Effect of conjugated bile salts on antibiotic susceptibility of bile salt-tolerant Lactobacillus and Bifidobacterium isolates.

Virtually every antibiotic may cause in vivo alterations in the number, level, and composition of the indigenous microbiotae. The degree to which the microbiotae are disturbed depends on many factors. Although bile may augment antibiotic activity, studies on the effect of bile on the antibiotic susceptibility of indigenous and exogenous probiotic microorganisms are lacking. It was against this background that the antibiotic susceptibility of 37 bile salt-tolerant Lactobacillus and 11 Bifidobacterium isolates from human and other sources was determined in the presence of 0.5% wt/wt oxgall (conjugated bile salts). Oxgall did not affect the intrinsic resistance of lactobacilli to metronidazole (5 microg), vancomycin (30 microg), and cotrimoxazole (25 microg), whereas it resulted in a complete loss of resistance to polymyxin B (300 microg) and the aminoglycosides gentamicin (10 microg), kanamycin (30 microg), and streptomycin (10 microg) for most strains studied (P < 0.001). Oxgall did not affect the intrinsic resistance of bifidobacteria to metronidazole and vancomycin, whereas polymyxin B and co-trimoxazole resistance was diminished (P < 0.05) and aminoglycoside resistance was lost (P < 0.001). Seven lactobacilli, but no bifidobacteria strain, showed unaltered intrinsic antibiotic resistance profiles in the presence of oxgall. Oxgall affected the extrinsic susceptibility of lactobacilli and bifidobacteria to penicillin G (10 microg), ampicillin (10 microg), tetracycline (30 microg), chloramphenicol (30 microg), erythromycin (15 microg), and rifampicin (5 microg) in a source- and strain-dependent manner. Human strain-drug combinations of lactobacilli (P < 0.05) and bifidobacteria (P < 0.01) were more likely to show no change or decreased susceptibility compared with other strain-drug combinations. The antimicrobial activity spectra of polymyxin B and the aminoglycosides should not be considered limited to gram-negative bacteria but extended to include gram-positive genera of the indigenous and transiting microbiotae in the presence of conjugated bile salts. Those lactobacilli (7 of 37) that show unaltered intrinsic and diminished extrinsic antibiotic susceptibility in the presence of oxgall may possess greater upper gastrointestinal tract transit tolerance in the presence of antibiotics

Antibiotic susceptibility of potentially probiotic Lactobacillus species.

In recent years, the time-honored reputation of lactobacilli as promoters of gastrointestinal and female urogenital health has been qualified. This has occurred due to a rare association with human infection in the presence of certain predisposing factors and their potential to act as a source of undesirable antibiotic resistance determinants to other members of the indigenous microbiota. This necessitates greater caution in their selection for use in microbial adjunct nutrition and disease management (prophylaxis and therapy). It was against this background that 46 Lactobacillus strains from human and dairy sources were assayed for susceptibility to 44 antibiotics. All strains were resistant to a group of 14 antibiotics, which included inhibitors of cell wall synthesis (cefoxitin [30 microg] and aztreonam [30 microg]), protein synthesis (amikacin [30 microg], gentamicin [10 microg], kanamycin [30 microg], and streptomycin [10 microg]), nucleic acid synthesis (norfloxacin [10 microg], nalidixic acid [30 microg], sulphamethoxazole [100 microg], trimethoprim [5 microg], co-trimoxazole [25 microg], and metronidazole [5 microg]), and cytoplasmic membrane function (polymyxin B [300 microg] and colistin sulphate [10 microg]). All strains were susceptible to tetracycline (30 microg), chloramphenicol (30 microg), and rifampicin (5 microg). Four human strains and one dairy strain exhibited atypical resistance to a penicillin, bacitracin (10 microg), and/or nitrofurantoin (300 microg). One human strain was also resistant to erythromycin (15 microg) and clindamycin (2 microg). These resistances may have been acquired due to antibiotic exposure in vivo, but conclusive evidence is lacking in this regard. Seven microorganism-drug combinations were evaluated for beta-lactamase activity using synergy and nitrocefin tests. The absence of activity suggested that cell wall impermeability appeared responsible for beta-lactam resistance. The occurrence of a minority of lactobacilli with undesirable, atypical resistance to certain antibiotics demonstrates that not all strains are suitable for use as probiotics or bacteriotherapeutic agents. The natural resistance of lactobacilli to a wide range of clinically important antibiotics may enable the development of antibiotic/probiotic combination therapies for such conditions as diarrhea, female urogenital tract infection, and infective endocarditis

A randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery for open globe trauma – the ASCOT study

