Opposite changes in the expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue: putative clathrin-mediated recycling of EGFR.

Endocytosis, an important macromolecule uptake process in cells, is known to be dysregulated in cancer. Clathrin and caveolin-1 proteins play a major role in receptor-mediated endocytosis. We have used a quantitative, unbiased and semi-automated method to measure in situ protein expression of clathrin and caveolin-1 in cancerous and paired normal (cancer adjacent, non-cancerous) human prostate tissue. There was a significant (p < 0.0001) increase in the expression of clathrin in prostate cancer samples (N = 29, n = 91) compared to normal tissue (N = 29, n = 67) (N = number of patients, n = number of cores in tissue arrays). Conversely, there was a significant (p < 0.0001) decrease in expression of caveolin-1 in prostate cancer tissue compared to normal prostate tissue. The opposite change in expression of the two proteins was highly correlated to increasing cancer aggressiveness. There was also a concurrent increase in the expression of epidermal growth factor receptor (EGFR), a key receptor in carcinogenesis, with clathrin in prostate cancer tissue, indicating recycling of EGFR through clathrin-mediated endocytosis (CME). These results indicate that in prostate cancer, caveolin-1-mediated endocytosis (CavME) may be acting as a brake and increase in CME may facilitate tumorigenicity and aggressiveness of prostate cancer through recycling of EGFR. Changes in the expression of these proteins can also potentially be used as a biomarker for prostate cancer to aid in diagnosis and prognosis and clinical decision-making.

Rapid intrapartum test for maternal group B streptococcal colonisation and its effect on antibiotic use in labouring women with risk factors for early-onset neonatal infection (GBS2): cluster randomised trial with nested test accuracy study.

BACKGROUND: Mother-to-baby transmission of group B Streptococcus (GBS) is the main cause of early-onset infection. We evaluated whether, in women with clinical risk factors for early neonatal infection, the use of point-of-care rapid intrapartum test to detect maternal GBS colonisation reduces maternal antibiotic exposure compared with usual care, where antibiotics are administered due to those risk factors. We assessed the accuracy of the rapid test in diagnosing maternal GBS colonisation, against the reference standard of selective enrichment culture. METHODS: We undertook a parallel-group cluster randomised trial, with nested test accuracy study and microbiological sub-study. UK maternity units were randomised to a strategy of rapid test (GeneXpert GBS system, Cepheid) or usual care. Within units assigned to rapid testing, vaginal-rectal swabs were taken from women with risk factors for vertical GBS transmission in established term labour. The trial primary outcome was the proportion of women receiving intrapartum antibiotics to prevent neonatal early-onset GBS infection. The accuracy of the rapid test was compared against the standard of selective enrichment culture in diagnosing maternal GBS colonisation. Antibiotic resistance profiles were determined in paired maternal and infant samples. RESULTS: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units; 906 mothers (951 babies) were in usual care units. There was no evidence of a difference in the rates of intrapartum antibiotic prophylaxis (relative risk 1.16, 95% CI 0.83 to 1.64) between the rapid test (41%, 297/716) and usual care (36%, 328/906) units. No serious adverse events were reported. The sensitivity and specificity measures of the rapid test were 86% (95% CI 81 to 91%) and 89% (95% CI 85 to 92%), respectively. Babies born to mothers who carried antibiotic-resistant Escherichia coli were more likely to be colonised with antibiotic-resistant strains than those born to mothers with antibiotic-susceptible E. coli. CONCLUSION: The use of intrapartum rapid test to diagnose maternal GBS colonisation did not reduce the rates of antibiotics administered for preventing neonatal early-onset GBS infection than usual care, although with considerable uncertainty. The accuracy of the rapid test is within acceptable limits. TRIAL REGISTRATION: ISRCTN74746075 . Prospectively registered on 16 April 2015.

Ethics of vaccination: Should capability measures be used to inform SARS-CoV-2 vaccination strategies?

