to GSM: Association of Total Vaginal Thickness via Transabdominal Ultrasound

IntroductionIt has previously been suggested in the literature that ultrasound measurement of total vaginal wall thickness (TVT) differs significantly between pre- and postmenopausal women, indicating that it may be a useful and noninvasive objective assessment to correlate the degree of vaginal atrophy to patient-reported symptoms.AimThe purpose of this cross-sectional pilot study was to determine whether TVT in postmenopausal women, as measured with transabdominal ultrasound, is associated with patient-reported dyspareunia and symptoms related to genitourinary symptomatology.MethodsPostmenopausal women presenting for pelvic ultrasound had TVT and total mucosal thickness (TMT) measured via transabdominal ultrasound. A questionnaire also was administered assessing menopausal status, relevant medical history, and self-report of dyspareunia and other symptoms related to the genitourinary syndrome of menopause (GSM). This questionnaire was derived from the Vulvovaginal Symptom Questionnaire, which has been validated in the literature.Main Outcome MeasureThe main outcome measures included the average TVT and TMT for postmenopausal women reporting any symptom of GSM and average TVT and TMT of women reporting no symptoms of GSM.ResultsData from 44 postmenopausal women showed no significant association between transabdominal ultrasound-measured TVT or TMT and patient report of dyspareunia or other genitourinary symptoms. Data were stratified by individual GSM symptoms, sexual symptoms as an aggregate, and individual sexual symptoms. Neither of these subgroups showed a statistically significant difference in TVT or TMT between symptomatic and asymptomatic women.Clinical ImplicationsAlthough no statistically significant data were derived from this study, we propose that future studies investigating the longitudinal relationship between TVT and GSM symptomatology may show an association between total vaginal thickness measurement change over time as determined by ultrasound with the presence of patient-reported dyspareunia and other GSM symptoms.Strengths & LimitationsThis study is limited by its small sample size as well as the patient population, which was restricted to postmenopausal women with a clinical indication for ultrasound. A major strength of this investigation is that it is the first study to look at the relationship between sexual pain and other GSM symptoms and TVT using transabdominal ultrasound, which is a readily available, non-invasive tool in most clinical settings.ConclusionBased on the results of this small pilot study, transabdominal pelvic ultrasound cannot be used at this time to objectively quantify the presence of sexual pain or other GSM symptoms; however, future studies should continue to investigate the longitudinal relationship between these 2 variables.Balica AC, Cooper AM, McKevitt MK, et al. Dyspareunia Related to GSM: Association of Total Vaginal Thickness via Transabdominal Ultrasound. J Sex Med 2019; 16:2038–2042.     

Research campaigns in the UK National Health Service: patient recruitment and questions of valuation

The National Institute for Health Research (NIHR) aims to improve national ‘health and wealth' by providing infrastructural support to enable clinical research in National Health Service settings in England and Wales. Cognisant of the consequences of studies' failure to achieve required numbers of participants, it also actively campaigns to promote patient awareness of research, and willingness to participate in trials. In this paper, we analyse recent NIHR campaigns and policies designed to encourage patients to participate in clinical research to interrogate how they are implicated in the national bioeconomy. In doing so we expand the notion of ‘clinical labour' to include the work of patient recruitment and highlight an emergent obligation on patients to contribute to research processes. Whereas once patient knowledge and experience may have been devalued, here we draw on the concept of ‘assetisation' (Birch 2012) to explore the emergent relationship between healthcare system and patient as research participant. We consider how patients' contribution goes beyond the provision of standardised objects of valuation so that patients themselves may be perceived as assets to, not only recipients of, the national healthcare system.