Background: Eyes sustaining open globe trauma are at high risk of severe visual impairment. Proliferative vitreoretinopathy is the most common cause of retinal detachment and visual loss in eyes with open globe trauma. There is evidence from experimental studies and pilot clinical trials that the use of adjunctive steroid medication triamcinolone acetonide can reduce the incidence of proliferative vitreoretinopathy and improve outcomes of surgery for open globe trauma. Objective: The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study aimed to investigate the clinical effectiveness of adjunctive triamcinolone acetonide given at the time of vitreoretinal surgery for open globe trauma. Design: A phase 3 multicentre double-masked randomised controlled trial randomising patients undergoing vitrectomy following open globe trauma to either adjunctive triamcinolone acetonide or standard care. Setting: Hospital vitreoretinal surgical services dealing with open globe trauma. Participants: Patients undergoing vitrectomy surgery who had sustained open globe trauma. Interventions: Triamcinolone acetonide 4 mg/0.1 ml into the vitreous cavity and 40 mg/1 ml sub-Tenon’s or standard vitreoretinal surgery and postoperative care. Main outcome measures: The primary outcome was the proportion of patients with at least 10 letters of improvement in corrected visual acuity at six months. Secondary outcomes included retinal detachment secondary to proliferative vitreoretinopathy, retinal reattachment, macula reattachment, tractional retinal detachment, number of operations, hypotony, elevated intraocular pressure and quality of life. Health-related quality of life was assessed using the EuroQol Five Domain and Visual Function Questionnaire 25 questionnaires.Results: A total of 280 patients were randomised; 129 were analysed from the control group and 130 from the treatment group. The treatment group appeared, by chance, to have more severe pathology on presentation. The primary outcome (improvement in visual acuity) and principal secondary outcome (change in visual acuity) did not demonstrate any treatment benefit for triamcinolone acetonide. The proportion of patients with improvement in visual acuity was 47% for triamcinolone acetonide and 43% for standard care (odds ratio 1.03, 95% confidence interval 0.61 to 1.75, p = 0.908); the baseline adjusted mean difference in the six-month change in visual acuity was –2.65 (95% confidence interval –9.22 to 3.92, p = 0.430) for triamcinolone acetonide relative to control. Similarly, the secondary outcome measures failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal reattachment and stable macular retinal reattachment, outcomes for the treatment group were significantly worse for triamcinolone acetonide at the 5% level (respectively, odds ratio 0.59, 95% confidence interval 0.36 to 0.99, p = 0.044 and odds ratio 0.59, 95% confidence interval 0.35 to 0.98, p = 0.041) compared with control in favour of control. The cost of the intervention was £132 per patient. Health economics outcome measures (Early Treatment Diabetic Retinopathy Study, Visual Function Questionnaire 25 and EuroQol Five Dimensions) did not demonstrate any significant difference in quality-adjusted life-years. Conclusions: The use of combined intraocular and sub-Tenon’s capsule triamcinolone acetonide is not recommended as an adjunct to vitrectomy surgery for intraocular trauma. Secondary outcome measures are suggestive of a negative effect of the adjunct, although the treatment group appeared to have more severe pathology on presentation

Randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery following open globe trauma: the ASCOT study

BACKGROUND/AIMS: To investigate the clinical effectiveness of adjunctive triamcinolone acetonide (TA) given at the time of vitreoretinal surgery following open globe trauma (OGT). METHODS: A phase 3, multicentre, double-masked randomised controlled trial of patients undergoing vitrectomy following OGT comparing adjunctive TA (intravitreal and subtenons) against standard care (2014-2020). The primary outcome was the proportion of patients with at least 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in corrected visual acuity (VA) at 6 months. Secondary outcomes included: change in ETDRS, retinal detachment (RD) secondary to PVR, retinal reattachment, macular reattachment, tractional RD, number of operations, hypotony, elevated intraocular pressure and quality of life. RESULTS: 280 patients were randomised over 75 months, of which 259 completed the study. 46.9% (n=61/130) of patients in the treatment group had a 10-letter improvement in VA compared with 43.4% (n=56/129) of the control group (difference 3.5% (95% CI -8.6% to 15.6%), OR=1.03 (95% CI 0.61 to 1.75), p=0.908)). Secondary outcome measures also failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal and macular reattachment, outcomes were worse in the treatment group compared with controls, respectively, 51.6% (n=65/126) vs 64.2% (n=79/123), OR=0.59 (95% CI 0.36 to 0.99), and 54.0% (n=68/126) vs 66.7% (n=82/123), OR=0.59 (95% CI 0.35 to 0.98), for TA vs control. CONCLUSION: The use of combined intraocular and sub-Tenons capsule TA is not recommended as an adjunct to vitrectomy surgery following OGT. TRIAL REGISTRATION NUMBER: NCT02873026