Proposals for SARS-CoV-2 virus vaccination priorities in the UK and in many other countries are heavily influenced by epidemiological models, which use outcome measures such as deaths or hospitalisation. Limiting the values under consideration to those attributable to the direct effects of infection has the advantage of simplifying the models and the process of decision-making. However, the consequences of the pandemic extend beyond outcomes directly attributable to SARS-CoV-2 infection, and include restrictions on educational and work opportunities, access to services, recreational activities, affiliations and relationships with others, freedom of movement (including escaping abusive relationships), and other determinants of human experience. Capability theory gives emphasis to the freedoms that individuals have to express themselves (in doings and beings). Restrictions on freedoms restrict our capabilities. Capability theory has been used to provide a framework for the evaluation and comparison of international development approaches and in the evaluation of public health policy. There is a clustering of disadvantages associated with this pandemic that adds to pre-existing inequalities. Much of the disadvantage engendered in the SARS-CoV-2 pandemic is left out when public health policy is based on a limited range of metrics. Acknowledging the impact of policy across the range of human freedoms at both a national and international level has the potential to improve policy, facilitate the mitigation of direct and indirect adverse consequences, and improve public confidence and the effectiveness of vaccine deployment strategies.

Bifidobacterium breve BBG-001 and intestinal barrier function in preterm babies: Exploratory Studies from the PiPS Trial.

BACKGROUND: Uncertainty remains about the role of probiotics to prevent necrotising enterocolitis (NEC) some of which arises from the variety of probiotic interventions used in different trials, many with no prior evidence of potential efficacy. Mechanistic studies of intestinal barrier function embedded in a large probiotic trial could provide evidence about which properties of probiotics might be important for NEC prevention thus facilitating identification of strains with therapeutic potential. METHODS: Intestinal permeability, stool microbiota, SCFAs and mucosal inflammation were assessed from the second postnatal week in babies enrolled to a randomised controlled trial of B. breve BBG-001 (the PiPS trial). Results were compared by allocation and by stool colonisation with the probiotic. RESULTS: Ninety-four preterm babies were recruited across six nested studies. B. breve BBG-001 content was higher by allocation and colonisation; Enterobacteriaceae and acetic acid levels were higher by colonisation. No measure of intestinal barrier function showed differences. The PiPS trial found no evidence of efficacy to reduce NEC. CONCLUSIONS: That the negative results of the PiPS trial were associated with failure of this probiotic to modify intestinal barrier function supports the possibility that the tests described here have the potential to identify strains to progress to large clinical trials. IMPACT: Uncertainty about the therapeutic role of probiotics to prevent necrotising enterocolitis is in part due to the wide range of bacterial strains with no previous evidence of efficacy used in clinical trials. We hypothesised that mechanistic studies embedded in a probiotic trial would provide evidence about which properties of probiotics might be important for NEC prevention. The finding that the probiotic strain tested, Bifidobacterium breve BBG-001, showed neither effects on intestinal barrier function nor clinical efficacy supports the possibility that these tests have the potential to identify strains to progress to large clinical trials.

Inequality and antibiotic resistance: A contractualist perspective.

There are substantial inequalities associated with antibiotics and the determinants of their effectiveness, including the risk of exposure to antibiotic-resistant microbes, access to relevant treatment advice, diagnostic facilities, risk of life-threatening infectious disease, and access to antibiotics. Current arrangements (social, political, economic) allow inequalities in the distribution of antibiotic benefits and burdens. This article focuses on the justification of relevant inequalities from a contractualist perspective.

Femoral cortical thickness influences the pattern of proximal femoral periprosthetic fractures with a cemented stem.

INTRODUCTION: Periprosthetic fractures of the proximal femur place a significant burden on the patients who endure them, as well as the medical health system that supports them. The purpose of this study was to determine whether femoral cortical thickness, as an absolute measurement, is a predictor of periprosthetic fracture pattern. METHOD: A cohort of 102 patients who had sustained a periprosthetic hip fracture were retrospectively identified. This included 58 males and 44 females with a mean age of 79.8 years. The femoral periprosthetic fracture pattern was classified based on the Vancouver classification system. Stem fixation was recorded and femoral cortical thickness measured. Patients were grouped into cemented and cementless stems. The relationship between cortical thickness and periprosthetic fracture pattern was assessed using the primary stem fixation method. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold in the cortical thickness that predicted fracture pattern. Multinomial logistic regression analysis was used to adjust for confounding variables to assess the independent influence of cortical thickness on the risk of sustaining a Vancouver type A, B or C. RESULTS: There were 65 (63.7%) patients in the cemented group and 37 (36.3%) in the cementless group. The pattern of periprosthetic fractures around cemented stems was significantly (p < 0.001) influenced by the femoral cortical thickness, with a thinner cortical thickness associated with a type A fracture pattern. In contrast, no association between femoral cortical thickness and fracture pattern assessment was demonstrated in the cementless group (p = 0.82 Chi square). Comparing the rate of type A fracture patterns between the groups illustrated a significantly decreased risk in the cemented group with a cortical thickness of > 7 mm (odds ratio 0.03, p < 0.001). ROC curve analysis of the cemented group demonstrated a threshold value of 6.3 mm, offering a sensitivity of 83.3% and a specificity of 78.9% in predicting an A type fracture. Using this threshold, patients with a cortical thickness of 6.3 mm or less were significantly more likely to sustain a Vancouver type A fracture (OR 18.9, 95% CI 2.0-166.7, p < 0.001) when compared to patients with a cortical thickness of > 6.3 mm. In contrast, the ROC curve analysis did not find cortical thickness to be a predictor of fracture pattern in the cementless group. When adjusting for confounding variables, multinomial logistic regression demonstrated a cortical thickness of 6.3 mm or less was a significant predictor of a type A fracture (OR 3.28, 95% CI 1.06-10.16, p = 0.04) relative to those sustaining a type B fracture. CONCLUSION: Cortical thickness was found to influence the periprosthetic fracture pattern around cemented femoral stems, but this was not observed with cementless stems. Type A fracture patterns were significantly more likely to occur with a cortical thickness of 6.3 mm or less around cemented stems.

Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial.

BACKGROUND: Probiotics may reduce necrotising enterocolitis and late-onset sepsis after preterm birth. However, there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely. We aimed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis, late-onset sepsis, and death in preterm infants. METHODS: In this multicentre, randomised controlled phase 3 study (the PiPS trial), we recruited infants born between 23 and 30 weeks' gestational age within 48 h of birth from 24 hospitals in southeast England. Infants were randomly assigned (1:1) to probiotic or placebo via a minimisation algorithm randomisation programme. The probiotic intervention was B breve BBG-001 suspended in dilute elemental infant formula given enterally in a daily dose of 8·2 to 9·2 log10 CFU; the placebo was dilute infant formula alone. Clinicians and families were masked to allocation. The primary outcomes were necrotising enterocolitis (Bell stage 2 or 3), blood culture positive sepsis more than 72 h after birth; and death before discharge from hospital. All primary analyses were by intention to treat. This trial is registered with ISRCTN, number 05511098 and EudraCT, number 2006-003445-17. FINDINGS: Between July 1, 2010, and July 31, 2013, 1315 infants were recruited; of whom 654 were allocated to probiotic and 661 to placebo. Five infants had consent withdrawn after randomisation, thus 650 were analysed in the probiotic group and 660 in the placebo group. Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups. 61 infants (9%) in the probiotic group had necrotising enterocolitis compared with 66 (10%) in the placebo group (adjusted risk ratio 0·93 (95% CI 0·68-1·27); 73 (11%) infants in the probiotics group had sepsis compared with 77 (12%) in the placebo group (0·97 (0·73-1·29); and 54 (8%) deaths occurred before discharge home in the probiotic group compared with 56 (9%) in the placebo group (0·93 [0·67-1·30]). No probiotic-associated adverse events were reported. INTERPRETATION: There is no evidence of benefit for this intervention in this population; this result does not support the routine use of B breve BBG-001 for prevention of necrotising enterocolitis and late-onset sepis in very preterm infants. FUNDING: UK National Institute for Health Research Health Technology Assessment programme.

Is the Presence of Actinomyces spp. in Blood Culture Always Significant?

The isolation ofActinomycesspp. from sterile clinical samples is traditionally regarded as significant. We reviewed the demographic characteristics, clinical risk factors, and outcomes of patients withActinomycesspp. isolated from blood cultures in our NHS Trust and found that this is not necessarily the case.

ESBL-producing Enterobacteriaceae in 24 neonatal units and associated networks in the south of England: no clustering of ESBL-producing Escherichia coli in units or networks.

OBJECTIVES: The objectives of this study were to characterize ESBL-producing Enterobacteriaceae present in 24 neonatal units (NNUs) in eight networks participating in a multicentre probiotic study and to test the hypothesis that specific strains would cluster within individual units and networks. METHODS: We performed analysis of stool samples for the presence of ESBL-producing Enterobacteriaceae at 2 weeks post-natal age and 36 weeks post-menstrual age. ESBL-producing Enterobacteriaceae were characterized and typed using molecular methods. RESULTS: ESBL-producing Enterobacteriaceae (n = 71) were isolated from 67/1229 (5.5%) infants from whom we received a sample at either sampling time or both sampling times, and from infants in 18 (75%) of the 24 recruiting NNUs. Thirty-three Escherichia coli, 23 Klebsiella spp. and 6 Enterobacter spp. strains were characterized. ESBL-producing E. coli were all distinguishable within individual NNUs by antibiotic resistance genotype, serogroup (O25b), phenotype, phylotype or ST. Ten of the 33 were ST131 and 9 of the 10 ST131 isolates were ciprofloxacin resistant. Seven of the 10 ST131 isolates carried genes encoding CTX-M group 1 enzymes. ST131 isolates were isolated from centres within five of the eight NNU networks. There were clusters of indistinguishable ESBL-producing Klebsiella and Enterobacter isolates associated with specific NNUs. CONCLUSIONS: Strains of E. coli ST131 were distributed across neonatal networks in the south of England. There was no evidence of clustering of clonally related ESBL-producing E. coli strains, by contrast with Klebsiella spp. and Enterobacter spp., which did cluster within units. The possibility that ESBL-producing E. coli strains are spread by vertical transmission requires further investigation.

Plates, Screws, or Combination? Radiologic Outcomes After Lisfranc Fracture Dislocation.

Traditionally, Lisfranc fracture dislocations have been treated with transarticular screw fixation. A more recent development has been the use of dorsal bridging plates. The aim of the present study was to compare the radiologic outcomes for these 2 methods. Currently, no data comparing the outcomes of these 2 treatment options have been reported. A total of 62 patients were treated for Lisfranc fracture dislocations during a 6-year period. The inclusion criteria included ≥6 months of follow-up data available. Each fracture was classified using the Hardcastle classification system. Each fracture was also allocated into 1 of 4 groups: transarticular screw fixation, dorsal plating, a combination of plate and screw fixation, and nonoperative management. The outcome measures included the Kellgren-Lawrence grading of osteoarthritis and the Wilppula classification of anatomic reduction. In terms of results, radiologic osteoarthritis is not associated with the type of injury according to the Hardcastle classification nor with having an open or closed fracture. The Hardcastle classification is not associated with the type of fixation used. Fractures fixed with a combination of plates and screws had a 3.01 (95% confidence interval 1.036 to 8.74) increased risk of having stage 3 or 4 radiologic osteoarthritis compared with being fixed solely with bridging plates (p = .009). Multivariate analysis revealed that this increased risk of osteoarthritis was dependent on the quality of reduction, with good reductions having a 18.2 (95% confidence interval 15.9 to 21.8) times decreased risk of severe osteoarthritis compared with fair or poor reductions, independent of the type of fixation used (p < .0001). No radiologic benefits were found when comparing plate or screw fixation for Lisfranc fracture dislocations (although screw fixation might be associated with a less planus foot and fewer complications). Instead, a good anatomic reduction was the only predictor of the radiologic outcome, and the Hardcastle classification of fractures did not predict the surgery type or radiologic outcome. Finally, treatment with combination plates and screws resulted in worse radiologic outcomes, possibly owing to more complex fracture patterns.

Unbiased species-level identification of clinical isolates of coagulase-negative Staphylococci: does it change the perspective on Staphylococcus lugdunensis?

Unbiased species-level identification of coagulase-negative staphylococci (CoNS) using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified Staphylococcus lugdunensis to be a more commonly isolated CoNS in our laboratory than previously observed. It has also highlighted the possibility of vertical transmission.

Activation of intracellular calcium by multiple Wnt ligands and translocation of ß-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/ß-catenin pathways.

Ca(2+) and ß-catenin, a 92-kDa negatively charged transcription factor, transduce Wnt signaling via the non-canonical, Wnt/Ca(2+) and canonical, Wnt/ß-catenin pathways independently. The nuclear envelope is a barrier to large protein entry, and this process is regulated by intracellular calcium [Ca(2+)]i and trans-nuclear potential. How ß-catenin traverses the nuclear envelope is not well known. We hypothesized that Wnt/Ca(2+) and Wnt/ß-catenin pathways act in a coordinated manner and that [Ca(2+)]i release facilitates ß-catenin entry into the nucleus in mammalian cells. In a live assay using calcium dyes in PC3 prostate cancer cells, six Wnt peptides (3A, 4, 5A, 7A, 9B, and 10B) mobilized [Ca(2+)]i but Wnt11 did not. Based upon dwell time (range = 15-30 s) of the calcium waveform, these Wnts could be classified into three classes: short, 3A and 5A; long, 7A and 10B; and very long, 4 and 9B. Wnt-activated [Ca(2+)]i release was followed by an increase in intranuclear calcium and the depolarization of both the cell and nuclear membranes, determined by using FM4-64. In cells treated with Wnts 5A, 9B, and 10B, paradigm substrates for each Wnt class, increased [Ca(2+)]i was followed by ß-catenin translocation into the nucleus in PC3, MCF7, and 253J, prostate, breast, and bladder cancer cell lines; both the increase in Wnt 5A, 9B, and 10B induced [Ca(2+)]i release and ß-catenin translocation are suppressed by thapsigargin in PC3 cell line. We propose a convergent model of Wnt signaling network where Ca(2+) and ß-catenin pathways may act in a coordinated, interdependent, rather than independent, manner.