Presenting clinical characteristics of open globe injuries in ocular trauma: baseline analysis of cases in the ASCOT national clinical trial

Background/Objectives The Adjunctive Steroid Combination in Ocular Trauma (ASCOT) trial is a unique pragmatic, multi-centre, patient and assessor masked, randomised controlled trial. We evaluate the clinical characteristics and pathology of this large trial cohort of patients with open globe injuries undergoing vitreoretinal surgery, including the associations between patient characteristics and their baseline vision. Subjects/Methods We (i) summarise demographics, injury history and ocular history of the 280 participants recruited into the ASCOT trial using descriptive statistics; (ii) analyse the national and seasonal variation across England and Scotland in these participant characteristics; and (iii) explore the associations between participant demographic, trauma history, ocular history and presenting baseline visual acuity (measured using the Early Treatment Diabetic Retinopathy Study, ETDRS) using multivariable regression analyses. Results The majority of participants with open globe penetrating injuries were of white ethnicity (233, 84%), male (246, 88%), with a median age of 43 years (IQR 30–55 years). There was considerable variability in presenting visual acuity with 75% unable to read any letters on the ETDRS chart, whilst the median ETDRS letter score was 58 (IQR 24–80) for those who could read ≥1 letter. The most common causes of injury were workplace related (31%) or interpersonal violence (24%). Previous eye surgery, visual axis corneal scar, lens status, hyphaemia and vitreous haemorrhaging were found to be associated with presenting vision as measured by the ETDRS chart. Conclusion The ASCOT trial provides valuable insights into the spectrum of pathology of patients with open globe eye injuries undergoing vitreoretinal surgery. The identified causes of injury and clinical presentation of the cases will help in training and resource planning to deal with these often challenging surgical cases. Trial registration EudraCT No. 014-002193-37. HTA Project 12/35/64

Circulating NK cells and their subsets in Behçet's disease

Behçet's disease (BD) is an autoinflammatory, chronic relapsing/remitting disease of unknown aetiology with both innate and acquired immune cells implicated in disease pathogenesis. Peripheral blood natural killer (NK) cells and their CD56Dim /CD56Bright subsets were surface phenotyped using CD27 and CD16 surface markers in 60 BD patients compared to 60 healthy controls (HCs). Functional potential was assessed by production of interferon (IFN)-γ, granzyme B, perforin and the expression of degranulation marker CD107a. The effects of disease activity (BDActive versus BDQuiet ) and BD medication on NK cells were also investigated. Peripheral blood NK cells (P < 0·0001) and their constituent CD56Dim (P < 0·0001) and CD56Bright (P = 0·0015) subsets were depleted significantly in BD patients compared to HCs, and especially in those with active disease (BDActive ) (P < 0·0001). BD patients taking azathioprine also had significantly depleted NK cells compared to HCs (P < 0·0001). A stepwise multivariate linear regression model confirmed BD activity and azathioprine therapy as significant independent predictor variables of peripheral blood NK percentage (P < 0·001). In general, CD56Dim cells produced more perforin (P < 0·0001) and granzyme B (P < 0·01) expressed higher CD16 levels (P < 0·0001) compared to CD56Bright cells, confirming their increased cytotoxic potential with overall higher NK cell CD107a expression in BD compared to HCs (P < 0·01). Interestingly, IFN-γ production and CD27 expression were not significantly different between CD56Dim /CD56Bright subsets. In conclusion, both BD activity and azathioprine therapy have significant independent depletive effects on the peripheral blood NK cell compartment.Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London Wellcome Trust . Grant Number: 096954/Z/1

The British Army, information management and the First World War revolution in military affairs

Information Management (IM) – the systematic ordering, processing and channelling of information within organisations – forms a critical component of modern military command and control systems. As a subject of scholarly enquiry, however, the history of military IM has been relatively poorly served. Employing new and under-utilised archival sources, this article takes the British Expeditionary Force (BEF) of the First World War as its case study and assesses the extent to which its IM system contributed to the emergence of the modern battlefield in 1918. It argues that the demands of fighting a modern war resulted in a general, but not universal, improvement in the BEF’s IM techniques, which in turn laid the groundwork, albeit in embryonic form, for the IM systems of modern armies. KEY WORDS: British Army, Information Management, First World War, Revolution in Military Affairs, Adaptatio

Age related macular degeneration: Smoking entails major risk of blindness

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