Constraining the use of antibiotics: applying Scanlon's contractualism.

Decisions to use antibiotics require that patient interests are balanced against the public good, that is, control of antibiotic resistance. Patients carry the risks of suboptimal antibiotic treatment and many physicians are reluctant to impose even small avoidable risks on patients. At the same time, antibiotics are overused and antibiotic-resistant microbes are contributing an increasing burden of adverse patient outcomes. It is the criteria that we can use to reject the use of antibiotics that is the focus of this paper. Scanlon's contractualism explains why antibiotics should not be used to gain small benefits, even when the direct costs of antibiotics are low. We know that some individuals now (and probably more in the future will) carry a burden of irretrievable harm as a consequence of treatment- (antibiotic-) resistant infection. If we accept that the dominant justification for use of antibiotics is to prevent irretrievable harm to an individual or contact, then the use of antibiotics for self-limiting conditions, or for the treatment of individuals with conditions for which antibiotics do not substantially impact on outcomes (eg, in the latter stages of terminal illness), or for access based on preference or willingness to pay (internet or over-the-counter access), or the use of antibiotics as animal growth promoters can be rejected. Scanlon's approach also suggests that, with few new antibiotics in the pipeline and an increasing burden of disease attributable to resistant microbes, control of the spread of antibiotic-resistant microbes should be given increasing priority.

The Australian arthroplasty thromboprophylaxis survey.

Previous surveys of orthopedic surgeons have shown considerable variation in thromboprophylaxis for venous thromboembolism after joint arthroplasty. This survey aimed to determine the current practice among Australian orthopedic surgeons. A questionnaire regarding the duration, reasons, and methods of chemical and mechanical prophylaxis for hip and knee arthroplasty patients was sent to the 1082 surgeons identified; 593 (55%) members completed the questionnaire. The survey revealed that 98% of surgeons used chemical thromboprophylaxis, mainly low-molecular-weight heparin (84% hip and 79% knee). Those who use low-molecular-weight heparin were more likely to prescribe anticoagulants in fear of litigation (19.2% vs 10.1%, P = .04) and more likely to rely on protocols or guidelines (32.2% vs 17.2%, P = .004) instead of basing their decision on their own reading (52.4% vs 71.3%, P = .001). Most orthopedic surgeons in our survey have indicated that they would welcome guidelines from their association or college regarding thromboprophylaxis in arthroplasty.

A rapid intrapartum test for group B Streptococcus to reduce antibiotic usage in mothers with risk factors: the GBS2 cluster RCT.

BACKGROUND: Mother-to-baby transmission of group B Streptococcus (Streptococcus agalactiae) is the main cause of early-onset infection. OBJECTIVES: We investigated if intrapartum antibiotic prophylaxis directed by a rapid intrapartum test reduces maternal and neonatal antibiotic use, compared with usual care (i.e. risk factor-directed antibiotics), among women with risk factors for vertical group B Streptococcus transmission, and examined the accuracy and cost-effectiveness of the rapid test. DESIGN: An unblinded cluster randomised controlled trial with a nested test accuracy study, an economic evaluation and a microbiology substudy. SETTING: UK maternity units were randomised to either a strategy of rapid test or usual care. PARTICIPANTS: Vaginal and rectal swabs were taken from women with risk factors for vertical group B Streptococcus transmission in established term labour. The accuracy of the GeneXpert® Dx IV GBS rapid testing system (Cepheid, Maurens-Scopont, France) was compared with the standard of selective enrichment culture in diagnosing maternal group B Streptococcus colonisation. MAIN OUTCOME MEASURES: Primary outcomes were rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection and accuracy estimates of the rapid test. Secondary outcomes were maternal antibiotics for any indication, neonatal antibiotic exposure, maternal antibiotic duration, neonatal group B Streptococcus colonisation, maternal and neonatal antibiotic resistance, neonatal morbidity and mortality, and cost-effectiveness of the strategies. RESULTS: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units and 906 mothers (951 babies) participated in usual-care units. There were no differences in the rates of intrapartum antibiotic prophylaxis for preventing early-onset group B Streptococcus infection in the rapid test units (41%, 297/716) compared with the usual-care units (36%, 328/906) (risk ratio 1.16, 95% confidence interval 0.83 to 1.64). There were no differences between the groups in intrapartum antibiotic administration for any indication (risk ratio 0.99, 95% confidence interval 0.81 to 1.21). Babies born in the rapid test units were 29% less likely to receive antibiotics (risk ratio 0.71, 95% confidence interval 0.54 to 0.95) than those born in usual-care units. The sensitivity and specificity of the rapid test were 86% (95% confidence interval 81% to 91%) and 89% (95% confidence interval 85% to 92%), respectively. In 14% of women (99/710), the rapid test was invalid or the machine failed to provide a result. In the economic analysis, the rapid test was shown to be both less effective and more costly and, therefore, dominated by usual care. Sensitivity analysis indicated potential lower costs for the rapid test strategy when neonatal costs were included. No serious adverse events were reported. CONCLUSIONS: The Group B Streptococcus 2 (GBS2) trial found no evidence that the rapid test reduces the rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection. The rapid test has the potential to reduce neonatal exposure to antibiotics, but economically is dominated by usual care. The accuracy of the test is within acceptable limits. FUTURE WORK: The role of routine testing for prevention of neonatal infection requires evaluation in a randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN74746075. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 12. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Group B Streptococcus is a common bacterium found in the vagina and intestines of approximately one in four women. Group B Streptococcus may be passed to the baby around birth and cause severe infection. In the UK, women are offered antibiotics in labour to protect their baby from group B Streptococcus infection when specific risk factors are present. Most women with risk factors do not carry group B Streptococcus and their babies are unnecessarily exposed to antibiotics. Most women carrying group B Streptococcus do not have risk factors and so will not be offered antibiotics to protect their babies. WHAT DID WE PLAN TO DO?: We planned to find out if, for women with risk factors, a 'rapid test' in labour resulted in fewer women receiving antibiotics compared with 'usual care'. We also wanted to establish if the test correctly identified if mothers were carrying group B Streptococcus, helped reduce infections in babies and represented value for money. WHAT DID WE FIND?: We involved 1627 women (1700 babies) from 20 hospitals randomly allocated to rapid test or usual care. Using the 'rapid test' did not reduce antibiotics provided to mothers (41% in rapid test units and 36% in usual-care units). The test correctly identified 86% of women carrying group B Streptococcus, 89% of those who did not and failed to provide a result in 14% of women. A rapid test policy resulted in 13% fewer babies receiving antibiotics. The rapid test generated no cost savings when only the mothers' care was considered, but there was potential for reduced costs when including the newborns' hospital stay. WHAT DOES THIS MEAN?: The rapid test is accurate; however, using it for women with risk factors for their baby developing group B Streptococcus infection does not reduce antibiotic usage in mothers, although it does in babies. Value for money is uncertain and depends on what costs are included.

Can antibiotic use be both just and sustainable... or only more or less so?

Antibiotic resistance threatens the capacity to treat life-threatening infections. If it is accepted that it will be many years (if not decades) until the production of new antibiotics overcomes current concerns with antibiotic resistance then ways to conserve the effectiveness of current antibiotics will have to be found. For many bacterial agents of infection levels of antibiotic resistance are directly dependent on the quantity of antibiotic prescribed. Antibiotics are currently underutilised in many parts of the world. If a just distribution of access to antibiotics requires equal access for individuals with equal need irrespective of wealth then responding to this requirement of justice has the potential to shorten the effective life of currently available antibiotics. Increasing the range and numbers of individuals treated with antibiotics would seem to threaten sustainability and also potentially undermine the access of future generations to cost-effective treatments for bacterial infection. The control of antibiotic resistance requires that the determinants of infectious disease transmission are addressed, such as poor housing, education and nutrition as well as the provision of antibiotics. The apparent tension between intragenerational justice and sustainability diminishes when the account of distributive justice extends beyond access to antibiotics and includes plural entitlements. Controlling antibiotic resistance requires more than the redistribution or reduction (in the overall use) of antibiotics.